Request to Reschedule Cannabis
For more information on rare diseases a place to start is :
Chapter 1 The Controlled Substances Act
International Treaty Obligations
United States treaty obligations may require that a drug or other substance be controlled under the CSA, or rescheduled if existing controls are less stringent than those required by a treaty. The procedures for these scheduling actions are found in Section 201 (d) of the Act. [21 U.S.C. 811 (d)]
Section 811. Authority and Criteria for Classification of Substances
(d) International treaties, conventions, and protocols requiring control; procedures respecting changes in drug schedules of Convention on Psychotropic Substances
(1) If control is required by United States obligations under international treaties,conventions, or protocols in effect on October 27, 1970, the Attorney General shall issue an order controlling such drug under the schedule he deems most appropriate to carry out such obligations, without regard to the findings required by subsection (a) of this section or section 812(b) of this title and without regard to the procedures prescribed by subsections (a) and (b) of this section.
Cannabis/marijuana is used as a medicineand is legal in a number of territories worldwide, including Canada, Austria, Germany, the Netherlands, Spain, Israel, Italy, Finland, and Portugal. In the United States, 14 states and Washington DC have accepted it for medicinal use. Oct 19, 2009 – US Attorney General Eric Holder announced formal guidelines for federal prosecutors in states that have enacted laws authorizing the use of marijuana for medical purposes. The guidelines make clear that the focus of federal resources should not be on individuals whose actions are in compliance with existing state laws. It has been decriminalized in Argentina, Australia, and Belgium. Thereby, existing controls are less stringent than those required by any treaty on October 27, 1970.
President Obama stated “It is not the need for big government or small government, but for smart government.”
July 1, 2010 – President Obama stated “This administration will not just kick the can down the road.”
FDA has wide control and can waive any and all process, control, and requirements for orphan drug and orphan diseases.
The department of Health and Human Services can under the Orphan Drug Act or otherwise find that cannabis/marijuana meets sufficient standards of safety and efficacy to warrant rescheduling.
With all due respect and no personal offense intended, with realization it comes with the job (which needs to change) : The DEA (along with other government officials, executives, departments and offices) can stop committing the criminal offense of officials or executives of the U.S. government to direct or conspire to wage a deliberate campaign of misinformation, omission of fact, and outright lies with our tax dollars and change the schedule, realizing without a medical need and valid prescription it would still be a crime they can pursue, along with all the other substances that are abused. It would be grand if they could eradicate cocaine, heroin and methamphetamines from this nation. Changing the schedule might give them the time and manpower to focus on the truly dangerous drugs that do in fact cost lives and the real criminals instead of so much concern over ill patients with no alternative. It impossible to watch the following video and deny the fact that cannabis has medicinal value :
Cured: A Cannabis Story (A film by David Triplett)
Professor at Hebrew University in Jerusalem, Dr. Mechoulam, describes the role of Cannabinoids as anti-inflammatory for arthritis, as neuroprotectant for brain injury and as a possible treatment for PTSD. Dr. Mechoulam first isolated THC in 1964. Conference hosted by Patients Out of Time. “My good Italian friend, Emazo, summarized the activity, which is really a summary says well what do the Cannabinoids do, they relax, help us eat, sleep, forget, and protect, not remember, forget, and don’t think that forgetting is less important than recalling, We should have a system to forget, otherwise, well if you wish, we can burst, if you go down a mall and see a thousand faces do you want to remember all of them, of course not. But there are also other memories we certainly try to forget, other wise each one of us would be in a constant trauma.”
Substance abuse and medical value are not the same by any means. For example there are many, many current pharmaceutical drugs prescribed and sold daily that are abused. Drug abusers and ill patients using the same drug can not be compared. Someone having a legitimate health need for the drug simply can not be put in the same category as an addict or drug abuser.
From USA Today May 10, 2006
“The data, to be released today by the Substance Abuse and Mental Health Services Administration (SAMHSA), show that 1.3 million people visited a hospital emergency room in 2004 for illnesses involving drug abuse. The administration collects data from 417 hospitals and 106 million total emergency room visits. One in four — or 495,732 — drug-related emergency room visits involved pharmaceuticals: over-the-counter or prescription drugs. One in five — 383,350 — visits involved cocaine. Marijuana was involved in 215,665 emergency room visits.”
As someone who has been in the emergency room on several occasions, often tested for substances, unaware as to why, I question whether marijuana was involved in the cause for the visit to the ER or simply found in the person’s blood, having nothing to do with why they were there. As shown later these suspicions are in fact correct.
According to the CDC
Rates of overdose deaths involving prescription drugs increased rapidly in the United States during 1999–2006. And prescription or over-the-counter drugs used nonmedically were involved in 0.5 million visits in 2004 and 1.0 million visits in 2008. The estimated number of ED visits involving nonmedical use of opioid analgesics§ increased from 144,600 in 2004 to 305,900 in 2008 (111%, p<0.001), whereas rates increased from 49.4 per 100,000 to 100.6 per 100,000, an increase of 104% (p<0.05). ED visit rates for opioid analgesics were highest for oxycodone, hydrocodone, and methadone during the entire study period (2004–2008). Estimated ED visits involving oxycodone increased from 41,700 to 105,200 (p<0.001), and rates increased from 14.2 per 100,000 to 34.6 per 100,000, an increase of 144% (p<0.05). The estimated number of ED visits involving nonmedical use of benzodiazepines increased from 143,500 in 2004 to 271,700 in 2008 (89%, p=0.01), and rates increased from 49.0 to 89.4 per 100,000, an increase of 82% (p<0.05). The increases in numbers of ED visits during 2004–2008 for individual benzodiazepines were significant: alprazolam (125%, p=0.01), clonazepam (72%, p<0.001), diazepam (70%, p=0.02), and lorazepam (107%, p=0.006), as was the increase for the sleep aid zolpidem (121%, p=0.002). Carisoprodol-related visits also increased significantly (132%, p=0.04). The estimated number of visits for alprazolam in 2008 (104,800) was more than twice the number for the next most common benzodiazepine, clonazepam, (48,400).
The Controlled Substance Act of 1970 and subsequent scheduling was done before science was even aware the human body has an endocannabinoid system. It was discovered in the mid 1980’s. Congress enacted laws against marijuana in 1970 based in part on its conclusion that marijuana has no scientifically proven medical value. In the last 40 years much scientific documentation has taken place. It must be taken into consideration.
It is a criminal offense for officials or executives of the U.S. government to direct or conspire to wage a deliberate campaign of misinformation, omission of fact, and outright lies with our tax dollars.
The documentation comes from the National Institute of Health, The New England Journal of Medicine, Max Planck Society for the Advancement of Science, Medical News Today, Science Direct, The Lancet, Medicine News, AGA Institute, JAMA, SACRA Research, Cannabis Science, Inc formerly known as Gulf Onshore, Common Sense for Drug Policy, CMAJ, University of California Center of Medicinal Cannabis Research, Report of the Senate Special Committee on Illegal Drugs Canada, the Norml Library plus many more, and supported by an extensive list of health organizations, and health care professionals in this nation and world wide.
Evidence for novel cannabinoid receptors
Before the 1980s, it was often speculated that cannabinoids produced their physiological and behavioral effects via nonspecific interaction with cell membranes, instead of interacting with specific membrane-bound receptors. The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate. At present, there are two known types of cannabinoid receptors, termed CB1 and CB2, with mounting evidence of more.
From : http://www.jaoa.org/cgi/content/full/108/10/586
This discussion brings us back to the medicinal uses of cannabis. Oral administration of cannabis shares drawbacks with dronabinol capsules—erratic gut bioavailability, poor dose titration, and THC taken by mouth is converted to an 11-hydroxy-THC metabolite with two to five times more psychoactivity.138 Oral administration is difficult in patients who are nauseated or vomiting. Smoking cannabis is a health hazard due to polyaromatic hydrocarbons formed during combustion. Vaporization of cannabis provides an alternative to smoking, recently described in the New England Journal of Medicine.17 Because THC vaporizes at a temperature below the ignition point of combustible plant material, few polyaromatic hydrocarbons appear in the vapor. Cannabis, of course, is more than THC. Other ingredients provide additional benefits and mitigate the adverse effects of THC.79 For this reason, many patients prefer cannabis to dronabinol. Cannabidiol, for example, reduces dysphoria and depersonalization provoked by THC while contributing its own anxiolytic, antipsychotic, analgesic, antiemetic, anticarcinogenic, antioxidant, and neuroprotective effects.139 Indeed, the risk posed by new high-potency cannabis may be the lack of cannabidiol in current strains of cannabis rather than the increase in THC levels.140 Median THC levels have only increased five fold since the 1970s, analogous to the five fold difference in caffeine between green tea and percolated coffee.140
Additional Fact : The Cannabis plant contains more than 60 cannabinoids, 66 have been found to date. Marinol has 1 cannabinoid which is not effective on everything. The other cannabinoids have great healing properties that science is just beginning to understand but years away from developing a synthetic compound in attempts to reproduce the natural.
Studying what all the fuss is about regarding medicinal use of cannabis I found themain issue – is the psychotropic effect. Research conducted on cannabis based medicine for a wide range of heath issues main attempt is to eliminate these effects. It must be pointed out that there is a wide range of medicines prescribed daily have psychotropic effects. Many of these are on the list of schedules 1 through 5, Marinol is currently placed on schedule 3. Examples of substances on Schedule 4 include Alprazolam (Xanax), Clonazepam (Klonopin, Clonopin), Diazepam (Valium, Valrelease), Lorazepam (Ativan), Phenobarbital, Sibutramine (Meridia) Temazepam (Restoril) Zolpidem (Ambien, Stilnoct,Ivadal). It must also be pointed out that Benadryl, available over the counter, as well as many cough medicines also have psychotropic effects. So just what is all the fuss about? No one had ever died from cannabis. Alcoholic beverages cause death on a regular basis yet they are legal for all adults yet also cause psychotropic effects.
The other issue being the concept that smoked marijuana has no documented medical value and that voices in the medical community likewise do not accept smoked marijuana as medicine. The American Cancer Society “does not advocate inhaling smoke,” although the organization does support carefully controlled clinical studies for alternative delivery methods, specifically a THC skin patch. Here again we have an other alternative, I repeat from earlier “Vaporization of cannabis provides an alternative to smoking, recently described in the New England Journal of Medicine. “Because THC vaporizes at a temperature below the ignition point of combustible plant material, few polyaromatic hydrocarbons appear in the vapor.”
From Wikipedia :
“Polyaromatic hydrocarbons or PAHs are also found in foods. Studies have shown that most food intake of PAHs comes from cereals, oils and fats. Smaller intakes come from vegetables and cooked meats. They are also found in the interstellar medium, in comets, and in meteorites and are a candidate molecule to act as a basis for the earliest forms of life.” These tend to be a concern due to their suppressive nature of the autoimmune system. For the many who suffer the various autoimmune diseases, it may well be what works best in preventing what attacks their bodies.
http://jama.ama-assn.org/cgi/content/full/289/15/1929-a
Modulation of the Immune System in Cannabis Users
To the Editor: In vitro studies and experiments in animal models have found that
cannabinoids modulate immune cell function.1 However, investigations of immune
effects in human subjects are scarce and contradictory. Gene expression of
cannabinoid receptors in peripheral blood mononuclear cells may be altered among
marijuana users.2 Experimental data in healthy persons have found abnormalities
in T lymphocyte and natural killer (NK) cell function, but have not confirmed that
these alterations might affect susceptibility to infections.3 We sought to investigate
cell-mediated immune response and cytokine release in cannabis users.
Methods. Participants were recruited by word of mouth and gave written consent to
participate in the study, which was approved by our institutional ethical committee
and conducted in accordance with the Declaration of Helsinki. Volunteers were
deemed healthy after a full medical history and examination. They were then
interviewed about their recent use of illicit drugs, and their statements were
confirmed by urine testing. A psychiatric screening excluded drug abuse or
dependence (except for cannabis or nicotine) or psychiatric disorders according
to criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth
Edition. exposure categories were performed using 2 tests or analysis of variance.
Multivariate linear regression models were fitted for each immune parameter to
analyze the effects of cannabis consumption after adjusting for sex, as well as
consumption of coffee, tobacco, and alcohol.Results. According to total cannabis
consumption and frequency of use during the previous 6 months, participants were
classified as controls (n = 32), occasional users (eventual to monthly use, n = 13)
and regular users (weekly to daily use, n = 16). Sex, tobacco smoking, and alcohol
consumption were unequally distributed between groupsA blood sample was
obtained between the hours of 8 and 11 AM to determine blood cell count and
differential, lymphocyte immunophenotyping, lymphocyte proliferative response
to mitogenic stimulation (stimulation index with phytohemoagglutinine [SI-PHA]
or concanavaline A [SI-ConA]), and levels of interleukin 2 (IL-2), interleukin
10 (IL-10), and transforming growth factor -1 (TGF1), as described previously.4
Comparisons between cannabis Cannabis use was associated with a decrease in NK
counts, lymphocyte proliferative response by SI-PHA and SI-ConA, and levels of
IL-2, and an increase in levels of IL-10 and TGF1. No differences were found in
counts of total lymphocytes or CD4, CD8, and CD19 cells (TABLE). The significant
effect of cannabis consumption on immune measures persisted after multivariate
analysis controlling for the possible confounding effects of sex and use of coffee,
tobacco, and alcohol. A significant dose-response relationship was found between
cannabis exposure (total life consumption, as the log-transformed number of
cannabis “joints”) and the decrease in counts of total lymphocytes, CD4 or NK cells,
and IL-2 levels, or the increase in IL-10 levels.
Comment. Cannabis use was associated with a decrease in levels of IL-2, a TH1-type cytokine related to cell-mediated immunity, and an increase in levels of IL-10, a TH2-type cytokine related to humoral immunity. The decrease of proinflammatory(IL-2) cytokines and the augment of anti-inflammatory (IL-10 and TGF1) cytokines was associated with a marked reduction in lymphocyte functionality, and a decrease in the number of NK cells. The suppression of immediate and innate responses of the immune system together with the disruption of TH1/TH2 balance might increase the susceptibility and promote the progression of infectious diseases and tumors, although the clinical relevance of these findings has not been clearly demonstrated in humans.3, 5 It also has been suggested that immunomodulatory effects of cannabinoids on inflammatory and autoimmune disorders could lead to new therapeutic interventions.6
1. Klein TW, Newton C, Friedman H. Cannabinoids receptors and immunity.
Immunol Today. 1998;19:373-381.
2. Nong L, Newton C, Cheng Q, Friedman H, Roth MD, Klein TW. Altered cannabinoid receptor mRNA expression in peripheral blood mononuclear cells from marijuana smokers. J Neuroimmunol. 2002;127:169-176.
3. Kaslow RA, Blackwelder WC, Ostrow DG, et al. No evidence for a role of
alcohol or other psychoactive drugs in accelerating immunodeficiency in
HIV-1-positive individuals: a report from the Multicenter AIDS Cohort Study.
JAMA. 1989;261:3424-3429.
4. Pacifici R, Zuccaro P, Hernández-López, et al. Acute effects of 3,
4-methylenedioxymethamphetamine alone and in combination with ethanol on the
immune system in humans. J Pharmacol Exp Ther. 2001;296:207-215.
5. Roth MD, Baldwin GC, Tashkin DP. Effects of delta-9-tetrahydrocannabinol
on human immune function and host defense. Chem Phys Lipids. 2002;121:229-239.
6. Zurier RB. Prospects for cannabinoids as anti-inflammatory agents. J Cell
Biochem. 2003;88:462-466.
From Webpage :http://www.patentstorm.us/patents/6410588/fulltext.html
Cannabis sativa, commonly known as marijuana, has been used for several years for its medicinal effects, including antipyretic and analgesic properties. Approximately 80 cannabis constituents, termed cannabinoids, naturally occur as 21 carbon atom com-pounds of cannabis and analogues of such compounds and their metabolites [Mechoulam, In "Marijuna Chemistry, Metabolism and Clinical effects, Academic Press, New York (1973), pages 1-99].
The major psychoactive component of marijuana is Delta-9-tetrahydrocannabinoid (THC), which has been widely studied. Studies have shown that THC affects growth, development and reproductive activity [Pharmacol Rev. 38 (1986), pages 1-18 and
151-178; Marihuana, Pharmacological Aspects of Drug Dependence, Springer Verlag
(1996), pages 83-158]. Studies in mice have shown that THC suppresses antibody formation against sheep red blood cells and causes changes in cytokine production. In vitro studies, however, have shown that THC may suppress or enhance (depending on dosage) the production of various cytokines such as IL-1, IL-6 and TNFα by leukocytic cells.
Cannabidiol (CBD) is present in most cannabis preparations (hashish, marijuana, ganja) in higher concentrations than THC. Cannabidiol. was, first isolated in 1940 by Todd and Adams [J. Amer. Chem. Soc., 6,2 2194 (1940), J. Chem. Soc., 649
(1940)]. Its structure was elucidated by Mechoulam and Shvo in 1963 [Tetrahedron,
19 (1963), page 2073]. Its absolute stereochemistry was determined in
1967 [Tet. Lett., 1109-1111 (1967)]. The synthesis of cannabidiol in its racemic form and its natural form were reported in the 1960’s [J. Amer. Chem. Soc., 87, 3273-3275 (1965), Helv. Chim. Acta, 50 719-723 (1967)].
From Webpage :http://medicalcannabis.com/images/pdf09/science/mcpartland_2008_endocannabinoid_review.pdf
JAOA review article page5
Inflammation and Connective Tissues
More than 4000 years ago, the Chinese physician Shen Nung recommended cannabis for rheumatic pains. More recently, patients with myofascial pain and arthritis are among those who most often use cannabis medicinally. Activation of CB2 suppresses proinflammatory cytokines such as IL-1 and TNF- while increasing anti-inflammatory cytokines such as IL-4 and IL-10.51,52 Although THC has
well-known anti-inflammatory properties, cannabidiol also provides clinical improvement in arthritis via a cannabinoid receptor–independent mechanism.
Many connective tissue–related cells express CB1, CB2, and
endocannabinoid-metabolizing enzymes such as fibroblasts, myofibroblasts, chondrocytes, and synoviocytes. The endocannabinoid system alters fibroblast “focal adhesions,” by which fibroblasts link the extracellular collegen matrix to their intracellular cytoskeleton—the mechanism of fascial remodeling.
Cannabinoids prevent cartilage destruction such as proteoglycan degradation and collagen breakdown by inhibiting chrondrocyte expression of cytokines and metalloproteinase enzymes. In addition, the tonic release of endocannabinoids is upregulated in rats that have experimentally induced osteoarthritis, thereby providing endogenous pain relief.The endocannabinoid system has been shown to
attenuate allergic contact dermatitis in rodent studies—THC decreases allergic inflammation whereas CB1-blocking agents exacerbate the condition. The endocannabinoid system likewise protects against Crohn’s disease—a TH1-mediated inflammatory bowel condition—and also perhaps ulcerative colitis. The endocannabinoid system dampens the inflammatory component of atherosclerosis in animal studies via CB2 receptors expressed by macrophages within atherosclerotic
plaques. Lastly, the endocannabinoid system is essential for the maintenance of normal bone mass: CB2 agonists enhance osteoblast activity and inhibit osteoclast activity, therefore offering a potential treatment option for osteoporosis.
From Webpage :http://www.sciencedaily.com/releases/2009/12/091220175502.htm
Cannabis Hope for Inflammatory Bowel Disease
ScienceDaily (Dec. 21, 2009) — Chemicals found in cannabis could prove an effective treatment for the inflammatory bowel diseases Ulcerative Colitis and Crohn’s Disease, say scientists. Laboratory tests have shown that two compounds found in the cannabis plant — the cannabinoids THC and cannabidiol — interact with the body’s system that controls gut function.
Crohn’s Disease and Ulcerative Colitis, which affect about one in every 250 people in Northern Europe, are caused by both genetic and environmental factors. The researchers believe that a genetic susceptibility coupled with other triggers, such
as diet, stress or bacterial imbalance, leads to a defective immune response.
Dr Karen Wright, Peel Trust Lecturer in Biomedicine at Lancaster University, presented her soon-to-be published work at The British Pharmacological Society’s Winter Meeting in London. She said: “The lining of the intestines provides a barrier against the contents of the gut but in people with Crohn’s Disease this barrier leaks and bacteria can escape into the intestinal tissue leading to an inappropriate immune
response. “If we could find a way to restore barrier integrity in patients we may be able to curb the inflammatory immune response that causes these chronic conditions.”
Dr Wright, working with colleagues at the School of Graduate Entry Medicine and Health in Derby, has shown that cells that react to cannabinoid compounds play an important role in normal gut function as well as the immune system’s inflammatory response. “The body produces its own cannabinoid molecules, called endocannabinoids, which we have shown increase the permeability of the epithelium
during inflammation, implying that overproduction may be detrimental,” said Dr. Wright. “However, we were able to reverse this process using plant-derived cannabinoids, which appeared to allow the epithelial cells to form tighter bonds with each other and restore the membrane barrier.”
The DEA and others often cite The British Medical Association concerns that smoking cannabis/marijuana has been linked to lung cancer, a statement from 2004.
Yet more recent science shows otherwise.
From Webpage :
http://www.sciencedaily.com/releases/2007/04/070417193338.htm
Marijuana Cuts Lung Cancer Tumor Growth In Half, Study Shows
ScienceDaily (Apr. 17, 2007) — The active ingredient in marijuana cuts tumor growth in common lung cancer in half and significantly reduces the ability of the cancer to spread, say researchers at Harvard University who tested the chemical in both lab and mouse studies.
They say this is the first set of experiments to show that the compound,
Delta-tetrahydrocannabinol (THC), inhibits EGF-induced growth and migration in epidermal growth factor receptor (EGFR) expressing non-small cell lung cancer cell lines. Lung cancers that over-express EGFR are usually highly aggressive and resistant to chemotherapy.
THC that targets cannabinoid receptors CB1 and CB2 is similar in function to endocannabinoids, which are cannabinoids that are naturally produced in the body and activate these receptors. The researchers suggest that THC or other designer agents that activate these receptors might be used in a targeted fashion to treat lung cancer. “The beauty of this study is that we are showing that a substance of abuse, if used prudently, may offer a new road to therapy against lung cancer,” said Anju Preet, Ph.D., a researcher in the Division of Experimental Medicine.
Acting through cannabinoid receptors CB1 and CB2, endocannabinoids (as well as THC) are thought to play a role in variety of biological functions, including pain and anxiety control, and inflammation.
Although a medical derivative of THC, known as Marinol, has been approved for use as an appetite stimulant for cancer patients, and a small number of U.S. states allow use of medical marijuana to treat the same side effect, few studies have shown that THC might have anti-tumor
activity, Preet says. The only clinical trial testing THC as a treatment against cancer growth was a recently completed British pilot study in human glioblastoma.
In the present study, the researchers first demonstrated that two different lung cancer cell lines as well as patient lung tumor samples express CB1 and CB2, and that non-toxic doses of THC inhibited growth and spread in the cell lines.
“When the cells are pretreated with THC, they have less EGFR stimulated invasion as measured by various in-vitro assays,” Preet said.
Then, for three weeks, researchers injected standard doses of THC into mice that had been implanted with human lung cancer cells, and found that tumors were reduced in size and weight by about 50 percent in treated animals compared to a control group. There was also about a 60 percent reduction in cancer lesions on the lungs in these mice as well as a significant reduction in protein markers associated with cancer progression, Preet says.
Although the researchers do not know why THC inhibits tumor growth, they say the substance could be activating molecules that arrest the cell cycle. They speculate that THC may also interfere with angiogenesis and vascularization, which promotes cancer growth.
Preet says much work is needed to clarify the pathway by which THC functions, and cautions that some animal studies have shown that THC can stimulate some cancers. “THC offers some promise, but we have a long way to go before we know what its potential is,” she said.
From Webpage :
http://www.sciencedaily.com/releases/2008/08/080801074056.htm
Turned-Off Cannabinoid Receptor Turns On Colorectal Tumor Growth
ScienceDaily (Aug. 4, 2008) — New preclinical research shows that cannabinoid cell surface receptor CB1 plays a tumor-suppressing role in human colorectal cancer, scientists report in the Aug. 1 edition of the journal Cancer Research.
CB1 is well-established for relieving pain and nausea, elevating mood and stimulating appetite by serving as a docking station for the cannabinoid group of signaling molecules. It now may serve as a new path for cancer prevention or treatment.
“We’ve found that CB1 expression is lost in most colorectal cancers, and when that happens a cancer-promoting protein is free to inhibit cell death,” said senior author Raymond DuBois, M.D., Ph.D., provost and executive vice president of The University of Texas M. D. Anderson Cancer Center.
DuBois and collaborators from Vanderbilt-Ingram Cancer Center also show that CB1 expression can be restored with an existing drug, decitabine. They found that mice prone to developing intestinal tumors that also have functioning CB1 receptors develop fewer and smaller tumors when treated with a drug that mimics a cannabinoid receptor ligand. Ligands are molecules that function by binding to specific receptors. Agonists are synthetic molecules that mimic the action of a natural molecule.“Potential application of cannabinoids as anti-tumor drugs is an exciting prospect, because cannabinoid agonists are being evaluated now to treat the side-effects of chemotherapy and radiation therapy,” DuBois said. “Turning CB1 back on and then treating with a cannabinoid agonist could provide a new approach to colorectal cancer treatment or prevention.”
Cannabinoids are a group of ligands that serve a variety of cell-signaling roles. Some are produced by the body internally (endocannabinoids). External cannabinoids include manmade versions and those present in plants, most famously the active ingredient in marijuana (THC).
Receptor shutdown by methylation
Endocannabinoid signaling is important to the normal functioning of the digestive system and has been shown to protect the colon against inflammation. Since chronic inflammation is a known risk factor for colorectal cancer, the researchers decided to look into the role of cannabinoid receptors in a mouse model of colon cancer.
“People have looked at cannabinoids in cancer earlier, mainly in cell culture experiments,” DuBois said. “The molecular mechanisms for loss of the receptor and its effect on cancer have not been previously shown.” First, the team found that CB1 was largely absent in 18 of 19 human tumor specimens and in 9 of 10 colorectal cancer cell lines. Further experimentation showed that the gene that encodes the CB1 protein was not damaged, but shut down chemically by the attachment of methyl groups – a carbon atom surrounded by three hydrogen atoms – to the gene encoding CB1. Treating cell lines with decitabine, a demethylating agent approved for some types of leukemia, removed the methyl groups, restoring gene expression in 7 of 8 cell lines and full expression of CB1 protein in three lines.
Next, the group found that deletion of the CB1 gene in a strain of mice that spontaneously develops precancerous polyps resulted in a 2.5-to-3.8-fold increase in the number of polyps and a 10-fold increase in the number of large growths, those most likely to develop into cancer.
Treating mice that had the CB1 receptor with an endocannabinoid agonist resulted in a decline in polyps ranging from 16.7 percent to 50 percent. The reduction was greater for larger polyps.
CB1 thwarts survivin, a protein that protects cancer
Cannabinoids previously had been shown to kill cancer cells in lab experiments by inducing apoptosis – programmed cell death. The team confirmed the role of CB1 in apoptosis, showing that tumor cells with high CB1 expression were sensitive to apoptosis when treated by a cannabinoid agonist. Cell lines with silenced CB1 resisted cell death.A series of experiments showed that CB1 increases cancer cell death by stifling a protein called survivin. Survivin is overexpressed in nearly every human tumor but is barely detectable in normal tissue, DuBois noted. Overexpression of survivin is associated with poor outcome and reduced apoptosis in colorectal cancer patients. The researchers pinpointed a cell signaling pathway by which activated CB1 cuts down survivin.“Just increasing the levels of cannabinoids to treat colorectal cancer won’t work if the CB1 receptor is not present,” DuBois said. This suggests that treating first with a demethylating agent, such as decitabine, to reactivate CB1 in the tumor and following up with a cannabinoid might be an effective attack on colorectal cancer. Scarcity of CB1 also is associated with Huntington’s disease, Alzheimer’s disease and multiple sclerosis. Further investigation, the researchers note, is needed to define its role in those diseases and other types of cancer. The team also analyzed the other main cannabinoid receptor, CB2, and found no role for it in colorectal cancer.They also treated the mice with a CB1 antagonist, a compound that binds to the receptor but does not
activate it. Mice with CB1 blocked in this manner also showed an increase in the number and size of polyps. A CB1 antagonist called rimonabant is currently marketed overseas for weight loss. The researchers note that a patient’s risk for colorectal cancer should be assessed when use “Just increasing the levels of cannabinoids to treat colorectal cancer won’t work if the CB1 receptor is not present,” DuBois said. This suggests that treating first with a demethylating agent,
such as decitabine, to reactivate CB1 in the tumor and following up with a
cannabinoid might be an effective attack on colorectal cancer. Scarcity of CB1 also is associated with Huntington’s disease, Alzheimer’s disease and multiple sclerosis. Further investigation, the researchers note, is needed to define its role in those diseases and other types of cancer. The team also analyzed the other main cannabinoid receptor, CB2, and found no role for it in colorectal cancer.
They also treated the mice with a CB1 antagonist, a compound that binds to the receptor but does not activate it. Mice with CB1 blocked in this manner also showed an increase in the number and size of polyps. A CB1 antagonist called rimonabant is currently marketed overseas for weight loss. The researchers note that a patient’s risk for colorectal cancer should be assessed when use of such drugs is being considered.
The study was funded by grants from the National Cancer Institute and the National Colorectal Cancer Research Alliance.
Co-authors with DuBois are first author Dingzhi Wang, Ph.D., Haibin Wang, Ph.D., Wei Ning, Michael Backlund, Ph.D., and Dushansu K. Dey, Ph.D., all of the Vanderbilt-Ingram Cancer Center.
Story Source:
The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by University of Texas M. D. Anderson Cancer Center, via EurekAlert!, a service of AAAS.
From Webpage :http://www.sciencedaily.com/releases/2007/08/070828084418.htm
A Gene For Metastasis
ScienceDaily (Aug. 29, 2007) — Colorectal cancer is one of the most prevalent cancers in the Western world. The tumor starts off as a polyp but then turns into an invasive and violent cancer, which often spreads to the liver. In an article recently published in the journal Cancer Research, Prof. Avri Ben-Ze’ev and Dr. Nancy Gavert of the Weizmann Institute’s Molecular Cell Biology Department reveal mechanisms that help this cancer metastasize. In a majority of cases, colorectal cancer is initiated by changes in a key protein — beta-catenin. One of the roles
of this protein is to enter the cell nucleus and activate gene expression. But in colorectal and other cancers, beta-catenin over-accumulates in the cell and inappropriately activates genes, leading to cancer. Surprisingly, one of the genes activated by beta-catenin, which had been previously detected in colorectal cancer cells by Ben-Ze’ev’s group, codes for a receptor called L1-CAM. This receptor is a protein usually found on nerve cells, where it plays a role in nerve cell recognition and motility. What is this receptor doing in cancer cells” Ben-Ze’ev’s previous research had shown that L1-CAM is only expressed on certain cells located
at the invasive front of the tumor tissue, hinting that it could be an important player in metastasis.
In this study, the scientists found that colorectal cancer cells engineered to express the L1-CAM gene indeed spread to the liver, while those cells lacking L1-CAM did not. In collaboration with Prof. Eytan Domany and research student Michal Sheffer of the Institute’s Physics of Complex Systems Department, Ben-Ze’ev then compared the expression of genes induced by L1-CAM in cultured colon cancer cells to those in 170 samples of colorectal cancer tissue removed from patients, and in 40 samples of normal colon tissue. Out of some 160 genes induced
by L1-CAM, about 60 were highly expressed in the cancerous tissue, but not in normal colon tissue. Ben-Ze’ev plans to conduct further research into the role of these genes, to uncover L1-CAM’s function in metastasis.
Prof. Avri Ben-Ze’ev’s research is supported by the Jean-Jacques Brunschwig Fund for the Molecular Genetics of Cancer; Curie–Weizmann; and the Eugene and Delores Zemsky Charitable Foundation Inc. Prof. Ben-Ze’ev is the incumbent of the Samuel Lunenfeld-Reuben Kunin Chair of Genetics.
Story Source : Adapted from materials provided by Weizmann Institute of Science.
The Journal of Pain, Vol 9, No 6 (June), 2008: pp 506-521
http://cdc.coop/docs/neuropathic_pain_wilsey.pdf
A Randomized, Placebo-Controlled, Crossover Trial of Cannabis Cigarettes in Neuropathic Pain Perspective: This study adds to a growing body of evidence that cannabis may be effective at ameliorating neuropathic pain, and may be an alternative for patients who do not respond to, or cannot tolerate, other drugs.
Psychoactive effects were minimal and well-tolerated.
© 2008 by the American Pain Society
Pain Unpleasantness
Pain unpleasantness, a measure of the emotional response to pain, was also measured by using a similar 100-mm VAS bordered by “not at all” at 0 and “extremely unpleasant” at 100. A trend for the treatment difference increase over time is found to be the same in 3.5% and 7% dose groups (mean difference change per minute 0.21, 95% CI: (0.33, 0.09), P .01), indicating that pain was more tolerable at higher cumulative doses of cannabis that it was with placebo.
The DEA also claims “At present, however, the clear weight of the evidence is that smoked marijuana is harmful. No matter what medical condition has been studied, other drugs already approved by the FDA, such as Marinol – a pill form of synthetic THC – have been proven to be safer and more effective than smoked marijuana.”
Omni Magazine, in 1982 “Marinol works as well as marijuana in only 13% of patients.”
It must also be noted Marinol is only available to cancer and HIV/AIDS patients.
Again, studies show otherwise, in an article “Marinol vs. Natural Cannabis
Pros, Cons and Options for Patients” By Paul Armentano, Senior Policy
Analyst – NORML/NORML Foundation, found on webpage :
http://www.kindgreenbuds.com/medical-marijuana/marinol_cannabis.html
Despite FDA approval, Marinol typically provides only limited relief to select patients, particularly when compared to natural cannabis and its cannabinoids.
Marinol should remain a legal option for patients and physicians; however, federal and state laws should be amended to allow for those patients who are unresponsive to synthetic THC the ability to use natural cannabis and its cannabinoids as a medical therapy without fear of arrest and/or criminal prosecution. By prohibiting the possession and use of natural cannabis and its cannabinoids, patients are unnecessarily restricted to use a synthetic substitute that lacks much of the therapeutic efficacy of natural cannabis.
I. Marinol Lacks Several of the Therapeutic Compounds Available in Natural
Cannabis Chemical compounds in cannabis, known as cannabinoids, are responsible for its numerous therapeutic benefits. Scientists have identified 66 naturally occurring cannabinoids.
The active ingredient in Marinol, synthetic delta-9-tetrahyrdocannabinol (THC), is an analogue of one such compound, THC. However, several other cannabinoids available in cannabis — in addition to naturally occurring terpenoids (oils) and flavonoids (phenols) — have also been clinically demonstrated to possess therapeutic utility. Many patients favor natural cannabis to Marinol because it includes these
other therapeutically active cannabinoids.
For example, cannabidol (CBD) is a non-psychoactive cannabinoid that has been clinically demonstrated to have analgesic, antispasmodic, anxiolytic, antipsychotic, antinausea, and anti-rheumatoid arthritic properties.
Animal and human studies have shown CBD to possess anti-convulsant properties, particularly in the treatment of epilepsy. Natural extracts of CBD, when administered in combination with THC, significantly reduce pain, spasticity and other symptoms in multiple sclerosis (MS) patients unresponsive to standard treatment medications.
Clinical studies also demonstrate CBD to be neuroprotective against glutamate neurotoxicity (i.e. stroke), cerebral infarction (localized cell death in the brain), and ethanol-induced neurotoxicity, with CBD being more protective against glutamate neurotoxicity than either ascorbate (vitamin C) or alpha-tocopherol (vitamin E). Clinical trials have also shown CBD to possess anti-tumoral properties, inhibiting the growth of glioma (brain tumor) cells in a dose dependent manner and selectively inducing apoptosis (programmed cell death) in malignant cells.
Additional cannabinoids possessing clinically demonstrated therapeutic properties include: cannabinol (anticonvulsant and anti-inflammatory activity); cannabichromine (anti-inflammatory and antidepressant activity); and cannabigerol (anti-tumoral and analgesic activity). Natural cannabis’ essential oil components (terpenoids) exhibit anti-inflammatory properties and its flavonoids possess
antioxidant activity. Emerging clinical evidence indicates that cannabinoids may slow disease progression in certain autoimmune and neurologic diseases, including multiple sclerosis (MS), Amyotrophic Lateral Sclerosis (Lou Gehrig’s disease) and Huntington’s Disease.
Clinical data indicate that the synergism of these compounds is likely more efficacious than the administration of synthetic THC alone. For example, McPartland and Russo write: “Good evidence shows that secondary compounds in cannabis may enhance beneficial effects of THC. Other cannabinoid and non-cannabinoid compounds in herbal cannabis … may reduce THC-induced anxiety, cholinergic deficits, and immunosuppression. Cannabis terpenoids and flavonoids may also increase cerebral blood flow, enhance cortical activity, kill
respiratory pathogens, and provide anti-inflammatory activity.” In an in vitro model of epilepsy, natural cannabis extracts performed better than THC alone. In human trials, patients suffering from multiple sclerosis experienced greater symptomatic relief from sublingual natural cannabis extracts than from the administration of oral THC. In 2005, Health Canada approved the oral spray Sati vex — which contains precise ratios of the natural cannabinoid extracts THC and CBD, among other
compounds — for prescription use for MS-related symptoms.
II. Marinol is More Psychoactive Than Natural Cannabis
Patients prescribed Marinol frequently report that its psychoactive effects are far greater than those of natural cannabis. Marinol’s adverse effects include: feeling “high,” drowsiness, dizziness, confusion, anxiety, changes in mood, muddled thinking, perceptual difficulties, coordination impairment, irritability, and depression.
These psychoactive effects may last four to six hours. About one-third of patients prescribed Marinol report experiencing one or some of these adverse effects.
Marinol’s oral route of administration is responsible, in part, for its heightened psychoactivity compared to inhaled cannabis. Once swallowed, Marinol passes from the stomach to the small intestine before being absorbed into the bloodstream.
Following absorption, Marinol passes through the liver where a significant proportion of the drug is metabolized into other chemicals. One of these chemicals, 11-hydroxy-THC, may be four to five times more potent than natural THC, and is produced in greater quantities. Thus, patients administered Marinol experience the psychoactive effects of both THC and 11-hydroxy-THC, greatly increasing the likelihood that they will suffer from an adverse psychological reaction.
By comparison, only minute quantities of 11-hydroxy-THC are produced when cannabis is inhaled.
Moreover, Marinol lacks the compound cannabidiol, which possesses anxiolytic activity and likely modifies and/or diminishes much of THC’s psychoactivity in natural cannabis.
III. Cannabis Vaporization Offers Advantages Over Orally Administered THC
Vaporization is an alternative method of cannabis administration that holds distinct advantages over both smoking and oral administration. Cannabis vaporization suppresses respiratory toxins by heating cannabis to a temperature where cannabinoid vapors form (typically around 180-190 degrees Celsius), but below the point of combustion where noxious smoke and associated toxins (i.e., carcinogenic hydrocarbons) are produced (near 230 degrees Celsius).
Although a comprehensive review of cannabis and health conducted by the National Academy of Sciences Institute of Medicine found “no conclusive evidence that marijuana causes cancer in humans, including cancers usually related to tobacco use,” studies have found that heavy cannabis smokers face a higher risk of contracting bronchitis and respiratory illnesses. This risk is likely not due to the inhalation of cannabinoids, but rather to the exposure of noxious smoke.
Because vaporization can deliver therapeutic doses of cannabinoids while reducing the users intake of pyrolytic smoke compounds, it is considered to be a preferred and likely safer method of cannabis administration than smoking.
In practice, cannabis vaporization offers considerable advantages over oral THC consumption. While the oral ingestion of Marinol avoids the potential risks of smoking, it has significant drawbacks. Because of synthetic THC’s poor bioavailability, only 5-20 percent of an oral dose ever reaches the bloodstream and the drug may not achieve peak effect until four hours after dosing. Moreover, because Marinol is metabolized slowly, its therapeutic and psychoactive effects may be unpredictable and vary considerably, both from one person to another, and in the same person from one episode of use to another. By contrast, cannabis
vaporization delivers cannabinoids to the bloodstream almost instantaneously.
Vaporization’s rapid onset also allows patients to self regulate their dosage of cannabinoids by immediately ceasing inhalation when/if their psychoactive effects become unpleasant. After oral administration of Marinol, patients have no choice but to experience the full psychoactive effects of the dose consumed. These dysphoric effects may last several hours.
Because of its rapid onset, vaporized cannabis is more desirable than Marinol for patients requiring a fast-acting therapeutic agent, such as those combating oncoming attacks of nausea, seizures or muscle spasms. Cannabis vaporization also offers a unique advantage to patients suffering from nausea and vomiting because it allows them an
alternative delivery route to swallowing. Cancer and HIV/AIDS patients often report that their stomachs cannot hold down Marinol capsules during bouts of severe nausea and many rely on natural cannabis and cannabinoids for symptom control. In a 1994 survey of oncologists, respondents ranked synthetic THC ninth on a list of available
antiemetic medications. In another survey of oncologists, 44 percent of respondents said that they believed natural cannabis to be more efficacious than oral synthetic THC; only 13 percent of respondents rated Marinol more effective. A 1997 survey of physicians found that a majority preferred megestrol acetate over Marinol as an appetite stimulant in patients with HIV/AIDS.
As a result of Marinol’s slow onset and poor bioavailablity, scientists are now in the process of developing a new formulation of pulmonary dronabinol, delivered with a pressurized metered dose inhaler. In a Phase I study, pulmonary Marinol delivered via an inhaler provided rapid systemic absorption. Unlike oral synthetic THC, it’s possible that pulmonary Marinol “could offer an alternative for patients when a fast onset of action is desirable.” However, FDA approval of pulmonary Marinol and/or its inhaler remains years away. Sativex, an oral cannabis spray consisting of natural cannabinoid extracts, has greater bioavailability and is faster acting than oral synthetic THC.
Clinical trials comparing its bioavailability and time of peak onset compared to vaporized cannabis have not been performed, though anecdotal reports indicate that vaporized cannabis and its cannabinoids likely possess greater bioavailability and are faster acting than the Sativex spray.
IV. Marinol is More Expensive Than Natural Cannabis ( current prices, at least where I live. 5mg pill is $20.00each and the 10mg is $30.00 at the pharmacy)
Synthetic THC is a costly and difficult compound to manufacture. Much of this cost is passed on to the patient consumer, particularly if the full cost of Marinol (approximately $200 to $800 per month, depending on the dosage) is borne out of pocket. Patients, particularly those with chronic conditions, often report that Marinol’s market cost limits their use of the drug. Doctors also report that Marinol’s high cost dissuades them from prescribing it to patients. In one survey of HIV/AIDS
specialists, among respondents who had never prescribed Marinol to their patients, 33 percent cited the high cost of the drug as the reason. Natural cannabis, even at its inflated black market value, often remains far less costly for patients than oral synthetic THC.
V. Patients Ultimately Prefer Natural Cannabis to Marinol
In the 1970s and 1980s, several states conducted patient trials of natural cannabis’ effectiveness as an anti-emetic in cancer patients unresponsive to conventional therapies. Some state protocols allowed patients to choose between inhaled cannabis and synthetic THC. In those studies which compared natural cannabis to dronabinol, inhaled cannabis was equal to or better than the oral administration of synthetic THC.
For example, researchers at the Tennessee Board of Pharmacy found a “23 percent higher success rate among those patients smoking than among those patients administered THC capsules” in the treatment of nausea and/or vomiting associated with cancer chemotherapy.
Researchers in New Mexico observed similar findings. “When the routes of [drug] administration were analyzed separately, it was found that inhalation was far superior to ingestion: 90.39 percent of the patients in the group that inhaled the marijuana showed improvement while only 59.65 percent of the patients in the group that orally ingested the delta-9-THC showed improvement,” they concluded.
Researchers at the California Board of Pharmacy found that inhaled cannabis and oral THC produced similar results in patients. However, physicians still rated natural cannabis as slightly more effective than oral THC as an anti-emetic.
A 1988 New York State pilot study comparing inhaled cannabis to oral THC in cancer chemotherapy patients who were unresponsive to standard antiemetic agents found:
“Twenty-nine percent of patients who failed oral THC responded to the cigarette form. … Our results demonstrate that inhalation marijuana is an effective therapy for the treatment of nausea and vomiting due to cancer chemotherapy.”
Today, several patient populations continue to use natural cannabis and its cannabinoids in large numbers despite its illegality and the availability of Marinol.
A 2005 British survey of more than 500 HIV/AIDS patients found that one-third of respondents use natural cannabis for symptomatic relief, with more than 90 percent of them reporting that it improves their appetite, muscle pain and other symptoms. A previous US survey found that approximately one out of four patients with HIV had used natural cannabis medicinally in the past month.
Cannabis use is also prevalent among patients with neurologic disorders. Nearly four out of ten Dutch patients with prescriptions for “medical grade cannabis”
(cannabis provided by Dutch pharmacies with a standardized THC content of 10.2 percent) use it to treat MS or spinal cord injuries, according to survey data published in 2005 in the journal Neurology. Perceived efficacy is greater among respondents who inhale cannabis versus those who ingest it orally, the study found.
A 2002 British survey of MS patients found that 43 percent of respondents used natural cannabis therapeutically, with about half admitting they used it regularly.
Seventy-six percent said they would do so if cannabis were legal. A Canadian survey of MS patients found that 96 percent of respondents were “aware cannabis was potentially therapeutically useful for MS and most (72 percent) supported [its] legalization for medicinal purposes.” Sixteen percent of respondents answered that they use natural cannabis for medical purposes to treat symptoms of anxiety/depression, spasticity and chronic pain.
A more recent Canadian survey published in Neurology reported that 14 percent of MS76 patients and 21 percent of respondents with epilepsy had used medical cannabis in the past year. Among epileptics, twenty-four percent of respondents said that they believed that cannabis was an effective therapy for the disease. A 2002 survey of patients with Parkinson’s Disease (PD) found that 25 percent of respondents had tried cannabis, with nearly half of those saying that it provided them symptomatic relief.
http://www.cannabismd.net/history-of-medical-cannabis/2008/8/4/history-of-medical-cannabis.html
Modern hybridization has altered the natural inclinations of the cannabis plant as growers have sought to promote particular traits, blurring distinction between the two primary species. However, those natural tendencies remain at least partially visible.
Typically, the tall stalks of Cannabis sativa are cultivated for fiber and seed industries, while the short Cannabis indica bushes are cultivated for the medicinal and psychoactive properties of their flowers. Cannabis sativa grown for industrial uses usually contains only minor amounts of psychoactive compounds. Proper cultivation can produce higher levels of therapeutic compounds in some types of Cannabis sativa. The more potent Cannabis indica varieties, on the other hand, are not suitable
for industrial fiber production due to the shortness of their bushy stalks. While this contrast distinguishes the natural tendencies of the two primary varieties, many medicinal growers have discovered that the most potent strains combine the best traits of both.
There are 30million patients with rare diseases, and many with autoimmune diseases, for which there is little (marginal effects) or no available treatment at all, and no known cures. Many of the treatments have side effects that can cause many detrimental additional health problems, some fatal. These patients have little to no hope or chance of any form of recovery. Many of the patients of these rare diseases
only have available temporary relief of the symptoms. We need more of a sense of urgency with this suffering population. Waiting 10, 20 to 30 years for pharmaceutical companies to manufacture a chemical component is just not an option. The Risk vs. Benefit ratio needs to be taken into consideration especially with these patients.
http://www.fda.gov/ohrms/dockets/dailys/02/Aug02/082202/80022395.pdf
Page 6
“The long-term use of high dosages of analgesics, especially combination products that also contain caffeine or codeine, can cause a specific form of renal disease known as analgesic nephropathy. This disease is characterized by renal papillary necrosis and chronic interstitial nephritis. It is different from NSAID-related renal toxicity, which is associated with acute renal failure. Analgesic nephropathy is a
chronic, progressive disorder that develops with years or decades of analgesic use.
It appears to require daily consumption of analgesics for a period of at least five years.
However, it has also been observed with acetaminophen and aspirin, especially when the two drugs are used in combination. Symptoms of analgesic nephropathy include headache, malaise, weight loss, flank pain and dyspepsia. Signs include hypotension, mild proteinuria and impaired urinary concentration.
Analgesics and caffeine may exert direct toxic effects on kidney cells. In one study that examined the effects of aspirin, NSAIDs, acetaminophen and caffeine, either alone or in combination, on renal medullary cells in a cell culture system, all of these drugs were directly toxic to cultured renal inner medullary cells.2’ The combination of acetaminophen and caffeine produced a large synergistic effect, a finding that seems to fit well with the role of caffeine-containing products in the risk of analgesic
nephropathy.”
We are talking Kidneys here!
Inhaled technologies are currently accepted and used as a delivery system for a variety of medications. In medicine, a nebulizer is a device used to administer medication in the form of a mist inhaled into the lungs.
Examples include :
Death-in-Patients-with-COPD-14122-1/
Inhaled Corticosteroids Reduce Death in Patients with COPD
Patients with chronic obstructive pulmonary disease (COPD) who use inhaled corticosteroids may have a significantly decreased mortality risk// , according to a new study published in the September issue of CHEST, the peer-reviewed journal of the American College of Chest Physicians (ACCP). New research shows that patients who received inhaled corticosteroids within 30 days of hospital discharge
had a 25 percent reduced all-cause mortality rate. Cardiovascular-related death alone in patients using steroids paired with beta-agonists was reduced by 38 percent.
Inhaled Steroids Used as Preventive Treatment Post 9/11
CHICAGO, Oct. 24 /PRNewswire/ — inhaled corticosteroids (ICS),
anti-inflammatory treatments often prescribed for asthma, may be beneficial in preventing respiratory illness, according to a new study. The research, presented at CHEST 2007, the 73rd annual international scientific assembly of the American College of Chest Physicians (ACCP), examined the effectiveness of ICS in preventing asthma and other respiratory illness due to inhalation exposures experienced by NYC firefighters after the World Trade Center (WTC) collapse.
Two years post-collapse, those firefighters treated with ICS reported positive feedback.
“Respiratory protection is often needed during disasters, but it is difficult to get it instantly, and many responders, without EMS or fire experience, have not been trained or fit-tested to wear equipment properly. Couple this with a disaster environment that is difficult in which to function, and it leads to exposures that could result in lung damage,” said study author David Prezant, MD, FCCP, Chief Medical Officer, Office of Medical Affairs and Co-Director WTC Medical Monitoring and Treatment Programs, New York City Fire Department. “However, our preliminary data suggest that combining prophylactic inhaled corticosteroids
with our best attempts to provide proper respiratory protection could reduce declines in lung function.”
Inhaling Concentrated Saline Could Benefit Cystic Fibrosis Patients
Researchers at the University of North Carolina (UNC) at Chapel Hill have revealed that inhaling hypertonic saline is good for the lungs of patients affected by cystic fibrosis (CF). Hypertonic saline// is a water-based salt solution with excess concentration of the salt. The researchers arrived at this conclusion after testing 24 patients aged 14 or older for two weeks., They found that inhaling the salt solution improved the health of the lungs and the mucus clearance was better. Lung function in general also showed a marked improvement.
The study titled “Sustained Improvement in Mucus Clearance and Lung Function in Cystic Fibrosis with Hypertonic Saline” will appear in the January 19 issue of the New England Journal of Medicine (NEJM). The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) and by the Cystic Fibrosis Foundation funded this particular study. Cystic fibrosis is a chronic, genetic often-fatal disease that affects children right from the birth. The most common cause of death is respiratory failure and this study if applicable in young
children as well as adults could delay the advent of lung damage due to the disease.
The UNC researchers say that concentrated saline helps by clearing the bacteria and debris in the airway and providing a relatively bacteria-free passage to inhaled air. Repeated lung infections are though to weaken the respiratory system in this disease.
For more information, please visit http://www.nhlbi.nih.gov .
Contact NHLBI Communications Office NHLBI_news@nhlbi.nih.gov
NIH/National Heart, Lung, and Blood Institutehttp://www.nhlbi.nih.gov
Date:1/21/2006
While
http://www.bio-medicine.org/medicine-news/Inhaling-Salt-Can-Lead-To-Hypertension-4068-1/
Inhaling Salt Can Lead To Hypertension
People working in the salt factories may be at a heightened risk from hypertension as they inhale salt// during their course of work.
Scientists from the Desert Medicine Research Centre in Jodhpur, India had measured the blood pressure of workers in two salt milling factories in Rajasthan.
They divided the workers into two groups: those working close to a salt milling plant and were directly involved in crushing, grinding, milling and packing salt and those who worked far away from the salt milling plant and were much less exposed to salt particles.
The results of the study show that the first group of workers had a mean systolic blood pressure of 122.1 mmHg, which is significantly higher than the mean systolic blood pressure of 118.8 mmHg measured in the second group.
In addition, workers from the first group had an incidence of hypertension of 12.2 percent compared to an incidence of 7.0 percent in the second group.
Wearing facemasks and plastic spectacles for four days caused the mean systolic
blood pressure of workers from the first group to drop significantly from
127.8 mmHg on the first day to 117.5 mmHg on the fourth day, the study said.
“This is a new observation, though it is in line with the hypothesis that, after being inhaled, salt may be absorbed from respiratory tract or the gastrointestinal tract.
Consequent increases in plasma sodium may be responsible for increase in blood pressure,” the researchers said.
Their findings also suggest that workers in factories such as the ones studied could easily protect themselves from the negative effects of exposure to salt particles by wearing masks and glasses.
A high consumption of salt is known to be directly linked to high blood pressure and the development of cardiovascular and kidney diseases, which are major causes of mortality worldwide.
It is important to remember we are not discussing healthy individuals here, but those suffering with rare diseases and autoimmune diseases. Such as the difference between healthy workers inhaling salt and those with cystic fibrosis.
Bayer is to collaborate with Nektar on the development of an inhaled formulation of Cipro (ciprofloxacin) for treating the common genetic disorder cystic fibrosis.
The aim of the project is to develop a dry powder formulation of ciprofloxacin that could be used to treat infections CF patients.
Related topics: Materials & Formulation, Drug delivery systems
Nektar Therapeutics is planning to buy fellow drug delivery specialist Aerogen for
$32 million (€26m), boosting its position in respiratory technologies.
Nektar is already a leader in drug delivery, with several approved products using its pegylation technology – used to improve the half-life of injectable drugs. It also has a strong portfolio of inhaleable drugs, most notably its inhaled insulin product Exubera for diabetes, partnered with Pfizer, which has been filed for approval in both the US and Europe.
The addition of Aerogen will shore up Nektar’s inhaled delivery portfolio, adding in liquid delivery technologies to complement Nektar’s powdered drug capabilities.
Aerogen’s lead liquid drug delivery platform is the OnQ Aerosol Generator, an electonic micropump that produces a fine liquid mist of precisely defined particle sizes which, according to the company, can be tailored for respiratory therapy or absorption into the blood via the lungs for systemic delivery. It is capable of delivering a broad range of drugs in solution or suspension, including proteins and peptides.
OnQ (pictured) is comprised of a unique dome-shaped aperture plate containing over 1,000 precision-formed tapered holes, surrounded by a vibrational element.
When energy is applied, the aperture plate vibrates over 100,000 times per second.
This rapid vibration causes each aperture to act as a micropump, drawing liquid through the holes to form consistently sized droplets. The result is a low-velocity liquid aerosol.
http://www.lfh.org/nuclear_medicine
Nuclear Medicine
In nuclear medicine, very small, safe doses of radioactive material are administered by mouth, IV, or they are inhaled as a gas. They then localize in a specific organ and special cameras produce images of organ function. At Northwestern Lake Forest Hospital Diagnostic Imaging Centers, we use nuclear medicine to detect tumors, infections and other disorders.
Posted on: Saturday, 28 January 2006, 15:00 CST
By Bruce Japsen, Chicago Tribune
medication-delivery option a potential alternative for “many of the more than 5
million Americans who take insulin injections.” It’s the first new delivery mechanism
for the treatment of adult patients with diabetes since the discovery of insulin in the
1920s.
Prior to the drug’s approval, “patients with diabetes who need insulin to manage
their disease had only one way to treat their condition,” said Dr. Steven Galson,
director of the FDA’s Center for Drug Evaluation and Research. “It is our hope
that the availability of inhaled insulin will offer patients more options to better
control their blood sugars.”
http://www.healthtech.com/datamonitor/inhalabledrugs/
suitable inhaled formulations. It represents an opportunity to provide an effective
delivery route for therapeutics, such as proteins, that are suitable for oral
administration. The delivery of insulin via inhalation has been suggested as a major commercial opportunity, However, commercial success necessitates identifying stable and effective formulations, combined with a suitable, convenient, device for delivering the inhaled formulation.
This report evaluates the current state of the inhaled market, examining the currently limited impact of inhaled formulations in non-respiratory segments and the dominance of the respiratory market, a major market segment, by inhaled formulations. It examines the formulations currently in development for both non-respiratory and respiratory indications as well as summarizing the inhaled formulations of new chemical entities being developed for the treatment of respiratory
disease. The development of methods of delivering biological products by inhalation is highlighted as a major opportunity for growth. The value of formulation and inhaler developments is highlighted by case histories that show how they can play a key role in product lifecycle management, by building and sustaining blockbuster revenues; while not providing suitable inhalers can lead to high profile, and very costly, failure. The critical role of specialist companies in advancing technological
developments with inhalers and inhaled formulations is highlighted, with the commercial opportunities that can be afforded by partnerships with such companies examined.
Key features of this report
- Analysis of inhaled drug market for both respiratory and non-respiratory indications.
- Detailed analysis of inhaled respiratory market, both by chemical
entity/formulation and by inhaler device type.
- Discussion of inhaled formulations in development and assessment of
opportunities offered, highlighting the current emphasis on developing new combination formulations and the challenges of developing inhaled protein formulations.
Key Market Issues
- Inhaled therapeutics represent a significant segment of the pharmaceutical market, generating revenues of $26.3 billion in 2008, and accounted for 78% of the revenues in the respiratory market segment.
- Growth opportunities are provided by the development of inhaled formulations of new chemical entities, or by developing and establishing inhaled formulations of other classes of agent, especially protein therapeutics.
- The high value of the combination steroid long acting b2 agonist segment ($10 billion) provides considerable opportunities for third parties to develop competing formulations of generically available agents.
Key findings from this report
- Revenues from inhaled therapeutics for non-respiratory indications are modest.
- Inhaled therapeutics dominate the respiratory market segment.
- There is increasing emphasis on the use of, and developing new, dry powder inhalers.
- The use of nebulizers is confined to certain classes of drug and specific indications,
in part due to their size and lack of portability.
- Pressurized metered dose inhalers remain a key delivery option for some classes of
drug.
- Inhaled combination formulations represent substantially the most valuable class of
inhaled therapeutics.
Key questions answered
- Where are the major opportunities in the inhaled therapeutic market?
- What strategies should be considered in developing inhaled products?
- Which companies have an expertise in developing proprietary inhaler devices?
- Which companies have expertise in developing inhaled formulations?
- Where are the commercially viable opportunities for developing inhaled
formulations of systemically acting agents?
Table of Contents
Drug Delivery Innovation in Inhalation Executive summary 10
Introduction 10
Respiratory diseases 11
Non-respiratory indications 12
New opportunities 12
Case studies 13
Specialist companies 14
New developments & market opportunities 15
Chapter 1 Introduction 18
Summary 18
Advantages of lung delivery of drugs 19
Formulations and devices 19
Nebulizers 19
Metered dose inhalers 20
Dry powder inhalers 21
Inhaled drug market 21
Respiratory diseases 22
Respiratory infections 24
Systemic diseases 25
An entry barrier for generics 25
Devices and innovation 26
New therapeutic opportunities 27
Chapter 2 Respiratory indications 30
Summary 30
Introduction 31
Respiratory diseases 31
Overview 31
Asthma 31
COPD 32
Cystic fibrosis 33
Rationale for using inhaled therapeutics 34
Devices 35
Innovation 35
Types of device 36
Nebulizers 38
Metered dose inhalers 39
Dry powder inhalers 40
Soft mist inhalers 41
Current classes of inhaled drug 42
Short acting 2 agonists 42
Long acting 2 agonists 44
Muscarinic antagonists 45
Corticosteroids 46
Combination products 48
2 agonists and anticholinergics 49
Corticosteroids and LABA 49
Chapter 3 Non-respiratory indications 54
Summary 54
Introduction 55
Strategic rationale 55
Delivery requirements 56
Respiratory infections 56
Pulmonary hypertension 57
Diabetes 59
Chapter 4 New opportunities 62
Summary 62
Introduction 63
New indications 63
Diabetes 64
CNS diseases 65
Migraine 66
Pain 67
Sexual dysfunction 67
Cancer 68
Vaccines 68
Antibiotics 68
New respiratory targets 69
Dual 2 agonists and Muscarinic antagonists (MABA) 70
Avoiding side effects 72
Ion channel modulators 73
Protein therapeutics 73
Oligonucleotides 76
New respiratory products 77
Monotherapies 78
Combination products 82
Chapter 5 Case studies 88
Summary 88
Introduction 89
Pulmicort 89
Formulation 89
Commercial 90
Strategy 92
Flutiform 93
Strategy 95
Commercial 96
Approval 97
Exubera 98
The device 99
Other issues 100
The cost to Pfizer 101
Conclusion 103
Chapter 6 Specialist companies 106
Summary 106
Introduction 107
3M Drug Delivery Systems 107
Activaero Technologies 108
airPharma 108
Akela Pharma 108
Alexza Pharmaceuticals 109
Alkermes 110
Almirall Sofotec 110
Altair Therapeutics 111
Aradigm 111
Battelle 112
Cambridge Consultants 112
Dance Pharmaceuticals 113
Direct-Haler A/S 113
Enhanced Pharmaceuticals 113
Inhaleness BV 114
IVAX 114
Kamada 114
Mannkind 115
MAP Pharmaceuticals 116
Meda AB 117
MicroDose Therapeutix 117
Nektar Therapeutics 119
Novaliq GmbH 119
Omron Healthcare 120
Oriel Therapeutics 120
Orion Corp. 121
PARI Pharma 121
Pearl Therapeutics 122
Prosonix 123
Respirics 123
Skye Pharma 124
Vectura Group 125
Chapter 7 New developments & market opportunities 128
Summary 128
New developments 129
Regulatory perspective 129
Inhaled particle distribution 130
Formulation technologies 131
Propellants 131
New aerosol generation approaches 133
Particle engineering 134
Inhaler technologies 136
DPIs 136
MDIs 138
Other inhalers 141
Biologic therapeutics 142
Oligonucleotides 142
Proteins 142
Deals and collaborative opportunities 144
Market opportunities 146
Drug types 146
New indications 146
Generic opportunities 147
Commercial deals 148
Appendix 149
Bibliography 149
Glossary 152
Index 154
List of Figures
Figure 1.1: Inhaled drug market share by indication 22
Figure 1.2: The dominance of the respiratory market by inhaled therapies 23
Figure 2.3: Opportunities for innovation 36
Figure 2.4: 2008 Market share breakdown of the respiratory market by inhaler
device type 37
Figure 2.5: Product share of short acting 2 agonists, 2008 43
Figure 2.6: Devices used for short acting 2 agonists 44
Figure 2.7: US sales of Advair, Serevent and Flixotide ($m), 2000-08 51
Figure 5.8: Pulmicort sales ($m) & impact of new delivery forms, 1991-2009 91
Figure 5.9: Exubera inhalation device 100
Figure 5.10: Exubera – the cost of failure 102
Figure 7.11: Semi-fluorinated alkanes (SFAs) 132
Figure 7.12: Improving MDIs 139
List of Tables
Table 2.1: Time line of key developments in inhaler technology 37
Table 2.2: Significant branded inhaled steroid products 47
Table 2.3: Inhaled corticosteroid plus LABA combination formulations 50
Table 4.4: Inhaled formulations in development for CNS conditions 65
Table 4.5: Inhaled NCE formulations in development for respiratory diseases 71
Table 4.6: Long acting agonists in clinical development 80
Table 4.7: Long acting muscarinic antagonists in clinical development 82
Table 4.8: New Steroid + LABA combination formulations in development 85
Table 4.9: Muscarinic antagonist combination formulations in development 86
Table 6.10: Alexza’s Staccato formulations in development 110
Table 6.11: Aradigm’s development pipeline of inhaled formulations 112
Table 6.12: MAPP’s development pipeline of inhaled formulations 117
Table 6.13: MicroDose’s development pipeline of inhaled formulations 118
Table 6.14: Oriel’s development pipeline of inhaled formulations 121
Table 6.15: PARI Pharma’s development pipeline of inhaled formulations 122
Table 6.16: Vectura’s development pipeline of inhaled formulations 126
Table 7.17: Summary of characteristics of newer DPIs 137
The book is available for $3,835 Delivering Opportunities in the Inhalable Drugs
Market.
FDA has wide control and can waive any and all process, control, and requirements
for orphan drug and orphan diseases. The FDA needs to accept the Marijuana has
medicinal value and reschedule it on the Schedule of Controlled Substances. The
FDA is responsible for protecting the public health not pharmaceutical companies
profits. Placing cannabis/marijuana on Schedule l l and limiting it’s use to only what
it is currently considered effective for in accordance of the states that currently permit
it’s use and what has been accepted in the medical and science community including
rare and autoimmune diseases especially for those who are allergic to NSAIDs and
other chemicals, those suffering from toxicity of current medicines and those which
have no current available treatments or those whose available treatments cause
detrimental additional health problems, some of which are fatal and those which
cannabinoids have been shown to be effective is the responsible thing to do.
Pharmaceutical cannabis/marijuana must be grown in this nation only, absolutely
no imported cannabis/marijuana and most importantly without any chemicals, most
of these patients cannot tolerate any chemicals, with the use of natural substances
only, garlic is an excellent and safe pest repellant, fish emulsion and bat guano are
safe effective natural fertilizers. All pest repellant and fertilizer must stop at least 2
weeks before harvest to give the plant time to flush out all substances. CO2 used in
the last stage provides ultimate conditions for food sugars to develop in the plant.
( I have never grown the plant, as you can tell I know how to research.) The side
effects of cannabis/marijuana pales in comparison to the chemical pharmaceuticals.
No one ever died from cannabis/marijuana.
Book chapters can also be found here :
>http://www.jackherer.com/chapters.html There is no pharmacological free lunch in cannabis or any drug. Negative reactions can result. A small percentage of people have negative or allergic reactions to marijuana. Heart patients could have problems, even though cannabis generally relieves stress, dilates the arteries, and in general lowers the diastolic pressure. A small percentage of people get especially high heart rates and anxieties with cannabis. These persons should not use it. Some bronchial asthma sufferers benefit from cannabis; however, for others it may serve as an additional irritant.Side effects/safety comparisons with other medications for various diseases :
http://www.alternet.org/drugs/80448/
March 21, 2008 |
According to a little noticed January report from the Centers for Disease Control(CDC), drug overdoses killed more than 33,000 people in 2005, the last year for which firm data are available. That makes drug overdose the second leading cause of accidental death,
behind only motor vehicle accidents (43,667) and ahead of firearms deaths (30,694).
What’s more disturbing is that the 2005 figures are only the latest in such a seemingly inexorable increase in overdose deaths that the eras of the 1970s heroin epidemic and the 1980s crack wave pale in comparison. According to the CDC, some 10,000 died of overdoses in 1990; by 1999, that number had hit 20,000; and in the six years between then and 2005, it increased by more than 60%.
Book chapters can also be found here :http://www.jackherer.com/chapters.html
Page 51
Marijuana was America’s number one analgesic for 60 years before the rediscovery of aspirin around 1900. From 1842 to 1900 cannabis made up half of all medicine sold, with virtually no fear of its high.
For those of us who can not take aspirin or other NSAIDs in comparison to narcotic painkillers cannabis/marijuana offers a relief with a much milder “high”, less physically addictive, and less damaging side effects. Page 59
ASTHMA
More than 15 million Americans are affected by asthma. Smoking cannabis (the “raw drug” as the AMA called it) would be beneficial for 80% of them and add 30-60 million person-years in the aggregate of extended life to current asthmatics over presently legal toxic medicines such as the Theophylline prescribed to children. “Taking a hit of marijuana has been known to stop a full blown asthma attack.”
(Personal communication with Dr. Donald Tashkin, December 12, 1989 and December 1, 1997.) The use of cannabis for asthmatics goes back thousands of years in literature. American doctors of the last century wrote glowing reports in medical papers that asthma sufferers of the world would “bless” Indian hemp cannabis) all their lives. Today, of the 16 million American asthma sufferers, only Californians, with a doctor’s recommendation, can legally grow and use cannabis medicines, even though it is generally the most effective treatment for asthma.
(Tashkin, Dr. Donald, UCLA Pulmonary Studies (for smoked marijuana), 1969-97;Ibid., asthma studies, 1969-76; Cohen, Sidney & Stillman, Therapeutic Potential of Marijuana, 1976; Life Insurance Actuarial rates; Life shortening effects of childhood asthma, 1983.)
Page 60-61
EPILEPSY, MULTIPLE SCLEROSIS, BACK PAIN, MUSCLE SPASMS
Cannabis users’ epileptic seizures are of less intensity than the more dangerous seizures experienced by users of pharmaceuticals. Similarly, smoking cannabis has proven to be a major source of relief for multiple sclerosis, which affects the nervous system and is characterized by muscular weakness, tremors, etc. Aside from addictive morphine, cannabis, whether smoked or applied as an herbal pack or poultice, is also the best muscle relaxant, back spasm medicine and general antispasmodic medication on our planet. In September 1993, in Santa Cruz County, California, Sheriffs rearrested eqileptic Valerie Corral and confiscated the five marijuana plants she was growing for medicine even though 77% of the citizens of Santa Cruz voted in November 1992 to instruct local law enforcement not to prosecute medical marijuana users. Charges against Corral had been dropped earlier in March 1993 because she was the first person in California to meet all six points of a medical necessity defense. In 1997, Valerie, who runs a compassionate use club, was named Citizen of the Year in Santa Cruz. (Cohen & Stillman,
Therapeutic Potential of Marijuana, 1976; Consult U.S. Pharmacopoeia prior to 1937; Mikuriya, Tod H., M.D., Marijuana Medical Papers, 1839-1972.)
Page 61
ANTIBIOTIC CBD DISINFECTANTS
Young un-budded hemp plants provide extractions of CBDs (cannabidiolic acids).
There are many antibiotic uses of the cannabidiols, including treatment for
gonorrhea. A 1990 Florida study indicated its use in treating herpes. The acid side
of tetrahydrocannabinol, cannabidiols occur inversely to the amount of the plant’s
THC and is therefore more acceptable to prohibitionists because “it won’t get you
high.” For virtually any disease or infection that can be treated with terramycin,
cannabis derivatives did better in Czechoslovakian studies, 1952-1955. The Czechs
in 1997 still published farm crop reports on strategies to grow cannabidiol rich hemp.
(Also see Cohen & Stillman, Therapeutic Potential of Marijuana; Mikuriya,
Tod H., M.D., Marijuana Medical Papers; Roffman, Marijuana as Medicine, 1982;
International Farm Crop abstracts.)
ARTHRITIS, HERPES, CYSTIC FIBROSIS AND RHEUMATISM
Cannabis is a topical analgesic.2Until 1937, virtually all corn plasters, mustard
plasters, muscle ointments, and fibrosis poultices were made from or with cannabis
extracts. Rheumatism was treated throughout South America until the 1960s with
hemp leaves and/or flower tops heated in water or alcohol and placed on painful
joints. In fact, this form of herbal medicine is still widely used in rural areas of
Mexico, Central and South America, and by California Latinos for relief of
rheumatism and arthritis pain. Direct contact with THC killed herpes virus in a
University of South Florida (Tampa) 1990 research study by Dr. Gerald Lancz,
who warns that “smoking marijuana will not cure herpes.” However, anecdotal
reports indicate a faster drying and healing of the outbreak after topical application
of “strong bud,” soaked in rubbing alcohol and crushed into a paste.
Page 61-62
LUNG CLEANER AND EXPECTORANT
Cannabis is the best natural expectorant to clear the human lungs of smog, dust
and the phlegm associated with tobacco use. Marijuana smoke effectively dilates
the airways of the lungs, the bronchi, opening them to allow more oxygen into
the lungs. It is also the best natural dilator of the tiny airways of the lungs, the
bronchial tubes – making cannabis the best overall bronchial dilator for 80% of
the population (the remaining 20% sometimes show minor negative reactions).
(See section on asthma – a disease that closes these passages in spasms – UCLA
Tashkin studies, 1969-97; U.S. Costa Rican, 1980-82; Jamaican studies
1969-74, 76.) Statistical evidence – showing up consistently as anomalies in
matched populations – indicates that people who smoke tobacco cigarettes are
usually better off and will live longer if they smoke cannabis moderately, too.
(Jamaican, Costa Rican studies.) Millions of Americans have given up or avoided
smoking tobacco products in favor of cannabis, which is not good news to the
powerful tobacco lobby – Senator Jesse Helms and his cohorts. A
turn-of-the-century grandfather clause in U.S. tobacco law allows 400 to 6,000
additional chemicals to be added. Additions since then to the average tobacco
cigarette are unknown, and the public in the U.S. has no right to know what they
are. Many joggers and marathon runners feel cannabis use cleans their lungs,
allowing better endurance. The evidence indicates that cannabis use will probably
increase these outlaw American marijuana-users’ lives by about one to two
years – yet they may lose their rights, property, children, state licenses, etc., just
for using that safest of substances: cannabis.
Page 64
ACCEPTABLE RISKS
Every U.S. commission or federal judge who has studied the evidence has agreed
that cannabis is one of the safest drugs known. With all its therapeutic uses, it has
only one side effect that has been exaggerated as a concern: the “high.” The DEA
says this is not acceptable, so cannabis continues to be totally illegal in utter
disregard for both doctor and patient. Every day we trust physicians to determine
whether the risks associated with therapeutic, yet potentially dangerous drugs are
acceptable for their patients. Yet, doctors are not allowed to prescribe the herb that
Federal Judge Francis Young in 1988 called “one of the safest therapeutically active
substances known to man.” We don’t put out doctors in charge of stopping violent
crimes. The police, prosecutors and prison guards should not be in charge of which
herbal therapies people may use to treat their personal health problems.
Footnotes:
1. Cohen & Stillman, Therapeutic Potential of Marijuana, UCLA, 1976; personal
interviewd in Washington, D.C. (1982) with researchers from the Medical College
of Virginia.
2. Cohen & Stillman, Therapeutic Potential of Marijuana, UCLA, 1976; Mikuriya,
Tod H., M.D., Marijuana Medical Papers 1839-1972, Medi-Comp Press, Oakland,
CA, 1973.
3. The Antibiotic Effect of Cannabis Indica, 1952-53-55. The Antibacterial Effect
of Cannabis Indica, 1955, from Marijuana Medical Papers; Cohen & Stillman,
Therapeutic Potential of Marijuana, UCLA, 1976.
4. Harvard Medical School Mental Health Letter, Vol. 4, No. 5, November 1987.
5. Ruben, Vera & Comitas, Lambros, Ganja in Jamaica, A Medical Anthropological
Study of Chronic Marijuana Use, Mouton & Co., The Hague an Paris, Anchor Books,
U.S.A., 1976.
6. Stopping Valium Public Citizen Health Research Group, 2000 P St. NW,
Washington, DC.
Page 87-88
“Natural Mind”
United States government-funded studies at St. Louis Medical University in 1989
and the U.S. government’s National Institute of Mental Health in 1990 moved
cannabis research into a new realm by confirming that the human brain has receptor
sites for THC and its natural cannabis cousins to which no other compounds known
thus far will bind. In order for a chemical to affect the brain it must bind to a receptor
site capable of receiving it
(Omni, August 1989; Washington Post, Aug 9, 1990)
Although morphine fits the receptor sites of beta-endorphin roughly, and
amphetamines correspond loosely to dopamine, these drugs as well as tricyclics and
other mood altering drugs present grave danger to the subtle balance of the nerves’
vital fluids. Omni and the Washington Post cited no physical dangers in natural
cannabis.
One reason cannabis is so safe to use is that it does not affect any of the involuntary
muscles of breathing and life support. Rather, it affects its own specific receptor cites
for motion (movement strategy) and memory (mental strategies).
On the molecular level, THC fits into receptor sites in the upper brain that seem to be
uniquely designed to accommodate THC.
Page 90
God makes the Earth yield healing herbs, which the prudent man should not
neglect.”Sirach: 38:4 (Catholic Bible).
Page 94 – 95
Abraham Lincoln was an avowed enemy of prohibition. His wife was prescribed
cannabis for her nerves after his assassination. Virtually every president from the mid-
19th Century up until prohibition routinely used cannabis medicines (See chapter 12:
19th Century use).
Close acquaintances of John F. Kennedy, such as entertainers Morey Amsterdam and
Eddie Gordon* say the president used cannabis regularly to control his back pain
(before and during his term) and actually planned on legalizing “marijuana” during
his second term a plan cut short by his assassination in 1963. “How Heads of State
Got High,” High Times, April, 1980 (see appendix in paper version of this book).
More recently, former president Gerald Ford’s son Jack and Jimmy Carter’s son Chip
admit to having smoked pot in the White House. George Bush’s vice president Dan
Quayle* had a reputation for smoking grass and using drugs in college. Ronald and
even former first lady Nancy “Just Say No” Reagan are reported to have smoked
pot in the California Governor’s mansion.
* “Smoke Screen: Inmate Sues Justice Department Over Quayle-Pot Cover-up,”
Dallas Observer, August 23, 1990. Kelley, Kitty, Nancy Reagan: The Unauthorized
Biography, Doubleday Co., NY, 1991
Page 103 – 104
From 1850 to 1937, cannabis was used as the prime medicine for more than 100
separate illnesses or diseases in U.S. pharmacopoeia.
During all this time (until the 1940s), science, doctors, and drug manufacturers (Lilly,
Parke-Davis, Squibb, etc.) had no idea of its active ingredients.
Yet from 1842 until the 1890s, marijuana, generally called Cannabis Indica or Indian
Hemp extractums, was one of the three items (after alcohol and opium) most used in
patent and prescription drugs (in massive* doses, usually by oral ingestion).
* Doses given during the 19th Century to American infants, children, youth, adults,
women in childbirth, and senior citizens, in one day, were, in many cases, equal to
what a current moderate-to-heavy American marijuana user probably consumes in
a month or two, using U.S. government’s 1983 guidelines for comparison.
For Pain :
The FDA is on the record saying that “drugs such as Vicodin, Percocet, Darvocet,
and Acetaminophen are safer than medical marijuana.” Not if one is allergic.
Vicodin, Percocet and Davocet contain some dangerous substances, hydrocodone,
oxycodone, and propoxyphene. The side effects can be found in searches at
Drugs.com and other sites including the manufactures website.
According to Wikipedia at :http://en.wikipedia.org/wiki/Vicodin#Ban_proposed_in_the_U.S.
On June 30, 2009, a U.S. Food and Drug Administration (FDA) advisory panel
voted by a narrow margin to advise the FDA to remove Vicodin and another
painkiller, Percocet, from the market because of “a high likelihood of overdose
from prescription narcotics and acetaminophen products”. The panel cited concerns
of liver damage from their acetaminophen component, which is also the main
ingredient in commonly-used nonprescription drugs such as Tylenol. Each year,
acetaminophen overdose is linked to about 400 deaths and 42,000 hospitalizations.
The FDA is not required to follow its advisory committee recommendations, but
usually does.
Hydrocodone, the narcotic component of Vicodin, is still available in Canada as a
single drug and marketed under the trade name Hycodan in syrup and tablet forms
by Bristol-Myers-Squibb.
http://en.wikipedia.org/wiki/Hydrocodone
It should also be noted : The trade name Vicodin refers to hydrocodone being six
times stronger than codeine by mouth, as in the Roman numeral VI.
Vicodin is a tablet containing a combination of acetaminophen and hydrocodone.
Hydrocodone is in a group of drugs called narcotic pain relievers. Acetaminophen
is a less potent pain reliever that increases the effects of hydrocodone.
Vicodin
The most frequently reported adverse reactions include: lightheadedness, dizziness,
sedation, nausea and vomiting. These effects seem to be more prominent in
ambulatory than in nonambulatory patients and some of these adverse reactions
may be alleviated if the patient lies down.
Other adverse reactions include:
Central Nervous System
Drowsiness, mental clouding, lethargy, impairment of mental and physical
performance, anxiety, fear, dysphoria, psychic dependence, mood changes.
Gastrointestinal System
Prolonged administration of Vicodin Tablets may produce constipation.
Genitourinary System
Ureteral spasm, spasm of vesical sphincters and urinary retention have been
reported with opiates.
Respiratory Depression
Hydrocodone bitartrate may produce dose-related respiratory depression by
acting directly on the brain stem respiratory center..
Special Senses
Cases of hearing impairment or permanent loss have been reported predominantly
in patients with chronic overdose.
Dermatological
Skin rash, pruritus.
The following adverse drug events may be borne in mind as potential effects of
acetaminophen: allergic reactions, rash, thrombocytopenia, agranulocytosis.
General
The adverse effects of hydrocodone are generally similar to the adverse effects
observed with other narcotic analgesics. Acetaminophen is generally well-tolerated
when administered in therapeutic doses.
Nervous system
One study has suggested that the respiratory depression caused by hydrocodone
may be of benefit in the treatment of dyspnea related to chronic obstructive
pulmonary disease and restrictive lung disease. However, the potential for the
precipitation of respiratory insufficiency makes such use of hydrocodone hazardous
and such use should be undertaken, if at all, only with extreme caution.
Nervous system side effects of hydrocodone include mental depression, dizziness,
lightheadedness, respiratory depression (which is sometimes fatal), stupor, delirium,
somnolence, agitation, and dysphoria.
Other
Other side effects have included withdrawal symptoms, after either abrupt cessation
or fast tapering of narcotic analgesics. Such symptoms may include agitation,
restlessness, anxiety, insomnia, tremor, abdominal cramps, blurred vision, vomiting,
and sweating.
Hepatic
Alcoholic patients may develop hepatotoxicity after even modest doses of
acetaminophen. In healthy patients, approximately 15 grams of acetaminophen is
necessary to deplete liver glutathione stores by 70% in a 70 kg person. However,
hepatotoxicity has been reported following smaller doses. Glutathione
concentrations may be repleted by the antidote N-acetylcysteine. One case report
has suggested that hypothermia may also be beneficial in decreasing liver damage
during overdose.
In a recent retrospective study of 306 patients admitted for acetaminophen overdose,
6.9% had severe liver injury but all recovered. None of the 306 patients died.
A 19-year-old female developed hepatotoxicity, reactive plasmacytosis and
agranulocytosis followed by a leukemoid reaction after acute acetaminophen toxicity.
The adverse effects of hydrocodone may be more likely and more severe in patients
with liver disease.
Hepatic side effects including severe and sometimes fatal dose dependent hepatitis
have been reported in alcoholic patients. Hepatotoxicity has been increased during
fasting. Several cases of hepatotoxicity from chronic acetaminophen therapy at
therapeutic doses have also been reported despite a lack of risk factors for toxicity.
Gastrointestinal
Gastrointestinal side effects with the use of acetaminophen are rare except in
alcoholics and after overdose. Cases of acute pancreatitis have been reported rarely.
Gastrointestinal side effect including nausea, vomiting, constipation, and dry mouth
are relatively common effects of narcotic analgesics.
One study has suggested that acetaminophen may precipitate acute biliary pain and
cholestasis. The mechanism of this effect may be related to inhibition of prostaglandin
and alterations in the regulation of the sphincter of Oddi.
Genitourinary
Genitourinary side effects including ureteral spasm, spasm of vesicle sphincters, and
urinary retention have been reported.
Dermatologic
Dermatologic side effects including narcotic-induced rashes have been reported.
General erythematous skin rashes associated with acetaminophen have been reported,
but are rare. A rare case of bullous erythema associated with acetaminophen has
been reported.
Renal
Renal side effects of acetaminophen are rare and include acute tubular necrosis and
interstitial nephritis. Adverse renal effects are most often observed after overdose,
from chronic abuse (often with multiple analgesics), or in association with
acetaminophen-related hepatotoxicity.
Acute tubular necrosis usually occurs in conjunction with liver failure, but has been
observed as an isolated finding in rare cases.
The adverse effects of hydrocodone may be more likely and more severe in patients
with renal insufficiency.
Hematologic
Hematologic side effects including rare cases of thrombocytopenia associated with
acetaminophen have been reported. Acute thrombocytopenia has also been reported
as having been caused by sensitivity to acetaminophen glucuronide, the major
metabolite of acetaminophen. Methemoglobinemia with resulting cyanosis has also
been observed in the setting of acute overdose.
Hypersensitivity
Hypersensitivity side effects to acetaminophen have been reported rarely.
Respiratory
Respiratory side effects have included a case of eosinophilic pneumonia which has
been associated with acetaminophen.
Metabolic
In the case of metabolic acidosis, causality is uncertain as more than one drug was
ingested. The case of metabolic acidosis followed the ingestion of 75 grams of
acetaminophen, 1.95 grams of aspirin, and a small amount of a liquid household
cleaner. The patient also had a history of seizures which the authors reported may
have contributed to an increased lactate level indicative of metabolic acidosis.
Metabolic side effects including metabolic acidosis have been reported following a
massive overdose of acetaminophen.
Percocet, a narcotic analgesic, is used to treat moderate to moderately severe pain.
It contains two drugs—acetaminophen and oxycodone. Acetaminophen is used to
reduce both pain and fever. Oxycodone, a narcotic analgesic, is used for its calming
effect and for pain.
Side Effects by Body System
General
Psychosis has also been reported during withdrawal from oxycodone.
In general, acetaminophen is well tolerated when administered in therapeutic doses.
Oxycodone may be habit forming. Withdrawal symptoms after either abrupt
cessation or fast tapering may occur and include agitation, restlessness, anxiety,
insomnia, tremor, abdominal cramps, piloerection, blurred vision, vomiting, and
sweating.
Dermatologic
Dermatologic side effects including general erythematous skin rashes associated
with acetaminophen have been reported, but are rare. Cases of bullous erythema
and purpura fulminans associated with acetaminophen have been reported.
Oxycodone may produce pruritus.
Gastrointestinal
Gastrointestinal side effects with acetaminophen are rare except in alcoholics and
after overdose. Cases of acute pancreatitis have been reported rarely. Nausea,
vomiting, and constipation occur commonly with oxycodone.
One study has suggested that acetaminophen may precipitate acute biliary pain
and cholestasis. The mechanism of this effect may be related to inhibition of
prostaglandin and alterations in the regulation of the sphincter of Oddi.
Hematologic
Hematologic side effects including rare cases of thrombocytopenia associated with
acetaminophen have been reported. Acute thrombocytopenia has also been reported
as having been caused by sensitivity to acetaminophen glucuronide, the major
metabolite of acetaminophen. Methemoglobinemia with resulting cyanosis has also
been observed in the setting of acute overdose.
Hepatic
Hepatotoxicity may be increased by thyroid drugs, zidovudine, fasting, or alcohol
use. Alcoholic patients may develop hepatotoxicity after even modest doses of
acetaminophen. In healthy patients, approximately 15 grams of acetaminophen is
necessary to deplete liver glutathione stores by 70% in a 70 kg person.
Hepatotoxicity has been reported following smaller doses. Glutathione concentrations
may be repleted by the antidote n-acetylcysteine. One case report has suggested that
hypothermia may also be beneficial in decreasing liver damage during overdose.
In a recent retrospective study of 306 patients admitted for acetaminophen overdose,
6.9% had severe liver injury but all recovered. None of the 306 patients died.
A 19-year-old female developed hepatotoxicity, reactive plasmacytosis and
agranulocytosis followed by a leukemoid reaction after acute acetaminophen toxicity.
Hepatic side effects have included hepatic dysfunction which may occur after
overdose. In this setting, severe and sometimes fatal dose-dependent hepatitis has
been reported. Several cases of hepatotoxicity from chronic acetaminophen therapy
at therapeutic doses have also been reported despite a lack of risk factors for toxicity
Hypersensitivity
Hypersensitivity side effects including anaphylaxis and fixed drug eruptions have
been reported rarely in association with acetaminophen use.
Nervous system
Severe adverse effects of oxycodone, such as respiratory depression, can be treated
with the opiate antagonist, naloxone. (The usual adult dose of naloxone is 1 to 2 mg
every 5 minutes as necessary to a maximum of 10 mg. The dose is usually
administered intravenously, but in an emergency may be given intramuscularly,
subcutaneously, or sublingually.)
Nervous system side effects with oxycodone containing products are common and
include drowsiness, sedation, dizziness, and lightheadedness. Respiratory depression
has also been reported.
Psychiatric
Psychiatric side effects of oxycodone reported include paranoia, psychosis, and
hallucinations.
Renal
Acetaminophen related acute tubular necrosis usually occurs in conjunction with
liver failure, but has been observed as an isolated finding in rare cases. A possible
increase in the risk of renal cell carcinoma has been associated with chronic
acetaminophen use.
A recent case-control study of patients with end-stage renal disease suggested that
long term consumption of acetaminophen may significantly increase the risk of
end-stage renal disease particularly in patients taking more than two tablets per day.
Renal side effects of acetaminophen are rare and include acute tubular necrosis
and interstitial nephritis. Additional adverse renal effects are most often observed
after overdose, after chronic abuse (often with multiple analgesics), or in association
with acetaminophen-related hepatotoxicity.
Respiratory
Respiratory side effects have included a case of eosinophilic pneumonia which has
been associated with acetaminophen.
Cardiovascular
Two cases of hypotension have been reported following the administration of
acetaminophen. Both patients experienced significant decreases in blood pressure.
One of the two patients required pressor agents to maintain adequate mean arterial
pressures. Neither episode was associated with symptoms of anaphylaxis. Neither
patient was rechallenged after resolution of the initial episode.
Cardiovascular side effects have included at least two cases of hypotension which
have been reported following the administration of acetaminophen.
Metabolic
Metabolic side effects including metabolic acidosis have been reported following
a massive overdose of acetaminophen.
In the case of metabolic acidosis, causality is uncertain as more than one drug was
ingested. The case of metabolic acidosis followed the ingestion of 75 grams of
acetaminophen, 1.95 grams of aspirin, and a small amount of a liquid household
cleaner. The patient also had a history of seizures which the authors reported may
have contributed to an increased lactate level indicative of metabolic acidosis.
Darvocet contains a combination of propoxyphene and acetaminophen.
Propoxyphene is in a group of drugs called narcotic pain relievers. Acetaminophen
is a less potent pain reliever and a fever reducer that increases the effects of
propoxyphene.
Side Effects by Body System
Nervous system
Nervous system side effects of propoxyphene have included dizziness, sedation,
stupor, delirium, somnolence, ataxia, coma, syncope, and respiratory depression.
The sedative effects of propoxyphene have been associated with a 60% increased
risk of hip fracture in elderly patients.
Other
Other side effects including propoxyphene dependence have been reported
(although the abuse liability of propoxyphene is less than that of some other narcotic
analgesics). Withdrawal symptoms (after either abrupt cessation or fast tapering)
have been reported to include agitation, restlessness, anxiety, insomnia, tremor,
tachycardia, hallucinations, psychosis, abdominal cramps, vomiting, sweating, and
seizures. Drug toxicity, multiple drug overdose, and narcotic overdose have also
been reported with propoxyphene.
Sensorineural deafness has been reported following chronic abuse and/or large doses
of propoxyphene-containing compounds. Optic atrophy has been reported following
overdose.
Gastrointestinal
Gastrointestinal side effects of acetaminophen are rare, except in alcoholics and
after overdose. Cases of acute pancreatitis have been reported rarely with
acetaminophen use. Nausea, vomiting, and constipation are relatively common
effects of propoxyphene. Gastrointestinal bleeding and acute pancreatitis have
also been reported with the use of propoxyphene.
One study has suggested that acetaminophen may precipitate acute biliary pain
and cholestasis. The mechanism of this effect may be related to inhibition of
prostaglandin and alterations in the regulation of the sphincter of Oddi.
Elevated liver function tests, jaundice and hepatotoxicity have been reported in
association with propoxyphene.
A case of ischemic colitis has been reported following an overdose of propoxyphene
which was complicated by severe hypotension.
Cardiovascular
Cardiovascular side effects of propoxyphene have included arrhythmia, bradycardia,
cardiac/respiratory arrest, congestive arrest, congestive heart failure (CHF),
tachycardia, myocardial infarction (MI), hypotension, decreased blood pressure,
elevated heart rate, abnormal heart rate, and dizziness. A variety of arrhythmias
(including heart block) have been reported most often in association with overdose.
Some of the cardiotoxic effects reported in association with propoxyphene may be
attributable to its major active metabolite, norpropoxyphene.
Renal
Renal side effects of acetaminophen have been rare and have included acute
tubular necrosis and interstitial nephritis. Cases of severe hypoglycemia have been
reported in patients with chronic renal failure who received propoxyphene.
Acute tubular necrosis associated with acetaminophen usually occurs in conjunction
with liver failure, but has been observed as an isolated finding in rare cases. Adverse
acetaminophen renal effects are most often observed after overdose, after chronic
abuse (often with multiple analgesics), or in association with acetaminophen-related
hepatotoxicity. A possible increase in the risk of renal cell carcinoma has been
associated with chronic acetaminophen use as well.
A single case of nephrogenic diabetes insipidus has been reported following overdose
of propoxyphene (however, other causes of diabetes insipidus in that patient were
not rigorously excluded).
The adverse effects of propoxyphene may be more likely and more severe in patients
with renal insufficiency.
Hypersensitivity
Hypersensitivity side effects to acetaminophen have been reported rarely.
Hypersensitivity side effects to propoxyphene have also been reported.
Genitourinary
Genitourinary side effects have included a case of retroperitoneal fibrosis in
association with propoxyphene therapy.
Hematologic
Hematologic side effects including rare cases of thrombocytopenia associated with
acetaminophen have been reported. Acute thrombocytopenia has also been reported
as having been caused by sensitivity to acetaminophen glucuronide, the major
metabolite of acetaminophen. Methemoglobinemia with resulting cyanosis has also
been observed in the setting of acute overdose. Cases of hemolytic anemia,
pancytopenia, and disseminated intravascular coagulation after administration
(or abuse) of propoxyphene-containing compounds have been reported rarely.
Dermatologic
General erythematous skin rashes associated with acetaminophen have been reported,
but are rare. A rare case of bullous erythema associated with acetaminophen has
been reported.
Dermatologic side effects including rashes have been reported in association with both
propoxyphene and acetaminophen. Itch has also been reported with the use of
propoxyphene.
Respiratory
Respiratory side effects including a case of acetaminophen-induced eosinophilic
pneumonia have been reported.
Respiratory side effects including dyspnea have been reported with the use of
propoxyphene.
Musculoskeletal
Musculoskeletal side effects including myopathy and rhabdomyolysis have been
reported after chronic oral use. Fibrous myopathy has also been reported in
propoxyphene-abusing patients who administer the drug via intramuscular injection.
Hepatic
Hepatic side effects of acetaminophen including severe and sometimes fatal dose
dependent hepatitis have been reported in alcoholic patients. Hepatotoxicity has
been increased during fasting. Several cases of hepatotoxicity from chronic
acetaminophen therapy at therapeutic doses have also been reported despite a lack
of risk factors for toxicity.
Hepatic side effects of propoxyphene have included elevated liver function tests,
jaundice, hepatic steatosis, hepatomegaly, hepatocellular injury, and hepatotoxicity.
Alcoholic patients may develop hepatotoxicity after even modest doses of
acetaminophen. In healthy patients, approximately 15 grams of acetaminophen is
necessary to deplete liver glutathione stores by 70% in a 70 kg person. However,
hepatotoxicity has been reported following smaller doses. Glutathione concentrations
may be repleted by the antidote N-acetylcysteine. One case report has suggested that
hypothermia may also be beneficial in decreasing liver damage during overdose.
In a recent retrospective study of 306 patients admitted for acetaminophen overdose,
6.9% had severe liver injury but all recovered. None of the 306 patients died.
A 19-year-old female developed hepatotoxicity, reactive plasmacytosis and
agranulocytosis followed by a leukemoid reaction after acute acetaminophen toxicity.
The adverse effects of acetaminophen-propoxyphene may be more likely and more
severe in patients with liver disease.
Metabolic
In the case of metabolic acidosis, causality is uncertain as more than one drug was
ingested. The case of metabolic acidosis followed the ingestion of 75 grams of
acetaminophen, 1.95 grams of aspirin, and a small amount of a liquid household
cleaner. The patient also had a history of seizures which the authors reported may
have contributed to an increased lactate level indicative of metabolic acidosis.
Metabolic side effects including metabolic acidosis have been reported following a
massive overdose of acetaminophen.
Metabolic side effects including metabolic acidosis have been reported with the use
of propoxyphene. Cases of severe hypoglycemia have been reported in patients with
chronic renal failure.
Ocular
Ocular side effects including eye swelling and vision blurred have been reported with
the use of propoxyphene.
General
General side effects including drug tolerance and influenza type illness have been
reported with the use of propoxyphene.
Psychiatric
Psychiatric side effects including abnormal behavior, confusional state, hallucinations,
and mental status change have been reported with the use of propoxyphene.
More on Darvocet from
http://en.wikipedia.org/wiki/Propoxyphene
Toxicity
Darvocet overdose is commonly broken into two categories: liver toxicity (from
paracetamol poisoning) and dextropropoxyphene overdose.
Many users experience toxic effects from the paracetamol (acetaminophen) in
pursuit of the endlessly-increasing dose required for pain relief. They suffer acute
liver toxicity, which causes severe stomach pains, nausea, and vomiting (all of
which are increased by light or stimulation of the sense of sight).
An overdose of dextropropoxyphene may lead to various systemic effects.
Excessive opioid receptor stimulation is responsible for the CNS depression,
respiratory depression, miosis, and gastrointestinal effects seen in propoxyphene
poisoning. It may also account for mood/thought altering effects.
In addition, both propoxyphene and its metabolite norpropoxyphene, have local
anesthetic effects at concentrations about 10 times those necessary for opioid effects.
Norpropoxyphene is a more potent local anesthetic than propoxyphene, and they
are both more potent than lidocaine.[9] Local anesthetic activity appears to be
responsible for the arrhythmias and cardiovascular depression seen in propoxyphene
poisoning.[10]
Both propoxyphene and norpropoxyphene are potent blockers of cardiac membrane
sodium channels and are more potent than lidocaine, quinidine, and procainamide in
this respect.[11] As a result, propoxyphene and norpropoxyphene appear to have the
characteristics of a Vaughn-Williams Class Ic antiarrhythmic.
These direct cardiac effects include decreased heart rate (i.e. cardiovascular
depression), decreased contractility, and decreased electrical conductivity
(i.e., increased PR, AH, HV, and QRS intervals). These effects appear to be due
to their local anesthetic activity and are not reversed by naloxone.[9][10][12]
Widening of the QRS complex appears to be a result of a quinidine-like effect of
propoxyphene, and sodium bicarbonate therapy appears to have a positive direct
effect on the QRS dysrhythmia.[13]
Seizures may result from either opioid or local anesthetic effects.[9] Pulmonary
edema may result from direct pulmonary toxicity, neurogenic/anoxic effects, or
cardiovascular depression.[10]
http://www.drugs.com/sfx/codeine-side-effects.html
Codeine Sulfate
All medicines may cause side effects, but many people have no, or minor, side
effects. Check with your doctor if any of these most COMMON side effects persist
or become bothersome when using Codeine Sulfate:
Constipation; dizziness; drowsiness; lightheadedness; nausea; sweating; tiredness;
vomiting.
Seek medical attention right away if any of these SEVERE side effects occur when
using Codeine Sulfate:
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the
chest; swelling of the mouth, face, lips, or tongue); chest pain; confusion; fainting;
fast or irregular heartbeat; mental or mood changes; numbness or pain of an arm or
leg; seizures; severe drowsiness or dizziness; severe or persistent constipation or
stomach pain; shortness of breath; slow or shallow breathing; sudden, severe
headache or vomiting; trouble urinating.
Side Effects by Body System
General
The side effects have been more likely and more severe in patients with liver
and/or renal disease.
Nervous system
Nervous system side effects have included mental and respiratory depression,
stupor, delirium, somnolence, and dysphoria. An increased risk of falls and hip
fractures has also been associated with codeine therapy, particularly in the elderly.
A case of seizures has been reported with the use of intravenous codeine phosphate.
Opiates may result in psychotic symptoms in some patients.
One retrospective study of elderly patients who sustained a hip fracture suggested
that the relative risk of hip fracture was 1.6 in patients using codeine compared to
age-matched nonusers.
Other
Other side effects including withdrawal symptoms after either abrupt cessation or
fast tapering of narcotic analgesics have been reported. These withdrawal
symptoms have included agitation, restlessness, anxiety, insomnia, tremor,
abdominal cramps, blurred vision, vomiting, and sweating.
Cardiovascular
Hypotension is rare and has been reported most frequently with high doses.
Cardiovascular side effects have included hypotension and dizziness.
Gastrointestinal
Gastrointestinal side effects including nausea, vomiting, and constipation have
been reported frequently. Severe constipation and ileus resulting in colonic
perforation have also been reported. Four cases of acute pancreatitis have been reported.
Genitourinary
Genitourinary side effects including urinary retention have been reported.
Dermatologic
Dermatologic side effects including rashes, severe scarlatiniform eruptions, and
generalized dermatitis have been reported rarely.
Codeine-induced rashes may be related to direct stimulation of histamine release.
Renal
Renal side effects including acute renal failure (which may respond to naloxone
therapy) have been reported in association with codeine therapy.
Immunologic
Immunologic side effects have included one study of a patient with exercise-induced
anaphylaxis and three control subjects which found a correlation between codeine
wheal size and recent exercise.
Hypersensitivity
Hypersensitivity side effects including a case of codeine phosphate-induced
hypersensitivity syndrome have been reported.
Ocular
Ocular side effects including a temporary 26% decrease in pupil diameter following
the administration of intravenous codeine have been reported
http://www.drugs.com/cons/codeine.html
Some side effects may occur that usually do not need medical attention. These side
effects may go away during treatment as your body adjusts to the medicine. Also,
your health care professional may be able to tell you about ways to prevent or reduce
some of these side effects. Check with your health care professional if any of the
following side effects continue or are bothersome or if you have any questions
about them:
More common
Drowsiness
relaxed and calm
Incidence not known
Abdominal or stomach pain or cramps
blurred or loss of vision
diarrhea
disturbed color perception
double vision
dry mouth
false or unusual sense of well-being
fear or nervousness
feeling of constant movement of self or surroundings
halos around lights
headache
hives or welts
itching skin
night blindness
overbright appearance of lights
redness of the skin
sensation of spinning
shakiness
skin rash
sleeplessness
trouble sleeping
tunnel vision
unable to sleep
weight loss
Other side effects not listed may also occur in some patients. If you notice any
other effects, check with your healthcare professional.
http://www.drugs.com/sfx/demerol-side-effects.html
Demerol Tablets
All medicines may cause side effects, but many people have no, or minor, side
effects. Check with your doctor if any of these most COMMON side effects persist
or become bothersome when using Demerol Tablets:
Constipation; dizziness; drowsiness; lightheadedness; loss of appetite; nausea;
sweating; vomiting.
Seek medical attention right away if any of these SEVERE side effects occur
when using Demerol Tablets:
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the
chest; swelling of the mouth, face, lips, or tongue); chest pain; difficulty urinating;
fainting; fast, slow, or irregular heartbeat; mental or mood changes; numbness of an
arm or a leg; seizure; severe or persistent dizziness; slowed or difficult breathing;
sudden severe headache, nausea, vomiting, or stomach pain; tremor; vision changes.
Demerol Side Effects – for the Professional
Demerol
The major hazards of meperidine, as with other narcotic analgesics, are respiratory
depression and, to a lesser degree, circulatory depression; respiratory arrest, shock,
and cardiac arrest have occurred.
The most frequently observed adverse reactions include lightheadedness, dizziness,
sedation, nausea, vomiting, and sweating. These effects seem to be more prominent
in ambulatory patients and in those who are not experiencing severe pain. In such
individuals, lower doses are advisable. Some adverse reactions in ambulatory patients
may be alleviated if the patient lies down.
Other adverse reactions include:
Nervous System: Euphoria, dysphoria, weakness, headache, agitation, tremor,
uncoordinated muscle movements (e.g. muscle twitches, myoclonus), severe
convulsions, transient hallucinations and disorientation, visual disturbances.
Gastrointestinal: Dry mouth, constipation, biliary tract spasm.
Cardiovascular: Flushing of the face, tachycardia, bradycardia, palpitation,
hypotension, syncope.
Genitourinary: Urinary retention.
Allergic: Pruritus, urticaria, other skin rashes, wheal and flare over the vein with
intravenous injection. Hypersensitivity reactions including anaphylaxis.
Side Effects by Body System
Nervous system
Central nervous system side effects include sleepiness, respiratory depression,
delirium, seizures, tremors, dizziness, visual disturbances, muscle twitches, dilated
pupils, and Parkinsonian symptoms. A case of seizures has been reported in a patient
with porphyria. A case of transient neurological symptoms has been reported after
use of subarachnoid meperidine.
Central nervous system side effects may be either depressant or excitatory.
Excitatory symptoms are sometimes ignored as possible side effects of meperidine,
but may be due to the accumulation of a metabolite, normeperidine. Accumulation
of normeperidine occurs more frequently in patients with renal insufficiency and in
patients who are receiving meperidine via a patient-controlled analgesia pump.
Severe adverse effects, such as respiratory depression, may be treated with the
opiate antagonist, naloxone.
Psychiatric
Psychiatric side effects include fearfulness, agitation, paranoia, hypervigilance, and
auditory and visual hallucinations.
Psychological dependence on meperidine may develop.
Gastrointestinal
Meperidine may cause contraction of the sphincter of Oddi, thereby increasing
intrabiliary pressure. As a result, meperidine may aggravate rather than relieve
biliary colic.
Constipation is less common with meperidine than some other narcotics.
Gastrointestinal side effects including increased gastroesophageal reflux, increased
biliary pressure, dry mouth, nausea, and vomiting have been reported.
Hypersensitivity
Hypersensitivity side effects including anaphylaxis have been reported.
Other
Other side effects including an opioid abstinence or withdrawal syndrome has been
reported.
The opioid abstinence or withdrawal syndrome is characterized by some or all of the
following: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia,
mydriasis. Other symptoms also may also develop, including: irritability, anxiety,
backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia,
vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate.
Respiratory
There are case reports of bronchospasm occurring in patients with a history of
asthma after receiving meperidine. Because of this effect and possible respiratory
depression, meperidine should be used with caution in patients with severe reactive
or obstructive pulmonary disease.
Respiratory side effects including bronchospasm have been reported in patients
with underlying pulmonary disease.
Cardiovascular
Hypotension occurs most commonly in patients who are under anesthesia, who are
dehydrated, and who are receiving other medications.
Cardiovascular side effects including phlebitis have been reported. Hypotension has
been reported rarely.
Genitourinary
Genitourinary side effects including urinary retention have been reported.
Dermatologic
Dermatologic side effects including rash and sweating have been reported.
Musculoskeletal
Musculoskeletal side effects including a case of meperidine-induced muscular
rigidity have been reported.
For Rheumatoid Arthritis:
Rheumatoid arthritis is a chronic (long-term) inflammatory disease that primarily
affects the joints and surrounding tissues, but it can involve almost all organs.
Problems that may occur include:
Anemia due to failure of the bone marrow to produce enough new red blood cells
Damage to the lung tissue (rheumatoid lung)
Injury to the spinal cord when the cervical spine (neck bones) becomes unstable
as a result of RA
Rheumatoid vasculitis (inflammation of the blood vessels), which can lead to skin
ulcers and infections, bleeding stomach ulcers, and nerve problems that cause pain,
numbness, or tingling. Vasculitis may also affect the brain, nerves, and heart, which
can cause stroke, heart attack, or heart failure.
Swelling and inflammation of the outer lining of the heart (pericarditis) and of the
heart muscle (myocarditis). Both of these conditions can lead to congestive heart
failure.
Sjogren syndrome
Excluding NSAIDs due to the fact many people just can not take NSAIDS and we
are looking for other options.
http://www.rxlist.com/enbrel-drug.htm
Enbrel – Serious and sometimes fatal infections due to bacterial, mycobacterial,
invasive fungal, viral, or other opportunistic pathogens have been reported in
patients receiving TNF-blocking agents. Among opportunistic infections, tuberculosis,
histoplasmosis, aspergillosis, candidiasis, coccidioidomycosis, listeriosis, and
pneumocystosis were the most commonly reported.
http://www.webmd.com/drugs/drug-16772-Enbrel+SubQ.aspx?drugid=16772&drugname=Enbrel+SubQ
Enbrel – (etanercent)
Because etanercept works by blocking the immune system, it may lower your ability
to fight infections. This may make you more likely to get a serious (rarely fatal)
infection or make any infection you have worse. You should tell your doctor if you
have lived or traveled in areas where certain fungal infections (such as
coccidioidomycosis, histoplasmosis) are common or if you have been near someone
with tuberculosis. Areas where these types of fungal infections are commonly found
include the Ohio and Mississippi River valleys and the southwestern United States.
You should be tested for tuberculosis (TB skin test or chest X-ray) before and during
treatment with etanercept. See Side Effects section for symptoms of infections to
watch out for, and seek immediate medical attention if you develop any of these
symptoms.
The immune system is also important in preventing and controlling cancer. Though
it is very unlikely to happen, there is a risk (especially in children and teenagers)
of developing cancer (such as lymphoma) due to this medication or due to your
medical condition. Discuss the risks and benefits of treatment with your doctor.
Tell your doctor immediately if you develop symptoms such as unusual
lumps/growths, swollen glands, unexplained weight loss.
Side Effects
Redness, itching, pain, or swelling at the injection site may occur. This usually starts
1-2 days after the injection and clears up in 3-5 days. Injection site reactions usually
lessen after the first month. Headache, nausea, vomiting and abdominal pain may
occur. If these effects persist or worsen, notify your doctor promptly.
Remember that your doctor has prescribed this medication because he or she has
judged that the benefit to you is greater than the risk of side effects. Many people
using this medication do not have serious side effects.
Tell your doctor immediately if you develop signs of infection while using this drug,
such as: fever, chills, persistent sore throat, persistent cough, night sweats, trouble
breathing, painful/frequent urination, unusual vaginal discharge, white patches in
the mouth (oral thrush).
Tell your doctor immediately if any of these unlikely but serious side effects occur:
a rash on nose and cheeks (butterfly rash), dizziness, extreme fatigue, hair loss,
severe stomach/abdominal pain, swelling of the arms/legs.
Tell your doctor immediately if any of these highly unlikely but very serious side
effects occur: unusual bruising or bleeding, severe headache, mental/mood changes,
unexplained muscle weakness, seizures, tingling of the hands/feet, unsteadiness,
vision changes, dark urine, persistent nausea/vomiting, yellowing eyes/skin.
An allergic reaction to this drug is unlikely, but seek immediate medical attention
if it occurs. Symptoms of an allergic reaction include: rash, itching/swelling
(especially of the face/tongue/throat), dizziness, trouble breathing.
This is not a complete list of possible side effects. If you notice other effects not
listed above, contact your doctor or pharmacist.
http://www.drugs.com/enbrel.html
Enbrel
What should I avoid while using Enbrel?
Do not receive a “live” vaccine while you are being treated with Enbrel, and avoid
coming into contact with anyone who has recently received a live vaccine. There
is a chance that the virus could be passed on to you.
Avoid being near people who are sick or have infections. Call your doctor for
preventive treatment if you are exposed to chicken pox.
Enbrel side effects
Get emergency medical help if you have any of these signs of an allergic reaction
to Enbrel: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.
Serious and sometimes fatal infections may occur during treatment with Enbrel.
Stop using this medicine and call your doctor right away if you have signs of
infection such as:
fever, sweating, chills, tired feeling;
feeling short of breath;
cough, sore throat; or
flu symptoms, weight loss.
Call your doctor at once if you have any of these other serious side effects:
shortness of breath with swelling, rapid weight gain;
chest pain, ongoing cough, coughing up blood;
easy bruising or bleeding, pale skin, unusual weakness;
signs of skin infection such as itching, swelling, warmth, redness, or oozing;
black, bloody, or tarry stools;
changes in mood or personality (in children);
numbness, burning, pain, or tingly feeling;
joint pain or swelling with fever, swollen glands, muscle aches, chest pain, unusual
thoughts or behavior, and/or seizure (convulsions); or
patchy skin color, red spots, or a butterfly-shaped skin rash over your cheeks and
nose (worsens in sunlight).
Less serious Enbrel side effects may include:
nausea, vomiting, diarrhea, stomach pain;
runny or stuffy nose, cold symptoms; or
headache.
See also: Enbrel side effects in more detail
Enbrel® has been studied in 1442 patients with RA, followed for up to 80 months,
in 169 patients with psoriatic arthritis for up to 24 months, in 222 patients with
ankylosing spondylitis for up to 10 months, and 1261 patients with plaque
psoriasis for up to 15 months. In controlled trials, the proportion of Enbrel®-treated
patients who discontinued treatment due to adverse events was approximately 4%
in the indications studied. The vast majority of these patients were treated with
25 mg SC twice weekly. In plaque psoriasis studies, Enbrel® doses studied were
25 mg SC once a week, 25 mg SC twice a week, and 50 mg SC twice a week.
Injection Site Reactions
In controlled trials in rheumatologic indications, approximately 37% of patients
treated with Enbrel® developed injection site reactions. In controlled trials in
patients with plaque psoriasis, 14% of patients treated with Enbrel® developed
injection site reactions during the first 3 months of treatment. All injection site
reactions were described as mild to moderate (erythema and/or itching, pain, or
swelling) and generally did not necessitate drug discontinuation. Injection site
reactions generally occurred in the first month and subsequently decreased in
frequency. The mean duration of injection site reactions was 3 to 5 days. Seven
percent of patients experienced redness at a previous injection site when subsequent
injections were given. In post-marketing experience, injection site bleeding and
bruising have also been observed in conjunction with Enbrel® therapy.
Infections
In controlled trials, there were no differences in rates of infection among RA,
psoriatic arthritis, ankylosing spondylitis, and plaque psoriasis patients treated
with Enbrel® and those treated with placebo (or MTX for RA and psoriatic arthritis
patients). The most common type of infection was upper respiratory infection, which
occurred at a rate of approximately 20% among both Enbrel®- and placebo-treated
patients in RA, psoriatic arthritis, and AS trials, and at a rate of approximately 12%
among both Enbrel®- and placebo-treated patients in plaque psoriasis trials in the
first 3 months of treatment.
In placebo-controlled trials in RA, psoriatic arthritis, ankylosing spondylitis, and
plaque psoriasis no increase in the incidence of serious infections was observed
(approximately 1% in both placebo- and Enbrel®-treated groups). In all clinical
trials in RA, serious infections experienced by patients have included: pyelonephritis,
bronchitis, septic arthritis, abdominal abscess, cellulitis, osteomyelitis, wound
infection, pneumonia, foot abscess, leg ulcer, diarrhea, sinusitis, and sepsis. The
rate of serious infections has not increased in open-label extension trials and is
similar to that observed in Enbrel®- and placebo-treated patients from controlled
trials. Serious infections, including sepsis and death, have also been reported during
post-marketing use of Enbrel®. Some have occurred within a few weeks after
initiating treatment with Enbrel®. Many of the patients had underlying conditions
(e.g., diabetes, congestive heart failure, history of active or chronic infections) in
addition to their rheumatoid arthritis. Data from a sepsis clinical trial not specifically
in patients with RA suggest that Enbrel® treatment may increase mortality in
patients with established sepsis.9
In patients who received both Enbrel® and anakinra for up to 24 weeks, the
incidence of serious infections was 7%. The most common infections consisted of
bacterial pneumonia (4 cases) and cellulitis (4 cases). One patient with pulmonary
fibrosis and pneumonia died due to respiratory failure.
In post-marketing experience in rheumatologic indications, infections have been
observed with various pathogens including viral, bacterial, fungal, and protozoal
organisms. Infections have been noted in all organ systems and have been reported
in patients receiving Enbrel® alone or in combination with immunosuppressive
agents. In clinical trials in plaque psoriasis, serious infections experienced by
Enbrel®-treated patients have included: cellulitis, gastroenteritis, pneumonia,
abscess, and osteomyelitis.
In global clinical studies of 20,070 patients (28,308 patient-years of therapy),
tuberculosis was observed in approximately 0.01% of patients. In 15,438 patients
(23,524 patient-years of therapy) from clinical studies in the US and Canada,
tuberculosis was observed in approximately 0.007% of patients. These studies
include reports of pulmonary and extra-pulmonary tuberculosis.
Malignancies
Patients have been observed in clinical trials with Enbrel® for over five years.
Among 4462 rheumatoid arthritis patients treated with Enbrel® in clinical trials
for a mean of 27 months (approximately 10000 patient-years of therapy), 9
lymphomas were observed for a rate of 0.09 cases per 100 patient-years. This
is 3-fold higher than the rate of lymphomas expected in the general population
based on the Surveillance, Epidemiology, and End Results Database.10 An
increased rate of lymphoma up to several fold has been reported in the rheumatoid
arthritis patient population, and may be further increased in patients with more
severe disease activity11, 12. Sixty-seven malignancies, other than lymphoma,
were observed. Of these, the most common malignancies were colon, breast, lung,
and prostate,
which were similar in type and number to what would be expected in the general
population.10 Analysis of the cancer rates at 6 month intervals suggest constant
rates over five years of observation.
In the placebo-controlled portions of the psoriasis studies, 8 of 933 patients who
received Enbrel® at any dose were diagnosed with a malignancy compared to 1
of 414 patients who received placebo. Among the 1261 patients with psoriasis
who received Enbrel® at any dose in the controlled and uncontrolled portions
of the psoriasis studies (1062 patient-years), a total of 22 patients were diagnosed
with 23 malignancies; 9 patients with non-cutaneous solid tumors, 12 patients with
13 non-melanoma skin cancers (8 basal, 5 squamous), and 1 patient with
non-Hodgkin’s lymphoma. Among the placebo-treated patients (90 patient-years
of observation) 1 patient was diagnosed with 2 squamous cell cancers. The size of
the placebo group and limited duration of the controlled portions of studies
precludes the ability to draw firm conclusions.
Among 89 patients with Wegener’s granulomatosis receiving Enbrel® in a
randomized, placebo-controlled trial, 5 experienced a variety of non-cutaneous
solid malignancies compared with none receiving placebo.
Immunogenicity
Patients with RA, psoriatic arthritis, ankylosing spondylitis, or plaque psoriasis
were tested at multiple timepoints for antibodies to Enbrel®. Antibodies to the
TNF receptor portion or other protein components of the Enbrel® drug product
were detected at least once in sera of approximately 6% of adult patients with
RA, psoriatic arthritis, ankylosing spondylitis, or plaque psoriasis. These
antibodies were all non-neutralizing. Results from JIA patients were similar to
those seen in adult RA patients treated with Enbrel®.
In PsO studies that evaluated the exposure of etanercept for up to 120 weeks, the
percentage of patients testing positive at the assessed time points of 24, 48, 72, and
96 weeks ranged from 3.6%- 8.7% and were all non-neutralizing. The percentage
of patients testing positive increased with an increase in the duration of study,
however, the clinical significance of this finding is unknown. No apparent
correlation of antibody development to clinical response or adverse events was
observed. The immunogenicity data of Enbrel® beyond 120 weeks of exposure
is unknown.
The data reflect the percentage of patients whose test results were considered
positive for antibodies to Enbrel® in an ELISA assay, and are highly dependent
on the sensitivity and specificity of the assay. Additionally, the observed incidence
of
any antibody positivity in an assay is highly dependent on several factors including
assay sensitivity and specificity, assay methodology, sample handling, timing of
sample collection, concomitant medications, and underlying disease. For these
reasons, comparison of the incidence of antibodies to Enbrel® with the incidence
of antibodies to other products may be misleading.
Autoantibodies
Patients with RA had serum samples tested for autoantibodies at multiple timepoints.
In RA Studies I and II, the percentage of patients evaluated for antinuclear
antibodies (ANA) who developed new positive ANA (titer ≥ 1:40) was higher in
patients treated with Enbrel® (11%) than in placebo-treated patients (5%). The
percentage of patients who developed new positive anti-double-stranded DNA
antibodies was also higher by radioimmunoassay (15% of patients treated with
Enbrel® compared to 4% of placebo-treated patients) and by Crithidia luciliae
assay (3% of patients treated with Enbrel® compared to none of placebo-treated
patients). The proportion of patients treated with Enbrel® who developed
anticardiolipin antibodies was similarly increased compared to placebo-treated
patients. In Study III, no pattern of increased autoantibody development was seen
in Enbrel® patients compared to MTX patients.
The impact of long-term treatment with Enbrel® on the development of
autoimmune diseases is unknown. Rare adverse event reports have described
patients with rheumatoid factor positive and/or erosive RA who have developed
additional autoantibodies in conjunction with rash and other features suggesting a
lupus-like syndrome.
Other Adverse Reactions
Table 10 summarizes events reported in at least 3% of all patients with higher
incidence in patients treated with Enbrel® compared to controls in placebo-
controlled RA trials (including the combination methotrexate trial) and relevant
events from Study III. In placebo-controlled plaque psoriasis trials, the percentages
of patients reporting injection site reactions were lower in the placebo dose group
(6.4%) than in the Enbrel® dose groups (15.5%) in Studies I and II. Otherwise,
the percentages of patients reporting adverse events in the 50 mg twice a week
dose group were similar to those observed in the 25 mg twice a week dose group
or placebo group. In psoriasis Study I, there were no serious adverse events of
worsening psoriasis following withdrawal of study drug. However, adverse events
of worsening psoriasis including three serious adverse events were observed during
the course of the clinical trials. Urticaria and non-infectious hepatitis were observed
in a small number of patients and angioedema was observed in one patient in
clinical studies. Urticaria and angioedema have also been reported in spontaneous
post-marketing reports. Adverse events in psoriatic arthritis, ankylosing spondylitis,
and plaque psoriasis trials were similar to those reported in RA clinical trials.
In controlled trials of RA and psoriatic arthritis, rates of serious adverse events were
seen at a frequency of approximately 5% among Enbrel®- and control-treated
patients. In controlled trials of plaque psoriasis, rates of serious adverse events
were seen at a frequency of < 1.5% among Enbrel®- and placebo-treated patients
in the first 3 months of treatment. Among patients with RA in placebo-controlled,
active-controlled, and open-label trials of Enbrel®, malignancies and infections
were the most common serious adverse events observed. Other infrequent serious
adverse events observed in RA, psoriatic arthritis, ankylosing spondylitis, or plaque
psoriasis clinical trials are listed by body system below:
Cardiovascular: heart failure, myocardial infarction, myocardial ischemia,
hypertension, hypotension, deep vein thrombosis, thrombophlebitis
Digestive: cholecystitis, pancreatitis, gastrointestinal hemorrhage, appendicitis
Hematologic/Lymphatic: lymphadenopathy
Musculoskeletal: bursitis, polymyositis
Nervous: cerebral ischemia, depression, multiple sclerosis
Respiratory: dyspnea, pulmonary embolism, sarcoidosis
Skin: worsening psoriasis
Urogenital: membranous glomerulonephropathy, kidney calculus
In a randomized controlled trial in which 51 patients with RA received Enbrel®
50 mg twice weekly and 25 patients received Enbrel® 25 mg twice weekly, the
following serious adverse events were observed in the 50 mg twice weekly arm:
gastrointestinal bleeding, normal pressure hydrocephalus, seizure, and stroke.
No serious adverse events were observed in the 25 mg arm.
Adverse Reactions in Patients with JIA
In general, the adverse events in pediatric patients were similar in frequency and
type as those seen in adult patients. Differences from adults and other special
considerations are discussed in the following paragraphs.
Severe adverse reactions reported in 69 JIA patients ages 4 to 17 years included
varicella, gastroenteritis, depression/personality disorder, cutaneous ulcer,
esophagitis/gastritis, group A streptococcal septic shock, Type 1 diabetes mellitus,
and soft tissue and post-operative wound infection.
Forty-three of 69 (62%) children with JIA experienced an infection while receiving
Enbrel® during three months of study (part 1 open-label), and the frequency and
severity of infections was similar in 58 patients completing 12 months of open-label
extension therapy. The types of infections reported in JIA patients were generally
mild and consistent with those commonly seen in outpatient pediatric populations.
Two JIA patients developed varicella infection and signs and symptoms of aseptic
meningitis which resolved without sequelae.
The following adverse events were reported more commonly in 69 JIA patients
receiving 3 months of Enbrel® compared to the 349 adult RA patients in
placebo-controlled trials. These included headache (19% of patients, 1.7 events
per patient-year), nausea (9%, 1.0 events per patient-year), abdominal pain
(19%, 0.74 events per patient-year), and vomiting (13%, 0.74 events per
patient-year).
In open-label clinical studies of children with JIA, adverse events reported in
those aged 2 to 4 years were similar to adverse events reported in older children.
In post-marketing experience, the following additional serious adverse events have
been reported in pediatric patients: abscess with bacteremia, optic neuritis,
pancytopenia, seizures, tuberculous arthritis, urinary tract infection, coagulopathy,
cutaneous vasculitis, and transaminase elevations. The frequency of these events
and their causal relationship to Enbrel® therapy are unknown.
Patients with Heart Failure
Two randomized placebo-controlled studies have been performed in patients with
CHF. In one study, patients received either Enbrel® 25 mg twice weekly, 25 mg
three times weekly, or placebo. In a second study, patients received either
Enbrel® 25 mg once weekly, 25 mg twice weekly, or placebo. Results of the first
study suggested higher mortality in patients treated with Enbrel® at either schedule
compared to placebo. Results of the second study did not corroborate these
observations. Analyses did not identify specific factors associated with increased
risk of adverse outcomes in heart failure patients treated with Enbrel®.
Adverse Reaction Information from Spontaneous Reports
Adverse events have been reported during post-approval use of Enbrel®. Because
these events are reported voluntarily from a population of uncertain size, it is not
always possible to reliably estimate their frequency or establish a causal relationship
to Enbrel® exposure.
Additional adverse events are listed by body system below:
Body as a whole: angioedema, fatigue, fever, flu syndrome, generalized pain, weight
gain
Cardiovascular: chest pain, vasodilation (flushing), new-onset congestive heart failure
Digestive: altered sense of taste, anorexia, diarrhea, dry mouth, intestinal perforation
Hematologic/Lymphatic: adenopathy, anemia, aplastic anemia, leukopenia,
neutropenia, pancytopenia, thrombocytopenia
Hepatobiliary: autoimmune hepatitis
Musculoskeletal: joint pain, lupus-like syndrome with manifestations including rash
consistent with subacute or discoid lupus
Nervous: paresthesias, stroke, seizures and central nervous system events suggestive
of multiple sclerosis or isolated demyelinating conditions such as transverse myelitis
or optic neuritis
Ocular: dry eyes, ocular inflammation
Respiratory: dyspnea, interstitial lung disease, pulmonary disease, worsening of prior
lung disorder
Skin: cutaneous vasculitis, erythema multiforme, Stevens-Johnson syndrome, toxic
epidermal necrolysis, pruritus, subcutaneous nodules, urticaria, new or worsening
psoriasis (all sub-types including pustular and palmoplantar)
Cannabis/Marijuana pales in comparison of adverse side effects and far outweighs
the benefits. In fact as shown prior it is beneficial to many of the side effects caused
by Enbrel and Humira, the next medication examined.
http://www.drugs.com/sfx/humira-side-effects.html
Humira Side Effects – for the Professional
Humira
Clinical Studies Experience
The most serious adverse reactions were [see Warnings and Precautions (5)]:
Serious Infections
Neurologic Reactions
Malignancies
The most common adverse reaction with Humira was injection site reactions. In
placebo-controlled trials, 20% of patients treated with Humira developed injection
site reactions (erythema and/or itching, hemorrhage, pain or swelling), compared to
14% of patients receiving placebo. Most injection site reactions were described as
mild and generally did not necessitate drug discontinuation.
The proportion of patients who discontinued treatment due to adverse reactions
during the double-blind, placebo-controlled portion of Studies RA-I, RA-II, RA-III
and RA-IV was 7% for patients taking Humira and 4% for placebo-treated patients.
The most common adverse reactions leading to discontinuation of Humira were
clinical flare reaction (0.7%), rash (0.3%) and pneumonia (0.3%).
Because clinical trials are conducted under widely varying and controlled conditions,
adverse reaction rates observed in clinical trials of a drug cannot be directly
compared to rates in the clinical trials of another drug and may not predict the rates
observed in a broader patient population in clinical practice.
Infections
In placebo-controlled rheumatoid arthritis trials, the rate of infection was 1 per
patient-year in the Humira-treated patients and 0.9 per patient-year in the
placebo-treated patients. The infections consisted primarily of upper respiratory
tract infections, bronchitis and urinary tract infections. Most patients continued on
Humira after the infection resolved. The incidence of serious infections was 0.04
per patient-year in Humira treated patients and 0.02 per patient-year in
placebo-treated patients. Serious infections observed included pneumonia,
septic arthritis, prosthetic and post-surgical infections, erysipelas, cellulitis,
diverticulitis, and pyelonephritis [see Warnings and Precautions (5.1)].
Tuberculosis and Opportunistic Infections
In completed and ongoing global clinical studies that include over 13,000 patients,
the overall rate of tuberculosis is approximately 0.26 per 100 patient-years. In over
4500 patients in the US and Canada, the rate is approximately 0.07 per 100
patient-years. These studies include reports of miliary, lymphatic, peritoneal, as
well as pulmonary. Most of the cases of tuberculosis occurred within the first eight
months after initiation of therapy and may reflect recrudescence of latent disease.
Cases of opportunistic infections have also been reported in these clinical trials at
an overall rate of approximately 0.075/100 patient-years. Some cases of
opportunistic infections and tuberculosis have been fatal [see Warnings and
Precautions (5.1)].
Malignancies
More cases of malignancy have been observed in Humira-treated patients
compared to control-treated patients in clinical trials [see Warnings and
Precautions (5.2)].
Autoantibodies
In the rheumatoid arthritis controlled trials, 12% of patients treated with Humira
and 7% of placebo-treated patients that had negative baseline ANA titers
developed positive titers at week 24. Two patients out of 3046 treated with
Humira developed clinical signs suggestive of new-onset lupus-like syndrome.
The patients improved following discontinuation of therapy. No patients developed
lupus nephritis or central nervous system symptoms. The impact of long-term
treatment with Humira on the development of autoimmune diseases is unknown.
Immunogenicity
Patients in Studies RA-I, RA-II, and RA-III were tested at multiple time points for
antibodies to adalimumab during the 6- to 12-month period. Approximately 5% (58
of 1062) of adult rheumatoid arthritis patients receiving Humira developed low-titer
antibodies to adalimumab at least once during treatment, which were neutralizing in
vitro. Patients treated with concomitant methotrexate had a lower rate of antibody
development than patients on Humira monotherapy (1% versus 12%). No apparent
correlation of antibody development to adverse reactions was observed. With
monotherapy, patients receiving every other week dosing may develop antibodies
more frequently than those receiving weekly dosing. In patients receiving the
recommended dosage of 40 mg every other week as monotherapy, the ACR 20
response was lower among antibody-positive patients than among antibody-negative
patients. The long-term immunogenicity of Humira is unknown.
In patients with juvenile idiopathic arthritis, adalimumab antibodies were identified
in 16% of Humira-treated patients. In patients receiving concomitant methotrexate,
the incidence was 6% compared to 26% with Humira monotherapy.
In patients with ankylosing spondylitis, the rate of development of antibodies to
adalimumab in Humira-treated patients was comparable to patients with rheumatoid
arthritis. In patients with psoriatic arthritis, the rate of antibody development in
patients receiving Humira monotherapy was comparable to patients with rheumatoid
arthritis; however, in patients receiving concomitant methotrexate the rate was 7%
compared to 1% in rheumatoid arthritis. In patients with Crohn’s disease, the rate of
antibody development was 2.6%. The immunogenicity rate was 8% for plaque
psoriasis patients who were treated with Humira monotherapy.
The data reflect the percentage of patients whose test results were considered
positive for antibodies to adalimumab in an ELISA assay, and are highly dependent
on the sensitivity and specificity of the assay. The observed incidence of antibody
(including neutralizing antibody) positivity in an assay is highly dependent on several
factors including assay sensitivity and specificity, assay methodology, sample
handling, timing of sample collection, concomitant medications, and underlying
disease. For these reasons, comparison of the incidence of antibodies to adalimumab
with the incidence of antibodies to other products may be misleading.
Other Adverse Reactions
The data described below reflect exposure to Humira in 2468 patients, including
2073 exposed for 6 months, 1497 exposed for greater than one year and 1380 in
adequate and well-controlled studies (Studies RA-I, RA-II, RA-III, and RA-IV).
Humira was studied primarily in placebo-controlled trials and in long-term follow
up studies for up to 36 months duration. The population had a mean age of 54 years,
77% were female, 91% were Caucasian and had moderately to severely active
rheumatoid arthritis. Most patients received 40 mg Humira every other week.
Table 1 summarizes reactions reported at a rate of at least 5% in patients treated
with Humira 40 mg every other week compared to placebo and with an incidence
higher than placebo. Adverse reaction rates in patients treated with Humira 40 mg
weekly were similar to rates in patients treated with Humira 40 mg every other week.
In Study RA-III, the types and frequencies of adverse reactions in the second year
open-label extension were similar to those observed in the one-year double-blind
portion.
Table 1. Adverse Reactions Reported by ≥5% of Patients Treated with Humira
During Placebo-Controlled Period of Rheumatoid Arthritis Studies
Humira
40 mg subcutaneous
Every Other Week
Placebo (N=705) (N=690)
Adverse Reaction (Preferred Term) Percentage Percentage
Respiratory Upper respiratory infection 17 13
Sinusitis 11 9
Flu syndrome 7 6
Gastrointestinal Nausea 9 8
Abdominal pain 7 4
Laboratory Tests*
Laboratory test abnormal 8 7
Hypercholesterolemia 6 4
Hyperlipidemia 7 5
Hematuria 5 4
Alkaline phosphatase increased 5 3
Other Injection site pain 12 12
Headache 12 8
Rash 12 6
Accidental injury 10 8
Injection site reaction ** 8 1
Back pain 6 4
Urinary tract infection 8 5
Hypertension 5 3
* Laboratory test abnormalities were reported as adverse reactions in European
trials
** Does not include erythema and/or itching, hemorrhage, pain or swelling
Other Adverse Reactions
Other infrequent serious adverse reactions occurring at an incidence of less than
5% in rheumatoid arthritis patients treated with Humira were:
Body As A Whole: Fever, infection, pain in extremity, pelvic pain, sepsis, surgery,
thorax pain, tuberculosis reactivated
Cardiovascular System: Arrhythmia, atrial fibrillation, cardiovascular disorder,
chest pain, congestive heart failure, coronary artery disorder, heart arrest,
hypertensive encephalopathy, myocardial infarct, palpitation, pericardial effusion,
pericarditis, syncope, tachycardia, vascular disorder
Collagen Disorder: Lupus erythematosus syndrome
Digestive System: Cholecystitis, cholelithiasis, esophagitis, gastroenteritis,
gastrointestinal disorder, gastrointestinal hemorrhage, hepatic necrosis, vomiting
Endocrine System: Parathyroid disorder
Hemic And Lymphatic System: Agranulocytosis, granulocytopenia, leukopenia,
lymphoma like reaction, pancytopenia, polycythemia [see Warnings and
Precautions (5.6)]
Metabolic And Nutritional Disorders: Dehydration, healing abnormal, ketosis,
paraproteinemia, peripheral edema
Musculo-Skeletal System: Arthritis, bone disorder, bone fracture (not spontaneous),
bone necrosis, joint disorder, muscle cramps, myasthenia, pyogenic arthritis,
synovitis, tendon disorder
Neoplasia: Adenoma, carcinomas such as breast, gastrointestinal, skin, urogenital,
and others; lymphoma and melanoma
Nervous System: Confusion, multiple sclerosis, paresthesia, subdural hematoma,
tremor
Respiratory System: Asthma, bronchospasm, dyspnea, lung disorder, lung function
decreased, pleural effusion, pneumonia
Skin And Appendages: Cellulitis, erysipelas, herpes zoster
Special Senses: Cataract
Thrombosis: Thrombosis leg
Urogenital System: Cystitis, kidney calculus, menstrual disorder, pyelonephritis
Juvenile Idiopathic Arthritis Clinical Studies
In general, the adverse reactions in pediatric patients were similar in frequency and
type to those seen in adult patients [see Warnings and Precautions (5) and other
sections under Adverse Reactions (6)]. Important findings and differences from
adults are discussed in the following paragraphs.
Humira has been studied in 171 pediatric patients, 4 to 17 years of age, with
polyarticular juvenile idiopathic arthritis. Severe adverse reactions reported in
the study included neutropenia, streptococcal pharyngitis, increased
aminotransferases, herpes zoster, myositis, metrorrhagia, appendicitis. Serious
infections were observed in 4% of patients within approximately 2 years of initiation
of treatment with Humira and included cases of herpes simplex, pneumonia, urinary
tract infection, pharyngitis, and herpes zoster.
A total of 45% of children experienced an infection while receiving Humira with or
without concomitant MTX in the first 16 weeks of treatment. The types of infections
reported in juvenile idiopathic arthritis patients were generally similar to those
commonly seen in outpatient JIA populations. Upon initiation of treatment, the
most common adverse reactions occurring in the pediatric population treated with
Humira were injection site pain and injection site reaction (19% and 16%,
respectively). A less commonly reported adverse event in children receiving
Humira was granuloma annulare which did not lead to discontinuation of Humira
treatment.
In the first 48 weeks of treatment, non-serious hypersensitivity reactions were seen
in approximately 6% of children and included primarily localized allergic
hypersensitivity reactions and allergic rash.
Isolated mild to moderate elevations of liver aminotransferases (ALT more common
than AST) were observed in children with juvenile idiopathic arthritis exposed to
Humira alone; liver function tests (LFT) elevations were more frequent among
those treated with the combination of Humira and MTX. In general, these elevations
did not lead to discontinuation of Humira treatment.
In the juvenile idiopathic arthritis trial, 10% of patients treated with Humira who had
negative baseline anti-dsDNA antibodies developed positive titers after 48 weeks of
treatment. No patient developed clinical signs of autoimmunity during the clinical trial.
Approximately 15% of children treated with Humira developed mild-to-moderate
elevations of creatine phosphokinase (CPK). Elevations exceeding 5 times the upper
limit of normal were observed in several patients. CPK levels decreased or returned
to normal in all patients. Most patients were able to continue Humira without
interruption.
Psoriatic Arthritis and Ankylosing Spondylitis Clinical Studies
Humira has been studied in 395 patients with psoriatic arthritis in two
placebo-controlled trials and in an open label study and in 393 patients with
ankylosing spondylitis in two placebo-controlled studies. The safety profile for
patients with psoriatic arthritis and ankylosing spondylitis treated with Humira
40 mg every other week was similar to the safety profile seen in patients with
rheumatoid arthritis, Humira Studies RA-I through IV. In the clinical trials of
patients with psoriatic arthritis and ankylosing spondylitis, elevations of
aminotransferases were observed (ALT more common than AST) in a greater
proportion of patients receiving Humira than in controls, both when Humira was
given as monotherapy and when it was used in combination with other
immunosuppressive agents. Most elevations of ALT and
AST observed were in the range of 1.5 to 3 times the upper limit of normal. In
general, patients who developed ALT and AST elevations were asymptomatic,
and the abnormalities decreased or resolved with either continuation or
discontinuation of Humira, or modification of concomitant medications.
Crohn’s Disease Clinical Studies
Humira has been studied in 1478 patients with Crohn’s disease in four
placebo-controlled and two open-label extension studies. The safety profile
for patients with Crohn’s disease treated with Humira was similar to the safety
profile seen in patients with rheumatoid arthritis.
,
Plaque Psoriasis Clinical Studies
Humira has been studied in 1696 patients with plaque psoriasis in placebo-
controlled and open-label extension studies. The safety profile for patients with
plaque psoriasis treated with Humira was similar to the safety profile seen in patients
with rheumatoid arthritis with the following exceptions. In the placebo-controlled
portions of the clinical trials in plaque psoriasis patients, Humira-treated patients
had a higher incidence of arthralgia when compared to controls (3% vs. 1%).
Elevations of aminotransferases were observed (ALT more common than AST) in
a greater proportion of patients receiving Humira than in controls. Most elevations
of ALT and AST observed were in the range of 1.5 to 3 times the upper limit of
normal. In general, patients who developed ALT and AST elevations were
asymptomatic, and most of the abnormalities decreased or resolved with either
continuation or discontinuation of Humira.
Postmarketing Experience
Adverse reactions have been reported during post-approval use of Humira.
Because these reactions are reported voluntarily from a population of uncertain
size, it is not always possible to reliably estimate their frequency or establish a
causal relationship to Humira exposure.
Hematologic reactions: Thrombocytopenia [see Warnings and Precautions (5.6)]
Hypersensitivity reactions: Anaphylaxis, angioneurotic edema [see Warnings and
Precautions (5.3)]
Respiratory disorders: Interstitial lung disease, including pulmonary fibrosis
Skin reactions: Cutaneous vasculitis, erythema multiforme, new or worsening
psoriasis (all sub-types including pustular and palmoplantar)
discontinued treatment due to adverse events (vs 4% with placebo).
Other
The incidence of infection was 1 per patient year (vs. 0.9 with placebo). The most
common infections were upper respiratory tract infections (17%), bronchitis, and
urinary tract infections (8%). The incidence of serious infections was 0.04 per
patient year (vs. 0.02 with placebo). Serious infections included pneumonia,
septic arthritis, prosthetic and postsurgical infections, erysipelas, cellulitis,
diverticulitis, pyelonephritis, tuberculosis (13 cases), and invasive opportunistic
infections (6 cases). One fatality due to herpes zoster with secondary streptococcal
necrotizing fasciitis was reported during a clinical trial (n=636). A leprosy reaction
has been reported following discontinuation of adalimumab.
Most of the tuberculosis cases occurred within the first 8 months of therapy and
included miliary, lymphatic, peritoneal, and pulmonary types. Opportunistic
infections were due to histoplasma, aspergillus, and nocardia.
Nervous system
Nervous system side effects have included headache (12%). Confusion, multiple
sclerosis, paresthesia, subdural hematoma, and tremor have been reported in less
than 5% of patients. A case of hypertrophic pachymeningitis has also been reported.
Adalimumab and other TNF blockers have been associated with symptoms or
evidence suggestive of demyelinating disease.
Oncologic
Oncologic side effects have included adenoma, carcinomas (breast, gastrointestinal,
skin, urogenital), lymphoma, and melanoma in less than 5% of patients. A case of
acute myelogenic leukemia has also been reported.
During the controlled portions of adalimumab trials in patients with moderately to
severely active rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis,
malignancies (other than lymphoma and non-melanoma skin cancer) were observed
at a rate of 0.7 per 100 patient-years among adalimumab-treated patients versus a
rate of 0.3 per 100 patient-years among control patients. The median duration of
treatment was 5.7 months for adalimumab-treated patients and 5.5 months for
control-treated patients.
During the controlled portions of adalimumab rheumatoid arthritis trials, the rate
of non-melanoma skin cancers was 0.9 per 100 patient-years among
adalimumab-treated patients and 0.2 per 100 patient-years among control patients.
More cases of malignancies have been observed among patients receiving
TNF blockers, including adalimumab, compared to controls. Patients with
rheumatoid arthritis, particularly those with highly active disease, are at a
higher risk for the development of lymphoma.
A meta-analysis has reported that there is dose-dependent increased risk of
malignancies in patients with rheumatoid arthritis treated with anti-TNF antibody
therapy.
Immunologic
Immunologic side effects have included development of autoantibodies. Positive
ANA titers were observed at week 24 in 12% of patients (vs 7% with placebo).
One patient (0.04%) developed symptoms of new-onset lupus-like syndrome and
recovered after discontinuation of adalimumab.
Low-titer antibodies to adalimumab have been observed at least once during
treatment in 5% of patients (n=1062). Antibodies developed in 12% of patients
on adalimumab monotherapy and in 1% of patients on concurrent methotrexate.
During monotherapy, the ACR20 (American College of Rheumatology criteria)
response was lower in antibody-positive patients.
A meta-analysis has reported that there is evidence of an increased risk of serious
infections in patients with rheumatoid arthritis treated with anti-TNF antibody therapy.
Musculoskeletal
Musculoskeletal side effects have included back pain in 6% of patients; and arthritis,
bone disorder, nonspontaneous bone fracture, bone necrosis, joint disorder, muscle
cramps, myasthenia, pyogenic arthritis, synovitis, and tendon disorder in less than
5% of patients. A case of severe myalgia has also been reported.
Respiratory
Respiratory side effects have included upper respiratory infection (17%),
sinusitis (11%), and flu syndrome (7%). Asthma, bronchospasm, dyspnea, lung
disorder, decrease lung function, pleural effusion, pneumonia, and interstitial lung
disease including pulmonary fibrosis have been reported in less than 5% of patients.
Gastrointestinal
Gastrointestinal side effects have included nausea (9%) and abdominal pain (7%).
Cholecystitis, cholelithiasis, esophagitis, gastroenteritis, gastrointestinal disorder,
gastrointestinal hemorrhage, hepatic necrosis, and vomiting have been reported in
less than 5% of patients.
Metabolic
Metabolic side effects have included hypercholesterolemia (6%), hyperlipidemia
(7%), increased alkaline phosphatase (5%), and unspecified abnormal laboratory
tests (8%). Dehydration, abnormal healing, ketosis, paraproteinemia, and
peripheral edema have been reported in less than 5% of patients.
Genitourinary
Genitourinary side effects have included urinary tract infection (8%) and hematuria
(5%). Cystitis, kidney calculus, menstrual disorder and pyelonephritis have been
reported in less than 5% of patients.
Local
Local side effects have included injection site pain (12%) and injection site reaction
(8%).
Dermatologic
Dermatologic side effects have included rash (12%). Cellulitis, erysipelas,
cutaneous vasculitis, and herpes zoster have been reported in less than 5% of patients.
There have been postmarketing reports of erythema multiforme and new
or worsening psoriasis (all subtypes including pustular and palmoplantar). A case of
alopecia areata universalis has also been reported.
Cardiovascular
Cases of worsening congestive heart failure (CHF) and new onset CHF have been
reported with TNF blockers, including adalimumab. In clinical studies of another
TNF blocker, a higher rate of serious CHF-related adverse events was observed.
Cardiovascular side effects have included hypertension (5%). Arrhythmia, atrial
fibrillation, cardiovascular disorder, chest pain, congestive heart failure, coronary
artery disorder, heart arrest, hypertensive encephalopathy, myocardial infarct,
palpitation, pericardial effusion, pericarditis, syncope, tachycardia, and vascular
disorder have been reported in less than 5% of patients. A case of vasculitis has
also been reported.
Endocrine
Endocrine side effects have included parathyroid disorder in less than 5% of
patients.
Hematologic
Hematologic side effects have included agranulocytosis, granulocytopenia,
leukopenia, thrombocytopenia, lymphoma-like reaction, pancytopenia,
polycythemia, and leg thrombosis in less than 5% of patients. A case of
hypertriglyceridemia has also been reported.
Other
Side effects affecting the body as a whole have included fever, infection, extremity
pain, pelvic pain, sepsis, surgery, thorax pain, and reactivated tuberculosis in less
than 5% of patients.
Other
Accidental injury has been reported in 10% of patients.
Ocular
Ocular side effects have included cataract (50% 28%
<2500 cells/mm3 16% 5.3%
Infections 20% <1%
Neoplasia *
Lymphoma 0.5%
Others 2.8%
* Data on the rate and risk of neoplasia among persons with rheumatoid arthritis
treated with azathioprine are limited. The incidence of lymphoproliferative disease
in patients with RA appears to be significantly higher than that in the general
population. In one completed study, the rate of lymphoproliferative disease in
RA patients receiving higher than recommended doses of azathioprine (5 mg/kg
per day) was 1.8 cases per 1000 patient-years of follow-up, compared with 0.8 cases
per 1000 patient-years of follow-up in those not receiving azathioprine. However,
the proportion of the increased risk attributable to the azathioprine dosage or to
other therapies (i.e., alkylating agents) received by patients treated with azathioprine
cannot be determined.
Hematologic: Leukopenia and/or thrombocytopenia are dose-dependent and may
occur late in the course of therapy with Imuran. Dose reduction or temporary
withdrawal may result in reversal of these toxicities. Infection may occur as a
secondary manifestation of bone marrow suppression or leukopenia, but the
incidence of infection in renal homotransplantation is 30 to 60 times that in
rheumatoid arthritis. Macrocytic anemia and/or bleeding have been reported.
TPMT genotyping or phenotyping can help identify patients with low or absent
TPMT activity (homozygous for non-functional alleles) who are at increased risk
for severe, life-threatening myelosuppression from Imuran. See CLINICAL
PHARMACOLOGY, WARNINGS and PRECAUTIONS:Laboratory Tests.
Death associated with pancytopenia has been reported in patients with absent
TPMT activity receiving azathioprine. 6, 20
Gastrointestinal: Nausea and vomiting may occur within the first few months of
therapy with Imuran, and occurred in approximately 12% of 676 rheumatoid
arthritis patients. The frequency of gastric disturbance often can be reduced by
administration of the drug in divided doses and/or after meals. However, in some
patients, nausea and vomiting may be severe and may be accompanied by
symptoms such as diarrhea, fever, malaise, and myalgias. Vomiting with abdominal
pain may occur rarely with a hypersensitivity pancreatitis. Hepatotoxicity manifest
by elevation of serum alkaline phosphatase, bilirubin, and/or serum transaminases
is known to occur following azathioprine use, primarily in allograft recipients.
Hepatotoxicity has been uncommon (less than 1%) in rheumatoid arthritis patients.
Hepatotoxicity following transplantation most often occurs within 6 months of
transplantation and is generally reversible after interruption of Imuran. A rare,
but life-threatening hepatic veno-occlusive disease associated with chronic
administration of azathioprine has been described in transplant patients and in one
patient receiving Imuran for panuveitis.21, 22, 23 Periodic measurement of serum
transaminases, alkaline phosphatase, and bilirubin is indicated for early detection
of hepatotoxicity.
If hepatic veno-occlusive disease is clinically suspected, Imuran should be
permanently withdrawn.
Others: Additional side effects of low frequency have been reported. These
include skin rashes, alopecia, fever, arthralgias, diarrhea, steatorrhea, negative
nitrogen balance, reversible interstitial pneumonitis and hepatosplenic T-cell
lymphoma.
Hematologic
Bone marrow suppression is dose related and is the most common cause for dosage
reductions. There are data to support an increased risk of bone marrow aplasia in
patients with very low or absent thiopurine methyltransferase (TPMT) activity. The
majority of the population has high TPMT activity, 11% have moderate activity, and
approximately one in 300 persons has very low to no activity. The main metabolic
pathway of azathioprine, conversion to 6-MP, involves TPMT. Limitations in this
pathway lead to increased metabolism via alternate pathways. In patients with low
TPMT activity, there is an increase in 6-thioguanine nucleotide (6-TGN)
concentrations, a cytotoxic metabolite which suppresses purine synthesis. Despite
these findings, bone marrow aplasia has been reported in patients with normal
TPMT activity. A 55-year-old male with pompholyx and deficiency of erythrocyte
thiopurine methyltransferase experienced pancytopenia coincident with azathioprine
therapy. Ten weeks after starting azathioprine 100 mg per day, a full blood count
(during routine monitoring) showed moderate pancytopenia. Azathioprine was
discontinued. Ten days later he was admitted to the hospital with malaise, lethargy,
and deterioration in blood count. He was treated with blood and platelet transfusions
and discharged eight days later with modest improvement in peripheral blood count.
Hematologic side effects have included reversible bone marrow suppression, resulting
in severe thrombocytopenia, anemia, and leukopenia in up to 50% of patients.
Macrocytosis (1%), hemolytic anemia, pure red cell aplasia (rare), and pancytopenia
(rare) have been reported. Fatal myelosuppression has been reported in a carrier of
heterozygous thiopurine S-methyl transferase *1/*3C.
Gastrointestinal
Gastrointestinal (GI) side effects have been reported the most frequently. These have
included nausea, vomiting, diarrhea, and anorexia. Severe villus, chronic malabsorption
syndrome, acute pancreatitis, GI discomfort, and steatorrhea have been reported. Case
reports of patients with symptoms that imitate viral gastroenteritis (nausea, vomiting,
diarrhea, and fever) hours after a single dose of azathioprine have also been reported.
Gastrointestinal side effects tend to be more problematic in the first few months of
therapy.
A 20-year-old man developed severe small-bowel villus atrophy and chronic
diarrhea after starting azathioprine 50 mg per day. Diarrhea completely resolved
within 2 weeks after azathioprine discontinuation. Mucosal biopsies at 4 months
post azathioprine discontinuation showed complete reversal of severe duodenal villus
atrophy.
Hepatic
Hepatotoxicity usually occurs within the first six months of therapy and is more
common in patients requiring immunosuppression following transplant than in
patients requiring therapy for rheumatoid arthritis. Hepatotoxicity, often manifest
as cholestasis and/or acute focal hepatocellular necrosis, is generally reversible
following discontinuation of azathioprine therapy. However, permanent hepatic
damage associated with cirrhosis, perisinusoidal fibrosis, hepatic peliosis, sinusoidal
dilatation, and veno-occlusive disease is also reported.
Veno-occlusive disease of the hepatic veins is due to an unknown mechanism, may
affect males more often, usually precedes portal hypertension, and carries a poor
prognosis. Numerous fatalities have been reported. Permanent discontinuation of
azathioprine therapy is indicated if hepatic veno-occlusive disease is suspected.
A 51-year-old man developed jaundice and diffuse abdominal pain two months after
the start of azathioprine 1.4 mg/kg/day. Biopsy reports confirmed destruction of the
bile ducts consistent with destructive cholangitis. After discontinuation of
azathioprine, the abdominal pain disappeared within 2 days; and liver function tests
improved and returned to normal values 8 weeks later. Hepatic side effects have
included elevations in alkaline phosphatase, bilirubin, and/or serum transaminases,
cholestatic jaundice, hepatitis, and hepatic veno-occlusive disease in up to 6% of
patients. Other hepatotoxic side effects have included cirrhosis, perisinusoidal
fibrosis, hepatic peliosis, sinusoidal dilatation, cholestasis, and acute focal
hepatocellular necrosis. In addition, several cases of nodular regenerative hyperplasia
of the liver and at least one case of destructive cholangitis have been reported.
Oncologic
Oncologic side effects have included an increased risk of cancer, particularly
lymphomas and leukemias. Case reports of common de novo tumors that have
developed in renal transplant patients have included basal cell (21.7%), squamous
cell carcinomas of the skin (13.9%), urogenital malformations (10.4%), lung
malformations (9.6%), and Kaposi’s sarcoma (9.6%; half cutaneous and half visceral).
Lymphoproliferative disease in azathioprine-treated rheumatoid arthritis patients
have been reported in approximately 1.8 cases per 1000 patient years of follow-up
compared to an incidence of 0.8 cases per 1000 patient years of follow-up in the
normal population. Epstein-Barr virus-positive lymphoma and hepatosplenic T-cell
lymphoma have also been reported.
The increased risk of cancer may be more pronounced when azathioprine is used
concomitantly with other immunosuppressive agents.
Renal transplant patients may have a higher risk of developing lymphoproliferative
disorders, lymphomas, and leukemia, as well as some solid tumors while receiving
azathioprine.
Transplant patients as well as those with rheumatoid arthritis are often treated with
multiple immunosuppressants; therefore, the true risk of neoplasia associated with
azathioprine alone has yet to be determined.
A small increase in the risk of Epstein-Barr virus-positive lymphoma was seen in a
study of patients with inflammatory bowel disease treated with azathioprine.
Hypersensitivity
Hypersensitivity side effects have included hypersensitivity rash (1%),
leukocytoclastic vasculitis (1%), skin rash, fever, chills, malaise, diarrhea, nausea,
hepatitis, hypotension, and circulatory collapse. Hypersensitivity has also been
implicated in cases of hepatotoxicity, interstitial nephritis, interstitial pneumonitis,
pancreatitis, and vasculitis. As azathioprine is metabolized to 6-mercaptopurine,
rechallenge with both agents should be avoided. Hypersensitivity reactions which
manifest from mild gastrointestinal disturbances, fever, and myalgias to severe
hypotension and shock have been reported. Rhabdomyolysis has been reported
as part of an azathioprine hypersensitivity syndrome. At least 3 cases of erythema
nodosum, 2 cases of pustules, and 1 case of contact dermatitis have been reported.
Erythema nodosum and pustules are rarely reported manifestations of azathioprine
hypersensitivity. Both types of skin lesions may be related to the clinical activity of
inflammatory bowel disease. Relapse of such lesions shortly after rechallenge
should raise the hypothesis of hypersensitivity rather than pharmacological
manifestations.
Gastrointestinal hypersensitivity is characterized by severe nausea and vomiting
which may be accompanied by diarrhea, rash, fever, malaise, myalgias, elevated
liver function tests, and hypotension.
Cardiovascular
A 52-year-old male with steroid-dependent ulcerative colitis experienced atrial
fibrillation coincident with azathioprine therapy. The drug had been started 3 years
earlier, but discontinued after a few months because the patient reported palpitations,
lipothymia, nausea, and vomiting. Upon a rechallenge with 50 mg of azathioprine,
the patient showed general malaise, nausea, and vomiting. An ECG showed atrial
fibrillation, and the patient reported that the symptoms were similar to those
experienced previously.
Azathioprine-induced hypotension is independent of dose and may accompany
signs and symptoms of hypersensitivity. Hypotension may be profound, although it
is usually responsive to intravenous fluids and, if hypersensitivity is suspected,
corticosteroids.
Cardiovascular side effects have included rare cases of hypotension, including
cardiogenic shock. At least three cases of atrial fibrillation have been reported
(one case involving a patient with ulcerative colitis), although causality is unknown.
Respiratory
Review of seven rare cases of azathioprine-associated interstitial pneumonitis
revealed that the progression from alveolitis to pulmonary fibrosis may be
dose-related. Respiratory side effects have included interstitial pneumonitis
associated with a restrictive pattern on pulmonary function tests.
Renal
A reduction in the incidence of chronic allograft nephropathy has been reported
during the extended follow-up (greater than or equal to 10 years) of patients (n=128)
participating in a randomized trial that examined the conversion from cyclosporine to
azathioprine as early as three months after renal transplantation.
A 47-year-old female with Wegener’s granulomatosis experienced rapid progression
of renal failure within 10 days of starting azathioprine for vasculitis. Her creatinine
was 119 mcmol/L at the time of presentation. Acute tubulointerstitial nephritis and
no active glomerulonephritis were observed on renal biopsy. Her renal function
started improving by day 6 post-admission and at one month post-admission her
serum creatinine was 116 mcmol/L. She continued to have reasonable renal function
and 16 months later had creatinine of 104 mcmol/L with no clinical evidence of
recurrent interstitial nephritis.
Renal side effects have included elevation in serum creatinine and BUN accompanied
by oliguria, but are usually associated with hypotension, and normalize after treatment
with intravenous hydration and steroids. Rare cases of hematuria secondary to
azathioprine-induced crystalluria have been reported, and may be less common with
high urine output. Chronic allograft nephropathy and at least one case of acute
interstitial nephritis have been reported.
Dermatologic
Dermatologic side effects have included alopecia (1%). Verrucae, zoster, increased
skin color, malignant neoplasms, Kaposi sarcoma, dermatomycoses, cytomegalovirus
infection, scabies, skin lesions, Sweet syndrome, and at least one case of skin peeling
syndrome have been reported.
A female patient developed skin peeling syndrome eight months after the dosage of
azathioprine was reduced to 25 mg daily. Skin lesions resolved 30 days after drug
withdrawal.
Excess sun exposure, pale skin types, and duration of allograft seem to be important
risk factors in the development of skin lesions.
Immunologic
A patient with systemic lupus erythematosus and end-stage renal disease experienced
CMV retinitis coincident with azathioprine therapy. It is theorized that
immunosuppressive therapy may have a role in the development of CMV retinitis in
this population. The patient responded to discontinuation of azathioprine, lowering
of the corticosteroid dose, and systemic administration of ganciclovir.
Immunologic side effects have included at least one case of bilateral cytomegalovirus
(CMV) retinitis.
Metabolic
Metabolic side effects have included negative nitrogen balance (less than 1%).
Musculoskeletal
Musculoskeletal side effects have included arthralgias (less than 1%).
Other
Other side effects have included infection in up to 20% of patients, even with
therapeutic doses of azathioprine. These have included fungal, protozoal, viral, and
uncommon bacterial infections, some of which have been fatal. Fever, delayed wound
healing, oral lesions, fatigue, and malaise have also been reported.
Plaquenil – an other Rheumatoid arthritis medication
http://www.drugs.com/sfx/plaquenil-side-effects.html
Ocular
Ocular side effects have included disturbances of accommodation with symptoms
of blurred vision (dose-related and reversible with treatment cessation). Corneal
side effects have included transient edema, punctate to lineal opacities, decreased
corneal sensitivity, corneal changes (with or without accompanying symptoms,
including blurred vision, halos around lights, photophobia), and corneal deposits.
Retinal (macular) side effects have included edema, atrophy, abnormal pigmentation
(mild pigment stippling to a “bullseye” appearance), loss of foveal reflex, increased
macular recovery time following exposure to a bright light (photostress test), and
elevated retinal threshold to red light in macular, paramacular, and peripheral retinal
areas. Other fundus changes have included optic disc pallor and atrophy, attenuation
of retinal arterioles, fine granular pigmentary disturbances in the peripheral retina,
and prominent choroidal patterns in advanced stage. Visual field defects have
included pericentral or paracentral scotoma, central scotoma with decreased visual
acuity, rarely field constriction, and abnormal color vision. The most common visual
symptoms attributed to retinopathy are reading and vision difficulties (words, letters,
or parts of objects missing), photophobia, blurred distance vision, missing or blacked
out areas in the central or peripheral visual field, and light flashes and streaks. Patients
with retinal changes may have visual symptoms or may be asymptomatic (with or
without visual field changes). Rarely scotomatous vision or field defects may occur
without obvious retinal change. A few cases of retinal changes consisting of change
in retinal pigmentation (detected on periodic ophthalmologic examination) with visual
field defects in some instances have been reported in patients receiving only
hydroxychloroquine. A case of delayed retinopathy with vision loss starting 1 year
after hydroxychloroquine discontinuation has been reported. Night vision difficulties
and immediate blurred vision have been reversible with treatment cessation.
The corneal changes (fairly common) have been reversible. Corneal deposits have
been reported as early as 3 weeks after the initiation of therapy.
Retinopathy appears to be dose related and has occurred within several months (rarely)
to several years of daily therapy.
Gastrointestinal
Gastrointestinal side effects have included diarrhea, anorexia, nausea, abdominal
cramps, vomiting, and epigastric pain. A case of pigmentation of the gums has
also been reported.
Nervous system
Nervous system side effects have included headache, dizziness, vertigo, tinnitus,
nystagmus, nerve deafness, convulsions, and ataxia.
Psychiatric
Psychiatric side effects have included irritability, nervousness, emotional changes,
nightmares, and psychosis.
Musculoskeletal
Musculoskeletal side effects have included skeletal muscle palsies, skeletal muscle
myopathy, or neuromyopathy leading to progressive weakness and atrophy of
proximal muscle groups which may be associated with mild sensory changes,
depression of tendon reflexes, and abnormal nerve conduction. Absent or
hypoactive deep tendon reflexes and extraocular muscle palsies have been reported.
Neuromyotoxicity has been associated with hydroxychloroquine concurrently with
worsening renal function.
Dermatologic
Mucocutaneous hyperpigmentation over all extremities, the torso, and the hairline
has been reported in an elderly man after long-term hydroxychloroquine use. Skin
biopsies demonstrated sharply defined red-brown fibers in the deep dermis and the
classic “banana-shaped body” associated with exogenous ochronosis.
Dermatologic side effects have included nonlight-sensitive psoriasis, bleaching of hair,
alopecia, pruritus, skin and mucosal pigmentation, photosensitivity, and skin eruptions
(urticarial, morbilliform, lichenoid, maculopapular, purpuric, erythema annulare
centrifugum, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis,
and exfoliative dermatitis). A case of generalized pustular drug rash has also been
reported.
Hematologic
Hematologic side effects have included various blood dyscrasias such as aplastic
anemia, agranulocytosis, leukopenia, anemia, and thrombocytopenia. Hemolysis
has been reported in individuals with glucose-6-phosphate dehydrogenase deficiency.
Cardiovascular
The causal relationship of hydroxychloroquine to cardiomyopathy has not been
established. Cardiovascular side effects have rarely included cardiomyopathy with
high daily dosages.
Hepatic
Hepatic side effects have included isolated cases of abnormal liver function and
fulminant hepatic failure.
Metabolic
Metabolic side effects have included weight loss and exacerbation or precipitation
of porphyria.
Other
Other side effects have included lassitude.
Hypersensitivity
Hypersensitivity side effects have included allergic reactions (urticaria, angioedema,
and bronchospasm) and hypersensitivity myocarditis.
Endocrine
Endocrine side effects have included a case report of hypoglycemia induced by
hydroxychloroquine in a type II diabetic treated for polyarthritis.
Solu-Medrol – a different class of Rheumatoid arthritis medication
http://www.drugs.com/sfx/solu-medrol-side-effects.html
Solu-Medrol Side Effects
Fluid and Electrolyte Disturbances
Sodium retention
Fluid retention
Congestive heart failure in susceptible patients
Potassium loss
Hypokalemic alkalosis
Hypertension
Musculoskeletal
Muscle weakness
Steroid myopathy
Loss of muscle mass
Severe arthralgia
Vertebral compression fractures
Aseptic necrosis of femoral and humeral heads
Pathologic fracture of long bones
Osteoporosis
Tendon rupture, particularly of the Achilles tendon
Gastrointestinal
Peptic ulcer with possible perforation and hemorrhage
Pancreatitis
Abdominal distention
Ulcerative esophagitis
Increases in alanine transaminase (ALT, SGPT), aspartate transaminase (AST, SGOT),
and alkaline phosphatase have been observed following corticosteroid treatment.
These changes are usually small, not associated with any clinical syndrome and are
reversible upon discontinuation.
Dermatologic
Impaired wound healing
Thin fragile skin
Petechiae and ecchymoses
Facial erythema
Increased sweating
May suppress reactions to skin tests
Neurological
Increased intracranial pressure with papilledema (pseudo-tumor cerebri) usually
after treatment
Convulsions
Vertigo
Headache
Endocrine
Development of Cushingoid state
Suppression of growth in children
Secondary adrenocortical and pituitary unresponsiveness, particularly
in times of stress,
as in trauma, surgery or illness
Menstrual irregularities
Decreased carbohydrate tolerance
Manifestations of latent diabetes mellitus
Increased requirements for insulin or oral hypoglycemic agents in diabetics
Ophthalmic
Posterior subcapsular cataracts
Increased intraocular pressure
Glaucoma
Exophthalmos
Metabolic
Negative nitrogen balance due to protein catabolism
The following additional adverse reactions are related to parenteral corticosteroid
therapy:
Hyperpigmentation or hypopigmentation
Subcutaneous and cutaneous atrophy
Sterile abscess
Anaphylactic reaction with or without circulatory collapse, cardiac
arrest, bronchospasm
Urticaria
Nausea and vomiting
Cardiac arrhythmias; hypotension or hypertension
weeks). Short-term effects have included sodium retention-related weight gain and
fluid accumulation, hyperglycemia and glucose intolerance, hypokalemia,
gastrointestinal upset and ulceration, reversible depression of the
hypothalamic-pituitary-adrenal (HPA) axis, and mood changes ranging from mild
euphoria and insomnia to nervousness, restlessness, mania, catatonia, depression,
delusions, hallucinations, and violent behavior.
Long-term effects have included HPA suppression, Cushingoid appearance, hirsutism
or virilism, impotence, and menstrual irregularities, peptic ulcer disease, cataracts
and increased intraocular pressure/glaucoma, myopathy, osteoporosis,
and vertebral compression fractures.
Cardiovascular
Cardiovascular side effects have included hypertension and congestive heart failure
due to long-term fluid retention as well as direct vascular effects. Bradycardia,
cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, fat
embolism, myocardial rupture following recent myocardial infarction, syncope,
tachycardia, thromboembolism, thrombophlebitis, and vasculitis have also been
reported. Hypertension has been associated with long-term therapy with
corticosteroids and is thought to be due to fluid retention.
Endocrine
Corticosteroid therapy may induce glucose intolerance by reducing the utilization of
glucose in tissues and increasing hepatic glucose output. Patients on alternate day
therapy may exhibit significantly higher serum glucose on the day methylprednisolone
is taken. Diabetes mellitus requiring diet modifications and hypoglycemic agents has
developed in some patients.
Adrenal suppression can persist for up to twelve months after long-term corticosteroid
therapy. Adrenal suppression may be reduced by giving corticosteroids once a day or
once every other day. After corticosteroid therapy has been tapered, supplemental
corticosteroid therapy during times of physical stress may be required.
Endocrine side effects have included decreased glucose tolerance and hyperglycemia
resulting in diabetes-like symptoms. Hypothalamic-pituitary-adrenal activity has been
suppressed 12 months or more following long-term corticosteroid administration.
Cushingoid appearance commonly has occurred with chronic therapy. Hirsutism or
virilism, impotence, and menstrual irregularities may occur. Glycosuria, hirsutism, and
hypertrichosis have also been reported.
Gastrointestinal
Gastrointestinal side effects have included gastrointestinal upset, nausea, vomiting,
and peptic ulcer disease. Pancreatitis, ulcerative esophagitis, gastrointestinal
perforation and hemorrhage have also been reported. Additionally, abdominal
distention, bowel/bladder dysfunction (after intrathecal administration), increased
appetite, and perforation of the small and large intestine (particularly in patients with
inflammatory bowel disease) have been reported.
Gastrointestinal effects most commonly occurring during corticosteroid therapy
have included nausea, vomiting, dyspepsia, and anorexia. Peptic ulcer disease has been
associated with long-term corticosteroid therapy, but is relatively uncommon. Routine
prophylactic therapy is not warranted in all individuals. Aluminum/magnesium c
ontaining antacids generally have been used to manage GI complaints without
significant drug interactions.
Metabolic
Metabolic side effects have included hypernatremia (rare), hypokalemia, fluid
retention, negative nitrogen balance and increase in blood urea nitrogen concentration.
Musculoskeletal
Musculoskeletal side effects have included myopathy, osteoporosis, vertebral
compression fractures, tendon rupture (particularly the Achilles tendon), and aseptic
necrosis of bone have occurred during corticosteroid therapy. Aseptic necrosis
most often has affected the femoral head. Charcot-like arthropathy, loss of muscle
mass, muscle weakness, osteoporosis, pathologic fracture of long bones, and vertebral
compression fractures has also been reported.
Corticosteroid myopathy presenting as weakness and wasting of the proximal limb
and girdle muscles has occurred, but has generally resolved following cessation of t
herapy.
Corticosteroids inhibit intestinal absorption and increase urinary excretion of calcium
leading to bone resorption and bone loss. Bone loss of 3% over one year has been
demonstrated with prednisolone 10 mg per day. Postmenopausal females are at risk
of loss of bone density. Up to 16% of elderly patients treated with corticosteroids for
5 years may experience vertebral compression fractures. One author reported
measurable bone loss over two years in women on concomitant therapy with
prednisone 7.5 mg per day and tamoxifen.
Hematologic
Hematologic side effects have included thrombocytopenia, lymphopenia, and
platelet alterations resulting in thrombolic events.
Immunologic
Immunologic side effects have included impairment in cell-mediated immunity and
increased susceptibility to bacterial, viral, fungal and parasitic infections. Immune
response to skin tests may be suppressed.
Hepatic
Hepatic side effects have included reversible increases in serum transaminase and
alkaline phosphatase concentrations. Hepatomegaly has also bee reported.
Ocular
In renal transplant patients maintained on prednisone 10 mg per day, 33% de-veloped
posterior subcapsular cataracts. Mean time to cataract development was 26 months.
Increased intraocular pressure has occurred in 5% of patients.
Ocular side effects have included increased intraocular pressure, glaucoma, and
posterior subcapsular cataracts.
Psychiatric
Psychiatric side effects have included psychoses, personality or behavioral changes,
depression, emotional instability, euphoria, mood swings, and psychic disorders.
Dermatologic
Dermatologic side effects have included bruising, ecchymosis, petechiae striae,
delayed wound healing, and acne. Allergic dermatitis, cutaneous and subcutaneous
atrophy, dry scaly skin, erythema, hyperpigmentation, hypopigmentation, increase
sweating, rash, sterile abscess, striae, thin fragile skin, and thinning scalp hair, and
urticaria have also been reported.
Other
Other side effects have included a glucocorticoid withdrawal syndrome seen upon
abrupt discontinuation of corticosteroid therapy that was not associated with adrenal
suppression.
Pseudorheumatism, or glucocorticoid-withdrawal syndrome not related to adrenal
insufficiency has occurred on withdrawal of corticosteroids. Patients experienced
anorexia, nausea, vomiting, lethargy, headache, fever, arthralgias, myalgias and
postural hypotension. Symptoms resolved when corticosteroid therapy was reinstated.
Oncologic
Oncologic side effects have included Kaposi’s sarcoma. Clinical remission may occur
with discontinuation of therapy.
Hypersensitivity
Hypersensitivity side effects have included anaphylaxis with or without
circulatory collapse, cardiac arrest, or bronchospasm with parenteral
administration of methylprednisolone. Anaphylactoid reactions and angioedema
have also been reported.
Local
Local side effects have included hyperpigmentation, hypopigmentation, subcutaneous
and cutaneous atrophy, and sterile abscess at injection sites following parenteral
administration.
Respiratory
Respiratory side effects have included pulmonary edema.
Nervous system
Nervous system side effects have included convulsions, headache, increased
intracranial pressure with papilledema (pseudotumor cerebri) usually following
discontinuation of treatment, insomnia, neuritis, neuropathy, paresthesia, and vertigo.
Common NSAID side effectsGastrointestinal
In a study designed to measure gastrointestinal blood loss associated with the oral
administration of nabumetone, aspirin, or placebo in healthy volunteers,
nabumetone was not statistically different from placebo while aspirin was
associated with significant gastrointestinal microbleeding. In addition, endoscopy
studies have confirmed a reduced incidence of gastropathy associated with
nabumetone compared to other nonsteroidal anti-inflammatory agents.
In a follow-up study involving 1,677 patients treated with nabumetone for up to 8
years, serious gastrointestinal side effects such as ulceration, bleeding, and/or
perforation, occurred in 16 patients, representing a cumulative incidence of 0.95%.
Patients with a history of serious gastrointestinal events or alcohol abuse are at
increased risk for severe gastrointestinal side effects. Nabumetone should be used
with caution in these patients.
Gastrointestinal side effects have been reported the most frequently. These have
included diarrhea (14%), dyspepsia (13%), and abdominal pain (12%). Between
3% to 9% of patients have reported nausea, constipation, positive stool guaiac,
and flatulence. Adverse effects occurring in less than 3% of the patients have
included dry mouth, gastritis, stomatitis, vomiting, anorexia, duodenal ulcer,
dysphagia, gastric ulcer, gastroenteritis, gastrointestinal bleeding, and increased
appetite. Despite the fact that nabumetone is a nonacidic prodrug, and as such,
has a decreased propensity for causing gastric mucosal damage, serious
gastrointestinal side effects, such as bleeding, ulceration, and perforation have been
reported in up to 0.95% of patients.
Hepatic
Elevations in serum transaminases three times normal values are reported in less
than 1% of patients treated with nabumetone. Serious hepatotoxicity, including fatal
fulminant hepatitis, is reported with other nonsteroidal anti-inflammatory agents.
Patients with signs or symptoms of hepatic dysfunction or who develop significant
elevations in serum transaminases during nabumetone therapy should be evaluated
for evidence of more serious hepatotoxicity.
Hepatic side effects have included borderline elevations in liver function tests in
up to 15% of patients as well as rare cases of cholestatic jaundice. Due to this patient’s
liver disease, cautious use of nabumetone and frequent monitoring of liver function
tests during therapy is recommended.
Renal
Renal side effects have included albuminuria, azotemia, nephrotic syndrome, and
interstitial nephritis, as well as rare reports of renal failure, dysuria, hematuria, and
renal stones. A fatal case of acute renal failure has also been reported. Due to this
patient’s liver disease, cautious use of nabumetone and frequent monitoring of liver
function tests during therapy is recommended.
Nabumetone may impair the ability of the kidney to cope with low renal blood flow
states due to inhibition of prostaglandin-dependent afferent arteriolar vasodilation.
Renal function may be further compromised in patients with heart failure,
hypovolemia, cirrhosis, nephrotic syndrome, or hypoalbuminemia. Additional risk
factors for nabumetone-induced renal insufficiency are advanced age and concomitant
use of diuretics.
A case-control study suggested that patients who consumed 5000 or more pills
containing NSAIDs during their lifetime may be at increased risk of end-stage renal
disease.
Dermatologic
Dermatologic side effects have included rash (6.9%) and pruritus (3.9%). Acne,
alopecia, bullous eruptions, photosensitivity, pseudoporphyria, erythema
multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have also
been reported.
Pseudoporphyria was diagnosed in two patients after approximately 16 months of
nabumetone therapy. Skin fragility persisted for longer than 12 months. High factor
sunscreens were used on these patients.
Hematologic
Hematologic side effects have rarely included iron deficiency anemia,
aplastic anemia, thrombocytopenia, granulocytopenia, and leukopenia.
Hypersensitivity
Hypersensitivity side effects have included anaphylactoid reactions, anaphylaxis,
facial itching, angioedema, urticaria, and bronchospasm.
Nervous system
Nervous system side effects have included headache (9.2%) and dizziness (5.7%).
Asthenia, fatigue, insomnia, nervousness, somnolence, tremor, agitation, anxiety,
confusion, depression, malaise, vertigo, and nightmares have also been reported.
Psychiatric
Psychiatric side effects have included rare reports of agitation, anxiety,
and depression.
Cardiovascular
Nonsteroidal anti-inflammatory drugs (NSAIDs) may elevate blood pressure and
increase the risk for the initiation of antihypertensive therapy. Furthermore, NSAIDs
may antagonize the blood pressure lowering effect of antihypertensive mediations
in patients already being treated with antihypertensive drugs.
Cardiovascular side effects have included vasculitis. Angina, arrhythmia,
hypertension, myocardial infarction, palpitations, syncope, and thrombophlebitis
have also been reported.
Respiratory
Pulmonary fibrosis was reported in a 68-year-old female with osteoarthritis and
osteoporosis treated with nabumetone 1500 mg per day. Symptoms of shortness
of breath and dry cough began within 2 weeks of initiation of therapy, and
progressed over a course of 6 weeks until the diagnosis of drug-induced pulmonary
fibrosis was made. Treatment, consisting of corticosteroids and discontinuation of
nabumetone, resulted in rapid resolution of physical signs and symptoms.
Respiratory side effects have rarely included dyspnea, asthma, cough, idiopathic
interstitial pneumonitis, eosinophilic pneumonia, and hypersensitivity pneumonitis.
A case of pulmonary fibrosis has also been reported.
Other
Other side effects have included tinnitus (3.9%), abnormal vision, taste disorder,
fever, and chills.
Genitourinary
Genitourinary side effects have included albuminuria, azotemia, hematuria, dysuria,
hyperuricemia, impotence interstitial nephritis, nephrotic syndrome, renal stones,
and vaginal bleeding.
Metabolic
Metabolic side effects have included weight loss, hyperglycemia, and hypokalemia
All Rheumatoid arthritis medications involve the side effects shown for the various
classes of medications listed above. Does anyone honestly believe the side effects
of these medications are safer than cannabis/marijuana? How can anyone in good
concience insist an informed patient be restricted to these and similar chemical
medications and refuse to allow a more effective, far safer natural substance to be
used instead? The choice should be made by the patient and his or her Doctor.
Why and how Marijuana really works and the benefits, compared to the chemical
pharmaceuticals it truly is the perfect healing herb for so many health conditions :
The following can be found here
http://www.cannabis-med.org/data/pdf/2001-03-04-7.pdf
that herbs contain many active ingredients. Primary active ingredients
may be enhanced by secondary compounds, which act in beneficial synergy.
Other herbal constituents may mitigate the side effects of dominant
active ingredients. We reviewed the literature concerning medical cannabis
and its primary active ingredient, Δ9-tetrahydrocannabinol (THC).
Good evidence shows that secondary compounds in cannabis may enhance
the beneficial effects of THC. Other cannabinoid and non-cannabinoid
compounds in herbal cannabis or its extracts may reduce THC-induced
anxiety, cholinergic deficits, and immunosuppression. Cannabis terpenoids
and flavonoids may also increase cerebral blood flow, enhance cortical
activity, kill respiratory pathogens, and provide anti-inflammatory activity.
[Article copies available for a fee from The Haworth Document Delivery
Service: 1-800-342-9678. E-mail address: getinfo@haworthpressinc.com
Website: http://www.HaworthPress.com 2001 by The Haworth Press, Inc.
All rights reserved.]
John M. McPartland, DO, MS, is affiliated with GW Pharmaceuticals, Ltd., Porton
Down Science Park, Salisbury, Wiltshire, SP4 0JQ, UK.
Ethan B. Russo, MD, is affiliated with Montana Neurobehavioral Specialists, 900
North Orange Street, Missoula, MT 59802 USA.
Address correspondence to: John M. McPartland, DO, Faculty of
Health&Environmental Science, UNITEC, Private Bag 92025, Auckland,
New Zealand (E-mail: jmcpartland @unitec.ac.nz).
The authors thank David Pate and Vincenzo Di Marzo for pre-submission reviews.
[Haworth co-indexing entry note]: “Cannabis and Cannabis Extracts: Greater Than
the Sum of Their
Parts?” McPartland, John M., and Ethan B. Russo. Co-published simultaneously in
Journal of Cannabis Therapeutics
(The Haworth Integrative Healing Press, an imprint of The Haworth Press, Inc.)
Vol. 1, No. 3/4,
2001, pp. 103-132; and: Cannabis Therapeutics in HIV/AIDS (ed: Ethan Russo)
The Haworth Integrative
Healing Press, an imprint of The Haworth Press, Inc., 2001, pp. 103-132. Single or
multiple copies of this article
are available for a fee from The Haworth Document Delivery Service
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Cannabis and Cannabis Extracts: Greater Than the Sum of Their Parts?
INTRODUCTION
Cannabis is an herb; it contains hundreds of pharmaceutical compounds
(Turner et al. 1980). Herbalists contend that polypharmaceutical herbs provide
two advantages over single-ingredient synthetic drugs: (1) therapeutic effects
of the primary active ingredients in herbs may be synergized by other compounds,
and (2) side effects of the primary active ingredients may be mitigated
by other compounds. Thus, cannabis has been characterized as a “synergistic
shotgun,” in contrast to Marinol (Δ9-tetrahydrocannabinol, THC), a synthetic,
single-ingredient “silver bullet” (McPartland and Pruitt 1999).
Mechoulam et al. (1972) suggested that other compounds present in herbal
cannabis might influence THC activity. Carlini et al. (1974) determined that
cannabis extracts produced effects “two or four times greater than that expected
from their THC content.” Similarly, Fairbairn and Pickens (1981) detected
the presence of unidentified “powerful synergists” in cannabis extracts
causing 330% greater activity in mice than THC alone.
Other compounds in herbal cannabis may ameliorate the side effects of
THC. Whole cannabis causes fewer psychological side effects than synthetic
THC, seen as symptoms of dysphoria, depersonalization, anxiety, panic reactions,
and paranoia (Grinspoon and Bakalar 1997). This difference in side effect
profiles may also be due, in part, to differences in administration: THC
taken by mouth undergoes “first pass metabolism” in the small intestine and
liver, to 11-hydroxy THC; the metabolite is more psychoactive than THC itself
(Browne and Weissman 1981). Inhaled THC undergoes little first-pass metabolism,
so less 11-hydroxy THC is formed. Thus, “smoking cannabis is a satisfactory
expedient in combating fatigue, headache and exhaustion, whereas the
oral ingestion of cannabis results chiefly in a narcotic effect which may cause
serious alarm” (Walton 1938, p. 49).
Respiratory side effects from inhaling cannabis smoke may be ameliorated by
both cannabinoid and non-cannabinoid components in cannabis. For instance,
throat irritation may be diminished by anti-inflammatory agents, mutagens in
the smoke may be mitigated by antimutagens, and bacterial contaminants in
cannabis may be annulled by antibiotic compounds (McPartland and Pruitt
1997). The pharmaceutically active compounds in cannabis that enhance beneficial
THC activity and reduce side effects are relatively unknown. The pur-
pose of this paper is to review the biochemistry and physiological effects of
those other compounds.
MATERIALS AND METHODS
MEDLINE (1966-2000) was searched using MeSH keywords: cannabinoids,
marijuana, tetrahydrocannabinol. AGRICOLA (1990-1999) was searched
using the keywords cannabis, hemp, and marijuana. Phytochemical and
ethnobotanicaldatabases were searched via the Agricultural Research Service
webpage . All reports were scanned for
supporting bibliographic citations; antecedent sources were retrieved to the
fullest possible extent. Data validity was assessed by source (peer-reviewed
article vs. popular press), identification methodology (analytical chemistry vs.
clinical history) and the frequency of independent observations.
RESULTS AND DISCUSSION
Turner et al. (1980) listed over 420 compounds in cannabis. Sparacino et al.
(1990) listed 200 additional compounds in cannabis smoke. We will highlight
six cannabinoids beyond THC, a dozen-odd terpenoids, three flavonoids, and
one phytosterol. Other non-cannabinoids with proven pharmacological activity
include poorly characterized glycoproteins, alkaloids, and compounds that
remain completely unidentified (Gill et al. 1970).
CANNABINOIDS
Mechoulam and Gaoni (1967) defined “cannabinoids” as a group of C21
terpenophenolic compounds uniquely produced by cannabis. The subsequent
development of synthetic cannabinoids (e.g., HU-210) has blurred this definition,
as has the discovery of endogenous cannabinoids (e.g., anandamide), defined
as “endocannabinoids” by DiMarzo and Fontana (1995). Thus, Pate
(1999) proposed the term “phytocannabinoids” to designate the C21 compounds
produced by cannabis. Phytocannabinoids exhibit very low mammalian
toxicity, and mixtures of cannabinoids are less toxic than pure THC
(Thompson et al. 1973).
Cannabidiol (CBD) is the next-best studied phytocannabinoid after THC
(Figure 1). The investigation of CBD by marijuana researchers is rather paradoxical,
considering its concentrations are notably lower in drug varieties of
cannabis than in fiber cultivars (Turner et al. 1980).
CANNABIS THERAPEUTICS IN HIV/AIDS
CBD possesses sedative properties (Carlini and Cunha, 1981), and a clinical
trial showed that it reduces the anxiety and other unpleasant psychological
side effects provoked by pure THC (Zuardi et al. 1982). CBD modulates the
pharmacokinetics of THC by three mechanisms: (1) it has a slight affinity for
cannabinoid receptors (Ki at CB1 = 4350 nM, compared to THC = 41 nM,
Showalter et al. 1996), and it signals receptors as an antagonist or reverse agonist
(Petitet et al. 1998), (2) CBD may modulate signal transduction by perturbing
the fluidity of neuronal membranes, or by remodeling G-proteins that
carry intracellular signals downstream from cannabinoid receptors, and (3)CBD
is a potent inhibitor of cytochrome P450 3A11 metabolism, thus it blocks the
hydroxylation of THC to its 11-hydroxy metabolite (Bornheim et al. 1995).
The 11-hydroxy metabolite is four times more psychoactive than unmetabolized
THC (Browne and Weissman 1981), and four times more immunosuppressive
(Klein et al. 1987).
CBD provides antipsychotic benefits (Zuardi et al. 1995). It increases dopamine
activity, serves as a serotonin uptake inhibitor, and enhances norepinephrine
activity (Banerjee et al. 1975; Poddar and Dewey 1980). CBD protects
neurons from glutamate toxicity and serves as an antioxidant, more potently
than ascorbate and α-tocopherol (Hampson et al. 1998). Auspiciously, CBD
does not decrease acetylcholine (ACh) activity in the brain (Domino 1976;
Cheney et al. 1981). THC, in contrast, reduces hippocampal ACh release in
rats (Carta et al. 1998), and this correlates with loss of short-term memory
consolidation. In the hippocampus THC also inhibits N-methyl-D-aspartate (NMDA)
receptor activity (Misner and Sullivan 1999; Shen and Thayer 1999), and
NMDA synaptic transmission is crucial for memory consolidation (Shimizu et
al. 2000). CBD, unlike THC, does not dampen the firing of hippocampal cells
(Heyser et al. 1993) and does not disrupt learning (Brodkin and Moerschbaecher
1997).
Consroe (1998) presented an excellent review of CBD in neurological disorders.
In some studies, it ameliorates symptoms of Huntington’s disease, such
as dystonia and dyskinesia. CBD mitigates other dystonic conditions, such as
torticollis, in rat studies and uncontrolled human studies. CBD functions as an
anticonvulsant in rats, on a par with phenytoin (Dilantin, a standard antiepileptic
drug).
CBD demonstrated a synergistic benefit in the reduction of intestinal motility
in mice produced by THC (Anderson, Jackson, and Chesher 1974). This
may be an important component of observed benefits of cannabis in inflammatory
bowel diseases.
The CBD in cannabis smoke may explain why inhaling it causes less airway
irritation and inflammation than inhalation of pure THC (Tashkin et al. 1977).
CBD imparts analgesia (more potently than THC), it inhibits erythema (much
more than THC), it blocks cyclooxygenase (COX) activity with a greater max-
imum inhibition than THC, and it blocks lipoxygenase (the enzyme that produces
asthma-provoking leukotrienes), again more effectively than THC (Evans
1991). Mice with inflammatory collagen-induced arthritis (a mouse model for
rheumatoid arthritis) were given oral CBD (5 mg/kg per day) and showed clinical
improvement, and the treatment effectively blocked progression of the arthritis
(Malfait et al. 2000).
CBD reportedly has little or no effect on the immune system (reviewed by
Klein et al. 1998), although the mouse arthritis study by Malfait et al. (2000)
showed CBD decreases the production of tumor necrosis factor (TNF) and
Interferon-gamma (IFN-γ), which are two immunomodulatory cytokines described
later. CBD actually kills bacteria and fungi, with greater potency than
THC (Klingeren and Ham 1976; ElSohly et al. 1982; McPartland 1984). Thus,
cannabis may have less microbial contamination than other herbs, an important
consideration for immunocompromised individuals (McPartland and Pruitt
1997).
Cannabinol (CBN) is the degradation product of THC (Turner et al. 1980),
and is found most often in aged cannabis products (Figure 1). CBN potentiates
the effects of THC in man (Musty et al. 1976), yet it antagonizes the effects of
THC in mice (Formukong et al. 1988). Studies reporting CBN’s effects upon
norepinephrine and dopamine also conflict–CBN may have negligible effects
on these biogenic amines (Banerjee et al. 1975), enhance their release (Poddar
and Dewey 1980), or decrease their release (Dalterio et al. 1985). CBN increases
plasma concentrations of follicle-stimulating hormone, and enhances
the production of testicular testosterone (Dalterio et al. 1985). CBN shares
some characteristics with CBD; for example, it has anti-convulsant activity
(Turner et al. 1980) and anti-inflammatory activity (Evans et al. 1991).
CBN has affinity for CB1 receptors (Ki at CB1 = 308 nM) and signals as an
agonist (Showalter et al. 1996). Further down the signal transduction cascade,
it stimulates the binding of GTP-γ-S (Petitet et al. 1998), but with half the efficacy
of THC; when CBN is added to THC, the effects are not significantly additive.
CBN has a three-fold greater affinity for CB2 receptors (Ki = 96 nM)
(Showalter et al. 1996), thus it may affect cells of the immune system more
than the central nervous system (Klein et al. 1998). CBN modulates thymocytes
(Herring and Kaminski 1999) by attenuating the activity of the c-AMP response
element-binding protein (CREB), nuclear factor κB (NF-κB), and
interleukin-2 (IL-2). IL-2 is regulated by activator protein-1 (AP-1) transcription
factor, a complex of c-Fos and c-Jun proteins (Foletta et al. 1998); CBN
inhibits the expression of these proteins in splenocytes, via decreased activation
of ERK MAP kinases (Faubert and Kaminski 2000).
Cannabichromene (CBC) is the fourth major cannabinoid, found predominantly
in tropical Cannabis spp. strains (Figure 1). Until the mid-1970s, CBC
was frequently misidentified as CBD, because CBC and CBD have nearly the
same retention times in gas chromatography. Like CBD, CBC decreases
inflammation (Wirth et al. 1980) and provides analgesic effects (Davis and
Hatoum 1983). CBC inhibits prostaglandin synthesis in vitro, but less potently
than CBD or THC (Burstein et al. 1973). CBC exhibits strong antibacterial activity
and mild antifungal activity, superior to THC and CBD in most instances
(ElSohly et al. 1982). Unlike CBD, CBC has no effect on cytochrome P450
enzymes
(Kapeghian et al. 1983), nor does it function as an anticonvulsant in rats
(Davis and Hatoum 1983).
The molecular affinity of CBC for cannabinoid receptors has not been measured.
In mice, CBC causes hypothermia, sedation, and synergizes the depressant
effects of hexobarbital (Hatoum et al. 1981). CBC also sedates dogs and
decreases muscular coordination in rats, but causes no cannabimimetic activity
in monkeys and people (Turner et al. 1980). In rats, the co-administration of
CBC with THC potentiates THC changes in heart rate, but does not potentiate
THC’s hypotensive effects (O’Neil et al. 1979). Co-administration of CBC
lowers the LD50 dose of THC in mice (Hatoum et al. 1981).
Cannabigerol (CBG) is the biosynthetic precursor of CBC, CBD, and THC,
and is present only in minor amounts (Figure 1). CBG has been called “inactive”
when compared to THC, but CBG has slight affinity for CB1 receptors,
approximately the same as CBD (Devane et al. 1988). In rat brains, CBG inhibits
the uptake of serotonin and norepinephrine, less effectively than CBD
and THC, but CBG inhibits GABA uptakemore effectively than CBD and THC
(Banerjee et al. 1975). CBG acts as an analgesic (more potently than THC), it
inhibits erythema (much more than THC), and it blocks lipoxygenase, again
more effectively than THC (reviewed by Evans 1991).
CBG has antibacterial properties (Mechoulam and Gaoni 1965). Its activity
against gram-positive bacteria, mycobacteria, and fungi is superior to that of
THC, CBD, and CBC (ElSohly et al. 1982). CBG inhibits the growth of human
oral epitheloid carcinoma cells (Baek et al. 1998).
Delta-8-THC (Δ8-THC) is an isomer of delta-9-THC; it differs only by the
location of the double bond in the cyclohexal “C” ring. The Ki of Δ8-THC is
126 nM (Compton et al. 1993), and this loosely correlates with human studies,
which show Δ8-THC is less psychoactive than Δ9-THC (Hollister 1974). The
chemical stability of Δ8-THC and its relative ease of synthesis compared to
Δ9-THC, have made Δ8-THC the template for the development of two important
synthetic derivatives, the extremely potent psychoactive CB1 agonist,
HU-210 (Mechoulam and Ben-Shabat 1999), and the non-psychoactive antiemetic
and neuroprotectant, HU-211 (dexanabinol) (Achiron et al. 2000;
Biegon and Joseph 1995; Gallily et al. 1997). Δ8-THC was employed clinically
in an important study (Abrahamov and Mechoulam 1995) in which 8
children with hematological malignancies were treated with the drug over the
course of 8 months at a dose of 18 mg/m2 to treat chemotherapy-associated
nausea and vomiting. Interestingly, not only was this agent uniformly effective
as an antiemetic, but it was also free of psychoactive effects in this age range
(2-13 years).
Tetrahydrocannabivarin (THCV) is a propyl analogue of Δ9-THC, primarily
appearing in indica and afghanica varieties of cannabis, such as hashish
from Nepal (Merkus 1971), dagga from South Africa (Boucher et al. 1977),
and in plants cultivated from seeds from Zambia (Pitts et al. 1992) (Figure 1).
THCV is only 20-25% as psychoactive as Δ9-THC (Hollister 1974). It has a
quicker onset of action than Δ9-THC (Gill et al. 1970), and is of briefer duration
(Clarke 1998). THCV may be clinically effective in migraine treatment
(Personal communication, HortaPharm, November 2000). Kubena and Barry
(1972) suggested THCV synergizes the effects of THC, but did not hypothesize
a mechanism. As a legal fine point, this analogue is not controlled in the
Netherlands, and is not specified in the USA as a Schedule I drug, but would
likely be considered illegal under the Controlled Substance Analogue Enforcement
Act of 1986 (Public Law 99-570). THCV is of interest from a medical-legal
standpoint in that is has been suggested as a biochemical marker of illicit
cannabis use, since it is not a metabolite of Marinol (synthetic THC) (ElSohly
et al. 1999).
TERPENOIDS
The unique smell of cannabis does not arise from cannabinoids, but from
over 100 terpenoid compounds (Turner et al. 1980). Terpenoids derive from
repeating units of isoprene (C5H8), such as monoterpenoids (with C10 skeletons),
sesquiterpenoids (C15), diterpenoids (C20), and triterpenoids (C30). The
final structure of terpenoids ranges from simple linear chains to complex
polycyclic molecules, and they may include alcohol, ether, aldehyde, ketone,
or ester functional groups. These compounds are easily extracted from plant
material by steam distillation or vaporization. This distillate is called the essential
oil or volatile oil of the plant. A range of researchers cite different
yields of essential oil from different types of cannabis: Martin et al. (1961)
cited yields of 0.05-0.11% essential oil from fresh, green leaves and flowers of
mixed male and female plants, from feral hemp growing in Canada. Nigram et
al. (1965) yielded 0.1% essential oil from fresh, whole, male plants from Kashmir.
Malingré et al. (1973) yielded 0.12% essential oil from fresh leaves of
“strain X” obtained from birdseed in the Netherlands. Ross and ElSohly
(1996) yielded 0.29% essential oil from fresh marijuana buds, reputed to be the
Afghani variety “Skunk #1.” Drying the plant material led to a loss of water
content and net weight, concentrating the essential oil to 0.80% in buds that
had been dried at room temperature for one week (Ross and ElSohly 1966).
Field-cultivated cannabis yields about 1.3 liter of essential oil per metric ton
of freshly harvested plant material (Mediavilla and Steinemann 1997). Preventing
pollination increases the yield of essential oil–18 l/ha in sinsemilla
crops, versus 8 l/ha in pollinated crops (Meier and Mediavilla 1998). The
composition of terpenoids varies between strains of cannabis (Mediavilla and
Steinemann 1997), and varies between harvest dates (Meier and Mediavilla
1998).
Many terpenoids vaporize near the same temperature as THC, which boils
at 157°C (see Figures 1-2). Terpenoids are lipophilic and permeate lipid membranes.
Many cross the blood-brain barrier (BBB) after inhalation (Buchbauer
et al. 1993; Nasel et al. 1994).
Meschler and Howlett (1999) discussed several mechanisms by which
terpenoids modulate THC activity. For instance, terpenoids may bind to
cannabinoid receptors. Thujone, from Artemisia absinthium, has a weak affinity
for CB1 receptors (Ki at CB1 = 130,000 nM). Terpenoids might modulate
the affinity of THC for its own receptor, by sequestering THC, by perturbing
annular lipids surrounding the receptor, or by increasing the fluidity of neuronal
membranes. Further downstream, terpenoids may alter the signal cascade by
remodeling G-proteins. Terpenoids may alter the pharmacokinetics of THC by
changing the BBB; cannabis extracts are known to cause a significant increase
in BBB permeability (Agrawal et al. 1989). Terpenoids may also act on other
receptors and neurotransmitters. Some terpenoids act as serotonin uptake inhibitors
(as does Prozac), enhance norepinephrine activity (as do tricyclic
antidepressants), increase dopamine activity (as do monoamine oxidase inhibitors
and bupropion), and augment GABA (as do baclofen and the benzodiazepines).
Recently, strong serotonin activity at the 5-HT1A and 5-HT2a receptors
has been demonstrated (Russo et al. 2000; Russo 2001) that may support synergistic
contributions of terpenoids on cannabis-mediated pain and mood
effects. Further studies are in progress to identify the most active terpenoid
components responsible, and whether synergism of the components is demonstrable.
The essential oil of cannabis is traditionally employed as an anti-inflammatory
in the respiratory and digestive tracts without known contraindications at
physiological dosages (Franchomme and Pénoël 1990). The essential oil of
black pepper, Piper nigrum, has a composition of terpenes that is qualitatively
quite similar to that of cannabis (Lawless 1995). It has often been claimed
anecdotally, that smoked cannabis may substitute for nicotine in attempts at
smoking cessation. Aside from cannabinoid influences, current evidence supports
this contention based on terpene content and its activity. A recent study
has shown that inhalation of black pepper essential oil vapor significantly reduced
withdrawal symptoms and anxiety in tobacco smokers (Rose and Behm
1994). Interestingly, the authors posited not a central biochemical mechanism,
—————————————————————————————————
*Structures of constituents obtained from Bissett and Wichtl 1994; British Medical
Association 1997; Buckingham 1992; Iversen 2000; Tisserand and Balacs 1995;
Turner et al. 1980.
†Concentrations of constituents (v/w or w/w) were calculated from various sources.
Fig 1 Phytocannabinoids
Structure* Concentration† (% dry weight) Boiling Properties
Point °C§
Δ-9-tetrahydrocannabinol (THC) 0.1-25% 157 Euphoriant
Analgesic
Antiinflammatory
Antioxidant
Antiemetic
cannabidiol (CBD) 0.1-2.89% 160-180 Anxiolytic
Analgesic
Antipsychotic
Antiinflammatory
Antioxidant
Antispasmodic
cannabinol (CBN) 0.0-1.6% 185 Oxidation
breakdown
product
Sedative
Antibiotic
cannabichromene (CBC) 0.0-0.65% 220 Antiinflammatory
Antibiotic
Antifungal
cannabigerol (CBG) 0.03-1.15% MP Antiinflammatory
52 Antibiotic
Antifungal
Structure* Concentration† (% dry weight) Boiling Properties
Point °C§
8-tetrahydrocannabinol (8-THC) 0.0-0.1% 175-178 Less
Resembles-9-THC psychoactive
More stable
Antiemetic
tetrahydrocannabivarin (THCV)0.0-1.36% 0.001% 176 AChE inhibitor
Increases cerebral
blood flow
Stimulant
Antibiotic
Antiviral
Antiinflammatory
Antinociceptive
Cannabinoid concentrations
(presented as a range, including cannabinoids and cannabinoidic acids) were primarily
obtained from Small, 1979;
Veszki et al., 1980; Fournier et al., 1987; and Pitts et al., 1992. Terpenoid data
(presented as maximum values)were calculated from Ross and El Sohly, 1996; and
Mediavilla and Steinemann, 1997. Flavonoid data came from
Paris et al., 1976; and Barrett et al., 1986.
§Boiling/melting points (MP) recorded at atmospheric pressure (760 mmHg) unless
otherise noted; values obtained from various sources, primarily Buckingham, 1992;
Guenther, 1948; Parry, 1918; and Mechoulam (personal communication, April 2001).
——————————————————————————————————-
but rather a peripheral one assuming physical cues of bronchial sensation as
operative in the origin of the benefit. The true scope of the essential oil benefits
in this context may be quite a bit broader.
Pate (1994), McPartland (1997), and McPartland, Clarke and Watson
(2000), have reviewed the pesticidal properties of cannabis attributable to its
terpenoid content. The essential oil of Eugenia dysenterica was recently demonstrated
to have significant inhibitory effects on Cryptococcus neoformans
strains isolated from HIV patients with cryptococcal meningitis (Costa et al.
2000). Key components of that oil were common to cannabis: β-caryophyllene,
α-humulene, α-terpineol, and limonene.
Additionally, monoterpenes such as those abundant in cannabis resin have
been suggested to: (1) inhibit cholesterol synthesis, (2) promote hepatic en-zyme
activity to detoxify carcinogens, (3) stimulate apoptosis in cells with
damaged DNA, and (4) inhibit protein isoprenylation implicated in malignant
deterioration (Jones 1999).
Myrcene, specifically β-myrcene, a noncyclic monoterpene, is the most
abundant terpenoid produced by cannabis (Ross and ElSohly 1996; Mediavilla
and Steinemann 1997). It also occurs in high concentrations in hops (Humulus
lupulus) and lemongrass (Cymbopogon citratus). Myrcene is a potent analgesic,
acting at central sites that are antagonized by naloxone (Rao et al. 1990).
Myrcene also works via a peripheral mechanism shared by CBD, CBG, and
CBC–by blocking the inflammatory activity of prostaglandin E2 (Lorenzetti et
al. 1991). This activity is expressed by other terpenoids in cannabis smoke,
such as carvacrol, which is more potent than THC or CBG (Burstein et al.
1975). The activity of many terpenoids may be cumulative: unfractionated
cannabis essential oil exhibits greater antiinflammatory activity than its individual
constituents, suggesting synergy (Evans et al. 1987).
Myrcene also synergizes the antibiotic potency of other essential oil components,
against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa,
and a specific strain of Escherichia coli (Onawunmi et al. 1984).
Myrcene inhibits cytochrome P450 2B1, an enzyme implicated in the metabolic
activation of promutagens (De Oliveira et al. 1997). Aflatoxin B1 is a
promutagen produced by Aspergillus flavus and Aspergillus parasiticus, two
fungal contaminants of moldy marijuana (reviewed by McPartland and Pruitt
1997).
Fig 2 Terpenoid essential oil components of cannabis.
Cannabis Constituen Concentration† Boiling Properties
Structure* Point °C§
β-myrcene 0.47% 166-168 Analgesic
Antiinflammatory
Antibiotic
Antimutagenic
β-caryophyllene 0.05% 119 Antiinflammatory
Cytoprotective
(gastric mucosa)
Antimalarial
d-limonene 0.14% 177 Cannabinoid agonist?
Immune potentiator
Antidepressant
Antimutagenic
linalool 0.002% 198 Sedative
Antidepressant
Anxiolytic
Immune potentiator
Pulegone 0.001% 224 Memory booster?
AChE inhibitor
Sedative
AntipyreticFig 2 continued Terpenoid essential oil components of cannabis.
Cannabis Constituent Concentration† Boiling Properties
Structure* Point °C§
1,8-cineole (eucalyptol) > 0.001% 176 AChE inhibitor
Increases cerebral
blood flow
Stimulant
Antibiotic
Antiviral
Antiinflammatory
Antinociceptive
α-pinene 0.04% 156 Antiinflammatory
Bronchodilator
Stimulant
Antibiotic
Antineoplastic
AChE inhibitor
α-terpineol 0.02% 217-218 Sedative
Antibiotic
AChE inhibitor
Antioxidant
Antimalarial
terpineol-4-ol 0.0004% 209 AChE inhibitor
Antibiotic
p-cymene 0.0004% 177 Antibiotic
Anticandidal
AChE inhibitor
borneol 0.008% 210 Antibiotic
Δ-3-carene 0.004% 168 Antiinflammatory
After aflatoxin B1 is metabolized by P450 2B1, it becomes extremely
hepatocarcinogenic. Myrcene blocks this metabolism, as do other terpenoids
in cannabis, including limonene, α-pinene, α-terpinene, and citronellal (De
Oliveira et al. 1997).
β-Caryophyllene is the most common sesquiterpenoid in cannabis (Mediavilla
and Steinemann 1997). It is the main component of copaiba balsam, from
Copaifera spp. (Lawless 1995), which is a popular oral and topical anti-inflammatory
agent in Brazil (Basile et al. 1988). The latter authors were able to
demonstrate anti-inflammatory effects of the oleoresin in rats comparable to
phenylbutazone, in reduction of granuloma formation. A decreased vascular
permeability to injected histamine was also observed.
A gastric cytoprotective effect of β-caryophyllene was demonstrated in rats
against challenge with absolute ethanol and hydrochloric acid (Tambe et al.
1996). This benefit was noted without influence on gastric acid or pepsin secretion.
The authors suggested this agent as clinically safe, and potentially useful.
Campbell et al. (1997) have demonstrated a moderate antimalarial effect
against two strains of Plasmodium falciparum by an essential oil rich in
β-caryophyllene and α-terpineol.
Limonene is a monocyclic monoterpenoid and a major constituent of citrus
rinds (Tisserand and Balacs 1995). It finds extensive use as a solvent and in the
perfumery and flavor industries. Because of limonene’s widespread occurrence
and application, its biological activity is well known. Limonene is highly
absorbed by inhalation and quickly appears in the bloodstream (Falk-Flilipsson
et al. 1993). According to Ross and ElSohly (1996), limonene is the second
most common terpenoid in an unidentified cultivar of cannabis.
Limonene may have a low-affinity interaction with cannabinoid receptors
(Meschler and Howlett 1999). Studies of long-term inhalation of lemon fragrance
(predominately limonene) have demonstrated inhibition of thymic involution
in stress-induced immunosuppression in mice (Ortiz de Urbina et al.
1989).
Limonene was the primary component of the essential oil mixture employed
by Komori et al. (1995), in their clinical study of immune function and
depressive states in humans. The key result of this experiment was the ability
to markedly reduce the dosage of, or even eliminate the need for, synthetic
antidepressant drugs.
As mentioned in the myrcene section, limonene protects against aflatoxin
B1-induced cancer by inhibiting the hepatic metabolism of the promutagen to
its active form. Limonene also blocks this process at two earlier steps by inhibiting
the growth of Aspergillus fungi and inhibiting their production of aflatoxins
(Greene-McDowelle et al. 1999). Limonene and other terpenoids suppress the
growth of many species of fungi and bacteria, demonstrated in hundreds of
published studies (reviewed by McPartland 1997).
Limonene blocks the carcinogenesis induced by benz[α]anthracene (Crowell
1999), a component of the “tar” generated by the combustion of herbal cannabis.
Thus, this terpenoid may reduce the harm caused by inhaling cannabis
smoke. Limonene blocks carcinogenesis by multiple mechanisms. It detoxifies
carcinogens by inducing Phase II carcinogen-metabolizing enzymes (Crowell
1999). It selectively inhibits the isoprenylation of Ras proteins, thus blocking
the action of mutant ras oncogenes (Hardcastle et al. 1999). It induces
redifferentiation of cancer cells (by enhancing expression of transforming growth
factor β1 and growth factor II receptors), and it induces apoptosis of cancer
cells (Crowell 1999). Orally administered limonene is currently undergoing
Phase II clinical trials in the treatment of breast cancer (Vigushin et al. 1998);
it also protects against lung, liver, colon, pancreas, and skin cancers (Vigushin
et al. 1998; Crowell 1999; Setzer et al. 1999).
Linalool is a noncyclic monoterpenoid, commonly extracted from lavender
(Lavandula spp.), rose (Rosa spp.), and neroli oil (from Citrus aurantium). It
usually constitutes 5% or less of cannabis essential oil (Ross and ElSohly
1996). Linalool nevertheless exhibits strong biological activity. Buchbauer et
al. (1993) assayed the sedative effects of over 40 terpenoids upon inhalation
by mice; linalool was the most powerful, reducing mouse motility 73% after 1
hour of inhalation. The study demonstrated that other terpenoids found in cannabis,
such as citronellol and α-terpineol, are also deeply sedating upon inhalation,
even in lowconcentrations. Furthermore, combinations of these terpenoids
(e.g., neroli oil) are synergistic in their sedative effects. These terpenoids may
mitigate the anxiety provoked by pure THC. Inhalation of such terpenoids also
provides antidepressant effects (Komori et al. 1995).
Reducing anxiety and depression will improve immune function via the
neuroendocrine system, by damping down the hypothalamic-pituitary-adrenal
(HPA) axis. Hence, inhalation of terpenoids reduces the secretion of HPA
stress hormones (e.g., corticosterone), and normalizes CD4-CD8 ratios (Komori
et al. 1995). By a similar mechanism, terpenoids in Ginkgo biloba inhibit
corticosterone secretion by attenuating corticotropin-releasing factor (CRF)
expression (Marcihac et al. 1998). CRF not only induces corticosterone secretion
via the HPA axis, it is also associated with anxiety. Rodríguez de Fonseca
et al. (1996) showed that the psychoactive cannabinoid HU-210 caused a release
of CRF. Thus, the terpenoids act synergistically with non-psychoactive
CBD, which may decrease CRF by inhibiting IFN-γ (Malfait et al. 2000).
Pulegone, a monocyclic monoterpenoid, is a minor constituent of cannabis
(Turner et al. 1980). Higher concentrations of pulegone are found in rosemary
(Rosmarinus officinalis), “the herb of remembrance.” Pulegone may alleviate
a major side effect of THC–loss of short-term memory consolidation. THC
causes acetylcholine (ACh) deficits in the hippocampus. Hippocampal ACh
deficits are also seen in people with Alzheimer’s disease. Alzheimer’s patients
can be treated with tacrine (Cognex), a drug that increases ACh activity by
inhibiting acetylcholinesterase (AChE). Indeed, tacrine has blocked THC-induced
memory loss behavior in rats. Pulegone exhibits the same activity as
tacrine, that of AChE inhibition (Miyazawa et al. 1997). Other terpenoids in
cannabis also provide AChE inhibition, including limonene, limonene oxide,
α-terpinene, γ-terpinene, terpinen-4-ol, carvacrol, l-and d-carvone, 1,8-cineole,
p-cymene, fenchone, and pulegone-1,2-epoxide (Perry et al. 1996; McPartland
and Pruitt 1999). The beneficial effects of AChE inhibitors, however, are decreased
in individuals carrying the E4 subtype of the apolipoprotein E gene,
ApoE E4 (Poirier et al. 1995). Pulegone has also demonstrated significant sedative
and antipyretic properties in a study in rats (Ortiz de Urbina et al. 1989).
1,8-Cineole, a bicyclic monoterpenoid, is a minor constituent of cannabis
and the major aromatic found in Eucalyptus species. Studies show the inhalation
of 1,8-cineole increases cerebral blood flow and enhances cortical activity
(Nasel et al. 1994). Brain function is enhanced by administering terpenoids
that improve cerebral blood flow, much as the ginkgolides in Ginkgo biloba
(Russo 2000). Similarly, cerebral blood flow increases after inhaling cannabis
smoke, and this increase is not related to plasma levels of THC (Mathew and
Wilson 1993).
A stimulatory effect on rat locomotion was demonstrated employing a
1,8-cineole-rich essential oil of rosemary with a terpene profile similar to that
of cannabis (Kovar et al. 1987). Blood levels correlated with the degree of
stimulation observed. Antinociceptive and anti-inflammatory effects of 1,8-
cineole were demonstrated at high doses in rats, using carrageenan rat paw and
cotton pellet-induced granuloma models (Santos and Rao 2000). An analgesic
effect of an essential oil was demonstrated in another animal study, and correlated
with the 1,8-cineole concentration (Aydin et al. 1999).
1,8-Cineole demonstrated antibacterial activity against Bacillus subtilis,
and antifungal properties against Trichophyton mentagrophytes, Cryptococcus
neoformans, and Candida albicans (Hammerschmidt et al. 1993). In subse-
quent assays, this essential oil component was cidal against Candida albicans
and Escherichia coli, and bacteriostatic against Staphylococcus aureus (Carson
and Riley 1995). In a rat study, 1,8-cineole prevented the sexual transmission
of Herpes simplex virus type 2 (HSV-2). HSV-2 is a frequently comorbid
condition with HIV, and its prevention has been suggested as one method of
lowering HIV transmission risks (Gwanzura et al. 1998).
Perry et al. (2000) demonstrated that 1,8-cineole was an inhibitor of human
erythrocyte acetylcholinesterase, but that an essential oil of Salvia lavandulaefolia
containing 1,8-cineole and other terpenoids produced a synergistic
inhibition of acetylcholinesterase that suggested utility in the clinical treatment
of Alzheimer’s disease. A similar mechanism may operate in cannabis
essential oil with the same components.
α-Pinene, a bicyclic monoterpenoid, was effective in prevention of acute
inflammation in a carrageenan-induced plantar edema model (Gil et al. 1989).
A pharmacokinetics study of inhaled α-pinene in humans demonstrated 60%
uptake, and a relative bronchodilation effect (Falk et al. 1990). After 1 hour of
inhalation, α-pinene produced a 13.8% increase in mouse motility measures
(Buchbauer et al. 1993). α-Pinene has inhibited acetylcholinesterase in a variety
of assays (Perry et al. 1996; McPartland and Pruitt 1999), suggesting utility
in the clinical treatment of Alzheimer’s disease. The antibiotic properties of
α-pinene, α-terpineol, and terpinen-4-ol have been demonstrated against
Staphylococcus aureus, S. epidermidis and Propionibacterium acnes (Raman
et al. 1995). α-Pinene and its isomer β-pinene were both cytotoxic in vitro
against Hep-G2 (human hepatocellular carcinoma) and Sk-Mel-28 (human
melanoma) tumor cell lines (Setzer et al. 1999).
α-Terpineol, terpinen-4-ol, and 4-terpineol are three closely related monoterpenoids.
Inhalation of α-terpineol reduced mouse motility 45% (Buchbauer
et al. 1993). Burits and Bucar (2000) demonstrated that 4-terpineol exhibits
“respectable” radical scavenging and antioxidant properties. Terpinen-4-ol,
α-terpineol, and α-pinene demonstrated dose-dependent antibiotic properties
against Staphylococcus aureus, S. epidermidis and Propionibacterium acnes
(Raman et al. 1995). Similar studies have demonstrated antimicrobial activity
against a wide range of pathogenic organisms, excluding Pseudomonas (Carson
and Riley 1995). Campbell et al. (1997) have demonstrated a moderate
antimalarial effect against two strains of Plasmodium falciparum by an essential
oil with major α-terpineol and α-caryophyllene components.
Cymene, or p-cymene, a monoterpenoid, is active against Bacterioides
fragilis, Candida albicans, and Clostridium perfringens (Carson and Riley
1995).
Borneol, a bicyclic monoterpenoid, was tested in walnut oil as an external
treatment for purulent otitis media (Liu 1990), where it proved to be 98% effective
(P < 0.001), to a greater degree than neomycin, and without toxicity.
Δ3-Carene, a bicyclic monoterpenoid, was effective in prevention of acute
inflammation in a carrageenan-induced plantar edema model (Gil et al.
1989).
FLAVONOIDS
Flavonoids are aromatic, polycyclic phenols. Cannabis produces about 20
of these compounds, as free flavonoids and conjugated glycosides (Turner et
al. 1980). Paris et al. (1976) estimated that cannabis leaves consist of 1%
flavonoids. Some flavonoids are volatile, lipophilic, permeate membranes,
and apparently retain pharmacological activity in cannabis smoke (Sauer et al.
1983). Flavonoids may modulate the pharmacokinetics of THC, via a mechanism
shared by CBD, the inhibition of P450 3A11 and P450 3A4 enzymes.
Naringenin, a flavonoid in grapefruit juice, also inhibits these enzymes, thus
blocking the metabolism of cyclosporine, caffeine, benzodiazepines, and calcium
antagonists (Fuhr 1998). Two related enzymes, P450 3A4 and P450 1A1,
metabolize environmental toxins from procarcinogens to their activated forms.
Thus, P450-suppressing compounds serve as chemoprotective agents, shielding
healthy cells from the activation of benzo[α]pyrene and aflatoxin B1
(Offord et al. 1997), which are two procarcinogens potentially found in cannabis
smoke (McPartland and Pruitt 1997).
Apigenin is a flavone found in nearly all vascular plants (Figure 3). It exerts
a wide range of biological effects, including many properties shared by
terpenoids and cannabinoids. Apigenin is the primary anxiolytic agent found
in chamomile, Matricaria recutita, (reviewed in Russo 2000). It selectively
binds with high affinity to central benzodiazepine receptors, which are located
in α- and β-subunits of GABAA receptors (Salgueiro et al. 1997); this anxiolytic
activity is not associated with the unwanted side effects caused by synthetic
benzodiazepines, such as muscular relaxation, amnesia, and sedation.
Apigenin inhibits the production of tumor necrosis factor-alpha (TNF-α), a
cytokine primarily expressed by monocytes and macrophages (Gerritsen et al.
1995). TNF-α induces and maintains inflammation, a pathological condition
in rheumatoid arthritis and multiple sclerosis. THC decreases TNF-α, probably
by a nonreceptor-mediated mechanism (Burnette-Curley and Cabral 1995),
although one study suggested THC might induce TNF-α (Shivers et al. 1994).
Either way, apigenin provides beneficial suppression of TNF-α, whether in
concert with THC or counteracting THC.
Apigenin and other flavonoids interact with estrogen receptors, and appear
to be the primary estrogenic agents in cannabis smoke (Sauer et al. 1983). Although
apigenin has a high affinity for estrogen receptors (especially β-estrogen
receptors), it has low estrogenic activity; apigenin actually inhibits estradiolinduced
proliferation of breast cancer cells (Wang and Kurzer 1998).
Quercetin is a flavonol found in nearly all vascular plants, including cannabis
(Turner et al. 1980). Quercetin is a potent antioxidant; by some measures
more potent than ascorbic acid, α-tocopherol, and BHT (Gadow et al. 1997).
Combinations of quercetin and other antioxidants work synergistically (Hudson
flavonoids should be tested against CBD, another potent antioxidant (Hampson
et al. 1998). Perhaps flavonoids can induce chemical reduction of CBD, effectively
recycling CBD as an antioxidant. Flavonoids block free radical formation
at several steps: by scavenging superoxide anions (in both enzymatic and
non-enzymatic systems), by quenching intermediate peroxyl and alkoxyl radicals,
and by chelating iron ions, which catalyze many Fenton reactions leadingto free
Fig3 Flavonoid and phytosterol components of cannabis.
Cannabis Constituent Concentration† Boiling Properties
Structure* Point °C§
apigenin > 0.1% 178 Anxiolytic
Antiinflammatory
Estrogenic
quercetin > 0.1% 250 Antioxidant
Antimutagenic
Antiviral
Antineoplastic
cannflavin A 0.02% 182 COX inhibitor
LO inhibitor
β-sitosterol ? 134 Antiinflammatory
5-α-reductase
inhibitor
Free radicals activate NF-κB, a transcription factor protein that induces the
expression of oncogenes, inflammation, and apoptosis. Quercetin arrests the
formation of NF-κB, by blocking the PKC-induced phosphorylation of an inhibitory
subunit of NF-κB called IκB (Musonda and Chipman 1998), consequently
quercetin hinders carcinogenesis and inflammatory diseases. NF-κB
also plays a role in the activation of HIV-1 (Greenspan 1993), so quercetin
may hinder the replication of that virus. In a similar fashion, silymarin (a
flavonoid produced by milk thistle, Silybum marianum) impedes NF-κB-induced
replication of the hepatitis C virus, and thus inhibits hepatic carcinoma
(McPartland 1996). These flavonoids may synergize with CBN, which also
downregulates NF-κB (Herring and Kaminski 1999), thereby counteracting
the effects of THC, which may increase NF-κB activity (Daaka et al. 1997).
Cannflavin A is one of a pair of prenylated flavones apparently unique to
cannabis (Barrett et al. 1986). The yield of cannflavin A is 0.02% of dry herb.
This compound is a potent inhibitor of prostaglandin E2 in human rheumatoid
synovial cells, with an IC50 of 31 ng/ml, about 30 times more potent than aspirin
in that system (Barrett et al. 1986). Cannflavin A inhibits cyclooxygenase
(COX) enzymes and lipoxygenase (LO) enzymes more potently than THC
(Evans et al. 1987). However, these assays were done with alcohol-extracted
cannflavin; we question whether cannflavin is sufficiently volatile. Other phenols
related to flavonoids are volatile and apparently retain pharmacological
activity in cannabis smoke, such as eugenol and p-vinylphenol (Burstein et al.
1976).
β-Sitosterol was demonstrated in significant concentrations in the red oil
extract of cannabis (Fenselau and Hermann 1972). In animal assays, this
phytosterol reduced acute inflammation 65% and chronic edema 40.6% (Gomez
et al. 1999). This agent has been the subject of most interest as the active ingredient
of Serenoa repens, the saw palmetto, and Urtica dioica, the nettle,
wherein β-sitosterol acts as a 5-α-reductase inhibitor. In numerous trials (Wilt
et al. 1998; McPartland and Pruitt 2000), standardized extracts of saw palmetto
have proven equivalent or superior to finasteride in treatment of benign
prostatic hyperplasia.
CONCLUSIONS
Does the body absorb non-cannabinoids in physiologically relevant concentrations?
In the absence of experimental data, we can estimate, using
limonene as an example of AChE inhibition. According to Ross and ElSohly
(1996), fresh, female flowering tops consist of 0.29% essential oil. Air drying
of female flowering tops decreases their moisture content (MC) from approximately
85% MC to 15% MC, with a concomitant loss in water weight
(McPartland and Pruitt 1997). Although some essential oil is volatilized and
lost in the drying process, the remaining terpenoids become concentrated. The
concentration of essential oil in air-dried cannabis is 0.8%, and limonene consists
of 17.2% of the essential oil (Ross and ElSohly 1996). Thus, air-dried
cannabis consists of 0.14% limonene; therefore a 500 mg cannabis cigarette
(which is half the size of a standard tobacco cigarette) would contain 0.7 mg
limonene. If we assume the systemic bioavailability of limonene from smoking
cannabis is 18%, the same as THC (Ohlsson et al. 1980), then 0.13 mg
would be absorbed. Distributing this dose evenly in the total body water of a 70
kg man, without metabolism or sequestration, would produce a maximum tissue
concentration of 1.3 μM. This concentration is an order of magnitude below
the IC50 concentration of limonene’s inhibition of AChE (Miyazawa et al.
1997). Hence, limonene must synergize with other AChE inhibitors in order to
be effective.
Vaporizer technology may improve the bioavailability of limonene and
other compounds, which volatilize around the same temperature as THC (see
Figures 1-3). Vaporizers are smoking apparati that heat cannabis to 185°C
(365°F), which vaporizes THC but is below the ignition point of combustible
plant material. Vaporized cannabis emits a thin gray vapor, whereas combusted
cannabis produces a thick smoke. Thus, vaporizers deliver a better cannabinoid-
to-tar ratio than cigarettes or water pipes (Gieringer 1996). In a recent
study, traces of THC were vaporized at temperatures as low as 140°C (284°F)
and the majority of THC vaporized by 185°C (365°F); benzene and other
carcinogenic vapors did not appear until 200°C (392°F), and cannabis combustion
occurred around 230°C (446°F) (Gieringer 2001).
Concerning bioavailability, it should be mentioned that cannabis compounds
need not be absorbed systemically through the lungs to produce CNS
activity. Inhaled compounds may reach receptors in the olfactory bulb, sending
mood-altering messages via olfactory nerves directly to the limbic region
and hippocampus. This route may be responsible for some sedative effects of
terpenoids upon inhalation (Buchbauer et al. 1993).
The paucity of research concerning non-THC synergists in cannabis is periodically
criticized (Mechoulam et al. 1972; McPartland and Pruitt 1999; Russo
2000). We have highlighted several cannabinoids, terpenoids, and flavonoids
that deserve further attention regarding their contributions to the effects of
clinical cannabis. Most of the data we present here is based on in vitro experiments
or animal studies. Clearly the next step should involve human clinical
trials of each constituent, alone, or in combination with THC, or combined
with a cocktail of cannabis compounds.
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Additional documentation on health issues and the benefits of cannabis/marijuana
http://arstechnica.com/science/news/2008/08/killing-bacteria-with-cannabis.ars
Killing bacteria with cannabis
By Yun Xie | Last updated August 26, 2008 4:31 PM
Pharmacists and chemists have found another use for the multipurpose cannabis as
a source of antibacterial chemicals for multidrug resistant bacteria. Ironically,
inhaling cannabis is known to damage the lung’s ability to fend off invading
pathogens, but the ingredients in cannabis, particularly the cannabinoids, have
antiseptic properties. Although scattered research has been conducted since the
1950s, no comprehensive study existed that relates the structure of cannabinoids
with antibacterial activity. Giovanni Appendino, Simon Gibbons, and coworkers
attempted to remedy that problem by examining the activity of five common
cannabinoids and their synthetic derivatives.
All five cannabinoids (THC, CBD, CBG, CBC, and CBN) were potent against
bacteria. Notably, they performed well against bacteria that were known to be
multidrug resistant, like the strains of MRSA that plagued U.K. hospitals. CBD
and CBG have the most potential for consumer use because they are
nonpsychotropic.
Besides identifying antibacterial capability, the researchers wanted to figure out
why these cannabinoids are so good at killing bacteria. They obviously are very
effective at specifically targeting some vital process in the bacteria. Unfortunately,
even after extensive work at modifying the cannabinoids and comparing their
activities, that targeting mechanism remains a mystery. The scientists were able
to figure out that the position of the n-pentyl chain (orange) relative to the terpenoid
moiety (blue) serves to control lipid affinity.
These cannabinoids are promising enough to warrant rigorous clinical trials. They are
applicable as topical antiseptics, biodegradable antibacterial compounds for cosmetics,
and systematic antibacterial agents.
J. Nat. Prod., 2008. DOI: 10.1021/np8002673
Much science has been done and currently being done on cannabinoids and their
synthetic derivatives. Why must we wait for synthetic derivatives? Would we outlaw
natural food and insist synthetic food was the only legal food source? Many people
have problems with synthetic substances such as chemical pharmaceuticals and most
synthetic pharmaceutical cause many problems and have bad side effects. These
people should be allowed to have the alternative of natural medication even if it
seems to some as crude, it is also crude to insist the only relief available to the ill
is dangerous chemical, often toxic substances marketed by the pharmaceutical
companies.
Page 53
Prior to 1976, reports of positive effects and new therapeutic indications for cannabis
were almost a weekly occurrence in medical journals and the national press.
In November 1975, virtually all of America’s leading researchers on marijuana met at
Asilomar Conference Center, Pacific Grove, California. Seminars were sponsored by
the National Institute on Drug Abuse (NIDA) to address a compendium of studies
from their earliest to most recent findings.
When the seminars were over, practically all the scientists concluded that the federal
government, with the hard evidence collected so far on the therapeutic potential of
marijuana, should be rushing to invest tax money into more research.
They felt the taxpayers should be informed that there was every legitimate reason for
the field of public health to continue large scale research on cannabis medicine and
therapies.
All the participants, it seems, believed this. Many of them (such as Mechoulam)
believed that cannabis would be one of the world’s major medicines by the mid-1980s.
In March 1997, Mechoulam, in a speech at the Bio-Fach in Frankfort, Germany, still
believed that cannabis is the world’s best overall medicine.
Page 54
U.S. government research (1966-76) had indicated or confirmed through hundreds
of studies that even “natural” crude cannabis was the “best and safest medicine
of choice” for many serious health problems.
Additional response to negative claims for cannabis/marijuana according to the
current standings of the DEA. FDA, ONDCP, and the NIH :
While it may not be considered “Modern Medicine” neither is chicken soup, yet
you would be hard pressed to find someone who would claim chicken soup does
not have any value. Chicken soup is credited with having all kinds of beneficial
properties which promote good health.
From : http://answers.yahoo.com/question/index?qid=20070731034916AAo3X2l
Here is the official answer courtesy of CNN:
Chicken soup is medicine, U.S. scientists confirm
WASHINGTON — Scientists say they have confirmed what grandmothers have
known for centuries — that chicken soup is good for colds.
Chicken soup — as made by grandma — contains several ingredients that affect the
body’s immune system, a team at the University of Nebraska Medical Center found.
Specifically, it has anti-inflammatory properties that could explain why it soothes
sore throats and eases the misery of colds and flu, Dr. Stephen Rennard and
colleagues said Monday.
“Chicken soup may contain a number of substances with beneficial medicinal
activity,” the researchers wrote in their report, published in the journal Chest.
“My wife was making chicken soup one year for the Jewish holidays and we
were talking about its effects on colds,” Rennard, a specialist in pulmonary medicine,
said in a telephone interview. “I said ‘well, maybe it has some anti-inflammatory
effect,’ and she said ‘really?’ and I said ‘why not?’ and I said maybe we could find
out in the lab.”
As it turned out, Rennard’s lab was well-suited to making such tests. “In the lab we
study inflammation and injury and repair mechanisms in the lung as related to asthma
and emphysema and so on,” he said.
So Rennard’s wife Barbara Rennard made up a batch of her grandmother’s chicken
soup, which includes chicken, onions, sweet potato, parsnips, turnips, carrots,
celery stems, and parsley. Rennard said his wife added no salt but did include
matzo balls, a kind of dumpling.
Then they ran laboratory tests. Not only did they test the soup as a whole, but they
separated out the components.
“These tests were in the laboratory and it doesn’t test (chicken soup) clinically in
colds,” Rennard stressed.
Neutrophil movement stopped
They found that chicken soup and many of its ingredients helped stop the movement
of neutrophils — white blood cells that eat up bacteria and cellular debris and which
are released in great numbers by viral infections like colds.
Neutrophil activity can stimulate the release of mucous, which may be the cause of
the coughs and stuffy nose caused by upper respiratory infections such as colds.
“All the ingredients were found to be inhibitory, including the boiled extract of
chicken alone,” they wrote.
Rennard said vitamins and other agents in the ingredients could, plausibly, have
biological action.
The researchers also went to the store and bought 13 different commercial brands
of soup to test.
“About a third of them were more active than grandma’s soup,” Rennard said,
adding that he could not remember which kinds of soup they were.
“One or two of them had very little activity at all. Vegetarian vegetable soup had
some activity.”
To be safe, they also tested plain Omaha tap water which, to their relief, had no
effect. “If tap water were active, that would be disturbing in a number of ways,”
Rennard said.
Some researchers have suggested in the past that perhaps the steam from the soup,
or the chicken fat, may play a role in soothing inflamed airways. Rennard said this
was possible.
He also said there could be a “TLC” (tender, loving care) factor. “If you know
somebody prepared soup for you by hand, that might have an effect,” he said.
Rennard said he had no immediate plans to test chicken soup any further. “I have
no doubt that generations from now, people will read this and the only thing of
interest will be the recipe,” he said.
“It really is good soup.”
Article Source(s):
http://archives.cnn.com/2000/HEALTH/diet…
http://marijuana.researchtoday.net/archive/7/1/2667.htm
Effects of cannabis on lung function: a population-based cohort study.
Hancox RJ, Poulton R, Ely M, Welch D, Taylor DR, McLachlan CR, Greene JM,
Moffitt TE, Caspi A, Sears MR
Dunedin Multidisciplinary Health and Development Research Unit, Dunedin School
of Medicine, University of Otago, Dunedin, New Zealand. bob.hancox@otago.ac.nz
The effects of cannabis on lung function remain unclear and may be different from
those of tobacco. We compared the associations between use of these substances
and lung function in a population-based cohort (n = 1,037). Cannabis and tobacco
use were reported at ages 18, 21, 26 and 32 yrs. Spirometry, plethysmography and
carbon monoxide transfer factor were measured at 32 yrs. Associations between
lung function and exposure to each substance were adjusted for exposure to the
other substance. Cumulative cannabis use was associated with higher forced vital
capacity, total lung capacity, functional residual capacity and residual volume.
Cannabis was also associated with higher airway resistance but not with forced
expiratory volume in 1 s, forced expiratory ratio or transfer factor. These findings
were similar among those who did not smoke tobacco. In contrast, tobacco use was
associated with lower forced expiratory volume in 1 s, lower forced expiratory ratio,
lower transfer factor and higher static lung volumes, but not with airway resistance.
Cannabis appears to have different effects on lung function from those of tobacco.
Cannabis use was associated with higher lung volumes, suggesting hyperinflation
and increased large-airways resistance, but there was little evidence for airflow
obstruction or impairment of gas transfer.
Published 1 January 2010 in Eur Respir J, 35(1): 42-7.
Inhaled medicines is actually the newest form of modern medicine as demonstrated
earlier and is currently considered as heavily underexploited.
http://www.hospitalpharma.com/pressreleases/pressrel.asp?ROW_ID=19167
The delivery of drugs using inhaled formulations is currently heavily underexploited
except for the treatment of respiratory diseases. However, the large surface area
offered by the lungs offers the opportunity to achieve rapid absorption of drugs from
suitable inhaled formulations. It represents an opportunity to provide an effective
delivery route for therapeutics, such as proteins, that are suitable for oral
administration. The delivery of insulin via inhalation has been suggested as a
major commercial opportunity, However, commercial success necessitates
identifying stable and effective formulations, combined with a suitable,
convenient, device for delivering the inhaled formulation.
One most often claimed problems is “approval would send the wrong message to
young people”
Since when is admitting a mistake was made – wrong? It is far more wrong to
continue in a stubborn manner with a decision made based on untruths by the
propaganda machine of two men (Harry Anslinger, Commissioner of the then
recently established Federal Bureau of Narcotics, and William Randolf Hearst,
owner of a huge chain of newspapers) to promote their personal agenda, serving
their own interest, not that of the population at large.
I suggest you read the book in its entirety, available at the above web address. You
may be quite surprised by most of the details. Only the details pertinent to
understanding this topic are mentioned here.
From 70-90% of all rope, twine, and cordage was made from hemp until 1937.
It was then replaced mostly by petrochemical fibers (owned principally by DuPont
under license from Germany’s I.G. Corporation patents) and by Manila (Abaca)
Hemp, with steel cables often intertwined for strength – brought in from our “new”
far-western Pacific Philippines possession, seized from Spain as reparation for the
Spanish American War in 1898.
After the 1937 Marijuana Tax law, new DuPont “plastic fibers,” under license since
1936 from the German company I.G. Farben (patent surrenders were part of
Germany’s World War I reparation payments to America), replaced natural hempen
fibers. (Some 30% of I.G. Farben, under Hitler, was owned and financed by America’s
DuPont.) DuPont also introduced Nylon (invented in 1935) to the market after they’d
patented it in 1938.
(Colby, Jerry, DuPont Dynasties, Lyle Stewart, 1984.)
Congress and the Treasury Department were assured through secret testimony given
by DuPont in 1935-37 directly to Herman Oliphant, Chief Counsel for the Treasury
Dept., that hempseed oil could be replaced with synthetic petrochemical oils made
principally by DuPont.
Coincidentally, in 1937, DuPont had just patented processes for making plastics from
oil and coal, as well as a new sulfate/sulfite process for making paper from wood pulp.
According to DuPont’s own corporate records and historians,* these processes
accounted for over 80% of all the company’s railroad carloadings over the next 60
years into the 1990s.
The Toxic Alternative to Natural Fibers
The late 1920s and 1930s saw continuing consolidation of power into the hands of a
few large steel, oil and chemical (munitions) companies. The U.S. federal government
placed much of the textile production for the domestic economy in the hands of its
chief munitions maker, DuPont.
The processing of nitrating cellulose into explosives is very similar to the process for
nitrating cellulose into synthetic fibers and plastics. Rayon, the first synthetic fiber, is
simply stabilized guncotton, or nitrated cloth, the basic explosive of the 19th Century.
“Synthetic plastics find application in fabricating a wide variety of articles, many of
which in the past were made from natural products,”* beamed Lammot DuPont
(Popular Mechanics, June 1939, pg. 805).
“Consider our natural resources,” the president of DuPont continued, “The chemist
has aided in conserving natural resources by developing synthetic products to
supplement or wholly replace natural products.”
Finally, it must be noted that approximately 50% of all chemicals used in American
agriculture today are used in cotton growing. Hemp needs no chemicals and has few
weed or insect enemies – except for the U.S. government and the DEA.
*Author’s research and communications with DuPont, 1985-1996.
If hemp had not been made illegal, 80% of DuPont’s business would never have
materialized and the great majority of the pollution which has poisoned our
Northwestern and Southeastern rivers would not have occurred.
Nylon fibers were developed between 1926-1937 by the noted Harvard chemist
Wallace Carothers, working from German patents. These polyamides are long
fibers based on observed natural products. Carothers, supplied with an open-ended
research grant from DuPont, made a comprehensive study of natural cellulose fibers.
He duplicated natural fibers in his labs and polyamides – long fibers of a specific
chemical process – were developed.
** It is interesting to note that on April 29, 1937, two weeks after the Marihuana
Tax Act was introduced, DuPont’s foremost scientist, Wallace Hume Carothers,
the inventor of nylon for DuPont, the world’s number one organic chemist,
committed suicide by drinking cyanide. Carothers was dead at age 41.
After the Supreme Court decision of March 29, 1937, upholding the prohibition of
machine guns through taxation, Herman Oliphant made his move. On April 14, 1937
he introduced the bill directly to the House Ways and Means Committee instead of
to other appropriate committees such as food and drug, agriculture, textiles,
commerce, etc.
His reason may have been that “Ways and Means” is the only committee that can
send its bills directly to the House floor without being subject to debate by other
committees.
Ways and Means Chairman Robert L. Doughton,* a key DuPont ally, quickly
rubber-stamped the secret Treasury bill and sent it sailing through Congress to the
President.
* Colby Jerry, The DuPont Dynasties, Lyle Stewart, 1984.
BookSources:
Encyclopedia of Textiles 3rd Edition by the editors of American Fabrics and
Fashions Magazine, William C. Legal, Publisher Prentice-Hall, Inc. Englewood
Cliffs, NJ 1980; The Emergence of Industrial America Strategic Factors in
American Economic Growth Since 1870, Peter George State University, NY;
DuPont (a corporate autobiography published periodically by E.I. DuPont
DeNemours and Co., Inc. Wilmington, DE); The Blasting Handbook, E.I. DuPont
DeNemours and Co., Inc., Wilmington, DE; Mechanical Engineering Magazine,
Feb. 1938; Popular Mechanics, Feb 1938; Journal of Applied Polymer Science,
Vol. 47, 1984; Polyamides, the Chemistry of Long Molecules (author unknown)
U.S. Patent #2,071,250 (Feb. 16, 1937), W.H. Carothers, DuPont Dynasties, Jerry
Colby; The American Peoples Encyclopedia, the Sponsor Press, Chicago, 1953.
Blatant Bigotry
Starting with the 1898 Spanish American War, the Hearst newspaper had denounced
Spaniards, Mexican-Americans and Latinos.
After the seizure of 800,000 acres of Hearst’s prime Mexican timberland by the
“marihuana” smoking army of Pancho Villa,* these slurs intensified.
*The song “La Cucaracha” tells the story of one of Villa’s men looking for his stash
of “marijuana por fumar!” (to smoke!)
Non-stop for the next three decades, Hearst painted a picture of the lazy,
pot-smoking Mexican – still one of our most insidious prejudices. Simultaneously,
he waged a similar racist smear campaign against the Chinese, referring to them as
the “Yellow Peril.”
From 1910 to 1920, Hearst’s newspapers would claim that the majority of incidents
in which blacks were said to have raped white women, could be traced directly to
cocaine. This continued for 10 years until Hearst decided it was not “cocaine-crazed
Negroes” raping white women – it was now “marijuana-crazed Negroes” raping white
women.
Hearst’s and other sensationalistic tabloids ran hysterical headlines atop stories
portraying “Negroes” and Mexicans as frenzied beasts who, under the influence
of marijuana, would play anti-white “voodoo-satanic” music (jazz) and heap
disrespect and “viciousness”
upon the predominantly white readership. Other such offenses resulting from this
drug-induced “crime wave” included: stepping on white men’s shadows, looking
white people directly in the eye for three seconds or more, looking at a white
woman twice, laughing at a white person, etc.
1937 Congressional Hearings
Dr. William G. Woodward, for instance, who was both a physician and an attorney
for the American Medical Association, testified on behalf of the AMA.
He said, in effect, the entire fabric of federal testimony was tabloid sensationalism!
No real testimony had been heard! This law, passed in ignorance, could possibly
deny the world a potential medicine, especially now that the medical world was just
beginning to find which ingredients in cannabis were active.
Woodward told the committee that the only reason the AMA hadn’t come out
against the marijuana tax law sooner was that marijuana had been described in the
press for 20 years as “killer weed from Mexico.”
The AMA doctors had just realized “two days before” these spring 1937 hearings,
that the plant Congress intended to outlaw was known medically as cannabis, the
benign substance used in America with perfect safety in scores of illnesses for over
one hundred years.
“We cannot understand yet, Mr. Chairman,” Woodward protested, “why this bill
should have been prepared in secret for two years without any intimation, even to
the profession, that it was being prepared.” He and the AMA” were quickly
denounced by Anslinger and the entire congressional committee, and curtly
excused.3
*The AMA and the Roosevelt Administration were strong antagonists in 1937.
When the Marijuana Tax Act bill came up for oral report, discussion, and vote on
the floor of Congress, only one pertinent question was asked from the floor: “Did
anyone consult with the AMA and get their opinion?”
Representative Vinson, answering for the Ways and Means Committee replied, “Yes,
we have. A Dr. Wharton [mistaken pronunciation of Woodward?] and {the AMA}
are in complete agreement!”
With this memorable lie, the bill passed, and became law in December 1937. Federal
and state police forces were created, which have incarcerated hundreds of thousands
of Americans, adding up to more than 14 million wasted years in jails and
prisons – even contributing to their deaths – all for the sake of poisonous, polluting
industries, prison guard unions and to reinforce some white politicians’ policies of
racial hatred.
(Mikuriya, Tod, M.C., Marijuana Medical Papers, 1972; Sloman, Larry, Reefer
Madness, Grove Press, 1979; Lindsmith, Alfred, The Addict and the Law,
Indiana U. Press; Bonnie & Whitebread; The Marijuana Conviction, U. of VA Press;
U.S. Cong. Records; et al.)
Others Spoke Out, Too
As the AMA’s Dr. Woodward had asserted, the government’s testimony before
Congress in 1937 had in fact consisted almost entirely of Hearst’s and other
sensational and racist newspaper articles read aloud by Harry J. Anslinger,* director
of the Federal Bureau of Narcotics (FBN). (This agency has since evolved into the
Drug Enforcement Administration [DEA]).
*Harry J. Anslinger was director of the new Federal Bureau of Narcotics from its
inception in 1931 for the next 31 years, and was only forced into retirement in
1962 by President John F. Kennedy after Anslinger tried to censor the publications
and publishers of Professor Alfred Lindsmith (The Addict and the Law, Washington
Post, 1961) and to blackmail and harass his employer, Indiana University. Anslinger
had come under attack for racist remarks as early as 1934 by a U.S. senator from
Pennsylvania, Joseph Guffey, for such things as referring to “ginger-colored niggers”
in letters circulated to his department heads on FBN stationery.
Prior to 1931, Anslinger was Assistant U.S. Commissioner for Prohibition. Anslinger,
remember, was hand-picked to head the new Federal Bureau of Narcotics by his
uncle-in-law, Andrew Mellon, Secretary of the Treasury under President Herbert
Hoover. The same Andrew Mellon was also the owner and largest stockholder of
the sixth largest bank (in 1937) in the United States, the Mellon Bank in Pittsburgh,
one of only two bankers for DuPont* from 1928 to the present.
* DuPont has borrowed money from banks only twice in its entire 190-year history,
once to buy control of General Motors in the 1920s. Its banking business is the
prestigious plum of the financial world.
In 1937, Anslinger testified before Congress saying, “Marijuana is the most
violence- causing drug in the history of mankind.”
This, along with Anslinger’s outrageous racist statements and beliefs, was made to
the southern dominated congressional committee and is now an embarrassment to
read in its entirety.
For instance, Anslinger kept a “Gore File,” culled almost entirely from Hearst and
other sensational tabloids – e.g., stories of axe murders, where one of the
participants reportedly smoked a joint four days before committing the crime.
Anslinger pushed on Congress as a factual statement that about 50% of all violent
crimes committed in the U.S. were committed by Spaniards, Mexican-Americans,
Latin Americans, Filipinos, African-Americans and Greeks, and these crimes could
be traced directly to marijuana.
(From Anslinger’s own records given to Pennsylvania State University, ref.; Li
Cata Murders, etc.)
Not one of Anslinger’s marijuana “Gore Files” of the 1930s is believed to be true
by scholars who have painstakingly checked the facts.4 Self-Perpetuating Lies
In fact, FBI statistics, had Anslinger bothered to check, showed at least 65-75%
of all murders in the U.S. were then – and still are – alcohol related. As an example
of his racist statements, Anslinger read into U.S. Congressional testimony (without
objection) stories about “coloreds” with big lips, luring white women with jazz
music and marijuana.
He read an account of two black students at the University of Minnesota doing
this to a white coed “with the result of pregnancy.” The congressmen of 1937
gasped at this and at the fact that this drug seemingly caused white women to
touch or even look at a “Negro.”
Virtually no one in America other than a handful of rich industrialists and their
hired cops knew that their chief potential competitor – hemp – was being outlawed
under the name “marijuana.”
That’s right. Marijuana was most likely just a pretext for hemp prohibition and
economic suppression.
The water was further muddied by the confusion of marijuana with “loco weed”
(Jimson Weed). The situation was not clarified by the press, which continued to
print the misinformation into the 1960s.
At the dawn of the 1990s, the most extravagant and ridiculous attacks on the hemp
plant drew national media attention – such as a study widely reported by health
journals* in 1989 that claimed marijuana smokers put on about a half a pound of
weight per day. Now in 1998, they just want to duck the issue.
*American Health, July/August 1989.
The U.S. Pharmacopoeia indicated that cannabis should be used for treating such
ailments as fatigue, fits of coughing, rheumatism, asthma, delirium tremens,
migraine headaches and the cramps and depressions associated with menstruation.
(Professor William EmBoden, Professor of Narcotic Botany, California State
University, Northridge.)
In early 1937, Assistant U.S. Surgeon General Walter Treadway told the Cannabis
Advisory Subcommittee of the League of Nations that, “It may be taken for a
relatively long time without social or emotional breakdown. Marihuana is
habit-forming. . . in the same sense as. . . sugar or coffee.” (Note He did not
state as alcohol, or heroin and sugar and coffee are quite legal substances still to
this day. While most people begin their day with a jolt of sugar and/or coffee to
get them going, for many suffering rare and/or autoimmune diseases a little
cannabis/marijuana is what is needed to kill enough pain to get them going, and
preferred over the harsher pharmaceuticals such as NSAIDs or painkillers which
often leave them unable to function well and often with a more severe
psychotropic effect than cannabis/marijuana.)
Why, you ask, was the AMA now on Anslinger’s side in 1944-45, after being
against the Marijuana Tax Act in 1937? Answer: since Anslinger’s FBN was
responsible for prosecuting doctors who prescribed narcotic drugs for what he,
Anslinger, deemed illegal purposes, they (the FBN) had prosecuted more than
3,000 AMA doctors for illegal prescriptions through 1939. In 1939, the AMA
made specific peace with Anslinger on marijuana. The results: only three doctors
were prosecuted for illegal drugs of any sort from 1939 to 1949.
However, from 1948 to 1950, Anslinger stopped feeding the press the story that
marijuana was violence-causing and began “red baiting”, typical of the McCarthy
era. Now the frightened American public was told that this was a much more
dangerous drug than he originally thought. Testifying before a strongly
anti-Communist Congress in 1948 – and thereafter continually to the press – Anslinger
proclaimed that marijuana rendered its users not violent at all, but so peaceful – and
pacifistic! – that the Communists could and would use marijuana to weaken our
American fighting men’s will to fight.
This was a 180-degree turnaround of the original pretext on which “violence-causing”
cannabis was outlawed in 1937. Undaunted, however, Congress now voted to
continue the marijuana law – based on the exact opposite reasoning they had used
to outlaw cannabis in the first place.
It is interesting and even absurd to note that Anslinger and his biggest supporters -
Southern congressmen and his best senatorial friend, Senator Joseph McCarthy* of
Wisconsin – from 1948 on, constantly received press coverage on the scare.
*According to Anslinger’s autobiographical book, The Murderers, and confirmed
by former FBN agents, Anslinger had been supplying morphine illegally to a U.S.
senator – Joseph McCarthy – for years. The reason given by Anslinger in his book?
So the Communists would not be able to blackmail this great American Senator
for his drug-dependency weakness. (Dean Latimer, Flowers in the Blood; Harry
Anslinger; The Murderers.)
Anslinger told congress the Communists would sell marijuana to American boys to
sap their will to fight – to make us a nation of zombie pacifists. Of course, the
Communists of Russia and China ridiculed this U.S. marijuana paranoia every
chance they got – in the press and at the United Nations.
Unfortunately, the idea of pot and pacifism got so much sensational world press
for the next 20 years that eventually Russia, China, and the Eastern Bloc
Communist countries (that grew large amounts of cannabis) outlawed marijuana
for fear that America would sell it or use it to make the communist soldiers docile
and pacifistic. This was strange because Russia, Eastern Europe, and China had
been growing and ingesting cannabis as a medical drug, relaxant and work tonic
for hundreds and even thousands of years, with no thought of marijuana laws.
(The J.V. Dialogue Soviet Press Digest, Oct. 1990 reported a flourishing illegal
hemp business, despite the frantic efforts by Soviet law enforcement agencies to
stamp it out. “In Kirghizia alone, hemp plantations occupy some 3,000 hectares.”
In another area, Russians are traveling three days into “one of the more sinister
places in the Moiyn-Kumy desert,” to harvest a special high-grade, drought resistant
variety of hemp known locally as anasha.)”
A Secret Program to Control Minds and Choices
Through a report released in 1983 under the Freedom of Information Act, it was
discovered (after 40 years of secrecy) that Anslinger was appointed in 1942 to a
top-secret committee to create a “truth serum” for the Office of Strategic Service
(OSS), which evolved into the Central Intelligence Agency (CIA). (Rolling Stone,
August 1983) Anslinger and his spy group picked, as America’s first truth serum,
“honey oil,” a much purer, almost tasteless form of hash oil, to be administered in
food to spies, saboteurs, military prisoners and the like, to make them unwittingly
“spill the truth.” Fifteen months later, in 1943, marijuana extracts were
discontinued by Anslinger’s group as America’s first truth serum because it was
noted that they didn’t work all the time. The people being interrogated would often
giggle or laugh hysterically at their captors, get paranoid, or have insatiable desires
for food (the munchies?). Also, the report noted that American OSS agents and
other interrogation groups started using the honey oil illegally themselves, and
would not give it to the spies. In Anslinger’s OSS group’s final
report on marijuana as a truth serum, there was no mention of violence caused
by the drug!
The empirical evidence in this book shows that the federal government – through
the 1937 Marijuana Tax Act – allowed this munitions maker to supply synthetic
fibers for the domestic economy without competition. The proof of a successful
conspiracy among these corporate and governing interests is simply this: in 1997
DuPont was still the largest producer of man-made fibers.
In America, marijuana’s most outspoken opponents are none other than former
First Lady Nancy Reagan (1981-1989) and former President George Bush
(1989-1993), the former Director of the CIA under Gerald Ford (1975-1977)
and past director of President Reagan’s “Drug Task Force” (1981-1988).
After leaving the CIA in 1977, Bush was made director of Eli Lily to none other
than Dan Quayle’s father and family, who owned controlling interest in the Lilly
company and the Indianapolis Star. Dan Quayle later acted as go-between for
drug kingpins, gun runners and government officials in the Iran-Contra scandals.
The entire Bush family was large stockholders in Lilly, Abbott, Bristol and
Pfizer, etc.
After Bush’s disclosure of assets in 1979, it became public that Bush’s family still
has a large interest in Pfizer and substantial amounts of stock in the other
aforementioned drug companies. In fact, Bush actively lobbied illegally both
within and without the administration as Vice President in 1981 to permit drug
companies to dump more unwanted, obsolete or especially domestically-banned
substances on unsuspecting Third World countries.
While Vice President, Bush continued to illegally act on behalf of pharmaceutical
companies by personally going to the IRS for special tax breaks for certain drug
companies (e.g. Lilly) manufacturing in Puerto Rico. In 1982, Vice President
Bush was personally ordered to stop lobbying the IRS on behalf of the drug
companies by the U.S. Supreme Court itself.
He did – but they (the pharmaceuticals) still received a 23% additional tax break
for their companies in Puerto Rico who make these American outlawed drugs for
sale to Third World countries.
(Financial disclosure statements; Bush 1979 tax report; “Bush Tried to Sway a
Tax Rule Change But Then Withdrew” NY Times, May 19, 1982; misc. corporate
records; Christic Institute “La Penca” affidavit; Lilly 1979 Annual Report.)
Bush managed to continue to direct this effort, simply by not allowing any grants
for private or public research with a positive implication to be issued by NIDA or
NIH, or approved any recent FDA applications unless they pursued negative results.
As of this writing (July 1998) President Clinton’s policy has remained the same.
This technique of biasing the outcome of a study is known among researchers as
“gutter science.”
Comparison to Alcohol
There are many terrible drug habits. The worst of which is alcohol, in both numbers
of users and the anti-social behavior associated with extreme use. Alcoholism is the
leading cause of teen-age deaths: 8,000 American teenagers are killed each year and
40,000 are maimed from mixing alcohol and driving. (MADD, Mothers Against
Drunk Driving; SADD, Students Against Drunk Driving; NIDA, National Institute
on Drug Abuse, etc.)
In fact, U.S. government/police statistics confirm the following strange numbers:
The mortality figure for alcohol use are 100,000 annually, compared with zero
marijuana deaths in 10,000 years of consumption.
From 40-50% of all murders and highway fatalities are alcohol related. In fact,
highway fatalities that are alcohol related might be as high as 90%, according to
the Chicago Tribune and L.A. Times.
Alcohol is also indicated in the majority (69-80%) of all child rape/incest cases;
wife beating incidents are in great majority (60-80%) alcohol influenced.
Heroin is indicated in 35% of burglaries, robberies, armed robberies, bank robberies,
grand theft auto, etc.
And there were more than 600,000 arrests for simple marijuana possession in the
U.S. in 1997 (up from 400,000 in 1992), according to the Uniform Crime Reporting
Statistics of the U.S. Department of Justice, Federal Bureau of Investigation.
Coming from a history of making explosives and munitions, the old “chemical dye
plants” now produce hosiery, mock linens, mock canvas, latex paint and synthetic
carpets. Their polluting factories make imitation leather, upholstery and wood
surfaces, while an important part of the natural cycle stands outlawed.
The standard fiber of world history, America’s traditional crop, hemp, could provide
our textiles and paper and be the premier source for cellulose. The war industries -
DuPont, Allied Chemical, Monsanto, etc., – are protected from competition by the
marijuana laws. They make war on the natural cycle and the common farmer.
- Shan Clark
“More Americans die in just one day in prisons, penitentiaries, jails and stockades
than have ever died from marijuana throughout history. Who are they protecting?
From what?” – Fred Oerther, M.D., Portland, Oregon, September 1986
It is a criminal offense for officials or executives of the U.S. government to direct or
conspire to wage a deliberate campaign of misinformation, omission of fact, and
outright lies with our tax dollars.
It stands worth repeating – Bush managed to continue to direct this effort, simply by
not allowing any grants for private or public research with a positive implication to
be issued by NIDA or NIH, or approved any recent FDA applications unless they
pursued negative results. As of this writing (July 1998) President Clinton’s policy
has remained the same.
July 1, 2010 – President Obama stated “This administration will not just kick the can
down the road.”
http://www.examiner.com/examiner/x-7002-Pittsburgh-Neighborhood-History-Examiner~y2009m6d3-Marijuana-Myths–Facts-Emerging-Clinical-Applications-for-Cannabis-and-Cannabinoids
Marijuana Myths & Facts Emerging Clinical Applications for Cannabis and
Cannabinoids
Myth: Marijuana is More Damaging to the Lungs Than Tobacco. Marijuana smokers
are at a high risk of developing lung cancer, bronchitis, and emphysema.
Fact: Moderate smoking of marijuana appears to pose minimal danger to the lungs.
Like tobacco smoke, marijuana smoke contains a number of irritants and carcinogens.
But marijuana users typically smoke much less often than tobacco smokers, and
over time, inhale much less smoke. As a result, the risk of serious lung damage
should be lower in marijuana smokers. There have been no reports of lung cancer
related solely to marijuana, and in a large study presented to the American Thoracic
Society in 2006, even heavy users of smoked marijuana were found not to have any
increased risk of lung cancer. Unlike heavy tobacco smokers, heavy marijuana
smokers exhibit no obstruction of the lung’s small airway. That indicates that people
will not develop emphysema from smoking marijuana.
Center on Addiction and Substance Abuse. “Legalization: Panacea or Pandora’s
Box.” New York. (1995): 36.
Turner, Carlton E. The Marijuana Controversy. Rockville: American Council for
Drug Education, 1981.
Nahas, Gabriel G. and Nicholas A. Pace. Letter. “Marijuana as Chemotherapy Aid
Poses Hazards.” New York Times 4 December 1993: A20.
Inaba, Darryl S. and William E. Cohen. Uppers, Downers, All-Arounders: Physical
and Mental Effects of Psychoactive Drugs. 2nd ed. Ashland: CNS Productions, 1995.
174.
Myth: Marijuana Has No Medicinal Value. Safer, more effective drugs are available.
They include a synthetic version of THC, marijuana’s primary active ingredient,
which is marketed in the United States under the name Marinol.
Fact: Marijuana has been shown to be effective in reducing the nausea induced by
cancer chemotherapy, stimulating appetite in AIDS patients, and reducing
intraocular pressure in people with glaucoma. There is also appreciable evidence
that marijuana reduces muscle spasticity in patients with neurological disorders. A
synthetic capsule is available by prescription, but it is not as effective as smoked
marijuana for many patients. Pure THC may also produce more unpleasant
psychoactive side effects than smoked marijuana. Many people use marijuana as
a medicine today, despite its illegality. In doing so, they risk arrest and imprisonment.
Vinciguerra, Vincent; Moore, Terry and Eileen Brennan. “Inhalation marijuana as
an antiemetic for cancer chemotherapy.” New York State Journal of
Medicine 85 (1988): 525-27.
McCabe M, Smith FP, Macdonald JS. “Efficacy of tetrahydrocannabinol in patients
refractory to standard antiemetic therapy.” Investigational New
Drugs 6.3 (1988): 243-46.
Gorter, R., et al. “Dronabionol effects on weight in patients with HIV
infection.” 1992. AIDS 6 (1992):127-38.
Foltin, R.W., et al. “Behavioral analysis of marijuana effects on food intake in
humans.” Pharmacology Biochemistry and Behavior 25 (1986): 577-82.
Crawford, W.J. and Merritt, J.C. “Effect of tetrahydrocannabinol on Arterial and
Intraocular Hypertension.” International Journal of Clinical of Pharmacology and
Biopharmaceuticals 17 (1979):191-96.
Merritt, J.C., et al. “Effects of marijuana on intraocular and blood pressure on
glaucoma.” Ophthamology 87 (1980):222-28.
Baker, D., Gareth Pryce and J. Ludovic Croxford. “Cannabinoids control spasticity
and tremor in a multiple sclerosis model.” Nature 404.6773 (2000): 84-7.
Hanigan, W.C., et al. “The Effect of Delta-9-THC on Human Spasticity.” Clinical
Pharmacology and Therapeutics 39 (1986):198.
Myth: Marijuana is a Gateway Drug. Even if marijuana itself causes minimal harm,
it is a dangerous substance because it leads to the use of “harder drugs” like heroin,
LSD, and cocaine.
Fact: Marijuana does not cause people to use hard drugs. What the gateway theory
presents as a causal explanation is a statistic association between common and
uncommon drugs, an association that changes over time as different drugs increase
and decrease in prevalence. Marijuana is the most popular illegal drug in the United
States today. Therefore, people who have used less popular drugs such as heroin,
cocaine, and LSD, are likely to have also used marijuana. Most marijuana users
never use any other illegal drug. Indeed, for the large majority of people, marijuana
is a terminus rather than a gateway drug.
Morral, Andrew R.; McCaffrey, Daniel F. and Susan M. Paddock. “Reassessing the
marijuana gateway effect.” Addiction 97.12 (2002): 1493-504.
United States. National Household Survey on Drug Abuse: Population Estimates
1994. Rockville, MD: U.S. Department of Health and Human Services, 1995.
National Household Survey on Drug Abuse: Main Findings 1994. Rockville, MD:
U.S. Department of Health and Human Services, 1996.
D.B. Kandel and M. Davies, “Progression to Regular Marijuana
Involvement: Phenomenology and Risk Factors for Near-Daily Use,”
Vulnerability to Drug Abuse, Eds. M. Glantz and R. Pickens. Washington, D.C.:
American Psychological Association, 1992: 211-253.
Myth: Marijuana’s Harms Have Been Proved Scientifically. In the 1960s and 1970s,
many people believed that marijuana was harmless. Today we know that marijuana
is much more dangerous than previously believed.
Fact: In 1972, after reviewing the scientific evidence, the National Commission on
Marihuana and Drug Abuse concluded that while marijuana was not entirely safe,
its dangers had been grossly overstated. Since then, researchers have conducted
thousands of studies of humans, animals, and cell cultures. None reveal any findings
dramatically different from those described by the National Commission in 1972. In
1995, based on thirty years of scientific research editors of the British medical journal
Lancet concluded that “the smoking of cannabis, even long term, is not harmful to
health.”
United States. National Commission on Marihuana and Drug Abuse. Marihuana:
A signal of misunderstanding. Shafer Commission Report. Washington, D.C.: U.S.
Government Printing Office, 1972.
“Deglamorising Cannabis.” Editorial. The Lancet 356:11(1995): 1241.
Myth: Marijuana Causes an Amotivational Syndrome. Marijuana makes users
passive, apathetic, and uninterested in the future. Students who use marijuana
become underachievers and workers who use marijuana become unproductive.
Fact: For twenty-five years, researchers have searched for a marijuana-induced
amotivational syndrome and have failed to find it. People who are intoxicated
constantly, regardless of the drug, are unlikely to be productive members of society.
There is nothing about marijuana specifically that causes people to lose their drive
and ambition. In laboratory studies, subjects given high doses of marijuana for
several days or even several weeks exhibit no decrease in work motivation or
productivity. Among working adults, marijuana users tend to earn higher wages
than non-users. College students who use marijuana have the same grades as
nonusers. Among high school students, heavy use is associated with school failure,
but school failure usually comes first.
Himmelstein, J.L. The Strange Career of Marihuana: Politics and Ideology of Drug
Control in America. Westport, CT: Greenwood Press, 1983.
Mellinger, G.D. et al. “Drug Use, Academic Performance, and Career
Indecision: Longitudinal Data in Search of a Model.” Longitudinal Research on
Drug Use: Empirical Findings and Methodological Issues. Ed. D.B. Kandel.
Washington, DC: American Psychological Association, 1978. 157-177.
Pope, H.G. et al., “Drug Use and Life Style Among College Undergraduates
in 1989: A Comparison With 1969 and 1978,” American Journal of Psychiatry
147 (1990): 998-1001.
Myth: Marijuana Policy in the Netherlands is a Failure. Dutch law, which allows
marijuana to be bought, sold, and used openly, has resulted in increasing rates of
marijuana use, particularly in youth.
Fact: The Netherlands’ drug policy is the most nonpunitive in Europe. For more
than twenty years, Dutch citizens over age eighteen have been permitted to buy
and use cannabis (marijuana and hashish) in government-regulated coffee shops.
This policy has not resulted in dramatically escalating cannabis use. For most age
groups, rates of marijuana use in the Netherlands are similar to those in the United
States. However, for young adolescents, rates of marijuana use are lower in the
Netherlands than in the United States. The Dutch people overwhelmingly approve
of current cannabis policy which seeks to normalize rather than dramatize cannabis
use. The Dutch government occasionally revises existing policy, but it remains
committed to decriminalization.
Fromberg, E. “The Case of the Netherlands: Contradictions and Values in
Questioning Prohibition.” 1994 International Report on Drugs, Brussels: International
Antiprohibitionist League, 1994. 113-124.
Sandwijk, J.P., et al. Licit and Illicit Drug Use in Amsterdam II. Amsterdam:
University of Amsterdam, 1995.
Gunning, K.F. Crime Rate and Drug Use in Holland. Rotterdam: Dutch National
Committee on Drug Prevention. 1993.
Myth: Marijuana Kills Brain Cells. Used over time, marijuana permanently alters
brain structure and function, causing memory loss, cognitive impairment,
personality deterioration, and reduced productivity.
Fact: None of the medical tests currently used to detect brain damage in humans
have found harm from marijuana, even from long term high-dose use. An early
study reported brain damage in rhesus monkeys after six months exposure to high
concentrations of marijuana smoke. In a recent, more carefully conducted study,
researchers found no evidence of brain abnormality in monkeys that were forced
to inhale the equivalent of four to five marijuana cigarettes every day for a year.
The claim that marijuana kills brain cells is based on a speculative report dating
back a quarter of a century that has never been supported by any scientific study.
Heath, R.G., et al. “Cannabis Sativa: Effects on Brain Function and Ultrastructure
in Rhesus Monkeys.” Biological Psychiatry 15 (1980): 657-690.
Ali, S.F., et al. “Chronic Marijuana Smoke Exposure in the Rhesus Monkey IV:
Neurochemical Effects and Comparison to Acute and Chronic Exposure to
Delta-9-Tetrahydrocannabinol (THC) in Rats.” Pharmacology Biochemistry and
Behavior 40 (1991): 677-82.
Myth: Marijuana Impairs Memory and Cognition. Under the influence of marijuana,
people are unable to think rationally and intelligently. Chronic marijuana use causes
permanent mental impairment.
Fact: Marijuana produces immediate, temporary changes in thoughts, perceptions,
and information processing. The cognitive process most clearly affected by marijuana
is short-term memory. In laboratory studies, subjects under the influence of marijuana
have no trouble remembering things they learned previously. However, they display
diminished capacity to learn and recall new information. This diminishment only lasts
for the duration of the intoxication. There is no convincing evidence that heavy
long-term marijuana use permanently impairs memory or other cognitive functions.
Wetzel, C.D. et al., “Remote Memory During Marijuana Intoxication,”
Psychopharmacology 76 (1982): 278-81.
Deadwyler, S.A. et al., “The Effects of Delta-9-THC on Mechanisms of Learning
and Memory.” Neurobiology of Drug Abuse: Learning and Memory. Ed. L. Erinoff.
Rockville, MD: National Institute on Drug Abuse 1990. 79-83.
Block, R.I. et al., “Acute Effects of Marijuana on Cognition: Relationships to Chronic
Effects and Smoking Techniques.” Pharmacology Biochemistry and Behavior 43
(1992): 907-917.
Myth: Marijuana Causes Crime. Marijuana users commit more property offenses
than nonusers. Under the influence of marijuana, people become irrational, aggressive,
and violent.
Fact: Every serious scholar and government commission examining the relationship
between marijuana use and crime has reached the same conclusion: marijuana does
not cause crime. The vast majority of marijuana users do not commit crimes other
than the crime of possessing marijuana. Among marijuana users who do commit crimes,
marijuana plays no causal role. Almost all human and animal studies show that
marijuana decreases rather than increases aggression.
Fagan, J., et al. “Delinquency and Substance Use Among Inner-City Students.”
Journal of Drug Issues 20 (1990): 351-402.
Johnson, L.D., et al. “Drugs and Delinquency: A Search for Causal Connections.”
Ed. D.B. Kandel. Longitudinal Research on Drug Use: Empirical Findings and
Methodological Issues. New York: John Wiley & Sons, 1978. 137-156.
Goode, E. “Marijuana and Crime.” Marihuana: A Signal of Misunderstanding,
Appendix I. National Commission on Marihuana and Drug Abuse Washington, DC:
U.S. Government Printing Office, 1972. 447-453.
Abram, K.M. and L.A. Teplin. “Drug Disorder, Mental Illness, and Violence.” Drugs
and Violence: Causes, Correlates, and Consequences. Rockville: National Institute
on Drug Abuse, 1990. 222-238.
Cherek, D.R., et al. “Acute Effects of Marijuana Smoking on Aggressive, Escape
and Point-Maintained Responding of Male Drug Users.” Psychopharmacology 111
(1993): 163-168.
Tinklenberg, J.R., et al. “Drugs and criminal assaults by adolescents: A Replication
Study.” Journal of Psychoactive Drugs 13 (1981): 277-287.
Myth: Marijuana Interferes With Male and Female Sex Hormones. In both men and
women, marijuana can cause infertility. Marijuana retards sexual development in
adolescents. It produces feminine characteristics in males and masculine
characteristics in females.
Fact: There is no evidence that marijuana causes infertility in men or women. In
animal studies, high doses of THC diminish the production of some sex hormones
and can impair reproduction. However, most studies of humans have found that
marijuana has no impact of sex hormones. In those studies showing an impact, it
is modest, temporary, and of no apparent consequence for reproduction. There is
no scientific evidence that marijuana delays adolescent sexual development, has
feminizing effect on males, or a masculinizing effect on females.
Parents Resource Institute for Drug Education. Marijuana and Cocaine.
Atlanta, GA: PRIDE, 1990.
Center for Substance Abuse Prevention. Female Adolescents and Marijuana Use;
Fact Sheet for Adults. Rockville: U.S. Department of Health and Human
Services, 1995.
Center for Substance Abuse Prevention. Marijuana: Tips for Teens.
Rockville: U.S. Department of Health and Human Services, 1995.
Swan, Neil. “A Look at Marijuana’s Harmful Effects.” NIDA
Notes. 9:2 (1994): 16.
Clinton, President Bill. Speech at Framingham High School. Framingham,
Massachusetts. 20 Oct. 1994.
Myth: Marijuana Use During Pregnancy Damages the Fetus. Prenatal marijuana
exposure causes birth defects in babies, and, as they grow older, developmental
problems. The health and well being of the next generation is threatened by
marijuana use by pregnant women.
Fact: Studies of newborns, infants, and children show no consistent physical,
developmental, or cognitive deficits related to prenatal marijuana exposure.
Marijuana had no reliable impact on birth size, length of gestation, neurological
development, or the occurrence of physical abnormalities. The administration of
hundreds of tests to older children has revealed only minor differences between
offspring of marijuana users and nonusers, and some are positive rather than
negative. Two unconfirmed case-control studies identified prenatal marijuana
exposure as one of many factors statistically associated with childhood cancer.
Given other available evidence, it is highly unlikely that marijuana causes cancer
in children.
Mann, Peggy. The Sad Story of Mary Wanna. NY: Woodmere Press, 1988. 30.
Fried, Peter. Quoted in “Marijuana: Its Use and Effects.” Prevention
Pipeline. 8:5 (1995): 4.
American Council for Drug Education. Drugs and Pregnancy. Rockville: Phoenix
House, 1994.
Swan, Neil. “A Look at Marijuana’s Harmful Effects.” NIDA
Notes. 9. 2 (1994): 16.
Parents Resource Institute for Drug Education. Marijuana – Effects on the Female.
Atlanta, GA: PRIDE, 1996.
Myth: Marijuana Use Impairs the Immune System. Marijuana users are at increased
risk of infection, including HIV. AIDS patients are particularly vulnerable to
marijuana’s immunopathic effects because their immune systems are already
suppressed.
Fact: There is no evidence that marijuana users are more susceptible to infections
than nonusers. Nor is there evidence that marijuana lowers users’ resistance to
sexually transmitted diseases. Early studies which showed decreased immune
function in cells taken from marijuana users have since been disproved. Animals
given extremely large doses of THC and exposed to a virus have higher rates of
infection. Such studies have little relevance to humans. Even among people with
existing immune disorders, such as AIDS, marijuana use appears to be relatively
safe. However, the recent finding of an association between tobacco smoking and
lung infection in AIDS patients warrants further research into possible harm from
marijuana smoking in immune suppressed persons.
Parents Resource Institute for Drug Education. Marijuana and Cocaine.
Atlanta: PRIDE, 1990.
Preate, Ernest D. Blowing Away the Marijuana Smokescreen. Scranton: Pennsylvania
Office of Attorney General, [no date]: 2.
Spence, W.R. Marijuana: Its Effects and Hazards. Waco: Health Edco, [no date].
Voth, Eric A. The International Drug Strategy Institute Position Paper on the Medical
Applications of Marijuana. Omaha: Drug Watch International, [no date].
Drug Watch International. By Any Modern Medical Standard, Marijuana is No
Medicine. Omaha: Drug Watch International, [no date].
Myth: Marijuana’s Active Ingredient, THC, Gets Trapped in Body Fat. Because THC
is released from fat cells slowly, psychoactive effects may last for days or weeks
following use. THC’s long persistence in the body damages organs that are high in
fat content, the brain in particular.
Fact: Many active drugs enter the body’s fat cells. What is different (but not unique)
about THC is that it exits fat cells slowly. As a result, traces of marijuana can be
found in the body for days or weeks following ingestion. However, within a few
hours of smoking marijuana, the amount of THC in the brain falls below the
concentration required for detectable psychoactivity. The fat cells in which THC
lingers are not harmed by the drug’s presence, nor is the brain or other organs. The
most important consequence of marijuana’s slow excretion is that it can be detected
in blood, urine, and tissue long after it is used, and long after its psychoactivity has
ended.
Committees of Correspondence. Drug Abuse Newsletter 16 (March 1984).
Mann, Peggy. Marijuana Alert. New York: McGraw-Hill Book Company. 1985. 184.
Nahas, Gabriel. “When Friends of Patients Ask About Marihuana.” Journal of the
American Medical Association 233 (1979): 79.
DuPont, Robert. Getting Tough on Gateway Drugs. Washington, DC: American
Psychiatric Press, 1984. 68.
Myth: Marijuana Related Hospital Emergencies Are Increasing, Particularly Among
Youth. This is evidence that marijuana is much more harmful than most people
previously believed.
Fact: Marijuana does not cause overdose deaths. The number of people in hospital
emergency rooms who say they have used marijuana has increased. On this basis,
the visit may be recorded as marijuana-related even if marijuana had nothing to do
with the medical condition preceding the hospital visit. Many more teenagers use
marijuana than use drugs such as heroin and cocaine. As a result, when teenagers
visit hospital emergency rooms, they report marijuana much more frequently than
they report heroin and cocaine. In the large majority of cases when marijuana is
mentioned, other drugs are mentioned as well. In 1994, fewer than 2% of drug related
emergency room visits involved the use of marijuana.
Brown, Lee. Quoted in U.S. Department of Health and Human Services Press
Release, National Drug Survey Results Released with New Youth Public Education
Materials. Rockville: 12 September 1995.
Shalala, Donna. “Say ‘No’ to Legalization of Marijuana.” Wall Street
Journal 18 August 1995: A10.
Shuster, Charles. Quoted in Drug Enforcement Administration. Drug
Legalization: Myths and Misconceptions. Washington, DC: U.S. Department
of Justice, 1994. 5.
Compiled by the same author:
http://www.examiner.com/examiner/x-7002-Pittsburgh-History-Examiner~y2009m6d27-Medicinal-Marijuana-Bibliography
Medicinal Marijuana Bibliography Medicine Medical Cannabis Reading List
Medicinal Marijuana Bibliography
General Information on Marijuana as Medicine
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Medical Marijuana and Cancer
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Response to the above article (same page)
M.Warner says:
Credible health organizations supporting access to medical Cannabis (marijuana).
Let’s bury the “no medical support” myth once and for all:
American Academy of Family Physicians, American College of Physicians,
American Medical Student Association, American Nurses Association, American
Preventive Medical Association, American Public Health Association, American
Society of Addiction Medicine, Arthritis Research Campaign (United Kingdom),
Australian Medical Association (New South Wales), Limited Australian National
Task Force on Cannabis, Belgian Ministry of Health, British House of Lords
Select Committee On Science and Technology (First & Second Report), British
Medical Association, Canadian AIDS Society, Canadian Special Senate Committee
on Illegal Drugs, Health Canada, Kaiser Permanente, Leukemia and Lymphoma
Society, Lymphoma Foundation of America, Multiple Sclerosis Society (Canada),
The Multiple Sclerosis Society (United Kingdom), National Association for Public
Health Policy, National Nurses Society on Addictions, Netherlands Ministry of
Health, New South Wales (Australia), New England Journal of Medicine, AIDS
Action Council, AIDS Treatment News, Parliamentary Working Party on the Use
of Cannabis for Medical Purposes, Dr. Andrew Weil, Alaska Nurses Association,
Being Alive: People With HIV/AIDS Action Committee (San Diego, CA), California
Academy of Family Physicians, California Nurses Association, California Pharmacists,
Colorado Nurses Association, Connecticut Nurses Association, Florida Governor’s
Red Ribbon Panel on AIDS, Florida Medical Association, Hawaii Nurses Association,
Illinois Nurses Association, Life Extension Foundation, Medical Society of the State
of New York, the Minnesota AIDS Council, New York State Nurses Association,
Medical Student Section of the American Medical Association, Mississippi Nurses
Association, New Jersey State Nurses Association, New Mexico Medical Society,
New Mexico Nurses Association, New York County Medical Society, New York
State Nurses Association, North Carolina Nurses Association, Rhode Island Medical
Society, Rhode Island State Nurses Association, San Francisco Mayor’s Summit on
AIDS and HIV, San Francisco Medical Society, Vermont Medical Marijuana Study
Committee, Virginia Nurses Association, Whitman-Walker Clinic (Washington, DC),
Wisconsin Nurses Association, etc…
And from the American College of Physicians (ACP):
“A CLEAR DISCORD exists between the scientific community and federal legal
and regulatory agencies over the medicinal value of marijuana, which impedes the
expansion of research.”
“Given marijuana’s PROVEN EFFICACY at treating certain symptoms and its
relatively low toxicity, reclassification would seem the most sensible thing to do
and increase availability of cannabinoid drugs to patients who have failed to respond
to other treatments.”“
(The ACP is the largest medical specialty organization in the U.S, representing 124,000
members specializing in internal medicine and related subspecialties, including
cardiology, neurology, pulmonary disease, oncology and infectious diseases. The
ACP publishes “Annals of Internal Medicine”, the most widely cited medical specialty
journal in the world.)
The under-staffed and under-funded FDA “fast tracks” killer-pharmaceuticals through
their trials “process”. For instance, Vioxx passed through the FDA’s process with
flying colors — in record time — and then it killed close to 30,000 people (the size
of my hometown) from sudden cardiac “events”, in just a few years, according to
the FDA.
Cannabis, on the other hand, has never killed from toxicity in thousands of years,
despite MILLIONS and MILLIONS of people using it. This is truly remarkable!
Shouldn’t we have the right to choose medications, like Cannabis, that cannot kill
us from toxicity?
Too many people know the truth for the FDA-charade to continue. The longer the
FDA tries to keep up this blatant and shameful lie (“Cannabis has no medical value”)
the more foolish and less credible they appear. The FDA is basically trying to
re-write history and science by lying about Cannabis’s well-known medical efficacy.
Blocking access to safe medicine is unconscionable.
http://www.fda.gov/downloads/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/UnderstandingOver-the-CounterMedicines/UCM094874.pdf
According to the FDA medicine is “something that change the way that your body
works or treat or prevent a disease or symptom“.
http://www.fda.gov/AboutFDA/CentersOffices/default.htm
The FDA is responsible for protecting the public health by assuring the safety,
efficacy, and security of human and veterinary drugs, biological products, medical
devices, our nation’s food supply, cosmetics, products that emit radiation, and
tobacco products.
The FDA is also responsible for advancing the public health by helping to speed
innovations that make medicines and foods more effective, safer, and more
affordable; and helping the public get the accurate, science-based information
they need to use medicines and foods to improve their health.
The FDA is responsible for protecting the public health not pharmaceutical
companies profits.
‘Body of Literature,’
Starting with ancient materia medicae, Chinese and Hindu pharmacopoeia and
Near Eastern cuneiform tablets, and continuing all the way into this century,
including the 1966-76 U.S. renaissance of cannabis studies – some 10,000 separate
studies on medicines and effects from the hemp plant. More recent studies
probably add a few hundred if not thousand more.
http://cc.msnscache.com/reference/semhtml/?title=Medical_cannabis&src=abop&qpvt=medical+marijuana&fwd=1&q=medical+marijuana
Medical cannabis (also referred to as medical marijuana) is the use of cannabis
(including the constituents of cannabis: THC and other cannabinoids) as a
physician-recommended form of medicine or herbal therapy. The Cannabis
plant (from which the cannabis drug is derived) has a long history of medicinal
use, with evidence dating back to 2,737 B.C.E.[1]
Although the extent of the medicinal value of cannabis has been disputed, it does
have several well-documented beneficial effects.[2][3][4][5] Among these are: the
amelioration of nausea and vomiting, stimulation of hunger in chemotherapy and
AIDS patients, lowered intraocular eye pressure (shown to be effective for treating
glaucoma), as well as general analgesic effects (pain reliever).
Synthetic cannabinoids are available as prescription drugs in many countries.
Examples include Marinol, available in Germany and the United States, and
Cesamet, available in Canada, Mexico, the United Kingdom, and also in the
United States.
There are several methods for administration of dosage, including vaporizing or
smoking dried buds, drinking or eating extracts, and taking capsules.[6] The
comparable efficacy of these methods was the subject of an investigative
study[5] conducted by the National Institutes of Health.
While cannabis for recreational use is illegal in most parts of the world, its use as
a medicine is legal in a number of territories worldwide, including Canada, Austria,
Germany, the Netherlands, Spain, Israel, Italy, Finland, and Portugal. In the United
States, federal law outlaws all cannabis use, while permission for medical cannabis
varies among states. Distribution is usually done within a framework defined by
local laws. Medical cannabis remains a controversial issue worldwide.
Clinical applications
In a 2002 review of medical literature, medical cannabis was shown to have
established effects in the treatment of nausea, vomiting, premenstrual syndrome,
unintentional weight loss, helps fight insomnia and lack of appetite. Other “relatively
well-confirmed” effects were in the treatment of “spasticity, painful conditions,
especially neurogenic pain, movement disorders, asthma, [and] glaucoma”.[7]
Preliminary findings indicate that cannabis-based drugs could prove useful in
treating inflammatory bowel disease (consisting of Crohn’s disease and ulcerative
colitis),[8] migraines, fibromyalgia, and related conditions.[9]
Medical cannabis has also been found to relieve certain symptoms of
multiple sclerosis[10] and spinal cord injuries[11][12][13] by exhibiting
antispasmodic and muscle-relaxant properties as well as stimulating appetite.
Clinical trials provide evidence that THC reduces motor and vocal tics of Tourette
syndrome and related behavioral problems such as obsessive–compulsive
disorders.[14][15]
Other studies have shown cannabis or cannabinoids may be useful in treating
alcohol abuse,[16] attention-deficit hyperactivity disorder
(ADHD or AD/HD)[17][18] amyotrophic lateral sclerosis,[19][20][21] collagen-induced
arthritis,[22] rheumatoid arthritis,[23] asthma,[24] atherosclerosis,[25] bipolar
disorder,[26][27] childhood mental disorders,[28] colorectal cancer,
[29] depression,[30][31][32][33] diabetic retinopathy,[34][35] dystonia,[36]
[37] epilepsy,[38][39] digestive diseases,[40][41] gliomas,[42][43] hepatitis
C,[44][45] Huntington’s disease,[46] hypertension,[47][48] urinary
incontinence,[49] leukemia,[50] skin tumors,[51] morning sickness,[52]
[53] methicillin-resistant Staphylococcus aureus (MRSA),[54][55] Parkinson’s
disease,[56] pruritus,[57][58] posttraumatic stress disorder (PTSD),
[59][60][61] sickle-cell disease,[62] sleep apnea,[63]tourette syndrome,
[64][65] and anorexia nervosa.[66]
Recent studies
Alzheimer’s disease
Research done by the Scripps Research Institute in California shows that the
active ingredient in marijuana, THC, prevents the formation of deposits in the
brain associated with Alzheimer’s disease. THC was found to prevent an enzyme
called acetylcholinesterase from accelerating the formation of “Alzheimer plaques”
in the brain more effectively than commercially marketed drugs. THC is also more
effective at blocking clumps of protein that can inhibit memory and cognition in
Alzheimer’s patients, as reported in Molecular Pharmaceutics.[67]
Lung cancer and chronic obstructive pulmonary disease
One of the more surprising research results from the last decade has been the
finding that smoking cannabis does not increase the risk of developing lung cancer
or chronic obstructive pulmonary disease (COPD) among people who do not smoke
tobacco, and may indeed confer a mildly protective effect. Beginning in 2001,
multiple research teams began to report results showing that smoking cannabis
does not, by itself, increase the risk of lung cancer, and this result is now
well-established. Many studies did report a strongly synergistic effect, however,
between tobacco use and smoking cannabis such that tobacco smokers who also
smoked cannabis dramatically increased their already very high risk of developing
lung cancer or chronic obstructive pulmonary disease by as much as 300%. Some
of these research results follow below:
In 2006, Hashibe, Morgenstern, Cui, and Tashkin, et al. presented the results from
a study involving 2,240 subjects that showed non-tobacco users who smoked
marijuana did not exhibit an increased incidence of lung cancer or head-and-neck
malignancies. These results were supported even among very long-term, very
heavy users of marijuana.[68]
Tashkin, a pulmonologist who has studied marijuana for 30 years, said, “It’s
possible that tetrahydrocannabinol (THC) in marijuana smoke may encourage
apoptosis, or programmed cell death, causing cells to die off before they have a
chance to undergo malignant transformation”. He further commented that “We
hypothesized that there would be a positive association between marijuana use
and lung cancer, and that the association would be more positive with heavier
use. What we found instead was no association at all, and even a suggestion of
some protective effect.”[69][70]
Researchers from the University of British Columbia presented a study at the
American Thoracic Society 2007 International Conference showing that smoking
marijuana and tobacco together more than tripled the risk of developing COPD
over just smoking tobacco alone.[71]
Similar findings were released in April 2009 by the Vancouver Burden of
Obstructive Lung Disease Research Group. The study reported that smoking
both tobacco and marijuana synergistically increased the risk of respiratory
symptoms and COPD. Smoking only marijuana, however, was not associated with
an increased risk of respiratory symptoms of COPD.[72][73] In a related
commentary, pulmonary researcher Donald Tashkin wrote, “…we can be close
to concluding that marijuana smoking by itself does not lead to COPD”.[74]
One of the principal constituents of cannabis, THC, has been found to reduce
tumor growth in common lung cancer by 50 percent and to significantly reduce
the ability of the cancer to spread, say researchers at Harvard University, who
tested the chemical in both in vitro lab studies and in mouse studies. The researchers
suggest that THC might be used in a targeted fashion to treat lung cancer.[75]
Breast cancer
According to a 2007 study at the California Pacific Medical Center Research
Institute, cannabidiol (CBD) may stop breast cancer from spreading throughout
the body.[76] These researchers believe their discovery may provide a non-toxic
alternative to chemotherapy while achieving the same results minus the painful and
unpleasant side effects. The research team says that CBD works by blocking the
activity of a gene called Id-1, which is believed to be responsible for a process
called metastasis, which is the aggressive spread of cancer cells away from the
original tumor site.[76]
HIV/AIDS
Investigators at Columbia University published clinical trial data in 2007 showing
that HIV/AIDS patients who inhaled cannabis four times daily experienced
substantial increases in food intake with little evidence of discomfort and no
impairment of cognitive performance. They concluded that smoked marijuana
has a clear medical benefit in HIV-positive patients.[77][78] In another study
in 2008, researchers at the University of California, San Diego School of Medicine
found that marijuana significantly reduces HIV-related neuropathic pain when
added to a patient’s already-prescribed pain management regimen and may be
an “effective option for pain relief” in those whose pain is not controlled with
current medications. Mood disturbance, physical disability, and quality of life
all improved significantly during study treatment.[79] Despite management with
opioids and other pain modifying therapies, neuropathic pain continues to reduce
the quality of life and daily functioning in HIV-infected individuals. Cannabinoid
receptors in the central and peripheral nervous systems have been shown to
modulate pain perception. No serious adverse effects were reported, according to
the study published by the American Academy of Neurology.[80]
Brain cancer
A study by Complutense University of Madrid found the chemicals in marijuana
promotes the death of brain cancer cells by essentially helping them feed upon
themselves in a process called autophagy. The research team discovered that
cannabinoids such as THC had anticancer effects in mice with human brain cancer
cells and in people with brain tumors. When mice with the human brain cancer
cells received the THC, the tumor shrank. Using electron microscopes to analyze
brain tissue taken both before and after a 26- to 30-day THC treatment regimen,
the researchers found that THC eliminated cancer cells while leaving healthy cells
intact.[81] The patients did not have any toxic effects from the treatment; previous
studies of THC for the treatment of cancer have also found the therapy to be well
tolerated. However, the mechanisms which promote THC’s tumor cell–killing action
are unknown.[81]
Opioid dependence
Injections of THC eliminate dependence on opiates in stressed rats, according to a
research team at the Laboratory for Physiopathology of Diseases of the Central
Nervous System (France) in the journal Neuropsychopharmacology.[82] Deprived
of their mothers at birth, rats become hypersensitive to the rewarding effect of
morphine and heroin (substances belonging to the opiate family), and rapidly
become dependent. When these rats were administered THC, they no longer
developed typical morphine-dependent behavior. In the striatum, a region of the
brain involved in drug dependence, the production of endogenous enkephalins was
restored under THC, whereas it diminished in rats stressed from birth which had
not received THC. Researchers believe the findings could lead to therapeutic
alternatives to existing substitution treatments.[82]
In humans, drug treatment subjects who use cannabis intermittently are found to
be more likely to adhere to treatment for opioid dependence.[83] Historically,
similar findings were reported by Clendinning, who in 1843 utilized cannabis
substitution for the treatment of alcoholism and opium addiction[84] and Birch,
in 1889, who reported success in treating opiate and chloral addiction with
cannabis.[85]
Spasticity in multiple sclerosis
A review of six randomized controlled trials of a combination of THC and CBD
extracts for MS related spasticity noted a “trend of reduced spasticity in treated
patients”, however, quantitative analysis was not prudent. The authors postulate
that “cannabinoids may provide neuroprotective and anti-inflammatory benefits
in MS.”[86]
Medicinal compounds
Cannabis contains over 300 compounds. At least 66 of these are
cannabinoids [87][88], which are the basis for medical and scientific use of
cannabis. This presents the research problem of isolating the effect of specific
compounds and taking account of the interaction of these
compounds.[20] Cannabinoids can serve as appetite stimulants, antiemetics,
antispasmodics, and have some analgesic effects.[14] Five important cannabinoids
found in the cannabis plant are tetrahydrocannabinol, cannabidiol,
cannabinol, β-caryophyllene, and cannabigerol.
Tetrahydrocannabinol
Main article: Tetrahydrocannabinol
Tetrahydrocannabinol (THC) is the primary compound responsible for the
psychoactive effects of cannabis. The compound is a mild analgesic, and cellular
research has shown the compound has antioxidant activity.[1] THC is believed to
interfere with parts of the brain normally controlled by the endogenous cannabinoid
neurotransmitter, anandamide.[89][90] Anandamide is believed to play a role in
pain sensation, memory, and sleep.
Cannabidiol
Main article: Cannabidiol
Cannabidiol (CBD), is a major constituent of medical cannabis. CBD represents up
to 40% of extracts of the medical cannabis plant.[91] Cannabidiol relieves
convulsion, inflammation, anxiety, nausea, and inhibits cancer cell growth.[92] Recent
studies have shown cannabidiol to be as effective as atypical antipsychotics in
treating schizophrenia.[93] Because cannabidiol relieves the aforementioned symptoms,
cannabis strains with a high amount of CBD would be ideal for people with multiple
sclerosis, frequent anxiety attacks and Tourette syndrome.[94][95][96]
Cannabinol
Main article: Cannabinol
Cannabinol (CBN) is a therapeutic cannabinoid found in Cannabis sativa and
Cannabis indica.[97] It is also produced as a metabolite, or a breakdown product,
of tetrahydrocannabinol (THC).[98] CBN acts as a weak agonist of the CB1 and
CB2 receptors, with lower affinity in comparison to THC.[99][100]
β-Caryophyllene
Main article: Caryophyllene
Part of the mechanism by which medical cannabis has been shown to reduce
tissue inflammation is via the compound β-caryophyllene.[101] A cannabinoid
receptor called CB2 plays a vital part in reducing inflammation in humans and
other animals.[101] β-Caryophyllene has been shown to be a selective activator
of the CB2 receptor.[101] β-Caryophyllene is especially concentrated in cannabis
essential oil, which contains about 12–35% β-caryophyllene.[101]
Cannabigerol
Main article: Cannabigerol
Like cannabidiol, cannabigerol is not psychoactive but has been shown to lower
blood pressure in rates greater than cannabinol.[102]
Pharmacologic THC and THC derivatives
In the USA, the FDA has approved two cannabinoids for use as medical
therapies: dronabinol (Marinol) and nabilone. These medicines are taken orally.
These medications are usually used when first line treatments for nausea and
vomiting associated with cancer chemotherapy fail to work. In extremely high
doses and in rare cases “psychotomimetic” side effects are possible. The other
commonly-used antiemetic drugs are not associated with these side effects.
The prescription drug Sativex, an extract of cannabis administered as a sublingual
spray, has been approved in Canada for the adjunctive treatment (use along side
other medicines) of both multiple sclerosis[103] and cancer related pain.[104] This
medication may be legally imported into the United Kingdom and Spain on
prescription.[105] William Notcutt is one of the chief researchers that has
developed Sativex, and he has been working with GW and founder Geoffrey
Guy since the company’s inception in 1998. Notcutt states that the use of MS
as the disease to study “had everything to do with politics.”[106]
Medication Approval Country Licensed indications Cost
Nabilone 1985 USA, Nausea of cancer chemotherapy $4000.00 U.S.
Canada that has failed to respond for a year’s supply
adequately to other antiemetics (in Canada)[107]
Marinol 1985 USA Nausea and vomiting associated $652 U.S. for 30
1992 Canada with cancer chemotherapy in doses @ 10 mg
Patients who have failed to online[108]
respond adequately to conventional treatments
Sativex 1995 Canada Adjunctive treatment for the $9,351 Canadian
symptomatic relief of per year[110]
neuropathic pain in
multiple sclerosis in
Adults
Sativex 1997 Canada Pain due to cancer
Criticism
One of the major criticisms of cannabis as medicine is opposition to smoking as
a method of consumption.[citation needed]
The United States Food and Drug Administration (FDA) issued an advisory against
smoked medical marijuana stating that, “marijuana has a high potential for abuse,
has no currently accepted medical use in treatment in the United States, and has
a lack of accepted safety for use under medical supervision. Furthermore, there
is currently sound evidence that smoked marijuana is harmful.”[111]
The Institute of Medicine, run by the United States National Academy of
Sciences, conducted a comprehensive study in 1999 to assess the potential health
benefits of cannabis and its constituent cannabinoids. The study concluded that
smoking cannabis is not recommended for the treatment of any disease condition,.
but did conclude that nausea, appetite loss, pain and anxiety can all be mitigated
by marijuana. While the study expressed reservations about smoked marijuana
due to the health risks associated with smoking, the study team concluded that
until another mode of ingestion was perfected that could provide the same relief
as smoked marijuana, there was no alternative. However, modern vaporizers and
the ingestion of cannabis in a decarboxylated state have laid most of these concerns
to rest.[citation needed] In addition, the study pointed out the inherent difficulty in
marketing a non-patentable herb. Pharmaceutical companies will not substantially
profit unless there is a patent. For those reasons, the Institute of Medicine concluded
that there is little future in smoked cannabis as a medically approved medication.
The report also concluded for certain patients, such as the terminally ill or those
with debilitating symptoms, the long-term risks are not of great concern.[112][113]
Marinol was less effective than the steroid megestrol in helping cancer patients regain
lost appetites.[114] A phase III study found no difference in effects of an oral
cannabis extract or THC on appetite and quality of life (QOL) in patients with
cancer-related anorexia-cachexia syndrome (CACS) to placebo.[115]
Harm reduction
The harm caused by smoking can be minimized or eliminated by the use of a
vaporizer[116] or ingesting the drug in an edible form. This risk is also thought to
be decreased by processing the cannabis leaves into hemp oil.[117]
Vaporizers are devices that heat the active constituents of cannabis in a partial
vacuum so that their vapors can be inhaled. Combustion of plant material is avoided,
thus preventing the formation of carcinogens such as polyaromatic hydrocarbons,
benzene and carbon monoxide. A pilot study led by Donald Abrams of UC San
Francisco showed that vaporizers eliminate the release of irritants and toxic
compounds, while delivering equivalent amounts of THC into the bloodstream.[118]
In order to kill microorganisms, especially the molds A. fumigatus, A. flavus
and A. niger, Levitz and Diamond suggested baking marijuana at 150 °C (302 °F)
for five minutes. They also found that tetrahydrocannabinol (THC) was not
degraded by this process.[119]
Organizational support
A number of medical organizations have endorsed allowing patients access to
medical marijuana with their physicians’ approval. These include, but are not
limited to, the following:
The American Medical Association[120][121]
The American College of Physicians – America’s second largest physicians group[122]
Leukemia & Lymphoma Society – America’s second largest cancer charity[123]
American Academy of Family Physicians[124]
American Alliance for Medical Cannabis
American Public Health Association
American Psychiatric Association
American Nurses Association
British Medical Association
AIDS Action
American Academy of HIV Medicine
Lymphoma Foundation of America
Health Canada
History
Ancient China and Taiwan
Cannabis, called má 麻 or dàmá 大麻 (with “big; great”) in Chinese, was used
in Taiwan for fiber starting about 10,000 years ago.[125] The botanist Li Hui-L
in wrote that in China, “The use of Cannabis in medicine was probably a very
early development. Since ancient men used hemp seed as food, it was quite natural
for them to also discover the medicinal properties of the plant.”[126] The oldest
Chinese pharmacopeia, the (ca. 100 CE) Shennong Bencaojing 神農本草經
(“Shennong’s Materia Medica Classic”), describes dama “cannabis”.
The flowers when they burst (when the pollen is scattered) are called 麻蕡
[mafen] or 麻勃 [mabo]. The best time for gathering is the 7th day of the 7th
month. The seeds are gathered in the 9th month. The seeds which have entered
the soil are injurious to man. It grows in [Taishan] (in [Shandong] …). The flowers,
the fruit (seed) and the leaves are officinal. The leaves and the fruit are said to be
poisonous, but not the flowers and the kernels of the seeds.[127]
Cannabis is one of the 50 “fundamental” herbs in traditional Chinese
medicine,[128] and is prescribed to treat diverse indications.
Every part of the hemp plant is used in medicine; the dried flowers (勃),
the achenia (蕡), the seeds (麻仁), the oil (麻油), the leaves, the stalk, the root,
and the juice. The flowers are recommended in the 120 different forms
of (風 feng) disease, in menstrual disorders, and in wounds. The achenia,
which are considered to be poisonous, stimulate the nervous system, and if
used in excess, will produce hallucinations and staggering gait. They are prescribed
in nervous disorders, especially those marked by local anaesthesia. The seeds, by
which is meant the white kernels of the achenia, are used for a great variety of
affections, and are considered to be tonic, demulcent, alterative, laxative,
emmenagogue, diuretic, anthelmintic, and corrective. They are made into a congee
by boiling with water, mixed with wine by a particular process, made into pills,
and beaten into a paste. A very common mode of exhibition, however, is by
simply eating the kernels. It is said that their continued use renders the flesh firm
and prevents old age. They are prescribed internally in fluxes, post-partum
difficulties, aconite poisoning, vermillion poisoning, constipation, and obstinate
vomiting. Externally they are used for eruptions, ulcers, favus, wounds, and
falling of the hair. The oil is used for falling hair, sulfur poisoning, and dryness
of the throat. The leaves are considered to be poisonous, and the freshly
expressed juice is used as an anthelmintic, in scorpion stings, to stop the hair from
falling out and to prevent it from turning grey. They are especially thought to
have antiperiodic properties. The stalk, or its bark, is considered to be diuretic,
and is used with other drugs in gravel. The juice of the root is used for similar
purposes, and is also thought to have a beneficial action in retained placenta and
post-partum hemorrhage. An infusion of hemp (for the preparation of which no
directions are given) is used as a demulcent drink for quenching thirst and
relieving fluxes.[129]
In the early 3rd century AD, Hua Tuo was the first person known to use cannabis
as an anesthetic. He reduced the plant to powder and mixed it with wine for
administration.[130]
Ancient Egypt
The Ebers Papyrus (ca. 1,550 B.C.) from Ancient Egypt describes medical
marijuana.[131] Other ancient Egyptian papyri that mention medical marijuana
are the Ramesseum III Papyrus (1700 BC), the Berlin Papyrus (1300 BC) and
the Chester Beatty Medical Papyrus VI (1300 BC).[132] The ancient Egyptians
even used hemp (cannabis) in suppositories for relieving the pain of
hemorrhoids.[133] The egyptologist Lise Manniche notes the reference to
“plant medical marijuana” in several Egyptian texts, one of which dates back
to the eighteenth century B.C.[134]
Ancient India
Surviving texts from ancient India confirm that cannabis’ psychoactive properties
were recognized, and doctors used it for a variety of illnesses and ailments. These
included insomnia, headaches, a whole host of gastrointestinal disorders, and
pain: cannabis was frequently used to relieve the pain of childbirth.[135]
Ancient Greece
The Ancient Greeks used cannabis not only for human medicine, but also in
veterinary medicine to dress wounds and sores on their horses.[136]
In humans, dried leaves of cannabis were used to treat nose bleeds, and cannabis
seeds were used to expel tapeworms.[136] The most frequently described use of
cannabis in humans was to steep green seeds of cannabis in either water or wine,
later taking the seeds out and using the warm extract to treat inflammation and
pain resulting from obstruction of the ear.[136]
In the 5th century BCE Herodotus, a Greek historian, described how the
Scythians of the Middle East used cannabis in steam baths.[136]
Medieval Islamic world
In the medieval Islamic world, Arabic physicians made use of the diuretic,
antiemetic, antiepileptic, anti-inflammatory, pain killing and antipyretic properties
of Cannabis sativa, and used it extensively as medication from the 8th to 18th
centuries.[137]
Modern history
An Irish physician, William Brooke O’Shaughnessy, is credited with introducing
the therapeutic use of cannabis to Western medicine. He was Assistant-Surgeon
and Professor of Chemistry at the Medical College of Calcutta, and conducted a
cannabis experiment in the 1830s, first testing his preparations on animals, then
administering them to patients in order to help treat muscle spasms, stomach
cramps or general pain.[138]
Cannabis as a medicine became common throughout much of the Western world
by the 19th century. It was used as the primary pain reliever until the invention
of aspirin.[139] Modern medical and scientific inquiry began with doctors like
O’Shaughnessy and Moreau de Tours, who used it to treat melancholia and
migraines, and as a sleeping aid, analgesic and anticonvulsant.
By the time the United States banned cannabis in a federal law, the 1937 Marijuana
Tax Act, the plant was no longer extremely popular.[140][citation needed]
Skepticism about cannabis arose in response to the bill.[citation needed] The situation
was exacerbated by the stereotypes promoted by the media, that the drug was used
primarily by Mexican and African immigrants.[140]
Later in the century, researchers investigating methods of detecting cannabis
intoxication discovered that smoking the drug reduced intraocular
pressure.[141] In 1973 physician Tod H. Mikuriya reignited the debate concerning
cannabis as medicine when he published “Marijuana Medical Papers”. High
intraocular pressure causes blindness in glaucoma patients, so he hypothesized that
using the drug could prevent blindness in patients. Many Vietnam War veterans also
believed[weasel words] that the drug prevented muscle spasms caused by
battle-induced spinal injuries.[142] Later medical use focused primarily on its role
in preventing the wasting syndromes and chronic loss of appetite associated with
chemotherapy and AIDS, along with a variety of rare muscular and skeletal
disorders. Later, in the 1970s, a synthetic version of THC, the primary active
ingredient in cannabis, was synthesized to make the drug Marinol. Users reported
several problems with Marinol leading many to abandon capsules and resume
smoking the plant.[by whom?] Patients complained that the violent nausea
associated with chemotherapy made swallowing capsules difficult. The effects
of smoked cannabis are felt almost immediately, and it is therefore easily
dosed.[143] Marinol, like ingested cannabis is harder to titrate than smoked
cannabis.[citation needed] Some studies have indicated that other chemicals in
the plant may have a synergistic effect with THC.[144]
In addition, during the 1970s and 1980s, six U.S. states’ health departments
performed studies on the use of medical cannabis. These are widely considered
some of the most useful and pioneering studies on the subject. Voters in eight states
showed their support for cannabis prescriptions or recommendations given by
physicians between 1996 and 1999, including Alaska, Arizona, California, Colorado,
Maine, Michigan, Nevada, Oregon, and Washington, going against policies of the
federal government.[145]
In May 2001, “The Chronic Cannabis Use in the Compassionate Investigational
New Drug Program: An Examination of Benefits and Adverse Effects of Legal
Clinical Cannabis” (Russo, Mathre, Byrne et al.) was completed. This three-day
examination of major body functions of four of the five living US federal cannabis
patients found “mild pulmonary changes” in two patients.[146]
On October 7, 2003 a patent entitled “Cannabinoids as Antioxidants and
Neuroprotectants”
http://www.patentstorm.us/patents/6630507/fulltext.html
(#6,630,507) was awarded to the United States Department of Health and
Human Services, based on research done at the National Institute of
Mental Health (NIMH), and the National Institute of Neurological Disorders
and Stroke (NINDS). This patent claims that cannabinoids are “useful in the
treatment and prophylaxis of wide variety of oxidation associated diseases,
such as ischemic, age-related, inflammatory and autoimmune diseases. The
cannabinoids are found to have particular application as neuroprotectants, for
example in limiting neurological damage following ischemic insults, such as stroke
and trauma, or in the treatment of neurodegenerative diseases, such as Alzheimer’s
disease, Parkinson’s disease and HIV dementia.”[147
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http://www.maps.org/mmj/vaporizer.html. Retrieved 2009-11-14.
↑ ‘Run from the Cure’ Rick Simpson video.
↑ Abrams DI, Vizoso HP, Shade SB, Jay C, Kelly ME, Benowitz NL (November 2007).
“Vaporization as a smokeless cannabis delivery system: a pilot study”.
Clinical Pharmacology and Therapeutics 82 (5): 572–8.
doi:10.1038/sj.clpt.6100200. ISSN 0009-9236. PMID 17429350.
↑ Levitz SM, Diamond RD (October 1991).
“Aspergillosis and marijuana”. Annals of Internal
Medicine 115 (7): 578–9.
doi:10.1059/0003-4819-115-7-578_2 (inactive 2009-09-08).
ISSN 0003-4819. PMID 1652910.
http://www.annals.org/cgi/content/abstract/115/7/578-a.
↑ “AMA Urges Reclassifying Marijuana”. Americans for Safe Access.
http://www.safeaccessnow.org/article.php?id=5870#5.
Retrieved 10 January 2010.
↑ “Use of Cannabis for Medicinal Purposes”.
Report 3 of the Council on Science and Public Health (I-09). American Medical Assn.
http://www.ama-assn.org/ama1/pub/upload/mm/443/csaph-report3-i09.pdf.
Retrieved 10 January 2010.
↑ “Supporting Research into the Therapeutic Role of Marijuana” (PDF).
The American College of Physicians. 2008.
http://www.acponline.org/advocacy/where_we_stand/other_issues/medmarijuana.pdf.
Retrieved 15 August 2009.
↑ “Medical Marijuana Endorsements and Statements of Support”.
Marijuana Policy Project. 2007.
http://www.mpp.org/library/medical-marijuana-endorsements-and-statements-of-support.html.
Retrieved 29 January 2008.
↑ “Marijuana: Policy & Advocacy”. American Academy of Family Physicians. 2009.
http://www.aafp.org/online/en/home/policy/policies/m/marijuana.html.
Retrieved 6 October 2009.
↑ Abel, Ernest L. (1980).
“Cannabis in the Ancient World”. Marihuana: the first twelve thousand years.
New York City: Plenum Publishers. ISBN 978-0-306-40496-2.
http://www.druglibrary.org/schaffer/hemp/history/first12000/1.htm.
↑ Li, Hui-Lin (1974).
“An Archaeological and Historical Account of Cannabis in China”,
Economic Botany 28.4:437-448, p. 444.
↑ Bretschneider, Emil (1895).
Botanicon Sinicum: Notes on Chinese Botany from Native and
Western Sources. Part III, Botanical Investigations in the Materia Medica of
the Ancient Chinese. Kelly & Walsh. p. 378.
↑ Wong, Ming (1976).
La Médecine chinoise par les plantes. Paris: Tchou. OCLC 2646789.
↑ Smith, Frederick Porter (1911).
Chinese Materia Medica: Vegetable Kingdom. Shanghai: American
Presbyterian Mission Press. pp. 90-91.
↑ de Crespigny, Rafe (2007). A Biographical Dictionary of
Later Han to the Three Kingdoms (23-220 AD). Leiden: Brill Publishers. p. 332.
ISBN 978-90-04-15605-0. OCLC 71779118.
↑ “The Ebers Papyrus The Oldest (confirmed) Written Prescriptions
For Medical Marihuana era 1,550 BC”.
www.onlinepot.org.
http://www.onlinepot.org/medical/eberspapyrus.htm.
Retrieved 2008-06-10.
↑ “History of Cannabis”. www.reefermadnessmuseum.org.
http://www.reefermadnessmuseum.org/history/AEgyptian.htm.
Retrieved 2008-07-09.
↑ Pain, Stephanie (2007-12-15).
“The Pharaoh’s pharmacists”. New Scientist (Reed Business Information Ltd.).
http://www.newscientist.com/channel/health/mg19626341.600-the-pharaohs-pharmacists.html.
↑ Lise Manniche, An Ancient Egyptian Herbal, University of
Texas Press, 1989, ISBN 978-0-292-70415-2
↑ Touw M (January 1981).
“The religious and medicinal uses of Cannabis in China, India and Tibet”.
Journal of Psychoactive Drugs 13 (1): 23–34. ISSN 0279-1072. PMID 7024492.
http://www.cnsproductions.com/pdf/Touw.pdf.
↑ 136.0 136.1 136.2 136.3 “The Haworth Press Online Catalog: Article Abstract”.
www.haworthpress.com.
http://www.haworthpress.com/store/ArticleAbstract.asp?sid=0JN5HCHTFHLA9LA1NQVRUKQM7C3RB5A4&ID=4344.
Retrieved 2009-01-18.
↑ Lozano, Indalecio (2001).
“The Therapeutic Use of Cannabis sativa (L.) in Arabic Medicine”.
Journal of Cannabis Therapeutics 1 (1): 63–70. doi:10.1300/J175v01n01_05.
↑ Mack, Allyson; Janet Elizabeth Joy (2001).
Marijuana as Medicine?: The Science Beyond the Controversy. National Academy Press.
↑ “History of Cannabis”. BBC News. 2 November 2001.
http://news.bbc.co.uk/1/hi/programmes/panorama/1632726.stm.
Retrieved 10 August 2009.
↑ 140.0 140.1 “Marijuana – The First Twelve Thousand Years – Reefer Racism”.
Druglibrary.org. http://www.druglibrary.org/schaffer/hemp/history/first12000/11.htm.
Retrieved 2009-04-26.
↑ “Golden Guide”. www.zauberpilz.com.
http://www.zauberpilz.com/golden/g31-40.htm.
↑ Zimmerman, Bill; Nancy Crumpacker and Rick Bayer (1998).
Is Marijuana the Right Medicine for You?:
A Factual Guide to Medical Uses of Marijuana. Keats Publishing.
ISBN 0879839066.
↑ Baker, D.; Pryce, G., Giovannoni, G., Thompson, A.J. (May 2003).
“The therapeutic potential of cannabis” (Reprint). Lancet Neurology
(London: The Lancet Publishing Group) 2 (5): 291–98.
doi:10.1016/S1474-4422(03)00381-8. ISSN 1474-4422.
http://www.ukcia.org/research/TherapeuticPotentialOfCannabis.pdf.
Retrieved 15 August 2009.
↑ McPartland, John M.; Russo, Ethan B..
“Cannabis and Cannabis Extracts: Greater Than the Sum of Their Parts?”.
Journal of Cannabis Therapeutics. International Association for Cannabis as Medicine.
http://www.cannabis-med.org/data/pdf/2001-03-04-7.pdf.
↑ Mack,Alison ; Joy, Janet (2001).
Marijuana As Medicine. National Academy Press. ISBN 0309065313.
↑ Russo, Ethan; Mathre, Mary Lynn; Byrne, Al; Velin, Robert; Bach, Paul J;
Sanchez-ramos, Juan; Kirlin, Kristin A (2002).
“Chronic Cannabis Use in the Compassionate Investigational New
Drug Program: An Examination of Benefits and Adverse Effects of
Legal Clinical Cannabis” (PDF). Journal of Cannabis Therapeutics
(The Haworth Press) 2 (1): 3. doi:10.1300/J175v02n01_02.
http://www.medicalcannabis.com/PDF/Chronic_Cannabis.pdf.
↑ 147.0 147.1 US6,630,507 (PDF version) (2003-10-07) Hampson, Aidan J.;
Axelrod, Julius; Grimaldi, Maurizio, Cannabinoids as antioxidants and neuroprotectants.
According to the Institute of Medicine cannabis is not a “gateway drug”.
Marijuana Two-Minute Truths: Gateway Myth (MPP-TV)
http://www.youtube.com/watch?v=I9-xOTsIhZk
Marijuana and Medicine: Assessing the Science Base page 99
http://books.nap.edu/openbook.php?record_id=6376&page=99
http://www.druglibrary.org/schaffer/library/studies/nc/nc1h_3.htm
National Commission on Marihuana and Drug Abuse
Investigations of Very Heavy, Very Long-Term Cannabis Users
JAMAICA
Another foreign investigation (Ruben et al., 1972) conducted in Jamaica (under contract
for the National Institute of Mental Health) studied chronic cannabis users and matched
nonuser controls. Preliminary findings have shown little evidence of significant
differences between the two groups in the extensive anthropological, medical,
psychiatric and psychological investigations.
Ganja use is widespread and endemic in the Jamaican lowest socioeconomic strata,
and in particular in a millenial-religious sect known as the Rastafarians. More than
50% of all male Jamaicans are estimated to use some form of cannabis, and probably
about 20% are regular heavy users of ganja.
The drug was brought to Jamaica from India over 130 years ago by indentured East
Indian laborers. However, presently the heaviest ganja users are Afro-Jamaicans who
comprise 90% of the population.
The Rastafarian religious sect, founded by Marcus Garvey, preach a “Back to Africa”
destiny and claim Haile Selassie to be God. The Rastafarians have always worn. long
hair and beards and dressed eccentrically. They believe that “the herb” was given
them by God to help them to understand his wisdom exemplified in their greeting,
“Peace and Love.”
The Rastas reject the values of the dominant society and regard the government
as “the powers of Babylon”. They have, chosen to opt out of conventional society
and instead work and live in a communal existence in poverty. They emphasize the
value of ganja in achieving a new level of meaning in this existence.
The Rastafarians add ganja to their infant first bath and start feeding the drug to
their infants from the time of weaning in an infusion known as ganja tea. They
continue to smoke and drink the drug throughout life.
They, like many other Jamaicans, believe in its medicinal properties especially for
asthma and indigestion and promotion of healing; that it gives protection from evil
spirits; that it cleanses the skin and purifies the blood; that it promotes sexual vigor;
that it gives energy for work and relieves fatigue and provides relaxation after work.
Extensive in-depth studies have been carried out by a team of anthropologists from
The Research Institute for the Study of Man in conjunction with The Departments of
Psychiatry, Pathology, Physiology and Medicine, of the University of the West Indies.
Anthropology field workers lived for extensive periods of time in five rural
communities (including fishing, farming and cane cutting areas) and two urban districts.
Over 2,000 people were observed and studied in these communities. Overall life styles
of the ganja users were not notably different from nonusing individuals in the Jamaican
lowest socioeconomic strata. Users are working, maintaining stable families and homes,
and actively participating in their society. No evidence was noted of crime or
aggressive behavior or drug use other than alcohol related to ganja use. No evidence
of physical dependence was demonstrated. Minimal psychological dependence was
observed but no drug craving was expressed.
Thirty long-term ganja smokers and 30 nonusers matched demographically to control
factors other than ganja use, were chosen as representative of this functioning lower
socioeconomic population and selected for intensive hospital study in order to
determine, differences between the two groups.
The mean age of the subjects was 33 with a range of 23 to 51. The primary occupation
of one-third of the subjects was farming. The next most common occupations were,
fishing, skilled and semiskilled laborers. Half practiced no formal religion, five were
Rastafarians and the remainder practiced a wide variety of traditional religious.
Almost three-fourths of the males had stable “marriages” and the remaining single
subjects were predominantly the younger ones.
The subjects were divided into three groups. Twenty-three were nonganja smokers,
28 were regular daily ganja smokers and 9 were occasional ganja smokers using the
drug several times a we or less. Three types of regular ganja smokers were
delineated: light smokers using one to four spliffs daily moderate smokers using four
to seven spliffs daily; and heavy smokers using eight or more spliffs per day.
Age of first use ranged from 8-36 years of age. Regular use of ganja occurred at a
median age of 16 years with a range of 9-25 years. All ganja smokers had used the
drug at least 7 years and some up to 37 years with a mean of 17.5 years.
The ganja users consumer on the average seven spliffs of ganja daily with a range of
one to 24 per day. The typical ganja cigarette or cigar, termed a spliff is roughly a
four-inch-long paper cone and contains about two to three grams of ganja with a
delta 9 THC content of about 2.9% on the average (range of 0.7-10.3%) mixed with
about half of a Tobacco cigarette. Also many smoke ganja in a Chillum pipe using
very deep inhalation to fill their lungs with smoke. They consume 14 pipe fulls per
week on the average, with a range of 1-25 per week.
No significant differences in neurological abnormalities, electroencephalographic
abnormalities, hemochemical changes including liver function, urinalysis,
chest X-ray abnormalities or chromosome damage in lymphocytes were found in
the users or controls.
One user had a long history of bronchial asthma and another had a mild case of
Jamaican neuropathy, but nothing suggests these disabilities were in any way related
to ganja use. Minor electrocardiographic abnormalities were present in about
one-third of both users and controls. This may be related to a syndrome of unknown
etiology known as Jamaican cardiomiyopathy.
Thorough physical examination and hematological studies revealed only minimal
significant differences between ganja smokers and non-ganja smoking controls.
Comprehensive evaluation of red blood cell indices revealed that the ganja smokers
had significantly higher hemoglobin levels and packed red cell volumes (hematocrit)
than the non-ganja smokers.
These hematologic findings are compatible with those reported recently (Sangan
and Balberzak, 1971) for heavy tobacco cigarette smokers. The authors noted that
cigarette smoking causes a functional tissue hypoxia due to deficits in lung function
with resultant arterial oxygen unsaturation. Thus, an increased demand is placed on
the bone marrow to provide more red blood cells to increase the oxygen carrying
capacity of the blood.
In addition to the heavy smoking of ganja in spliffs and pipes, 27 of the 30 ganja
smokers were tobacco smokers, and several have smoked tobacco cigarettes heavily.
19 of the 30 non-ganja smokers were tobacco cigarette smokers and tended to be
light tobacco cigarette smokers.
Thus, the data appears to suggest that a combination of factors including number
of years and quantity of cigarette smoking, ganja spliff smoking and ganja chilum
pipe smoking is significantly correlated with the hematological changes indicative
of functional hypoxia. However, pulmonary function studies did not demonstrate
significant decrements correlated with ganja or tobacco smoking.
No significant differences were found between groups by a thorough psychiatric
and psychological examination. All subjects were judged to be in normal mental
health. Subjects were administered a battery of standardized reliable American
psychological tests known to be sensitive to impairment in brain function. These
tests were not culture free so that comparison of performance, between Jamaicans
and Americans is meaningless Nineteen tests evaluating 47 variables were performed
including one personality test, three tests of intelligence and verbal abilities, and 15
neuropsychological tests.
Two of 47 variables had statistically significant differences between ganja smokers
and non-smokers. The smokers scored higher on the digit span subtest of the
Wechsler Adult Intelligence Scale and bad a more centralized personality organization
on the Lowenfeld Mosaic Test.
Non-smokers had the best performance on the number of edge contacts with the
non-dominant hand on the Holes Test. These few significant differences were
considered chance findings by the investigators.
In general no consistent differences were found on these psychological tests between
ganja smokers and non-smokers. The data clearly indicate that the long-term ganja
use by these men did not produce demonstrable intellectual or ability deficits when
they were without the drug for three days. No evidence in these results suggest
permanent brain damage.
The alleged role of ganja in producing personality change in the direction of a loss
of competitive striving and an unwillingness to work, termed the amotivational
syndrome was also investigated.
Based on clinical impressions gained from careful sociological and psychological
techniques, the investigators noted that the chronic ganja smoker differed little in
work habits or record from his matched control. No evidence of an amotivational
syndrome was found. In fact, the subjects believe ganja has a functional value as a
work adjunct. It provides energy for work and helps them do arduous boring jobs.
In the Jamaican culture, ganja may produce a “motivational syndrome”. In an
objective videotape evaluation of work energy output and ganja smoking, ganja
use did not lower productivity on simple repetitive tasks, such as woodcutting
which requires compulsive concentrated effort.
A study of cultivators points up the relationship of population, land, and economic
pressures to ganja use. In the area studied land resources are scarce, farms small
and cultivation difficult on the hilly slopes. Market conditions determine income
from cash crops and restrictions on migration maintain population pressures on
limited resources.
For these farmers, the researchers suggest that ganja use, decreases total cultivated
acreage and consolidates production while disruption of competition and social
cohesiveness among the farmers is avoided.
These data may indicate that heavy ganja use during cultivation in farming situations
with limited alternatives may serve to maintain the status quo. However, it is possible
that the compulsive concentrated effort experienced by the cultivators with heavy
ganja use may be productive in areas with good soil and climatic conditions where
systematic weeding can increase crop yields.
As a result of the extensive anthropological study, the investigators believe that ganja
use in Jamaica is a culturally determined phenomenon. A “ganja complex” exists
which consists of closely related, learned patterns of behavior manifested by the
members of the society.
The ganja complex appears to be functional for the working-class Jamaican. Various
elements Of the complex including economic, social and personal are interrelated in
ways that contribute to operation of the whole culture.
http://www.druglibrary.org/schaffer/library/studies/cu/cu53.html
The Consumers Union Report on Licit and Illicit Drugs
by Edward M. Brecher and the Editors of Consumer Reports Magazine, 1972
Marijuana and hashish are commonly smoked in the United States; they can also be
taken orally in foods or beverages. They are not addicting. Neither tolerance nor
withdrawal symptoms have been reliably reported. The lethal dose is not known;
no human fatalities have been documented.
Marijuana is the popular name for a plant, Cannabis Sativa, also known as hemp.
Marijuana is also the common name of the drug prepared by drying the leaves and
flowering tops of the plant. The leaves and tops contain several members of a group o
f chemicals known as the cannabinoids. Hashish is the drug produced by drying the
resin exuded by the marijuana plant. The resin is richer in cannabinoids than the leaves
and tops–– one gram of hashish is said to have the effectiveness of five to eight grams
of marijuana–– but the potency of both marijuana and hashish varies widely from
sample to sample.
Many medications are offered in a variety of strength. Many doctors listen to their
patients in determining the strength to prescribe, sometimes it is higher, sometimes
lower than original determination. Many medications are adjusted over time at the
patients needs.
Evidence that even George Washington cultivated cannabis for medicinal purposes
and more information again from The Consumers Union Report on Licit and Illicit
Drugs by Edward M. Brecher and the Editors of Consumer Reports Magazine, 1972
http://www.druglibrary.org/schaffer/library/studies/cu/cu54.html
Jamestown settlers did bring the plant to Virginia in 1611, and cultivated it for its
fiber. 3 Marijuana was introduced into New England in 1629. 4 From then until after
the Civil War, the marijuana plant was a major crop in North America, and played an
important role in both colonial and national economic policy. In 1762, “Virginia
awarded bounties for hemp culture and manufacture, and imposed penalties upon
those who did not produce it.” 5
George Washington was growing hemp at Mount Vernon three years later–– presumably
for its fiber, though it has been argued that Washington was also concerned to increase
the medicinal or intoxicating potency of his marijuana plants. *
* The argument depends on a curious tradition, which may or may not be sound, that
the quality or quantity of marijuana resin (hashish) is enhanced if the male and female
plants are separated before the females are pollinated. There can be no doubt that
Washington separated the males from the females. Two entries in his diary supply
the evidence:
May 12-13, 1765: “Sowed Hemp at Muddy hole by Swamp.”
August 7, 1765: “–– began to seperate [sic] the Male from the Female Hemp at Do––
rather too late.” 6
George Andrews has argued, in The Book of Grass: An Anthology of Indian
Hemp (1967), that Washington’s August 7 diary entry “clearly indicates that he
was cultivating the plant for medicinal purposes as well as for it’s fiber.” 7 He might
have separated the males from the females to get better fiber, Andrews concedes––
but his phrase “rather too late” suggests that he wanted to complete the separation
before the female plants were fertilized–– and this was a practice related to drug
potency rather than to fiber culture.
Many eminent British and American physicians recommended marijuana as an
effective therapeutic agent. Dr. J. Russell Reynolds, Fellow of the Royal Society
and Physician in Ordinary to Her Majesty’s (Queen Victoria’s) Household, reported
in Lancet in 1890, for example, that he had been prescribing cannabis for thirty years
and that he considered it “one of the most valuable medicines we possess” 20 Sir
William Osler, professor of medicine at the Johns Hopkins and later Regius Professor
of Medicine at the University of Oxford, stated in his 1898 discussion of migraine
headaches that marijuana “is probably the most satisfactory remedy” for that
distressing condition.*
* Others who recommended marijuana for migraine headaches included the Committee
on Cannabis Indica of the Ohio State Medical Society (1860); 21 Dr. G. S. D. Anderson
in the Boston Medical and Surgical Journal (now the New England Journal of Medicine)
(1863); 22 Dr. Edward John Waring in his textbook, Practical
Therapeutics (1874); 23 Dr. C. W. Suckling in the British Medical Journal (1881);
24 Dr. J. B. Mattison in the St. Louis Medical and Surgical Journal (1891); 25 and
Dr. A. A. Stevens in his textbook, Modern Materia Medica (1903). 26 (We are indebted
to Dr. Tod H. Mikuriya 27 for a number of these and other historical references to the
medical history of marijuana.)
To meet the substantial nineteenth- and early twentieth-century medical demand for
marijuana, fluid extracts were marketed by Parke Davis, Squibb, Lilly, Burroughs
Wellcome, and other leading firms 29 and were sold over the counter by drugstores
at modest prices. Grimault and Sons actually marketed ready-made marijuana cigarettes
for use as an asthma remedy. 30 As medicine progressed after 1903, marijuana’s use d
eclined, but its therapeutic value remained unchallenged, and doctors continued to
prescribe it.
Footnotes
3. Richard Brotman and Alfred M. Freedman, “Perspectives on Marijuana Research,”
prepared for Center for Studies in Substance Use, unpublished, p. 19.
4. S. S. Boyce, Hemp, A Practical Treatise on the Culture of Hemp for Seed and. Fiber
with a Sketch of the History and Nature of the Hemp Plant (New York: Orange
Judd, 1900), p. 35.
5. Ibid.
6. Cited by George Andrews and Simon Vinkenoog, eds., The Book of Grass: An
Anthology of Indian Hemp (New York: Grove Press 1967), p. 34
20. J. Russell Reynolds, “On the Therapeutic Uses and Toxic Effects of Cannabis
Indica,” Lancet (March 22, 1970): 637,
21. R. R. McMeens, “Report of the Committee on Cannabis Indica,” from Transactions
of the 50th Annual Meeting of the Ohio State Medical Society (Columbus, Ohio: Follett,
Foster, 1860), pp. 75-100.
22. G. S. D. Anderson, “Remarks on the Remedial Virtues of Cannabis Indica, or Indian
Hemp,” Boston Medical and Surgical Journal, 67 (1863): 427-430.
23. Edward J. Waring, Practical Therapeutics (Philadelphia: Lindsay and
Blakiston, 18741), pp. 157-161.
24. C. W. Suckling, “On the Therapeutic Value of Indian Hemp,” British Medical
journal, 2 (1881): 12.
25. J. B. Mattison, “Cannabis Indica as an Anodyne and Hypnotic,” St. Louis Medical
and Surgical Journal, 61 (1891): 265-271.
26. A. A. Stevens, Modern Materia Medica and Therapeutics (Philadelphia: W. B.
Saunders, 1903), pp. 77-78.
27. Tod H. Mikuriya, “Marijuana in Medicine, Past, Present and Future,” California
Medicine, 110 (January, 1969): 34-40,
29. Marty Sasman, “Cannabis Indica in Pharmaceuticals,” Journal of the Medical Society
of New Jersey, 35 (1938): 51-52.
30. P. H. Blachly, “Use of Amphetamines, Marijuana and LSD by Students,” New
Physician, 15 (April, 1966): 90.
http://www.scribd.com/doc/17717921/The-Emperor-Wears-No-Clothes
Page 128 – 136
Government Doublespeak
Since 1976, our federal government (e.g., NIDA, NIH, DEA*, and Action), police
sponsored groups (like DARE*), and special interest groups (like PDFA*) have
proclaimed to public, press, and parent groups alike that they have “absolute evidence”
of the shocking negative effects of marijuana smoking.
* National Institute on Drug Abuse, National Institutes of Health, Drug Enforcement
Agency, Drug Abuse Resistance Education, Partnership for a Drug Free America. All
subsequent researchers found Heath’s marijuana findings to be of no value, because
carbon monoxide poisoning and other factors were totally left out.
When U.S. government sponsored research prior to 1976 indicated that cannabis was
harmless or beneficial, the methodology of how each study was done was always
presented in detail in the reports; e.g., read The Therapeutic Potential of Marijuana
(1976) and you will see exactly what the methodology of each medical study was.
However, when our government bureaucrats deliberately sponsored negative marijuana
research, time and time againPlayboy magazine, NORML, High Times, etc. had to sue
under the new Freedom of Information Act to find out the actual laboratory methodology
these “experiments” employed.
What they found was shocking.
Dr. Heath/Tulane Study, 1974
The Hype:
Brain Damage and Dead Monkeys
In 1974, California Governor Ronald Reagan was asked about decriminalizing marijuana.
After producing the Heath/Tulane University study, the so-called “Great Communicator”
proclaimed, “The most reliable scientific sources say permanent brain damage is one of
the inevitable results of the use of marijuana.”
(L.A. Times)
The report from Dr. Heath had concluded that Rhesus monkeys, smoking the equivalent
of only 30 joints a day, began to atrophy and die after 90 days.
And ever since, dead brain cells found in monkeys who were forced to smoke marijuana
has been given maximum scare play in federal booklets and government sponsored
propaganda literature against pot.
Senator Eastland of Mississippi used it throughout the mid-1970s to horrify and stop
national legislators from supporting NORML’s decriminalization bills in Congress,
mostly sponsored by the late Senator Jacob Javitts of New York.
Reports of the study have also been distributed by the hierarchy of drug rehabilitation
professionals as part of their rationalization for wanting to get kids off pot, based on
supposed scientific studies. It is used to terrorize parent groups, church organizations,
etc., who redistribute it still further.
Heath killed the half-dead monkeys, opened their brains, counted the dead brain cells,
and then took control monkeys, who hadn’t smoked marijuana, killed them too, and
countedtheir brain cells. The pot smoking monkeys had enormous amounts of dead
brain cells as compared to the “straight” monkeys.
Ronald Reagan’s pronouncement was probably based on the fact that marijuana
smoking was the only difference in the two sets of monkeys. Perhaps Reagan trusted
the federal research to be real and correct. Perhaps he had other motives.
Whatever their reasons, this is what the government ballyhooed to press and PTA, who
trusted the government completely.
In 1980,Playboy and NORML finally received for the first time after six years of
requests and suing the government an accurate accounting of the research procedures
used in the infamous report:
When NORML/Playboy hired researchers to examine the reported results against the
actual methodology, they laughed.
The Facts:
Suffocation of Research Animals
As reported inPlayboy, the Heath “Voodoo” Research methodology involved strapping
Rhesus monkeys into a chair and pumping them with equivalent of 63 Colombian
strength joints in “five minutes, through gas masks,” losing no smoke.Playboy
discovered that Heath had administered 63 joints in five minutes over just three months
instead of administering 30 joints per day over a one-year period as he had first reported.
Heath did this, it turned out, in order to avoid having to pay an assistant’s wages every
day for a full year.
The monkeys were suffocating! Three to five minutes of oxygen deprivation causes
brain damage “dead brain cells.” (Red Cross Lifesaving and Water Safety Manual)
With the concentration of smoke used, the monkeys were a bit like a person running
the engine of a car in a locked garage for 5, 10, 15 minutes at a time every day!
The Heath Monkey study was actually a study in animal asphyxiation and carbon
monoxide poisoning.
Among other things, Heath had completely (intentionally? incompetently?) omitted
discussion of the carbon monoxide the monkeys inhaled.
Carbon monoxide, a deadly gas that kills brain cells, is given off by any burning object.
At that smoke concentration, the monkeys were, in effect, like a person locked in a
garage with the car engine left running for five, 10, 15 minutes at a time every day!
All subsequent researchers agree the findings in Heath’s experiment regarding
marijuana were of no value, because carbon monoxide poisoning and other factors
were totally left out and had not been considered in the report. This study and others,
like Dr. Gabriel Nahas’ 1970s studies, tried to somehow connect the THC metabolites
routinely found in the fatty tissue of human brains, reproductive organs, and other
fatty areas of the body to the dead brain cells in the suffocated monkeys.
Now, in 1999, 17 years have passed and not a single word of Dr. Heath’s or Dr. Nahas’
research has been verified! But their studies are still hauled out by the Partnership for a
Drug Free America, the Drug Enforcement Administration, city and state narcotics
bureaus, plus politicians and, in virtually all public instances, held up as scientific proof
of the dangers of marijuana.
This is U.S. government propaganda and disinformation at its worst! The public paid for
these studies and has the right to the correct information and history being taught in our
taxpayer sponsored schools.
Lingering THC Metabolites
The Hype:
It Stays in Your System for 30 Days
The government also claimed that since “THC metabolites” stay in the body’s fatty cells
for up to 30 days after ingestion, just one joint was very dangerous; inferring that the
long range view of what these THC metabolites eventually could do to the human race
could not even be guessed and other pseudo-scientific double-talk (e.g., phrases like:
“might be,” “could mean,” “possibly,” “perhaps,” etc.)*
* “May, might, could, and possibly are not scientific conclusions.” Dr. Fred
Oerther, M.D., September
1986.
The Facts:
Government’s Own Experts Say That Metabolites Are Non-Toxic, Harmless Residue.
We interviewed three doctors of national reputation either currently working (or having
worked) for the U.S. government on marijuana research:
-Dr. Thomas Ungerlieder, M.D., UCLA, appointed by Richard Nixon in 1969 to the
President’s Select Committee on Marijuana, re-appointed by Ford, Carter, and Reagan,
and currently head of California’s “Marijuana Medical Program;”
- Dr. Donald Tashkin, UCLA, M.D., for the last 29 years the U.S. government’s and the
world’s leading marijuana researcher on pulmonary functions; and
-Dr. Tod Mikuriya, M.D., former national administrator and grant distributor of the U.S.
government’s marijuana research programs in the late 1960s.
In effect these doctors said that the active ingredients in THC are used-up in the first or
second pass through the liver. The leftover THC metabolites then attach themselves,
in a very normal way, to fatty deposits, for the body to dispose of later, which is a safe
and perfectly natural process.
Many chemicals from foods, herbs, and medicines do this same thing all the time in
your body. Most are not dangerous and THC metabolites show less toxic* potential than
virtually any known metabolic leftovers in your body!
* The U.S. government has also known since 1946 that the oral dose of cannabis
required to kill a mouse is about 40,000 times the dose required to produce typical
symptoms of intoxication. (Mikuriya, Tod, Marijuana Medical Papers, 1976; Loewe,
journal of Pharmacological and Experimental Therapeutics, October, 1946.)
THC metabolites left in the body can be compared to the ash of a cigarette: The inert
ingredient left over after the active cannabinoids have been metabolized by the body.
These inert metabolites are what urinary analysis studies show when taken to discharge
military or factory or athletic personnel for using, or being in the presence of cannabis
within the last 30 days.
Lung Damage Studies
The Hype:
More Harmful Than Tobacco
According to the American Lung Association, cigarettes and tobacco smoking related
diseases kill more than 430,000 Americans every year. Fifty million Americans smoke,
and 3,000 teens start each day. The Berkeley carcinogenic tar studies of the late 1970s
concluded that “marijuana is one-and-a-half times more carcinogenic than tobacco.”
The Fact:
Not One Documented Case of Cancer
There are lung irritants involved in any smoke. Cannabis smoke causes mild irritation to
the large airways of the lungs. Symptoms disappear when smoking is discontinued.
However, unlike tobacco smoke, cannabis smoke does not cause any changes in the
small airways, the area where tobacco smoke causes long term and permanent damage.
Additionally, a tobacco smoker will smoke 20 to 60 cigarettes a day, while a heavy
marijuana smoker may smoke five to seven joints a day, even less when potent high-
quality flower tops are available.
While tens of millions of Americans smoke pot regularly, cannabis has never caused a
known case of lung cancer as of December 1997, according to America’s foremost lung
expert, Dr. Donald Tashkin of UCLA. He considers the biggest health risk to the lungs
would be a person smoking 16 or more “large” spliffs a day of leaf/bud because of the
hypoxia of too much smoke and not enough oxygen.
Tashkin feels there is no danger for anyone to worry about potentiating emphysema “in
any way” by the use of marijuana totally the opposite of tobacco.
Cannabis is a complex, highly evolved plant. There are some 400 compounds in its
smoke. Of these, 60 are presently known to have therapeutic value.
Cannabis may also be eaten, entirely avoiding the irritating effects of smoke. However,
four times more of the active ingredients of smoked cannabis are absorbed by the human
body than when the same amount is eaten. And the prohibition inflated price of black
market cannabis, combined with harsh penalties for cultivation, prevent most persons
from being able to afford the luxury of a less efficient, though healthier, means of
ingestion. Lab Studies Fail to Reflect the Real World
Studies have proven that many of the carcinogens in cannabis can be removed by using
a water pipe system. Our government omitted this information and its significance
when speaking to the press. At the same time politicians outlawed the sale of water
pipes, labeling them “drug paraphernalia.”
How Rumors Get Started
In 1976, Dr. Tashkin, M.D., UCLA, sent a written report to Dr. Gabriel Nahas at the
Rheims, France, Conference on “Potential Cannabis Medical Dangers.” That report
became the most sensationalized story to come out of this negative world conference
on cannabis. This surprised Tashkin, who had sent the report to the Rheims conference
as an afterthought.
What Tashkin reported to the Rheims conference was that only one of the 29 pulmonary
areas of the human lung studied the large air passageway Did he find marijuana to be
more of an irritant (by 15 times) than tobacco. This figure is insignificant, however,
since Tashkin also notes that tobacco has almost no effect on this area. Therefore,
15 times almost nothing is still almost nothing. in any event, cannabis has a positive
or neutral effect in most other areas of the lung. (See Chapter 7, “Therapeutic Uses of
Cannabis.”)
(Tashkin, Dr. Donald, UCLA studies, 1969-83; UCLA Pulmonary Studies, 1969-95.)
Afterwards in 1977, the U.S. government resumed funding for ongoing cannabis
pulmonary studies which it had cut two years earlier when Tashkin reported
encouraging therapeutic results with marijuana/lung studies. But now the government
limited funding only to research to the large air passageway.
We have interviewed Dr. Tashkin dozens of times. In 1986 I asked him about an
article he was preparing for the New England Journal of Medicine, indicating that
cannabis smoke caused as many or more pre-cancerous lesions as tobacco in “equal”
amounts.
Most people do not realize, nor are the media told, that any tissue abnormality
(abrasion, eruption, or even redness) is called a pre-cancerous lesion. Unlike lesions
caused by tobacco, the THC-related lesions contain no radioactivity.
We asked Tashkin how many persons had gone on to get lung cancer in these or any
other studies of long-term cannabis-only smokers (Rastas, Coptics, etc.)
Sitting in his UCLA laboratory, Dr. Tashkin looked at me and said, “That’s the strange
part. So far no one we’ve studied has gone on to get lung cancer.”
“Was this reported to the press?”
“Well, it’s in the article,” Dr. Tashkin said. “But no one in the press even asked. They
just assumed the worst.” His answer to us was still that not one single case of lung
cancer in someone who only smoked cannabis, has ever been reported. It should be
remembered that he and other doctors had predicted 20 years ago, their certainty that
hundreds of thousands of marijuana smokers would by now (1997) have developed
lung cancer.
Another Fact:
Emphysema Suffers Benefit
During a later interview, Tashkin congratulated me on the tip I’d given him that
marijuana used for emphysema produced good results among persons we knew.
He laughed at me originally, because he had presumed that marijuana aggravated
emphysema, but after reviewing his evidence found that, except in the rarest of cases,
marijuana was actually of great benefit to emphysema suffers due to the opening and
dilation of the bronchial passages.
And so the relief reported to us by cannabis smoking emphysema patients was confirmed.
Marijuana smoke is not unique in its benefits to the lungs. Yerba Santa, Colt’s foot,
Horehound, and other herbs have traditionally been smoked to help the lungs.
Tobacco and its associated dangers have so prejudiced persons against “smoking” that
most persons believe cannabis smoking to be as or more dangerous than tobacco. With
research banned, these public health and safety facts are not readily available.
In December 1997, we asked Dr. Tashkin again, and he unequivocably stated that
“marijuana does not cause or potentiate emphysema in any way.” In addition, there has
not been one case of lung cancer ever attributed to smoking cannabis.
. . .And So On
Most of the anti-marijuana literature we have examined does not cite as much as one
single source for us to review. Others only refer to DEA or NIDA. The few studies we
have been able to track down usually end up being anecdotal case histories, artificial
groupings of data, or otherwise lacking controls and never replicated.
Reports of breast enlargement, obesity, addiction, and the like all remain unsubstantiated,
and are given little credence by the scientific community. Other reports, like the
temporary reduction in sperm count, are statistically insignificant to the general public,
yet get blown far out of proportion when presented by the media. Still others, like the
handful of throat tumors in the Sacramento area and the high rate of injuries reported
in a Baltimore trauma unit are isolated clusters that run contrary to all other statistics
and have never been replicated.
The spurious results of Heath, Nahas, and the pregnant mice and monkey studies at
Temple University and UC Davis (where they injected mice with synthetic third-cousin
analogues of THC) are now discredited in the body of scientific and medical literature.
Though these studies are not used in scientific discourse, mountains of DEA and
pharmaceutical company-sponsored literature about the long-term possible effects
of these metabolites on the brain and reproduction still goes to parent groups as if they
were brand new studies. This disinformation is still very much alive in U.S. government,
DEA, DARE, and PDFA reports.
(Read the 1982 N.I.H.; the National Academy of Science’s evaluation on past studies;
and the Costa Rica report, 1980.)
No Harm to Human Brain or Intelligence Hemp has been used in virtually all societies
since time immemorial as a work motivator and to highlight and renew creative energies.
Brand new studies. This disinformation is still very much alive in U.S. government,
DEA, DARE, and PDFA reports.
(Read the 1982 N.I.H.; the National Academy of Science’s evaluation on past
studies; and the Costa Rica report, 1980.) No Harm to Human Brain or Intelligence
Hemp has been used in virtually all societies since time immemorial as a work motivator
and to highlight and renew creative energies.
Nahas’ Prescription for Bloated Police Budgets
Incredibly, a famous study which found that cannabis reduces tumors (see Chapter 7),
was originally ordered by the Federal Government on the premise that pot would
hurt the immune system. This was based on the “Reefer Madness” studies done by the
disreputable Dr. Gabriel Nahas of Columbia University in 1972.
This is the same Dr. Nahas who claimed his studies showed pot created chromosome,
testosterone (male hormone) damage, and countless other horrible effects which
suggested the breaking down of the immune system. Nahas’ background is in the
OSS/CIA and later the U.S. where he worked closely with Lyndon LaRouche and
Kurt Waldheim.
In 1998, Nahas is still the darling favorite of the DEA and NIDA (National Institute on
Drug Abuse) yet no anti-marijuana studies of Nahas’ have every been replicated in
countless other research attempts. Columbia University specifically disassociated itself
from Nahas’ marijuana research in a specially called press conference in 1975!
Old, discredited Nahas studies are still trotted out by the Drug Enforcement
Administration today and deliberately given to unknowledgeable parents’ groups,
churches, and PTAs as valid research regarding the evils of pot.
The dissemination of Nahas’* dangerous horror stories is paid for with your tax dollars,
even years after the National Institutes of Health (NIH) in 1976 specifically forbade
Nahas from getting another penny of U.S. government money for cannabis studies
because of his embarrassing research in the early 1970s.
* Nahas, in December 1983, under ridicule from his peers and a funding cut-off from
NIDA renounced all his old THC metabolite build-up and unique chromosome Petri dish
tissue damage studies, conclusions, and extrapolations
Yet the DEA, NIDA, VISTA, the “War on Drugs,” and now-deceased writer Peggy
Mann (in Reader’s Digest articles and her book Marijuana Alert, with foreword by
Nancy Reagan) have used these discredited studies on parents’ groups such as Parents
for a Drug Free Youth, etc., often with Nahas as a highly paid guest lecturer, without
a word of how his studies are really considered by this peers.
This, we assume, is done to scare parents, teachers, legislators and judges, using scientific
terminology and bogus non-clinical statistics, ultimately aimed at selling more
urine-testing equipment. Therefore, more profits are created for the drug-rehabilitation
clinics and their staffs of professionals; and to maintain funding for the DEA, local police,
judicial, penal, corrections and other government pork barrel, police state interests.
The “War on Drugs” is big money, so the shameless petitioning for more police and more
jail cells continues. And we still have thousands of judges, legislators, police, Reader’s
Digest readers, and parents who have for years used and cited Nahas’ studies in particular
as the prime reasons to continue these unjust laws and to jail millions of Americans over
the last decade.
The DEA, after Nahas’ 1983 waffling renouncement, consciously and criminally
continues to use his studies to polarize ignorant judges, politicians, press, and parent
groups, who are unaware of Nahas’ denouncement. These groups trust the government
to tell them the truth their tax dollars paid for. Most of the media, press, and television
commentators still use Nahas’ 1970s, unreplicated studies as gospel, and much of the
frightening folklore and street myths that are whispered around school yards spring
from the deceitful “scientist’s” work.
Refuted and never replicated results are still taught, while the honest researcher faces
prison if he attempts to test any thoughts about the medical use of cannabis.
In fact, using Nahas’ refuted and unreplicated synthetic THC Petri dish studies on the
immune system, hysterical Families for Drug Free Youth, or “Just Say No” organizations
have gotten the press to say marijuana could cause AIDS – which has no basis whatsoever,
but the press published all this rhetoric creating more Reefer Madness!
Gabriel Nahas, in 1998, is living in Paris and goes around Europe teaching as gospel the
same old lies to less informed Europeans. When asked to debate us (H.E.M.P.) on
cannabis before the world press on June 18, 1993 in Paris, he first enthusiastically
accepted until he found out that we would be speaking on all aspects of the hemp plant
(e.g. paper, fiber, fuel, medicine). Then he declined, even though we met all of his
requirements.
http://www.scribd.com/doc/17717921/The-Emperor-Wears-No-Clothes
Page 137
Former Surgeon General C. Everett Koop said on national television that radioactivity
contained in tobacco leaves is probably responsible for most tobacco-related cancer.
No radioactivity exists in cannabis tars.
Page 138 – 142
Longer Life, Fewer Wrinkles
Most studies (matched populations, past and present) indicate that everything else
being equal an average American pot smoker will live longer than his counterpart
who does no drugs at all; with fewer wrinkles, and generally less stress thereby having
fewer illnesses to upset the immune system, and being a more peaceful neighbor.
(Costa Rican and Jamaican Studies)
Jamaican Studies
(1968-74, 1975)
Definite Benefits For Marijuana Smokers
The most exhaustive study of hemp smoking in its natural setting is probably Ganja in
Jamaica A Medical Anthropological Study of Chronic Marijuana Use by Vera Rubin
and Lambros Comitas (1975; Mouton & Co., The Hague, Paris/Anchor Books, NY).
The Jamaican study, sponsored by the National Institute of Mental Health (NIMH)
Center for Studies of Narcotic and Drug Abuse, was the first project in medical
anthropology to be to be undertaken and is the first intensive, multi-disciplinary study
of marijuana use and users to be published.
From the Jamaican Study introduction: “Despite its illegality, ganja use is pervasive,
and duration and frequency are very high; it is smoked over a longer period in heavier
quantities with greater THC potency than in the U.S. without deleterious social or
psychological consequences. The major difference is that both use and expected
behaviors are culturally conditioned and controlled by well established tradition.”
“No impairment of physiological, sensory and perceptual-motor performance, tests
of concept formation, abstracting ability, and cognitive style and test of memory.
Positive Social Attitudes
The study outlines the positive reinforcement given socially to ganja smokers in
Jamaica, the universal praise for the practice among users, who smoke it as a work
motivator. Subjects described the effects of smoking making them “brainier”, lively,
merry, more responsible and conscious. They reported it was good for meditation
and concentration, and created an general sense of well-being and self-assertiveness.
No Link to Criminal Behavior
Vera Rubin and her colleagues found no relation of cannabis to crime (except
marijuana busts), no impairment of motor skills, and smokers and non-smokers
alike had identical extroversion scores with no difference in work records or
adjustment. Heavy use of ganja was not found to curtail the motivation to work.
From the psychological assessment the smokers seemed to be more open in their
expressions of feeling, somewhat more carefree, and somewhat more distractable.
There was no evidence of organic brain damage or schizophrenia.
No Physiological Deterioration
Marilyn Bowman, in a battery of psychological tests on chronic cannabis users in
Jamaica in 1972, found “no impairment of physiological, sensory and perceptual-motor
performance, tests of concept formation, abstracting ability and cognitive style and
tests of memory.” These Jamaicans had smoked anywhere from six to 31 years
(16.6 mean average) and the average age at the first puff was at 12 years and six
months. In the 1975 study between users and non-users, no difference was found
in plasma testosterone, no difference in total nutrition, slightly higher performance
on the intelligence sub-tests (not statistically significant), and “a basic measure of
cell-mediated immunity was no less vigorous in the users.”
Finally, “Users in our matched pair sample smoked marijuana in addition to as many
tobacco cigarettes as did their partners. Yet their airways were, if anything, a bit
healthier than their matches.”
“We must tentatively conclude either that marijuana has no harmful effects on such
passages or that it actually offers some slight protection against the harmful effects of
tobacco smoke. Only further research will clarify which, if either, is the case.”
No “Stepping Stone”/Gateway Effect
As to the stepping-stone or gateway drug charges leveled against cannabis: “The use of
hard drugs is as yet virtually unknown among working class Jamaicans no one in the
study (Rubin’s) had ever taken any narcotics, stimulants, hallucinogens, barbiturates or
sleeping pills.”
In America during the late 1800s cannabis was used in treating addiction. Opiate,
chloralhydrate, and alcohol addicts were successfully treated with potent cannabis
extracts. Some patients recovered with less than a dozen doses of cannabis
extract.
1 L i k e w i se , smoking cannabis has been found to be valuable in modern
alcohol addiction treatment.
2 Costa Rican Study (1980)
The Jamaican results were largely confirmed by another Carribean study, the 1980
Cannabis in Costa Ricah – A Study in Chronic Marijuana Use edited by William Carter
for the Institute for Study of Human Issues. (ISHI, 3401 Science Center, Philadelphia.)
Again researchers found no palpable damage to the native population’s chronic
cannabis smokers. Alcoholic social problems, so evident on neighboring
cannabis-free islands, are not found in Costa Rica.
This study makes clear that socially approved ganja use will largely replace or mitigate
the use of alcohol (rum) if available.
The Amsterdam Model
Since adopting a policy of tolerance and non-prosecution of cannabis/hashish
smokers (it is available in cafes and bars) and rehabilitation and diversion programs
for hard drug users, Holland has seen a substantial reduction in cannabis
consumption among teenagers2 and a 33% drop in the number of heroin addicts.
The strategy of separating cannabis sales from hard drug dealers by bringing pot
above-ground has been quite successful. (L.A. Times, August 1989). In 1998,
despite constant pressure from the U.S. government and the DEA, the Dutch
government has totally refused to recriminalize marijuana!
Footnotes:
1. “Cannabis Indica as an Anodyne and Hypnotic,” J.B. Mattison, M.D.,
The St. Louis Medical and Surgical Journal, vol. LVI, no. 5, Nov. 1891,
pg 265-271, reprinted in Marijuana: The Medical Papers, Tod Mikuriya, M.D.
2. “Cannabis Substitution: An Adjunctive Therapeutic Tool in the Treatment of
Alcoholism,” Tod H. Mikuriya, M.D., Medical Times, vol. 98, no. 4, April, 1970,
reprinted in Marijuana Medical Papers, Tod Mikuriya, M.D.)
More Prohibitionist Deceptions
Scientific American reported in 1990: “The alarming statistics, cited by testing
advocates, to demonstrate the high costs of drug abuse . . . do not always accurately
reflect the research on which they are based. In fact, some of the data could be
used to ‘prove’ that drug use has negligible or even beneficial effects.” (March 1990,
page 18) One of the examples given is the often cited statistic former president
George Bush utlized in 1989: “Drug abuse among American workers costs businesses
anywhere from $60 billion to $100 billion a year in lost productivity, absenteeism,
drug-related accidents, medical claims and theft.” Yet according to a 1989
assessment by NIDA, all such claims derive from a single study that grew out of
a 1982 survey of 3,700 households.
The Research Triangle Institute (RTI) found that households where at least one
person admitted having used marijuana regularly reported average incomes 28%
lower than average reported income of otherwise similar households. RTI researchers
ascribed the income difference to “loss due to marijuana use.”
RTI then extrapolated costs of crime, health problems and accidents to arrive at
a “cost to society of drug abuse” of $47 billion. The White House “adjusted” for
inflation and population increases to provide the basis for Bush’s statement.
Yet the RTI survey also included questions about current drug use. The answers
revealed no significant difference between income levels of households with current
users of illegal drugs, including cocaine and heroin, and other households.
Thus the same statistics “prove” that current use of hard drugs does not result in
any “loss,” in contrast to a single marijuana binge in the distant past!
Official Corruption: Carlton Turner
In all the research this author has done about the misapplication of public funds and
trusts, nothing, it seems, compares with the either totally ignorant or willful
manslaughter of fellow Americans by the bureaucrats and politicians of the
following story:
One Man & His Drug Scams
The U.S. government policy, starting in the Nixon and Ford administrations and
continuing under Carlton Turner* (Drug Czar under Reagan 1981-1986), allowed
federal medical marijuana, supplied to the individual state marijuana medical
programs, to consist only of the leaf of the marijuana plant, even though it’s usually
only one-third as strong as the bud and doesn’t contain the same whole spectrum of
the “crude drug,” i.e. the THC and CBNs.
* Prior to becoming Special White House Advisor (read: National Drug Czar)
Carlton Turner, from 1971 to 1980, was the head of all U.S. government marijuana
grown for drugs by reason of his position at the University of Mississippi. The U. of
Mississippi Marijuana Research Program is directed by state charter to discover
initiate or sort out the constituents of Thc a “simple” crude cannabis drug that works
as a medicine then synthesize the substances with beneficial medicinal properties to
attain their full potential for pharmaceutical companies.
For example, the leaf’s relief of ocular pressure for glaucoma patients is much
shorter lasting and therefore unsatisfactory, compared to the bud. Also, the leaf
sometimes gives smokers a headache. The federal government until 1986 used only
the leaf. Turner said to the pharmaceutical companies and in interview, that leaf is
all Americans would ever get although the bud works better. Still today in 1999,
the seven legal marijuana users in the U.S. only get leaf, branch, and bud chopped
up and rolled together. Although buds work better for chemotherapy, glaucoma,
etc., the branches can be as toxic as smoking wood.
The Reasons Given:
- Buds are too hard to roll through a cigarette machine. (Forget the 25 million
Americans who do quite well at rolling bud everyday.)
- By extracting compounds from the “crude drug” of the bud, there would be no
pharmaceutical patents, therefore no profits. Therefore, his program would have
worked against his former employers, the Mississippi University’s legislative charter
and funding.
(Interviews by Ed Rosenthal for High Times Magazine; Dean Latimer, et al;
National Organization for the Reform of Marijuana Laws, or NORML.)
Although buds work better for chemotherapy, glaucoma, etc., Turner said they
will “never” be given. It also became evident the famous marijuana ‘munchies’
(appetite stimulation) were not working for the cancer chemotherapy patients
using federal leaf.
And even though no studies have been allowed to compare leaf with bud, we know
of doctors who unofficially recommended bud and watch their wasting cancer
patients put on weight (NORML).
http://www.scribd.com/doc/17717921/The-Emperor-Wears-No-Clothes
After the 1938-1944 New York City “LaGuardia Marijuana Report” refuted his
argument, by reporting that marijuana caused no violence at all and citing other
positive results, Harry J. Anslinger, in public tirade after tirade, denounced
Mayor Fiorello, LaGuardia, the New York Academy of Medicine and the doctors
who researched the report.
To refute the LaGuardia report, the AMA, at Anslinger’s personal request,
conducted a 1944-45 study showing that 34 “Negro” GI’s and one white GI
(for statistical control) who smoked marijuana, became disrespectful of white soldiers
and officers in the segregated military. (See Appendix, “Army Study of Marijuana,”
Newsweek, Jan 15, 1945.)
Throughout man’s history hemp has always been known as the most medicinal
plant in the world. Even with this knowledge hemp has always been used as a
political and religious football.
Jack Herer believed as I do that the key to hemp´s complete legalisation is
in the magnificent medicine this plant can produce. Once the public becomes
aware of the fact that properly made hemp medicine can cure or control practically
any medical condition, who is going to stand against the use of hemp.
We are at the dawn of new age in medicine and a new day for mankind. Not only
can hemp save the world, it can eliminate a great deal of human suffering and can
even put an end to starvation. What are we waiting for? Join with me and let us put
an end to this madness. It can only survive if we continue to sit on our backsides
and do nothing. Stand up and be counted and let us give ourselves a chance to heal.
- Rick Simpson
MARIAJUANA SMOKING IN PANAMA
Taken from: The Military Surgeon Volume 73 – July-December 1933
http://www.druglibrary.org/schaffer/library/studies/panama/panama1.htm
UNITED STATES DEPARTMENT OF JUSTICE
Drug Enforcement Administration
In The Matter Of
MARIJUANA RESCHEDULING PETITION
Docket No. 86-22
OPINION AND RECOMMENDED RULING, FINDINGS OF
FACT, CONCLUSIONS OF LAW AND DECISION OF
ADMINISTRATIVE LAW JUDGE
FRANCIS L. YOUNG, Administrative Law Judge
DATED: SEPTEMBER 6, 1988
The entire court document can be found here
http://www.druglibrary.org/schaffer/library/studies/YOUNG/index.html
The judge’s conclusion and recommended decision was as follows :
CONCLUSION
AND
RECOMMENDED DECISION
Based upon the foregoing facts and reasoning, the administrative law
judge concludes that the provisions of the Act permit and require the
transfer of marijuana from Schedule I to Schedule II. The Judge realizes
that strong emotions are aroused on both sides of any discussion
concerning the use of marijuana. Nonetheless it is essential for this
Agency, and its Administrator, calmly and dispassionately to review the
evidence of record, correctly apply the law, and act accordingly.
Marijuana can be harmful. Marijuana is abused. But the same is
true of dozens of drugs or substances which are listed in Schedule II so
that they can be employed in treatment by physicians in proper cases,
despite their abuse potential.
Transferring marijuana from Schedule I to Schedule II will not, of
course, make it immediately available in pharmacies throughout the
country for legitimate use in treatment. Other government authorities,
Federal and State, will doubtless have to act before that might occur.
But this Agency is not charged with responsibility, or given authority,
over the myriad other regulatory decisions that may be required before
marijuana can actually be legally available. This Agency is charged
merely with determining the placement of marijuana pursuant to the
provisions of the Act. Under our system of laws the responsibilities of
other regulatory bodies are the concerns of those bodies, not of this
Agency,
There are those who, in all sincerity, argue that the transfer of
marijuana
- 67 -
to Schedule II will “send a signal” that marijuana is “OK” generally for
recreational use. This argument is specious. It presents no valid
reason for refraining from taking an action required by law in light of
the evidence. If marijuana should be placed in Schedule II, in obedience
to the law, then that is where marijuana should be placed, regardless of
misinterpretation of the placement by some. The reasons for the
placement can, and should, be clearly explained at the time the action is
taken. The fear of sending such a signal cannot be permitted to override
the legitimate need, amply demonstrated in this record, of countless
suffers for the relief marijuana can provide when prescribed by a
physician in a legitimate case.
The evidence in this record clearly shows that marijuana has been
accepted as capable of relieving the distress of great numbers of very
ill people, and doing so with safety under medical supervision. It would
be unreasonable, arbitrary and capricious for DEA to continue to stand
between those sufferers and the benefits of this substance in light of
the evidence in this record.
The administrative law judge recommends that the Administrator
conclude that the marijuana plant considered as a whole has a currently
accepted medical use in treatment in the United States, that there is no
lack of accepted safety for use of it under medical supervision and that
it may lawfully be transferred from Schedule I to Schedule II. The judge
recommends that the Administrator transfer marijuana from Schedule I to
Schedule II.
Dated: SEP 6 1988
Francis L. Young
Administrative Law Judge
- 68 -
CERTIFICATE OF SERVICE
This is to certify that the undersigned on SEP 6 1988, caused a copy
of the foregoing to be delivered to
Madeleine R. Shirley, Esq.
Office of Chief Counsel
Drug Enforcement Administration
1405 I Street, N.W.
Washington, D.C. 20537
and caused a copy to be mailed, postage paid, to each of the following:
National Organization for the Carl Eric Olsen
Reform of Marijuana Laws Post Office Box 5034
Attn: Kevin B. Zeese, Esq. Des Moines, Iowa 50306
Zwerling, Mark, Ginsberg and Lieberman, P.C.
1001 Duke Street Cannabis Corporation of
Alexandria, Virginia 22313 America
Attn: Laurence O. McKinney
National Federation of Parents President
for Drug-Free Youth c/o McKinney & Company
Attn: Karl Bernstein 881 Massachusetts Avenue
Vice President Cambridge, Massachusetts 02139
8730 Georgia Avenue
Suite 200 International Association of
Silver Spring, Maryland 20910 Chiefs of Police
Attn: Virginia Peltier, Esq.
Alliance for Cannabis Therapeutics Assistant Legal Counsel
c/o Frank B. Stillwell, III, Esq. 13 Firstfield Road
Steptoe & Johnson P.O. Box 6010
Attorneys at Law Gaithersburg, Maryland 20878
1330 Connecticut Avenue, N.W.
Washington, D.C. 20036
David C. Beck, Esq.
McDermott, Will & Emery
1850 K Street, N.W.
Washington, D.C. 20006
Attorney for Cannabis Corporation
of America
Dianne L. Martin
Hearing Clerk
Additional reports and readings for consideration :
The Report of the National Commission on Marihuana and Drug Abuse
Marihuana: A Signal of Misunderstanding
Commissioned by President Richard M. Nixon, March, 1972
led by then-Gov. Raymond Shafer of Pennsylvania
Also known as the Schafer Commission Report
http://www.druglibrary.org/schaffer/library/studies/nc/ncmenu.htm
The History of Medical Cannabis – (from it’s earliest findings to today)
http://www.cannabismd.net/history-of-medical-cannabis/2008/8/4/history-of-medical-cannabis.html
Direct suppression of autoreactive lymphocytes in the central nervous system
via the CB2 receptor
http://www.cannabisscience.com/images/downloads/autoimmune_disease1.pdf
Medical marijuana histories to provide insight into uses for this medicine featured
patient accounts.
http://rxmarijuana.com/shared.htm
Shared comments or observations from individuals regarding the medical value
of marijuana, read the experiences of patient with various health problems.
http://rxmarijuana.com/comments_and_observations.htm
Rick Simpson discovered the cure for cancer his library is located :
http://www.phoenixtears.ca/article/
Suggested viewing :
Run From the Cure
http://www.youtube.com/watch?v=0psJhQHk_GI
“Run From the Cure” Producer, Christian Laurette Calls New York City’s MNN
http://www.youtube.com/watch?v=D9cQZ8DX6nw&feature=related
Sincerely,
Kathy Day
Suffering Celiac – Autoimmune Disease and Rare Disease
Rheumatory Arthritis – Autoimmune Disease
Osteoperosis – Rare Disease and Autoimmune Disease
Hypokalemia – Rare Disease
Peripherial Neuropathy – Rare Disease related/induced (Hypokalemia)
Duendonitis – Autoimmune related/induced (Celiac)
Hiatal Hernia – Autoimmune related/induced (Celiac)
Gerd – Autoimmune related/induce (Celiac)
Persistent Low Grade Fever – Autoimmune and Rare Disease
related/induced
