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I thought this was a neat symbol to represent ourselves in relation to the world as we preceive it to be around us. I bet you thought the study of herb(s) was about Marijuana, it is not the sole study of that particular remedy or herb, but it is a herb. But if you surfed here thinking you'll learn about pot you thought in error and I suggest that you look to why you were interested in that subject as a source for a drug or for medicinal properties. I am in the process of inserting an article debating that very issue next.


CUTTING EDGE Waiting to Inhale Synopsis of the Medical Use of Marijuana Debate by Moderator Richard Musty (Posted May 15, 1998 Issue 30) Should marijuana be used medically? This simple question provokes impassioned responses, with the incomplete scientific evidence often taking a back seat to moral admonitions, angry assertions for the right to free choice, and desperate pleas from patients in many countries. In a debate held March 8-13, 1998, experts were asked to discuss both scientific and policy issues. The group included basic scientists (Nancy Buckley, MacDonald Christie, Roger Pertwee, and me), clinicians (Tod Mikuriya and Eric Voth), and a cannabis buyers club director, patient advocate, and patient himself (Scott Imler). This debate is unusual, because basic scientists often avoid policy discussions, and clinicians and/or medical marijuana service providers infrequently discuss their issues with scientists (and even less frequently speak directly with Medical Marijuana Users, in the clinicians' case). As moderator, I posed questions starting with the basic science that addresses the medicinal value of smoked marijuana and moving on to the immediate and future needs of clinicians and their patients. Historical Background Cannabis sativa has a long medicinal history dating back as far as 4,000 years. Its legal trajectory has varied in different countries, but I will review its history in the United States as an example of how it came to be defined as a drug of abuse. This started in the United States only after a former Prohibition bureaucrat, Harry J. Anslinger, became the first Commissioner of Narcotics in the newly created Federal Bureau of Narcotics. His National Conference on Uniform Drug Laws in 1933 did not ban marijuana, but states were encouraged to do so (Brecher et al., 1972), especially once Anslinger wrote popular magazine articles describing Southwestern Hispanics going on crime sprees under the influence of marijuana (McWilliams, 1990). Anslinger's Marijuana Tax Act of 1937 taxed marijuana prescribers $1 per year, druggists $15 and growers $25. By about 1937, state penalties for marijuana were about the same as those for heroin. New York Mayor Fiorello LaGuardia's 1944 report found little evidence of serious health problems among marijuana users (Mayor's Committee on Marihuana, 1944). Between 1937 and the early 1960s, marijuana was illegal, but little attention was given to its use or abuse, and little research was conducted. Raphael Mechoulam isolated and synthesized the principal psychoactive ingredient of marijuana, delta-9-tetrahydrocannabinol (THC), in 1964 after he received an unsolicited award from the U.S. Public Health Service (USPHS). Part of the contract required delivery of THC to the USPHS. According to Mechoulam, the drug sat on the shelves of USPHS for several years (R. Mechoulam, personal communication). The Uniform Drug Control Act, which was passed by Congress in 1970, placed marijuana (and chemical derivatives) on Schedule I, meaning that it had a high potential for abuse and no accepted medical use. Other examples of Schedule I drugs include LSD, heroin and Methamphetamine. In 1972, President Richard Nixon's National Commission on Marijuana and Drug Abuse issued a report recommending that possession for personal use or casual distribution in small quantities should not be a federal or state offense (National Commission on Marijuana and Drug Abuse, 1972). Research on the medicinal applications of marijuana was also recommended. After this report, basic research was stimulated, which led to a special symposium held by the National Institute on Drug Abuse in 1975 (Braude et al., 1976). During the 1970s, several states followed the recommendations of the commission; for example, Ann Arbor, Michigan, made simple possession a misdemeanor. Public use in the city was treated like a traffic ticket. Clinical evidence led to studies of marijuana's ability to reduce interocular pressure in glaucoma patients (Hepler et al., 1971). Patients who smoked marijuana also reported relief of nausea and vomiting after cancer chemotherapy, and many states passed laws to allow the medical use of marijuana. Between 1980 and 1986, at least seven states conducted research on the efficacy of marijuana in the treatment of nausea and vomiting following chemotherapy. In some of these studies, comparisons were made with the THC pill, dronabinol (Musty et al., 1997b). A 1982 report on marijuana by the Institute of Medicine, part of the National Academy of Sciences, recommended that marijuana possession be decriminalized, and medical research be continued. It also suggested that lawmakers give serious consideration to creating a system of regulated distribution and sale (Marijuana and Health [Washington: National Academy Press, 1982). Based on the state studies, the orally ingested capsule form of THC, dronabinol (trade name Marinol), was approved by the U.S. Food and Drug Administration for use as an antiemetic for chemotherapy patients in 1985 and as an appetite stimulant for AIDS patients in 1992 (Plasse et al., 1995; Musty et al., 1995). Although dronabinol is readily available, it is on Schedule II. Physicians are reluctant to administer Schedule II drugs (examples include morphine, cocaine, barbiturates and amphetamine). A synthetic cannabinoid called Nabilone was never marketed in the United States because it was placed on Schedule II (Lemberger, 1998). Many people who try dronabinol find that it makes them feel ill or that they cannot keep the pill down; these folks often revert to the use of marijuana. The Institute of Medicine now has funding to hold a series of information-gathering meetings on the medicinal value of marijuana (still a Schedule I substance), and The National Academy of Sciences is charged with assessing the science. But, as succinctly stated by Eric Voth during our debate, "One of the major issues surrounding the 'medical marijuana' debate is not so much whether individuals obtained some perceived benefit but rather, What is medicine? How do we hold a smoked herbal substance to standards of not only efficacy but also safety? And are there effective medicines that at least equal if not exceed the needs of patients?" (Day 1, #3). The Debate We discussed the following questions: What does the scientific evidence lead us to conclude about the medical use of marijuana (Day 1)? What research should be funded to increase the chances of developing cannabinoid drugs to help those who use marijuana (Day 2)? In the meantime, should marijuana be made available to people suffering from cachexia, nausea, glaucoma, chronic pain, and spasticity if conventional medications are ineffective or intolerable (Day 3)? What should be done about the fact that many people who use marijuana for medicinal purposes have been given long prison sentences (Day 4)? Finally, Day 5 was left open for participants to talk about any issues that remained. Day 1: Scientific Evidence About Medical Use of Marijuana There was disagreement about the state of knowledge concerning the efficacy of smoked marijuana as a therapeutic agent. I described unpublished studies from several states that showed either that smoked marijuana could help patients where dronabinol could not, or that patients given a choice overwhelmingly chose smoked marijuana over dronabinol (Day 1, #1). Pertwee said that there is little objective evidence for the efficacy of plant material, or on the question of whether it is preferable to synthetic cannabinnoids, but good evidence for the usefulness of synthetic cannabinoids (and therefore, most likely, of the plant; Day 1, #2). The studies are small but support the initiation of much larger trials. Voth asserted that the state studies of marijuana were poorly designed, uncontrolled, and lacked direct comparisons with dronabinol and the new anti-emetics (selective serotonin antagonists; Day 1, #3). He urged the testing of pure cannabinoids and their analogs. I disagree with Voth's claim. Some of the studies included comparisons to dronabinol. And in the other studies, patients smoked marijuana only after other anti-emetics failed, and the marijuana was 70% to 100% effective. Comparisons with new anti-emetic drugs have not been done because these drugs are so new. The range of effectiveness for the new anti-emetics is from 70% to 100% (Musty, 1997b), almost identical to that for smoked marijuana. Gralla claims that the newer anti-emetics (eg, granisetron and ondansetron) can be 100% effective, but in published double-blind studies efficacy ranges from 38% to 100% (Ritter et al., 1998) and seems to average about 80% (Farley et al., 1997). Granisetron is not effective in alleviating delayed emesis (Latreille et al., 1998), although marijuana is (Musty, unpublished data). Christie (Day 1, #4) and I (Day 1, #10) presented evidence that inhalation was the best way to titrate THC; this was contested by Voth. Christie and others did agree that smoking was not the most desirable drug delivery system in the long run, and that alternative inhalation-based delivery methods should be pursued. Mikuriya (Day 1, #13) and I (Day 1, #7) urged participants not to ignore usage data from before the start of criminalization in 1937. Mikuriya also pointed out that fear of prosecution and complicated approval processes discourage further research. Day 2: Future Research on Cannabinoids: What's Needed? On the issue of research there was almost a consensus: more research should be done. Beyond this level of agreement, however, are very divergent views. Both Imler (Day 2, #4) and Mikuriya (Day 5, #2) think there is enough evidence to allow patients to use marijuana for medical purposes without further research, although they do not oppose further research. I think that smoking studies should be conducted because many patients will continue to use this form of administration despite marijuana laws.Voth was the only participant who opposed smoking studies, because of uncertain chemical content and a lack of safety studies (Day 2, #3). A recent report by the National Institutes of Health (NIH) recommended that further studies should be carried out (Day 3, #5), but the NIH never articulated a policy position on this report, nor did they allocate specific funds for these studies. One clinical trial with smoked marijuana in patients with weight loss due to HIV is underway: a three-arm study with smoked marijuana, dronabinol, and dronabinol placebo. This is the only study sponsored by the National Institute on Drug Abuse (NIDA) at present. Abrams reported that NIDA is funding the project only because they are investigating the possibility that these patients may show compromised immune function during marijuana or THC use. Buckley (Day 2, #7), Christie (Day 2, #8), and Pertwee (Day 5, #1) think that work aimed at developing specific synthetic cannabinoid-like drugs should be accelerated, although Christie emphasized that this is a long-term goal that may not even be attainable if the desired and undesired effects of the drug arise from stimulation of the same receptor subtype. THC and cannabinoids are lipophilic. This means that absorption by oral administration is problematic, and it explains the preference for smoking often reported by patients and researchers (Day 1, #6). Voth argued, however, that smokable marijuana might not pass FDA standards for safety if approval for prescription were sought (Day 1, #8), and I challenged this (Day 1,#10). Debate over the absorption of THC via the smoke route was heated, but all the participants agreed that an inhalation route would be ideal for cannabinoids. Other possibilities were also discussed, such as a nasal inhaler, transdermal patch, or suppository (Day 2, #3). Buckley said that, since the discovery of cannabinoid receptors in the brain and the periphery as well as at least two endogenous ligands (Musty et al., 1995), there has been a need for basic research to test many of the novel compounds known to bind to these receptors(Day 2, #7). Pertwee also posed several specific questions for future research (Day 2, #2; Day 2, #6). Are the different effects of smoked marijuana and pure cannabinnoids a result of the route of administration or differing chemical content? Does tolerance to the psychotropic effects arise more readily than tolerance to analgesic effects? Can new delivery methods overcome problems with inter-patient variability and a narrow therapeutic window seen with oral dronabinol? And from Buckley (Day 3, #5): What exactly are the detrimental effects of marijuana and cannabinnoids? Another important area for research may come from the observation that different types of marijuana seem to have differing clinical effects. Mikuriya expressed some frustration at not being able to test samples that patients use because labs are afraid the DEA will come after them (Day 1, #13). Buckley (Day 5, #4) described a related vicious cycle: Restricted access to a Schedule I drug (marijuana) discourages research, meaning there is little data to support moving the drug to Schedule II. Day 3: The Whys and Why Nots of Making Marijuana Available for Medical Uses There was general agreement that new drugs and delivery mechanisms would help divorce the debate from drug prohibition/decriminalization politics. But, until that happens, Buckley (Day 3, #5), Christie (Day 3, #7), Imler (Day 3, #6), Mikuriya (Day 3, #8), and I all agree that marijuana should be made available to patients. Pertwee is silent on this issue, and Voth is opposed. Voth suggested that an independent panel evaluate scientific claims, paying special attention to whether patients really had tried all other available medications (Day 3, #1). We did not discuss how cannabis should be made available, but there are several possibilities. California, Arizona, and 35 other states have laws on the books that allow for patients to have some form of access to cannabis, according to the Marijuana Policy Project. Representative Barney Frank and 13 cosigners sponsored a bill in Congress this year that would make cannabis a Schedule II drug. I think that it would also be possible to reinstate the Compassionate Investigational New Drug program. Finally, cannabis possession by adults could be decriminalized. In a poll conducted for the Lindesmith Center in 1997, 65% of Americans said that cannabis should be available for medical use. In the Netherlands, individuals can possess 5 grams of cannabis for any purpose, so patient access is not an issue. A recent study by the Centre for Drug Research at the University of Amsterdam shows that cannabis use is much lower in the Netherlands than in the U.S. Day 4: Harm Reduction: An Approach Imler (Day 4, #3), Mikuriya (Day 4, #4), and I (Day 4, #2) believe that patients who use cannabis should not be imprisoned. Voth and his organization Drug Watch International, on the other hand, support strict enforcement of marijuana laws. I argued for a harm-reduction approach, setting up laws much like those in California to allow patients and doctors unfettered access. Voth argued against this, claiming that a 'hands off' attitude leading to self-medication is ethically irresponsible (Day 4, #1). He described harm reduction as "a euphemistic name given to pass along the social stances of decriminalization, legalization, personal use, etc." and cited the Drug Watch International site. This was followed by my analysis of the Drug Watch statement of principles (Day 4, #2). Imler, Mikuriya and I stated that moralism should be replaced by the medical imperative, and emphasized the harm caused to innocent patients who are desperately trying to medicate symptoms. Mikuriya argued against prohibition (Day 4, #4) and spoke about the fight over California's medical marijuana law (Day 5, #5). Noam Chomsky recently commented in detail on this issue (Veit, 1998). None of us argued against efforts to educate and prevent drug misuse. Perhaps the common ground can be found by allowing medical use of marijuana and emphasizing health promotion to reduce abuse; after all, these are separate issues. Read on. You will find the debate interesting and challenging. We welcome your comments and reactions. Andrzej Krauze is an illustrator, poster maker, cartoonist, and painter who illustrates regularly for HMS Beagle, The Guardian, The Sunday Telegraph, Bookseller, and New Statesman. Endlinks Information on Marijuana The Marihuana Tax Act Of 1937 - includes the full text of this ban on medical and recreational use of marijuana and an introduction describing its impact. An extensive collection of information about pre-1937 marijuana use in the United States, is available from The Fitz Hugh Ludlow Hypertext Library. The Marijuana Policy Project - an organization concerned solely with lobbying to reform the marijuana laws on the federal level, this site provides news releases on medicinal marijuana stories, legislative updates, and information about the MPP's current projects. The Schaffer Library of Drug Policy - is a comprehensive website covering most aspects of marijuana and other drug use in the US. Of particular note is Medical Marijuana - Master Reference. The Lindesmith Center - a drug policy research institute that focuses on the issues of drug policy from an economic, criminal justice, and public health perspective. This comprehensive website has an extensive online library. Crude Marijuana for Medical Purposes - presents information and opinions from a different bias about the dangers of marijuana use for medical purposes. From the International Drug Strategy Institute site, which promotes drug policies that will reduce drug use. Commentary: Marihuana as Medicine - A Plea for Reconsideration - from the 21 June 1995 issue of JAMA, by Lester Grinspoon, MD and James B. Bakalar, JD of the Department of Psychiatry, Harvard Medical School, and the Massachusetts Mental Health Center, Boston. Medical Cannabis - a resource from UK Cannabis Information. For a sociopolitical history of cannabis and the British Empire 1840-1928, see Indian Hemp and the Dope Fiends of Old England. DrugText Reports - is a collection of historical documents related to drugs and drug policies from various governments. DrugText is an information service provided by the International Foundation for Drug Policy and Human Rights. Medical Marijuana: Logical Couplet or Oxymoron? - a series of opinions, both pro and con, for the legalization of marijuana for medical use from the clinicians viewpoint. As a part of Medscape's Journal Club Forum, you can submit your own comments on this topic. Free registration is required for access. Cannabis as Medicine: Time for the Phoenix to Rise? - commentary from the 4 April 1998 issue of the British Medical Journal summarizing recent studies into the benefits and health risks of medical marijuana. Research on Marijuana Medical Use of Marijuana: Assessment of the Science Base - an ongoing 18-month study from the Institute of Medicine at the National Academy of Sciences to determine the benefits and risks of therapeutic uses of marijuana. Health Care Use By Frequent Marijuana Users Who Do Not Smoke Tobacco - Details of a study comparing the health of self-reporting frequent marijuana users with non-smokers. From Frontline Online. The Pharmacology & Biochemistry of Cannabinoid Receptors - gives a brief overview of cannabinoid receptors. International Cannabinoid Research Society - provides membership information and registration details for the 1998 meeting. Research Must Determine Medical Potential of Marijuana, NIH Expert Panel Concludes - a summary of the NIH's report that calls for more research into the potential clinical benefits of marijuana. The full text of the 37 page report, which was issued in August of 1997 is available from the Workshop on the Medical Utility of Marijuana. For some background information about the workshop, see For Medicinal Purposes: Expert Group Examines Science Of Smoking Marijuana. Marijuana-Like Drugs May be Effective Painkillers - a summary of recent research into one aspect of the clinical application of marijuana. From the 27 October 1997 issue of DayBreak from UCSF. Cannabinoid Investigations Entering The Mainstream - summarizes recent research advances into the pharmacology and medical uses of cannabinoids. From the 2 February 1998 issue of The Scientist. Tell us what you think. 1998 BioMedNet Ltd. All rights reserved.
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