Pubdate: 01 Nov 1999 Source: International Journal of Drug Policy Copyright: International Journal of Drug Policy, 1999 Contact: http://www.elsevier.com/locate/drugpo Page: Lead article, p358 Author: Peter Webster, The author is the review editor for the International Journal of Drug Policy Related: The report is at http://www.drugsense.org/iom_report/ Commentary Counterblaste to the I.O.M. In mid-March of this year, the report of the U.S. Institute of Medicine (Joy et al., 1999) on the topic of 'medical marijuana' was finally published, having been commissioned by the U.S. Drug Czar and his White House Office of National Drug Control Policy in January 1997. The widespread and growing use of marijuana for medicinal purposes and the passage of legislation in several U.S. states recognising patients' rights to use, and physicians' rights to recommend marijuana had been countered by the Drug Czar's denunciation of medical marijuana as "a cruel hoax," "Cheech and Chong medicine," and a "Trojan horse" for across-the-board legalisation of drugs. A review of the scientific evidence on marijuana by an organisation with irreproachable credentials was thus called for, although at the time - January 1997 - the request to the I.O.M. was widely seen as merely a stalling tactic by an unremittingly prohibitionist federal government pressed to divert attention from the recent successes of the drug policy reform movement. The I.O.M. document, summarising a purportedly scientific and thorough review of all available evidence, left no doubt that marijuana - or at least some of its active ingredients - showed significant promise for certain conditions: "For [some] patients...cannabinoid drugs might offer broad spectrum relief not found in any other single medication." Examined from the point of view of the U.S. federal government's long-standing prohibitionist policies, however, the report's findings were not considered significant enough to justify any change of direction: Even for the terminally ill and severely afflicted who find marijuana of some use or comfort, harassment, arrest, seizure of assets, and imprisonment are still deemed appropriate federal action for 'sending the right message' about the 'great danger to society' posed by the weed, medicinal or not. The stark 'message' that the Feds were sending was unmistakably loud and clear: In 1997 there were three-quarters of a million marijuana arrests in the U.S., 90 percent of them for simple possession. Even larger figures are expected for 1998 and 1999. The I.O.M. study shunned consideration of the larger social questions: "Can marijuana relieve health problems? Is it safe for medical use? Those straightforward questions are embedded in a web of social concerns, most of which lie outside the scope of this report." The I.O.M. report went on to recommend further extensive research on the medical use of cannabis: "Recommendation 1: Research should continue into the physiological effects of synthetic and plant-derived cannabinoids and the natural function of cannabinoids found in the body." Publicly, at least, the U.S. federal government agrees. But marijuana research, according to some top scientists, has been actively thwarted by the U.S. government for decades, and there has been little if any loosening of the stringent requirements for approval of proposed research projects. As an example of recent stonewalling, Rick Doblin of the Multidisciplinary Association for Psychedelic Studies writes, "Obtaining approval for MAPS-sponsored medical marijuana research has ...been difficult. As reported in the last Bulletin, the National Institutes of Health (NIH) rejected for the second time the grant application of Dr. Ethan Russo, U. of Montana, for a study of the use of smoked marijuana in people whose migraines are not successfully treated by currently available medicines. The NIH letter explaining the rationale for its decision arrived well after the news of the rejection of the grant. The NIH reviewers focused in large part on an issue that cannot be resolved and that has nothing to do with the scientific merit of the protocol design, the supposed need for preliminary data to supplement extensive historical and anecdotal reports. It is difficult to imagine that the NIH reviewers didn't realize that it is impossible to obtain permission to conduct preliminary studies, or didn't know that the NIH Expert Committee on the Medical Uses of Marijuana recommended full-scale trials. Despite the Clinton Administration rhetoric in favor of medical marijuana research, the reality is continued obstructionism. In a victory for the opponents of medical marijuana, Dr. Russo has decided that it is futile to reapply to NIH a third time. The Clinton Administration position that the controversy over the medical use of marijuana should be resolved through scientific research rather than at the ballot box will remain dishonest and deceptive until good-faith efforts to conduct research, such as attempted by Dr. Russo and supported by MAPS, are permitted to proceed." (Doblin, 1999) Indeed, while marijuana officially remains a schedule I drug "with high potential for abuse and no accepted medical use" it is difficult to see how any U.S. research agenda could attain the necessary freedom from corrupting political imperatives rooted deep in moralistic and religious convictions. Under such pressure, what little research as has been allowed over the years has been largely directed at supporting prohibitionist policy and prejudice, and there is little sign that the tendency will improve in the near-term, the I.O.M. recommendation notwithstanding. The lack of adequate research uncontaminated by ideology, especially with regard to understanding the illegal 'recreational' use of marijuana, has of course permitted the long-standing demonisation of cannabis and the dismissal of claims for its utility and safety as mere 'anecdotal evidence' of little or no use as 'scientific proof.' Thus the I.O.M. report could 'safely ignore' not only sociological concerns but a vast body of common knowledge about cannabis that remains 'illegitimate' simply by virtue of the illegality and demonisation of 'the evil weed,' and use what little government-approved research as existed to disguise, more than reveal, the true medical and social potentials of cannabis. The facts that were thus ignored or discredited by the report, as well as the objections to the medical use of whole smoked cannabis presented there, reveal that to a significant extent the essential substance of the I.O.M. report is ideology dressed up as science. When social and scientific concerns are as interfused as they are today concerning medical marijuana and the larger issue of substance prohibition in general - especially in view of the overwhelming evidence that prohibitions are invariably self-defeating and in the long run may amount to crimes against humanity - no study which rejects important evidence as 'anecdotal' and 'outside its scope' will be truly objective, nor will it resolve, but instead perpetuate the problems it has been commissioned to clarify. Amid all the calls for exacting scientific evidence for the efficacy and safety of the medical use of marijuana, where are the equally stringent requirements for scientific evidence which proves the merit of current repressive prohibitionist policy? Much testimony that would lead to wide-ranging changes in approaches to drug use is dismissed as "anecdotal", yet the evidence that putting drug users in prison has any benefit to society falls short even of the anecdotal, indeed, the entire concept and practice of drug prohibition seems based primarily on misplaced moralism, lies, racism and historical errors. Why should science require far more stringent evidence for recommending the reversal of bad drug policy than for supporting its continuation? ~~~~~ Let us evaluate certain aspects of the I.O.M report, and especially its stated objections to the use of whole 'crude' smoked marijuana as a medicinal product, from a position less beholden to U.S. prohibitionist convictions than mainstream institutions today appear capable of. To its small credit, the I.O.M. Report did stress the lack of evidence that marijuana was significantly 'addictive,' or a 'gateway' drug that in itself enticed users to graduate to 'harder drugs,' ("it is the legal status of marijuana that makes it a gateway drug"), and also found no convincing evidence that medical availability of cannabis would stimulate illegal 'recreational' use of the drug. These were not revolutionary admissions however: considering the wealth of evidence showing such suspicions as products of 'reefer madness' fanaticism, the I.O.M. would have severely tarnished its credibility had it stated otherwise. But the superficially generous admission of the obvious may often be a way to disguise a partisan evaluation of the controversial. "Because marijuana is a crude THC delivery system that also delivers harmful substances, smoked marijuana should generally not be recommended for medical use. Nonetheless, marijuana is widely used by certain patient groups, which raises both safety and efficacy issues," states the I.O.M. Report. "If there is any future for marijuana as a medicine, it lies in its isolated components, the cannabinoids and their synthetic derivatives." "Marijuana's future as a medicine does not involve smoking," insisted Dr. Stanley Watson, a neuroscientist and substance-abuse researcher from the University of Michigan and co-author of the report. Despite the authors' insistence that scientific rigor was their rule, embedded in the above quotes and in the substance of the Report are value judgements and prejudices, and we can discern the way in which scientific objectivity has fallen prey to moralistic conviction by way of the following arguments. The principal stated and implied conclusions of the report in objection to the use of smoked marijuana - which reflect current medical and scientific paradigms - need some careful examination and rebuttal. Among those conclusions and paradigms are: o Smoking "delivers harmful substances" and is dangerous to health and unsuitable as a drug delivery method. No other drugs are smoked. o An efficient medicinal product should ideally consist of a single purified substance. When herbal remedies or mixtures are found to be of value, research then isolates the active ingredient and industry produces a standardised and scientifically-tested pharmacological product. o Whole ('crude') marijuana contains variable and uncertain amounts of active ingredients, as well as a range of inert and inactive substances. The 'efficiency' of 'crude' marijuana is thus uncertain. o Certain substances and activities are 'harmful'. "Marijuana is not a completely benign substance," the report stresses. Prohibitionists and government spokesmen seized upon the objection to smoking as a route for the administration of a therapeutic drug despite the report's recommendation that smoking might be an interim solution for certain patients and through research a "step towards the possible development of nonsmoked, rapid-onset cannabinoid delivery systems." Ideologues routinely confuse themselves with their own convictions, even when the facts are imposing, so we might excuse them from parroting the anti-smoking conclusions of the I.O.M. Report. But scientists should be ashamed for jumping on the anti-smoke bandwagon without a moment of reflection. True, in the modern pharmacopoeia, there are no medicinal substances delivered by smoking, and in the absence of evidence to the contrary such a route of administration might be avoided. But the argument that smoking is an inappropriate drug delivery method because no other drugs are administered that way is logically weak, at least insofar as uniqueness of method is concerned. Before the hypodermic syringe was invented no drugs were administered by injection, but with the advent of the method there was no great movement by government and medical authorities denouncing injection merely on the basis of novelty, since the delivery method was found to be effective. (And presumably, drug injection in those days, with the primitive equipment and minimal understanding of infections prevalent, involved significant risk of complications.) With marijuana, however, the nature and effects of the drug make its smoking far more effective and acceptable for patients than oral preparations, for problems of solubility make absorption by the oral route far too dependent on the presence of fats. Indeed, for the minority of medical users who are averse to smoking, marijuana may be prepared into 'brownies' or other fatty pastries, and as a starting point in the recipe, the cannabis is usually heated in butter or other oil to dissolve and disperse the active cannabinoids. Absorption in the gut is then far more reliable and predictable, if still unduly delayed. In addition, all medical marijuana users stress the importance of self-titration of the drug, and insist that smoking is by far the best existing route for implementing this technique, oral ingestion resulting in little ability to control the onset of effect or the size of dose. Presumably, similar and additional concerns would make an injected cannabis preparation both impractical and unacceptable to the great majority of patients. Obviously, the primary consideration of a drug/delivery-method combination is that it should work, and if no other delivery method can be found superior, it would be absurd to reject the 'novel' or unusual solely on the basis of its curiosity. And it must be added that in the case of marijuana, the unusual chemical, biological, and medicinal qualities of the drug make it unlike any other in the pharmacopoeia, thus the 'novel' route of administration must be given much leeway until extensive clinical trials have definitively shown that a safer and equally patient-acceptable route is in every way equivalent or superior to smoking. Thus, at least for the present, the peculiarities of marijuana and its use for various medical applications leave smoking as the superior route of administration, despite any drawbacks. "Although marijuana smoke delivers THC and other cannabinoids to the body, it also delivers harmful substances, including most of those found in tobacco smoke." The fallacy of believing that 'harm' and 'risk' (and even 'safety') are not entirely relative to one's premises has been philosophically explored since time immemorium. Likewise, labelling a substance as "not completely benign" tells us nothing. And calling a mere substance 'harmful' without reference to how it is used nor concerns of relativity or value judgement should be an intellectual trap scrupulously avoided by scientists, at the least. The contention that marijuana smoke delivers "most of the harmful [sic] substances...found in tobacco smoke" is a howler, however, and produces the suspicion that lapses of scientific rigor by the I.O.M. were intentional, allowing the report to legitimate the continuing and very unscientific status quo of marijuana prohibition. Paradoxically, even tobacco smoke itself does not necessarily deliver all the harmful substances "found in tobacco smoke," as we can ascertain from recent research indicating that bacteria in tobacco leaf that produce nitrosamines - the chemicals thought to be the biggest cancer hazard in tobacco smoke - can easily be killed to produce a potentially far safer tobacco. (Day, 1999) Does marijuana contain such bacteria-produced nitrosamines? The I.O.M. Report does not say, nor do the references cited. Certainly marijuana does not contain nicotine, nor does it contain tobacco-specific bio-accumulated radionuclides such as Polonium210, an alpha-emitter also suspected of being highly carcinogenic to lung tissue. And what about other key tobacco toxins such as 4-aminobiphenyl? Are they to be found in marijuana? True, burning one leaf or another is likely to produce hundreds of practically identical combustion products, so that a list of chemicals found in tobacco smoke vs. marijuana smoke might seem superficially equivalent. But if even one or two of the principal disease-producing substances in tobacco smoke are absent, or even significantly reduced in marijuana smoke, the contention that the two smokes deliver equivalent 'harmful substances' is merely capitalising on current anti-tobacco hysteria in the attempt to denounce marijuana smoking when the preponderance of evidence indicates that smoked marijuana may not be a carcinogen at all. In fact, a United Press International article from January 30, 1997 reports that, "The U.S. federal government has failed to make public its own 1994 study that undercuts its position that marijuana is carcinogenic - a $2 million study by the National Toxicology Program. The program's deputy director, John Bucher says the study found absolutely no evidence of cancer. In fact, animals that received THC had fewer cancers." Certainly I do not propose that smoking is 'harmless' when indulged in to excess, and tobacco smoking is renowned for excess. The effect of nicotine is so short-lived that most tobacco habituE9s require a new dose every half-hour. And surely, marijuana when burned produces carbon monoxide and a few more or less carcinogenic combustion products as do cigarettes, fireplace logs, power stations, and barbecue fuel. But it would not be stretching credulity to argue that mankind has developed a fairly robust resistance to breathing smoke for at least part of the day, having lived for 99% of his time on earth in dwellings with open hearths. In these dwellings even the pregnant and the new-born would breathe all sorts of combustion products. Natural selection must certainly have acted to produce some immunity to smoke inhalation, or it would now be impossible to live in many of our major cities. The comparison of the daily use of a few puffs of medical marijuana and living in London or Los Angeles must surely reveal the latter the more dangerous for the respiratory passages. This must certainly be the case when the quantity and frequency of marijuana use required for a given application such as anti-nausea is low and the variety of cannabis employed one of the potent high-quality strains favoured by users, so that the smoke intake is very modest compared with the round-the-clock breathing of polluted air. There are thousands of deaths yearly in many major cities directly caused by air polluted with a wide range of carcinogens and irritants, (in the U.K., microparticulates from diesel exhaust alone are thought to kill 10,000 people a year), yet no one has identified a single death or cancer caused by marijuana smoking. Why should living in polluted air seem an acceptable, even disregarded risk while light to moderate medical marijuana smoking be denounced as unconscionable? Extending the argument into sacred pharmacological territory, it cannot be ignored that all medical preparations have side-effects. Even an aspirin has potentially dangerous and common, occasionally fatal side-effects, and in the case of aspirin as for smoked marijuana and many other drugs, it is the route of administration which leads to the potentially threatening side effects! The oral method of aspirin use leads to possibly severe and not uncommon gastro-intestinal consequences having nothing to do with the purpose of the drug nor its targeted site in the body. The smoked method of using medical marijuana may lead to some as yet unproved harm to the respiratory passages. There is simply no practical, logical, or medical argument which can justify risking stomach lesions taking aspirin for its neurological effects while denouncing as prohibitive the risk of possible lung damage smoking medical marijuana for effective therapeutic purposes. Is lung tissue more sacred than the stomach lining? We use warning labels on the product's package to alert the physician and user of side-effects, not logical fallacy disguised as medical truth, as is now being done for marijuana. To proceed yet further with standard pharmacological tenets, no medicine, even a totally purified single chemical entity, affects all persons the same or to an equal degree, nor will it work equally at all times for the same person. Sometimes an aspirin works fine, sometimes even several doses fail to deliver any analgesia whatsoever. The idea that a single purified substance is the summum bonum in pharmacology, which the IOM report supports by implication, is rendered uncertain both by this non-specificity argument and the fact that custom mixtures of drugs sometimes prove the best for not a few individual cases. In the case of a simple disease or condition such as an infection, a single purified substance is often desirable, such as a condition-specific antibiotic. It is no doubt through the successes of the treatment of such well-defined conditions that the 'single purified substance paradigm' has attained its current prominence, but there are many conditions which are complex, involving several aspects of health and multiple bodily systems including psychological manifestations. The relief of pain and other conditions for which marijuana has been found useful fall into the category of being multiple-causation, complex physical and psychological syndromes, and positing that a single pharmaceutical product MUST be the best remedy is an invalid extension of the 'simple-disease/simple cure' paradigm. It is obvious to medical marijuana users and to a growing number of physicians and scientists that strict reductionism in medical treatment is severely limiting, and that the synergistic effects of a drug like marijuana on several bodily systems as well as positive psychological effects combine to produce a wide-spectrum medicinal potential that we should in principle not expect of a single purified substance. Objecting to the proven efficacy of marijuana use on the basis that the drug contains a complex and varying mixture of substances might be a valid complaint if the pharmaceutical houses had already produced condition-specific cannabinoid preparations therapeutically equal to whole smoked cannabis. The only pharmaceutical preparation that science has brought us so far is Marinol, consisting of only one active ingredient (synthetic THC) dissolved in sesame oil to be taken orally, a preparation which few patients or physicians find as useful or effective as smoked marijuana. It is possible that the chemistry and pharmacology of cannabis is so complex that it will require decades of research to produce medicines tailor-made for conditions which are suitable for treatment right now with various strains of whole cannabis, and we can imagine that the price tag of those future researched-for-decades preparations will result in easily- and cheaply-grown whole cannabis still being the intelligent choice for many. With respect to cannabis at least, much of the pharmacological argument against 'herbal medicine' is a symptom of the dollar-signs-in-the-eyes syndrome. There is a further possible factor complicating the argument against smoked cannabis: burning the substance in a certain way may actually produce altered cannabinoids which are therapeutically useful. It is known, for example, that cannabinoids in fresh green cannabis are to some degree carboxylated and largely inactive, and that curing and drying, smoking, (or heating in butter as mentioned above) de-carboxylates and thus activates the drug. The hypothesis that smoking itself makes cannabis more therapeutically active cannot be ruled out but must be thoroughly tested. Thus medicinal cannabis preparations taken with yet-to-be-developed inhalers mentioned in the I.O.M. document may still not completely reproduce the effect of smoked whole cannabis. Let research on vaporisers and inhalers begin in earnest (and here the I.O.M. report notes that such delivery methods might not be perfected for many years). But for the time being, and as has been noted by many, asking patients in need to wait years for a substitute for what they already have that works, or go to prison and forfeit their homes for insisting, is a bit extreme! The argument that whole cannabis supplies unknown and uncertain doses of active products is flawed in another respect, and here it is the smoked delivery method itself which supplies the rebuttal. As noted above, medical marijuana users insist on the importance of self-titration for administering the drug, so as to obtain the desired level of relief of symptoms while avoiding taking a dose which produces excess psychological effects or renders them temporarily overwhelmed, a frequent complaint with the oral preparation Marinol. The onset of action of the drug when smoked is particularly rapid, so that no matter what the strength of the whole cannabis, or its particular blend of active and inert ingredients, a smoker may arrive at his required dose within a few minutes solely on the basis of perceived desired effect. Thus may he also select among varieties of whole cannabis for the best perceived remedy for his particular condition. And if there are inert and ineffective substances in the collection of "400 chemicals in marijuana," so what? Read the label of any medical preparation and see: 'active ingredients,' and then 'inert ingredients.' No one would insist that the food we eat be completely analysed and consist only of ingredients 'recognised by science' to have benefit to the body. Indeed, many foodstuffs contain toxins, carcinogens, and irrelevant substances. And a recommendation to eat only purified vitamins, nutrients, minerals and sterile bulking agents would be considered absurd by all except the companies which intended to market such products. The pharmaceutical and medical paradigms which will not allow medicines to be at all analogous to foods in their application and benefit is certainly too narrow, and should be relaxed. And in the case of medical marijuana and other herbal preparations whose effectiveness depends on their wide-spectrum influence on both body and mind, current pharmaceutical paradigms become an absurdity. Let research show which ingredients in natural herbs are effective, just as research has shown which nutrients in food are required for various aspects of health. But let us not get sucked into approving the blinkered profit motives of pharmaceutical companies by supporting the dictum that 'acceptable medicine' may not be a natural plant or combination of plants, especially when the desired effect is relief of pain and psychological distress or other objectives for which the subjective evaluation of efficacy by the patient must reign supreme. The onus is on science, industry and government to improve therapy, even (need I say it?) at the sacrifice of profits and prestige, and not to attempt to remove currently effective if imperfect therapy from the scene (and what therapy has been proved perfect?). Current arguments against cannabis are morality dressed up as science, and (to quote the Drug Czar) "a cruel hoax." References Day, Michael. The Lesser Of Two Evils: If people can't stop smoking, the next best thing is to make tobacco less harmful. New Scientist, May 8, 1999. Doblin, Rick. Letter from Rick Doblin, MAPS President. Multidisciplinary Association for Psychedelic Studies, Bulletin 1999, Vol IX, No. 1, p.3. Joy, J.E., et al. Marijuana and Medicine: Assessing the Science Base. Janet E. Joy, Stanley J. Watson, Jr., and John A. Benson, Jr., Editors, Division of Neuroscience and Behavioral Health, Institute Of Medicine, National Academy Press, Washington, D.C. 1999. - --- MAP posted-by: Richard Lake