Counterblast 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 finallypublished, having been commissioned by the U.S. Drug Czar and his WhiteHouse Office of National Drug Control Policy in January 1997. Thewidespread and growing use of marijuana for medicinal purposes and thepassage of legislation in several U.S. states recognising patients' rightsto use, and physicians' rights to recommend marijuana had been countered bythe Drug Czar's denunciation of medical marijuana as "a cruel hoax,""Cheech and Chong medicine," and a "Trojan horse" for across-the-boardlegalisation of drugs. A review of the scientific evidence on marijuana byan organisation with irreproachable credentials was thus called for,although at the time - January 1997 - the request to the I.O.M. was widelyseen as merely a stalling tactic by an unremittingly prohibitionist federalgovernment pressed to divert attention from the recent successes of thedrug policy reform movement.

The I.O.M. document, summarising a purportedly scientific and thoroughreview of all available evidence, left no doubt that marijuana - or atleast some of its active ingredients - showed significant promise forcertain conditions: "For [some] patients...cannabinoid drugs might offerbroad spectrum relief not found in any other single medication." Examinedfrom the point of view of the U.S. federal government's long-standingprohibitionist policies, however, the report's findings were not consideredsignificant enough to justify any change of direction: Even for theterminally ill and severely afflicted who find marijuana of some use orcomfort, harassment, arrest, seizure of assets, and imprisonment are stilldeemed 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: In1997 there were three-quarters of a million marijuana arrests in the U.S.,90 percent of them for simple possession. Even larger figures are expectedfor 1998 and 1999. The I.O.M. study shunned consideration of the largersocial questions: "Can marijuana relieve health problems? Is it safe formedical use? Those straightforward questions are embedded in a web ofsocial concerns, most of which lie outside the scope of this report."

The I.O.M. report went on to recommend further extensive research on themedical use of cannabis: "Recommendation 1: Research should continue intothe physiological effects of synthetic and plant-derived cannabinoids andthe natural function of cannabinoids found in the body." Publicly, atleast, 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 thestringent requirements for approval of proposed research projects. As anexample of recent stonewalling, Rick Doblin of the MultidisciplinaryAssociation for Psychedelic Studies writes,

"Obtaining approval for MAPS-sponsored medical marijuana research has...been difficult. As reported in the last Bulletin, the NationalInstitutes of Health (NIH) rejected for the second time the grantapplication of Dr. Ethan Russo, U. of Montana, for a study of the use ofsmoked marijuana in people whose migraines are not successfully treated bycurrently available medicines. The NIH letter explaining the rationale forits decision arrived well after the news of the rejection of the grant. TheNIH reviewers focused in large part on an issue that cannot be resolved andthat has nothing to do with the scientific merit of the protocol design,the supposed need for preliminary data to supplement extensive historicaland anecdotal reports. It is difficult to imagine that the NIH reviewersdidn't realize that it is impossible to obtain permission to conductpreliminary studies, or didn't know that the NIH Expert Committee on theMedical Uses of Marijuana recommended full-scale trials. Despite theClinton Administration rhetoric in favor of medical marijuana research, thereality is continued obstructionism. In a victory for the opponents ofmedical marijuana, Dr. Russo has decided that it is futile to reapply toNIH a third time. The Clinton Administration position that the controversyover the medical use of marijuana should be resolved through scientificresearch rather than at the ballot box will remain dishonest and deceptiveuntil 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 highpotential for abuse and no accepted medical use" it is difficult to see howany U.S. research agenda could attain the necessary freedom from corruptingpolitical imperatives rooted deep in moralistic and religious convictions.Under such pressure, what little research as has been allowed over theyears has been largely directed at supporting prohibitionist policy andprejudice, and there is little sign that the tendency will improve in thenear-term, the I.O.M. recommendation notwithstanding.

The lack of adequate research uncontaminated by ideology, especially withregard to understanding the illegal 'recreational' use of marijuana, has ofcourse permitted the long-standing demonisation of cannabis and thedismissal 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 commonknowledge about cannabis that remains 'illegitimate' simply by virtue ofthe illegality and demonisation of 'the evil weed,' and use what littlegovernment-approved research as existed to disguise, more than reveal, thetrue medical and social potentials of cannabis. The facts that were thusignored or discredited by the report, as well as the objections to themedical use of whole smoked cannabis presented there, reveal that to asignificant extent the essential substance of the I.O.M. report is ideologydressed up as science. When social and scientific concerns are asinterfused as they are today concerning medical marijuana and the largerissue of substance prohibition in general - especially in view of theoverwhelming evidence that prohibitions are invariably self-defeating andin the long run may amount to crimes against humanity - no study whichrejects important evidence as 'anecdotal' and 'outside its scope' will betruly objective, nor will it resolve, but instead perpetuate the problemsit has been commissioned to clarify. Amid all the calls for exactingscientific evidence for the efficacy and safety of the medical use ofmarijuana, where are the equally stringent requirements for scientificevidence which proves the merit of current repressive prohibitionistpolicy? Much testimony that would lead to wide-ranging changes inapproaches to drug use is dismissed as "anecdotal", yet the evidence thatputting drug users in prison has any benefit to society falls short even ofthe anecdotal, indeed, the entire concept and practice of drug prohibitionseems based primarily on misplaced moralism, lies, racism and historicalerrors. Why should science require far more stringent evidence forrecommending the reversal of bad drug policy than for supporting its continuation?

Let us evaluate certain aspects of the I.O.M report, and especially itsstated objections to the use of whole 'crude' smoked marijuana as amedicinal product, from a position less beholden to U.S. prohibitionistconvictions than mainstream institutions today appear capable of. To itssmall credit, the I.O.M. Report did stress the lack of evidence thatmarijuana was significantly 'addictive,' or a 'gateway' drug that in itselfenticed users to graduate to 'harder drugs,' ("it is the legal status ofmarijuana that makes it a gateway drug"), and also found no convincingevidence that medical availability of cannabis would stimulate illegal'recreational' use of the drug. These were not revolutionary admissionshowever: considering the wealth of evidence showing such suspicions asproducts of 'reefer madness' fanaticism, the I.O.M. would have severelytarnished its credibility had it stated otherwise. But the superficiallygenerous admission of the obvious may often be a way to disguise a partisanevaluation of the controversial.

"Because marijuana is a crude THC delivery system that also deliversharmful substances, smoked marijuana should generally not be recommendedfor medical use. Nonetheless, marijuana is widely used by certain patientgroups, 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 itsisolated 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 theUniversity 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 valuejudgements and prejudices, and we can discern the way in which scientificobjectivity has fallen prey to moralistic conviction by way of thefollowing arguments. The principal stated and implied conclusions of thereport in objection to the use of smoked marijuana - which reflect currentmedical and scientific paradigms - need some careful examination andrebuttal. Among those conclusions and paradigms are:

o Smoking "delivers harmful substances" and is dangerous to health andunsuitable as a drug delivery method. No other drugs are smoked.o An efficient medicinal product should ideally consist of a singlepurified substance. When herbal remedies or mixtures are found to be ofvalue, research then isolates the active ingredient and industry produces astandardised and scientifically-tested pharmacological product.o Whole ('crude') marijuana contains variable and uncertain amounts ofactive 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 acompletely benign substance," the report stresses.

Prohibitionists and government spokesmen seized upon the objection tosmoking as a route for the administration of a therapeutic drug despite thereport's recommendation that smoking might be an interim solution forcertain patients and through research a "step towards the possibledevelopment of nonsmoked, rapid-onset cannabinoid delivery systems."Ideologues routinely confuse themselves with their own convictions, evenwhen the facts are imposing, so we might excuse them from parroting theanti-smoking conclusions of the I.O.M. Report. But scientists should beashamed for jumping on the anti-smoke bandwagon without a moment ofreflection. True, in the modern pharmacopoeia, there are no medicinalsubstances delivered by smoking, and in the absence of evidence to thecontrary such a route of administration might be avoided. But the argumentthat smoking is an inappropriate drug delivery method because no otherdrugs are administered that way is logically weak, at least insofar asuniqueness of method is concerned. Before the hypodermic syringe wasinvented no drugs were administered by injection, but with the advent ofthe method there was no great movement by government and medicalauthorities denouncing injection merely on the basis of novelty, since thedelivery method was found to be effective. (And presumably, drug injectionin those days, with the primitive equipment and minimal understanding ofinfections prevalent, involved significant risk of complications.)

With marijuana, however, the nature and effects of the drug make itssmoking far more effective and acceptable for patients than oralpreparations, for problems of solubility make absorption by the oral routefar too dependent on the presence of fats. Indeed, for the minority ofmedical 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 anddisperse the active cannabinoids. Absorption in the gut is then far morereliable and predictable, if still unduly delayed.

In addition, all medical marijuana users stress the importance ofself-titration of the drug, and insist that smoking is by far the bestexisting route for implementing this technique, oral ingestion resulting inlittle ability to control the onset of effect or the size of dose.Presumably, similar and additional concerns would make an injected cannabispreparation both impractical and unacceptable to the great majority ofpatients. Obviously, the primary consideration of a drug/delivery-methodcombination is that it should work, and if no other delivery method can befound superior, it would be absurd to reject the 'novel' or unusual solelyon the basis of its curiosity. And it must be added that in the case ofmarijuana, the unusual chemical, biological, and medicinal qualities of thedrug make it unlike any other in the pharmacopoeia, thus the 'novel' routeof administration must be given much leeway until extensive clinical trialshave definitively shown that a safer and equally patient-acceptable routeis in every way equivalent or superior to smoking. Thus, at least for thepresent, the peculiarities of marijuana and its use for various medicalapplications leave smoking as the superior route of administration, despiteany drawbacks.

"Although marijuana smoke delivers THC and other cannabinoids to the body,it also delivers harmful substances, including most of those found intobacco smoke." The fallacy of believing that 'harm' and 'risk' (and even'safety') are not entirely relative to one's premises has beenphilosophically explored since time immemorium. Likewise, labelling asubstance as "not completely benign" tells us nothing. And calling a meresubstance 'harmful' without reference to how it is used nor concerns ofrelativity or value judgement should be an intellectual trap scrupulouslyavoided by scientists, at the least. The contention that marijuana smokedelivers "most of the harmful [sic] substances...found in tobacco smoke" isa howler, however, and produces the suspicion that lapses of scientificrigor by the I.O.M. were intentional, allowing the report to legitimate thecontinuing and very unscientific status quo of marijuana prohibition.Paradoxically, even tobacco smoke itself does not necessarily deliver allthe harmful substances "found in tobacco smoke," as we can ascertain fromrecent research indicating that bacteria in tobacco leaf that producenitrosamines - the chemicals thought to be the biggest cancer hazard intobacco smoke - can easily be killed to produce a potentially far safertobacco. (Day, 1999) Does marijuana contain such bacteria-producednitrosamines? The I.O.M. Report does not say, nor do the references cited.Certainly marijuana does not contain nicotine, nor does it containtobacco-specific bio-accumulated radionuclides such as Polonium210, analpha-emitter also suspected of being highly carcinogenic to lung tissue.And what about other key tobacco toxins such as 4-aminobiphenyl? Are theyto be found in marijuana?

True, burning one leaf or another is likely to produce hundreds ofpractically identical combustion products, so that a list of chemicalsfound in tobacco smoke vs. marijuana smoke might seem superficiallyequivalent. But if even one or two of the principal disease-producingsubstances in tobacco smoke are absent, or even significantly reduced inmarijuana smoke, the contention that the two smokes deliver equivalent'harmful substances' is merely capitalising on current anti-tobaccohysteria in the attempt to denounce marijuana smoking when thepreponderance of evidence indicates that smoked marijuana may not be acarcinogen at all. In fact, a United Press International article fromJanuary 30, 1997 reports that,

"The U.S. federal government has failed to make public its own 1994 studythat undercuts its position that marijuana is carcinogenic - a $2 millionstudy 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 toexcess, and tobacco smoking is renowned for excess. The effect of nicotineis so short-lived that most tobacco habitu=E9s require a new dose everyhalf-hour. And surely, marijuana when burned produces carbon monoxide and afew more or less carcinogenic combustion products as do cigarettes,fireplace logs, power stations, and barbecue fuel. But it would not bestretching credulity to argue that mankind has developed a fairly robustresistance to breathing smoke for at least part of the day, having livedfor 99% of his time on earth in dwellings with open hearths. In thesedwellings even the pregnant and the new-born would breathe all sorts ofcombustion products. Natural selection must certainly have acted to producesome immunity to smoke inhalation, or it would now be impossible to live inmany of our major cities.

The comparison of the daily use of a few puffs of medical marijuana andliving in London or Los Angeles must surely reveal the latter the moredangerous for the respiratory passages. This must certainly be the casewhen the quantity and frequency of marijuana use required for a givenapplication such as anti-nausea is low and the variety of cannabis employedone of the potent high-quality strains favoured by users, so that the smokeintake is very modest compared with the round-the-clock breathing ofpolluted air. There are thousands of deaths yearly in many major citiesdirectly caused by air polluted with a wide range of carcinogens andirritants, (in the U.K., microparticulates from diesel exhaust alone arethought to kill 10,000 people a year), yet no one has identified a singledeath or cancer caused by marijuana smoking. Why should living in pollutedair seem an acceptable, even disregarded risk while light to moderatemedical marijuana smoking be denounced as unconscionable?

Extending the argument into sacred pharmacological territory, it cannot beignored that all medical preparations have side-effects. Even an aspirinhas potentially dangerous and common, occasionally fatal side-effects, andin the case of aspirin as for smoked marijuana and many other drugs, IT ISTHE ROUTE OF ADMINISTRATION WHICH LEADS TO THE POTENTIALLY THREATENING SIDEEFFECTS! The oral method of aspirin use leads to possibly severe and notuncommon gastro-intestinal consequences having nothing to do with thepurpose of the drug nor its targeted site in the body. The smoked method ofusing medical marijuana may lead to some as yet unproved harm to therespiratory passages. There is simply no practical, logical, or medicalargument which can justify risking stomach lesions taking aspirin for itsneurological effects while denouncing as prohibitive the risk of possiblelung damage smoking medical marijuana for effective therapeutic purposes.Is lung tissue more sacred than the stomach lining? We use warning labelson 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 formarijuana.

To proceed yet further with standard pharmacological tenets, no medicine,even a totally purified single chemical entity, affects all persons thesame or to an equal degree, nor will it work equally at all times for thesame person. Sometimes an aspirin works fine, sometimes even several dosesfail to deliver any analgesia whatsoever. The idea that a single purifiedsubstance is the summum bonum in pharmacology, which the IOM reportsupports by implication, is rendered uncertain both by this non-specificityargument and the fact that custom mixtures of drugs sometimes prove thebest for not a few individual cases. In the case of a simple disease orcondition such as an infection, a single purified substance is oftendesirable, such as a condition-specific antibiotic. It is no doubt throughthe 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 aspectsof health and multiple bodily systems including psychologicalmanifestations. The relief of pain and other conditions for which marijuanahas been found useful fall into the category of being multiple-causation,complex physical and psychological syndromes, and positing that a singlepharmaceutical product MUST be the best remedy is an invalid extension ofthe 'simple-disease/simple cure' paradigm. It is obvious to medicalmarijuana users and to a growing number of physicians and scientists thatstrict reductionism in medical treatment is severely limiting, and that thesynergistic effects of a drug like marijuana on several bodily systems aswell as positive psychological effects combine to produce a wide-spectrummedicinal potential that we should in principle not expect of a singlepurified substance.

Objecting to the proven efficacy of marijuana use on the basis that thedrug contains a complex and varying mixture of substances might be a validcomplaint if the pharmaceutical houses had already producedcondition-specific cannabinoid preparations therapeutically equal to wholesmoked cannabis. The only pharmaceutical preparation that science hasbrought us so far is Marinol, consisting of only one active ingredient(synthetic THC) dissolved in sesame oil to be taken orally, a preparationwhich few patients or physicians find as useful or effective as smokedmarijuana. It is possible that the chemistry and pharmacology of cannabisis so complex that it will require decades of research to produce medicinestailor-made for conditions which are suitable for treatment right now withvarious strains of whole cannabis, and we can imagine that the price tag ofthose future researched-for-decades preparations will result in easily- andcheaply-grown whole cannabis still being the intelligent choice for many.With respect to cannabis at least, much of the pharmacological argumentagainst 'herbal medicine' is a symptom of the dollar-signs-in-the-eyessyndrome.

There is a further possible factor complicating the argument against smokedcannabis: burning the substance in a certain way may actually producealtered cannabinoids which are therapeutically useful. It is known, forexample, that cannabinoids in fresh green cannabis are to some degreecarboxylated and largely inactive, and that curing and drying, smoking, (orheating in butter as mentioned above) de-carboxylates and thus activatesthe drug. The hypothesis that smoking itself makes cannabis moretherapeutically active cannot be ruled out but must be thoroughly tested.Thus medicinal cannabis preparations taken with yet-to-be-developedinhalers mentioned in the I.O.M. document may still not completelyreproduce the effect of smoked whole cannabis. Let research on vaporisersand inhalers begin in earnest (and here the I.O.M. report notes that suchdelivery methods might not be perfected for many years). But for the timebeing, and as has been noted by many, asking patients in need to wait yearsfor a substitute for what they already have that works, or go to prison andforfeit their homes for insisting, is a bit extreme!

The argument that whole cannabis supplies unknown and uncertain doses ofactive products is flawed in another respect, and here it is the smokeddelivery method itself which supplies the rebuttal. As noted above, medicalmarijuana users insist on the importance of self-titration foradministering the drug, so as to obtain the desired level of relief ofsymptoms while avoiding taking a dose which produces excess psychologicaleffects or renders them temporarily overwhelmed, a frequent complaint withthe oral preparation Marinol. The onset of action of the drug when smokedis particularly rapid, so that no matter what the strength of the wholecannabis, or its particular blend of active and inert ingredients, a smokermay arrive at his required dose within a few minutes solely on the basis ofperceived desired effect. Thus may he also select among varieties of wholecannabis for the best perceived remedy for his particular condition.

And if there are inert and ineffective substances in the collection of "400chemicals in marijuana," so what? Read the label of any medical preparationand see: 'active ingredients,' and then 'inert ingredients.' No one wouldinsist that the food we eat be completely analysed and consist only ofingredients 'recognised by science' to have benefit to the body. Indeed,many foodstuffs contain toxins, carcinogens, and irrelevant substances. Anda recommendation to eat only purified vitamins, nutrients, minerals andsterile bulking agents would be considered absurd by all except thecompanies which intended to market such products. The pharmaceutical andmedical paradigms which will not allow medicines to be at all analogous tofoods in their application and benefit is certainly too narrow, and shouldbe relaxed. And in the case of medical marijuana and other herbalpreparations whose effectiveness depends on their wide-spectrum influenceon both body and mind, current pharmaceutical paradigms become anabsurdity. Let research show which ingredients in natural herbs areeffective, just as research has shown which nutrients in food are requiredfor various aspects of health. But let us not get sucked into approving theblinkered profit motives of pharmaceutical companies by supporting thedictum that 'acceptable medicine' may not be a natural plant or combinationof plants, especially when the desired effect is relief of pain andpsychological distress or other objectives for which the subjectiveevaluation 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 toattempt to remove currently effective if imperfect therapy from the scene(and what therapy has been proved perfect?). Current arguments againstcannabis are morality dressed up as science, and (to quote the Drug Czar)"a cruel hoax."

Peter Webstervignes@monaco.mc

ReferencesDay, 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. MultidisciplinaryAssociation for Psychedelic Studies, Bulletin 1999, Vol IX, No. 1, p.3.

Joy, J.E., et al. Marijuana and Medicine: Assessing the Science Base. JanetE. Joy, Stanley J. Watson, Jr., and John A. Benson, Jr., Editors, Divisionof Neuroscience and Behavioral Health, Institute Of Medicine, NationalAcademy Press, Washington, D.C. 1999.