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With the passage of the Marijuana Tax Act of 1937, physicians first became severely constrained in their ability to prescribe cannabis as a medicine and, as a consequence, over the next three or four decades became increasingly ignorant of both its remarkable therapeutic utility and limited toxicity. Pari passu with the explosive growth of the use of marijuana as a recreational drug in the 60s, many users serendipitously rediscovered its usefulness for a variety of medical problems .By the mid-90s, its popularity as a medicine became so great that states, beginning with California in 1996, began to make its use legal for specified medical conditions. At present 20 states and the District of Columbia allow for its use as a medicine, despite the fact that the federal government still considers it a most dangerous substance. This rapid growth of marijuana as a medicine has occurred in the face of the threat of punishment by the federal government. Furthermore, it cannot be legally sold as a medicine because the US government will not remove cannabis from Schedule I of the 1970 Comprehensive Drug Abuse and Control Act ; this precludes the possibility of acquiring the research data which is needed before a drug can be approved by the Food and Drug Administration (FDA)) for commercial distribution . The government will, sooner or later, abandon its archaic view of cannabis and this will legitimize the use of marijuana as a medicine: this will not, however, ensure its rightful place in the pharmacopeia of modern Western medicine (allopathic medicine). The American Medical Association’s House of Delegates in their November, 2013 meeting voted to retain their long-standing position that “cannabis is a dangerous drug and as such is a public health concern.” Should modern medicine persist in ignoring the use of cannabis as a medicine, this growing practice will surely continue to develop, perhaps into a school or philosophy of medicine which might be referred to as cannabinopathic medicine. This paper will attempt to elucidate the problem.
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by
Lester Grinspoon M.D.
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A native of Central Asia, cannabis (hemp) may have been cultivated as long as 10,000 years ago. It was certainly cultivated in China by 4000 BC and in Turkestan by 3000 BC. It has long been used as a medicine in India, China, the Middle East, Southeast Asia, South Africa, and South America. In an herbal published during the reign of the Chinese emperor Chen Nung 5000 years ago cannabis was recommended for malaria, constipation, rheumatic pains, “absentmindedness” and “female disorders.” One Chinese herbalist recommended a mixture of hemp, resin, and wine as an analgesic during surgery. In India cannabis had been recommended to quicken the mind, lower fevers, induce sleep, cure dysentery, stimulate appetite, improve digestion, relieve headache, and cure venereal disease. In Africa it was used for dysentery, malaria, and other fevers. Today certain tribes treat snakebite with hemp or smoke it before childbirth. Hemp was also noted as a remedy by Galen and other physicians of the classical and Hellenistic eras, and it was highly valued in medieval Europe. The English clergyman Robert Burton, in his famous work The Anatomy of Melancholy, published in 1621, suggested the use of cannabis in the treatment of depression. The New English Dispensatory of 1764 recommended applying hemp roots to the skin for inflammation, a remedy that was already popular in Eastern Europe. The Edinburgh New Dispensary of 1794 included a long description of the effects of hemp and stated that the oil was useful in the treatment of coughs, venereal disease, and urinary incontinence.
However, in the West cannabis did not come into its own as a medicine until the mid-19th century. The first Western physician to take an interest in cannabis as medicine was W.B. O’ Shaughnessy, a young professor at the Medical College of Calcutta, who had observed its use in India. He gave cannabis to animals, satisfied himself that it was safe, and began to use it with patients suffering from rabies, rheumatism, epilepsy, and tetanus. In a report published in 1839, he wrote that he had found Cannabis Indica (a solution of cannabis in alcohol, taken orally) to be an effective analgesic. He was also impressed with its muscle-relaxant properties and called it “an anticonvulsive remedy of the greatest value.”
O’Shaughnessy returned to England in 1842 and provided cannabis to pharmacists. Doctors in Europe and the United States soon began to prescribe it for a variety of physical conditions. Cannabis was even given to Queen Victoria for the treatment of her painful pre-menstrual cramps by her court physician. It was admitted to the United States Pharmacopeia in 1850, and commercial cannabis preparations soon became widely distributed through drugstores. Pharmacies welcomed the arrival of this “new” medicine, Cannabis Indica, because at that time their shelves held few truly effective drugs to offer the practitioners of allopathic medicine. As its use became increasingly widespread, clinical reports on cannabis accumulated, and by the turn of the century more than 100 papers had been published in the Western medical literature recommending it for various illnesses and discomforts and extolling its remarkably limited toxicity.
The decline in the usage of Cannabis Indica began toward the end of the century. Both the potency of cannabis preparations and its absorption from the bowel were too variable, and individual responses to orally ingested cannabis seemed erratic and unpredictable. Another reason for the neglect of research on the analgesic properties of cannabis was the greatly increased use of opiates after the invention of the hypodermic syringe in the 1850s allowed soluble drugs to be injected for fast relief of pain; cannabis products are insoluble in water and so cannot easily be administered by injection. The end of the 19th century saw the development of such synthetic drugs as aspirin, chloral hydrate, and barbiturates. Two of the most common symptoms for which Cannabis Indica was prescribed were pain and insomnia, and now physicians could prescribe easy-to-take pills of known potency for these two problems, hastening the decline of cannabis as a medicine. But the new drugs had striking disadvantages. More than 1000 people die from aspirin-induced bleeding each year in the United States, and barbiturates are, of course, far more dangerous.
But the Marijuana Tax Act of 1937 was the ultimate death-knell for Cannabis Indica. This law was the culmination of a campaign organized by the Federal Bureau of Narcotics under Harry Anslinger in which the public was led to believe that cannabis, now commonly referred to as marijuana, was addictive and that its use led to violent crimes, psychosis, and mental deterioration; it is now confined to Schedule I under the Controlled Substances Act of 1970 as a drug that has a high potential for abuse, lacks accepted medical use, and is unsafe for use even under medical supervision. The film Reefer Madness, made as part of Anslinger’s campaign, may be a joke to the sophisticated today, but it was once regarded as a serious attempt to address a social problem; the atmosphere and attitudes it exemplified and promoted continue to influence our culture, albeit much less so today. The Marijuana Tax Act was not directly aimed at the medical use of cannabis; its purpose was to discourage recreational marijuana smoking. Almost incidentally the law made medical use of cannabis difficult because of the extensive paperwork and fees required of doctors who wanted to prescribe it. The Federal Bureau of Narcotics followed up with “anti-divergent” regulations that contributed to physicians’ disenchantment. Its removal from the United States Pharmacopeia and the National Formulary in 1942 signaled both the end of physicians’ interest in and allopathic medicine’s institutional embrace of cannabis. Furthermore, physicians allowed themselves to become ignorant about this drug as they have, since the mid-1930s, been increasingly exposed along with every other citizen to the deceptive propaganda against marijuana propagated by the United States government and such private organizations as the Partnership for a Drug Free America.
The concept of marijuana as a medicine virtually disappeared for several decades. Then in the 1960s, as large numbers of people began to use marijuana recreationally, claims of its medical utility began to appear, not in the medical literature but in the form of letters to popular magazines like Playboy. Typically these accounts were written by surprised and excited recreational users who had serendipitously discovered that marijuana relieved one or another of a variety of symptoms and syndromes. Over the next several decades, the grapevine word of these rediscovered medical utilities continued to grow. With the advent of the AIDS epidemic and the discovery of marijuana’s ability to reduce the nausea and therefore the threat of the “weight reduction syndrome of AIDS”, this reappearance of the concept of cannabis as a medicine gathered enough momentum to be publicly palpable. It was at this time that public pressure on the government to reconsider its obdurately held position developed in earnest, but with little success to date at the federal level.
There is an important difference in the way cannabis was used as a medicine in the latter
half of the 19th century and the way it has been generally administered since its reemergence as a sub rosa medicine in the mid-20th century. In its earlier iteration it was dispensed orally as an alcoholic solution; now it is primarily taken through the pulmonary system, vaporized or as smoke. The emergence of cannabis as a recreational drug began in the early part of the 20th century and has continued to grow. One of the reasons it has grown to the point where it can now be considered a part of Western culture is its introduction as a smokable drug. A good deal of mystery and uncertainty surrounds the story of the “reefer’s” debut in the United States. It is generally thought that in the early decades of the 20th century the custom of smoking “the weed” in cigarette form traveled with groups of itinerant Mexican workers across the border in the southern and southwestern states; it is now overwhelmingly the mode of administration used by the millions who use it as a medicine or for any other reason.
This change in the route of administration has greatly enhanced its usefulness as a medicine because it solved the problem of providing the correct dose. One of the major problems that doctors in the 19th century faced with Cannabis Indica was that there were no reliable bioassays at that time and so physicians could never be sure that they had prescribed the correct dose. If too much were prescribed, the patient might experience discomfort in the form of anxiety, but this would not be immediately evident because it takes about one to two hours for the effects of orally administered cannabis to be experienced. However, because physicians of the 19th century understood that this was a drug of unusually limited toxicity, they were not as concerned about overdosing as they were about providing an inadequate dose. The major advantage of smoking is the rapidity with which the medicinal effect appears; symptom relief will occur in a matter of minutes. And perhaps even more importantly, this very rapid feedback allows the patient to titrate his own dose for his particular symptom with much more precision than can his physician. He just leisurely puffs until one of two things happens: he either begins to experience symptom-relief or he becomes somewhat high or anxious, at which point he stops. It is no longer believed that the smoke from marijuana is harmful to pulmonary or oropharyngeal tissues. But, for those patients who prefer not to smoke, there now is the option of using an instrument called a vaporizer which allows one to inhale the cannabinoids free of the combustion products of the cannabis plant.
In what may be the first attempt to reestablish the place of cannabis in mainstream Western medicine, the National Organization for the Reform of Marijuana Laws (NORML) in 1972 petitioned the Bureau of Narcotics and Dangerous Drugs, later renamed the Drug Enforcement Administration (DEA), to transfer marijuana from Schedule I to II so that the research necessary for the Food and Drug Administration (FDA) approval could be undertaken. Without this approval it cannot be clinically researched nor can it be legally prescribed. As the proceedings continued, other parties joined, including the Physicians Association for AIDS Care. It was only in 1986, after many years of legal maneuvering, that the DEA acceded to the demand for public hearings required by law. During the hearings, which lasted two years, many patients and physicians testified and thousands of pages of documentation were introduced. In 1988 the DEA’s own Administrative Law Judge, Francis L. Young, declared in his opinion that marijuana in its natural form fulfilled the legal requirement of currently accepted medical use in treatment in the United States. He added that it was “one of the safest therapeutically active substances known to man.” His order that the marijuana plant be transferred to Schedule II was overruled, not by any medical authority, but by the DEA itself, which issued a final rejection of all pleas for reclassification in March 1992.
Meanwhile, growing demand forced the FDA to institute the Individual Treatment IND (commonly referred to as a Compassionate IND) for the use of physicians whose patients needed marijuana. The application process was made enormously complicated, and most physicians did not want to become involved, especially since many believed there was some stigma attached to prescribing marijuana. Between 1976 and 1988 the government reluctantly awarded about a half-dozen Compassionate INDs for the use of marijuana. In 1989 the FDA was deluged with new applications from people with AIDS, and the number granted rose to 34 within the year. In June 1991, the Public Health Service announced that the program would be suspended because it undercuts the Administration’s opposition to the use of illegal drugs. After that no new Compassionate IND’s were granted, and the program was discontinued in March 1992. Four patients are still receiving marijuana under the original program; for everyone else it is at the federal level an outlaw medicine.
Despite its federal illegality, beginning in 1996 with California’s passage of its Proposition 215, 19 other states and the District of Columbia have established legislation which makes it possible for patients suffering from a variety of disorders to use the drug legally with a recommendation from a physician. Unfortunately, because most of them are so restrictive in their specifications of which symptoms and syndromes may be lawfully treated with cannabis, many patients with legitimate claims to the therapeutic usefulness of this plant must continue to use it illegally and therefore endure the extra layer of anxiety imposed by its illegality. California and Colorado are the two states in which the largest number of patients for whom it would be medically useful have the freedom to access it legally. New Jersey appears to be shaping up as one of the most restrictive, and for that reason it is likely that only a small fraction of the pool of patients who would find marijuana to be as or more useful than the invariably more toxic conventional drugs it will displace will be allowed legal access to it. The framers of the New Jersey legislation may fear what they see as chaos in the distribution of medical marijuana in California and Colorado, a fear born of their concern that the more liberal parameters of medical use adopted in these states have allowed its access to many people who use it for other than strictly medical reasons.
Because so many people are now having an opportunity to observe relatives or friends who are successfully, safely and relatively inexpensively using marijuana as a medicine, it will not be long before an overwhelming majority of citizens demand the same rights. There are now six other states working on medical marijuana legislation; this is a reflection of recent polls which show that more than 70% of American citizens now support the legal availability of marijuana as a medicine. These additional states and their citizens will inadvertently become part of an ongoing large social experiment in how best to deal with the reinvention of the “cannabis as medicine” phenomenon. Already we have learned a great deal from this ongoing experiment; one of the most important lessons is that the states which have the more restricted and limited
medical indications for allowable use of marijuana as a medicine have the largest number of patients who are compelled to use it illegally, while those which are the least restricted with respect to allowable medical indications inadvertently provide it to many people who use it for other purposes.
Shortly after O’ Shaughnessy introduced cannabis as a new medicine, modern Western medicine (allopathic medicine) signaled its acceptance when it was entered into the various Western pharmacopeia in the mid-19th century. It was expected, certainly by the 1990s, that it would be readmitted as a legitimate medicine, given the mountain of largely anecdotal evidence which establishes both its efficacy and safety, and its potential (once free of the prohibition tariff) to be much less expensive than pharmaceutical industry products it will replace. The two major agencies of this resistance to its readmission are the US government and the medical/pharmaceutical establishment.
Today drugs must undergo rigorous, expensive and time-consuming research to win approval by the FDA before they can be marketed as medicines. The first step made in trying to move the federal government was to petition it to move cannabis from its Schedule I status in the Controlled Substances Act to Schedule II so that it would then be possible to do the kinds of controlled studies essential to the presentation of any new drug to the FDA for approval in accordance with the protocol used by the pharmaceutical industry. As noted above, the first attempt to petition the FDA and DEA to move marijuana to Schedule II was initiated in 1972 and after two decades of hearings and delays the DEA rejected all pleas for reclassification. Another two decades have passed and, with the exception of a handful of small-to-medium-sized randomized controlled trials of smoked cannabis in chronic pain, spasticity, and wasting syndrome, the federal government continues to block the possibility of demonstrating that marijuana could satisfy the FDA criteria for a safe and efficacious addition to the pharmacopeia by continuing to insist, against overwhelming evidence to the contrary, that it is properly placed in Schedule I. In actuality it is now clear that marijuana no more belongs in Schedule I than does aspirin.
The purpose of the FDA testing is to protect the consumer by establishing both safety and efficacy. First, the drug’s safety (or rather, limited toxicity) is established through animal and then human experiments. Next, double-blind controlled studies are conducted to determine whether the drug has more than a placebo effect and is more useful than an available drug for a particular symptom or syndrome. As the difference between drug and placebo may be small, large numbers of patients are often needed in these studies for a statistically significant effect. Medical and governmental authorities insist that before marijuana is made legally available to patients, this kind of study should be performed for each of the indications for which it is proposed to be used (labels). At the same time, the government refuses to reconsider its inappropriate assignment of marijuana to Schedule I, therein making it impossible, by imposing a tight and heavily controlled monopoly on research-approved cannabis production and distribution, to undertake the kind of studies presently demanded by the FDA for its reintegration into modern Western medicine.
But with the accumulation of an enormous amount of anecdotal evidence, it has now become doubtful whether these FDA rules should apply to marijuana. There is now little question about its safety. It has been used for thousands of years by millions of people with very little evidence of significant toxicity. Similarly, no further double-blind studies are needed to prove marijuana’s efficacy. Any astute clinician who has some knowledge of the accumulated clinical experience of patients who have used marijuana as a medicine knows that it is efficacious to some degree for many people with various symptoms and syndromes. Anecdotal evidence commands much less attention than it once did, yet it is the source of much of our knowledge of synthetic medicines as well as plant derivatives. Controlled experiments were not needed to recognize the therapeutic potential of chloral hydrate, barbiturates, aspirin, curare, insulin, or penicillin— pharmaceuticals introduced before the double-blind controlled study was invented.
Anecdotes present a problem that has always haunted medicine: the anecdotal fallacy or the fallacy of enumeration of favorable circumstances (counting the hits and ignoring the misses). If many people suffering from, say, muscle spasms caused by multiple sclerosis take marijuana and only a few get much better relief than they could get from conventional drugs, those few patients would stand out and come to our attention. They and their physicians would understandably be enthusiastic about marijuana and might proselytize for it. These people are not dishonest, but they are not dispassionate observers. Therefore, some may regard it as irresponsible to suggest on the basis of anecdotes that cannabis may help people with a variety of disorders. That might be a problem if cannabis were a dangerous drug but, in fact, it is remarkably safe. Even in the unlikely event that only a few people with multiple sclerosis find that it provides relief from muscle spasm, it can be argued that cannabis should be available to them because the risks are so small and it costs so little to produce.
The benefits of any medicine must be weighed against the risks. Fortunately, there is unusually good evidence on the potential health hazards of marijuana—far better than the evidence on most prescription drugs. Not only has cannabis been used for thousands of years by many millions of people, but there is much recent research on its safety inspired by the federal government’s interest in discovering toxic effects to justify its policy of prohibition. The potential dangers of marijuana when taken for pleasure and its possible usefulness as a medicine are historically and practically interrelated issues: historically, because the arguments used to justify the suppression of recreational use have had a disastrous influence on views of its medical potential; practically, because it is more likely to be safe as a medicine if it is relatively safe as a euphoriant. As the evidence makes it increasingly clear that cannabis is relatively benign, it is becoming more and more difficult to deny that a risk-benefit analysis now satisfies all requirements for medical use.
Penicillin was discovered in 1928 but the discovery was ignored by the medical establishment for more than a decade until the first clinical trial with six patients who suffered from a variety of infections; all were successfully treated. After this debut in 1941, penicillin rapidly earned the reputation as the wonder drug of the 1940s. It earned that reputation for three reasons: it was remarkably non-toxic, even at high doses; it could be produced inexpensively on a large scale; and it was extremely versatile, acting against microorganisms that cause a great variety of diseases, from pneumonia to syphilis. In all three respects cannabis suggests parallels: it is remarkably safe; once it is free of the prohibition tariff it will be inexpensive; and it is effective against a large number of symptoms and syndromes. Penicillin did not undergo modern FDA approval scrutiny because its safety and efficacy had been well established by the time the FDA adopted the present protocol for approving new drugs. Marijuana is now in the same position vis-à-vis the FDA; it has accumulated, both from recreational and medicinal use, more than enough evidence of its safety and efficacy.
As its reputation as a medicine grew, so did the demand for legal access. In 1996, California became the first state to provide legal (as far as the state was concerned) access for specified signs and symptoms. Over the next 17 years 19 other states and the District of Columbia followed suit, but the defined parameters of availability, particularly the rules for distribution and the medical reasons for which use would be allowed, have generally become more constricted. In these states the only involvement with the medical establishment is the requirement that the patient receive a note from a physician stating that he believes the patient’s condition would be helped by cannabis; these notes allow the patient to receive a state-issued medical marijuana registration card which may cost $100 or more annually. Each state establishes its own rules for the growing and dispensing of medical marijuana. These states now allow thousands of people to legally purchase a growing variety of marijuana products upon the presentation of these cards or, in some states, the physician’s letter to one of the state-sanctioned dispensaries. It is estimated that 2 1/2 to 3% of the residents of California are now credentialed to buy marijuana legally in what is estimated to be between a 1 1/2 to 2 1/2 billion dollar business. One has only to visit one of the California dispensaries to see how sophisticated this industry is becoming, with a range of newly developed cannabis products as well as newly invented delivery means. Beyond having perhaps several dozen or more different strains of herbal cannabis to choose from, there is a large choice of edible and even topical marijuana medications. The patient who wants to use a pipe, bong, vaporizer or vape stick will find a large and growing selection to choose from. There now exist a few laboratories equipped to measure the percentage of individual cannabinoids and terpenes, and to provide assurance against contamination with insecticides, fungi or bacteria. The rapidly increasing number of patients who are now seeking cannabis as a medicine is fueling a burgeoning medical marijuana enterprise which is becoming increasingly sophisticated. There are growers who are becoming more adept at breeding new strains which may be more beneficial to patients with particular needs, as for example the present effort to develop strains high in cannabidiol (CBD, a non-psychoactive cannabinoid).
Despite harassment by the federal authorities, especially in California and Colorado, all aspects of this alternative medicine, which is beginning to resemble a new school or philosophy of medicine, will continue to grow and become more sophisticated as it is embraced by more and more patients, legally or illegally. This new medicine arose from the past and the still growing collection of anecdotal evidence. It is now bolstered by the fundamental understandings in biology and physiology that have come from the discovery and study of the endogenous cannabinoid signaling system (the endocannabinoid system). All of this is developing outside of allopathic medicine; in what may be called “cannabinopathic medicine”. It joins other alternative schools of medicine such as naturopathic medicine, homeopathic medicine and osteopathic medicine. Cannabinopathic medicine is being practiced all over this country, openly in the states which have made it legal, and clandestinely in those which have yet to do so. Osteopathic medicine, which was first practiced in the latter part of the 19th century, has now moved so close to allopathic medicine in its education, training and practice that it has become integrated with allopathic medicine (modern Western medicine). In the early days of medical marijuana it was assumed that it would become integrated into Western medicine as a new therapeutic; thus the effort which began in 1972 to persuade the federal government to change its Controlled Substances Act Schedule I status to Schedule II as the essential first step toward collecting the kind of data necessary for the FDA’s medicinal drug approval process. The government has in the past made tentative moves in the direction of accepting the reality of marijuana’s medical capacities, including the now defunct Compassionate IND program and its mid-80s involvement with dronabinol, a pharmaceutical industry-developed synthetic THC (Marinol), which is the same 21 carbon molecule as the THC (tetrahydrocannabinol) produced by nature.
Today, even if it were free of its Schedule I chains, its path to legitimacy as a pharmaceutical faces other obstacles. A big one is the availability of funding for the kind of research which would allow it to be presented to the FDA. The cost of this research runs to upwards of $800 million per drug. Because, as a plant, it cannot be patented, the pharmaceutical companies have no interest in herbal marijuana. Only in the case of some orphan drugs does the government support these developmental costs. As noted above, an exception to this rule occurred in the early 1980s when the government provided major funding to a small pharmacedeutical company, Unimed, towards its development of the synthetic tetrahydrocannabinol THC (Marinol). Because it cannot be marketed as a Schedule I drug, the government placed it in Schedule II despite the fact that this THC is precisely the same 21 carbon molecule that is found in the naturally occurring THC in marijuana which it will not release from Schedule I. Several years later, because Marinol was not selling as well and was originally hoped, it was placed in the even less restrictive Schedule III. The government assumed that with Marinol’s legal availability it would then be possible to assert that there was no longer a need for medicinal marijuana as there was now a commercially available cannabinoid pharmaceutical product. The problem with this strategy became obvious to nearly every patient who tried to substitute Marinol for smoked or ingested marijuana: it simply did not work nearly as well as herbal marijuana. It is becoming increasingly clear that the salutary properties of marijuana do not reside exclusively in THC but are due to an ensemble effect of herbal components including THC, cannabadiol (CBD) and terpenes. The primary reason that some patients use Marinol today is because it is legal; it is as safe as herbal marijuana, but not nearly as efficacious.
The vast majority of people who use cannabis as a medicine must suffer the anxiety, uncertainty, and risk associated with obtaining and using an illegal substance. The responses of physicians, as indicated by patients’ stories, vary a great deal. With the exception of a small minority of physicians, their attitudes toward marijuana as a medicine generally range from outspokenly negative to varying degrees of skepticism; a few are hostile or contemptuous, some are indifferent or unconvinced, and a growing number offer at least some encouragement or moral support. Unfortunately, even the most sympathetic are either afraid to do more because of the law or are unable to provide advice because they have been misinformed about cannabis and simply know too little about its therapeutic value. Physicians of one and a half centuries ago knew much more about cannabis than do contemporary physicians, whose education about new drugs comes largely from the pharmaceutical industry. Today’s physicians are often introduced to therapeutic marijuana by their patients, but even those physicians who become educated about this drug may be afraid to recommend what they know or suspect to be the best treatment out of fear that they might lose their reputations, licenses, and careers. Even if marijuana were available as a Schedule II medicine, pharmacies would be reluctant to carry it and physicians would hesitate to prescribe it. Through computerized monitoring, the DEA could know who was receiving prescription marijuana and how much. It could identify physicians who, by its standards, prescribed cannabis too freely or for reasons it considered unacceptable. The potential for harassment would be extremely discouraging. Unlike other Schedule II drugs, such as cocaine and morphine, cannabis has many potential medical uses rather than just a few. Many people would undoubtedly try to persuade their doctors that they had a legitimate claim to a prescription. Doctors would not want the responsibility of making such decisions if they were constantly under threat of discipline by the DEA. Furthermore, many doctors would not consider prescribing cannabis at all because they are victims of the government’s misinformation campaign. Some still believe and promote such hoary myths as the notion that marijuana is addictive or leads to the use of more dangerous drugs.
Despite the growing appreciation of its safety and usefulness as a medicine there is, after more than three decades of effort, little hope that herbal marijuana will soon be integrated into modern Western medicine. And even if it were, there would be enormous problems in controlling the distribution of a controlled medicine which has now become an established and popular Western culture recreational drug The pharmaceutical industry will continue to develop cannabinoid products and the government will hypocritically make Controlled Substances Act scheduling accommodations, as they did with Marinol, to make them available as prescription drugs. Some of them will be useful and a few may, for specific symptoms or syndromes, be more useful than herbal marijuana, but it is unlikely that they will ever displace it; herbal marijuana will always provide more choice, be less expensive and more readily available. Because the commercial success of its cannabinoid products will vary directly with the severity of the prohibition, the pharmaceutical industry will predictably put even more pressure on the government to maintain or even strengthen its prohibition.
However, the realities of human need are incompatible with the demand for a legally enforceable distinction between medicine and all other uses of cannabis. Marijuana simply does not conform to the conceptual boundaries established by 20th century institutions. It is truly a sui generis substance; is there another relatively benign drug which is capable of heightening many pleasures, has a large and growing number of medical uses and has the potential to enhance some individual human capacities? The only workable way of realizing the potential of this remarkable substance, including its full medical potential, is to free it from the present dual set of regulations – – those that control prescription drugs in general and the special criminal laws that control psychoactive substances. These mutually reinforcing laws establish a set of social categories that strangle its uniquely multifaceted potential. The only way out is to cut the knot by giving marijuana the same status as alcohol – – legalizing it for adults for all uses and removing it entirely from both the medical and criminal control systems.
Perhaps in part because so many Americans have discovered for themselves that marijuana is both relatively benign and remarkably useful, moral consensus about the evil of cannabis is becoming uncertain and shallow. The authorities pretend that eliminating marijuana traffic is like eliminating slavery or piracy, or eradicating smallpox or malaria. The official federal government view is that everything possible has to be done to prevent everyone from ever using marijuana, even as a medicine. But there is also an informal lore of marijuana use that is far more tolerant. Many of the millions of cannabis users in this country not only disobey the drug laws but feel a principled lack of respect for them. They do not conceal their bitter resentment of laws that render them criminals. They believe that many people have been deceived by their government, and they have come to doubt that the “authorities” understand much about either the deleterious or the useful properties of this drug. This undercurrent of ambivalence and resistance in public attitudes towards marijuana leaves room for the possibility of change, especially since the costs of prohibition are so high and rising.
Because multifaceted marijuana is now here to stay as a very useful and safe medicine, as a superior recreational drug, and as an enhancer of a variety of human capacities, this more than 75-year-old destructive prohibition cannot endure much longer. It is reasonable to assume that had there never been a marijuana prohibition, smoked marijuana, because it is both more reliable and easier to titrate, would have displaced Cannabis Tincture as the cannabinoid medicine of choice. Without prohibition, marijuana would have become as easily accessible as aspirin. It would have provided the first opportunity for herbal marijuana to compete with pharmaceutical products and its success would have been assured. But now, even with the termination of the prohibition against herbal marijuana, which is now inevitable, will it regain its rightful place in modern medicine? Given the enormous influence of contemporary big Pharma on the medical establishment and the government, this is not so clear. It is presently rapidly growing as a very useful and safe medicine, which is being largely ignored by allopathic medicine. It is as though we are witnessing the birth of the new school of medicine – – – cannabinopathic medicine.
Invariably, when a newly discovered substance even hints at having therapeutic value, a pharmaceutical company will immediately do some preliminary testing to satisfy itself that it may be both safe and efficacious for certain symptoms and syndromes. Once satisfied that it does, it will, if it is not an in-house discovery, acquire it and then seek the 20 year new drug patent. Once it has the patent, it will undertake the protocol for developing the data which the FDA demands before it will allow the drug to be licensed for sale. Fulfilling the demands of this protocol may take upwards of $8,000,000 and as long as up to three years. FDA approval will then allow the company about 17 years to recover its developmental costs and earn a profit. This is the way most new drug products enter the pharmaceutical marketplace.
Needless to say, the pharmaceutical industry is aware of the therapeutic value of herbal cannabis and is increasingly devoting resources to the development of cannabinoid analogs or other products which can compete with herbal marijuana. The industry is mindful not just of the profits that such products would ensure, but as well the losses it will incur as many of its own products are displaced by the less expensive and less toxic herbal marijuana and its products. But the drug companies are stymied because it is not possible to patent a naturally occurring substance. They have produced several synthetic cannabinoids: dronabinol (Marinol) and nabilone (Cesamet), and what is best described as liquid marijuana (Sativex), which is a liquid solution of two (THC and CBD) naturally occurring cannabinoids in a patented delivery system. None of these products is as inexpensive or useful as ingested or smoked (or vaporized) herbal marijuana. Legality, not efficacy, is their major appeal. Patients who are sophisticated about cannabinopathic medicine and live in the growing number of states where it is legal to use herbal marijuana or its products generally prefer it to the pharmaceutical cannabinoids for a number of reasons: it is more efficacious, less toxic and less expensive; and also because when it is smoked or vaporized, it is very easy for the patient to titrate the precise dose that he/she requires.
The use of cannabis as a medicine continues to be illegal as far as the federal government is concerned despite the fact that 20 states have now approved its medical use for specified symptoms and syndromes; and there is every expectation that before long this will be the case in the majority of states. But because states arrogate to themselves the decisions about which symptoms and syndromes are allowed to be treated with marijuana, its legal availability as a medicine varies greatly from state to state. In some states, like New Jersey, its use as a medicine is so restrictive that few patients are able to avail themselves of it. On the other hand, while the regulations in California are much more liberal in allowing a wider variety of symptoms and syndromes which can be legally treated with cannabis, this also makes it easier to acquire by people who want to use it for purposes the authorities do not approve of. And given the large and growing number of medical uses for which cannabis can provide relief, it would be difficult if not impossible to codify them in regulations. In terms of its overall therapeutic utility, marijuana is at least as useful as aspirin; cannabis has both a broader therapeutic spectrum and a smaller risk of significant toxicity.
The present frustration that legal herbal cannabis is not medically generally available has some parallels to the history of the availability in the United States of lithium carbonate as a therapeutic in the treatment of bipolar disorder. In 1948, Dr. John Cade, an Australian psychiatrist, made a most important medical contribution when he discovered that lithium carbonate was a very useful mood stabilizer in the treatment of bipolar disorder. In the absence of any other drug which would as effectively deal with episodes of mania, the publication of this discovery was greeted with great enthusiasm. At the time of this discovery there were few treatments available to patients with this psychosis and most of these patients were treated with either electroconvulsive therapy or lobotomy. Elsewhere in the world where it attracted a great deal of attention as the first drug which could be effective in the treatment of this type of this disorder, lithium carbonate soon became available to psychiatrists and their patients, but not in the United States, causing considerable frustration to American psychiatrists and the unnecessarily prolonged suffering of patients and their families. It did not become available for prescription in the United States until 1970.
The enormous potential of lithium salt as a psychiatric therapeutic was, of course, known to the U.S. pharmaceutical industry from the time Cade published his ground-breaking paper in 1949. However, because it is a naturally-occurring substance and as such could not be patented, the pharmaceutical industry saw it as having no commercial value. Eventually the United States government, through its Orphan Drug Act, supported the testing that was essential for FDA approval. Its approval in 1970 made it possible for it to finally appear on the market in the United States. It was immediately adopted by allopathic medicine as a valuable drug in the treatment of bipolar disorder.
Inevitably, the number of states which have decided to ignore the federal government’s Reefer Madness view of cannabis and have allowed marijuana to be legally available as a medicine will continue to grow; and just as certainly so will the number of states which, like Washington and Colorado, have abandoned prohibition altogether and substituted regulations for responsible adult use. At the present time, there is an uneasy detente which makes for a lot of uncertainty particularly for cannabinopathic patients and the owners of the dispensaries from which they buy their medicine. That the federal government should cling to its outdated notions of cannabis is difficult to understand.
The recent history of both the growth of interest and use of marijuana as a medicine and the extraordinary rise in the number of citizens who believe that marijuana should now be legalized (according to a 2013 Gallup poll, legalization is now supported by 58%, 10% higher than it was one year earlier) have so undermined the federal government’s posture toward cannabis that it now appears inevitable that the prohibition will be repealed in the near future. It is possible that this will be preceded by the long overdue decision to free cannabis from Schedule I which defines it as a substance which is highly abusable, has no medical utility, and cannot be used safely even under the supervision of a physician. Either of these events will make it legally possible to do the large double-blind controlled studies which are required for approval as a legal therapeutic by the FDA. However, there is some questions as to whether they should or could be undertaken for several reasons. Physicians have always had available evidence of a different kind, whose value is often underestimated. Anecdotal evidence commands much less attention than it once did, yet it is the source of much of our knowledge of synthetic medicines as well as plant derivatives. Controlled experiments to determine both efficacy and toxicity were not needed to recognize the therapeutic potential of chloral hydrate, barbiturates, aspirin, curare, insulin, or penicillin. The anecdotal evidence which underlies the success of marijuana as a medicine exceeds by at least an order of magnitude that which allowed the above-mentioned drugs admittance to the pharmacopeia. Furthermore, it is questionable whether these studies will be undertaken for lack of a sponsor to provide the enormous funds which would be necessary.. It seems unlikely that the federal government would, any time in the near future, be willing to take a lithium-like approach to herbal marijuana even after the prohibition has been repealed. The pharmaceutical industry will not undertake such an endeavor because it is impossible for them to patent marijuana and, in any event, it would be worthless after the repeal of the prohibition. The 20 states which have now accepted medicinal marijuana and the two which have made it available for any use have obviously been convinced by this mountain of anecdotal evidence that herbal marijuana is both safe and efficacious. Some may regard it as irresponsible to suggest on the basis of anecdotes that cannabis may help people with a variety of disorders. That might be a problem if marijuana were a dangerous drug, but we now know that it is remarkably safe.
Perhaps the most interesting question about the future of cannabinopathic medicine is whether it will continue to develop on its own as an alternative medicine with its growing literature, newly developed strains, edible and other products, delivery devices, publications, experience and experts, or whether it will be absorbed into modern Western medicine much as did one branch of osteopathy. Presently, the only mandated connection of cannabinopathic medicine to allopathic medicine is the requirement by the states in which cannabis is legally available as a medicine for the patient to first present to the state authorities a letter from a physician stating that the patient has a need for cannabis in the treatment of a health problem specified in that particular state’s medical marijuana law. Not all physicians are willing to provide such a letter and many who do, know very little about cannabis. Unfortunately, among these physicians there are some who, for a fee, are willing to sign such a letter with little or no attempt to verify the presenting medical problem.
Medicine, as it is practiced in the United States today, is synergistically related to the pharmaceutical industry. While in medical school, students’ education in pharmacology has less to do with individual pharmaceutical products than it does with the principles of pharmacology. They learn much of what they know about specific pharmaceutical products in their post-medical school training in internships and residencies. They are introduced to new drugs through medical journals, both their papers and drug advertisements. Physicians are regularly visited by pharmaceutical company salespeople (“detail men or women”) who provide them with formulaic accounts of the usefulness of a particular pharmaceutical and samples of the new drug along with other pharmaceuticals they may personally desire . They also provide many physicians with gifts, such as golfing fees, travel expenses and even money.
At the present time and for the foreseeable future herbal marijuana and its products are the gold standard of cannabinopathic medicine. Let us consider what might be involved in integrating it into allopathic medicine at this time. The first requirement is that the FDA approve herbal marijuana as a medicine. One can argue, however, that FDA approval is superfluous where cannabis as a medicine is concerned. Drugs must undergo the above-described rigorous, expensive, and time-consuming tests before granted FDA approval for marketing as medicines. The purpose is to protect the consumer by establishing safety and efficacy and to regulate the commercial distribution of drug company products and protect the public against false or misleading claims about their efficacy and safety. The drug is generally a single synthetic chemical pharmaceutical company has acquired or developed and patented. It submits an application to the FDA and tests it, first for safety in animals and then for clinical safety and efficacy. The company must present evidence from double-blind controlled studies demonstrating that the drug is more effective than a placebo. Case reports, expert opinion, and clinical experience are not considered sufficient. But there is considerable doubt whether the FDA rules should apply to cannabis as there is no question regarding its safety. Thousands of years of experience have demonstrated its medical value, and government efforts through the National Institute of Drug Abuse to establish a level of toxicity sufficient to support its prohibition have instead provided a record of its safety.
Even if it were legally and practically possible to conduct the various phased studies to win FDA approval, where would the money to finance the studies come from? New medicines are almost invariably introduced by drug companies that spend many millions of dollars on the development of each product. They are willing to undertake these costs only because of the large profits they anticipate during the 20 year they own the patent, and marijuana cannot be patented. For this and other reasons it is unlikely that the pharmaceutical industry will ever develop herbal marijuana as an officially recognized medicine via this route. It is not even necessary to establish this kind of certification. The modern FDA protocol is not needed to establish a risk-benefit estimate for a drug with the therapeutic history of marijuana. To impose this protocol on cannabis would be like making the same demand of aspirin, which was accepted as a medicine more than 60 years before the advent of the double-blind controlled study. Many years of experience have demonstrated that aspirin has many uses and limited toxicity, yet today it could not be marshaled through the FDA approval process. The patent has long since expired and without the incentive to underwrite this substantial cost of this modern seal of approval. Other reasons for doubting the possibility of official approval include today’s antismoking climate and most importantly, the widespread use of cannabis for purposes that lack government approbation.
To understand some of the obstacles to this approach, consider the effects of granting marijuana legitimacy as a medicine while prohibiting it for any other use. Imagine that somehow the FDA approved herbal marijuana for the treatment of Crohn’s disease (the “labeled use”) affirming that cannabis is safe and effective as a treatment for Crohn’s disease and physicians may then prescribe it for this condition. This would present unique problems for the DEA which is charged with monitoring the use of psychoactive drugs because when a drug is approved for one medical condition, physicians are generally free to write off-label prescriptions – – that is, to prescribe it for other conditions as well. Knowledgeable physicians would want to prescribe it for some patients who suffered from multiple sclerosis, migraine headaches, compulsive disorders, spastic symptoms, depression, premenstrual syndrome and many other conditions for which the use of marijuana is well-established by a plethora of anecdotal evidence. They are also free to prescribe it for “conditions” for which there is little or no evidence of efficacy.
If the benefit of a drug is very large and the risk very small, the medicine is distributed “over-the-counter” (OTC). These drugs are considered so useful and safe that patients are allowed to use their own judgment without a physician’s permission or advise. Thus, today anybody can buy and use aspirin for any purpose. This is permissible because aspirin is considered extremely safe; it takes “only” 1000 to 2000 lives a year in the United States. One can also purchase remarkably versatile drugs such as ibuprofen (Advil) and other non—steroidal anti-inflammatory drugs (NSAIDs) OTC as well, because they are considered safe; “only” of about 10,000 Americans lose their lives to this class of drugs annually. Acetaminophen (Tylenol), another useful OTC drug, is responsible for about 10% of cases of end-stage renal disease. The public is allowed to purchase many herbal remedies whose dangers and efficacy remain unaddressed. Comparing these drugs with marijuana today, there is no doubt that it is a remarkably safe drug and if it regains its place in the official pharmacopeia it would rank as a serious contender for the title of least toxic substance in that compendium.
Then there is the question of who will provide the cannabis. The federal government now provides marijuana from its farm in Mississippi to the four surviving patients covered by the now-discontinued Compassionate IND program. Surely the government could not and would not produce marijuana for the many thousands of patients who need it, any more than it does for other prescription drugs. If production is contracted out, will the farmers have to enclose their fields with security fences and protect them with security guards? How will the marijuana be distributed; if through pharmacies how would they provide secure facilities capable of keeping fresh supplies? Would the government need to control the price of pharmaceutical marijuana: not too high lest patients are tempted to buy it on the street or grow their own; not too low lest people with marginal or fictitious “medical” conditions beseech their doctors for prescriptions? What about the parallel problems with potency? When urine tests are demanded of workers, what would emerge as the bureaucratic and other costs of identifying those who use marijuana legally as a medicine, as distinguished from those who use it for other purposes?
To realize the full potential of cannabis as a medicine within the setting of the present prohibition, one would have to address all these problems and more. A delivery system that would successfully navigate this minefield would prove cumbersome, inefficient, and bureaucratically top-heavy. Government and licensing boards would insist on tight restrictions, challenging physicians as though cannabis was a dangerous drug every time is used for any new patient or purpose. Constant conflict would exist, with one of two outcomes: patients would not receive all the benefits they should, or they would obtain the benefits by abandoning the legal system for the black market or their own gardens and closets.
Meanwhile, a number of drug companies, attracted by the obvious medicinal properties of marijuana, are pursuing what one might refer to as the “pharmaceuticalization” of marijuana, the development of synthetic prescription drugs derived from cannabis: isolated individual cannabinoids; synthetic cannabinoids; and cannabinoid -analogs. The question is whether these developments will make herbal marijuana medically obsolete. Many of these new products may prove useful and safe enough for commercial development. It is uncertain, however, whether pharmaceutical companies will find them worth the enormous developmental costs. Some may prove worthwhile – – for example, an inverse agonist that reduces appetite (the opposite of the marijuana effect called the “ “munchies”) might be highly lucrative – – but for most specific symptoms, analogs or combinations of analogs are unlikely to emerge as more useful than natural cannabis.
In the end, the commercial success of any pharmaceutical industry cannabinoid product will depend on how vigorously the prohibition against marijuana is enforced. It is safe to predict the new analogs and extracts would cost much more than whole smoked or ingested marijuana, even at the inflated prices imposed by the prohibition tariff. It is doubtful that pharmaceutical companies would seem interested in developing these products if they have to compete with natural marijuana on a level playing field. The most common reason for using Marinol or Sativex is the illegality of marijuana, and many patients choose to ignore the law for reasons of efficacy and costs. The number of arrests on marijuana charges has steadily increased, yet patients continue to use smoked marijuana as a medicine. One wonders whether any level of enforcement would compel enough compliance with the law to embolden drug companies to commit the many millions of dollars it would take to develop new cannabinoid products. Pharmaceutical companies may develop some useful cannabinoid products, but it is unlikely that this pharmaceuticalization will displace natural marijuana for most medical purposes.
It is also clear that the realities of human need are incompatible with the demand for a legally enforceable distinction between medicine and all other uses of cannabis. Marijuana use simply does not conform to the conceptual boundaries established by 20th century institutions. It enhances many pleasures and it has many medical uses, but even these two categories are not the only relevant one. The kind of therapy often used to ease everyday discomforts does not fit any such scheme. In many cases, what lay people do in prescribing marijuana for themselves is not very different from what physicians do when they provide prescriptions for psychoactive or other drugs. The only workable way of realizing the full potential of this remarkable substance, including its full medical potential, is to free it from the dual set of regulations: those which control prescription drugs in general and the special criminal laws that control psychoactive substances. These mutually reinforcing laws establish a set of social categories that strangle marijuana’s uniquely multifaceted potential. The only way out is to cut the knot by giving marijuana the same status as alcohol; legalizing it for adults for all uses, and removing it entirely from both the medical and criminal control systems.
In the face of the ongoing prohibition and the standoffish attitude of allopathic medicine, cannabinopathic medicine will continue to grow and develop. It will continue to collect data to help it discover new medicinal uses; to develop new strains to more effectively target particular symptoms and illnesses; to generate new modifications of herbal products to facilitate topical application, ingestion and smoking or vaporization; and it will continue to train people in the newest and best ways to use these products. In states which have not legalized the use of cannabis as a medicine, all aspects of the practice of cannabinopathic medicine will continue to be subterranean. In the states which have already made it more or less legally available as a medicine (depending on the comprehensiveness of the list of symptoms and syndromes for which the state allows it to be used) cannabinopathic practice continues to be only partially transparent. Because it is unlikely that any state will ever include such problems as pre-menstrual syndrome or intractable hiccups, for example, as indications for which cannabis may be useful, patients suffering from these and many other disorders will have to continue to use cannabis covertly or wait until after the prohibition comes to an end, as it recently has in Colorado and Washington. This is consistent with my belief that it will be impossible to realize the full potential of this plant as a medicine, not to speak of the other ways in which it is useful, in the setting of prohibition.
Two powerful forces are now colliding: the growing acceptance of cannabinopathic medicine and the proscription against any use of the plant marijuana, medical or non-medical. As a result, two distribution systems will emerge for medical cannabis: the conventional model of pharmacy-filled prescriptions for FDA-approved cannabinoid medicines, and a model closer to the distribution of alternative herbal medicines. The only difference, albeit an enormous one, will be the continued illegality of whole smoked or ingested cannabis. In any case, increasing medical use by either distribution pathway will inevitably make a great number of people familiar with cannabis and its derivatives. As they learn that its harmfulness has been greatly exaggerated and its usefulness under- estimated, the pressure will increase for drastic changes in the way that we as a society deal with this drug.
