Dr. Lester Grinspoon: Whither Cannabinopathic Medicine

CANNABIS CULTURE – Given all the excitement and activity surrounding cannabis as a medicine over the last few decades, one might think that this is a new therapeutic discovery. Actually, its use as a medicine is ancient.

A native of Central Asia, cannabis (hemp) may have been cultivated as long ago as 10,000 years. 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 it 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 by her court physician to Queen Victoria for the treatment of her painful pre-menstrual cramps. 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. It was admitted to the United States Pharmacopeia in 1850, and commercial cannabis preparations soon became widely distributed through drugstores.

The decline in the usage of Cannabis Indica began toward the end of the 19th 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. (The fact that cannabis could be smoked was unknown at that time and so it was delivered as an alcoholic solution.)

Another reason for the decline of interest in 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 and the first barbiturate. 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. Many people die from aspirin-induced bleeding each year in the United States, and barbiturates were, 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 (predecessor to today’s Drug Enforcement Administration) 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 behavior, psychosis, and mental deterioration. 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 use. Almost incidentally the law made medical use of cannabis difficult because of the extensive paperwork and fees required. 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.

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 desirability 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 23 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. It continues to be confined to Schedule 1 of the Comprehensive Drug Abuse Prevention and Control 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. It cannot be legally sold as a medicine because the US government will not remove cannabis from Schedule 1; furthermore, its inclusion in Schedule 1 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.

In 1967, I began my studies of the scientific, medical and other literature with the goal of providing a reasonably objective summary of the data which underlay its prohibition. Much to my surprise, I found no credible medical or scientific basis for the justification of the prohibition which at that time was responsible for about 300,000 arrests annually. The assertion that it is a very toxic drug was based on old and new myths. In fact, one of the many exceptional features of this drug is its remarkably limited toxicity. Compared to aspirin, which people are free to purchase and use without the advice or prescription of a physician, cannabis is much safer: there are well over 1000 deaths annually from aspirin in the United States alone, whereas there has never been a death anywhere from marijuana. In fact, by the time cannabis regains its rightful place in the pharmacopoeia around the world, it will be seen as one of the safest drugs in those compendiums. Moreover, it will eventually be hailed as a “wonder drug” just as penicillin was in the 1940s. Penicillin achieved this reputation because (1) it was remarkably non-toxic, (2) it was, once it was produced on an economy of scale, quite inexpensive, and (3) it was effective in the treatment of a variety of infectious diseases. Similarly, cannabis (1) is exceptionally safe, and (2) once freed of the prohibition tariff, will be significantly less expensive than the conventional pharmaceuticals it replaces while (3) its already impressive medical versatility continues to expand.

Given these characteristics, it should come as no surprise that its use as a medicine, legally or illegally, with or without a recommendation from a physician, is now growing exponentially around the world. Marijuana is here to stay; there can no longer be any doubt that it is not just another transient drug fad. Like alcohol, it has become a part of Western culture, a culture which is now trying to find appropriate social, legal and medical accommodations for this new kid on the block.

In the United States, 23 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 each state arrogates to itself the right to define 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 is the most restrictive, and I would guess that only a small fraction of the pool of patients in these states who would find marijuana to be as or more useful than the invariably more toxic conventional drugs it will displace are allowed legal access to it. Like legislatures in many other states, 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 medicinal reasons.

If this is correct, it is consistent with my view 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 this destructive prohibition. But this is rapidly changing as in 2013 both Colorado and Washington repealed, as far as the state is concerned, the prohibition of cannabis for anyone over the age of 21 making it possible for patients in these two states to obtain it without medical consultation. And, this year Alaska, Oregon and the district of Columbia joined them.

During the last three years we have arrested annually approximately 750,000 people; we are now gradually realizing after arresting over 24 million marijuana users since the 1960s, most of them young and 89% for mere possession, that “making war” against cannabis does not work anymore now than it did for alcohol during the days of the Volstead Act. Many people are expressing their impatience with the federal government’s intransigence as it obdurately maintains its dual archaic positions that “marijuana is harmful” and that it “is not a medicine”.

The states that have made it possible for at least some patients to use cannabis legally as a medicine are inadvertently constructing a large social experiment in how best to deal with the reinvention of the “cannabis as medicine” phenomenon, while at the same time sending a powerful message to the federal government. Each of these state actions, plus those that have now freed themselves of the prohibition altogether, have taken a slice out of the extraordinary popular delusion, cannabinophobia.

There are presently some states which are in the process of enacting medical marijuana legislation which would restrict the legal availability of cannabis to the single cannabinoid cannabidiol (CBD) a policy which makes little sense. CBD is one of the more than 60 cannabinoids in the plant but it is, in itself, not nearly as useful as a medicine. The most useful medical strains are those which contain tetrahydrocannabinol (THC) and CBD in the presence of terpinoids. Patients who wish to have some degree of psychoactive effect (often for its antidepressant capacity or because they find the “high” pleasant) will choose a high THC/low CBD strain. Similarly, those who wish to avoid the psychoactive effects while maximizing the therapeutic capacity will seek strains wherein that ratio is reversed. These two cannabinoids along with the terpinoids behave in what I refer to as the ensemble phenomenon to provide the best therapeutic effect.

Many of those who staunchly defend sustaining the prohibition against marijuana believe we do not yet know enough about cannabis to be able to make the kinds of decisions which are now necessary. Despite the US government’s three-quarter century-long prohibition of marijuana and its confinement to Schedule 1, it is nonetheless one of the most studied therapeutically active substances in history. At this time a keyword search on PebMed reveals that there are over 20,000 published studies or reviews in the scientific literature referencing the cannabis plant and its cannabinoids, and the number is growing almost exponentially; half of them were published within the past five years. Over 1,400 peer-reviewed papers were published in 2013 alone.

These studies reveal that marijuana and its active constituents, the cannabinoids and terpinoids are safe and effective therapeutic and/or recreational compounds. Unlike alcohol and many prescription or over-the-counter medications, cannabinoids are virtually non-toxic to the health of cells and organs, and they are incapable of causing the user to experience a fatal overdose; unlike opioids or ethanol, cannabinoids are not central nervous system depressants and cannot cause respiratory failure. In fact, a 2008 meta-analysis published in the Journal of the Canadian Medical Association reported that cannabis-based drugs were associated with virtually no elevated incidences of serious side-effects in over 30 years of investigative use.

Cannabinopathic medicine, because it has developed so rapidly since the late 90s, has provided many patients and the people to whom they matter the opportunity to observe for themselves that cannabis is both relatively benign and remarkably useful. This growing new increment of people who have personal experience with cannabis may be contributing significantly to the observation that the moral consensus about the evil of marijuana is becoming uncertain and shallow. Conservative authorities pretend that eliminating cannabis traffic is like eliminating slavery or piracy, or eradicating smallpox or malaria. The official view, at least as far as the federal government is concerned, is that everything possible has to be done to prevent everyone from ever using marihuana, even as a medicine. But there is also an informal lore of marihuana use that is far more tolerant. Many of the millions of cannabis users around the world not only disobey the drug laws but feel a principled lack of respect for them. They do not conceal their bitter yes yes resentment of laws that render them criminals. They believe that many people have been deceived by their governments, and they have come to doubt that the “authorities” understand much about either the deleterious or the useful properties of the drug. This undercurrent of ambivalence and resistance in public attitudes towards marihuana laws leaves room for the possibility of change, especially since the costs of prohibition are all so high and rising.

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 simply does not conform to the conceptual boundaries established by twentieth-century institutions. It is truly a sui generis substance; is there another relatively non-toxic 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 capacities? The only workable way of realizing the full 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 marihuana the same status as alcohol – legalizing it for adults for all uses and removing it entirely from the medical and criminal control systems.

It is now clear that we know as much or more about cannabis than we know about many if not most prescription pharmaceuticals. And we most certainly now know enough about its limited toxicity and remarkable medical potential to readmit it as a significant contribution to the pharmacopeia of allopathic (or modern Western) medicine. Shortly after O Shaughnessy introduced cannabis as a new medicine, Western medicine signaled its acceptance when it was entered into the various Western pharmacopoeia in the mid-19th century. It was expected, certainly by the 1990s, that it would be readmitted as a legitimate medicine given the growth of a 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 the 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.

The government will, sooner or later, abandon its archaic view of cannabis and free it from this costly prohibition and thereby free the millions of people who are over the age of 21 who want to use it. This will not, however, ensure its rightful place in the pharmacopeia of 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.” As modern medicine continues to ignore 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.

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, the identification of the endo-cannabinoid system, newly developed strains, the development of new and faster breeding techniques, the inventions of new delivery devices, publications, experience and experts, or whether it will, at least to some extent, be absorbed into modern Western medicine.

To the extent that cannabinopathic medicine continues to exist as an entity it will be adjunctive to allopathic medicine as it will be limited to therapy, mostly as a palliative, and possibly as a preventative. Presently it’s only connection 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 document 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 document 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 document with little or no attempt to verify either the presenting medical problem or the appropriateness of cannabis for that symptom or syndrome. While most physicians presently know too little about the use of cannabis as a medicine to competently sign this document, there is a relatively small but rapidly growing number sufficiently versed in its use to provide medical authority with their signature; they can also offer recommendations and advice to patients concerning its use.

The recent history of both the growth of interest in and use of marijuana as a medicine, and the extraordinary rise in the number of citizens who believe that marijuana should now be legalized 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.

According to a 2013 Gallup poll, legalization is now supported by 58%, 10% higher than it was one year earlier. It is possible that this will be preceded by the long overdue decision to free cannabis from Schedule I. 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 question 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 an Orphan Drug Law approach to herbal marijuana even after the prohibition has been repealed. The pharmaceutical industry will not undertake such an endeavor because it is impossible to patent marijuana and, in any event, it would be worthless after the repeal of the prohibition. The 23 states which have now accepted medicinal marijuana and the four (plus the district of Columbia) 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.

Two powerful forces are now colliding: the growing acceptance of cannabinopathic medicine and the proscription against any use of the plant marijuana, medical or nonmedical. As a result, two distribution systems are now emerging for cannabinopathic medicine: 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.

Lester Grinspoon, M.D. is Associate Professor of Psychiatry, emeritus, at Harvard Medical School and the author of Marihuana Reconsidered and (with James B Bakalar) Marijuana, the Forbidden Medicine.