[I.M. Boggled]

Source:
"American Council on Science and Health" Publication Date: April 2001

Reefer Sanity
By Lester Grinspoon, M.D.
Associate Professor Emeritus of Psychiatry at Harvard Medical School.


Cannabis—
also known as Cannabis sativa, hemp, and marijuana—first became a part of Western pharmacopoeias 150 years ago.
In 1839, W. B. O'Shaughnessy of the Medical College of Calcutta observed its use in traditional Indian treatment of various disorders and found that tincture of hemp was effective as an analgesic, an anticonvulsant, and a muscle relaxant.

In the next several decades, many papers on cannabis appeared in Western medical journals.
And it was in widespread medical use in the West, especially as an analgesic and a hypnotic (sleep inducer), until the early 1900s.
Symptoms and conditions for which cannabis was found helpful included asthma, convulsions, dysmenorrhea, labor pain, neuralgia, rheumatism, and tetanus.
In the heyday of Western medical use of cannabis, physicians in the West generally administered it as a tincture (alcoholic solution), which was typically referred to as "tincture of hemp," "tincture of cannabis," or "Cannabis indica" (the species name "indica" means "of or relating to India").

Physicians did not know that smoking cannabis would have brought relief sooner than did ingesting its tincture.
Moreover, the variance of tincture of hemp, in terms of potency and bioavailability, was considerable, and no reliable bioassay techniques existed.
Nevertheless, physicians prescribed it without much concern about overdosing or side effects.
On the other hand, they with good reason considered cannabis less reliable as an analgesic than opium or its derivatives. And unlike such drugs, the bioactive principles of cannabis are insoluble in water and are thus totally unsuitable for administration by injection.


Reefer Madness and the Re-medicalizing of Marijuana

At the turn of the 19th century, both aspirin (the first manmade analgesic) and the first barbiturate became available. These drugs attracted physicians immediately, because their potencies were fixed and their administration was simple. From the 1920s, as the medical attractiveness of cannabis continued to fall, interest in it as an aid to recreation—and a disinformation campaign against such use—grew. In 1937 came the first draconian federal enactment against marijuana use: the Marijuana Tax Act, which made prescribing marijuana so cumbersome that most physicians abandoned its medical use. And with an editorial published in The Journal of the American Medical Association in 1945 began the medical establishment's becoming one of the most effective agents of cannabis prohibition.

The revival of cannabis as a medicinal began in the early 1970s, when several young subjects of new modes of cancer chemotherapy found that smoking marijuana was much more effective than were conventional treatments in relieving nausea and vomiting. These are side effects of some anticancer drugs and as such can be intense and lasting. Word of these patients' experience with marijuana spread quickly over the cancer-treatment grapevine. By the middle of the decade the capacity of marijuana to lower pressure inside the eyeball was observed, and patients with glaucoma (which is characterized by abnormally high intraocular pressure) began to try it as a treatment for this disorder. And as the AIDS epidemic snowballed, many patients wasting because of HIV infection found that smoking marijuana was both more effective in preventing weight loss and less troubling in terms of side effects than were conventional treatments for this life-threatening symptom.

These uses of cannabis have led to wider health-related folk uses of the plant, and its utility in the symptomatic treatment of convulsive disorders, migraine, insomnia, and dysmenorrhea has been rediscovered. Indeed, cannabis has currently been found useful against some 30 symptoms and syndromes. And many patients regard smoking marijuana as more effective, and as having a smaller downside, than conventional treatments for those of their health problems against which they are using the drug. Osteo-arthritis is a case in point. In the 19th century tincture of cannabis was often used to treat the pain of osteoarthritis. Shortly after its introduction, aspirin—one of the early non-steroidal anti-inflammatory drugs, or NSAIDs—displaced cannabis as the treatment of choice for osteoarthritic and many other types of non-intense pain. But NSAIDs are responsible for the loss of about 10,000 American lives annually, while cannabis has never been demonstrably responsible for the death of anyone using it—irrespective of one's reason for using it. Moreover, the pain relief that smoking cannabis brings can be better than that of NSAIDs, and unlike NSAIDs, cannabis can improve the mood of those who use it. Thus, it should surprise no one that many patients with osteoarthritis treat its pain with cannabis.

"Pot-pourri"

Apparently, the number of Americans who understand the medical utility of cannabis has increased in the last few years. This positive interest has been marked politically by the passage in nine states of initiatives or legislation to permit limited use of cannabis as a medicine. The enactment of such legislation has led to a clash with federal authorities who recently were blasting the medical usage of marijuana as a hoax. Under public pressure to acknowledge the medical potential of marijuana, Barry McCaffrey—the director of the Office of National Drug Policy—authorized a review by the Institute of Medicine (IOM) of the National Academy of Sciences. In its report of this review, published in March 1999, the IOM admitted, restrainedly, that cannabis had medical value.

But the IOM stated that smoking is too dangerous a mode of drug delivery for cannabis—a conclusion based on an overestimate of the toxicity of marijuana smoke. Among its major recommendations was that patients with "debilitating symptoms (such as intractable pain or vomiting)" be permitted to smoke marijuana only after all conventional treatment options have failed—and then, only for six months and under "an oversight strategy comparable to an institutional review board process." Following this recommendation would make the legal use of cannabis unworkable in most clinical settings. It seems that the IOM would have patients who find cannabis healthful when they smoke it await, for years, introduction of a mode of drug delivery for cannabis that does not involve smoking the drug. Devices are in development that take advantage of the fact that cannabinoids vaporize at temperatures below the ignition point of marijuana.

The Institute of Medicine report treats marijuana—a versatile drug with a long history and low toxicity—as if it were comparable to thalidomide, a drug whose possible side effects include phocomelia (a severe birth defect) and whose medical utility is limited to Hansen's disease (leprosy) and multiple myeloma (a type of bone cancer).
But at least the report confirms that even U.S. government officials recognize the medical utility of cannabis.
The development of cannabinoids into lawful treatment options for various symptoms and conditions appears inevitable.
Chiefly in question is how cannabinoids will be administered.

Schedules and Agendas

It was in the early 1970s that I first considered the issue of legalizing the use of marijuana in medical practice.
Then, I assumed that the cannabis used medically would be the same as that used recreationally, which typically consisted of the dried flowering tops of female Cannabis indica plants.
I assumed so partly because such material had minimal toxicity and would have been inexpensive if it weren't prohibited.
I thought the main obstacle to medical use of marijuana was its classification in Schedule I of the Comprehensive Drug Abuse and Control Act of 1970, which describes it as (a) having a high potential for being abused, (b) having no accepted medical use, and (c) lacking safety for administration even under medical supervision. American physicians could not (and cannot) legally prescribe Schedule I drugs, which include heroin and LSD.
In those days, I believed that making marijuana a Schedule II drug would greatly facilitate the legal availability of marijuana as a medicine.
I had come to believe that prohibition of marijuana, not the drug itself, was responsible for the greatest harm in using marijuana recreationally.
But I saw the prohibition of recreational use of marijuana as an issue independent from that of its medical use.
The use of opiates and cocaine as restricted medicines was lawful, while all other uses were unlawful.
I reasoned that the cannabis situation should be no different.
I thought that categorizing marijuana as a Schedule II drug would fast result in the eager pursuit of clinical research on it in the U.S.
More than 25 years later, I came to doubt this.


The extensive government-supported campaign of the last three decades to generate and publicize evidence that cannabis is toxic enough to call for its drastic prohibition has furnished a record of safety for the drug that is more encouraging than the safety record of most FDA-approved medicines.

The Drug Enforcement Administration (DEA) treats Schedule II drugs, which include cocaine and morphine, as having some medical utility but also a high potential for being abused. Thus, making marijuana a Schedule II drug would not be an adequate measure for making it available as a prescription medication. Among the prerequisites for FDA approval of any drug as a prescription product is rigorous, expensive, time-consuming testing of the drug.

The FDA's approval process was designed to regulate the commercial distribution of pharmaceutical company products and to defend the public against false or misleading claims about pharmaceutical product safety and efficacy. In general, the product subjected to this process is a single manmade chemical that a pharmaceutical company has developed and patented. According to this process, the pharmaceutical company submits an application to the FDA; tests its product for safety in laboratory animals and then for safety and efficacy in humans; and presents evidence from double-blind controlled studies that the product is significantly more effective than a placebo—and at least as effective as drugs legally on the market in the U.S.—against the ailment or symptom for which the product was developed. Case studies, the opinions of experts, and clinical experience are unimportant in this process. The cost to pharmaceutical companies for putting a product completely through it exceeds $200 million per drug. It is unlikely that any marijuana product designed to be smoked will ever become an officially recognized medicine by this means.

The extensive government-supported campaign of the last three decades to generate and publicize evidence that cannabis is toxic enough to call for its drastic prohibition has furnished a record of safety for the drug that is more encouraging than the safety record of most FDA-approved medicines. To require that subjecting smokable cannabis to the process described above precede its legal medical use is like requiring the same for aspirin—which was in widely accepted medical use in Europe and the U.S. more than 60 years before the advent of the double-blind controlled study. That aspirin is versatile and of low toxicity has been known clinically for many years. But marshaling aspirin through the FDA's drug-approval process would be improbable—only because its patent has expired. Cannabis, too, is un-patentable, and, under the current protocol, there is little or no incentive to invest in seeking FDA approval of anything unpatentable. So the only potential funder for subjecting canna-bis to the FDA's approval process is the federal government of the United States, which—in light of America's anti-smoking climate and the prevalence in the U.S. of nonmedical uses of cannabis that the government condemns—is extremely unlikely to fund such studies.

Stumbling Blocks to Establishing the Dichotomization of Marijuana Use

Permitting particular medical uses of marijuana while trying to prevent any other use would be difficult. Then there is the question of how cannabis would be provided. Under a program in phaseout, the federal government supplies marijuana grown on its farm in Mississippi to eight patients. But the federal government has never been in the business of producing any prescription drug for thousands of patients and is very unlikely to do so, especially if the drug is marijuana. If the government contracted with nongovernmental farmers to produce marijuana, security might be costly. Other important questions include those stated below.

* If pharmacies filled cannabis prescriptions, protecting the drug in terms of freshness and thievery would become an extra burden for them.

* The federal government might delimit prices for pharmaceutical marijuana.
If the prices to patients are too high, they might provoke patients' buying cannabis from pushers or growing it on their own.
If they're too low, they might prompt consumers' besieging physicians for cannabis prescriptions on the purported basis of dubious or trifling health problems.

* Testing an individual's urine for controlled substances or illicit drugs yields no information on whether the individual used the chemical legally.


. . . [A]gainst any definite symptom, using cannabinoid analogs . . . is unlikely to be more effective than smoking cannabis.

In the current socio-political climate, to legitimize cannabis as a prescription medicine in the U.S. would prerequire exploring each of the matters stated above, and others. And any system of cannabis legitimization that might emerge from such an exploration would be cumbersome, inefficient, and top-heavy.
Governmental bodies and medical licensing boards would demand tight restrictions on the prescribing of cannabis, challenging any physician who does so whenever a patient first receives a prescription for it or receives the prescription on a diagnostic basis new to him. Consequently, many patients likely to benefit from the medical use of marijuana would settle for their benefiting sub-optimally from its medical availability, whereas many other patients of this kind would obtain the drug from the black market or from their own gardens.

Reeferoids

According to one of the major current proposals that bear on making the dichotomization of cannabis use effective, lawful cannabis
prescriptions would be restricted to isolated natural cannabinoids (THC and other derivatives of Cannabis sativa), manmade cannabinoids, and analogs (close structural relatives) of cannabinoids.
The IOM report states that "if there is any future for marijuana as a medicine," it lies in cannabinoids and analogs of such.
It further states: "Therefore, the purpose of clinical trials of smoked marijuana would not be to develop marijuana as a licensed drug, but such trials could be a first step towards the development of rapid-onset, non-smoked cannabinoid delivery systems."

In certain circumstances, taking isolated cannabinoids and/or analogs of them may be more advantageous than smoking or ingesting marijuana.
For example, ingesting cannabidiol without other constituents of marijuana may be more effective in reducing anxiety than is ingesting it with THC—a cannabinoid that sometimes causes anxiety. Analogs of cannabinoids may prove more medically useful than smoked marijuana at least partly because they can be safely administered into veins.
An example is dexanabinol (HU-211).
In 15-20 percent of cases of thrombotic or embolic stroke, loss of consciousness ensues. Such also ensues in some persons who sustain a severe blow to the head resulting in a brain syndrome. In both of these situations, dexanabinol has proved protective of brain cells—and that it can be safely introduced into veins is a big plus.
It is presumable that other cannabinoid analogs have advantages over the dried leaves and/or dried flowers of Cannabis sativa.
And any cannabinoid or analog thereof that has none of the effects that make marijuana desirable as an aid to recreation would not fall under the constraints of the Comprehensive Drug Abuse and Control Act.
Further, cannabinoids and their analogs could be administered in a way that does not entail smoking anything (e.g., as an aerosol or by suppository or transdermal patch).
Inhalation is a very effective means of administering cannabinoids, and except for injection there are no means of getting cannabinoid analogs to function sooner.

Vaporization devices can separate cannabinoids in marijuana from burnt marijuana, and mass production would make such devices inexpensive. It is dubitable, however, whether the availability of nonsmokable cannabis-related medicinals would render pot smoking unfit or superfluous as a medical treatment.

Moreover, although doubtless there could be many such medicinals useful enough and safe enough for commercial development, it is not certain that pharmaceutical companies would consider most of them worthy of the costs of seeking FDA approval. It might be lucrative to subject to this approval process, say, a cannabinoid that could reduce the desire to eat. But against any definite symptom, using cannabinoid analogs—singly or in combination—is unlikely to be more effective than smoking cannabis. For example, on the whole, patients evidently find smoking marijuana more effective than taking manmade THC (known as Marinol or Dronabinol), which has been available for years.

Under the current system, any analog without a therapeutic ratio (a safety rating) acceptable to the FDA would not become legally available outside medical research. Because evidently no one has ever died directly because of ingesting or smoking marijuana, its therapeutic ratio is unknown, but from animal-experiment data it has been extrapolated at 20,000 to 40,000. It is unlikely that any new cannabinoid analog would rate higher. Indeed, such an analog might be less safe than smoked marijuana—simply because one can take cannabis-related chemicals more efficiently by swallowing pills than by smoking marijuana.

Psychoactive cannabinoid analogs would fall under the constraints of the Comprehensive Drug Abuse and Control Act. The more restrictive the law is concerning a specific type of drug, the less likely a pharmaceutical company will develop—and the less likely a physician will prescribe—any drug of that type. Unimed attained FDA approval of the exorbitantly expensive drug Marinol relatively inexpensively only because Marinol was identical to the marijuana constituent THC and the U.S. government had underwritten much of the cost. And although Marinol has been re-categorized from Schedule II to Schedule III, it is almost certain that, for fear of the DEA, physicians will continue refusing to prescribe it.

Ultimately, whether any cannabis-related medicinal becomes a commercial success will depend on the degree to which authorities try to enforce the ban on traditional marijuana. Almost certainly, such medicinals will cost much more than does traditional marijuana, even with its prohibition-inflated prices. I doubt that any pharmaceutical company would be inclined to develop cannabic products if it had to compete on a level playing field with street vendors of marijuana. The general illegality of marijuana in the U.S. is the commonest reason for taking Marinol. Many patients smoke street marijuana instead of taking Marinol because they find smoked marijuana more effective and because marijuana is less expensive than Marinol.

Ultimately, whether any cannabis-related medicinal becomes a commercial success will depend on the degree to which authorities try to enforce the ban on traditional marijuana.

There is little doubt that pharmaceutical companies will develop useful cannabis-related products, some of which may not fall under the constraints of the Comprehen-sive Drug Abuse and Control Act. But, in my opinion, it is unlikely that such products will replace traditional marijuana as a medicine. Many Americans use it as such despite that arrests on marijuana-related charges in the U.S. have steadily increased to 700,000 annually.

The Bottom Line

Two major forces are in opposition: the growing acceptance of cannabis as a remedy worthy of mainstream medical approval, and the blanket proscription* of marijuana.

Two very different distribution pathways for cannabis-related products may emerge from this conflict: one conventional, with pharmacies filling prescriptions for FDA-approved cannabis-related products; the other similar to that of ethnic medicinals and herbal and other dietary supplements, except that marijuana would continue to be prohibited.

The coexistence of these pathways would result in an increase both in the medical use of cannabis and in the number of persons who are familiar with cannabis and its derivatives.

In my opinion, the American public would eventually learn that the harmfulness of marijuana was greatly exaggerated and its utility underestimated—and would therefore demand drastic change in how institutions and regulatory agencies deal with its use.

[*Proscription ... is the public identification and official condemnation of enemies of the state.]

[I.M. Boggled]

Op-Ed
The Baltimore Sun.

Is Marijuana Medicine?
Decision to smoke pot shouldn't involve doctor
By Jeffrey A. Schaler
Originally published May 12, 2003

THE ATTEMPT by drug policy reformers in Maryland to legalize marijuana for medicinal purposes is bad medicine masquerading as harm reduction.

Marijuana is no more a medicine than is water. It is neither safe nor dangerous, good nor bad. Marijuana is a plant that people have a right to grow, purchase, sell, own and ingest as they see fit.

Anything can be labeled a medicine, just as anything can be diagnosed as a disease - provided the people applying the label and diagnosis have the authority to do so. It all depends on who says something is medicine, who is using it and for what purposes it is being used. Is water a medicine? Yes and no. If a person is dehydrated, water becomes a life-saving medicine.

Most of the time water is not medicine, despite the fact it is essential to our survival and consumed regularly. Is water safe or dangerous? People can safely drink and swim in it. When people consume too much water they may suffer from electrolyte imbalance. A person can drown in water. Does that make it dangerous? No. It all depends on how you use it.

Is water good or bad? The question is meaningless. Just as dangerous and safe are not properties we can detect through water analysis, there is no goodness or badness we can detect in water. Water is just water. A priest sees "holy" water. An atheist sees "plain" water. Doctors and scientists cannot tell the difference, only priests and theologians can. How can they tell the difference between holy water and secular water? By who uses the water, by the ways in which they use it, by the way it has been blessed and consecrated.

The same is true for marijuana. Medical marijuana advocates argue that marijuana is a panacea. Prohibitionists argue that marijuana is a panapathogen (something that causes illness). Who is right? Neither. It all depends on how you use it. Marijuana is no more medicine than water is medicine. And marijuana is just as dangerous as water.

So why all the fuss about marijuana as medicine? The Maryland General Assembly passed a bill legalizing marijuana for medical purposes. Could it be because those who hold that marijuana is medicine, safe and a panacea are not far away from those who think marijuana is bad, dangerous and a panapathogen? Both sides attribute nonexistent qualities to marijuana.

Is the fuss because people who want to smoke marijuana need it to treat any number of diseases such as glaucoma or multiple sclerosis or the nausea that often accompanies chemotherapy? Of course not. Plenty of effective drugs are available for these diseases and conditions.

Medical marijuana advocates hide behind sick people in order to get marijuana without penalty in order to get high. They believe the laws against marijuana possession and use are inhumane - and the laws are inhumane, but not for the reasons they state. The medical marijuana pushers lie about the drug just as much as the prohibitionists do.

The medicinal marijuana argument is as red a herring as they come. People have a right to use marijuana or any drug in any way they see fit - as medicine, as religious ritual, or simply to make themselves feel good, as long as they don't hurt anyone else in the process.

However, the medical marijuana peddlers are not satisfied with such an honest and principled stand. They trust doctors to make lifestyle decisions for them. They want doctors in charge of who gives them their recreational drugs. Medicinal marijuana peddlers fear autonomy and embrace the paternalism of the therapeutic state.

Medicalizing marijuana, like medicalizing behavior, is bad medicine. Two wrongs don't make a right. The best solution to the harm created by drug prohibition is repeal of drug prohibition in its entirety. And that is a federal issue, not a state one.

Jeffrey A. Schaler teaches psychology at Johns Hopkins University and is the author of "Addiction Is a Choice" (Open Court Publishers, 2001).