Medical Marijuana Verdict Elusive Despite Study, Debate

So stated William C. Woodward, M.D., J.D., legislative counsel to the AMA, in testimony in 1937 before the House Ways and Means Committee on the“ Marijuana Taxation Bill,” which would have taxed physicians who prescribed—and pharmacies that dispensed—cannabis.

(The bill passed, and in 1942 “cannabis” was officially removed from the U.S. Pharmacopeia.)

Seventy years after Woodward's testimony, whether research has proven“ substantial medical uses” for cannabis—either smoked in the form of the marijuana plant or taken in some other form—still appears to be a matter of passionate debate.

Thirteen states have passed laws to make marijuana more accessible for medical use. Many physicians and patients cite anecdotal evidence of the efficacy of cannabis for chemotherapy-related nausea, AIDS-related wasting, neuropathic pain, and other conditions; and a body of randomized controlled trials exists—mostly with relatively small samples and short follow-up times—documenting the benefits of cannabis for discrete conditions.

The American College of Physicians, among other groups, has called for reclassification of marijuana under the Controlled Substances Act from a Schedule I drug—under which it is deemed to have high abuse potential and no proven medical uses—to another schedule that would make it more available to researchers and clinicians.

On the opposing side are many physicians, including psychiatrists and addiction specialists, who say that research on cannabis, especially its long-term effects, is not sufficient to warrant rescheduling; that legalization would lead to greater abuse—by nonpatients in the general population, if not by patients; and that the medical community should proceed with great caution before declaring marijuana “safe.”

At the meeting of the AMA's House of Delegates last November, a resolution to advocate for rescheduling marijuana was the subject of unusually lengthy and passionate debate, only to be sent to the AMA's Council on Science and Public Health for a report back to the House and the AMA Board of Trustees (Psychiatric News, January 2).

Council chair and past APA President Carolyn Robinowitz, M.D., said she could not comment on the issue prior to the council's deliberations except that “there seem to be more opinions than data.”

She said, “The council will look at the available evidence and consider it carefully, and present—to the extent that it is possible—an evidence-based report to the house.”

Studies Indicate Some Acute Benefit

To Sunil Aggarwal, Ph.D., the verdict is already in.

Aggarwal is a third-year medical student at the University of Washington School of Medicine and a fellow in the Medical Scientist Training Program. His doctoral dissertation, titled “The Medical Geography of Cannabinoid Botanicals in Washington State: Access, Delivery, and Distress,” discussed the successful use of medical marijuana or cannabinoid botanicals by 176 chronically and critically ill patients in Washington state.

(The term “cannabinoids” refers to any of the substances that are structurally related to tetrahydrocannabinol, or THC, the psychoactive ingredient in marijuana.)

At the AMA meeting, Aggarwal spoke to the Section Council on Psychiatry and asserted that since 2001—when the House of Delegates last voted to retain the Schedule I status of marijuana pending the outcome of research—at least 10 randomized, controlled trials had been completed on the use of cannabis for chronic neuropathic pain of multiple etiologies, appetite and weight loss in HIV/AIDS, spasticity in multiple sclerosis, and severe nausea.

In each of these studies, researchers used a federal-government supply of marijuana grown in Mississippi.

Aggarwal told psychiatrists at the meeting that the total body of literature on the subject shows “that cannabinoids, of which cannabis contains roughly 100 ... have activity at the body's cannabinoid receptors and have many distinct pharmacologic properties, including analgesic, antiemetic, antispasmodic, antioxidative, neuroprotective, antidepressant, anxiolytic, and anti-inflammatory properties, as well as glial cell modulation and tumor growth regulation.”

The 10 randomized controlled trials published since 2001 have relatively small numbers—four had sample sizes of under 20 subjects, and the largest had 62. And all were looking only at acute effects.

A meta-analysis of studies looking at longer-term effects published in the July 2003 Journal of the International Neuropsychological Society found that few studies on nonacute neurocognitive effects met current research standards, but the studies that do exist suggest neurocognitive risks may be minimal.

“Our results indicate that there might be decrements in the ability to learn and remember new information in chronic users, whereas other cognitive abilities are unaffected,” the analysis concluded.“ However, from a neurocognitive standpoint, the small magnitude of these effect sizes suggests that if cannabis compounds are found to have therapeutic value, they may have an acceptable margin of safety under the more limited conditions of exposure that would likely obtain in a medical setting.”

But for addiction psychiatrists like Stuart Gitlow, M.D., M.P.H., the question is far from resolved. “Do the benefits outweigh the risks?” he asked in an interview with Psychiatric News.“ We don't have anything in the literature to suggest that the answer is yes. None of the damage that has been shown to result from marijuana use is evident in a short-term observation.”

Gitlow said he is not opposed to marijuana's being used individually in discrete situations, such as end-of-life care. But the question of legalizing marijuana for medical uses, he said, cannot be disentangled from the larger social context in which marijuana is widely used—addictively by many—for recreational purposes.

He added, “At the individual level, there may not be a problem, but when you look at it from a population basis, it's a different story. We know from experience that when opioids, stimulants, and sedatives are present in the home, they frequently find their way to people who aren't prescribed the drug.”

Making Marijuana Accessible for Research

Yet the individual cases can be emotionally compelling. Said Aggarawal,“ If you see someone suffering from neuropathic pain and there is no opioid that is helping, but you know that cannabinoids have a unique therapeutic effect on this type of pain, are you going to let the person suffer because his neighbor uses marijuana recreationally to enhance listening to music? Morally, I fall on the side of treating.”

On the question of whether legalization of marijuana for medical uses would increase potential for drug abuse, a 1999 Institute of Medicine (IOM) report (see Original article: IOM Report Still Sets Standard on Medical Marijuana) is agnostic.“ [P]resent data on drug use progression neither support nor refute the suggestion that medical availability would increase drug abuse,” the IOM report concluded.

The report also noted, “This question is beyond the issues normally considered for medical uses of drugs and should not be a factor in evaluating the therapeutic potential of marijuana or cannabinoids.”

Perhaps the most enduring conclusion from the IOM report is the need for more research—the one point on which everyone agrees. Gitlow said he looks for some provision to make marijuana accessible to researchers without changing the schedule status for the general population.

“We need controlled trials for an extended period of time, because many of the effects are not going to show up in an eight-week trial,” Gitlow said. “Ideally, this would be research in a controlled setting without making the drug accessible to the public at large. The first step is therefore to figure out the marijuana ingredient providing benefit and then determine a safe method of dosing that ingredient. We can't jump to the end of the process without first going through the necessary intermediate steps.”

An abstract of “Nonacute (Residual) Side Effects of Cannabis Use: A Meta-Analytic Study” is posted at<www.ncbi.nlm.nih.gov/pubmed/12901774>.▪