Pubdate: Wed, 28 Apr 1999 Source: Journal of the American Medical Association (US) Copyright: 1999 American Medical Association. Contact: http://www.ama-assn.org/public/journals/jama/ Author: Mike Mitka THERAPEUTIC MARIJUANA USE SUPPORTED WHILE THOROUGH PROPOSED STUDY DONE Advocates for the medical use of marijuana received support recently from Institute of Medicine (IOM), recommendations that clinical trials and drug development should proceed. But its acceptance into the general population of prescribed drugs appears to be years away-if it happens at all. The coinvestigators of the report, Marijuana and Medicine: Assessing the Science Base, said advances in cannabinoid science over the last 16 years offer opportunities for the development of medical marijuana. The report summarizes and analyzes what is known about the medical use of marijuana, emphasizing evidence-based medicine. The investigators said the data suggest marijuana may help with pain relief, nausea, and appetite stimulation. Still, there are downsides to marijuana, said John A. Benson, Jr, MD, coprincipal investigator of the report and dean and professor of medicine emeritus at Oregon Health Sciences University School of Medicine in Portland. "Marijuana's potential as medicine is seriously undermined by the fact that people smoke it, thereby increasing their chance of cancer, lung damage, and problems with pregnancies, including low birth weight," Benson said. "For that reason, we do not recommend smoking marijuana for long-term medical use. While we see a future in the development of chemically defined cannabinoid drugs, we see little future in smoked marijuana as a medicine." Cannabinoids are the group of compounds related to 9-tetrahydrocannabinol (THC), the primary psychoactive ingredient in marijuana. TWO POINTS OF VIEW Quick to pick up on the smoking comments was the White House Office of National Drug Control Policy (ONDCP), whose director, Gen Barry R. McCaffrey, has been critical of legalizing marijuana for medical use. In a statement, the ONDCP said it was "delighted that science is the basis of the discussion of this issue," and said it would carefully study the recommendations and conclusions of the IOM report. The ONDCP added, however, "We note in the report's conclusion that 'the future of cannabinoid drugs lies not in smoked marijuana, but in chemically defined drugs that act on the cannabinoid systems that are a natural component of human physiology.' " The IOM report is the result of a request from the ONDCP in January 1997 to review the scientific evidence to assess the potential health benefits and risks of marijuana and its constituent cannabinoids. [An IOM report says marijuana may have a future in medicine, but not in a smoked form. Credit: Tony Stone ] On the other side of the legalization issue is the Marijuana Policy Project, which said the IOM report presents ample scientific evidence confirming the benefits of marijuana as medicine and proves McCaffrey wrong on his statements over the years in opposition to legalization. Marijuana was not found effective in several areas in which anecdotal evidence said otherwise. The report stated that data did not support using marijuana to treat glaucoma. It noted that smoked marijuana can reduce some of the eye pressure associated with glaucoma, but only for a short time, and that its benefit did not outweigh the hazards associated with regular long-term use. There is also little evidence for marijuana's potential for treating movement disorders like Parkinson disease or Huntington disease, although some studies were presented showing THC reduced, to varying degrees, muscle spasticity associated with multiple sclerosis. REPORT RECOMMENDATIONS The IOM report investigators made six recommendations: Research should continue into the physiological effects of synthetic and plant-derived cannabinoids and the natural function of cannabinoids found in the body. Because different cannabinoids appear to have different effects, research should include but not be restricted to effects attributable to THC alone. Clinical trials of cannabinoid drugs for symptom management should be conducted with the goal of developing rapid-onset, reliable, and safe delivery systems. Psychological effects of cannabinoids, such as anxiety reduction and sedation, that can influence medical benefits should be evaluated in clinical trials. Studies to define the individual health risks of smoking marijuana should be conducted, particularly among populations in which marijuana use is prevalent. Clinical trials of marijuana use for medical purposes should be conducted under the following limited circumstances: trials should involve only short-term use (less than 6 months); be conducted in patients with conditions for which there is reasonable expectation of efficacy; be approved by institutional review boards; and collect data about efficacy. Short-term use of smoked marijuana for patients with debilitating symptoms (such as intractable pain or vomiting) must meet the following conditions: failure of all approved medications to provide relief has been documented; the symptoms can reasonably be expected to be relieved by rapid-onset cannabinoid drugs; such treatment is administered under medical supervision in a manner that allows for assessment of treatment effectiveness; and use involves an oversight strategy, comparable to an institutional review board process, that could provide guidance within 24 hours of a submission by a physician to provide marijuana to a patient for a specified use. Stanley J. Watson, Jr, MD, PhD, coprincipal investigator and codirector and research scientist at the Mental Health Research Institute, University of Michigan, said the goal of medical marijuana clinical trials should be to develop an inhaler to deliver the drug because capsule or pill forms take too long to work. "There are many symptoms for which a quick-acting drug is ideal, such as pain, nausea, and vomiting," Watson said. "For that reason, we recommend development of a rapid-onset but nonsmoked delivery system, such as an inhaler. Something like an inhaler would deliver precise doses without the health problems associated with smoking." - --- MAP posted-by: Derek Rea