Clinical Trials, Drug Development Should Proceed, Experts Advise
WASHINGTON -- Marijuana's active components are potentially effective in treating pain, nausea, the anorexia of AIDS wasting, and other symptoms, and should be tested rigorously in clinical trials, according to a new report from the Institute of Medicine (IOM). Such trials should be carried out in parallel with the development of new delivery mechanisms for the drug that are safe, fast-acting, and reliable, but do not involve inhaling harmful smoke, the report says. Moreover, it adds, clinical trials of marijuana use should be approved by institutional review boards, and should involve only short-term use among patients who are most likely to benefit from treatment.
"Marijuana has potential as medicine, but it is undermined by the fact that patients must inhale harmful smoke," said Stanley Watson, co-principal investigator of the IOM study, and co-director and research scientist at the Mental Health Research Institute, University of Michigan, Ann Arbor. "Until researchers develop a safe and effective delivery system, caregivers must consider the health problems that can result from smoking when deciding whether to recommend marijuana to patients."
Voters in Alaska, Arizona, Colorado, Nevada, Oregon, and Washington approved referenda in 1998 in support of the legal medical use of marijuana; California passed such an initiative in 1996. Public opinion on medical use of marijuana has been sharply divided. To help illuminate the policy debate, the IOM examined all relevant scientific evidence and found "substantial consensus" about the drug's potential effectiveness, as well as the health problems it can cause.
Marijuana is a powerful drug that produces a variety of biological effects. While the most common effect is euphoria, it also can lower a user's control over movement and cause occasional disorientation and other unpleasant feelings. Some chronic users can develop dependence on marijuana, though withdrawal symptoms are relatively mild and short-lived.
The usefulness of medical marijuana is limited by the harmful effects of smoking, which can increase a person's risk of cancer, lung damage, and problems with pregnancies, such as low birth weight. Therefore, smoking marijuana should only be recommended for terminally ill patients, or those with debilitating symptoms that do not respond to approved medications, the report says. Beyond the harmful effects from smoking, however, the range of problems associated with marijuana is not out of line with those of substances used in other medicines.
"Marijuana's medical effects are generally modest, and for most symptoms there are more effective medicines already available on the market," said co-principal investigator John Benson Jr., dean and professor of medicine emeritus, Oregon Health Sciences University School of Medicine, Portland. "For patients who do not respond well to other medications, however, short-term marijuana use appears to be suitable in treating conditions like chemotherapy-induced nausea and vomiting, or the wasting caused by AIDS."
Data do not support the contention that marijuana should be used to treat glaucoma, which is one of its most frequently cited medical applications. Smoked marijuana can reduce some of the eye pressure associated with glaucoma, but only for a short period of time. These short-term effects do not outweigh the hazards associated with regular long-term use of the drug. Also, with the exception of muscle spasms in multiple sclerosis, there is little evidence of its potential for treating movement disorders like Parkinson's disease or Huntington's disease, the report says.
For people with chronic conditions and no alternative to smoking marijuana, one approach would be to permit them to smoke marijuana on an experimental basis, fully informing them that they are experimental subjects and are using a harmful drug delivery system. Their condition also should be closely monitored and documented under medical supervision, which would increase what is known about the risks and benefits of medical marijuana use. For these and other patients, clinical trials should be designed to study the psychological effects of the compounds in marijuana, such as anxiety reduction and sedation, which the report says are probably important determinants of the drugs' potential therapeutic value.
Future Drug Development
The effects of marijuana derive from a group of compounds known as cannabinoids, including THC, the primary psychoactive ingredient of marijuana. Some compounds act on cannabinoid receptors that occur naturally in the body, where they are involved in pain, control of movement, and memory. Cannabinoids also may play a role in the immune system, though that role remains unclear.
Knowledge of cannabinoid biology has progressed rapidly in recent years, pointing the way to new, potentially promising avenues for drug development. Basic research has revealed a variety of cellular pathways through which potentially therapeutic drugs could act on cannabinoid receptor systems. Such drugs might include chemical derivatives of plant-derived cannabinoids, of those compounds that occur naturally in the body, or even of other drugs that act on the cannabinoid system.
The only cannabinoid-based drug on the market, Marinol, is THC in pill form. It is approved by the FDA for nausea and vomiting associated with chemotherapy, as well as for anorexia and weight loss associated with AIDS.
For drug development, cannabinoid compounds that are produced in the laboratory are preferable to plant products because they deliver a consistent dose and are made under controlled conditions. Research should continue into the physiological effects of both synthetic and plant-derived compounds and the natural function of those found in the body, the report says. New drugs will only be developed from marijuana's compounds if public investments are made in research, or if the private sector has enough incentives to develop and market such drugs.
In addition to the medical questions, the IOM was asked to assess other issues related to marijuana use. The report says that although marijuana use often precedes the use of harder drugs, there is no conclusive evidence that marijuana acts as a "gateway" drug that actually causes people to make this progression. Also, there is no evidence that approving the medical use of marijuana would increase its use among the general population, particularly if marijuana were regulated as closely as other medications with the potential to be abused.
The study was funded by the Office of the National Drug Control Policy, Executive Office of the President. The Institute of Medicine is a private, non-profit organization that provides health policy advice under a congressional charter granted to the National Academy of Sciences.
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