From Marijuana to Medicine

Voters in several states across the nation were recently asked to decide whether marijuana can be used as a medicine. They made their decisions on the basis of medical anecdotes, beliefs about the dangers of illicit drugs, and a smattering of inconclusive science. In order to help policymakers and the public make better-informed decisions, the White House Office of National Drug Control Policy asked the Institute of Medicine (IOM) to review the scientific evidence and assess the potential health benefits and risks of marijuana.

The IOM report, Marijuana and Medicine: Assessing the Science Base, released in March 1999, found that marijuana’s active components are potentially effective in treating pain, nausea and vomiting, AIDS-related loss of appetite, and other symptoms and should be tested rigorously in clinical trials. The therapeutic effects of smoked marijuana are typically modest, and in most cases there are more effective medicines. But a subpopulation of patients do not respond well to other medications and have no effective alternative to smoking marijuana.

In addition to its therapeutic effect and its ability to create a sense of well-being or euphoria, marijuana produces a variety of biological effects, many of which are undesirable or dangerous. It can reduce control over movement and cause occasional disorientation and other unpleasant feelings. Smoking marijuana is associated with increased risk of cancer, lung damage, and problems with pregnancies, such as low birth weight. In addition, some marijuana users can develop dependence, though withdrawal symptoms are relatively mild and short-lived.

Because the chronic use of marijuana can have negative effects, the benefits should be weighed against the risks. For example, marijuana should not be used as a treatment for glaucoma, 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 such as Parkinson’s disease or Huntington’s disease. But in general, the adverse effects of marijuana use are within the range of those tolerated for other medications. 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. Nor is there convincing evidence to justify the concern that sanctioning the medical use of marijuana might increase its use among the general population, particularly if marijuana were regulated as closely as other medications that have the potential to be abused.

In some limited situations, smoked marijuana should be tested in short-term trials of no more than six months that are approved by institutional review boards and involve only patients that are most likely to benefit. And because marijuana’s psychological effects, such as anxiety reduction and sedation, are probably important determinants of potential therapeutic value, psychological factors need to be closely evaluated in the clinical trials. The goal of these trials should not be to develop marijuana as a licensed drug. Rather, they should be a stepping stone to the development of new drugs related to the compounds found in marijuana and of safe delivery systems. The effects of marijuana derive from a group of compounds known as cannabinoids, which include tetrahydrocannabinol (THC), the primary psychoactive ingredient of marijuana. Related compounds occur naturally in the body, where they are involved in pain, control of movement, and memory. Cannabinoids may also play a role in the immune system, although that role remains unclear. Knowledge of cannabinoid biology has progressed rapidly in recent years, making it possible for the IOM to draw some science-based conclusions about the medical usefulness of marijuana. Basic research has revealed a variety of cellular and brain pathways through which potentially therapeutic drugs could act on cannabinoid receptor systems. Such drugs might be derived from plant-based cannabinoids, from compounds that occur naturally in the body, or even from other drugs that act on the cannabinoid system. Because different cannabinoids appear to have different effects, cannabinoid research should include, but not be restricted to, effects attributable to THC.

Most of the identified health risks of marijuana use are related to smoke, not to the cannabinoids that produce the benefits. Smoking is a primitive drug delivery system. The one advantage of smoking is that it provides a rapid-onset drug effect. The effects of smoked marijuana are felt within minutes, which is ideal for the treatment of pain or nausea. If marijuana is to become a component of conventional medicine, it is essential that we develop a rapid-onset cannabinoid delivery system that is safer and more effective than smoking crude plant material. 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.

The only cannabinoid-based drug on the market is Marinol. It is approved by the U.S. Food and Drug Administration for nausea and vomiting associated with chemotherapy and for loss of appetite that leads to serious weight loss among people with AIDS, but it takes about an hour to take effect. Other cannabinoid-based drugs will become available only if public investment is made in cannabinoid drug research or if the private sector has enough incentive to develop and market such drugs. Although marijuana abuse is a serious concern, it should be not be confused with exploration of the possible therapeutic benefits of cannabinoids. Prevention of drug abuse and promotion of medically useful cannabinoid drugs are not incompatible.