In January 1997, the Institute of Medicine (IOM) was asked to conduct a review of the scientific evidence to assess the potential health benefits and risks of marijuana and its constituent cannabinoids. This request came as a result of State “medical marijuana” initiatives in California, Arizona, Alaska, Colorado, Nevada, Oregon, and Washington. The three focal concerns in evaluating the medical use of marijuana are the evaluation of the effects of isolated cannabinoids, the risks associated with the medical use of marijuana, and the use of smoked marijuana. Information was gathered through scientific workshops, site visits to cannabis buyers’ clubs and HIV/AIDS clinics, analysis of the relevant scientific literature, and extensive consultation with biomedical and social scientists. It was concluded that the different cannabinoid receptor types found in the body appear to play different roles in normal human physiology. Scientific data indicate the potential therapeutic value of cannabinoid drugs, primarily THC, for pain relief, control of nausea and vomiting, and appetite stimulation. Smoked marijuana is a crude THC delivery system that also delivers harmful substances. The psychological effects of cannabinoids such as anxiety reduction and sedation, which can influence medical benefits, should be evaluated in clinical trials. Studies suggest that marijuana smoke is an important risk factor in the development of respiratory disease. A distinctive marijuana withdrawal syndrome has been identified but it is mild and short-lived. The syndrome includes restlessness, irritability, mild agitation, insomnia, sleep EEG disturbance, nausea, and cramping. Data on drug use progression neither support nor refute the suggestion that medical availability would increase drug abuse. Research should continue into the physiological effects of synthetic and plant-derived cannabinoids. The individual health risks of smoking marijuana should be studied. Clinical trials of cannabinoid drugs for symptom management should be conducted, along with trials of marijuana use for medical purposes.