and in some cases outright malignancies—in isolated human and animal lung cells. Similar alterations have been detected in the actual lung cells of marijuana smokers and at even higher levels among those who also smoked tobacco.

An especially convincing study evaluated changes in blood cells taken from pregnant women who were exclusive smokers of marijuana and also from their babies after they were born.6 In a class of white blood cells called lymphocytes, the researchers found significantly more DNA aberrations of a type linked to cancer development as compared with lymphocytes from nonsmoking women and their newborns. In previous studies the same group of investigators had found similar changes in the DNA of tobacco smokers, indicating that the substances responsible for this damage are present in both marijuana smoke and tobacco smoke.

Marijuana smoking has also been associated with increased mortality among men with AIDS. This finding is especially important since such patients comprise the largest group of medical marijuana users in the United States. Several factors may contribute to this trend, which is still largely unexplained. It may be that people who use marijuana also tend to engage in risky sexual behavior or intravenous drug use, either of which puts them at higher risk for developing AIDS, but it is also likely that smoking marijuana adds to the burden that HIV places on the immune system. HIV-seropositive individuals who use marijuana regularly appear to be at increased risk of opportunistic infections and Kaposi's sarcoma; for those who smoke more than one-half pack of cigarettes per day, the risk is somewhat lower. If smoking marijuana indeed makes AIDS patients sicker, it remains to be determined whether smoke, cannabinoids, or both are to blame (see Chapter 5).

THE ROLE OF CANNABINOIDS

The vast majority of studies on the physiological consequences of marijuana use have focused on smoking. However, a few researchers have directly evaluated the effects of cannabinoids on isolated cells, experimental animals, and human subjects. Most such studies have examined one of three areas of po-



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