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drugs other than marijuana,7,129 and it is not unexpected that genetic factors play a role in the marijuana experience, including the likelihood of abuse. A study of over 8,000 male twins listed in the Vietnam Era Twin Registry indicated that genes have a statistically significant influence on whether a person finds the effects of marijuana pleasant.97 Not surprisingly, people who found marijuana to be pleasurable used it more often than those who found it unpleasant. The study suggested that, although social influences play an important role in the initiation of use, individual differences—perhaps associated with the brain's reward system—influence whether a person will continue using marijuana. Similar results were found in a study of female twins.86 Family and social environment strongly influenced the likelihood of ever using marijuana but had little effect on the likelihood of heavy use or abuse. The latter were more influenced by genetic factors. Those results are consistent with the finding that the degree to which rats find THC rewarding is genetically based.92

In summary, although few marijuana users develop dependence, some do. But they appear to be less likely to do so than users of other drugs (including alcohol and nicotine), and marijuana dependence appears to be less severe than dependence on other drugs. Drug dependence is more prevalent in some sectors of the population than others, but no group has been identified as particularly vulnerable to the drug-specific effects of marijuana. Adolescents, especially troubled ones, and people with psychiatric disorders (including substance abuse) appear to be more likely than the general population to become dependent on marijuana.

If marijuana or cannabinoid drugs were approved for therapeutic uses, it would be important to consider the possibility of dependence, particularly for patients at high risk for substance dependence. Some controlled substances that are approved medications produce dependence after long-term use; this, however, is a normal part of patient management and does not generally present undue risk to the patient.

Progression from Marijuana to Other Drugs

The fear that marijuana use might cause, as opposed to merely precede, the use of drugs that are more harmful is of great concern. To judge from comments submitted to the IOM study team, it appears to be of greater concern than the harms directly related to marijuana itself. The discussion that marijuana is a "gateway" drug implicitly recognizes that other illicit drugs might inflict greater damage to health or social relations than marijuana. Although the scientific literature generally discusses drug use progression between a variety of drug classes, including alcohol and tobacco, the public discussion has focused on marijuana as a "gateway"



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