Drug abuse continues to be a major health problem in the United States. Adverse effects of drug use on cognition are of serious concern. If some drug users develop long-term cerebral dysfunction, the potential costs to society in increased health care costs and decreased productivity are high. Surprisingly, although acute impairments of cognition from many drugs have been demonstrated, experimental studies of chronic drug effects on cognition have been few in number, methodologically weak, and ambiguous in outcome. The broad, long-term objectives of our research are to understand effects of chronic use of several drugs, alone and in combination, on cognition. The study proposed in this application will examine cognitive effects of marijuana alone and in combination with alcohol by comparing individuals engaging in frequent marijuana use, frequent alcohol use, or frequent use of both substances with individuals who rarely use either substance; and will examine cognitive effects of multiple illicit drugs by studying individuals who use both marijuana and cocaine frequently, in combination with other illicit drugs. Groups will be matched on intellectual function before the onset of drug use, using records of scores on standardized tests that are available for virtually all children in Iowa. Similar, highly correlated, standardized tests that are suitable for adults and that emphasize utilization of previously acquired information will be administered, along with computerized tests that emphasize abstraction ability and learning and remembering new information. Four groups of drug users who are patients will be tested under non-drug conditions 14 to 21 days after admission to drug and alcohol treatment facilities, and will be retested 3 months after admission to assess possible changes in cognitive deficits with continued abstinence. The study will determine whether individuals engaging in four patterns of chronic drug use show impairments relative to matched non-users, specifically examining interactive effects of the most widely used illicit and licit drugs (marijuana and alcohol) and effects of involvement with cocaine and other illicit drugs, in addition to marijuana.