DESCRIPTION: (Applicant's Abstract) Cocaine is so addictive, it stands apart from other drugs and deserves special study. Chronic cocaine abuse is associated with changes in the central nervous system (CNS) in humans. For example, the results of neurochemical, neurobehavioral, and neuroimaging studies report that chronic cocaine abuse is selectively associated with abnormalities in the limbic prefrontal cortex. This study will evaluate abstinent cocaine abusers: 1) to determine the magnitude and specific patterns of the neurobehavioral performance in chronic cocaine abuse and relate these to measures of regional cerebral blood flow (rCBF) and brain structure; 2) to determine if chronic cocaine abuse relates to abnormalities of rCBF in orbitofrontal and anterior cingulate cortices during cognitive activation; 3) to determine if chronic cocaine abuse is associated with structural deficits (i.e. smaller brain volumes) in different regions of the prefrontal lobe. Three groups each with 25 participants will be studied. Group 1 (cocaine abusers) will meet DSM IV criteria for cocaine dependance or abuse; Group 2 (polysubstance abusers) will be dependent on or abuse drugs other than cocaine; and Group-3 will consist of a non-drug using control group. Groups will include men and woman, aged 20 to 45 years. They will be matched for age, sex, race, socioeconomic status (SES), and maternal education. The drug using groups will stay for 30 days on the Clinical Inpatient Research Unit of NIDAIRP. All testing in Groups 1 and 2 will occur in the 4th week to minimize the effects of both physical and psychological withdrawal from drugs and alcohol. Group 3 (controls) will undergo testing during a seven-day stay in the Johns Hopkins Bayview General Clinical Research Center. Neurobehavioral characteristics will be assessed using neuropsychological tests and questionnaires that evaluate history of drug use, drug craving, personally characteristics, and neuropsychiatric symptoms. Physiological and neuroanatomical characteristics will be determined with rCBF activation, positron emission tomography (PET) and brain magnetic resonance imaging (MRI). This study proposes to develop insights into the relationship between neurobehavioral functioning and neurobiological mechanisms in chronic cocaine abusers. Such insights will lead to a more complete understanding of the neurobiology and neurological effects of cocaine abuse and will promote the development of more efficacious treatments.