Preliminary studies have suggested that chronic cocaine abuse has definite morphologic and electrophysiologic effects on the brain. The work proposed will test the following hypotheses: (1) the long-term abuse of cocaine induces cerebral atrophy, (2) this atrophy has functional consequences detectable as cognitive and electrophysiologic abnormalities, (3) the pathogenic basis for the atrophy is cerebral ischemia related to direct and indirect effects of the agent on cerebral vessels. and (4) these consequences are partially reversible with abstinence from cocaine. Subjects will be recruited at three chemical dependency treatment programs and will be divided into two groups: (1) cocaine abusers and (2) abusers of other single substances. All subjects will be evaluated after two weeks of inpatient chemical dependency treatment; the cocaine abusers will also undergo a follow-up evaluation after a six-month period of abstinence. All evaluations will be comprised of a general clinical assessment (interview. physical examination, blood and urine tests) and a battery of specialized tests (cranial magnetic resonance imaging [MRI] yielding both volumetric and clinical data, single photon emission computed tomography [SPECT], neuropsychological testing, and quantitative electroencephalography [EEG]). Groups of normals will also be studied. A cross-sectional limb of the study will compare cocaine abusers with abusers of other single substances and with normal subjects. Hypothesis 1, that the long-term abuse of cocaine induces cerebral atrophy, will be tested by cross-sectional comparisons of volumetric MRI. Hypothesis 2, that this atrophy has functional consequences, will be tested by cross-sectional comparisons of neuropsychological and quantitative EEG data and by correlation of these data with volumetric MR] results. Hypothesis 3, that the pathogenetic basis for the atrophy is cerebral ischemia, will be tested by correlation of volumetric MRI measures of atrophy with SPECT and clinical MRI indicators of ischemia within the cocaine abusers group. A longitudinal limb of the study will compare the cocaine abusers before and after abstinence. Hypothesis 4. that the consequences (cerebral atrophy and dysfunction) of the long-term abuse of cocaine are partially reversible with abstinence, will be tested by longitudinal comparisons within the cocaine abusers group. Given the inherent difficulties in a clinical investigation of cocaine abuse, the prospective design of our study will provide the greatest opportunity to obtain accurate information about the severity (frequency of abuse, quantity of drug typically taken) and pattern (intermittent binging vs. regular daily use) of cocaine abuse and also to detect and exclude potentially confounding influences. Awareness of the occurrence of long-term effects will deter some potential abusers. A keener understanding of neuropsychological deficits will influence the treatment of cocaine addiction. Evidence for an ischemic mechanism for brain damage will suggest approaches to treatment. Finally, documentation of reversibility may provide added incentive for remaining abstinent.
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