The aim of this component is to improve the pharmacological treatment of cocaine abuse. Fluoxetine has been shown to be effective in improving cocaine abuse treatment outcome in some studies but not in others. The proposed projects encompass a five year program of work aimed at resolving these discrepancies and clarifying the efficacy of fluoxetine alone or in combination with a dopaminergic agonist in the treatment of primary (non-methadone) crack cocaine abusers. The proposed work consists of three experiments, each being a separate randomized, double- blind, placebo-controlled parallel groups trial. Study 1 will test the efficacy of Fluoxetine versus placebo in newly admitted outpatient cocaine abusers to initiate abstinence or reduce cocaine use, as well as to improve retention. Study 2 will test the efficacy of Fluoxetine versus placebo in abstinent outpatient cocaine abusers in promoting relapse prevention. Study 3 will be a pilot study to test the utility of Fluoxetine when combined with the dopaminergic agent maxindol or with placebo to initiate abstinence, reduce cocaine use, and improve retention in newly admitted outpatient cocaine abusers. This series of controlled studies aim to test the following primary hypothesis: 1. Fluoxetine will be more effective than placebo in initiating abstinence, reducing cocaine use, and in improving retention in active cocaine abusers entering outpatient treatment. 2. Fluoxetine will be more effective than placebo in relapse prevention in newly abstinent outpatient cocaine abusers. 3. Fluoxetine will be more effective than placebo in reducing certain clinically important behaviors and psychological states associated with cocaine use, such as addiction severity, cocaine craving, alcohol use, depressed mood, and AIDS-risk behaviors. 4. Quantitative urine BE will be a more accurate measure of cocaine use and associated behaviors than qualitative urine drug testing. Quantitative measures of urine BE will therefore be more significantly correlated than a qualitative analysis (using a 300 ng/ml BE cutoff), with clinical measures of drug use, such as self-report, ASI subscale scores, clinician rating, and AIDS-risk behavior. 5. Commitment of abstinence, level of social support, and level of adherence to medications will be associated with lower cocaine use outcome, whereas diagnosis of antisocial personality, major depression, and alcohol abuse will correlate with worse cocaine use outcome.
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