BUPRENORPHINE MAINT FOR COCAINE ABUSING OPIOID ADDICTS

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This is a competing renewal requesting three years funding for a 24 week double blind, double dummy randomized controlled clinical trial comparing the clinical efficacy of maintenance on low dose buprenorphine (4 mg SL daily), high dose buprenorphine (12 mg SL daily) or methadone (65 mg PO daily) for cocaine abusing opiate dependent patients (n = 120). We have hypothesized that maintenance on buprenorphine, a partial opioid antagonist with limited agonist activity, will not reinforce cocaine use by ameliorating dysphoria or enhancing cocaine euphoria and thus will have improved efficacy compared to maintenance on methadone. During the first 16 months of the initial two year funding period, we completed a dose-ranging study to determine optimal buprenorphine dose(s) to reduce opioid and cocaine abuse, modified the study protocol for the double blind study and initiated enrollment in the double blind study. Modifications in the double blind study include: 1) comparison of high and low dose buprenorphine and high dose methadone; 2) enrollment of street addicts to ensure maintenance of the double blind; 3) stringent eligibility requirements to ensure homogeneity of drug use severity and pre-randomization stratification based on presence/absence of depression; 4) use of contingencies throughout study to ensure maximal likelihood of clinically significant outcome differences among treatment groups and relevance of study to standard treatment programs; 5) increased length of clinical trial to 24 weeks to provide sufficient time for treatment effectiveness in street addicts and to facilitate pooling the study results with our recently completed comparison of two doses of buprenorphine (2 mg, 6 mg) and methadone (35 mg, 65 mg); 6) increased sample size to 120 subjects to increase statistical power to evaluate predictors of improvement and patient-treatment matching. Evaluation of alternative maintenance agents, such as buprenorphine, with potentially improved efficacy compared to methadone for the reduction of cocaine and illicit opioid use is essential since cocaine abuse among methadone maintained patients is endemic and undermines the effectiveness of this treatment.