The efficacy of behavior therapies may be enhanced by certain medications, particularly those that act on dopaminergic systems. This project will examine effects of bupropion on initiation and maintenance of cocaine abstinence in a population of cocaine dependent methadone maintenance patients. Bupropion appears to be the most promising medication for this purpose because of its previously demonstrated efficacy and safety as well as its pharmacological actions at dopamine systems. Study participants will be stratified according to their initial response to an abstinence incentive (contingency management) procedure targeting cocaine negative urines. Those who stop their cocaine use will enter a study that examines effects of bupropion XL (300mg/day) versus placebo on relapse prevention. Those who fail to stop cocaine use after initial exposure to the CM procedure will enter a parallel study that examines the effects of bupropion XL (300mg/day) on abstinence initiation. The two studies will be conducted concurrently with N = 100 in each. Our hypothesis is that bupropion as compared to placebo treatment will both enhance rates of abstinence initiation in those who have difficulty stopping cocaine and retard rates of relapse in those who initially stopped their cocaine use. Each study will involve a CM schedule that is uniquely tailored to the questions being asked but that is equated on total amount that can be earned. Both studies will track outcomes over a 6-month time frame that includes assessment of drug use outcomes after incentives have stopped. In addition, the project will provide novel information about mechanisms of medication effects by measuring subjective drug effects, drug vs money choices, and self-reports of pleasure derived from daily non-drug activities. We hypothesize that bupropion compared to placebo participants will report non-drug activities as more pleasurable (reinforcing), will engage in more of them and that measures of non-drug reinforcement will mediate abstinence outcomes. Overall, this research will provide new and valuable information about combined behavioral-pharmacological treatments and specifically the conditions under which medication may enhance effects of CM. If hypothesized synergies can be demonstrated, the study will point the way to a significant advance in improved treatment outcomes for this critical group of drug abusers. The research will also add to understanding of the interplay between brain reinforcement systems and drug-seeking behavior. Finally, it will make an important contribution to behavioral therapy development by exploring a novel solution to limitations previously noted for CM that include lack of response in some patients and relapse after abstinence incentives are withdrawn. Overall, the proposed study is compelling because it conceptually differentiates the two key clinical issues in treatment of stimulant abusers- abstinence initiation and relapse prevention, uses a design that efficiently and effectively tests combined treatment approach on each and examines cognitive function and reinforcement- based mediators of treatment response.

R01DA034047

2013-09-30

2020-11-30