Bupropion-Enhanced CM for Cocaine Dependence

描述（由申请人提供）：某些药物可能会增强行为疗法的功效，特别是那些作用于多巴胺能系统的药物。该项目将检查安非他酮对可卡因依赖美沙酮维持患者群体开始和维持可卡因戒断的影响。安非他酮似乎是最有前途的药物，因为它以前证明的疗效和安全性，以及其在多巴胺系统的药理作用。将根据研究受试者对针对可卡因阴性尿液的禁欲激励（应急管理）程序的初始反应对他们进行分层。那些停止使用可卡因的人将进入一项研究，研究安非他酮XL（300毫克/天）与安慰剂对预防复发的影响。那些在首次接触CM程序后未能停止可卡因使用的人将进入一项平行研究，该研究检查了安非他酮XL（300 mg/天）对戒断开始的影响。这两项研究将同时进行，每项研究N = 100。我们的假设是，与安慰剂治疗相比，安非他酮将提高那些难以停止可卡因的人的戒断率，并延缓那些最初停止使用可卡因的人的复发率。每项研究都将涉及一个CM时间表，该时间表针对所问的问题量身定制，但与可以获得的总金额相等。这两项研究将在6个月的时间范围内跟踪结果，其中包括在奖励措施停止后评估药物使用结果。此外，该项目还将通过测量主观药物效应、药物与金钱的选择以及来自日常非药物活动的快乐自我报告，提供有关药物效应机制的新信息。我们假设，安非他酮与安慰剂相比，参与者将报告非药物活动更愉快（强化），将参与更多的活动，非药物强化措施将介导禁欲结果。总体而言，这项研究将提供有关行为药理学联合治疗的新的有价值的信息，特别是药物可能增强CM效果的条件。如果假设的协同作用能够得到证实，该研究将为改善这一关键药物滥用者群体的治疗结果指明方向。这项研究还将增加对大脑强化系统和药物寻求行为之间相互作用的理解。最后，它将通过探索一种新的解决方案，对行为治疗的发展做出重要贡献，以解决以前注意到的CM的局限性，包括一些患者缺乏反应和戒断激励措施撤回后复发。总的来说，拟议的研究是令人信服的，因为它在概念上区分了治疗兴奋剂滥用者的两个关键临床问题-戒断启动和复发预防，使用了一种设计，有效地测试了每种治疗方法的组合，并检查了认知功能和治疗反应的强化介质。

DESCRIPTION (provided by applicant): 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.