Bupropion-Enhanced CM for Cocaine Dependence

描述(申请人提供)：行为疗法的疗效可以通过某些药物来增强，特别是那些作用于多巴胺能系统的药物。本项目将研究安非他酮对可卡因依赖型美沙酮维持患者开始和维持可卡因戒断的影响。安非他酮似乎是最有希望用于这一目的的药物，因为它以前被证明是有效和安全的，以及它在多巴胺系统中的药理作用。研究参与者将根据他们对针对可卡因阴性尿液的禁欲激励(应急管理)程序的初步反应进行分层。那些停止使用可卡因的人将进入一项研究，检查安非他酮XL(300毫克/天)与安慰剂在预防复发方面的效果。那些在最初接触CM程序后未能停止使用可卡因的人将进入一项平行研究，检查安非他酮XL(300毫克/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，安非他酮既能提高难以戒除可卡因的人的戒断率，又能延缓最初停止使用可卡因的人的复发率。每项研究都将涉及到一个针对所提出的问题量身定做的CM时间表，但这是等同于可以赚取的总金额。这两项研究都将跟踪6个月的结果，其中包括在激励措施停止后评估药物使用结果。此外，该项目将通过测量主观药物效果、药物与金钱的选择以及日常非药物活动所产生的快感的自我报告，提供关于药物效果机制的新信息。我们假设，与安慰剂参与者相比，安非他酮将报告非药物活动更令人愉悦(加强)，将参与更多的活动，非药物强化的措施将调解戒断结果。总体而言，这项研究将提供有关行为-药物联合治疗的新的有价值的信息，特别是在什么情况下药物可以增强CM的效果。如果能够证明假想的协同效应，这项研究将为改善这一关键吸毒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寻求毒品行为之间的相互作用的理解。最后，它将通过探索一种新的解决方案，为行为疗法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，以及在戒断激励被取消后复发。总体而言，拟议的研究是令人信服的，因为它在概念上区分了兴奋剂滥用者治疗中的两个关键临床问题--戒断开始和复发预防，采用了一种设计，有效地测试了两种治疗方法的联合治疗方法，并检查了认知功能和基于强化的治疗反应中介。

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.