Bupropion-Enhanced CM for Cocaine Dependence

安非他酮增强 CM 治疗可卡因依赖

• 批准号: 8862440
• 负责人: Maxine L Stitzer
• 金额: $ 52.76万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8862440
• 关键词: Abstinence; Attention; Behavior Therapy; Brain; Brain region; Bupropion; Clinical; Clinical Trials; Cocaine; Cocaine Dependence; Cocaine Users; Cognition; Combined Modality Therapy; Combined Pharmacological and Behavioral Treatment; Counseling; Dopamine; Drug usage; Effectiveness; Exposure to; HIV risk; Health; Impulsivity; Incentives; Intervention; Lead; Learning; Maintenance; Marketing; Measures; Mediating; Mediator of activation protein; Medicine; Outcome; Outcome Measure; Participant; Patient Self-Report; Patients; Pharmaceutical Preparations; Placebos; Population; Procedures; Psychological reinforcement; Relapse; Reporting; Research; Rewards; Risk Behaviors; Safety; Schedule; Short-Term Memory; Site; System; Testing; Time; Tobacco smoking; Treatment outcome; Urine; Work; base; clinical efficacy; cocaine use; cognitive function; cognitive process; contingency management; design; disorder later incidence prevention; dopamine system; drug abuser; drug seeking behavior; improved; instrument; methadone maintenance; non-drug; novel; pleasure; prevent; reinforcer; relapse patients; relating to nervous system; response; secondary outcome; stimulant abuse; therapy development; treatment response

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.

描述（由申请人提供）：行为疗法的功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。该项目将研究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。安非他酮似乎是用于此目的最有前途的药物，因为其先前已证明的功效和安全性以及其对多巴胺系统的药理作用。研究参与者将根据他们对针对可卡因阴性尿液的戒断激励（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参加一项研究，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。那些在初次接触 CM 程序后未能停止使用可卡因的人将进入一项平行研究，该研究检查安非他酮 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 N = 100。我们的假设是，与安慰剂治疗相比，安非他酮既可以提高那些难以停止使用可卡因的人的戒断率，又可以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 计划，该计划是针对所提出的问题专门定制的，但等同于可以获得的总金额。这两项研究都将跟踪 6 个月时间范围内的结果，包括对激励措施停止后的药物使用结果进行评估。此外，该项目将通过测量主观药物效应、药物与金钱的选择以及日常非药物活动带来的快乐的自我报告，提供有关药物效应机制的新颖信息。我们假设，与安慰剂参与者相比，安非他酮参与者将报告非药物活动更令人愉快（强化），将参与更多非药物活动，并且非药物强化措施将调解戒断结果。总体而言，这项研究将提供关于行为药物联合治疗的新的和有价值的信息，特别是药物可以增强 CM 效果的条件。如果假设的协同作用能够得到证实，这项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。该研究还将加深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来解决先前提到的 CM 局限性，包括某些患者缺乏反应以及戒断激励措施取消后复发等局限性，从而为行为疗法的发展做出重要贡献。总体而言，拟议的研究引人注目，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——戒断开始和预防复发，采用的设计可以有效且有效地测试每个问题的组合治疗方法，并检查认知功能和基于强化的中介因素的治疗反应。