Contingency Management plus Levodopa/Carbidopa for Trtment. of Cocaine Dependence

描述（由申请人提供）：可卡因依赖是一个主要的公共卫生问题，开发这种疾病的治疗方法是当务之急。迄今为止，基于强化原则的治疗干预措施显示出对改善物质使用结果的最有力的实证支持。一个例子是应急管理（CM）的干预措施，其中非药物替代品被引入到环境中，目的是增加来自非药物刺激的强化比药物衍生的强化比。然而，药物依赖个体对非药物依赖的反应性或敏感性各不相同，这一直是CM干预疗效的限制因素。最近的证据表明，某些药物增加CM干预的疗效，特别是针对可卡因强化中多巴胺能（DA）作用的药物。我们研究的一种特别有前途的药物是DA前体左旋多巴，这是一种增加DA缺乏个体中可用的中央DA储存的药物。我们已经观察到最强的作用时，左旋多巴的药物是在CM治疗的背景下管理。观察到的疗效的一个合理解释是，左旋多巴，当伴随给予CM，提高了显着价值的激励，这反过来又激励目标导向的行为（禁欲）。这项研究旨在复制，预测和扩展这种有前途的治疗方法的效果。依赖于多巴胺的门诊患者将参加一项随机、2组（左旋多巴vs.安慰剂）、双盲临床试验。基于禁欲的CM程序将作为行为治疗平台。将在基线和治疗期间评估与注意力偏差（可卡因Stroop任务）和动机（改良的累进比率程序）相关的潜在预测因素。我们假设CM+左旋多巴在减少可卡因使用方面比CM+安慰剂更有效，并且CM+左旋多巴的效果与治疗前和治疗期间的注意力偏差和动机水平相关。第二个目的是探索左旋多巴治疗是否有助于CM停药后的持续禁欲。总之，本研究将验证一种新的行为药理学治疗的有效性，并阐明DA增强策略和基于骨水泥的治疗之间协同作用的机制。

DESCRIPTION (provided by applicant): Cocaine dependence is a major public health problem and the development of a treatment for this disorder is a priority. To date, treatment interventions based on reinforcement principles have shown the most robust empirical support for improving substance use outcomes. One example is contingency management (CM) interventions in which nondrug alternatives are introduced into the environment with the goal of increasing the ratio of reinforcement derived from nondrug stimuli to the ratio of drug-derived reinforcement. Cocaine dependent individuals vary in their responsiveness or sensitivity to nondrug reinforcers, however, which has been a limiting factor in the efficacy of CM interventions. Recent lines of evidence suggest that certain medications add efficacy to CM interventions, particularly agents that target dopaminergic (DA) actions in cocaine reinforcement. A particularly promising medication that we have investigated is the DA precursor levodopa, an agent that increases the store of available central DA in DA-deficient individuals. We have observed the strongest effects of levodopa when the medication is administered in the context of CM therapy. A plausible explanation for the observed efficacy is that levodopa, when given concomitantly with CM, enhances the saliency value of the incentives, which in turn motivates goal-directed behavior (abstinence). The proposed study is designed to replicate, predict, and extend the effects of this promising treatment approach. Cocaine dependent outpatients will participate in a randomized, 2-group (levodopa vs. placebo), double-blind clinical trial. Abstinent-based CM procedures will serve as the behavioral therapy platform. Potential predictors related to attentional bias (cocaine Stroop task) and motivation (modified progressive-ratio procedure) will be assessed at baseline and during treatment. We hypothesize that CM+levodopa will be more effective than CM+placebo in reducing cocaine use and that the effects of CM+levodopa will be associated with levels of attentional bias and motivation before and during treatment. A secondary aim will explore whether levodopa therapy contributes to the persistence of abstinence after discontinuation of 'CM. In conclusion, this study will validate the usefulness of a novel behavioral-pharmacological treatment and shed light on the mechanisms underlying the synergism between DA augmentation strategies and reinforcement-based therapies.