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，开发治疗这种疾病的方法是一个优先事项。迄今为止，基于强化原则的治疗干预已显示出改善药物使用结果的最强有力的实证支持。一个例子是应急管理（CM）干预措施，其中将非药物替代方案引入环境，目标是增加非药物刺激引起的强化与药物引起的强化的比例。然而，可卡因依赖个体对非药物强化物的反应性或敏感性各不相同，这一直是CM干预效果的限制因素。最近的证据表明，某些药物增加了CM干预的有效性，特别是针对可卡因强化中的多巴胺能（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，它可以增加缺乏DA的个体体内可用的中央DA的储存。我们观察到左旋多巴的最强效应，当药物在CM治疗的背景下进行管理。对于观察到的效果，一个合理的解释是，当左旋多巴与CM同时给予时，会增强激励的显着性值，从而激发目标导向的行为（戒断）。该研究旨在复制、预测和扩展这种有前途的治疗方法的效果。可卡因依赖门诊患者将参加一项随机、两组（左旋多巴vs安慰剂）双盲临床试验。以戒断为基础的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偏倚（可卡因Stroop任务）和动机（改进的渐进比率程序）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+左旋多巴的效果将与治疗前和治疗期间的注意偏差和动机水平有关。第二个目的是探讨左旋多巴治疗是否有助于停药后的持续禁欲。总之，本研究将验证一种新的行为药理学治疗方法的有效性，并阐明DA增强策略和强化疗法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.