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优先事项。到目前为止，基于强化原则的治疗干预措施显示出对改善药物使用结果的最有力的经验支持。一个例子是应急管理(CM)干预，将非药物替代品引入环境，目的是增加非药物刺激产生的强化比药物衍生强化的比率。然而，可卡因依赖者对非药物增强剂的反应或敏感性各不相同，这一直是CM干预效果的限制因素。最近的一系列证据表明，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(DA)作用的药物。我们研究的一种特别有希望的药物是DA前体左旋多巴，一种增加DA缺乏个体可用中央DA储存的药物。我们观察到，当左旋多巴在CM治疗的背景下使用时，其效果最强。对观察到的疗效的一个看似合理的解释是，当左旋多巴与CM一起服用时，增强了激励的显著价值，这反过来又激发了目标导向行为(禁欲)。这项拟议的研究旨在复制、预测和扩大这种有希望的治疗方法的效果。依赖可卡因的门诊患者将参加一项随机、2组(左旋多巴与安慰剂)的双盲临床试验。以禁欲为基础的CM程序将作为行为治疗的平台。与注意偏差(可卡因Stroop任务)和动机(改进的累进比率程序)相关的潜在预测因素将在基线和治疗期间进行评估。我们假设，在减少可卡因使用方面，CM+左旋多巴将比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向和动机水平有关。第二个目标将探索左旋多巴治疗是否有助于戒断‘CM后的持续戒断。总之，这项研究将验证一种新的行为-药物治疗的有效性，并阐明DA增强策略和强化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.