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

应急管理加左旋多巴/卡比多巴进行治疗。

• 批准号: 7622158
• 负责人: JOY Marie SCHMITZ
• 金额: $ 36.38万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7622158
• 关键词: Abstinence; Alcohol or Other Drugs use; Attention; Behavior; Behavior Therapy; Behavioral; Carbidopa; Clinical Trials; Cocaine; Cocaine Dependence; Cues; Data; Development; Disease; Double-Blind Method; Environment; Goals; Incentives; Individual; Intervention; Laboratories; Levodopa; Light; Measures; Motivation; Outcome; Outpatients; Patients; Pharmaceutical Preparations; Pharmacological Treatment; Phase; Placebos; Procedures; Psychological reinforcement; Public Health; Randomized; Relative (related person); Research; Stimulus; Subgroup; Urine; base; cocaine use; contingency management; design; improved; non-drug; novel; reinforcer; response; synergism; therapy development; voucher

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.

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，而对这种疾病的治疗的发展是优先事项。迄今为止，基于加强原则的治疗干预措施显示了改善物质使用结果的最强大的经验支持。一个例子是应急管理（CM）干预措施，其中将Nondrug替代方案引入环境中，目的是增加从Nondrug刺激与药物衍生增强的比率提出的加固之比。然而，可卡因依赖性个体的反应性或对非加增强剂的敏感性各不相同，这一直是CM干预措施功效的限制因素。最近的证据表明，某些药物为CM干预增加了功效，尤其是针对可卡因增强中多巴胺能（DA）作用的药物。我们已经研究的一种特别有希望的药物是DA前体左旋多巴，该药物可增加缺乏DA的个体中可用中央DA的存储。当在CM治疗的背景下给药时，我们已经观察到左旋多巴的最强作用。对观察到的功效的合理解释是，当左旋多巴与CM同时给出时，增强了激励措施的显着性价值，这反过来又激发了目标指导的行为（禁欲）。拟议的研究旨在复制，预测和扩展这种有前途的治疗方法的影响。可卡因依赖性门诊患者将参加一项随机的2组（左旋多巴与安慰剂），双盲临床试验。避免基于CM的CM程序将作为行为疗法平台。将在基线和治疗期间评估与注意力偏见（可卡因stroop任务）和动机（修改的进行性比率程序）有关的潜在预测因素。我们假设CM+Levodopa在减少可卡因的使用方面将比CM+安慰剂更有效，并且CM+Levodopa的影响将与治疗前和治疗过程中的注意力偏见和动机水平有关。次要目标将探索左旋多巴治疗是否有助于停止'CM之后的禁欲。总之，这项研究将验证一种新型的行为 - 药物治疗方法的实用性，并阐明DA增强策略和基于增强疗法之间协同作用的机制。