Modafinil Treatment for Cocaine Dependence

描述（由申请人提供）：该项目的目的是评估莫达非尼作为可卡因依赖的解毒和预防复发剂的功效。我们假设莫达非尼将逆转可卡因诱导的影响多巴胺、谷氨酸和GABA神经递质系统的神经适应。由于其类似兴奋剂的特性，莫达非尼还可能缓解严重的可卡因戒断症状，这些症状与不良的临床结果有关。此外，最近来自我们中心和另一个研究小组的对照研究表明，莫达非尼会减弱可卡因引起的欣快感。莫达非尼的滥用可能性低，其作用机制与可卡因明显不同。我们对有可卡因选择性严重程度评估（CSSA）的严重可卡因戒断症状的受试者进行了一项小型（n=13）、8周、开放标签的莫达非尼门诊研究。莫达非尼治疗的受试者无可卡因尿毒理学率（48%）和治疗保留率（74%）更高，与我们诊所同期进行的另一项临床试验中安慰剂治疗的高CSSA受试者组（n=23）的无可卡因尿毒理学率（6.5%）和治疗保留率（43%）相比，这一比例更高。此外，一些受试者表示莫达非尼消除或降低了他们在使用可卡因后体验快感的能力。拟议的项目将招募可卡因依赖的受试者，他们将随机分为三组之一，双盲治疗8周，分别使用莫达非尼（200毫克/天，n=70）、莫达非尼（400毫克/天，n=70）或安慰剂（n=90）。我们将采用Urn随机化方法，根据三个基线变量对不同实验条件下的受试者进行分层：高基线CSSA评分（等于或低于22分）、性别和筛查时可卡因毒理学阳性。受试者将接受每周两次的认知行为治疗（CBT）和每周3次的研究评估，包括尿检和问卷调查，测量渴望、可卡因戒断、可卡因使用和药物副作用。随机分组后3个月和6个月安排随访。我们的主要目的是确定莫达非尼是否能改善可卡因戒断（通过尿检测量）和治疗效果。次要目的是确定莫达非尼对次要结局的影响，CSSA评分对莫达非尼反应的调节作用，以及莫达非尼潜在效应的持续时间。

DESCRIPTION (provided by applicant): The goal of this project is to evaluate the efficacy of modafinil as a detoxification and relapse-prevention agent for cocaine dependence. We hypothesize that modafinil will reverse cocaine-induced neuroadaptations affecting dopamine, glutamate, and GABA neurotransmitter systems. Because of its stimulant-like properties, modafinil is also likely to relieve severe cocaine withdrawal symptoms, which are associated with poor clinical outcome. In addition, recent controlled studies from our Center and another research group indicate that modafinil attenuates cocaine-induced euphoria. Modafinil has low abuse potential and its mechanism of action differs markedly from that of cocaine. We conducted a small (n=13), 8-week, open-label, outpatient study of modafinil in subjects with severe cocaine withdrawal symptoms, as measured by the Cocaine Selective Severity Assessment (CSSA). Modafinil-treated subjects had superior rates of cocaine-free urine toxicology (48%) and treatment retention (74%), which compared favorably to cocaine-free urine toxicology (6.5%) and treatment retention (43%) rates in a group (n=23) of placebotreated, high CSSA subjects from another clinical trial conducted concurrently in our clinic. Also, several subjects indicated that modafinil eliminated or reduced their ability to experience euphoria after using cocaine. The proposed project will recruit cocaine-dependent subjects who will be randomized into one of three arms and treated double-blind for 8 weeks with either modafinil (200 mg/day, n=70), modafinil (400 mg/day, n=70), or placebo (n=90). We will use Urn randomization to stratify subjects across the experimental conditions on three baseline variables: high baseline CSSA scores (equal to or >22), gender, and positive cocaine toxicology at screening. Subjects will receive twice-weekly cognitive behavioral therapy (CBT) and 3 research assessments per week, including urine testing and questionnaires measuring craving, cocaine withdrawal, cocaine use, and medication side effects. Follow-up visits will be scheduled 3 and 6 months after randomization. Our primary aim is to determine whether modafinil improves cocaine abstinence (as measured by urine testing) and treatment retention. The secondary aims are to determine the effects of modafinil on secondary outcomes, the moderating effects of CSSA scores on response to modafinil, and the duration of potential modafinil effects.