Modafinil Treatment for Cocaine Dependence

描述（由申请人提供）：本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药物的疗效。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，莫达非尼也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，我们中心和另一个研究小组最近的对照研究表明，莫达非尼减弱可卡因诱导的欣快感。莫达非尼的滥用可能性很低，其作用机制与可卡因明显不同。我们进行了一项小型（n=13），8周，开放标签，门诊研究莫达非尼的受试者与严重的可卡因戒断症状，通过测量的可卡因选择性严重程度评估（CSSA）。莫达非尼治疗受试者的无可卡因尿液毒理学（48%）和治疗保持率（74%）优于我们诊所同时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）的无可卡因尿液毒理学（6.5%）和治疗保持率（43%）。此外，一些受试者表示，莫达非尼消除或降低了他们使用可卡因后体验欣快的能力。该项目将招募可卡因依赖受试者，将其随机分配至三个治疗组中的一组，并采用莫达非尼（200 mg/天，n=70）、莫达非尼（400 mg/天，n=70）或安慰剂（n=90）进行为期8周的双盲治疗。我们将使用Urn随机化在三个基线变量上对实验条件下的受试者进行分层：高基线CSSA评分（等于或>22）、性别和筛选时的阳性可卡因毒理学。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。将在随机化后3个月和6个月安排随访访视。我们的主要目的是确定莫达非尼是否改善可卡因戒断（通过尿检测量）和治疗保留。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，以及潜在莫达非尼效应的持续时间。

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.