Modafinil Treatment for Cocaine Dependence

描述(由申请人提供)：本项目的目标是评估莫达非尼作为可卡因依赖的戒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，莫达非尼可以减轻可卡因引起的快感。莫达非尼的滥用潜力低，其作用机制与可卡因明显不同。我们在有严重可卡因戒断症状的受试者中进行了一项小型(n=13)、为期8周的开放标签莫达非尼门诊研究，根据可卡因选择性严重性评估(CSSA)的衡量。接受莫达非尼治疗的受试者的无可卡因尿毒学发生率(48%)和治疗滞留率(74%)高于同期在我们临床进行的另一项临床试验中接受安慰剂治疗的高综援受试者(n=23)的无可卡因尿毒学发生率(6.5%)和治疗滞留率(43%)。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，他们将被随机分成三组之一，接受莫达非尼(200毫克/天，n=70)、莫达非尼(400毫克/天，n=70)或安慰剂(n=90)的双盲治疗8周。我们将使用骨灰盒随机化来根据三个基线变量对实验条件下的受试者进行分层：高基线综援得分(等于或&gt；22)、性别和筛查时可卡因毒物阳性。受试者将接受每周两次的认知行为疗法(CBT)和每周3次研究评估，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。随机化后3个月和6个月将安排后续访问。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)和治疗保留。次要目的是确定莫达非尼对二次结局的影响、综援评分对莫达非尼反应的缓和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.