A dose ranging study of modafinil for methamphetamine dependence

项目摘要/摘要 对甲基苯丙胺(MA)的依赖在美国许多地区很普遍。严重的后遗症 这种疾病包括认知障碍、乙肝和丙型肝炎以及艾滋病毒感染。认知障碍和 戒断症状，例如嗜睡、疲劳和渴望，可能会使使用者面临复发的风险。 对于MA依赖，目前还没有确定的药物治疗方法。莫达非尼是一种新型的促醒剂 缓解疲劳，增强认知功能，耐受性好，滥用倾向低。莫达非尼钝化 可卡因的主观影响，减少门诊患者可卡因的使用，这是我们小组最近完成的工作 表明与静脉注射MA联合给药是安全的。 将进行为期8周的剂量范围研究，以评估莫达非尼治疗MA的效果大小 依赖。MA依赖的受试者将被随机分配为每天接受200或400毫克的 莫达非尼或安慰剂。评估将包括MA的尿检、MA使用的自我报告、成瘾严重程度 指数，艾滋病行为风险，神经认知测试，苯丙胺戒断问卷， 血浆莫达非尼水平、血液化学指标和不良事件报告。 自我报告与尿毒学综合检测的广义估计方程模型 评估莫达非尼剂量对MA使用的影响。药代动力学/药效学(PK/PD)建模将 用于确定莫达非尼血药浓度与预后的关系。我们假设 1)莫达非尼将是安全的，耐受性良好，2)服用400毫克莫达非尼的人使用的MA将比 给予安慰剂，3)PK/PD模型将揭示莫达非尼水平之间的浓度-效应关系 A)认知功能，b)戒断症状，c)MA使用。项目叙事 甲基苯丙胺成瘾在美国是一个严重的问题， 没有任何药物被证明是有帮助的。莫达非尼是一种药物， 用于治疗睡眠障碍，已显示出作为可卡因成瘾的前景 治疗，并可能有助于戒断和难以思考 甲基苯丙胺使用者戒烟时有。我们将进行一项随机试验 安慰剂(糖丸)和两个剂量的莫达非尼，看看哪个剂量最多 对治疗甲基苯丙胺成瘾的门诊病人很有用。

Project Summary/Abstract Methamphetamine (MA) dependence is prevalent in many regions of the United States. Important sequelae of this illness include cognitive impairment, hepatitis B and C, and HIV infection. Cognitive impairment and withdrawal symptoms, e.g., somnolence, fatigue, and craving, may put users at risk for relapse. There is no established pharmacotherapy for MA dependence. Modafinil is a novel wake-promoting agent that relieves fatigue, enhances cognitive function, is well tolerated, and has low abuse liability. Modafinil blunts the subjective effects of cocaine, reduces cocaine use in outpatients, and recently completed work by our group indicates that it is safe when co-administered with intravenous MA. An 8-week dose ranging study will be conducted to assess the effect size of modafinil for treatment of MA dependence. MA dependent subjects will be randomly assigned to receive either 200 or 400 mg per day of modafinil or placebo. Assessments will include urinalysis for MA, self-report of MA use, the Addiction Severity Index, the Risk for AIDS Behaviors, a neurocognitive test battery, the Amphetamine Withdrawal Questionnaire, plasma modafinil levels, blood chemistries, and adverse event reports. A generalized estimating equation model of a composite measure of self-report and urine toxicology be used to assess the effect of modafinil dose on MA use. Pharmacokinetic/pharmacodynamic (PK/PD) modeling will used to determine the relationship between modafinil plasma concentration and outcomes. We hypothesize that 1) modafinil will be safe and well tolerated, 2) persons given 400 mg modafinil will use less MA than those given placebo, and 3) PK/PD modeling will reveal concentration-effect relationships between modafinil levels and a) cognitive function, b) withdrawal symptoms, and c) MA use. Project Narrative Methamphetamine addiction is a serious problem in the United States for which no medications have been shown to be helpful. Modafinil is a medication that is used to treat sleep disorders, has shown promise as a cocaine addiction treatment, and may help the withdrawal and difficulty thinking that methamphetamine users have when quitting. We will conduct a randomized trial of placebo (sugar pill) and two doses of modafinil to see which dose is most useful in treating methamphetamine-addicted outpatients.