Selegiline for Treatment of Cannabis Dependence

描述(由申请人提供)：在过去的15年里，美国对大麻相关问题的治疗需求增加了近2倍。尽管行为疗法很有效，但许多人在治疗期间并不主动戒烟，许多人在治疗期间或治疗后复发使用，这表明治疗大麻依赖的难度很大，需要有效的药物治疗。司来吉兰是一种单胺氧化酶-B抑制剂，它增加了中脑边缘和其他与尼古丁、可卡因和大麻等成瘾药物依赖有关的脑区的多巴胺活性。司来吉兰最近在治疗尼古丁依赖和减少尼古丁和可卡因的奖赏效应方面显示出有效性，但尚未对大麻依赖进行研究。因此，我们建议进行一项安慰剂对照、双盲、试验性的司来吉兰治疗大麻依赖的临床试验。拟议研究的具体目的是：1)进行一项初步研究，以获得司来吉兰与安慰剂在减少大麻依赖患者使用大麻方面的疗效数据；以及2)探讨司来吉兰和安慰剂对急性和长期戒断症状的影响。大麻依赖参与者(N=40)将被随机分配到使用司来吉兰(10毫克/天)或安慰剂治疗8周。所有参与者将每周接受由一位特别的：雨后医生提供的个人标准医疗管理。主要结果衡量标准包括大麻使用频率的减少和连续数周的大麻戒除(通过自我报告进行评估，并通过每周两次定量尿液测试加以证实)。次要结果包括大麻戒断症状的减少、情绪变化以及药物的安全性和耐受性。数据分析将重点放在意向处理样本上，并将利用混合模型的方差分析。研究结果将对司来吉兰和安慰剂之间的差异的影响大小提供可靠的估计，这将被用来确定在随后的全面临床试验中提供足够的力量来检测显著差异所需的样本量。研究结果对探索司来吉兰的潜在作用机制和建立评估大麻依赖药物的研究计划也将是重要的。

DESCRIPTION (provided by applicant): Demand for treatment for marijuana-related problems in the U.S. increased nearly 2-fold during the past 15 years. Despite the efficacy of behavioral treatments, many individuals do not initiate abstinence during treatment and many who do relapse to use either during or after treatment, pointing to the difficulty treating cannabis dependence and the need for efficacious pharmacological treatments. Selegiline, a monoamine oxidase-B inhibitor, increases dopamine activity in mesolimbic and other brain regions involved in dependence on addictive drugs, including nicotine, cocaine and cannabis. Selegiline has recently shown efficacy in treating nicotine-dependence and reducing the rewarding effects of nicotine and cocaine, but it has not yet been studied in cannabis-dependence. Consequently, we are proposing a placebo-controlled, double blind, pilot clinical trial of selegiline for treating cannabis dependence. Specific aims of the proposed study are: 1) to conduct a pilot study to obtain efficacy data regarding the effect size between selegiline compared to placebo for reducing cannabis use in cannabis-dependent patients; and 2) to explore the impact of selegiline and placebo on acute and protracted withdrawal symptoms. Cannabis-dependent participants (N=40) will be randomly assigned to 8 weeks of treatment with selegiline (10 mg/day) or placebo. All participants will receive weekly individual standard medical management provided by a specially :rained physician. Primary outcome measures include reduction in frequency of cannabis use and weeks of consecutive cannabis abstinence (as assessed by self-report and verified by twice weekly quantitative urine tests). Secondary outcomes include reduction in cannabis withdrawal symptoms, mood change, and safety and tolerability of the medication. Data analyses will focus on an intention-to-treat sample and will utilize mixed-model analysis of variance. Findings will provide a reliable estimate of the effect size of the difference between selegiline and placebo that will be used to determine the sample size needed to provide sufficient power to detect significant differences in a subsequent full-scale clinical trial. Study findings will also be important in exploring potential mechanism of action of selegiline and establishing a program of research to evaluate medications for cannabis-dependence.