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。尽管行为治疗有效，但许多人在治疗期间并没有开始禁欲，许多人在治疗期间或治疗后复发，这表明难以治疗大麻依赖和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，可增加中脑边缘和其他与成瘾药物（包括尼古丁、可卡因和大麻）依赖有关的大脑区域的多巴胺活性。司来吉兰最近显示出治疗尼古丁依赖和减少尼古丁和可卡因的奖励作用的功效，但尚未在大麻依赖中进行研究。因此，我们提出了一个安慰剂对照，双盲，试点临床试验司来吉兰治疗大麻依赖。拟议研究的具体目的是：1）进行一项试点研究，以获得关于司来吉兰与安慰剂相比减少大麻依赖患者大麻使用的效应量的疗效数据; 2）探索司来吉兰和安慰剂对急性和持久性戒断症状的影响。大麻依赖受试者（N=40）将被随机分配接受8周司来吉兰（10 mg/天）或安慰剂治疗。所有参与者每周将接受一次个人标准的医疗管理，由一位专门的医生提供。主要结果指标包括大麻使用频率的减少和连续大麻戒断周数（通过自我报告评估，并通过每周两次定量尿检验证）。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。数据分析将侧重于意向治疗样本，并将采用混合模型方差分析。结果将提供司来吉兰和安慰剂之间差异的效应量的可靠估计，该估计将用于确定提供足够把握度所需的样本量，以在随后的全规模临床试验中检测显著差异。研究结果对于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很重要。

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.