Nicotine for Marijuana Withdrawal

描述（由申请人提供）：本提案是对RFA-DA-10-016（R 01）大麻相关疾病药物开发的回应。与本RFA的目标一致，拟议项目的总体目标是评估经皮尼古丁贴片（TNP）治疗对MJ依赖个体大麻（MJ）戒断（负面影响和由负面影响引起的渴望）症状的影响。本提案的目的是使用安慰剂对照、双盲、随机分配的治疗设计，准确评估TNP对MJ戒断症状的影响，这些症状经过15天的生化证实的MJ戒断。为了实现这些目标，116名经过仔细筛选的大麻依赖者（58名女性）将被随机分配到两个剂量（0 mg或7 mg尼古丁）的TNP中的一个，同时他们戒除MJ 15天。将使用大量财务应急资金来提供高度的禁欲和研究完成。这将是第一个充分把握度的研究，以评估TNP对MJ负面影响相关的戒断症状和使用MJ的冲动的影响。将在两组MJ依赖者中评估戒断模式和戒烟情况：1）很少或从不吸烟的人，2）每天吸烟4支或更少的人（极轻度吸烟者）。将使用分层随机化方法控制性别和吸烟者状态。假设分配至7 mg贴剂的组中MJ戒断症状的严重程度低于分配至安慰剂的组。也有人假设，高焦虑/神经质和那些高侵略/敌意的个人将表现出更大的好处，从TNP比那些低这些特质。鉴于在我们的初步研究中没有观察到性别差异，因此无法预测性别差异。与TNP相关的非处方可用性、最小的滥用风险和最小的不良副作用将使其成为MJ依赖的理想且高度可实施的治疗，如果它可以被证明在减少MJ戒断症状方面有效的话。有时候简单的解决方案是最好的。 公共卫生相关性：大麻依赖增加了各种社会心理和医疗问题的风险，与尝试戒烟有关的戒断症状似乎是美国越来越多的大麻依赖者戒烟的重要障碍。我们的研究将测试一种重要的可能性，即具有非常低的滥用潜力的药物治疗，透皮尼古丁贴片（TNP），在大麻依赖者15天的禁欲期内有效减少大麻戒断症状。测试TNP在减少大麻戒断症状方面的功效的基本原理是基于我们实验室的初步证据，表明TNP可能能够减少这些症状，以及来自许多实验室的证据表明大麻戒断症状在性质和严重程度方面与烟草戒断症状基本平行。我们的初步研究结果表明，TNP减少了负面影响和负面影响动机的冲动，使用大麻在MJ依赖者（包括那些不使用烟草）大麻禁欲期间。因此，有理由相信TNP也可以帮助寻求治疗的大麻依赖者保持大麻戒断，无论他们是否吸烟。有时候最简单的解决方案就是最好的。

DESCRIPTION (provided by applicant): This proposal is in response to RFA-DA-10-016(R01) Medications Development for Cannabis-Related Disorders. Consistent with the goals of this RFA, the overall goal of the proposed project is to assess the impact of transdermal nicotine patch (TNP) treatment on marijuana (MJ) withdrawal (negative affect and craving motivated by negative affect) symptoms in MJ-dependent individuals. The aim of this proposal is to accurately assess the effects of TNP on MJ withdrawal symptoms across 15 days of biochemically confirmed MJ abstinence using a placebo-controlled, double-blind, randomly assigned treatment design. To achieve these goals, 116 carefully screened cannabis-dependent individuals (58 female) will be randomly assigned to one of two doses (0 mg or 7mg nicotine) of TNP while they abstain from MJ for 15 days. Large financial contingencies will be used to provide a high degree of abstinence and study completion. This will be the first adequately powered study to assess the effects of TNP on MJ negative affect-related withdrawal symptoms and urges to use MJ. Withdrawal patterns and abstinence will be assessed in two groups of MJ-dependent individuals: 1) those who rarely or never smoke tobacco, and 2) those who smoke four or fewer tobacco cigarettes per day (very light tobacco smokers). A stratified randomization method will be used to control for gender and tobacco-smoker status. It is hypothesized that MJ withdrawal symptoms will be less severe in the group assigned to the 7 mg patch than in the group assigned to the placebo. It is also hypothesized that individuals high in anxiety/neuroticism and those high in aggression/hostility will exhibit greater benefits from TNP than those low in these traits. Given that no gender differences were observed in our preliminary study, gender differences are not predicted. The over-the-counter availability, minimal abuse risks, and minimal adverse side-effects associated with TNP would make it an ideal and highly implementable treatment for MJ dependence if it can be demonstrated to be efficacious in reducing MJ withdrawal symptoms. Sometimes simple solutions are the best. PUBLIC HEALTH RELEVANCE: Marijuana dependence increases risks for a variety of psychosocial and medical problems and withdrawal symptoms associated with attempts to quit using marijuana appear to be an important obstacle to quitting for many of the increasing number of marijuana dependent individuals in the United States. Our study would test the important possibility that a pharmacotherapy with a very low abuse potential, transdermal nicotine patch (TNP), is efficacious in reducing marijuana withdrawal symptoms across a 15-day period of abstinence in marijuana-dependent individuals. The rationale for testing the efficacy of TNP in reducing marijuana withdrawal symptoms is based on preliminary evidence from our laboratory suggesting that TNP may be able to reduce these symptoms, as well as evidence from a number of laboratories indicating that marijuana withdrawal symptoms largely parallel those of tobacco withdrawal symptoms both in terms of nature and severity. Our preliminary findings suggest that TNP reduces negative affect and negative affect-motivated urge to use marijuana during abstinence from marijuana in MJ-dependent-users (including those who do not use tobacco). Thus, there is reason to believe that TNP could also assist treatment-seeking marijuana dependent individuals in maintaining marijuana abstinence, whether or not they are tobacco smokers. Sometimes the simplest solutions are the best.