Nicotine for Marijuana Withdrawal

描述(由申请人提供)：本提案是对RFA-DA-10-016(R01)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依赖者的大麻(MJ)戒断症状(负面情绪和由负面情绪驱动的渴望)的影响。这项建议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在生化确诊的MJ戒断15天期间对MJ戒断症状的影响。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)将被随机分配到两种剂量(0毫克或7毫克尼古丁)的TNP中的一种，同时他们将戒除MJ 15天。大量的财务应急资金将用于提供高度戒酒和完成学习。这将是第一个评估TNP对MJ消极情感相关戒断症状和使用MJ的冲动的影响的充足动力的研究。将对两组依赖MJ的人的戒烟模式和戒断情况进行评估：1)很少或从不吸烟的人，以及2)每天吸烟四支或更少的人(非常轻的吸烟者)。将使用分层随机方法对性别和吸烟者状况进行控制。据推测，在被分配到7毫克贴片的组中，MJ戒断症状将没有被分配到安慰剂组中那么严重。研究还假设，焦虑/神经质和攻击性/敌意性高的个体将比低焦虑/神经质和高攻击性/敌意性的个体从TNP中获得更多的好处。由于在我们的初步研究中没有观察到性别差异，因此不能预测性别差异。TNP的非处方药可获得性、最小的滥用风险和最小的不良副作用将使其成为一种理想的、高度可实施的MJ依赖治疗方法，如果能证明它在减少MJ戒断症状方面有效的话。有时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心理社会和医疗问题的风险，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中许多人戒烟的重要障碍。我们的研究将测试一种滥用潜力非常低的药物疗法--经皮尼古丁贴片(TNP)--在大麻依赖者15天的戒断期间有效地减少大麻戒断症状的重要可能性。测试TNP在减少大麻戒断症状方面的有效性的理由是基于我们实验室的初步证据表明TNP可能能够减轻这些症状，以及来自多个实验室的证据表明大麻戒断症状在性质和严重程度上与烟草戒断症状基本相似。我们的初步发现表明，在MJ依赖使用者(包括那些不使用烟草的人)戒除大麻期间，TNP减少了负面情绪和负面情绪动机的大麻使用冲动。因此，有理由相信，TNP还可以帮助寻求治疗的大麻依赖者保持大麻戒断，无论他们是否吸烟者。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.