Marijuana Relapse: Influence of Tobacco Cessation and Varenicline

对大麻治疗的需求远远超过了治疗策略的发展。我们的人类 实验室研究表明，药物可以：减少大麻戒断症状和复发 (洛非西定和屈诺比诺)，不影响结果(巴氯芬，米氮平)，也不增加对大麻的渴望 和复发(奎硫平)。此外，吸烟者(占样本的54%)复发的可能性是吸烟者的9.5倍 吸食大麻的人比不吸烟的人多。这项提案将评估吸烟和药物治疗对健康的影响。 旨在利用这些数据来改善大麻的治疗结果。 目标1：比较吸食大麻的吸烟者目前正在吸烟时吸食大麻和复发的情况 在他们戒烟之后。烟草依赖，每天吸食大麻的人将在我们的住院模型中进行测试 在戒烟和正常吸烟的情况下，大麻都会复发。我们假设香烟 吸烟直接增加了大麻复发的可能性，这样吸食大麻的人就会减少复发 经常处于戒烟阶段，而不是在正常吸烟阶段。如果戒烟能减少大麻复发， 将戒烟纳入大麻治疗将有很强的理由来改善 结果。如果戒烟对复发没有影响，那么未来的研究可以集中在开发 针对这一更难对付的大麻吸烟者的强化大麻治疗策略。 目的#2：确定烟碱型乙酰胆碱受体(NAChR)部分激动剂varenicline单独和在 与大麻素激动剂Dronabinol联合使用，可以减少大麻的戒断和复发。烟草- 依赖大麻的吸烟者将戒烟(使用应急管理)并 随机接受安慰剂或瓦伦克林治疗。在住院期间，安慰剂组和瓦伦克林组都将 以平衡顺序给予活性和非活性Dronabinol。我们假设瓦伦克林联合 使用大麻素激动剂将最有效地减少大麻在这一人群中的复发。 探索性目标3：评估应激反应和靶基因多态作为预测 复发和大麻效应所有参与者都将捐献DNA样本并接受特里尔社会压力 测试(TSST)。我们预测：(1)对TSST表现出较大反应(皮质醇、心率)的个体将 更有可能再次吸食大麻，以及(2)特定的基因多态将预测大麻的增加 醉酒、渴望和故态复萌。这些研究的结果可能被用来更好地靶向治疗 易受伤害的大麻吸烟者亚型。 影响：因为大多数日常吸食大麻的人都吸烟草香烟，而且吸烟是 预测大麻复发，这项提议将通过针对以下目标来促进大麻治疗结果 难以对付且数量可观的吸食大麻的人群。

Demand for marijuana treatment has far outpaced the development of treatment strategies. Our human laboratory studies have shown that medications may: decrease marijuana withdrawal symptoms and relapse (lofexidine and dronabinol), not affect either outcome (baclofen, mirtazapine), or increase marijuana craving and relapse (quetiapine). Further, cigarette smokers (54% of sample) were 9.5 times more likely to relapse to marijuana than nonsmokers. This proposal will assess how cigarette smoking and medications influence marijuana withdrawal and relapse, with the aim of using these data to improve marijuana treatment outcome. Aim #1: Compare marijuana withdrawal and relapse when marijuana smokers are currently smoking cigarettes and after they have quit. Tobacco-dependent, daily marijuana smokers will be tested in our inpatient model of marijuana relapse during both a Quit and a Smoking-as-Usual condition. We hypothesize that cigarette smoking directly increases the likelihood of marijuana relapse, so that marijuana smokers will relapse less frequently in the Quit than in the Smoking-as-Usual phase. If quitting cigarettes decreases marijuana relapse, there would be a strong rationale for incorporating smoking cessation into marijuana treatment to improve outcome. If tobacco cessation has no effect on relapse, then future studies could focus on developing intensive marijuana treatment strategies for this more intractable subset of marijuana smokers. Aim #2: Determine if the nicotinic acetylcholine receptor (nAChR) partial agonist, varenicline, alone and in combination with the cannabinoid agonist, dronabinol, decreases marijuana withdrawal and relapse. Tobacco- dependent, marijuana smokers will quit smoking cigarettes (using contingency management) and be randomized to receive Placebo or Varenicline. While inpatient, both the Placebo and the Varenicline group will be given active and inactive dronabinol in counter-balanced order. We hypothesize that varenicline combined with a cannabinoid agonist will most efficaciously decrease marijuana relapse in this population. Exploratory Aim #3: To assess stress-responsivity and targeted genetic polymorphisms as predictors of relapse and marijuana effects All participants will contribute a DNA sample and undergo the Trier Social Stress Test (TSST). We predict that: (1) individuals who show a large response (cortisol, heart rate) to the TSST will be more likely to relapse to marijuana, and (2) specific genetic polymorphisms will predict enhanced marijuana intoxication, craving and relapse. The outcome of these studies may be used to better target treatment for vulnerable subtypes of marijuana smokers. Impact: Because most daily marijuana smokers smoke tobacco cigarettes, and because cigarette smoking is predictive of marijuana relapse, this proposal will contribute to marijuana treatment outcome by targeting this intractable and sizable population of marijuana smokers.