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 （洛非西定和屈大麻酚），不影响任何结果（巴氯芬，米氮平），或增加大麻渴望 复吸（quetiabe）。此外，吸烟者（54%的样本）复发的可能性是吸烟者的9.5倍。 大麻比不吸烟者。这项提案将评估吸烟和药物如何影响 大麻戒断和复发，目的是利用这些数据来改善大麻治疗结果。 目标#1：比较大麻戒断和复吸时，大麻吸烟者目前正在吸烟 在他们退出之后。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， 在戒烟和吸烟的情况下大麻复发。我们假设香烟 吸烟直接增加了大麻复吸的可能性，这样大麻吸食者就会少复吸 在戒烟阶段比在戒烟阶段更常见。如果戒烟能减少大麻的复吸， 将戒烟纳入大麻治疗以改善 结果。如果戒烟对复吸没有影响，那么未来的研究可以集中在开发 强化大麻治疗策略，这更棘手的大麻吸烟者的子集。 目标#2：确定尼古丁乙酰胆碱受体（nAChR）部分激动剂伐尼克兰是否单独使用和联合使用 与大麻素激动剂屈大麻酚组合，减少大麻戒断和复发。烟草- 依赖，大麻吸烟者将戒烟（使用应急管理）， 随机接受安慰剂或伐尼克兰。在住院期间，安慰剂组和伐尼克兰组将 以平衡的顺序给予活性和非活性屈大麻酚。我们假设伐尼克兰结合了 与大麻素激动剂将最有效地减少大麻复吸在这一人群。 探索性目标#3：评估压力反应性和靶向遗传多态性作为 复发和大麻的影响所有参与者将贡献一个DNA样本，并接受特里尔社会压力 试验（TSST）。我们预测：（1）对TSST表现出较大反应（皮质醇，心率）的个体将 更有可能复发大麻，（2）特定的遗传多态性将预测增强大麻 中毒，渴望和复发。这些研究的结果可用于更好地靶向治疗 脆弱的大麻吸食者亚型 影响：因为大多数每天吸食大麻的人都吸食烟草香烟，而且因为吸烟是 预测大麻复发，这项建议将有助于大麻治疗的结果，针对这一点， 棘手的和相当大的人口大麻吸烟者。

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.