Marijuana Relapse: Influence of Tobacco Cessation and Varenicline

大麻复吸：戒烟和伐尼克兰的影响

• 批准号: 8282795
• 负责人: MARGARET HANEY
• 金额: $ 51.67万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8282795
• 关键词: Abstinence; Affect; Agonist; Baclofen; Cannabinoids; Cigarette; Cigarette Smoker; Clinical; Cues; DNA; Data; Development; Equilibrium; Funding; Future; Genetic Polymorphism; Genetic Predisposition to Disease; Goals; Heart Rate; Human; Hydrocortisone; Individual; Inpatients; Intoxication; Laboratories; Laboratory Study; Maintenance; Marijuana; Marijuana Dependence; Marijuana Smoking; Mirtazapine; Modeling; Nicotinic Agonists; Nicotinic Receptors; Outcome; Outcome Study; Participant; Pharmaceutical Preparations; Phase; Placebos; Population; Procedures; Randomized; Relapse; Sample Size; Sampling; Self Administration; Smoke; Smoker; Smoking; Stress; Testing; Tetrahydrocannabinol; Time; Tobacco; Tobacco Use Cessation; Treatment outcome; Trier Social Stress Test; Withdrawal; Withdrawal Symptom; cigarette smoking; contingency management; craving; effective therapy; improved; lofexidine; marijuana user; non-smoker; quetiapine; response; smoking cessation; treatment strategy; varenicline

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.

对大麻治疗的需求远远超过了治疗策略的发展。我们的人 实验室研究表明，药物可以：减轻大麻戒断症状并复发 （Lofexidine和Dronabinol），不影响结果（Baclofen，Mirtazapine）或增加大麻渴望 和复发（喹硫平）。此外，吸烟者（样品的54％）复发的可能性高9.5倍 大麻比非吸烟者。该建议将评估吸烟和药物如何影响 大麻戒断和复发，目的是使用这些数据来改善大麻治疗结果。 目的＃1：比较大麻抽烟时抽烟大麻的戒断和复发 在他们退出之后。依赖烟草的每日吸烟者将在我们的住院模型中进行测试 在戒烟和与普遍的情况下，大麻复发。我们假设那香烟 吸烟直接增加了大麻复发的可能性，从而使大麻吸烟者复发较少 在戒烟中，通常比在普遍的阶段相比。如果戒烟会减少大麻复发， 将戒烟纳入大麻治疗以改善的基本原理将有很强的理由 结果。如果烟草戒烟对复发没有影响，那么将来的研究可以集中于发展 大麻治疗策略的这一更棘手的大麻吸烟者子集。 AIM＃2：确定烟碱乙酰胆碱受体（NACHR）部分激动剂，varenicline，单独和中 与大麻素激动剂Dronabinol结合使用，减少了大麻的戒断和复发。烟草- 依赖的大麻吸烟者会戒烟（使用应急管理），并 随机接收安慰剂或varenicline。在住院时，安慰剂和varenicline组都将 以平衡的顺序为主动和无活跃的dronabinol。我们假设varenicline合并 使用大麻素激动剂将最有效地减少该人群中的大麻复发。 探索性目的＃3：评估应力反应性和靶向遗传多态性作为预测指标 复发和大麻效应所有参与者将贡献DNA样本并承受Trier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）的个人将会 更有可能复发到大麻，（2）特定的遗传多态性将预测大麻 中毒，渴望和复发。这些研究的结果可用于更好地靶向治疗 大麻吸烟者的脆弱亚型。 影响：因为大多数每日吸烟者都会抽大​​麻烟草香烟，并且因为吸烟是 预测大麻复发，该提案将通过目标来促进大麻治疗结果 大麻吸烟者的顽固且相当大的人群。