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: 8144933
• 负责人: MARGARET HANEY
• 金额: $ 50.63万
• 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/8144933
• 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; public health relevance; quetiapine; response; smoking cessation; treatment strategy; varenicline

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Demand for marijuana treatment has far outpaced the development of effective treatment strategies. Recent data from our human laboratory model of marijuana dependence show that daily marijuana smokers who also smoke tobacco cigarettes (54% of sample) were 9.5 times more likely to relapse to marijuana than nonsmokers. We will directly assess how cigarette smoking and medication maintenance influence marijuana withdrawal and relapse, with the aim of using these data to improve marijuana treatment outcome.

描述（由申请人提供）：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，药物可能：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），或增加大麻渴望和复发（奎替卡松）。此外，吸烟者（54%的样本）比不吸烟者更容易复发大麻。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，并在他们戒烟后。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，在戒烟和吸烟的条件下大麻复发。我们假设吸烟直接增加了大麻复吸的可能性，因此大麻吸烟者在戒烟阶段的复吸频率低于吸烟作为替代品阶段。如果戒烟可以减少大麻的复发，那么将戒烟纳入大麻治疗以改善结果就有了很强的理由。如果戒烟对复发没有影响，那么未来的研究可以集中在为这个更棘手的大麻吸烟者子集开发强化大麻治疗策略上。目标二：确定是否烟碱乙酰胆碱受体（nAChR）部分激动剂，伐尼克兰，单独和与大麻素激动剂，屈大麻酚，减少大麻戒断和复发。烟草依赖的大麻吸烟者将戒烟（使用应急管理），并随机接受安慰剂或伐尼克兰。住院期间，安慰剂组和伐尼克兰组均将以平衡顺序给予活性和非活性屈大麻酚。我们假设伐尼克兰与大麻素激动剂联合使用将最有效地减少这一人群的大麻复吸。探索性目标3：为了评估压力反应性和靶向遗传多态性作为复发和大麻效应的预测因子，所有参与者将提供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）的个体更有可能对大麻复发，（2）特定的遗传多态性将预测增强的大麻中毒，渴望和复发。这些研究的结果可用于更好地针对大麻吸烟者的脆弱亚型进行治疗。影响力：由于大多数每日吸食大麻的人都吸食烟草卷烟，而且吸烟是大麻复发的预测因素，因此这项提案将通过针对这一棘手的、相当大的大麻吸食者群体来促进大麻治疗的结果。 公共卫生相关性：对大麻治疗的需求远远超过了有效治疗策略的发展。我们的人类实验室大麻依赖模型的最新数据显示，每天吸食大麻的人（54%的样本）比不吸烟者更容易复发大麻。我们将直接评估吸烟和药物维持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。