Division on Substance Use Disorders, New York State Psychiatric Institute, Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
Addict Biol. 2019 Jul;24(4):765-776. doi: 10.1111/adb.12664. Epub 2018 Oct 31.
Tobacco and cannabis co-users (T+CUs) have poor cannabis cessation outcomes, but the mechanisms underlying this are not well understood. This laboratory study examined the effects of (1) the partial nicotinic agonist, varenicline, on tobacco cessation among T+CUs, and (2) varenicline, alone, and when combined with the cannabinoid agonist nabilone, on cannabis withdrawal and a laboratory model of cannabis relapse. Non-treatment-seeking T+CUs were randomized to active-varenicline or placebo-varenicline, and completed a 15-day outpatient phase; varenicline was titrated to 1 mg BID during days 1-8, and participants were instructed to abstain from tobacco during days 9-15. Participants then moved inpatient for 16 days, where they continued their outpatient medication and tobacco abstinence. Inpatient testing included two, 8-day medication periods, where active-nabilone and placebo-nabilone were administered in counterbalanced order, and measures of acute cannabis effects (days 1-2), withdrawal (days 4-5) and 'relapse' (days 6-8) were collected. Participants in the active-varenicline group were more likely to achieve cotinine-verified tobacco abstinence during the outpatient period versus placebo-varenicline group (46 percent versus 24 percent, respectively), and also reported less mood disturbance and cigarette craving while inpatient. Active-nabilone attenuated cannabis withdrawal in both groups but did not affect cannabis relapse. Regression analyses revealed that two tobacco-related variables, i.e. age of first cigarette use, and cigarette craving while inpatient, were independent predictors of cannabis relapse outcomes. Thus, varenicline holds promise in this population, as a tool to examine the effects of tobacco abstinence on cannabis use outcomes, and as a component of smoking cessation treatments targeting T+CUs.
烟草和大麻共同使用者（T+CUs）的大麻戒除效果不佳，但其中的机制尚不清楚。本实验室研究考察了（1）部分烟碱型乙酰胆碱受体激动剂伐伦克林对 T+CUs 中烟草戒除的影响，以及（2）伐伦克林单独使用，以及与大麻素激动剂纳布啡联合使用对大麻戒断和大麻复吸的实验室模型的影响。非治疗寻求的 T+CUs 被随机分配到活性伐伦克林或安慰剂伐伦克林组，并完成了为期 15 天的门诊阶段；在第 1-8 天，伐伦克林滴定至 1mg BID，参与者被指示在第 9-15 天内戒除烟草。然后，参与者搬入住院病房 16 天，继续进行门诊药物治疗和烟草戒断。住院期间测试包括两个为期 8 天的药物期，以交替方式给予活性纳布啡和安慰剂纳布啡，并在第 1-2 天（急性大麻效应）、第 4-5 天（戒断）和第 6-8 天（复吸）采集测量指标。与安慰剂伐伦克林组相比，活性伐伦克林组在门诊期间更有可能实现可替宁验证的烟草戒断（分别为 46%和 24%），并且在住院期间报告的情绪障碍和香烟渴求也较少。活性纳布啡在两组中均减轻了大麻戒断，但对大麻复吸没有影响。回归分析显示，两个与烟草相关的变量，即首次吸烟年龄和住院期间的香烟渴求，是大麻复吸结果的独立预测因子。因此，伐伦克林有望成为研究烟草戒断对大麻使用结果影响的工具，以及针对 T+CUs 的戒烟治疗的组成部分。
