Marijuana's Impact on Alcohol Motivation and Consumption

 描述(申请人提供)：在酒精使用障碍(AUD)患者中，大麻使用障碍(CUD)是最普遍的共病药物使用障碍[1-3]。大麻的使用与更多的大量饮酒[2，4-7]和更差的AUD治疗结果[8]相关。在酒精依赖患者中，在酒精治疗后使用大麻似乎会减少酒精的持续缓解，并增加酒精复发的风险[9，10]。大麻增强了酒精的主观影响[11]，并增加了饮酒的动机[12-16]，这可能解释了为什么它阻碍酒精治疗并保持大量饮酒。大麻可以显著增加酒精动机的机制包括大麻诱导的积极主观效应；更高的大麻剂量也可能引起厌恶效应(例如焦虑)，这反过来可能导致预期通过酒精缓解这种负面情感状态；大麻可能影响包括去抑制和工作记忆在内的执行功能，这可能会增加对酒精的偏好，可能达到过高的水平。然而，还没有一项人体研究充分研究大麻是否以及如何增加酒精和酒精消费的动机[11，17，18]。这项实验室研究将采用重复测量实验设计，以检验与安慰剂相比，高剂量(6.9%THC)和中等剂量(3%THC)大麻对酒精渴求的影响，以及暴露于酒精提示后对酒精需求的行为经济学衡量，以及在酒精选择任务中，参与者选择喝酒或接受金钱补贴的酒精选择任务的影响[19，20]。将测试大麻对酒精相关依赖变量影响的调节因素：DSM5酒精使用障碍严重程度、情感脆弱性(焦虑敏感、痛苦不耐受)和特质冲动。这项研究将招募150名寻求重度间歇性酒精饮酒者的未接受治疗的人，他们每周至少吸食两次大麻。这一发现将让研究人员和临床医生了解大麻是如何显著增加饮酒欲望和消费的。这项提议的策略是使用最全面的受控测试来表征大麻对酒精的假定影响。来自这项研究的大麻对酒精渴望和复发相关行为有害影响的经验证据可以指导临床决策，为寻求治疗AUDS或减少大量饮酒模式的大麻使用者提供有针对性的治疗建议。美国目前大麻合法化的趋势，以及过度饮酒对健康和经济的重大影响，突显了调查吸食大麻对酒精消费的影响，以便为大麻政策和预防提供信息的紧迫性。这项研究与NIH伙伴关系--NIH成瘾合作研究(CRAN)[21]的目标很好地一致，并有可能获得关于大麻可能对维持问题饮酒和酒精使用障碍构成风险的机制的大量信息。

 DESCRIPTION (provided by applicant): Among individuals with alcohol use disorders (AUDs), cannabis use disorder (CUD) is the most prevalent comorbid drug use disorder [1-3]. Marijuana use has been associated with greater number of heavy drinking episodes [2, 4-7] and worse AUD treatment outcomes [8]. Among patients with alcohol dependence, marijuana use following alcohol treatment appears to reduce sustained remission from alcohol and increases risk of alcohol relapse [9, 10]. Marijuana enhances the subjective effects of alcohol [11] and increases motivation for alcohol use [12-16], which may explain why it hinders alcohol treatment and maintains heavy drinking. Mechanisms whereby marijuana may acutely increase alcohol motivation include marijuana-induced positive subjective effects; higher marijuana dose may also induce aversive effects (e.g., anxiety) that may in turn lead to anticipation of relief from such negative affective state with alcohol; marijuana may affect executive functions including disinhibition and working memory, which could increase preference for alcohol, potentially at excessive levels. However, no human studies have fully examined whether and how marijuana increases motivation for alcohol and alcohol consumption [11,17,18]. This laboratory study will employ a repeated measures experimental design to examine the effect of high (6.9% THC) and moderate (3% THC) dose of marijuana, relative to placebo, on alcohol craving and on behavioral economic measure of alcohol demand after exposure to alcohol cues, and on subsequent drinking in an alcohol choice task in which participants choose either to drink or receive monetary reinforcement for drinks not consumed [19, 20]. Moderators of the marijuana's effects on alcohol-related dependent variables will be tested: DSM5 alcohol use disorder severity, affective vulnerability (anxiety sensitivity, distress intolerance), and trait impulsivit. The study will recruit 150 non-treatment seeking heavy episodic alcohol drinkers who smoke marijuana at least twice weekly. The findings will inform researchers and clinicians about how marijuana acutely increases alcohol craving and consumption. The strategy of this proposal is to use the most comprehensive controlled test characterizing marijuana's putative effects on alcohol. Empirical evidence on marijuana's deleterious effects on alcohol craving and relapse-related behaviors from this study can guide clinical decisions with respect to targeted treatment recommendations for marijuana users seeking treatment for AUDs or making reductions in heavy drinking patterns. The current trend to legalize marijuana along with the significant health and economic impact of excessive alcohol consumption in the U.S. highlight the urgency to investigate effects of marijuana smoking on alcohol consumption in order to inform marijuana policy and prevention. This research is well-aligned with the objectives of the NIH partnership, the Collaborative Research on Addiction at NIH (CRAN) [21], and has the potential to yield substantial information about the mechanisms whereby marijuana may pose a risk for the maintenance of problem drinking and alcohol use disorders.