Marijuana's Impact on Alcohol Motivation and Consumption

 描述（由申请人提供）：在酒精使用障碍（AUD）患者中，大麻使用障碍（CUD）是最常见的共病药物使用障碍[1-3]。Maritime的使用与大量饮酒事件[2，4-7]和AUD治疗结局更差[8]相关。在酒精依赖患者中，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]。Marijuana增强了酒精的主观影响[11]并增加了酒精使用的动机[12-16]，这可能解释了为什么它阻碍了酒精治疗并保持大量饮酒。大麻可能急剧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诱导厌恶效应（例如，焦虑），这可能反过来导致预期从酒精的这种负面情感状态中解脱出来;大麻可能影响执行功能，包括去抑制和工作记忆，这可能会增加对酒精的偏好，可能是过量的。然而，没有人类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]。本实验室研究将采用重复测量的实验设计，以检查高浓度的（6.9%THC）和中等剂量（3%THC）大麻，相对于安慰剂，对酒精渴望和暴露于酒精线索后酒精需求的行为经济学指标，在酒精选择任务中，参与者选择喝酒或接受饮料的货币强化，[19][20]。大麻对酒精相关因变量的影响的调节剂将被测试：DSM 5酒精使用障碍的严重程度，情感脆弱性（焦虑敏感性，痛苦不耐受性）和特质冲动。这项研究将招募150名每周至少抽两次大麻的非治疗寻求重度间歇性饮酒者。研究结果将告知研究人员和临床医生大麻如何急剧增加酒精渴望和消费。这项建议的策略是使用最全面的控制测试来表征大麻对酒精的推定影响。这项研究中大麻对酒精渴望和复发相关行为的有害影响的经验证据可以指导临床决策，为寻求治疗AUD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。当前大麻合法化的趋势沿着美国过量饮酒对健康和经济的重大影响，突出了调查大麻吸烟对酒精消费影响的紧迫性，以便为大麻政策和预防提供信息。这项研究与NIH伙伴关系的目标一致，NIH成瘾合作研究（CRAN）[21]，并有可能产生有关大麻可能对问题饮酒和酒精使用障碍的维持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.