Cannabis' Impact on Alcohol Consumption: Integrating Laboratory and Ecological Momentary Assessment Methods

项目总结/摘要 大麻是酒精使用者中最常见的与酒精同时使用的精神活性药物 疾病（AUD）。目前的提案推进了我们团队对大麻使用（CU）影响的研究， 大麻-酒精联合使用对酒精相关结果的影响。临床研究结果表明，CU是 与饮酒密切相关，尽管关于大麻是否减少或增加饮酒的证据 是混合的。我们的研究表明，Δ-9-四氢大麻酚（THC）可以显著降低相对酒精含量， 在受控实验室条件下，大量大麻和酒精共同使用者的价值和消费量。 来自大麻二酚（CBD）动物模型的证据表明，CBD也可以减少酒精渴望， 消费目前临床研究的一个重要空白是缺乏人体实验室研究， 酒精消费与大麻有关，大麻素成分（THC和CBD）不同。此外，委员会认为， 除了大麻和酒精之间的药效学相互作用的数据外， 已经研究了酒精和大麻的综合作用（即，大麻;同时使用-SAM） 酒精消费。最后，以前的研究没有评估大麻对酒精使用的影响， 在受控实验室条件下和自然环境中的同一个体。该项目将 使用多种方法提供大麻对酒精结果影响的最全面测试 设计：（1）实验室对照给药THC与单独吸烟与同时吸烟的CBD 酒精和（2）生态瞬时评估（EMA）的事件水平的背景因素，可以帮助 阐明CU与日常生活中酒精相关结果之间的关联。实验室 阶段将采用3（受试者内大麻素剂量：12%THC/<1%CBD，12%CBD/<1%THC，安慰剂）X 2（受试者间：大麻+酒精预激剂量vs大麻+酒精安慰剂）混合因子 研究设计旨在检查200例非寻求治疗的重度间歇性饮酒对后续饮酒的影响 每周使用大麻的饮酒者（目标1）。该实验室阶段的数据将与智能手机集成- 基于CU模式（数量，THC/CBD比例，效力，模式），背景（位置，社会），酒精 在为期4周的EMA期间，从同一个人那里收集渴望，消费和后果。 实验室和EMA数据的整合使研究实验室大麻的独特影响成为可能 状态依赖的酒精反应变量和基于场的CU和情境因素对酒精渴望的影响， 消费和后果（目标2）。大麻（医疗和娱乐）和SAM动机和AUD 严重程度将被探讨为潜在的调解人之间的联系CU和酒精行为在 自然环境（目标3）。这项研究与合作研究的目标一致， 成瘾在NIH和大麻监管科学和AUD治疗具有重要意义， 解决特定大麻素的相对影响以及大麻-酒精共同使用的背景风险。

PROJECT SUMMARY/ABSTRACT Cannabis is the most common psychoactive drug co-used with alcohol among individuals with alcohol use disorder (AUD). The current proposal advances our team’s research on the impact of cannabis use (CU) and cannabis-alcohol co-use on alcohol-related outcomes. Findings from clinical studies indicate that CU is strongly linked with alcohol use, although evidence regarding whether cannabis reduces or increases drinking is mixed. Our research has demonstrated that Δ-9-tetrahydrocannabinol (THC) acutely reduces relative alcohol value and consumption in heavy cannabis and alcohol co-users under controlled laboratory conditions. Evidence from animal models on cannabidiol (CBD) suggests CBD may also reduce alcohol craving and consumption. An important gap in current clinical research is lack of human laboratory studies that examine alcohol consumption in relation to cannabis varying in cannabinoid composition (THC and CBD). Moreover, aside from data on pharmacodynamic interactions between cannabis and alcohol, no human laboratory studies have examined the combined effects of alcohol and cannabis (i.e., marijuana; simultaneous use-SAM) on alcohol consumption. Finally, no previous study has evaluated the impact of cannabis on alcohol use within the same individual under both controlled laboratory conditions and in the natural environment. This project will provide the most comprehensive tests of the impact of cannabis on alcohol outcomes using a multi-method design: (1) controlled laboratory administration of THC versus CBD smoked alone versus simultaneously with alcohol and (2) ecological momentary assessment (EMA) of event-level contextual factors that can help elucidate the associations between CU and alcohol-related outcomes in daily life contexts. The laboratory phase will employ a 3 (within-subjects cannabinoid dose: 12% THC/<1% CBD, 12% CBD/<1%THC, placebo) X 2 (between-subjects: cannabis + an alcohol-priming dose versus cannabis + alcohol placebo) mixed factorial design to examine these effects on subsequent drinking in 200 nontreatment-seeking heavy episodic alcohol drinkers who use cannabis weekly (Aim 1). Data from this laboratory phase will be integrated with smartphone- based data on CU patterns (amount, THC/CBD ratio, potency, mode), context (location, social), alcohol craving, consumption, and consequences collected from the same individuals over a 4-week EMA period. Integration of laboratory and EMA data enables examining the unique influences of laboratory-based cannabis state-dependent alcohol response variables and field-based CU and contextual factors on alcohol craving, consumption, and consequences (Aim 2). Cannabis (medical and recreational) and SAM motives and AUD severity will be explored as potential moderators of the associations between CU and alcohol behaviors in the natural environment (Aim 3). This research is well-aligned with the objectives of the Collaborative Research on Addiction at NIH and has important implications for cannabis regulatory science and AUD treatment by addressing the relative impact of specific cannabinoids as well as contextual risk in cannabis-alcohol co-use.