Exploring differential biological and psychological effects of regular alcohol and cannabis use in humans

项目概要/摘要 大麻是饮酒者最常用的物质，但存在相互矛盾的情况 有关大麻对饮酒和特定健康结果影响的证据。此外， 长期和经常使用这些物质的生理反应有很大不同。目前的研究 旨在调查具有不同模式的个体之间的生理和心理差异 酒精和大麻的使用（专门且定期仅使用大麻、仅使用酒精的个人，以及 经常使用酒精和大麻的人）。具体目标是 (1) 研究以下因素的影响： 定期摄入大麻和酒精对三组肠道微生物组和肠道通透性的影响， (2) 检查内源性大麻素的基线循环水平以及与物质使用相关的差异 模式，以及（3）探索三组抑郁症和焦虑症的特征症状和诊断 经验证的指数，例如贝克的抑郁和焦虑量表。这些目标将通过收集来测试 粪便和血液样本，以及进行一些心理评估和药物使用 对年龄在 21 至 40 岁之间经常使用酒精或大麻或两者兼而有之的个人进行问卷调查 两者都有。当前的提案在其多方面方法来检查酒精和酒精的影响方面具有创新性。 大麻，其新颖之处在于考虑了内源性大麻素-微生物群-肠-脑轴。结构方程 建模将用于利用来自微生物组先进生物统计管道的数据来研究目标 分析。该提案旨在推进候选人成为独立候选人的长期目标 具有先进方法和统计知识的科学家，可应用于临床治疗 物质使用和精神健康障碍。培训目标是 (a) 培养技能和知识 连接生理过程和人类精神病理学/行为（酒精和药物使用、抑郁症 和焦虑），(b) 培养人类肠道微生物组研究和分析的熟练程度和应用专业知识，以及 (c) 发展大麻素和内源性大麻素系统研究的能力和应用专门知识 （方法和分析）。从该提案中产生的基础知识将告知候选人 未来的研究方向和资助申请。培训将使候选人成为一名创新、 熟练的研究人员能够利用先进的方法和统计数据进行严格的研究 综合心理生理过程及其如何受到酒精和大麻的影响。

Project Summary/Abstract Cannabis is the most commonly used substance among individuals who consume alcohol, but there is conflicting evidence regarding the effects of cannabis on alcohol use and specific health outcomes. Furthermore, physiological responses to long-term and regular use of these substances differ substantially. The present study aims to investigate physiological and psychological differences across individuals with different patterns of alcohol and cannabis use (individuals who exclusively and regularly use cannabis-only, alcohol-only, and individuals who regularly use both alcohol and cannabis). The specific aims are to (1) investigate the effects of regular cannabis and alcohol consumption on the gut microbiome and intestinal permeability in the three groups, (2) examine baseline circulating levels of endocannabinoids and differences in relation to substance use patterns, and (3) explore trait depression and anxiety symptoms and diagnoses among the three groups with validated indices such as Beck’s depression and anxiety inventories. These aims will be tested through collection of fecal and blood samples, as well as administration of several psychological assessments and substance use questionnaires to individuals between the ages of 21-40 who regularly use alcohol or cannabis or a combination of both. The current proposal is innovative in its multi-faceted approach to examining the effects of alcohol and cannabis, and novel in its consideration of an endocannabinoid-microbiota-gut-brain axis. Structural equation modeling will be used to investigate the aims, with data from an advanced biostatistics pipeline for microbiome analysis. This proposal is designed to advance the candidate’s long-term goal of becoming an independent scientist with advanced methodological and statistical knowledge that can be applied to clinical treatment of substance use and mental health disorders. The training objectives are to (a) develop skills and knowledge to bridge physiological processes and human psychopathology/behavior (alcohol and substance use, depression and anxiety), (b) develop proficiency and applied expertise in human gut microbiome research and analysis, and (c) develop competency and applied expertise in cannabinoid and endocannabinoid system research (methodology and analysis). Foundational knowledge generated from this proposal will inform the candidate’s future research directions and grant applications. The training will enable the candidate to become an innovative, skilled researcher capable of utilizing advanced methods and statistics to conduct rigorous research on integrative psycho-physiological processes and how they are impacted by alcohol and cannabis.