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

项目摘要/摘要 大麻是饮酒个人最常用的物质，但两者之间存在矛盾 关于大麻对酒精使用和特定健康后果影响的证据。此外， 长期和定期使用这些物质的生理反应有很大不同。目前的研究 目的是调查具有不同模式的个体之间的生理和心理差异 酒精和大麻使用(专门和定期使用大麻的个人，仅酒精使用，以及 经常饮酒和吸食大麻的人)。具体目的是(1)调查 定期吸食大麻和饮酒对三组肠道微生物群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有关的差异 模式，和(3)探讨特质抑郁和焦虑症状和诊断三组 经过验证的指数，如贝克的抑郁和焦虑问卷。这些目标将通过收集来检验 粪便和血液样本，以及若干心理评估和物质使用的管理 向21-40岁经常饮酒或吸食大麻或混合吸食者发放问卷 两者都是。目前的提案在研究酒精和酒精的影响的多方面方法方面是创新的 大麻，在考虑内源性大麻素-微生物区系-肠道-脑轴方面是新颖的。结构方程 建模将用于调查目标，数据来自微生物组的先进生物统计管道 分析。这项提议旨在推进候选人成为独立人士的长期目标 具有先进的方法学和统计学知识并可应用于临床治疗的科学家 物质使用和精神健康障碍。培训目标是：(A)发展技能和知识，以 桥梁生理过程和人类精神病理/行为(酒精和药物使用、抑郁 和焦虑症)，(B)培养在人体肠道微生物组研究和分析方面的熟练程度和应用专门知识，以及 (C)培养大麻和大麻内毒素系统研究方面的能力和应用专门知识 (方法和分析)。从这份建议书中产生的基础知识将为候选人 未来的研究方向和拨款申请。培训将使应聘者成为一名创新的、 熟练的研究人员，能够利用先进的方法和统计方法对 综合心理生理过程以及酒精和大麻对这些过程的影响。

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.