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

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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.