EXPLORING DIFFERENTIAL BIOLOGICAL AND PSYCHOLOGICAL EFFECTS OF REGULAR ALCOHOL AND CANNABIS USE IN HUMANS

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. Research has established deleterious health effects of heavy and persistent alcohol use, including imbalance of the gut microbiome (termed dysbiosis) and systemic inflammation. Conversely, research shows cannabis to have consistent anti-inflammatory properties and support mucosal defense and repair of the intestinal wall. However, very little research investigates the effects of alcohol and cannabis co-use on these biological symptoms. Even further, the microbiota-gut-brain axis details the bidirectional relationship between the gut and psychological function. Current literature demonstrates an inarguable influence of gut health and systemic inflammation on psychiatric symptoms such as depression and anxiety. Even further, certain personality traits have been linked to behavioral tendencies such as substance use.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, individuals who regularly use both alcohol and cannabis, and individuals who abstain from both substances). The study encompassed 4 multi-disciplinary aims spanning health outcomes impacted by substance use. The aims were to: (1) explore trait depression, anxiety and impulsivity as well as personality traits among the four groups, (2) examine differences in baseline circulating levels of endocannabinoids related to substance use patterns, (3) investigate group differences in gut microbiome composition and intestinal permeability, and (4) explore group differences in circulating inflammatory markers. These aims were 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 21-58 who were screened into groups according to their reported use of alcohol and cannabis. An observational cross-sectional design was used to collect data from the alcohol-only, cannabis-only and abstinence groups, while the alcohol and cannabis co-use data was supplied by a sister experimental study following identical eligibility criteria and near-identical data collection methods (barring some design constraints within the co-use group). The control group was expected to exhibit the healthiest profiles in all measures, followed by the exclusive cannabis use group. The exclusive alcohol use group was expected to exhibit the poorest health outcomes, with the co-use group falling between the exclusive alcohol and cannabis use groups. Eligible participants completed a virtual consent and instructional session followed by 14 days of online daily diaries detailing substance use, exercise and mood, and then completed their participation with a laboratory session involving biological sample collection and several electronic surveys. Statistical evaluation of group differences included analyses of covariance as well as non-parametric Kruskal-Wallis tests to investigate aims 1, 2 and 4. Aim 3 analyzed data from an advanced biostatistics pipeline for microbiome analysis, comparing alpha and beta diversity metrics as well as relative abundance and total read counts of identified taxa. Results revealed some persistent themes suggesting that cannabis use in the absence of alcohol predominantly exhibits protective or regulatory effects on immune and microbiome homeostasis, while alcohol consumption supports a more inflammatory and dysbiotic profile. While these data cannot speak to causality of observed relationships, the overall results support the notion that alcohol and cannabis use display differential influences on the gut microbiome and immune signaling in ways that may converge with mental health symptoms and personality traits. The current F31-supported study establishes a preliminary groundwork for more extensive and rigorous research on integrative psycho-physiological processes and how they are impacted by differing patterns of alcohol and cannabis use.