Alcohol and Cannabis Co-Use and the Gut-Brain Axis

NCT04998006 | Completed DMC

• 2 other identifiers: 24-2424K23AA028238
• Study Type: observational
• Target: 77
• Locations: 1 country
• Sites: 1

Brief Summary

This observational study aims to improve our understanding of how legal market cannabis use impacts acute and long-term alcohol use, the microbiota-gut-brain-axis (MGBA), and neurobehavioral alcohol use phenotypes such as impulsivity, impaired cognitive functioning, and craving, among individuals who regularly use both alcohol and cannabis. Over a period of one month, subjects will participate in this three-visit study. Blood samples will be collected to allow for the assessment of inflammatory markers and cannabinoids, a fecal sample will be collected to allow for the analysis of the gut microbiome, and participants will complete cognitive and impulsivity tasks and provide craving ratings during the course of an alcohol self-administration procedure. Subjects will also participate in two 14-day daily diary data collection periods between lab sessions. Daily diary data collection will be used to assess the effects of cannabis use on alcohol use and craving longitudinally.

Conditions

Cannabis Use; Alcohol Use; Inflammation

Keywords

Alcohol; Cannabis; Microbiome; Marijuana

Outcome Measures

Primary Outcomes (5)

• Acute alcohol consumption

  Total number of drinks consumed (out of 4) in a one-hour period.

  Change over two time points: Session A (alcohol administration only) and Session B (alcohol administration + ad-libitum cannabis administration). Sessions A and B are 2 weeks apart.

• Impulsivity Cognition: Stop Signal Task

  This task requires responding quickly to "go" signals, and occasionally inhibiting those responses when a "stop" signal is displayed.

  Change over two time points (Session A [alcohol administration only] and Session B [alcohol administration + ad-libitum cannabis administration]) 2 weeks apart: Pre-alcohol/cannabis consumption, Post-alcohol/cannabis consumption

• Daily alcohol consumption

  Two 14-day daily data collection periods using self-report of alcohol craving and amount of alcohol consumed

  Change over two consecutive 14-day daily time periods

• Inflammation

  Test levels of inflammation (panel of inflammatory cytokines) at Session A (following 2 weeks of no cannabis use) and Session B (following 2 weeks of ad lib cannabis use).

  Change over two time points (Session A [alcohol administration only] and Session B [alcohol administration + ad-libitum cannabis administration]) 2 weeks apart

• Gut microbiota

  Outcomes of interest include gut bacterial diversity and composition. Gut microbiome data from Session A will be compared with gut microbiome data from Session B.

  Change over two time points (Session A [alcohol administration only] and Session B [alcohol administration + ad-libitum cannabis administration]) 2 weeks apart.

Secondary Outcomes (4)

• Change in Alcohol Craving (Visual-Analog Scale

  Change over two time points: Session A (alcohol administration only) and Session B (alcohol administration + ad-libitum cannabis administration). Sessions A and B are 2 weeks apart

• NIH Toolbox Flanker Test

  Change over two time points (Session A [alcohol administration only] and Session B [alcohol administration + ad-libitum cannabis administration]) 2 weeks apart: Pre-alcohol/cannabis consumption, Post-alcohol/cannabis consumption

• Intestinal permeability

  Change over two time points (Session A [alcohol administration only] and Session B [alcohol administration + ad-libitum cannabis administration]) 2 weeks apart

• The Alcohol Purchase Task (APT)

  Change between reward value of alcohol when cannabis is on board (session B) compared to when it is not (session A). This task will also be administered at baseline (when not intoxicated) to compare sober state-level alcohol reward

Other Outcomes (3)

• Exploratory: Daily Follow-up Messages

  Brief self-report from participants on cannabis use, exercise, and mood in the past 24 hours.

• Plasma Gamma-Glutamyl Transferase (GGT)

  Change over two time points (Session A [alcohol administration only] and Session B [alcohol administration + ad-libitum cannabis administration]) 2 weeks apart

• Change in Rey Auditory Verbal Learning Test (RAVLT)

  Change over two time points (Session A [alcohol administration only] and Session B [alcohol administration + ad-libitum cannabis administration]) 2 weeks apart: Pre-alcohol/cannabis consumption, Post-alcohol/cannabis consumption

Study Arms (1)

Overall Study Cohort

Over a period of four weeks, participants completed two Phases (A and B) followed by two visits in our mobile laboratory (Visits A and B). The order of which was counterbalanced across participants so that approximately half of the participants completed Phase A/Visit A first, and the other half completed Phase B/Visit B first. Phase A involved 2 weeks of no cannabis use followed by a mobile laboratory session (Visit A), involving biological sample collection, neurobehavioral testing, and an alcohol self-administration task. Phase B involved 2 weeks of ad-libitum use of participant-preferred cannabis products, followed by a session in the mobile laboratory (Visit B) in which participants completed the same neurobehavioral tasks, biological sample collection, and alcohol self-administration task immediately following acute ingestion of preferred cannabis strain in participant homes.

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Community Sample

You may qualify if:

• years of age
• Able to provide consent
• Heavy drinker, defined as: for men, consuming more than 4 drinks on any day or more than 14 drinks per week OR, for women, consuming more than 3 drinks on any day or more than 7 drinks per week over the last 3 months.
• Regular legal-market cannabis smoker, defined as using smoked flower cannabis obtained from a dispensary at least 3 days per/week over the past 3 months
• Willing to abstain from cannabis use for 14 days
• We are prioritizing the recruitment of participants in the Fort Collins/Loveland area

You may not qualify if:

• Daily tobacco use\*\*\* (Vape and Hooka included)
• Actively seeking treatment for alcohol use disorder or other substance use disorder
• Females cannot be pregnant, breastfeeding or trying to become pregnant
• Meet criteria for psychotic, bipolar or major depressive disorder with suicidal ideation, or history of these disorders
• Immune-relevant disease (e.g., osteoarthritis, HIV, cancer, recent infection, other autoimmune disorder) or currently taking an immune-modulating medication\*\*\*
• Current use of psychotropic medications (except anti-depressants )
• Report illicit drug use in past 60-days or fail drug screen
• Major medical condition that contraindicates the consumption of alcohol or cannabis.
• Use of an antibiotic medication in the past 3 months
• Current GI disorder including: inflammatory bowel disease, irritable bowel disease, diverticular disease, peptic ulcer/gastritis and gastroesophageal reflux disease.
• Use of probiotic or supplement drinks at least once per week over the last 3 months

Sponsors & Collaborators

• University of Colorado, Denver: lead
• University of Colorado, Boulder: collaborator
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

CU Anschutz School of Medicine

Aurora, Colorado, 80045, United States

Location

Related Publications (1)

• Gowin JL, Stallsmith V, Weldon K, Dooley G, Karoly HC. Effects of legal-market cannabis and alcohol on verbal learning and memory. Psychopharmacology (Berl). 2025 Sep 25. doi: 10.1007/s00213-025-06882-z. Online ahead of print.

  PMID: 40996525 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Biospecimen description: whole blood will be collected, plasma will be retained, fecal samples

MeSH Terms

Conditions

Alcohol Drinking; Inflammation; Marijuana Abuse

Condition Hierarchy (Ancestors)

Drinking Behavior; Behavior; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Hollis C. Karoly, PhD

  CU Anschutz School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 30, 2021
• First Posted: August 10, 2021
• Study Start: February 25, 2022
• Primary Completion: December 23, 2024
• Study Completion: December 23, 2024
• Last Updated: November 10, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Time Frame: Human phenotypic data will be uploaded at least twice a year. Non-human genomes from fecal samples will be shared within 3 months of processing and genotyping all meta-genomes
• Access Criteria: Data access through the National Institute of Mental Health Data Archive (NIAAA) and dbGaP.

Locations

US (1)