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

NCT ID: NCT04998006

Last Updated: 2025-11-10

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 77 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-02-25
• Study Completion Date: 2024-12-23

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.

Detailed Description

At present, the consumption of alcohol and alcohol use disorder (AUD) constitute a public health crisis. Due to the neurobiological complexity of AUD, the development of new treatments requires a deeper understanding of the molecular mechanisms underlying etiology and course of AUD. This includes the degree to which cannabis use may reduce or enhance harms of alcohol consumption through cannabinoid influence on gut and immune functions. One potential mechanism through which cannabinoids may exert beneficial effects in heavy drinkers is through their role in modulating the gut microbiome and immune system, which have been found to be disrupted by alcohol. However, it is also possible that cannabinoids, specifically delta-9-Tetrahydrocannabinol (THC), may confer harms in heavy drinkers by enhancing the intoxicating effects of alcohol. The current study will be the first to explore the acute and long-term effects of cannabis on alcohol use and neurobehavioral phenotypes, including alcohol craving, impulsivity, and impaired cognition, as well as the impact of cannabinoids on the microbiota-gut-brain-axis (MGBA) in human non-treatment-seeking, regular-cannabis-using heavy drinkers.

This study examines the effects of legal market cannabis on acute and long-term alcohol use, (specifically the effects of alcohol and cannabis use on gut microbiome and inflammatory markers in the blood) in a 4-week, observational design using both traditional and mobile lab settings, as well as self-report, daily diary methodology. Participants will complete two Phases (A and B) following by two visits to our mobile laboratory (Visits A and B), the order of which will be counterbalanced across participants so that half of participants will complete phase A/visit A first, and the other half will complete Phase B/Visit B first. Phase A involves 2 weeks of no cannabis use followed by a mobile lab session (Visit A), involving biological sample collection, neurobehavioral testing and an alcohol self-administration task. Phase B involves 2 weeks of ad lib use of participant preferred cannabis product, followed by a session in the mobile lab session (Visit B) in which participants will complete the same neurobehavioral tasks, biological sample collection, and alcohol self-administration task immediately following acute ingestion of preferred cannabis strain in participant homes.

Conditions

Cannabis Use; Alcohol Use; Inflammation

Keywords

Alcohol; Cannabis; Microbiome; Marijuana

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

1. 21-60 years of age

2. Able to provide consent

3. 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.

4. 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

5. Willing to abstain from cannabis use for 14 days

6. We are prioritizing the recruitment of participants in the Fort Collins/Loveland area

Exclusion Criteria

1. Daily tobacco use*** (Vape and Hooka included)

2. Actively seeking treatment for alcohol use disorder or other substance use disorder

3. Females cannot be pregnant, breastfeeding or trying to become pregnant

4. Meet criteria for psychotic, bipolar or major depressive disorder with suicidal ideation, or history of these disorders

5. Immune-relevant disease (e.g., osteoarthritis, HIV, cancer, recent infection, other autoimmune disorder) or currently taking an immune-modulating medication***

6. Current use of psychotropic medications (except anti-depressants )

7. Report illicit drug use in past 60-days or fail drug screen

8. Major medical condition that contraindicates the consumption of alcohol or cannabis.

9. Use of an antibiotic medication in the past 3 months

10. Current GI disorder including: inflammatory bowel disease, irritable bowel disease, diverticular disease, peptic ulcer/gastritis and gastroesophageal reflux disease.

11. Use of probiotic or supplement drinks at least once per week over the last 3 months

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Colorado, Boulder

OTHER

Sponsor Role: collaborator

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Hollis Karoly

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hollis C. Karoly, PhD

Role: PRINCIPAL_INVESTIGATOR

CU Anschutz School of Medicine

Locations

CU Anschutz School of Medicine

Aurora, Colorado, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 40996525 (View on PubMed)

Other Identifiers

K23AA028238

Identifier Type: NIH

Identifier Source: secondary_id

View Link

24-2424

Identifier Type: -

Identifier Source: org_study_id