Cannabis UseFRACTALNCT04998006
Alcohol and Cannabis Co-Use and the Gut-Brain Axis
An observational study of Cannabis Use and Alcohol Use, run by University of Colorado, Denver at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 21 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Cannabis Use, Alcohol Use, Inflammation
- How many people
- 77 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Feb 2022to 23 Dec 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: Community Sample
Who may be able to join
- 21-60 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
Who cannot join
- 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 )
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
CU Anschutz School of Medicine
Aurora, Colorado, 80045
About this study
Official title: Exploring the Effects of Cannabinoids on Alcohol Consumption and the Microbiota-Gut-Brain Axis
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.
Read the 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
- Medical subject headings
- Alcohol Drinking, Inflammation, Marijuana Abuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acute alcohol consumption
Total number of drinks consumed (out of 4) in a one-hour period.
Measured: 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.
Measured: 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
Measured: 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).
Measured: 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.
Measured: 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
Test differences in alcohol craving using Visual Analog Scale in laboratory sessions in which only alcohol is consumed (Session A) and in which cannabis is self-administered prior to alcohol administration (Session B). Possible values range from 0-10, with higher scores indicating greater alcohol craving.
Measured: 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
This task requires participants to sustain attention on a stimulus while inhibiting attention to stimuli flanking it.
Measured: 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
Test levels of recent intestinal permeability measured in blood at Session A (following 2 weeks of no cannabis use) and Session B (following 2 weeks of ad lib cannabis use).
Measured: 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)
The APT is a is a well-validated, easy-to-administer measure that will be given at baseline and multiple times during session A and B. This task measures the reinforcing value of alcohol using simulated marketplace survey techniques (i.e. - how many drinks would you purchase if they cost 50 cents?)
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2021
- Study start25 Feb 2022
- Primary completion23 Dec 2024
- Study completion23 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cannabis UseStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 77 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- University of Colorado, Boulder, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Responsible party
- Sponsor
- Investigators
- Hollis C. Karoly, PhD, Principal investigator, CU Anschutz School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04998006
- Sponsor's protocol ID
- 24-2424
- Other IDs
- K23AA028238
- Acronym
- FRACTAL
- Status last verified
- May 2026
- First submitted
- 30 Jun 2021
- Last updated
- 15 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The investigators will submit all de-identified individual level phenotypic human subjects data from this project to the NIAAA data archive. The project also involves collection of human specimens (fecal samples) which will generate non-human genomic data. Specifically, the investigators plan to generate 122 (61 subjects x 2 timepoints) human gut microbiota metagenomes (i.e., gut microbiome). Deidentified genomic data from microbiome assays (and relevant phenotypic data) will be submitted to the database of Genotypes and Phenotypes (dbGaP).
Publications
Pince CL, Piercey CJ, Stallsmith VT, Weldon K, Ruehrmund J, Dooley G, Karoly HC. Behavioral phenotypes associated with cannabis and alcohol substitution. Harm Reduct J. 2026 Mar 6;23(1):74. doi: 10.1186/s12954-026-01432-y.
PubMed 41792806Gowin JL, Stallsmith V, Weldon K, Dooley G, Karoly HC. Effects of legal-market cannabis and alcohol on verbal learning and memory. Psychopharmacology (Berl). 2026 Apr;243(4):805-818. doi: 10.1007/s00213-025-06882-z. Epub 2025 Sep 25.
PubMed 40996525
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploring the Effects of Cannabinoids on Alcohol Consumption and the Microbiota-Gut-Brain Axis
- ClinicalTrials.gov ID
- NCT04998006
- Acronym / sponsor ID
- FRACTAL / 24-2424
- Conditions
- Cannabis Use, Alcohol Use, Inflammation
- Keywords
- Alcohol, Cannabis, Microbiome, Marijuana
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 77 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- University of Colorado, Boulder, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Study start
- 25 Feb 2022 (actual)
- Primary completion
- 23 Dec 2024 (actual)
- Study completion
- 23 Dec 2024 (actual)
- First posted
- 10 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 21 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Community Sample
Key inclusion criteria (6 listed)
- 21-60 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
Key exclusion criteria (11 listed)
- 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***
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Acute alcohol consumption
Time frame: 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.
Total number of drinks consumed (out of 4) in a one-hour period.
Impulsivity Cognition: Stop Signal Task
Time frame: 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
This task requires responding quickly to "go" signals, and occasionally inhibiting those responses when a "stop" signal is displayed.
Daily alcohol consumption
Time frame: Change over two consecutive 14-day daily time periods
Two 14-day daily data collection periods using self-report of alcohol craving and amount of alcohol consumed
Inflammation
Time frame: Change over two time points (Session A [alcohol administration only] and Session B [alcohol administration + ad-libitum cannabis administration]) 2 weeks apart
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).
Gut microbiota
Time frame: Change over two time points (Session A [alcohol administration only] and Session B [alcohol administration + ad-libitum cannabis administration]) 2 weeks apart.
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.
4 secondary outcomes
Change in Alcohol Craving (Visual-Analog Scale
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2026.
- Derived from this study: PubMed 41792806Pince CL, Piercey CJ, Stallsmith VT, Weldon K, Ruehrmund J, Dooley G, Karoly HC. Behavioral phenotypes associated with cannabis and alcohol substitution. Harm Reduct J. 2026 Mar 6;23(1):74. doi: 10.1186/s12954-026-01432-y.
- Derived from this study: PubMed 40996525Gowin JL, Stallsmith V, Weldon K, Dooley G, Karoly HC. Effects of legal-market cannabis and alcohol on verbal learning and memory. Psychopharmacology (Berl). 2026 Apr;243(4):805-818. doi: 10.1007/s00213-025-06882-z. Epub 2025 Sep 25.
- Individual participant dataSharing planned: Yes. The investigators will submit all de-identified individual level phenotypic human subjects data from this project to the NIAAA data archive. The project also involves collection of human specimens (fecal samples) which will generate non-human genomic data. Specifically, the investigators plan to generate 122 (61 subjects x 2 timepoints) human gut microbiota metagenomes (i.e., gut microbiome). Deidentified genomic data from microbiome assays (and relevant phenotypic data) will be submitted to the database of Genotypes and Phenotypes (dbGaP).
Related trials for Cannabis Use
Active, not recruitingObservational study
Cannabis Use and Outcomes in Black and White Patients With Cancer
Cancer
Recruiting
MATAspire: Mental Health Awareness Tailored App for Substance Prevention and Integrated Resilience Education
Alcohol Use, Cannabis Use
RecruitingObservational study
A Study in Patients Reporting Cannabis Use Followed With an Application-Based Cannabis Journal
Cancer
RecruitingObservational study
Study of an Oral Fluid Testing Approach
Cannabis Use, Cannabis Intoxication
Not yet recruitingEarly Phase 1
Research Investigating Drug Effects-2 (RiDE-2)
Cannabis Use, Substance Use Disorder (SUD)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hollis C. Karoly, PhD principal investigator
CU Anschutz School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cannabis Use and Alcohol Use, run by University of Colorado, Denver at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Acute alcohol consumption (time frame: 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.). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04998006, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2026.