CBD for the Treatment of Alcohol Use Disorder

• ClinicalTrials.gov Identifier: NCT04873453
• Recruitment Status: Recruiting
• First Posted: May 5, 2021
• Last Update Posted: March 6, 2023
• Sponsor: University of Colorado, Denver
• Information provided by (Responsible Party): University of Colorado, Denver

Study Description

Brief Summary:

This is a double-blind, placebo-controlled, parallel group study designed to assess the efficacy of full spectrum CBD and broad spectrum CBD, compared to a placebo control (PC), to reduce drinking in participants with moderate alcohol use disorder according to the DSM-V. If eligible for the study, subjects will be randomized to receive one of the conditions for 8 weeks.

Condition or disease	Intervention/treatment	Phase
Alcohol Use Disorder	Drug: Cannabidiol; Drug: Placebo	Phase 2

Detailed Description:

The current study will directly test the hypothesis that a moderate dose of CBD leads to a reduction in alcohol consumption, alcohol craving, peripheral markers of inflammation, and anxiety. It is further hypothesized that CBD will lead to increased sleep duration and quality among individuals with AUD who want to quit or reduce their drinking. The study will also determine whether the small amount of THC found in full spectrum hemp-derived CBD products produces any negative effects. The hypotheses are grounded in previous studies suggesting that CBD reduces the reinforcing properties of alcohol and decreases drinking motivation and consumption (Viudez-Martínez, García-Gutiérrez, Fraguas-Sánchez, et al., 2018). Further, CBD has shown clinical promise for tobacco, cannabis, and opioid use disorders (Hurd, 2017; Hurd et al., 2015; Prud'homme et al., 2015), and evidence indicates that these effects may be due to the ability of CBD to reduce cue-induced craving and anxiety (Gonzalez-Cuevas et al., 2018; Hurd et al., 2019). The hypotheses are also grounded in the pre-clinical literature suggesting that CBD may modulate the immune system and have anti-inflammatory effects which also helps to reduce harm associated with alcohol and may have a positive effect on those attempting to quit. Other potential mechanisms that might underlie the effects of CBD include a reduction in the severity of acute withdrawal, a reduction in protracted withdrawal, and the neuroprotective effects of CBD. Given the background literature with respect to CBD and AUDs, a logical next step is for human studies to address these questions.

To better understand the effects of hemp-derived CBD with and without a small amount of THC, the investigators propose a Phase II randomized clinical trial (RCT) to examine the safety, tolerability, and clinical effects of Full Spectrum CBD (fsCBD, contains less than 0.3% THC) vs. Broad Spectrum CBD (bsCBD, does not contain THC), vs. a matching placebo in a population of AUD subjects.

This is a double-blind, placebo-controlled, parallel group study designed to assess the efficacy of fsCBD and bsCBD, compared to a placebo control (PC), to reduce drinking in participants with moderate alcohol use disorder according to the DSM-V. If eligible for the study, subjects will be randomized to receive one of the conditions for 8 weeks.

To minimize risk of COVID transmission, the investigators will utilize Zoom for weekly subject check-ins and our Mobile Pharmacology Lab (MPL) for the collection of blood samples and clinical data for the majority of in-person visits. The initial Week 0 / Baseline visit will take place at the University of Colorado Anschutz Medical Campus. There will be MPL follow-up visits at Weeks 1, 4, and 8. Participants will be contacted by Zoom each remaining week during the 8-week period. A follow up Zoom interview will occur in Week 16 approximately 8 weeks after the end of dosing.

Overall, the clinical study is expected to take 1-2 years to complete enrollment and data analysis.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 45 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This is a double-blind, placebo-controlled, parallel group study.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Tolerability and Efficacy of Hemp-Derived CBD for the Treatment of Alcohol Use Disorder
• Actual Study Start Date: August 30, 2021
• Estimated Primary Completion Date: May 31, 2023
• Estimated Study Completion Date: May 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Full-spectrum Cannabidiol; 150mg/day of full-spectrum cannabidiol, containing less than 0.3%THC.	Drug: Cannabidiol; The current study will directly test the hypothesis that a moderate dose of CBD leads to a reduction in alcohol consumption, alcohol craving, peripheral markers of inflammation, and anxiety.; Other Name: CBD
Experimental: Broad-spectrum Cannabidiol; 150mg/day of broad-spectrum cannabidiol, containing 0%THC.	Drug: Cannabidiol; The current study will directly test the hypothesis that a moderate dose of CBD leads to a reduction in alcohol consumption, alcohol craving, peripheral markers of inflammation, and anxiety.; Other Name: CBD
Placebo Comparator: Placebo; 150mg/day of hemp-seed oil with no cannabinoids present.	Drug: Placebo; Placebo arm

Outcome Measures

Primary Outcome Measures :

1. Drinks per Drinking Day [ Time Frame: 0-8 weeks ]
   The Time Line Follow Back is a calendar-assisted measure that can be used to assess alcohol, tobacco, cannabis, and other substance use. The investigators will use this measure to create the Drinks per Drinking Day variable.
2. Drinks per Drinking Day [ Time Frame: 0-16 weeks ]
   The Time Line Follow Back is a calendar-assisted measure that can be used to assess alcohol, tobacco, cannabis, and other substance use. The investigators will use this measure to create the Drinks per Drinking Day variable.
3. Drinks per Drinking Day [ Time Frame: 0-4 weeks ]
   The Time Line Follow Back is a calendar-assisted measure that can be used to assess alcohol, tobacco, cannabis, and other substance use. The investigators will use this measure to create the Drinks per Drinking Day variable.
4. Drinks per Drinking Day [ Time Frame: 4-8 weeks ]
   The Time Line Follow Back is a calendar-assisted measure that can be used to assess alcohol, tobacco, cannabis, and other substance use. The investigators will use this measure to create the Drinks per Drinking Day variable.
5. Alcohol Dependence/Craving [ Time Frame: 0-16 weeks ]
   The Alcohol Dependence Scale measures the severity of alcohol dependence and craving symptoms. Possible scores range from 0 to 47 with higher scores indicating a worse outcome/more severe symptoms of alcohol dependency/craving.
6. Alcohol Dependence/Craving [ Time Frame: 0-8 weeks ]
   The Alcohol Dependence Scale measures the severity of alcohol dependence and craving symptoms. Possible scores range from 0 to 47 with higher scores indicating a worse outcome/more severe symptoms of alcohol dependency/craving.
7. Alcohol Dependence/Craving [ Time Frame: 0-4 weeks ]
   The Alcohol Dependence Scale measures the severity of alcohol dependence and craving symptoms. Possible scores range from 0 to 47 with higher scores indicating a worse outcome/more severe symptoms of alcohol dependency/craving.
8. Alcohol Dependence/Craving [ Time Frame: 4-8 weeks ]
   The Alcohol Dependence Scale measures the severity of alcohol dependence and craving symptoms. Possible scores range from 0 to 47 with higher scores indicating a worse outcome/more severe symptoms of alcohol dependency/craving.

Secondary Outcome Measures :

1. Cue-reactivity [ Time Frame: 0-4 weeks ]
   Cue-elicited urge to drink will be assessed using the cue-reactivity assessment, per protocol (Hutchison, 2006).
2. Cue-reactivity [ Time Frame: 4-8 weeks ]
   Cue-elicited urge to drink will be assessed using the cue-reactivity assessment, per protocol (Hutchison, 2006).
3. Cue-reactivity [ Time Frame: 0-8 weeks ]
   Cue-elicited urge to drink will be assessed using the cue-reactivity assessment, per protocol (Hutchison, 2006) .
4. Anxiety [ Time Frame: 0-4 weeks ]
   The Beck Anxiety Inventory measures the severity of anxiety symptoms. Possible scores range from 0 to 63 with higher scores indicating a worse outcome/more severe symptoms of anxiety.
5. Anxiety [ Time Frame: 4-8 weeks ]
   The Beck Anxiety Inventory measures the severity of anxiety symptoms. Possible scores range from 0 to 63 with higher scores indicating a worse outcome/more severe symptoms of anxiety.
6. Anxiety [ Time Frame: 0-8 weeks ]
   The Beck Anxiety Inventory measures the severity of anxiety symptoms. Possible scores range from 0 to 63 with higher scores indicating a worse outcome/more severe symptoms of anxiety.
7. Anxiety [ Time Frame: 0-16 weeks ]
   The Beck Anxiety Inventory measures the severity of anxiety symptoms. Possible scores range from 0 to 63 with higher scores indicating a worse outcome/more severe symptoms of anxiety.
8. Subjective Pain Level [ Time Frame: 0-4 weeks ]
   The McGill Pain Questionnaire measures the severity of subjective pain. Possible scores range from 0 to 78 with higher scores indicating a worse outcome/more severe symptoms of subjective pain.
9. Subjective Pain Level [ Time Frame: 4-8 weeks ]
   The McGill Pain Questionnaire measures the severity of subjective pain. Possible scores range from 0 to 78 with higher scores indicating a worse outcome/more severe symptoms of subjective pain.
10. Subjective Pain Level [ Time Frame: 0-8 weeks ]
    The McGill Pain Questionnaire measures the severity of subjective pain. Possible scores range from 0 to 78 with higher scores indicating a worse outcome/more severe symptoms of subjective pain.
11. Subjective Pain Level [ Time Frame: 0-16 weeks ]
    The McGill Pain Questionnaire measures the severity of subjective pain. Possible scores range from 0 to 78 with higher scores indicating a worse outcome/more severe symptoms of subjective pain.
12. Sleep Quality [ Time Frame: 0-16 weeks ]
    The Pittsburgh Sleep Quality Index measures the severity of sleep disturbances. Possible scores range from 0 to 21 with higher scores indicating a worse outcome/more severe symptoms of sleep disturbance.
13. Sleep Quality [ Time Frame: 0-8 weeks ]
    The Pittsburgh Sleep Quality Index measures the severity of sleep disturbances. Possible scores range from 0 to 21 with higher scores indicating a worse outcome/more severe symptoms of sleep disturbance.
14. Sleep Quality [ Time Frame: 4-8 weeks ]
    The Pittsburgh Sleep Quality Index measures the severity of sleep disturbances. Possible scores range from 0 to 21 with higher scores indicating a worse outcome/more severe symptoms of sleep disturbance.
15. Sleep Quality [ Time Frame: 0-4 weeks ]
    The Pittsburgh Sleep Quality Index measures the severity of sleep disturbances. Possible scores range from 0 to 21 with higher scores indicating a worse outcome/more severe symptoms of sleep disturbance.

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Must be between 21-60 years old.
2. Meets Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V) criteria for current Alcohol Use Disorder (AUD) of at least moderate severity (i.e., 4 or more DSM-V symptoms).
3. Currently seeking treatment for AUD.
4. If male, reports drinking, on average, at least 21 standard alcoholic drinks per week prior to screening; if female, reports drinking, on average, at least 14 standard drinks per week prior to screening.
5. Have at least one heavy drinking day (4 or more drinks per day for women/5 or more drinks per day for men) during the 7-day period prior to screening.
6. Live within 35 miles of the study site.

Exclusion Criteria:

1. Self-reported DSM-V diagnosis of any other substance use disorder.
2. Use nicotine daily.
3. Self-report use of cocaine, amphetamines, opioids, cannabis, or benzodiazepines in the last 30 days.
4. Report having or being treated for a current DSM-V Axis I diagnosis, including major depression, panic disorder, obsessive/compulsive disorder, post-traumatic stress disorder, bipolar affective disorder, schizophrenia, dissociative disorders, eating disorders, or any other psychotic or organic mental disorder.
5. Endorsing an item on the RMTS-S measure of suicide risk.

6. Currently taking any of the following medications:

   1. Those known to have a major interaction with Epidiolex.
   2. Acute treatment with any antiepileptic medications.
   3. Medication known to affect alcohol intake (e.g., disulfiram, naltrexone, acamprosate, and/or topiramate).
7. Self-reported history of severe alcohol withdrawal (e.g., seizure, delirium tremens).
8. Clinically significant medical problems such as cardiovascular, renal, gastrointestinal, or endocrine problems that would impair participation or limit medication ingestion.
9. Current or past alcohol-related medical illness, such as gastrointestinal bleeding, pancreatitis, hepatocellular disease, or peptic ulcer.
10. Females of childbearing potential who are pregnant, nursing, or who are not using a reliable form of birth control.
11. Current charges pending for a violent crime (not including DUI-related offenses).
12. Lack of a stable living situation.

Contacts and Locations

Contacts

Contact: Raeghan Mueller, MA; 303.724.2208; raeghan.mueller@cuanschutz.edu

Contact: Jamie Cavanaugh; jamie.cavanaugh@cuanschutz.edu

Locations

United States, Colorado

University of Colorado Denver; Recruiting

Aurora, Colorado, United States, 80045

Contact: Raeghan Mueller 303-724-2208 raeghan.mueller@cuanschutz.edu

Principal Investigator: Kent Hutchison, PhD

Sponsors and Collaborators

University of Colorado, Denver

More Information

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT04873453
• Other Study ID Numbers: 20-2694
• First Posted: May 5, 2021
• Last Update Posted: March 6, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Colorado, Denver:

Alcohol; Cannabidiol; CBD; Cannabis

Additional relevant MeSH terms:

Alcoholism; Alcohol Drinking; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Cannabidiol; Anticonvulsants