CBD for the Treatment of Alcohol Use Disorder

Tolerability and Efficacy of Hemp-Derived CBD for the Treatment of Alcohol Use Disorder

This is a double-blind, placebo-controlled, parallel group study designed to assess the efficacy of full spectrum cannabidiol (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.

Study Overview

• Status: Completed
• Conditions: Alcohol Use Disorder
• Intervention / Treatment: Drug: Cannabidiol; Drug: Placebo

Detailed Description

The current study will directly test the hypothesis that a moderate dose of cannabidiol (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 Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Raeghan Mueller, MA; Phone Number: 303.724.2208; Email: raeghan.mueller@cuanschutz.edu
• Study Contact Backup: Name: Jamie Cavanaugh; Email: jamie.cavanaugh@cuanschutz.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / 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 Names: 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 Names: CBD
Placebo Comparator: Placebo; 150mg/day of hemp-seed oil with no cannabinoids present.	Drug: Placebo; Placebo arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Drinks per Drinking Day	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.	0-8 weeks
Drinks per Drinking Day	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.	0-16 weeks
Drinks per Drinking Day	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.	0-4 weeks
Drinks per Drinking Day	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.	4-8 weeks
Alcohol Dependence/Craving	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.	0-16 weeks
Alcohol Dependence/Craving	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.	0-8 weeks
Alcohol Dependence/Craving	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.	0-4 weeks
Alcohol Dependence/Craving	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.	4-8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cue-reactivity	Cue-elicited urge to drink will be assessed using the cue-reactivity assessment, per protocol (Hutchison, 2006).	0-4 weeks
Cue-reactivity	Cue-elicited urge to drink will be assessed using the cue-reactivity assessment, per protocol (Hutchison, 2006).	4-8 weeks
Cue-reactivity	Cue-elicited urge to drink will be assessed using the cue-reactivity assessment, per protocol (Hutchison, 2006) .	0-8 weeks
Anxiety	The Depression Anxiety and Stress Scale (DASS-21) is a 21-item self-report questionnaire designed to measure three related negative emotional states and yields three subscale scores for depression, anxiety and tension/stress. Possible scores on the anxiety subscale range from 0 to 21, with higher scores indicating more severe symptoms of anxiety.	0-4 weeks
Anxiety	The Depression Anxiety and Stress Scale (DASS-21) is a 21-item self-report questionnaire designed to measure three related negative emotional states and yields three subscale scores for depression, anxiety and tension/stress. Possible scores on the anxiety subscale range from 0 to 21, with higher scores indicating more severe symptoms of anxiety.	4-8 weeks
Anxiety	The Depression Anxiety and Stress Scale (DASS-21) is a 21-item self-report questionnaire designed to measure three related negative emotional states and yields three subscale scores for depression, anxiety and tension/stress. Possible scores on the anxiety subscale range from 0 to 21, with higher scores indicating more severe symptoms of anxiety.	0-8 weeks
Anxiety	The Depression Anxiety and Stress Scale (DASS-21) is a 21-item self-report questionnaire designed to measure three related negative emotional states and yields three subscale scores for depression, anxiety and tension/stress. Possible scores on the anxiety subscale range from 0 to 21, with higher scores indicating more severe symptoms of anxiety.	0-16 weeks
Subjective Pain Level	The Adult PROMIS Numerical Rating Scale v1.0 Pain Intensity 1a measures the severity of subjective pain. Possible scores range from 0 to 10, with higher scores indicating more severe symptoms of subjective pain.	0-4 weeks
Subjective Pain Level	The Adult PROMIS Numerical Rating Scale v1.0 Pain Intensity 1a measures the severity of subjective pain. Possible scores range from 0 to 10, with higher scores indicating more severe symptoms of subjective pain.	4-8 weeks
Subjective Pain Level	The Adult PROMIS Numerical Rating Scale v1.0 Pain Intensity 1a measures the severity of subjective pain. Possible scores range from 0 to 10, with higher scores indicating more severe symptoms of subjective pain.	0-8 weeks
Subjective Pain Level	The Adult PROMIS Numerical Rating Scale v1.0 Pain Intensity 1a measures the severity of subjective pain. Possible scores range from 0 to 10, with higher scores indicating more severe symptoms of subjective pain.	0-16 weeks
Sleep Quality	The Adult PROMIS Short Form v1.0 Sleep Disturbance 4a measures the severity of sleep disturbances. Possible scores range from 4 to 20, with higher scores indicating more severe symptoms of sleep disturbance.	0-16 weeks
Sleep Quality	The Adult PROMIS Short Form v1.0 Sleep Disturbance 4a measures the severity of sleep disturbances. Possible scores range from 4 to 20, with higher scores indicating more severe symptoms of sleep disturbance.	0-8 weeks
Sleep Quality	The Adult PROMIS Short Form v1.0 Sleep Disturbance 4a measures the severity of sleep disturbances. Possible scores range from 4 to 20, with higher scores indicating more severe symptoms of sleep disturbance.	4-8 weeks
Sleep Quality	The Adult PROMIS Short Form v1.0 Sleep Disturbance 4a measures the severity of sleep disturbances. Possible scores range from 4 to 20, with higher scores indicating more severe symptoms of sleep disturbance.	0-4 weeks

Collaborators and Investigators

• Sponsor: University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2021
• Primary Completion (Actual): May 31, 2023
• Study Completion (Actual): May 31, 2023

Study Registration Dates

• First Submitted: April 20, 2021
• First Submitted That Met QC Criteria: April 29, 2021
• First Posted (Actual): May 5, 2021

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: CBD; Alcohol; Cannabis; Cannabidiol
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Alcohol Drinking; Alcoholism; Anticonvulsants; Cannabidiol
• Other Study ID Numbers: 20-2694

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No