Clinical trial NCT03252756: Effects of Cannabidiol in Alcohol Use Disorder
Official title: Effects of Cannabidiol in Alcohol Use Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Alcohol Use Disorder
Keywords: Cannabidiol
Alcohol Use Disorder
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: Tilray
First posted: 2017-08-17
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind, randomized proof-of-concept study
Primary purpose: TREATMENT

Brief summary: The goal of the proposed project is to begin rigorous study of the clinically relevant effects of non-psychoactive phytocannabinoid cannabidiol (CBD) in patients with severe alcohol use disorder (AUD). This double-blind, randomized proof-of-concept study (n = 40) is designed to assess feasibility and contrast effects of extended (8 weeks) treatment with CBD to those of placebo in AUD patients. Participants with AUD will be randomized to receive either placebo or 600mg CBD/day (PO) for 4 weeks, immediately followed by 1200mg CBD/day (PO) for an additional 4 weeks (8 total weeks). These doses were chosen to reproduce serum CBD levels reported to reduce alcohol-seeking behavior in animal studies. Measures will include circulating levels of CBD, safety measures (THC serum levels, adverse events, cognitive and motoric function), and physiological and psychological domains relevant to AUD (including self-reported craving, depression, and anxiety, and responses to personalized scripts designed to elicit stress- and cue-induced craving and anxiety). Assessments will be conducted following 1 day, 1 week, and 4 weeks of treatment with each dose of CBD vs. placebo, and 1 and 4 weeks after the cessation of treatment. Drinking outcomes across 8 weeks of treatment and 4 weeks of follow-up will also be assessed as an exploratory outcome.

Detailed description: There is increasing recognition of the roles of the endocannabinoid system in neurobiological processes and behavioral domains relevant to addiction. The non-psychoactive phytocannabinoid cannabidiol (CBD) has attracted considerable attention due to its lack of abuse potential, its excellent safety profile, its unique and complex pharmacology, and evidence that it affects anxiety and stress response in animal models and humans. There is a growing body of preclinical data demonstrating that CBD produces marked and persisting decreases in alcohol self-administration and preference for alcohol, and alcohol-, cue- and stress-induced reinstatement of alcohol-seeking behavior, yet there are few studies of the effects of CBD in humans with addictive disorders, and none in alcohol dependent patients.

Eligibility criteria: Inclusion Criteria:

* Males and females age 18-65
* DSM-5 diagnosis of moderate or severe AUD
* Able to provide voluntary informed consent
* At least 8 heavy drinking days (4 or more drinks for a woman, 5 or more drinks for a man) in the 30 days prior to screen
* If of childbearing potential (male or female), are willing to use approved form of contraception from screening for duration of the trial
* Able to provide at least two locators
* Endorse desire to cut down or stop drinking
* Agrees to abstain from all other cannabinoid use for duration of the study

Exclusion Criteria:

* Current alcohol withdrawal (CIWA-Ar score \>7)
* Exclusionary medical conditions (e.g. current severe alcohol withdrawal requiring medical hospitalization, significantly impaired liver function)
* DSM-5 diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder
* High risk of adverse emotional or behavioral reaction based on investigator's clinical evaluation (e.g., evidence of serious personality disorder, antisocial behavior, serious current stressors, lack of meaningful social support)
* Current significant suicidality (assessed using the C-SSRS), any suicidal behavior in the past 12 months, or any history of serious suicide attempts requiring hospitalization, or current significant homicidality
* History of severe Traumatic Brain Injury (LOC \> 24 hours)
* DSM-5 diagnosis of current mild cannabis use disorder and/or moderate or severe substance use disorder for a substance other than alcohol or nicotine
* Significant laboratory abnormalities, including significantly impaired liver function, serious abnormalities of complete blood count or metabolic panel
* Active legal problems likely to result in incarceration within 12 weeks of treatment initiation
* Pregnancy or lactation
* Current use of exclusionary medications, including cannabinoids; treatments for addictions including alcohol; moderate to strong inhibitors of CYP3A4 or CYP2C19; medications metabolized primarily by CYP3A4, CYP3A5, or CYP3A7; and medications with a narrow therapeutic index which are substrates of UGT1A9, UGT2B7, CYP2C8, CYP2C9, CYP2C19, CYP1A2, or CYP2B6.
* Allergy to any ingredient of the study compound.
* Current treatment for AUD, with exception of AA/12-step treatment
* No inpatient psychiatric treatment in the last 12 months, with the exception of detox and extended Emergency Department stays
* A positive urine drug screen for THC, cocaine and/or opioids at screen

Primary outcomes:
measure: Trough CBD Plasma Levels
timeFrame: Baseline
measure: Trough CBD Plasma Levels
timeFrame: Week 1
measure: Trough CBD Plasma Levels
timeFrame: Week 4
measure: Trough CBD Plasma Levels
timeFrame: Week 5
measure: Trough CBD Plasma Levels
timeFrame: Week 8
measure: Trough CBD Plasma Levels
timeFrame: Week 9
measure: Peak CBD Plasma Levels
timeFrame: Baseline
measure: Peak CBD Plasma Levels
timeFrame: Day 1
measure: Peak CBD Plasma Levels
timeFrame: Week 1
measure: Peak CBD Plasma Levels
timeFrame: Week 4
measure: Peak CBD Plasma Levels
timeFrame: Week 4 + 1 Day
measure: Peak CBD Plasma Levels
timeFrame: Week 5
measure: Peak CBD Plasma Levels
timeFrame: Week 8
Secondary outcomes:
measure: Percentage of Heavy Drinking Days
timeFrame: Baseline
measure: Percent of Heavy Drinking Days
timeFrame: Week 1
measure: Percent of Heavy Drinking Days
timeFrame: Week 2
measure: Percent of Heavy Drinking Days
timeFrame: Week 3
measure: Percent of Heavy Drinking Days
timeFrame: Week 4
measure: Percent of Heavy Drinking Days
timeFrame: Week 5
measure: Percent of Heavy Drinking Days
timeFrame: Week 6
measure: Percent of Heavy Drinking Days
timeFrame: Week 7
measure: Percent of Heavy Drinking Days
timeFrame: Week 8
measure: Percent of Heavy Drinking Days
timeFrame: Week 9
measure: Number of Drinks Per Day
timeFrame: Baseline
measure: Number of Drinks Per Day
timeFrame: Week 1
measure: Number of Drinks Per Day
timeFrame: Week 2
measure: Number of Drinks Per Day
timeFrame: Week 3
measure: Number of Drinks Per Day
timeFrame: Week 4
measure: Number of Drinks Per Day
timeFrame: Week 5
measure: Number of Drinks Per Day
timeFrame: Week 6
measure: Number of Drinks Per Day
timeFrame: Week 7
measure: Number of Drinks Per Day
timeFrame: Week 8
measure: Number of Drinks Per Day
timeFrame: Week 9
measure: Penn Alcohol Craving Scale (PACS) Score
timeFrame: Baseline
measure: Penn Alcohol Craving Scale (PACS) Score
timeFrame: Week 1
measure: Penn Alcohol Craving Scale (PACS) Score
timeFrame: Week 4
measure: Penn Alcohol Craving Scale (PACS) Score
timeFrame: Week 5
measure: Penn Alcohol Craving Scale (PACS) Score
timeFrame: Week 8
measure: Penn Alcohol Craving Scale (PACS) Score
timeFrame: Week 9
measure: Beck Anxiety Inventory (BAI) Score
timeFrame: Baseline
measure: Beck Anxiety Inventory (BAI) Score
timeFrame: Week 1
measure: Beck Anxiety Inventory (BAI) Score
timeFrame: Week 4
measure: Beck Anxiety Inventory (BAI) Score
timeFrame: Week 5
measure: Beck Anxiety Inventory (BAI) Score
timeFrame: Week 8
measure: Beck Anxiety Inventory (BAI) Score
timeFrame: Week 9
measure: Beck Depression Inventory (BDI) Score
timeFrame: Baseline
measure: Beck Depression Inventory (BDI) Score
timeFrame: Week 1
measure: Beck Depression Inventory (BDI) Score
timeFrame: Week 4
measure: Beck Depression Inventory (BDI) Score
timeFrame: Week 5
measure: Beck Depression Inventory (BDI) Score
timeFrame: Week 8
measure: Beck Depression Inventory (BDI) Score
timeFrame: Week 9
Other outcomes:
Locations:
city: New York
country: United States
facility: New York University School of Medicine
state: New York
Study officials:
affiliation: NYU Langone Health
name: Michael Bogenschutz, PhD
role: PRINCIPAL_INVESTIGATOR
References: