Cannabidiol (CBD) for the Treatment of Alcohol Withdrawal

A Randomised Controlled Trial of Cannabidiol (CBD) for the Treatment of Alcohol Withdrawal

This study will explore the effectiveness and tolerability of Cannabidiol (CBD) in the treatment of alcohol withdrawal symptoms in an inpatient setting, in a double-blind randomised placebo-controlled trial.

Study Overview

• Status: Unknown
• Conditions: Alcohol Dependence; Alcohol Withdrawal
• Intervention / Treatment: Drug: Cannabidiol; Drug: Placebo

Detailed Description

New treatment strategies for treating symptoms of alcohol dependence are urgently needed. Although alcohol related disorders are a leading cause of preventable death in Australia, their treatment is generally not evidence-based. Contemporary treatment for managing alcohol withdrawal in Australia involves administration of benzodiazepines that, while often effective for managing withdrawal symptoms, have concerns regarding their use including: a major abuse liability potential in this population; their sedating effects and potential for adverse events (e.g. falls, overdose, cognitive impairment) if used in combination with other sedatives; and an increased risk of relapse due to symptoms of alcohol dependence that return after cessation of treatment (e.g. increased sleep problems and anxiety). However, no other safe and effective alternatives to benzodiazepines in treating alcohol withdrawal have yet been demonstrated.

This project will pilot the clinical efficacy and tolerability of Cannabidiol (CBD) relative to placebo in the treatment of alcohol withdrawal in an inpatient setting across two study sites.

This is a double-blind, randomised controlled design. The trial will recruit 52 participants undergoing alcohol withdrawal, using a 1:1 random allocation into one of two treatment groups as follows: (1) CBD (Day 1: 1200 mg/day; Day 2-4: 800 mg/day; Day 5: placebo washout; n = 26), or (2) matched placebo (n = 26). All participants will be administered a symptom triggered diazepam medication regimen, as per conventional best-practice management of alcohol withdrawal.

• Study Type: Interventional
• Enrollment (Anticipated): 52
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Kirsten Morley, PhD; Phone Number: +61295153636; Email: kirsten.morley@sydney.edu.au

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
      • Contact: Kirsten Morley, PhD; Phone Number: +61295153636; Email: kirsten.morley@sydney.edu.au
      • Principal Investigator: Paul Haber, MBBS
    • Sydney, New South Wales, Australia, 2000
      • Sydney and Sydney Eye Hospital
      • Contact: Nicholas Lintzeris, MBBS; Email: nicholas.lintzeris@health.nsw.gov.au
      • Principal Investigator: Nicholas Lintzeris, MBBS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 18-65 years;
• At least one prior episode 2 days or longer in duration during which the participant experienced withdrawal symptoms that caused significant incapacitation (e.g. inability to work or do normal activities) OR at least one prior inpatient or outpatient medical detoxification during which the participant exhibited withdrawal symptoms of significant magnitude that sedative-hypnotic or anticonvulsant medication was required at least once on 2 consecutive days after cessation of or reduction in the use of alcohol following 2 weeks or more of heavy daily consumption;
• Average consumption of at least 8 standard drinks per day for at least 2 weeks prior to enrolment in the study;
• Adequate cognition and English language skills to give valid consent and complete research interviews;
• Willingness to give written informed consent

Exclusion Criteria:

• Treatment/ingestion during the previous week of benzodiazepines or other sedative-hypnotic medications or history of recent chronic treatment with sedative-hypnotic medication as evidenced by a negative urine drug screen at baseline
• History of alcohol withdrawal related seizures
• Substance use in the previous week, defined as > 3 times per week (not including nicotine or caffeine), inclusive of non-prescribed pharmaceuticals (ATOP to be collected at screening)
• Active major psychiatric disorder associated with psychosis, or significant suicide risk (e.g. Bipolar, Schizophrenia)
• Pregnancy or lactation - Women shall be advised to use reliable contraception for the duration of drug therapy and a urine pregnancy test will be performed where necessary
• History of confirmed seizures during adulthood, and/or current use of anti-epileptic drugs (AED)
• Diagnosis of epilepsy, and/or current use of anti-epileptic drugs (AED)
• Serious medical illness impacting on safety/participation, defined as an unstable medical state in the opinion of the trial medical officer
• Low body weight (body mass index < 17)
• Severe cognitive impairment or insufficient English or literacy to complete study processes
• Concurrent use of drugs potentially exacerbated by CBD via CYP3A5

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cannabidiol (CBD); Drug: Cannabidiol (day 1: 1200 mg (800 mg BD); day 2-4: 800 mg (400 mg BD); day 5: placebo BD).	Drug: Cannabidiol; CBD capsules administered BD for 4-days (800-1200 mg/day), placebo day 5
Placebo Comparator: Placebo; Drug: Placebo (days 1-5: placebo matched BD)	Drug: Placebo; Placebo capsules administered BD for 5 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diazepam	Diazepam use over the 5-day withdrawal period (which due to symptom triggered regimen is a proxy measure for withdrawal severity). Measured by total diazepam use over 5 day period.	5 day admission period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alcohol Withdrawal Severity	Measured by Alcohol Withdrawal Scale (AWS), minimum score is 0, maximum score is 27 where higher scores indicate greater withdrawal severity.	5 day admission period
Self-reported Alcohol Withdrawal Severity	As measured by the Alcohol Withdrawal Severity Checklist (AWSC), a self-report measure of withdrawal severity, minimum score is 0, maximum score is 64 where higher scores indicate greater self-reported withdrawal severity.	5 day admission period (twice daily)
Self-reported alcohol craving	As measured by the Penn Alcohol Craving Scale (PACS), minimum score is 0, maximum score is 30 where higher scores indicate greater alcohol craving	Baseline, Day 5, and Day 12 and 33 Follow Up
Self-reported urges to drink	As measured by the Alcohol Urge Questionnaire (AUQ), minimum score is 8, maximum score is 56, where higher scores indicate greater urges to drink	Twice Daily, days 1-5
Actiwatch for sleep quality	as measured using data obtained from the actiwatch worn by participants for duration of inpatient stay	5 day admission period
Self-reported sleep quality	as measured using the Insomnia Severity Index (ISI), minimum score is 0, maximum score is 28, where higher scores indicate greater insomnia severity.	Baseline, Day 5, and Follow Up (Day 12, Day 33)
Subjective measure of patient satisfaction	Measured using the Treatment Satisfaction Questionnaire for Medication (TSQM), minimum score is 13, maximum score is 80, where higher scores indicate greater treatment satisfaction.	Day 5 and follow up (day 12 and 33)
Liver function tests for clinical markers of liver injury	as measured by levels of liver enzymes, Alanine Transaminase (ALT), Alkaline Phosphatase (ALP) and Aspartate Transaminase (AST) in blood	Baseline and follow up (day 12 and 33).
Plasma levels of benzodiazepines	As measured by concentration of benzodiazepines in blood plasma	Daily (days 1-5)
Plasma levels of cannabidiol	As measured by concentration of cannabidiol in blood plasma	Daily (days 1-5)
Mood	Depression, Anxiety and Stress Symptoms measured by the Depression, Anxiety and Stress Scale (DASS-21), minimum score is 0, maximum score is 63, where higher scores indicate greater levels of depression, anxiety and stress.	Baseline, day 5 and follow up day 12 and 33.
Cognitive Functioning	As measured by the Montreal Cognitive Assessment (MoCA), maximum score is 30 and where higher scores indicate greater cognitive functioning.	Baseline, day 5 and follow up day 12 and 33.
Cognitive Functioning	Executive functioning measured by time taken to complete the Trail Making Test A and B (in seconds), where lower scores indicate greater functioning.	Baseline, day 5 and follow up day 12 and 33.
Comorbid Anxiety Disorders	Assessed using the MINI Neuropsychiatric Interview indicating the presence or absence of anxiety disorders	4 week follow up (day 33)

Collaborators and Investigators

• Sponsor: South West Sydney Local Health District
• Collaborators: University of Sydney; South Eastern Sydney Local Health District
• Investigators: Principal Investigator: Paul Haber, MBBS, Sydney Local Health District; Principal Investigator: Nicholas Lintzeris, MBBS, South Eastern Sydney Local Health District; Principal Investigator: Iain McGregor, PhD, University of Sydney; Principal Investigator: Kirsten Morley, PhD, University of Sydney

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2020
• Primary Completion (Anticipated): January 1, 2021
• Study Completion (Anticipated): January 1, 2021

Study Registration Dates

• First Submitted: November 5, 2019
• First Submitted That Met QC Criteria: December 17, 2019
• First Posted (Actual): December 19, 2019

Study Record Updates

• Last Update Posted (Actual): January 9, 2020
• Last Update Submitted That Met QC Criteria: January 6, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Alcoholism; Anticonvulsants; Cannabidiol
• Other Study ID Numbers: X18-0163

Drug and device information, study documents

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