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Cannabidiol (CBD) for the Treatment of Alcohol Withdrawal

Primary Purpose

Alcohol Withdrawal, Alcohol Dependence

Status
Unknown status
Phase
Early Phase 1
Locations
Australia
Study Type
Interventional
Intervention
Cannabidiol
Placebo
Sponsored by
South West Sydney Local Health District
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alcohol Withdrawal

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Sydney and Sydney Eye Hospital
  • Royal Prince Alfred Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Cannabidiol (CBD)

Placebo

Arm Description

Drug: Cannabidiol (day 1: 1200 mg (800 mg BD); day 2-4: 800 mg (400 mg BD); day 5: placebo BD).

Drug: Placebo (days 1-5: placebo matched BD)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Alcohol Withdrawal Severity
Measured by Alcohol Withdrawal Scale (AWS), minimum score is 0, maximum score is 27 where higher scores indicate greater withdrawal severity.
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.
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
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
Actiwatch for sleep quality
as measured using data obtained from the actiwatch worn by participants for duration of inpatient stay
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.
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.
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
Plasma levels of benzodiazepines
As measured by concentration of benzodiazepines in blood plasma
Plasma levels of cannabidiol
As measured by concentration of cannabidiol in blood plasma
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.
Cognitive Functioning
As measured by the Montreal Cognitive Assessment (MoCA), maximum score is 30 and where higher scores indicate greater cognitive functioning.
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.
Comorbid Anxiety Disorders
Assessed using the MINI Neuropsychiatric Interview indicating the presence or absence of anxiety disorders

Full Information

First Posted
November 5, 2019
Last Updated
January 6, 2020
Sponsor
South West Sydney Local Health District
Collaborators
University of Sydney, South Eastern Sydney Local Health District
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1. Study Identification

Unique Protocol Identification Number
NCT04205682
Brief Title
Cannabidiol (CBD) for the Treatment of Alcohol Withdrawal
Official Title
A Randomised Controlled Trial of Cannabidiol (CBD) for the Treatment of Alcohol Withdrawal
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Unknown status
Study Start Date
January 2020 (Anticipated)
Primary Completion Date
January 2021 (Anticipated)
Study Completion Date
January 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
South West Sydney Local Health District
Collaborators
University of Sydney, South Eastern Sydney Local Health District

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcohol Withdrawal, Alcohol Dependence

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
52 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cannabidiol (CBD)
Arm Type
Experimental
Arm Description
Drug: Cannabidiol (day 1: 1200 mg (800 mg BD); day 2-4: 800 mg (400 mg BD); day 5: placebo BD).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Drug: Placebo (days 1-5: placebo matched BD)
Intervention Type
Drug
Intervention Name(s)
Cannabidiol
Intervention Description
CBD capsules administered BD for 4-days (800-1200 mg/day), placebo day 5
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo capsules administered BD for 5 days
Primary Outcome Measure Information:
Title
Diazepam
Description
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.
Time Frame
5 day admission period
Secondary Outcome Measure Information:
Title
Alcohol Withdrawal Severity
Description
Measured by Alcohol Withdrawal Scale (AWS), minimum score is 0, maximum score is 27 where higher scores indicate greater withdrawal severity.
Time Frame
5 day admission period
Title
Self-reported Alcohol Withdrawal Severity
Description
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.
Time Frame
5 day admission period (twice daily)
Title
Self-reported alcohol craving
Description
As measured by the Penn Alcohol Craving Scale (PACS), minimum score is 0, maximum score is 30 where higher scores indicate greater alcohol craving
Time Frame
Baseline, Day 5, and Day 12 and 33 Follow Up
Title
Self-reported urges to drink
Description
As measured by the Alcohol Urge Questionnaire (AUQ), minimum score is 8, maximum score is 56, where higher scores indicate greater urges to drink
Time Frame
Twice Daily, days 1-5
Title
Actiwatch for sleep quality
Description
as measured using data obtained from the actiwatch worn by participants for duration of inpatient stay
Time Frame
5 day admission period
Title
Self-reported sleep quality
Description
as measured using the Insomnia Severity Index (ISI), minimum score is 0, maximum score is 28, where higher scores indicate greater insomnia severity.
Time Frame
Baseline, Day 5, and Follow Up (Day 12, Day 33)
Title
Subjective measure of patient satisfaction
Description
Measured using the Treatment Satisfaction Questionnaire for Medication (TSQM), minimum score is 13, maximum score is 80, where higher scores indicate greater treatment satisfaction.
Time Frame
Day 5 and follow up (day 12 and 33)
Title
Liver function tests for clinical markers of liver injury
Description
as measured by levels of liver enzymes, Alanine Transaminase (ALT), Alkaline Phosphatase (ALP) and Aspartate Transaminase (AST) in blood
Time Frame
Baseline and follow up (day 12 and 33).
Title
Plasma levels of benzodiazepines
Description
As measured by concentration of benzodiazepines in blood plasma
Time Frame
Daily (days 1-5)
Title
Plasma levels of cannabidiol
Description
As measured by concentration of cannabidiol in blood plasma
Time Frame
Daily (days 1-5)
Title
Mood
Description
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.
Time Frame
Baseline, day 5 and follow up day 12 and 33.
Title
Cognitive Functioning
Description
As measured by the Montreal Cognitive Assessment (MoCA), maximum score is 30 and where higher scores indicate greater cognitive functioning.
Time Frame
Baseline, day 5 and follow up day 12 and 33.
Title
Cognitive Functioning
Description
Executive functioning measured by time taken to complete the Trail Making Test A and B (in seconds), where lower scores indicate greater functioning.
Time Frame
Baseline, day 5 and follow up day 12 and 33.
Title
Comorbid Anxiety Disorders
Description
Assessed using the MINI Neuropsychiatric Interview indicating the presence or absence of anxiety disorders
Time Frame
4 week follow up (day 33)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kirsten Morley, PhD
Phone
+61295153636
Email
kirsten.morley@sydney.edu.au
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Haber, MBBS
Organizational Affiliation
Sydney Local Health District
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Nicholas Lintzeris, MBBS
Organizational Affiliation
South Eastern Sydney Local Health District
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Iain McGregor, PhD
Organizational Affiliation
University of Sydney
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kirsten Morley, PhD
Organizational Affiliation
University of Sydney
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sydney and Sydney Eye Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2000
Country
Australia
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nicholas Lintzeris, MBBS
Email
nicholas.lintzeris@health.nsw.gov.au
First Name & Middle Initial & Last Name & Degree
Nicholas Lintzeris, MBBS
Facility Name
Royal Prince Alfred Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kirsten Morley, PhD
Phone
+61295153636
Email
kirsten.morley@sydney.edu.au
First Name & Middle Initial & Last Name & Degree
Paul Haber, MBBS

12. IPD Sharing Statement

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Cannabidiol (CBD) for the Treatment of Alcohol Withdrawal

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