Cannabidiol (CBD) for the Treatment of Alcohol Withdrawal

• ClinicalTrials.gov Identifier: NCT04205682
• Recruitment Status: Not yet recruiting
• First Posted: December 19, 2019
• Last Update Posted: January 9, 2020
• Sponsor: South West Sydney Local Health District
• Collaborators: University of Sydney; South Eastern Sydney Local Health District
• Information provided by (Responsible Party): Professor Paul Haber, South West Sydney Local Health District

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.

Condition or disease	Intervention/treatment	Phase
Alcohol Withdrawal; Alcohol Dependence	Drug: Cannabidiol; Drug: Placebo	Early Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 52 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomised Controlled Trial of Cannabidiol (CBD) for the Treatment of Alcohol Withdrawal
• Estimated Study Start Date: January 2020
• Estimated Primary Completion Date: January 2021
• Estimated Study Completion Date: January 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Diazepam [ Time Frame: 5 day admission period ]
   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 :

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

Eligibility Criteria

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

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

Contacts and Locations

Contacts

Contact: Kirsten Morley, PhD; +61295153636; kirsten.morley@sydney.edu.au

Locations

Australia, New South Wales

Sydney and Sydney Eye Hospital

Sydney, New South Wales, Australia, 2000

Contact: Nicholas Lintzeris, MBBS nicholas.lintzeris@health.nsw.gov.au

Principal Investigator: Nicholas Lintzeris, MBBS

Royal Prince Alfred Hospital

Sydney, New South Wales, Australia, 2050

Contact: Kirsten Morley, PhD +61295153636 kirsten.morley@sydney.edu.au

Principal Investigator: Paul Haber, MBBS

Sponsors and Collaborators

South West Sydney Local Health District

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

More Information

• Responsible Party: Professor Paul Haber, Director, South West Sydney Local Health District
• ClinicalTrials.gov Identifier: NCT04205682
• Other Study ID Numbers: X18-0163
• First Posted: December 19, 2019
• Last Update Posted: January 9, 2020
• Last Verified: January 2020

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

Additional relevant MeSH terms:

Alcoholism; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Epidiolex; Anticonvulsants