Clinical trial NCT04205682: 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
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Alcohol Withdrawal
Alcohol Dependence
Lead sponsor: South West Sydney Local Health District
Sponsor class: OTHER
Collaborators: name: University of Sydney
name: South Eastern Sydney Local Health District
First posted: 2019-12-19
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Diazepam
timeFrame: 5 day admission period
Secondary outcomes:
measure: Alcohol Withdrawal Severity
timeFrame: 5 day admission period
measure: Self-reported Alcohol Withdrawal Severity
timeFrame: 5 day admission period (twice daily)
measure: Self-reported alcohol craving
timeFrame: Baseline, Day 5, and Day 12 and 33 Follow Up
measure: Self-reported urges to drink
timeFrame: Twice Daily, days 1-5
measure: Actiwatch for sleep quality
timeFrame: 5 day admission period
measure: Self-reported sleep quality
timeFrame: Baseline, Day 5, and Follow Up (Day 12, Day 33)
measure: Subjective measure of patient satisfaction
timeFrame: Day 5 and follow up (day 12 and 33)
measure: Liver function tests for clinical markers of liver injury
timeFrame: Baseline and follow up (day 12 and 33).
measure: Plasma levels of benzodiazepines
timeFrame: Daily (days 1-5)
measure: Plasma levels of cannabidiol
timeFrame: Daily (days 1-5)
measure: Mood
timeFrame: Baseline, day 5 and follow up day 12 and 33.
measure: Cognitive Functioning
timeFrame: Baseline, day 5 and follow up day 12 and 33.
measure: Cognitive Functioning
timeFrame: Baseline, day 5 and follow up day 12 and 33.
measure: Comorbid Anxiety Disorders
timeFrame: 4 week follow up (day 33)
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: Sydney and Sydney Eye Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
Study officials:
affiliation: Sydney Local Health District
name: Paul Haber, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: South Eastern Sydney Local Health District
name: Nicholas Lintzeris, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Sydney
name: Iain McGregor, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Sydney
name: Kirsten Morley, PhD
role: PRINCIPAL_INVESTIGATOR
References: