A Randomised Controlled Trial of Cannabidiol (CBD) for the treatment of Cannabis Use Disorder (CUD)
University of Sydney
250 participants
May 14, 2024
Interventional
Conditions
Summary
The study is a parallel group double-blind Phase 3 randomised control trial comparing a 12-week treatment period of oral Cannabidiol (CBD) (400mg daily, Experimental) to Placebo (Control). The research hypothesis is that CBD, compared to placebo, will achieve significant reductions in cannabis use, as measured by number of self-reported cannabis-free days and urinary THC-COOH levels, among treatment-seeking patients with moderate-severe CUD. Participants will be treatment-seeking clients recruited from study sites under conditions of informed consent. Participants will be randomly allocated to either CBD or placebo (1:1 ratio, double blind conditions), and attend every 3 weeks (weeks 1-12) for (a) clinical review with study doctor, (b) dispensing of medication, (c) collection of urine drug screen and (d) a research interview with an independent researcher. Participants will have up to 4 sessions of Cognitive Behavioural Therapy-based counselling over the 12 weeks. Final research interview will occur at week 24, 12 weeks after the study intervention. Additional qualitative research interviews will be conducted with Aboriginal participants in a sub-study examining their perspectives of treatment. Sample size is 250 participants, with approximately 125 randomised to each condition. It is estimated that approximately 20% of participants (n=50) will be Aboriginal. The study will use an intention to treat between-group analysis.
Eligibility
Inclusion Criteria4
- Aged 18 to 65 years.
- Meeting DSM-5 criteria for moderate or severe Cannabis Use Disorder (more than or equal to 4 out of 11 criteria), with recent frequent cannabis use (more than or equal to 4 days per week in the preceding 4 weeks).
- Willing and able to provide informed consent to study procedures.
- Proficient in English at a conversational level sufficient to participate in counselling intervention (assessed by Study Medical Officer (SMO) at medical assessment).
Exclusion Criteria10
- Prescribed medicinal cannabis products (e.g., CBD, THC) for any indication in the previous 4 weeks.
- Another active (past year) moderate-severe substance use disorder other than tobacco; operationalised on clinical assessment by SMO using DSM5 criteria.
- Active or severe medical (e.g., pain, epilepsy, cardiovascular disease) or psychiatric conditions (e.g., psychosis, severe affective disorder) as identified by the Study Medical Officer; moderate to severe hepatic disease (transaminase elevations more than 3 times, bilirubin more than 2 times upper normal limits).
- Pregnant or lactating women (urine beta-hCG).
- Hypersensitivity to CBD or excipients of Epidyolex.
- Using medications with known drug-drug hepatic CYP-450 interactions with CBD: 3A4, (e.g., carbamazepine, fluvoxamine, methadone), 2C19 (e.g., rifampin); CYP2B6 (e.g., bupropion), CYP2C9 (e.g., warfarin). The potential range of drug-drug interactions are considerable, and the SMO will make an assessment whether the potential for DDI is clinically significant (e.g., as for medications such as warfarin, HIV or anticonvulsant medications), and the SMO can discuss with PI Lintzeris if uncertain.
- Not available for follow-up (e.g., travel, impending imprisonment).
- Court-mandated treatment requiring abstinence from drugs.
- Current active treatment for cannabis use disorder. People in existing treatment counselling and/or medication-based treatment for their cannabis use disorders (e.g., Alcohol and Other Drug services, private health services) are not eligible for the trial at the time of application. To participate, clients would have to choose to cease their existing treatment (counselling, medication) for a 4-week period prior to being formally assessed for the trial.
- Received an investigational medicinal product within the last 4 weeks (or 5 half-lives if using long-acting investigational drugs).
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Interventions
1. Cannabidiol: A parallel experimental group will receive oral Cannabidiol (400mg daily) for a 12-week treatment period. Cannabidiol is the generic name, Epidyolex is the brand name. Epidyolex is an oral liquid (clear, colourless to yellow solution) containing 100mg per ml, and dispensed in 100 ml containers (bottles). Epidyolex also contains sesame oil, ethanol absolute, sucralose, strawberry flavour. Participants will be instructed to take their dose of medication at the same time each day. Each medication container has a measuring syringe for participants to accurately administer their dose, and participants will be instructed by the study medical officer on dosing procedures. Participants will be instructed to resume normal dosing regimen in the event they have missed one or more doses. Participants who miss 3 or more consecutive weeks of study medication dosing will be deemed to have withdrawn from the trial intervention. Participants will be requested to bring their medication bottles to their next appointment with the research team or medical officer to review adherence to taking study medication. 2. Cognitive Behavioural Therapy: All participants will be offered 4 structured 40-50 minute counselling sessions over the 12 week medication phase (Sessions 1-3 during the first 6 weeks; Session 4 in weeks 7-12). The sessions will be based on cognitive behavioural therapy (CBT) and motivation enhancement for relapse prevention, consistent with identified best practice for cannabis cessation interventions and structured (each of the four counselling sessions has a number of target goals) to ensure consistency between counsellors, although there is some flexibility to address issues identified by each participant. An outline of the sessions are as follows: Session 1: introduction to the counselling sessions, establishing treatment goals and attitudes to change to tailor the intervention, identify personal triggers, cues and high-risk situations and discuss associated strategies to quit or reduce. Session 2: manage withdrawal symptoms and cognitive restructuring. Session 3: review of cognitive strategies and skills enhancement, such as (i) problem-solving skills, (ii) management of insomnia, (iii) relaxation strategies, (iv) stress/anger management and (v) dealing with separation. Session 4: relapse prevention, lifestyle modification and future goals. A counselling manual will be developed for the study, and study clinicians (psychologists) will be trained by one of the study's investigators (Dr Steven Childs) to deliver the manualised counselling interventions. The Study Counsellor will keep a log of attendance at counselling sessions (including whether conducted face to face or telehealth, duration, and whether the counselling session was consistent with the intended counselling plan). Participation at counselling will be encouraged for all participants, although is not a mandatory requirement (that is, participants will not be terminated from the study for not participating in counselling). 3. Qualitative Research Interviews Qualitative research interviews will be conducted with Aboriginal participants in a sub-study examining their perspectives of treatment. Approximately 20% of participants (n=50) will be Aboriginal. All Aboriginal participants will be invited to participate in the qualitative interviews and will sign a separate consent form to the main study. We expect approximately 20-30 Aboriginal participants to agree to take part in the interviews. Qualitative interviews will be conducted either in person (face to face) or by telephone and estimated to take between 30 to 60 minutes. Interviews will be recorded digitally and transcribed. Interviews will follow a semi-structured format, with a number of ‘lead’ questions regarding key themes to be explored. The Aboriginal qualitative researcher will be skilled in qualitative interview techniques and supervised by an investigator on the study (Dr Michael Doyle).
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ACTRN12623000526673