Using Cannabidiol to Treat Bipolar Depression

Cannabidiol Adjunctive Therapy for Acute Bipolar Depression: A Randomized Double-Blind, Placebo Controlled Trial

This study is testing if adding cannabidiol (CBD) to the treatment plan can help people with bipolar depression who haven't felt better with standard medications.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 360 (estimated)
• Ages: 19 Years to 70 Years
• Sex: All
• Sponsor: University of British Columbia (Academic / other)
• Locations: 6 sites (Vancouver, British Columbia and 5 other locations)
• Trial ID: NCT05867849 on ClinicalTrials.gov

What this trial studies

This Phase 3 clinical trial investigates the effectiveness, safety, and tolerability of cannabidiol (CBD) as an adjunctive treatment for patients with bipolar depression who have not responded to standard treatments. The study involves a 6-week, double-blind, randomized controlled design where participants will receive either CBD or a placebo while continuing their prescribed mood stabilizers or atypical antipsychotics. Participants will be assessed at multiple points throughout the trial to monitor their mood symptoms and overall well-being.

Who should consider this trial

Good fit: Ideal candidates are adults aged 19 to 70 with a diagnosis of bipolar disorder I or II currently experiencing a major depressive episode.

Not a fit: Patients who are not currently taking a mood stabilizer or atypical antipsychotic, or those who have not been diagnosed with bipolar disorder, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new option for patients with bipolar depression who have not found relief with existing medications.

How similar studies have performed: While small studies have suggested potential benefits of CBD for mood disorders, this is one of the first large-scale trials specifically targeting bipolar depression.

Eligibility criteria

Inclusion Criteria:

1. Males or females aged 19 to 70 years (inclusive).
2. DSM-5 diagnosis of BD I or BD II, AND a current major depressive episode confirmed by MINI 7.0.2 .
3. All patients must be taking either a mood stabilizer (i.e. lithium or valproate; lamotrigine monotherapy as a mood stabilizer is acceptable for BD II patients only and not for BD I) OR an atypical antipsychotic OR a combination of these (two mood stabilizers or a mood stabilizer plus an atypical antipsychotic), at therapeutic doses. Medications and therapeutic doses are: lithium, serum level 0.6-1.2 mEq/L; divalproex/sodium valproate, serum level 350-700 uM/L(45-125 mcg/ml); risperidone 2-6 mg/day; olanzapine 5-30 mg/day; quetiapine IR or XR 300-900 mg/day; aripiprazole 10-30 mg/day; cariprazine 1.5-6 mg/day; and ziprasidone 80-160 mg/day. Combinations of these medications as outlined above, or the combination of any of them with lamotrigine 100-400 mg daily, or the combination of a mood stabilizer plus asenapine 5-20 mg/day are also permitted.
4. Have received a minimum of 6-weeks treatment at adequate doses for treatment of current depressive episode with at least one CANMAT recommended first-line treatment for bipolar I disorder (i.e. lithium, lamotrigine, lurasidone, or quetiapine either as monotherapy or adjunctive therapy), or at least one first or second-line treatment for bipolar II depression (i.e. quetiapine, lithium, lamotrigine, sertraline, or venlafaxine as monotherapy or adjunctive therapy, or bupropion adjunctive therapy).
5. A MADRS score of ≥ 20 and a YMRS score of ≤ 12 (these cut off scores are standard in bipolar depression RCTs).
6. Inpatient or outpatient status.
7. All participants are required to agree to practice highly effective methods of contraception (i.e. hormonal contraceptives, intrauterine device or system, vasectomy and tubal ligation, or double barrier methods of contraception) OR agree to completely abstain from heterosexual intercourse. Females who do not have childbearing potential are required to be postmenopausal for at least 1 year before the screening visit (confirmed by an FSH test) OR surgically sterile.
8. The capability of understanding, consenting to and complying with study requirements.
9. All concomitant medication must be at a stable dose for two weeks prior to the randomization visit.

Exclusion Criteria:

1. Current depressive episode greater than 12 months.
2. A history of rapid cycling, defined as ≥ 4 mood episodes in the preceding 12 months.
3. Current unstable or inadequately treated medical illness with the exception of current depression.
4. Recently started taking a CANMAT-recommended treatment for the management of acute bipolar depressive episode, but has not had a trial for a minimum of 6 weeks with adequate doses.
5. Recently (i.e. within the past 8 weeks) began structured psychotherapy (i.e. cognitive-behavioral therapy, interpersonal psychotherapy, family-focused therapy, or interpersonal and social rhythm therapy).
6. Recently (i.e. within the past 8 weeks) started taking a stimulant medication. Concomitant treatment with stimulant medication is acceptable provided that the dose has been stable for a minimum of 8 weeks and is taken as prescribed by a physician.
7. Current use of clozapine, tricyclic antidepressants, monoamine oxidase inhibitors, and first-generation antipsychotics.
8. A history of non-response or intolerance to CBD.
9. Current or past month daily use of CBD, or any product or drug that contains CBD. Occasional users will be included if they agree to refrain from using during the trial.
10. A history of non-response to electroconvulsive therapy for the current depressive episode.
11. A current diagnosis of other primary psychiatric disorders as assessed by a study investigator to be primary and causing greater impairment than BD.
12. A lifetime history of a primary psychotic disorder (e.g. schizoaffective disorder, bipolar subtype) according to DSM-5 criteria.
13. Patients who have met the DSM-5 criteria for a substance use disorder (except for nicotine or caffeine) within the past 6 months.
14. Significant active suicidal ideation (as evidenced by MADRS suicide item ≥ 4).
15. Pregnancy or lactation.
16. Liver function tests (AST and ALT) three times the upper limit of normal.

Where this trial is running

Vancouver, British Columbia and 5 other locations

• UBC Mood Disorders Centre — Vancouver, British Columbia, Canada (Recruiting)
• St. Joseph's Healthcare — Hamilton, Ontario, Canada (Recruiting)
• Providence Care Hospital — Kingston, Ontario, Canada (Recruiting)
• Sunnybrook Health Sciences Centre — Toronto, Ontario, Canada (Not_yet_recruiting)
• Centre for Addiction and Mental Health (CAMH) — Toronto, Ontario, Canada (Not_yet_recruiting)
• Douglas Mental Health University Institute — Montreal, Quebec, Canada (Not_yet_recruiting)

Study contacts

• Principal investigator: Lakshmi N Yatham, MBBS, MRCPsy — University of British Columbia, Department of Psychiatry
• Study coordinator: Nazlin Walji, BSc

Conditions Bipolar Disorder; Cannabidiol; Bipolar Depression; Mood Disorder; CBD; Depression