Cannabidiol for Bipolar Depression (CBD-BD)

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 confirmedby 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 onlyand not for BD I) OR an atypical antipsychotic OR a combination of these (two moodstabilizers or a mood stabilizer plus an atypical antipsychotic), at therapeuticdoses. 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. Combinationsof these medications as outlined above, or the combination of any of them withlamotrigine 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 ofcurrent depressive episode with at least one CANMAT recommended first-line treatmentfor bipolar I disorder (i.e. lithium, lamotrigine, lurasidone, or quetiapine eitheras monotherapy or adjunctive therapy), or at least one first or second-linetreatment for bipolar II depression (i.e. quetiapine, lithium, lamotrigine,sertraline, or venlafaxine as monotherapy or adjunctive therapy, or bupropionadjunctive therapy).

5. A MADRS score of ≥ 20 and a YMRS score of ≤ 12 (these cut off scores are standard inbipolar depression RCTs).

6. Inpatient or outpatient status.

7. All participants are required to agree to practice highly effective methods ofcontraception (i.e. hormonal contraceptives, intrauterine device or system,vasectomy and tubal ligation, or double barrier methods of contraception) OR agreeto completely abstain from heterosexual intercourse. Females who do not havechildbearing potential are required to be postmenopausal for at least 1 year beforethe screening visit (confirmed by an FSH test) OR surgically sterile.

8. The capability of understanding, consenting to and complying with studyrequirements.

9. All concomitant medication must be at a stable dose for two weeks prior to therandomization 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 ofcurrent depression.

4. Recently started taking a CANMAT-recommended treatment for the management of acutebipolar depressive episode, but has not had a trial for a minimum of 6 weeks withadequate 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 dosehas 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 thetrial.

10. A history of non-response to electroconvulsive therapy for the current depressiveepisode.

11. A current diagnosis of other primary psychiatric disorders as assessed by a studyinvestigator 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 fornicotine 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.