Cannabidiol for Bipolar Depression

(CBD-BD Trial)

Recruiting at 7 trial locations

Overseen By Alexander McGirr, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of British Columbia

Must be taking: Mood stabilizers, Atypical antipsychotics

Must not be taking: Clozapine, Tricyclics, MAOIs, others

Disqualifiers: Rapid cycling, Psychotic disorders, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

Duration: 6 weeks

360 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether cannabidiol (CBD), a compound from the cannabis plant, can treat depressive episodes in people with bipolar disorder who haven't found relief with other treatments. The trial compares CBD to a placebo (inactive substance) to determine its effect on mood symptoms. Participants will continue their current medication and receive either CBD or a placebo for 6 weeks. Those with bipolar disorder experiencing frequent depressive episodes despite other treatments may be a good fit. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

No, you will not have to stop taking your current medications. The trial allows participants to continue their existing mood stabilizers or atypical antipsychotics, as long as the doses are stable for two weeks before starting the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Earlier studies have found cannabidiol (CBD) to be safe and generally well-tolerated. Research shows that CBD did not cause more side effects than a placebo (a substance with no active ingredients) in trials with people who have bipolar disorder. This suggests that CBD could be a safe option for managing symptoms. However, these studies were small, and more research is needed to confirm these results. Prospective participants might find this information helpful in understanding the safety of CBD as a treatment option. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bipolar depression?

Unlike the standard treatments for bipolar depression, which typically involve mood stabilizers like lithium or antipsychotics, cannabidiol (CBD) offers a novel approach. CBD is derived from the cannabis plant but doesn't produce the "high" associated with THC. Researchers are excited because CBD has anti-inflammatory and neuroprotective properties that might help balance mood without the side effects common to existing medications. Additionally, CBD's unique mechanism of action targets the endocannabinoid system, which could provide a new pathway for managing bipolar depression symptoms effectively.

What evidence suggests that cannabidiol could be an effective treatment for bipolar depression?

Research has shown that cannabidiol (CBD) might help with mood issues, based on small studies for various mental and physical conditions. In this trial, some participants will receive cannabidiol, while others will receive a placebo. Some studies indicate that CBD is safe and does not cause more side effects than a placebo, which contains no active ingredients. Although large studies have not yet proven CBD's effectiveness specifically for bipolar depression, early research suggests it could safely manage symptoms. Researchers hope CBD can help with depression and anxiety in people with bipolar disorder. However, more information is needed to fully understand its effects on bipolar depression. ^{1 2 3 5 6}

Who Is on the Research Team?

Lakshmi N Yatham, MBBS, MRCPsy

Principal Investigator

University of British Columbia, Department of Psychiatry

Are You a Good Fit for This Trial?

Adults aged 19-70 with Bipolar Disorder (Type I or II) experiencing a major depressive episode, despite having tried at least one recommended treatment. They must be on stable doses of mood stabilizers or antipsychotics and agree to contraception if applicable. Excluded are those with certain liver issues, recent substance abuse, non-response to ECT, other primary psychotic disorders, severe suicidal ideation, pregnancy/lactation, intolerance to CBD or rapid cycling bipolar disorder.

Inclusion Criteria

MADRS score of ≥ 20 and YMRS score of ≤ 12

I am currently receiving medical care, either staying in the hospital or visiting as an outpatient.

I have been diagnosed with Bipolar Disorder and am currently experiencing a major depressive episode.

Exclusion Criteria

CBD treatments haven't worked for me or caused side effects.

I have been experiencing a depressive episode for more than 6 months.

History of rapid cycling

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline

Baseline assessments are conducted to establish initial health status

1 day

1 visit (in-person)

Treatment

Participants receive either Cannabidiol or placebo added to their current treatment for 6 weeks

6 weeks

5 visits (in-person), 1 visit (phone)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (phone)

What Are the Treatments Tested in This Trial?

Interventions

• Cannabidiol
• Placebo

Trial Overview The trial is testing the effectiveness of Cannabidiol (CBD) for treating depression in bipolar disorder compared to a placebo. Participants will add either CBD or placebo to their current treatment over 10 weeks and attend clinical appointments. The study is randomized and double-blind so neither participants nor researchers know who receives which treatment.

How Is the Trial Designed?

Group I: Cannabidiol Experimental Treatment 1 Intervention

Cannabidiol 200 - 600 mg / day added to current treatment for 6 weeks.

Group II: Placebo Placebo Group 1 Intervention

Placebo added to current treatment for 6 weeks.

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Published Research Related to This Trial

A systematic review of 12 clinical trials involving 803 participants found that cannabidiol (CBD) is associated with a higher likelihood of withdrawal due to adverse effects compared to placebo, particularly in studies related to childhood epilepsy.

While CBD generally appears well tolerated, significant adverse effects such as abnormal liver function tests and sedation were noted, especially in combination with other medications, highlighting the need for careful monitoring of drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials. Chesney, E., Oliver, D., Green, A., et al.[2021]

In a pilot study involving 35 participants, cannabidiol (300 mg/day) showed a significant reduction in depression scores from week 2 to week 8, suggesting potential efficacy in treating bipolar depression, although it did not outperform placebo overall.

Cannabidiol was well tolerated, with no significant increase in adverse effects compared to placebo, indicating its safety as an adjunctive treatment option for bipolar depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol as an Adjunctive Treatment for Acute Bipolar Depression: A Pilot Study. Pinto, JV., Crippa, JAS., Ceresér, KM., et al.[2023]

In a small inpatient study involving two patients with bipolar I disorder experiencing a manic episode, CBD was well-tolerated with no reported side effects, indicating a good safety profile.

However, the efficacy of CBD was limited; one patient showed improvement only when CBD was combined with olanzapine, while the other patient did not experience any symptom improvement with CBD alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol was ineffective for manic episode of bipolar affective disorder. Zuardi, A., Crippa, J., Dursun, S., et al.[2018]

There are no systematic studies on the use of cannabinoids for bipolar disorder, but anecdotal evidence suggests that some patients find relief from symptoms of mania and depression through cannabis use.

Cannabinoids like THC and CBD have potential therapeutic effects, including sedative and antidepressant properties, indicating that controlled trials are needed to explore their efficacy as adjunctive treatments for bipolar disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabinoids in bipolar affective disorder: a review and discussion of their therapeutic potential. Ashton, CH., Moore, PB., Gallagher, P., et al.[2016]

A systematic review of 13 studies involving 201 subjects found that the evidence for the efficacy of cannabidiol (CBD) in treating psychiatric disorders is limited, with most studies showing no statistical significance.

While CBD was associated with some adverse events like sedation and dizziness, these were generally mild, indicating that CBD may be safe for use, but more robust research is needed to confirm its effectiveness in conditions like schizophrenia and anxiety disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there a role for cannabidiol in psychiatry? Khoury, JM., Neves, MCLD., Roque, MAV., et al.[2019]

In a study involving both male and female rats with depressive-like behaviors, oral administration of Cannabidiol (CBD) at 30 mg/kg showed a pro-hedonic effect, increasing the preference for sweet solutions in female Wistar Kyoto rats, similar to previous findings in males.

CBD also significantly reduced immobility in the forced swim test for both male and female WKY rats, indicating its potential as a treatment for mental disorders characterized by feelings of helplessness and lack of pleasure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of cannabidiol in males and females in two different rat models of depression. Shbiro, L., Hen-Shoval, D., Hazut, N., et al.[2020]

A systematic review of 34 studies found that high doses of cannabidiol (CBD) may be effective in treating conditions like social anxiety disorder, insomnia, and epilepsy, particularly at doses between 150-600 mg/day.

The review also highlighted that CBD can interact with ∆9-THC in complex ways, sometimes enhancing and other times inhibiting its effects, indicating the need for careful dosing and consideration of CBD's role in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol in humans-the quest for therapeutic targets. Zhornitsky, S., Potvin, S.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05867849

Cannabidiol for Bipolar Depression (CBD-BD) The primary objective of this study is to assess the effectiveness, safety and tolerability of cannabidiol in patients with bipolar depression (BD I or BD II) ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37920963/

Cannabidiol as an Adjunctive Treatment for Acute Bipolar ... Conclusion: Cannabidiol did not show significantly higher adverse effects than placebo. Despite the negative finding on the primary outcome, an ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10924581/

Cannabidiol as an Adjunctive Treatment for Acute Bipolar ... Our results suggest that cannabidiol may be a safe option to be used in bipolar disorder; however, the present clinical trial is limited, and ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03310593

Cannabidiol as an Adjunctive Treatment for Bipolar ... The investigators hypothesize that treatment with cannabidiol will result in improvement of depressive and anxiety symptoms, as well as, improvement in ...

5. med.ubc.ca med.ubc.ca/news/ubc-researchers-launch-clinical-trial-exploring-cbd-for-bipolar-depression/

UBC researchers launch clinical trial exploring CBD for ... The first-of-its-kind clinical trial will explore whether CBD can help manage acute bipolar depression alongside primary courses of ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05867849?term=AREA%5BNCTIdSearch%5D(NCT05867849)&rank=1

Cannabidiol for Bipolar Depression (CBD-BD) The primary objective of this study is to assess the effectiveness, safety and tolerability of cannabidiol in patients with bipolar depression (BD I or BD II) ...