Cannabidiol for Bipolar Disorder

Overseen By Rosemary Smith, B.S.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mclean Hospital

Must not be taking: Valproate, Divalproex

Disqualifiers: Substance use, Psychotic, Eating disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 4 weeks

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a high-CBD solution (Cannabidiol) to determine its effects on people with bipolar disorder who also experience anxiety. Researchers aim to discover if CBD can reduce anxiety and improve mood in these individuals. Participants will take the CBD solution twice daily for four weeks. The trial seeks individuals diagnosed with bipolar disorder (type I or II), who experience moderate anxiety, and are on a stable medication routine. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial requires that participants are on a stable medication regimen, but it does not specify if you need to stop any current medications. However, if you are using valproate or divalproex, you cannot participate.

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

Research has shown that cannabidiol (CBD) is generally safe for people. Studies have found that most individuals tolerate CBD well. Common side effects, such as reduced appetite, are usually mild. In these studies, CBD did not cause anxiety or mood issues, making it a promising option for treating conditions like bipolar disorder. Additionally, CBD has already received approval for some other medical conditions, further supporting its safety. Overall, current evidence suggests that CBD is a safe treatment option for many people. ^{1 2 3 4 5}

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

Unlike standard treatments for bipolar disorder, which often include mood stabilizers like lithium or antipsychotics, the treatment under study uses cannabidiol (CBD), a compound derived from hemp. Researchers are excited about CBD because it has a new mechanism of action, potentially offering mood stabilization without the side effects commonly associated with traditional medications. Additionally, CBD is known for its anti-inflammatory and neuroprotective properties, which could provide a more holistic approach to managing bipolar disorder symptoms. This treatment could offer a natural alternative with fewer side effects, making it an appealing option for patients seeking different ways to manage their condition.

What evidence suggests that cannabidiol might be an effective treatment for bipolar disorder?

Research has shown that cannabidiol (CBD) might help stabilize mood, potentially benefiting people with bipolar disorder. Some small studies found that CBD can improve mood-related issues such as depression and anxiety. It generally has a good safety record, meaning it usually doesn't cause negative effects like anxiety or psychotic symptoms. Although more research is needed, early results suggest CBD could help manage mood disorders. Participants in this trial will receive a custom-formulated, hemp-derived, high-CBD solution to further evaluate its effects. ^{2 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-55 with bipolar disorder who are fluent in English, on a stable medication regimen, and have moderate anxiety but not severe depression. Participants must not be using cannabinoid products or have certain medical conditions like serious illnesses, neurological disorders, or elevated liver enzymes.

Inclusion Criteria

Provides informed consent

Is not currently experiencing greater than moderate levels of depression (evidenced by administered rating scales)

My medication doses have not changed recently.

Exclusion Criteria

Experiencing acute manic episode

Estimated IQ <75

I am not fluent in English.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Baseline

Eligible participants complete additional assessments and receive study product

1 day

1 visit (in-person)

Treatment

Participants self-administer the high-CBD solution twice daily for four weeks

4 weeks

4 visits (in-person or remote)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cannabidiol

Trial Overview

The study tests the effects of a high-CBD product on anxiety and depression in bipolar disorder over four weeks. It's an open-label pilot trial, meaning everyone knows they're taking CBD without any placebo control group involved.

How Is the Trial Designed?

Group I: Hemp-Derived Cannabidiol Solution Experimental Treatment 1 Intervention

Patients will administer a custom-formulated, hemp-derived, high-CBD solution twice daily for 4 weeks

Cannabidiol is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Approved in European Union as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome
• Seizures associated with tuberous sclerosis complex

Approved in Canada as Epidiolex for:

• Seizures associated with Lennox-Gastaut syndrome
• Seizures associated with Dravet syndrome

Who Is Running the Clinical Trial?

Mclean Hospital

Lead Sponsor

Trials

221

Recruited

22,500+

Published Research Related to This Trial

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]

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]

Serious suspected adverse reactions (SARs) to unlicensed cannabidiol (CBD) products were found to be 18.9% of all adverse events, with a higher frequency in men and adults, indicating a need for careful monitoring of its use.

The most common adverse effects associated with unlicensed CBD included mental disorders, hepatic disorders, and worsening of pre-existing epilepsy, particularly in patients also taking antiepileptic medications like clobazam and valproic acid.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacovigilance of unlicensed cannabidiol in European countries. Calapai, F., Esposito, E., Ammendolia, I., et al.[2023]

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]

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]

Both deoxycholate amphotericin B (DAMB) and lipid formulations of amphotericin B show equal efficacy in treating invasive fungal disease in neonates, based on retrospective studies and case series.

DAMB is generally safe for neonates, with fewer adverse effects compared to older children and adults, and can be used as a first-line therapy if renal function is monitored, especially with a sodium intake of 4 mEq/kg/day to reduce nephrotoxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amphotericin B in neonates: deoxycholate or lipid formulation as first-line therapy - is there a 'right' choice? Turkova, A., Roilides, E., Sharland, M.[2013]

Ketoconazole, an antifungal medication, can lead to symptoms of androgen deficiency in men, such as decreased libido and lower testosterone levels, indicating its significant impact on hormonal function during treatment for chronic infections.

In vitro studies show that ketoconazole competes with androgens for binding to androgen receptors, but the concentrations needed for this effect are unlikely to be reached in the body, suggesting limited clinical relevance for its androgen-blocking properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketoconazole binds to the human androgen receptor. Eil, C.[2013]

Fluconazole has shown rapid relief and eradication of oropharyngeal and esophageal candidiasis in 50 to 90% of patients, making it an effective treatment option, especially for those with compromised immune systems.

While fluconazole is promising for treating various mycoses, including cryptococcal meningitis, further studies are needed to establish optimal dosages and its efficacy compared to established antifungal agents, as well as to monitor potential side effects like hepatotoxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluconazole. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in superficial and systemic mycoses. Grant, SM., Clissold, SP.[2018]

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]

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]

The novel encochleated amphotericin B deoxycholate (cAMB) formulation demonstrated excellent tolerability in HIV-positive patients with cryptococcosis, with 100% of subjects able to take their full daily dose without vomiting during the initial phase I trial.

Compared to traditional intravenous amphotericin B, 96% of participants preferred the oral cAMB experience, which also showed minimal adverse effects and no kidney toxicity, indicating a safer and more patient-friendly treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I EnACT Trial of the Safety and Tolerability of a Novel Oral Formulation of Amphotericin B. Skipper, CP., Atukunda, M., Stadelman, A., et al.[2021]

Intrathecal amphotericin B deoxycholate (IT AmBd) has been a crucial treatment for coccidioidal meningitis (CM), reducing mortality rates from 100% to about 30% since the late 1950s, making it the only known curative option for this condition.

The article emphasizes the importance of proper preparation, titration, and dosing strategies for IT AmBd, based on over 60 years of clinical experience at Kern Medical, which can enhance treatment outcomes for patients with CM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrathecal Amphotericin B: A 60-Year Experience in Treating Coccidioidal Meningitis. Ho, J., Fowler, P., Heidari, A., et al.[2018]

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