Cannabidiol as an Adjunctive Treatment for Bipolar Depression

Study Overview
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Brief Summary
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Depressive symptoms are associated with significant psychosocial impairment. However, current treatments of bipolar depression are only partially effective. Cannabidiol is a natural component of cannabis without psychotomimetic or addictive properties. Cannabidiol has been shown to produce therapeutic effects including anticonvulsive, anxiolytic, antipsychotic and neuroprotective effects. The investigators hypothesize that treatment with cannabidiol will result in improvement of depressive and anxiety symptoms, as well as, improvement in functioning and inflammatory biomarkers. During the clinical trial, subjects will receive study medication (cannabidiol 150-300mg/day) or placebo for a period of 12 weeks.

Official Title
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A Double-blind, Randomized, Placebo-controlled Clinical Trial of Adjunctive Cannabidiol for Bipolar Depression

Conditions
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Bipolar Disorder, Bipolar Depression, Bipolar Affective Disorder

Intervention / Treatment
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* Drug: Cannabidiol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Major depressive episode as part of bipolar I disorder or bipolar II disorder according to Fifth Edition of Diagnostic and Statistical Manual for Mental Disorders (DSM-5) and are able to provide written informed consent. Montgomery-Asberg Depression Rating Scale (MADRS) score ≥ 12 and MADRS items 1 (Apparent Sadness) and 2 (Reported Sadness) scores ≥ 2 at baseline. Young Mania Rating Scale (YMRS) ≤ 11. Currently prescribed lithium or valproic acid and derivates (divalproex sodium, sodium valproate) or atypical antipsychotics at therapeutic dosage for at least 04 weeks before the baseline. Females must test negative for pregnancy and must be using adequate birth control measures throughout the study. Exclusion Criteria: Another concurrent mental or behavioral disorder that requires psychiatric attention in the past 6 months. Young Mania Rating Scale (YMRS) score > 12. Current or past drug sensitivity/intolerance to cannabidiol. Substance Use Disorder according to DSM-5 within past 6 months, except for nicotine Substance Use Disorder. Clinically significant unstable medical illness, neurological disorders or inflammatory/autoimmune diseases. Any autoimmune, inflammatory or neurologic disorders that requires treatment with steroidal anti-inflammatory medications or immunotherapy with biologic drugs. Actively suicidal or homicidal risk. Females who are pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blind, randomized and placebo controlled study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cannabidiol<br>Cannabidiol 150-300mg per day for 12 weeks. | Drug: Cannabidiol<br>* Cannabidiol as active intervention.<br>|
| Placebo Comparator: Placebo<br>Cannabidiol comparator for 12 weeks. | Drug: Placebo<br>* Placebo intervention.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline Montgomery-Asberg Depression Rating Scale (MADRS) scores. | Change from baseline Montgomery-Asberg Depression Rating Scale (MADRS) scores. Scale range: from 0 to 60. Higher values represent more severe symptoms of depression. | 08 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in clinical global impression. | Change from baseline in Clinical Global Impression(CGI-BP) scores. Scale range: from 1 to 7. Higher values represent more severe symptoms of bipolar disorder. | Up to weeks 08 and 12 | 
| Improvement in anxiety symptoms | Change from baseline in Hamilton Anxiety Rating Scale (HAMA). Scale range: from 0 to 56. Higher values represent more severe symptoms of anxiety. | Up to weeks 08 and 12 | 
| Improvement in functioning. | Change from baseline Functioning Assessment Short Test (FAST) scores. Scale range: from 0 to 72. Higher values represent more severe functional impairment. | Up to weeks 08 and 12 | 
| Improvement in biological rhythms. | Improvement in biological rhythms according to Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN). Scale range: from 0 to 88. Higher values represent more severe symptoms of biological rhythms. | Up to weeks 08 and 12 | 
| Change in BDNF levels in the blood. | Change in brain-derived neurotrophic factor (BDNF) levels in the blood. | Up to weeks 08 and 12 | 
| Change in inflammatory levels in the blood. | Change in inflammatory levels in the blood (cytokines, chemokines and C-reactive protein). | Up to weeks 08 and 12 | 
| Change in endocannabinoid levels in the blood. | Change in endocannabinoid levels in the blood (anandamide and 2-arachidonoylglycerol). | Up to weeks 08 and 12 | 
| Remission of manic symptoms. | Change from baseline in the Young Mania Rating Scale (YMRS) score. Scale range: from 0 to 58. Higher values represent more severe symptoms of mania. | Up to weeks 08 and 12 | 
| Change in depressive symptoms | Change from baseline in Hamilton Depression Rating Scale (HAMD) score. Scale range: from 0 to 52. Higher values represent more severe symptoms of depression. | Up to weeks 08 and 12 | 
| Change in psychotic symptoms | Change from baseline in Brief Psychiatric Rating Scale (BPRS) score. Scale range: from 0 to 108. Higher values represent more severe symptoms of psychosis. | Up to weeks 08 and 12 | 
| Change in depressive symptoms according to MADRS | Higher values represent more severe symptoms of depression. Scale range: from 0 to 60. | Up to week 12 | 
| Change in depressive symptoms according to PHQ-9 | Change from baseline in Patient Health Questionnaire (PHQ-9) score. Scale range: from 0 to 27. | Up to weeks 08 and 12 | 
| Change in oxidative stress markers levels in the blood. | Change in oxidative stress markers levels in the blood. | Up to weeks 08 and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bipolar disorder, bipolar depression, cannabidiol, endocannabinoids