Cannabidiol as an Adjunctive Treatment for Bipolar Depression

Phase 2

Terminated

• Conditions: Bipolar Disorder; Bipolar Depression; Bipolar Affective Disorder
• Interventions: Drug: Cannabidiol; Drug: Placebo

• Registration Number: NCT03310593
• Lead Sponsor: Hospital de Clinicas de Porto Alegre

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-06-15
• Study First Submitted QC: 2017-10-13
• Study First Posted: 2017-10-16
• Study Start: 2017-11-01
• Primary Completion: 2020-02-24
• Study Completion: 2020-03-24
• Status Verified: 2021-06
• Last Update Submitted: 2021-06-30
• Last Update Posted: 2021-07-02

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 36

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cannabidiol	Cannabidiol	Cannabidiol 150-300mg per day for 12 weeks.
Placebo	Placebo	Cannabidiol comparator for 12 weeks.

Primary Outcome Measures

Name	Time	Method
Change from baseline Montgomery-Asberg Depression Rating Scale (MADRS) scores.	08 weeks	* Change from baseline Montgomery-Asberg Depression Rating Scale (MADRS) scores.; * Scale range: from 0 to 60.; * Higher values represent more severe symptoms of depression.

Secondary Outcome Measures

Name	Time	Method
Improvement in clinical global impression.	Up to weeks 08 and 12	* 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.
Improvement in anxiety symptoms	Up to weeks 08 and 12	* Change from baseline in Hamilton Anxiety Rating Scale (HAMA).; * Scale range: from 0 to 56.; * Higher values represent more severe symptoms of anxiety.
Improvement in functioning.	Up to weeks 08 and 12	* Change from baseline Functioning Assessment Short Test (FAST) scores.; * Scale range: from 0 to 72.; * Higher values represent more severe functional impairment.
Change in endocannabinoid levels in the blood.	Up to weeks 08 and 12	Change in endocannabinoid levels in the blood (anandamide and 2-arachidonoylglycerol).
Change in depressive symptoms	Up to weeks 08 and 12	* Change from baseline in Hamilton Depression Rating Scale (HAMD) score.; * Scale range: from 0 to 52.; * Higher values represent more severe symptoms of depression.
Change in depressive symptoms according to MADRS	Up to week 12	* Higher values represent more severe symptoms of depression.; * Scale range: from 0 to 60.
Improvement in biological rhythms.	Up to weeks 08 and 12	* 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.
Change in psychotic symptoms	Up to weeks 08 and 12	* Change from baseline in Brief Psychiatric Rating Scale (BPRS) score.; * Scale range: from 0 to 108.; * Higher values represent more severe symptoms of psychosis.
Change in depressive symptoms according to PHQ-9	Up to weeks 08 and 12	* Change from baseline in Patient Health Questionnaire (PHQ-9) score.; * Scale range: from 0 to 27.
Change in oxidative stress markers levels in the blood.	Up to weeks 08 and 12	Change in oxidative stress markers levels in the blood.
Change in BDNF levels in the blood.	Up to weeks 08 and 12	Change in brain-derived neurotrophic factor (BDNF) levels in the blood.
Change in inflammatory levels in the blood.	Up to weeks 08 and 12	Change in inflammatory levels in the blood (cytokines, chemokines and C-reactive protein).
Remission of manic symptoms.	Up to weeks 08 and 12	* 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.

Trial Locations

Locations (1)

Hospital de Clínicas de Porto Alegre; 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil