Cannabidiol as an Adjunctive Treatment for Bipolar Depression (CBDBD)

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

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.

Study Overview

• Status: Terminated
• Conditions: Bipolar Disorder; Bipolar Depression; Bipolar Affective Disorder
• Intervention / Treatment: Drug: Cannabidiol; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
      • Hospital de Clinicas de Porto Alegre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side effects	Evaluation of side effects according Udvalg for Kliniske Undersogelser (UKU) side effects rating scale.; Scale range: from 0 to 144.; Higher values represent more severe side effects associated to medications.	Up to weeks 08 and 12

Collaborators and Investigators

• Sponsor: Hospital de Clinicas de Porto Alegre
• Collaborators: University of Sao Paulo; Federal University of Rio Grande do Sul
• Investigators: Study Chair: Márcia Kauer-Sant'Anna, MD, PhD, Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2017
• Primary Completion (Actual): February 24, 2020
• Study Completion (Actual): March 24, 2020

Study Registration Dates

• First Submitted: June 15, 2017
• First Submitted That Met QC Criteria: October 13, 2017
• First Posted (Actual): October 16, 2017

Study Record Updates

• Last Update Posted (Actual): July 2, 2021
• Last Update Submitted That Met QC Criteria: June 30, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: bipolar disorder; bipolar depression; cannabidiol; endocannabinoids
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Bipolar and Related Disorders; Depression; Depressive Disorder; Disease; Bipolar Disorder; Mood Disorders; Anticonvulsants; Cannabidiol
• Other Study ID Numbers: 63811317300005327

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No