Bipolar Affective Disorder, Bipolar Depression, Bipolar Disorder
Conditions
Keywords
bipolar disorder, bipolar depression, cannabidiol, endocannabinoids
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.
Interventions
DRUGCannabidiol
Cannabidiol as active intervention.
DRUGPlacebo
Placebo intervention.
Sponsors
Hospital de Clinicas de Porto Alegre
Federal University of Rio Grande do Sul
University of Sao Paulo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Double-blind, randomized and placebo controlled study
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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 inflammatory levels in the blood. | Up to weeks 08 and 12 | Change in inflammatory levels in the blood (cytokines, chemokines and C-reactive protein). |
| Change in endocannabinoid levels in the blood. | Up to weeks 08 and 12 | Change in endocannabinoid levels in the blood (anandamide and 2-arachidonoylglycerol). |
| 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. |
| 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 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 MADRS | Up to week 12 | * Higher values represent more severe symptoms of depression. * Scale range: from 0 to 60. |
| Change in BDNF levels in the blood. | Up to weeks 08 and 12 | Change in brain-derived neurotrophic factor (BDNF) levels in the blood. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Side effects | Up to weeks 08 and 12 | * 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. |
Countries
Brazil
Outcome results
None listed