Cannabidiol as a Treatment for Mood Disorders : A Systematic Review
Le cannabidiol comme traitement des troubles de l’humeur : une revue systématique

Jairo Vinicius Pinto, MD, Gayatri Saraf, MD, Christian Frysch, MD, Daniel Vigo, MD, DrPH, Kamyar Keramatian, MD, MSc, FRCPC, Trisha Chakrabarty, MD, Raymond W. Lam, MD, Marcia Kauer-Sant’Anna, MD, PhD, and Lakshmi N. Yatham, MBBS, FRCPC

The Canadian Journal of Psychiatry /La Revue Canadienne de Psychiatrie, 2020, Vol. 65, (4), 213-227.

Doi : 10.1177/0706743719895195

 

Abstract

Objective : To review the current evidence for efficacy of cannabidiol in the treatment of mood disorders.

Methods : We systematically searched PubMed, Embase, Web of Science, PsychInfo, Scielo, ClinicalTrials.gov, and The Cochrane Central Register of Controlled Trials for studies published up to July 31, 2019. The inclusion criteria were clinical trials, observational studies, or case reports evaluating the effect of pure cannabidiol or cannabidiol mixed with other cannabinoids on mood symptoms related to either mood disorders or other health conditions. The review was reported in accordance with guidelines from Preferred Reporting Items for Systematic reviews and Meta-Analyses protocol.

Results : Of the 924 records initially yielded by the search, 16 were included in the final sample. Among them, six were clinical studies that used cannabidiol to treat other health conditions but assessed mood symptoms as an additional outcome. Similarly, four tested cannabidiol blended with D-9 tetrahydro-cannabinol in the treatment of general health conditions and assessed affective symptoms as secondary outcomes. Two were case reports testing cannabidiol. Four studies were observational studies that evaluated the cannabidiol use and its clinical correlates. However, there were no clinical trials investigating the efficacy of cannabidiol, specifically in mood disorders or assessing affective symptoms as the primary outcome. Although some articles point in the direction of benefits of cannabidiol to treat depressive symptoms, the methodology varied in several aspects and the level of evidence is not enough to support its indication as a treatment for mood disorders.

Conclusions : There is a lack of evidence to recommend cannabidiol as a treatment for mood disorders. However, considering the preclinical and clinical evidence related to other diseases, cannabidiol might have a role as a treatment for mood disorders. Therefore, there is an urgent need for well-designed clinical trials investigating the efficacy of cannabidiol in mood disorders.

 

Abrégé

Objectif : Examiner les données probantes actuelles sur l’efficacité du cannabidiol dans le traitement des troubles de l’humeur.

Méthodes : Nous avons systématiquement recherché dans PubMed, Embase, Web of Science, PsychInfo, Scielo, Clinical- Trials.gov et CENTRAL des études publiées jusqu’au 31 juillet 2019. Les critères d’inclusion étaient des essais cliniques, des études par observation ou des rapports de cas qui  évaluent l’effet du cannabidiol pur ou du cannabidiol mélangé avec d’autres cannabinoïdes sur les symptômes de l’humeur li´es aux troubles de l’humeur ou à d’autres états de santé. La revue a été rédigée conformément aux lignes directrices du protocole PRISMA.

Résultats : Sur les 924 études d’abord produites par la recherche, 16 ont été incluses dans l’échantillon final. Sur celles-ci, six étaient des études cliniques qui utilisaient le cannabidiol pour traiter d’autres états de santé mais qui évaluaient les symptômes de l’humeur comme resultat additionnel. De même, quatre études testaient le cannabidiol melangé avec du D-9-tetrahydrocannabinol dans le traitement d’états de santé généraux et évaluaient les symptômes affectifs comme résultats secondaires. Deux étaient des rapports de cas testant le cannabidiol. Quatre études étaient des études par observation qui évaluaient l’utilisation du cannabidiol et ses corrélats cliniques. Cependant, aucun essai clinique n’investiguait l’efficacité du cannabidiol, spécifiquement dans les troubles de l’humeur, ni n’évaluait les symptômes affectifs comme résultat principal. Bien que certains articles laissent présager les avantages du cannabidiol pour traiter les symptômes dépressifs, la méthodologie variait à plusieurs égards et le niveau des données probantes ne suffit pas à l’indiquer comme traitement des troubles de l’humeur.

Conclusions : Les données probantes actuelles ne suffisent pas pour recommander le cannabidiol comme traitement des troubles de l’humeur. Toutefois, compte tenu des données probantes précliniques et cliniques li´ees `a d’autres maladies, le cannabidiol pourrait jouer un rôle comme traitement des troubles de l’humeur. Il y a donc un urgent besoin d’essais cliniques bien conçus qui recherchent l’efficacité du cannabidiol dans les troubles de l’humeur.

Keywords : cannabidiol, cannabinoids, mood disorders, affective disorders, major depressive disorder, depressive disorders, bipolar disorder, mania

 

Introduction

Mood disorders are common psychiatric conditions, with major depressive disorder (MDD) reaching a lifetime prevalence of up to 14.6%,1 affecting more than 300 million people worldwide,2 while bipolar disorder reaches a prevalence of 4.4%, including subthreshold cases.3 Both are chronic mental disorders that usually start early in life and follow a chronic course, commonly resulting in significant functional impairment and are associated with premature death due to comorbid medical illness and suicide.4-6 Both conditions are also among the leading causes of years lived with disability directly and of years of life lost due to suicide. 7-9 Long-term treatment strategies are, therefore, the mainstay of management. However, especially in the case of bipolar disorder, the most efficacious medications are associated with adverse effects, which can lead to noncompliance with treatment and poor clinical and functional outcomes. 10,11 In this context, new treatments with novel mechanisms of action and good tolerability profile which are suitable for long-term use are urgently needed.

The plant Cannabis sativa contains more than 600 compounds, among which 100 share similar structures and are known as cannabinoids.12 Cannabidiol is one of these phytocannabinoids; preclinical and clinical studies have suggested its therapeutic utility in brain disorders. While D-9- tetrahydro-cannabinol (THC), the main active component of the plant, is related to psychotomimetic effects, inducing anxiety and psychotic symptoms, cannabidiol can reverse these effects due to its impact on CB1 and 5-hydroxytryptamine (5-HT1A) receptors.13,14Recent clinical studies have shown the anti-convulsant,15,16 antipsychotic,17,18 and anxiolytic19-21 properties of cannabidiol; preclinical studies have also shown antidepressant-like effects in several animal models of depression.22-25 Acting in the endocannabinoid system, cannabidiol has a unique pharmacological profile with promising results in neuropsychiatric disorders.

Briefly, the endocannabinoid system consists of the CB1 and CB2 receptors and their endogenous ligands. While the CB1 receptors are primarily present in the cortex, basal ganglia, hippocampus, and cerebellum,26 the CB2 receptors are less prevalent in the central nervous system but can be
found in microglia and vascular elements.27,28 The endocannabinoid system is a neuromodulator in both the central and peripheral nervous systems influencing several biological functions including mood, anxiety, appetite, sleep, memory processing, pain sensation, and immune functions.29,30 There
is evidence that schizophrenia is associated with alterations in the endocannabinoid system,17,31,32 which could explain favorable results with cannabidiol in some clinical trials in patients with schizophrenia.17,18 Furthermore, with receptors and ligands present in neurons and immune cells, the endocannabinoid system is especially interesting in the context of mood disorders since both MDD and bipolar disorder are illnesses whose pathophysiology involves changes in the brain33-37 and the immune system.36-39

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10.1177_0706743719895195