Cannabidiol as an Adjunctive Treatment for Acute Bipolar Depression: A Pilot Study: Le cannabidiol comme traitement d'appoint de la dépression bipolaire aiguë : une étude pilote.

OBJECTIVE: The treatment of bipolar depression remains challenging due to the limited effective and safe therapeutic options available; thus, developing newer treatments that are effective and well tolerable is an urgent unmet need. The objective of the present trial was to test 150 to 300 mg/day of cannabidiol as an adjunctive treatment for bipolar depression. METHOD: A randomized, double-blind, placebo-controlled pilot study to assess the efficacy of adjunctive cannabidiol in bipolar depression was used. Efficacy parameters were changes in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to week 8. Secondary outcomes included response and remission rates, changes in anxiety and psychotic symptoms, and changes in functioning. Patients continued double-blind treatment until week 12 to monitor for adverse effects, laboratory analysis, and manic symptoms. Study registry: NCT03310593. RESULTS: A total of 35 participants were included. MADRS scores significantly decreased from baseline to the endpoint (placebo, -14.56; cannabidiol, -15.38), but there was no significant difference between the groups. Similarly, there were no other significant effects on the secondary outcomes. However, an exploratory analysis showed a significant effect of cannabidiol 300 mg/day in reducing MADRS scores from week 2 to week 8 (placebo, -6.64; cannabidiol, -13.72). There were no significant differences in the development of manic symptoms or any other adverse effects. CONCLUSION: Cannabidiol did not show significantly higher adverse effects than placebo. Despite the negative finding on the primary outcome, an exploratory analysis suggested that cannabidiol should be further studied in bipolar depression in higher doses of at least 300 mg/day and under research designs that could better control for high placebo response.

The prevalence and clinical correlates of cannabis use and cannabis use disorder among patients with bipolar disorder: A systematic review with meta-analysis and meta-regression.

Bipolar disorder (BD) is commonly associated with comorbidities, especially substance use disorders. In light of this, the present review aimed to investigate the prevalence and clinical correlates of cannabis use in BD. Studies evaluating the prevalence of cannabis use among patients with BD and studies reporting a dichotomous sample of patients with cannabis use compared to those without the use were included. Meta-analyses using random-effects models were performed, and sources of heterogeneity were explored using meta-regression. The search resulted in 2918 publications, of which 53 were included. The prevalence of cannabis use was 24% (95%CI:18-29; k = 35; n = 51,756). Cannabis use was significantly associated with being younger, male, and single; having fewer years of education and an earlier onset of affective symptoms; and lifetime psychotic symptoms, suicide attempts, and use of tobacco, alcohol, and other substances. In conclusion, cannabis use present in almost one-quarter of patients with BD and is associated with factors that are highly relevant for both clinical practice and public health.