International forskning

Cannabidiol as an Adjunctive Treatment for Acute Bipolar Depression: A Pilot Study

Jairo Vinícius Pinto 1 2 3, José Alexandre S Crippa 4 5, Keila Maria Ceresér 1 2, Miréia Fortes Vianna-Sulzbach 1 2, Érico de Moura Silveira Júnior 1 2, Gabriel Santana da Rosa 1, Manoella Guatimuzim Testa da Silva 1, Gabriel Henrique Hizo 1 6, Leonardo Simão Medeiros 1, Carlos Eduardo Santana de Oliveira 1, Giovana Bristot 1 6, Alline Cristina Campos 5 7, Francisco Silveira Guimarães 5 7, Jaime E C Hallak 4 5, Antonio W Zuardi 4 5, Lakshmi N Yatham 8, Flávio Kapczinski 1 2 5 9, Márcia Kauer-Sant'Anna 1 2 6

  • 1Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
  • 2Graduate Programme in Psychiatry and Behavioural Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
  • 3University Hospital, Federal University of Santa Catarina, Florianópolis, SC, Brazil.
  • 4Department of Neuroscience and Behavioural Sciences, University of São Paulo, Ribeirão Preto, SP, Brazil.
  • 5National Institute for Science and Technology in Translational Medicine (INCT-TM), CNPq/FAPESP/CAPES, Ribeirão Preto, Brazil.
  • 6Graduate Programme in Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
  • 7Department of Pharmacology, University of São Paulo, Ribeirão Preto, SP, Brazil.
  • 8Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
  • 9Department of Psychiatry and Behavioral Neuroscience, McMaster University, Hamilton, ON, Canada.


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.

Keywords: Trouble bipolaire; bipolar depression; bipolar disorder; cannabidiol; cannabinoids; cannabinoïdes; clinical trial; dépression bipolaire; essai clinique.; essai randomisé contrôlé; mood disorders; randomized controlled trial.