Skip to main content
SpringerLink
Log in

Cannabidiol in the Treatment of Mood Disorders

  • Novel Therapeutics in Mood Disorders (R Mansur, Section Editor)
  • Published:
Current Treatment Options in Psychiatry Aims and scope Submit manuscript

Abstract

Purpose of Review

Preclinical studies have demonstrated that cannabidiol improves depressive-like behaviors in animal models, raising its plausibility to be investigated as a treatment for major depressive disorder (MDD) and bipolar disorder (BD). Therefore, our aim is to review the available clinical data of cannabidiol in the treatment of mood disorders.

Recent Findings

There are no published randomized clinical trials (RCTs) that investigated the efficacy of cannabidiol in mood disorders, either alone or in combination with other cannabinoids. Similarly, there are no published trials with affective symptoms as the primary outcome. There are a few studies which investigated mood symptoms as secondary outcomes within medical conditions or non-mood disorder psychiatric conditions, and the results are conflicting due to the methodological differences between studies. Nevertheless, studies have found cannabidiol to be well-tolerated with few adverse effects such as diarrhea and somnolence.

Summary

There are no RCT data for the efficacy of cannabidiol in the treatment of MDD or BD, but few studies assessed its efficacy on mood symptoms as secondary outcomes in medical and non-psychiatric disorders populations with conflicting results. Thus, currently, there is insufficient evidence to recommend cannabidiol as a treatment for mood disorders, and high-quality clinical trials are urgently needed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Devinsky O, Cross JH, Laux L, et al. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med. 2017;376:2011–20. https://doi.org/10.1056/NEJMoa1611618.

    Article  CAS  PubMed  Google Scholar 

  2. Devinsky O, Patel AD, Cross JH, et al. Effect of cannabidiol on drop seizures in the Lennox-Gastaut syndrome. N Engl J Med. 2018;378:1888–97. https://doi.org/10.1056/NEJMoa1714631.

    Article  CAS  PubMed  Google Scholar 

  3. Freeman TP, Hindocha C, Baio G, et al. Cannabidiol for the treatment of cannabis use disorder: a phase 2a, double-blind, placebo-controlled, randomised, adaptive Bayesian trial. Lancet Psychiatry. 2020;7:865–74. https://doi.org/10.1016/S2215-0366(20)30290-X.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Hurd YL, Spriggs S, Alishayev J, et al. Cannabidiol for the reduction of cue-induced craving and anxiety in drug-abstinent individuals with heroin use disorder: a double-blind randomized placebo-controlled trial. Am J Psychiatry. 2019;176(11):911–22. https://doi.org/10.1176/appi.ajp.2019.18101191.

    Article  PubMed  Google Scholar 

  5. Bergamaschi MM, Queiroz RHC, Chagas MHN, et al. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients. Neuropsychopharmacology. 2011;36:1219–26. https://doi.org/10.1038/npp.2011.6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Linares IM, Zuardi AW, Pereira LC, et al. Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test. Rev Bras de Psiquiatr (Sao Paulo, Brazil : 1999). 2019;41:9–14. https://doi.org/10.1590/1516-4446-2017-0015.

  7. Zuardi AW, Rodrigues NP, Silva AL, et al. Inverted U-shaped dose-response curve of the anxiolytic effect of cannabidiol during public speaking in real life. Front Pharmacol. 2017;8:259. https://doi.org/10.3389/fphar.2017.00259.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Leweke FM, Piomelli D, Pahlisch F, et al. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry. 2012;2:e94. https://doi.org/10.1038/tp.2012.15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. McGuire P, Robson P, Cubala WJ, et al. Cannabidiol (CBD) as an adjunctive therapy in schizophrenia: a multicenter randomized controlled trial. Am J Psychiatry. 2018;175:225–31. https://doi.org/10.1176/appi.ajp.2017.17030325.

    Article  PubMed  Google Scholar 

  10. Crippa JA, Guimaraes FS, Campos AC, Zuardi AW. Translational investigation of the therapeutic potential of cannabidiol (CBD): toward a new age. Front Immunol. 2018;9:2009. https://doi.org/10.3389/fimmu.2018.02009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Szkudlarek HJ, Desai SJ, Renard J, et al. Delta-9-tetrahydrocannabinol and cannabidiol produce dissociable effects on prefrontal cortical executive function and regulation of affective behaviors. Neuropsychopharmacology. 2019;44:817–25. https://doi.org/10.1038/s41386-018-0282-7.

    Article  CAS  PubMed  Google Scholar 

  12. • Pinto JV, Saraf G, Frysch C, et al. Cannabidiol as a Treatment for Mood Disorders: A Systematic Review. Can J Psychiatry. 2019;65(4):213–227. https://doi.org/10.1177/0706743719895195

  13. Britch SC, Babalonis S, Walsh SL. Cannabidiol: pharmacology and therapeutic targets. Psychopharmacology. 2021;238:9–28.

    Article  CAS  Google Scholar 

  14. Shoval G, Shbiro L, Hershkovitz L, et al. Prohedonic effect of cannabidiol in a rat model of depression. Neuropsychobiology. 2016;73:123–9. https://doi.org/10.1159/000443890.

    Article  CAS  PubMed  Google Scholar 

  15. Shbiro L, Hen-Shoval D, Hazut N, et al. Effects of cannabidiol in males and females in two different rat models of depression. Physiol Behav. 2019;201:59–63. https://doi.org/10.1016/j.physbeh.2018.12.019.

    Article  CAS  PubMed  Google Scholar 

  16. Sales AJ, Fogaca MV, Sartim AG, et al. Cannabidiol induces rapid and sustained antidepressant-like effects through increased BDNF signaling and synaptogenesis in the prefrontal cortex. Mol Neurobiol. 2019;56:1070–81. https://doi.org/10.1007/s12035-018-1143-4.

    Article  CAS  PubMed  Google Scholar 

  17. Linge R, Jimenez-Sanchez L, Campa L, et al. Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: role of 5-HT1A receptors. Neuropharmacology. 2016;103:16–26. https://doi.org/10.1016/j.neuropharm.2015.12.017.

    Article  CAS  PubMed  Google Scholar 

  18. Sales AJ, Fogaca MV, Sartim AG, et al. Cannabidiol induces rapid and sustained antidepressant-like effects through increased BDNF signaling and synaptogenesis in the prefrontal cortex. Mol Neurobiol. 2019;56:1070–81. https://doi.org/10.1007/s12035-018-1143-4.

    Article  CAS  PubMed  Google Scholar 

  19. de Morais H, Chaves YC, Waltrick APF, et al. Sub-chronic treatment with cannabidiol but not with URB597 induced a mild antidepressant-like effect in diabetic rats. Neurosci Lett. 2018;682:62–8. https://doi.org/10.1016/j.neulet.2018.06.006.

    Article  CAS  PubMed  Google Scholar 

  20. Sales AJ, Crestani CC, Guimaraes FS, Joca SRL. Antidepressant-like effect induced by cannabidiol is dependent on brain serotonin levels. Prog Neuropsychopharmacol Biol Psychiatry. 2018;86:255–61. https://doi.org/10.1016/j.pnpbp.2018.06.002.

    Article  CAS  PubMed  Google Scholar 

  21. Zanelati TV, Biojone C, Moreira FA, et al. Antidepressant-like effects of cannabidiol in mice: possible involvement of 5-HT1A receptors. Br J Pharmacol. 2010;159:122–8. https://doi.org/10.1111/j.1476-5381.2009.00521.x.

    Article  CAS  PubMed  Google Scholar 

  22. Reus GZ, Stringari RB, Ribeiro KF, et al. Administration of cannabidiol and imipramine induces antidepressant-like effects in the forced swimming test and increases brain-derived neurotrophic factor levels in the rat amygdala. Acta Neuropsychiatr. 2011;23:241–8. https://doi.org/10.1111/j.1601-5215.2011.00579.x.

    Article  PubMed  Google Scholar 

  23. Bromet E, Andrade LH, Hwang I, et al. Cross-national epidemiology of DSM-IV major depressive episode. BMC Med. 2011;9:90. https://doi.org/10.1186/1741-7015-9-90.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Merikangas KR, Jin R, He J, et al. Prevalence and correlates of bipolar spectrum disorder in the World Mental Health Survey Initiative. Arch Gen Psychiatry. 2012;68:241–51. https://doi.org/10.1001/archgenpsychiatry.2011.12.Prevalence.

    Article  Google Scholar 

  25. GBD. Disease and Injury Incidence and Prevalence Collaborators (2017) Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2016;390:1211–59. https://doi.org/10.1016/S0140-6736(17)32154-2.

    Article  Google Scholar 

  26. Mokdad AH, Forouzanfar MH, Daoud F, et al. Global burden of diseases, injuries, and risk factors for young people’s health during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2016;387:2383–401. https://doi.org/10.1016/S0140-6736(16)00648-6.

    Article  PubMed  Google Scholar 

  27. Holtzheimer PE, Mayberg HS. Stuck in a rut: rethinking depression and its treatment. Trends Neurosci. 2011;34:1–9. https://doi.org/10.1016/j.tins.2010.10.004.

    Article  CAS  PubMed  Google Scholar 

  28. Johnston KM, Powell LC, Anderson IM, et al. The burden of treatment-resistant depression: a systematic review of the economic and quality of life literature. J Affect Disord. 2019;242:195–210. https://doi.org/10.1016/j.jad.2018.06.045.

    Article  PubMed  Google Scholar 

  29. Davis J, Desmond M, Berk M. Lithium and nephrotoxicity: a literature review of approaches to clinical management and risk stratification. BMC Nephrol. 2018;19:305. https://doi.org/10.1186/s12882-018-1101-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Vancampfort D, Vansteelandt K, Correll CU, et al. Metabolic syndrome and metabolic abnormalities in bipolar disorder: a meta-analysis of prevalence rates and moderators. Am J Psychiatry. 2013;170:265–74. https://doi.org/10.1176/appi.ajp.2012.12050620.

    Article  PubMed  Google Scholar 

  31. Vancampfort D, Stubbs B, Mitchell AJ, et al. Risk of metabolic syndrome and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder: a systematic review and meta-analysis. World Psychiatry. 2015;14:339–47. https://doi.org/10.1002/wps.20252.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Fornaro M, Anastasia A, Novello S, et al. Incidence, prevalence and clinical correlates of antidepressant-emergent mania in bipolar depression: a systematic review and meta-analysis. Bipolar Disord. 2018;20:195–227. https://doi.org/10.1111/bdi.12612.

    Article  PubMed  Google Scholar 

  33. Liu B, Zhang Y, Fang H, et al. Efficacy and safety of long-term antidepressant treatment for bipolar disorders - a meta-analysis of randomized controlled trials. J Affect Disord. 2017;223:41–8. https://doi.org/10.1016/j.jad.2017.07.023.

    Article  CAS  PubMed  Google Scholar 

  34. • Black N, Stockings E, Campbell G, et al. Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: a systematic review and meta-analysis. Lancet Psychiatry. 2019;6:995–1010. https://doi.org/10.1016/S2215-0366(19)30401-8. (Systematic review investigating cannabidiol and other cannabinoids for the treatment of psychiatric disorders.)

  35. Wade DT, Makela P, Robson P, et al. Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients. Mult Scler. 2004;10:434–41. https://doi.org/10.1191/1352458504ms1082oa.

    Article  CAS  PubMed  Google Scholar 

  36. Zajicek J, Fox P, Sanders H, et al. On behalf of the UKMS Research Group: Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. Lancet. 2003;362:7.

    Article  Google Scholar 

  37. Rog DJ, Nurmikko TJ, Friede T, Young CA. Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology. 2005;65:812–9.

    Article  Google Scholar 

  38. Aragona M, Onesti E, Tomassini V, et al. Psychopathological and cognitive effects of therapeutic cannabinoids in multiple sclerosis: a double-blind, placebo controlled, crossover study. Clin Neuropharmacol. 2009;32:41–7. https://doi.org/10.1097/WNF.0B013E3181633497.

    Article  CAS  PubMed  Google Scholar 

  39. Portenoy RK, Ganae-Motan ED, Allende S, et al. Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial. J Pain. 2012;13:438–49.

    Article  CAS  Google Scholar 

  40. López-Sendón Moreno JL, García Caldentey J, Trigo Cubillo P, et al. A double-blind, randomized, cross-over, placebo-controlled, pilot trial with Sativex in Huntington’s disease. J Neurol. 2016;263:1390–400.

    Article  Google Scholar 

  41. Allsop DJ, Copeland J, Lintzeris N, et al (2014) Nabiximols as an agonist replacement therapy during cannabis withdrawal: a randomized clinical trial. JAMA Psychiatry 71:281–291. https://doi.org/10.1001/jamapsychiatry.2013.3947

  42. Jadoon KA, Ratcliffe SH, Barrett DA, et al. Efficacy and safety of cannabidiol and tetrahydrocannabivarin on glycemic and lipid parameters in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel group pilot study. Diabetes Care. 2016;39:1777–86. https://doi.org/10.2337/dc16-0650.

    Article  CAS  PubMed  Google Scholar 

  43. Notcutt W, Price M, Miller R, et al. Initial experiences with medicinal extracts of cannabis for chronic pain: results from 34 “N of 1” studies. Anaesthesia. 2004;59:440–52. https://doi.org/10.1111/j.1365-2044.2004.03674.x.

    Article  PubMed  Google Scholar 

  44. Meneses-Gaya C de, Crippa JA, Hallak JE, et al. Cannabidiol for the treatment of crack-cocaine craving: an exploratory double-blind study. Braz J Psychiatry. 2021;43(5):467–76. https://doi.org/10.1590/1516-4446-2020-1416.

  45. Solowij N, Broyd SJ, Beale C, et al. Therapeutic effects of prolonged cannabidiol treatment on psychological symptoms and cognitive function in regular cannabis users: a pragmatic open-label clinical trial. Cannabis Cannabinoid Res. 2018;3:21–34. https://doi.org/10.1089/can.2017.0043.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Crippa JAS, Hallak JEC, Machado-de-Sousa JP, et al. Cannabidiol for the treatment of cannabis withdrawal syndrome: a case report. J Clin Pharm Ther. 2013;38:162–4. https://doi.org/10.1111/jcpt.12018.

    Article  CAS  PubMed  Google Scholar 

  47. Morgan CJA, Das RK, Joye A, et al. Cannabidiol reduces cigarette consumption in tobacco smokers: preliminary findings. Addict Behav. 2013;38:2433–6. https://doi.org/10.1016/j.addbeh.2013.03.011.

    Article  PubMed  Google Scholar 

  48. Gaston TE, Szaflarski M, Hansen B, et al. Quality of life in adults enrolled in an open-label study of cannabidiol (CBD) for treatment-resistant epilepsy. Epilepsy Behav. 2019;95:10–7. https://doi.org/10.1016/j.yebeh.2019.03.035.

    Article  PubMed  Google Scholar 

  49. Zuardi A, Crippa J, Dursun S, et al. Cannabidiol was ineffective for manic episode of bipolar affective disorder. J Psychopharmacol. 2010;24:135–7. https://doi.org/10.1177/0269881108096521.

    Article  CAS  PubMed  Google Scholar 

  50. Martin-Santos R, Crippa JA, Batalla A, et al. Acute effects of a single, oral dose of d9-tetrahydrocannabinol (THC) and cannabidiol (CBD) administration in healthy volunteers. Curr Pharm Des. 2012;18:4966–79.

    Article  CAS  Google Scholar 

  51. • Chesney E, Oliver D, Green A, et al. Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials. Neuropsychopharmacology. 2020;45:1799–1806. https://doi.org/10.1038/s41386-020-0667-2. (Systematic review and meta-analysis investigating the adverse cannabidiol in randomized clinical trials.)

Download references

Author information

Authors and Affiliations

  1. University Hospital, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil

    Jairo Vinícius Pinto MD PhD

  2. School of Medicine, Faculdade Pequeno Príncipe, Curitiba, PR, Brazil

    Mauren Letícia Ziak MD MSc

  3. Department of Psychiatry, University of Toronto, Toronto, ON, Canada

    Ayal Schaffer MD FRCPC

  4. Department of Psychiatry, University of British Columbia, Detwiller Pavilion, 2255 Wesbrook Mall, Vancouver, BC, V6T 2A1, Canada

    Lakshmi N. Yatham MBBS FRCPC

Authors
  1. Jairo Vinícius Pinto MD PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mauren Letícia Ziak MD MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ayal Schaffer MD FRCPC
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lakshmi N. Yatham MBBS FRCPC
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lakshmi N. Yatham MBBS FRCPC.

Ethics declarations

Conflict of Interest

LNY has been on speaker or advisory boards for, or has received research grants from, Alkermes, Abbvie, AstraZeneca, Bristol- Myers Squibb, Canadian Network for Mood and Anxiety Treatments, Canadian Institutes of Health Research, Sumitomo Dainippon Pharma, Eli Lilly, GlaxoSmithKline, Intracellular Therapies, Janssen, Merck, the Michael Smith Foundation for Health Research, Pfizer, Sanofi, Servier, Sunovion, and the Stanley Foundation, all outside this work. AS has been on speaker or advisory boards for AbbVie, Otsuka, Lundbeck, and GlaxoSmithKline. JVP and MLZ report no biomedical financial interests or potential conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Novel Therapeutics in Mood Disorders

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pinto, J.V., Ziak, M.L., Schaffer, A. et al. Cannabidiol in the Treatment of Mood Disorders. Curr Treat Options Psych 9, 140–150 (2022). https://doi.org/10.1007/s40501-022-00265-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40501-022-00265-3

Keywords

Search

Navigation