By Rajnish Mago, MD (bio)
I continue to receive questions from our Members about scientific data for or against the utility of cannabidiol (CBD) for the treatment of various mental disorders. Some believe that there are is no scientific basis for considering this and others believe the opposite—that there are several good studies to support the use of cannabidiol as a treatment for mental disorders. Mental health clinicians are also often asked about cannabidiol by their patients, in part because there has been a lot of discussion of it in the media.
Taking one disorder at a time, what data are available about the use of cannabidiol as a potential treatment for schizophrenia and other psychotic disorders? To answer this question, we can look at several types of data. These include, among others:
1. The three randomized, double-blind clinical trials of cannabidiol in schizophrenia published as of October 2019 (Leweke et al., 2012; Boggs et al., 2018; McGuire et al., 2018). For my brief summary of what these clinical trials found and commentary about what to make of the findings, please see the following article on this website:
What did randomized, double-blind clinical trials of cannabidiol in schizophrenia find?
2. Very preliminary data on the possible use of cannabidiol in other psychotic disorders like Parkinson’s disease psychosis (Zuardi et al., 2009)
3. Antagonism by cannabidiol of the potential of delta-9-tetrahydrocannabinol (THC) to induce psychotic symptoms. This includes the lower risk of psychotic symptoms due to cannabis if the preparation has higher CBD content (Englund et al., 2017, Morgan et al., 2012) and, related to this, the ability of cannabidiol to reduce the induction of psychotic symptoms by THC (Bhattacharya et al., 2010; Englund et al., 2013).
4. Efficacy of cannabidiol in the many studies using animal models of schizophrenia
5. Biological plausibility—the role of the endocannabinoid system in the pathophysiology of schizophrenia; the effect of cannabidiol on biological systems known to be involved in schizophrenia.
Related Pages
What did randomized, double-blind clinical trials of cannabidiol in schizophrenia find?
What is cannabidiol (CBD)?
Potential adverse effects of cannabidiol (CBD)
Effects of cannabis or cannabinoids on the cytochrome P450 enzymes
*You* Ask the Expert: Interview with Ethan Russo, MD
Cannabis (“Marijuana”): Terminology
Cannabis (marijuana): Resources for patients
The endocannabinoid system: An introduction
References
Systematic reviews/ Meta-analyses
Iseger TA, Bossong MG. A systematic review of the antipsychotic properties of cannabidiol in humans. Schizophr Res. 2015 Mar;162(1-3):153-61. doi: 10.1016/j.schres.2015.01.033. Epub 2015 Feb 7. Review. PubMed PMID: 25667194.
Osborne AL, Solowij N, Weston-Green K. A systematic review of the effect of cannabidiol on cognitive function: Relevance to schizophrenia. Neurosci Biobehav Rev. 2017 Jan;72:310-324. doi: 10.1016/j.neubiorev.2016.11.012. Epub 2016 Nov 22. Review. PubMed PMID: 27884751.
Rohleder C, Müller JK, Lange B, Leweke FM. Cannabidiol as a Potential New Type of an Antipsychotic. A Critical Review of the Evidence. Front Pharmacol. 2016 Nov 8;7:422. eCollection 2016. Review. PubMed PMID: 27877130; PubMed Central PMCID: PMC5099166.
Other review articles/ commentaries
Bassir Nia A, Hurd YL. Cannabidiol, an Adjunct Player in the Antipsychosis Arsenal. Am J Psychiatry. 2018 Mar 1;175(3):197-198. doi: 10.1176/appi.ajp.2017.17121295. PubMed PMID: 29490489.
Batalla A, Janssen H, Gangadin SS, Bossong MG. The Potential of Cannabidiol as a Treatment for Psychosis and Addiction: Who Benefits Most? A Systematic Review. J Clin Med. 2019 Jul 19;8(7). pii: E1058. doi: 10.3390/jcm8071058. Review. PubMed PMID: 31330972; PubMed Central PMCID: PMC6678854.
Diviant JP, Vigil JM, Stith SS. The Role of Cannabis within an Emerging Perspective on Schizophrenia. Medicines (Basel). 2018 Aug 8;5(3). pii: E86. doi: 10.3390/medicines5030086. PubMed PMID: 30096776; PubMed Central PMCID: PMC6164121.
Englund A, Freeman TP, Murray RM, McGuire P. Can we make cannabis safer? Lancet Psychiatry. 2017 Aug;4(8):643-648. doi: 10.1016/S2215-0366(17)30075-5. Epub 2017 Mar 2. Review. PubMed PMID: 28259650.
Englund A, Morrison PD, Nottage J, Hague D, Kane F, Bonaccorso S, Stone JM, Reichenberg A, Brenneisen R, Holt D, Feilding A, Walker L, Murray RM, Kapur S. Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment. J Psychopharmacol. 2013 Jan;27(1):19-27. doi: 10.1177/0269881112460109. Epub 2012 Oct 5. PubMed PMID: 23042808.
Fakhoury M. Could cannabidiol be used as an alternative to antipsychotics? J Psychiatr Res. 2016 Sep;80:14-21. doi: 10.1016/j.jpsychires.2016.05.013. Epub 2016 May 28. Review. PubMed PMID: 27267317.
Guinguis R, Ruiz MI, Rada G. Is cannabidiol an effective treatment for schizophrenia? Medwave. 2017 Aug 9;17(7):e7010. doi: 10.5867/medwave.2017.07.7010. Spanish, English. PubMed PMID: 28820868.
Gururajan A, Malone DT. Does cannabidiol have a role in the treatment of schizophrenia? Schizophr Res. 2016 Oct;176(2-3):281-290. doi: 10.1016/j.schres.2016.06.022. Epub 2016 Jul 1. Review. PubMed PMID: 27374322.
Hahn B. The Potential of Cannabidiol Treatment for Cannabis Users With Recent-Onset Psychosis. Schizophr Bull. 2018 Jan 13;44(1):46-53. doi: 10.1093/schbul/sbx105. Review. PubMed PMID: 29083450; PubMed Central PMCID: PMC5768049.
Leweke FM, Mueller JK, Lange B, Fritze S, Topor CE, Koethe D, Rohleder C. Role of the Endocannabinoid System in the Pathophysiology of Schizophrenia: Implications for Pharmacological Intervention. CNS Drugs. 2018 Jul;32(7):605-619. doi: 10.1007/s40263-018-0539-z. Review. PubMed PMID: 30022465.
Leweke FM, Mueller JK, Lange B, Rohleder C. Therapeutic Potential of Cannabinoids in Psychosis. Biol Psychiatry. 2016 Apr 1;79(7):604-12. doi: 10.1016/j.biopsych.2015.11.018. Epub 2015 Nov 28. Review. PubMed PMID: 26852073.
Manseau MW, Goff DC. Cannabinoids and Schizophrenia: Risks and Therapeutic Potential. Neurotherapeutics. 2015 Oct;12(4):816-24. doi: 10.1007/s13311-015-0382-6. Review. PubMed PMID: 26311150; PubMed Central PMCID: PMC4604190.
McGuire P, Englund A, Bhattacharyya S. Commentary on “The Potential of Cannabidiol Treatment for Cannabis Users With Recent-Onset Psychosis”. Schizophr Bull. 2018 Jan 13;44(1):18-19. doi: 10.1093/schbul/sbx124. PubMed PMID: 29346673; PubMed Central PMCID: PMC5768041.
McLoughlin BC, Pushpa-Rajah JA, Gillies D, Rathbone J, Variend H, Kalakouti E, Kyprianou K. Cannabis and schizophrenia. Cochrane Database Syst Rev. 2014 Oct 14;(10):CD004837. doi: 10.1002/14651858.CD004837.pub3. Review. PubMed PMID: 25314586.
Pushpa-Rajah JA, McLoughlin BC, Gillies D, Rathbone J, Variend H, Kalakouti E, Kyprianou K. Cannabis and schizophrenia. Schizophr Bull. 2015 Mar;41(2):336-7. doi: 10.1093/schbul/sbu168. Epub 2014 Dec 30. Review. PubMed PMID: 25552590; PubMed Central PMCID: PMC4332954.
Seeman P. Cannabidiol is a partial agonist at dopamine D2High receptors, predicting its antipsychotic clinical dose. Transl Psychiatry. 2016 Oct 18;6(10):e920. doi: 10.1038/tp.2016.195. PubMed PMID: 27754480; PubMed Central PMCID: PMC5315552.
Zuardi AW, Crippa JA, Hallak JE, Bhattacharyya S, Atakan Z, Martin-Santos R, McGuire PK, Guimarães FS. A critical review of the antipsychotic effects of cannabidiol: 30 years of a translational investigation. Curr Pharm Des. 2012;18(32):5131-40. Review. PubMed PMID: 22716160.
Randomized, double-blind clinical trials in humans
Boggs DL, Surti T, Gupta A, Gupta S, Niciu M, Pittman B, Schnakenberg Martin AM, Thurnauer H, Davies A, D’Souza DC, Ranganathan M. The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia a randomized placebo controlled trial. Psychopharmacology (Berl). 2018 Jul;235(7):1923-1932. doi: 10.1007/s00213-018-4885-9. Epub 2018 Apr 5. PubMed PMID: 29619533.
Leweke FM, Piomelli D, Pahlisch F, Muhl D, Gerth CW, Hoyer C, Klosterkötter J, Hellmich M, Koethe D. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry. 2012 Mar 20;2:e94. doi: 10.1038/tp.2012.15. PubMed PMID: 22832859; PubMed Central PMCID: PMC3316151.
McGuire P, Robson P, Cubala WJ, Vasile D, Morrison PD, Barron R, Taylor A, Wright S. Cannabidiol (CBD) as an Adjunctive Therapy in Schizophrenia: A Multicenter Randomized Controlled Trial. Am J Psychiatry. 2018 Mar 1;175(3):225-231. doi: 10.1176/appi.ajp.2017.17030325. Epub 2017 Dec 15. PubMed PMID: 29241357.
Case reports
Makiol C, Kluge M. Remission of severe, treatment-resistant schizophrenia following adjunctive cannabidiol. Aust N Z J Psychiatry. 2019 Mar;53(3):262. doi: 10.1177/0004867418815982. Epub 2018 Dec 13. PubMed PMID: 30543310.
Zuardi AW, Hallak JE, Dursun SM, Morais SL, Sanches RF, Musty RE, Crippa JA. Cannabidiol monotherapy for treatment-resistant schizophrenia. J Psychopharmacol. 2006 Sep;20(5):683-6. Epub 2006 Jan 9. PubMed PMID: 16401651. Three patients, titrated cannabidiol up to 1280 mg/day.
Animal studies
Abílio VC. Antipsychotic profile of cannabidiol and rimonabant in an animal model of emotional context processing in schizophrenia. Curr Pharm Des. 2012;18(32):4960-5. PubMed PMID: 22716146.
Arnold JC, Boucher AA, Karl T. The yin and yang of cannabis-induced psychosis: the actions of Δ(9)-tetrahydrocannabinol and cannabidiol in rodent models of schizophrenia. Curr Pharm Des. 2012;18(32):5113-30. PubMed PMID: 22716133.
Gururajan A, Taylor DA, Malone DT. Effect of cannabidiol in a MK-801-rodent model of aspects of schizophrenia. Behav Brain Res. 2011 Sep 23;222(2):299-308. doi: 10.1016/j.bbr.2011.03.053. Epub 2011 Mar 31. PubMed PMID: 21458498.
Peres FF, Diana MC, Levin R, Suiama MA, Almeida V, Vendramini AM, Santos CM, Zuardi AW, Hallak JEC, Crippa JA, Abílio VC. Cannabidiol Administered During Peri-Adolescence Prevents Behavioral Abnormalities in an Animal Model of Schizophrenia. Front Pharmacol. 2018 Aug 21;9:901. doi: 10.3389/fphar.2018.00901. eCollection 2018. PubMed PMID: 30186164; PubMed Central PMCID: PMC6113576.
Peres FF, Diana MC, Suiama MA, Justi V, Almeida V, Bressan RA, Zuardi AW, Hallak JE, Crippa JA, Abilio VC. Peripubertal treatment with cannabidiol prevents the emergence of psychosis in an animal model of schizophrenia. Schizophr Res. 2016 Apr;172(1-3):220-1. doi: 10.1016/j.schres.2016.02.004. Epub 2016 Feb 5. PubMed PMID: 26856781.
Stark T, Ruda-Kucerova J, Iannotti FA, D’Addario C, Di Marco R, Pekarik V, Drazanova E, Piscitelli F, Bari M, Babinska Z, Giurdanella G, Di Bartolomeo M, Salomone S, Sulcova A, Maccarrone M, Wotjak CT, Starcuk Z Jr, Drago F, Mechoulam R, Di Marzo V, Micale V. Peripubertal cannabidiol treatment rescues behavioral and neurochemical abnormalities in the MAM model of schizophrenia. Neuropharmacology. 2019 Mar 1;146:212-221. doi: 10.1016/j.neuropharm.2018.11.035. Epub 2018 Nov 26. PubMed PMID: 30496751.
Other articles
Bhattacharyya S, Morrison PD, Fusar-Poli P, Martin-Santos R, Borgwardt S, Winton-Brown T, Nosarti C, O’ Carroll CM, Seal M, Allen P, Mehta MA, Stone JM, Tunstall N, Giampietro V, Kapur S, Murray RM, Zuardi AW, Crippa JA, Atakan Z, McGuire PK. Opposite effects of delta-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology. Neuropsychopharmacology. 2010 Feb;35(3):764-74. doi: 10.1038/npp.2009.184. Epub 2009 Nov 18. PubMed PMID: 19924114; PubMed Central PMCID: PMC3055598.
Englund A, Morrison PD, Nottage J, Hague D, Kane F, Bonaccorso S, Stone JM, Reichenberg A, Brenneisen R, Holt D, Feilding A, Walker L, Murray RM, Kapur S. Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment. J Psychopharmacol. 2013 Jan;27(1):19-27. doi: 10.1177/0269881112460109. Epub 2012 Oct 5. PubMed PMID: 23042808.
Morgan CJ, Gardener C, Schafer G, Swan S, Demarchi C, Freeman TP, Warrington P, Rupasinghe I, Ramoutar A, Tan N, Wingham G, Lewis S, Curran HV. Sub-chronic impact of cannabinoids in street cannabis on cognition, psychotic-like symptoms and psychological well-being. Psychol Med. 2012 Feb;42(2):391-400. doi: 10.1017/S0033291711001322. Epub 2011 Jul 29. PubMed PMID: 21798112.
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