Cannabidiol monotherapy for treatment-resistant schizophrenia
Abstract
Cannabidiol (CBD), one of the major products of the marijuana plant, is devoid of marijuana's typical psychological effects. In contrast, potential antipsychotic efficacy has been suggested based on preclinical and clinical data (Zuardi et al., 2002). In this report, we further investigated the efficacy and safety of CBD monotherapy in three patients with treatment-resistant schizophrenia (TRS). This was an in-patient study. All patients were given placebo for the initial 5 days, and from the 6th to 35th day (inclusive) they received CBD (initial oral dose of 40 mg reaching 1280 mg/day). On the 36th day, CBD treatment was discontinued and replaced by placebo for 5 days, which was subsequently switched to olanzapine for over 15 days. Efficacy, tolerability and side effects were assessed. One patient showed mild improvement, but two patients didn't show any improvement during CBD monotherapy. All patients tolerated CBD very well and no side effects were reported. These preliminary data suggest that CBD monotherapy may not be effective for TRS.
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In three male patients with treatment-resistant schizophrenia treated with CBD (up to 1,280 mg/day) for 30 days, only one had a partial improvement.
“In a later trial, three male patients with treatment-resistant schizophrenia were treated with CBD (up to 1,280 mg/day) for 30 days, but only one had a partial improvement (75).”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [75]
Cites
The Positive and Negative Syndrome Scale (PANSS) for schizophrenia.
Kay, S. R., Fiszbein, A., & Opler, L. A. (1987) · Schizophrenia Bulletin · doi:10.1093/schbul/13.2.261 · Cited by 21,378 · see citing works
The Brief Psychiatric Rating Scale.
Overall, J. E., & Gorham, D. R. (1962) · Psychological Reports · doi:10.2466/pr0.1962.10.3.799 · Cited by 11,090 · see citing works
A RATING SCALE FOR EXTRAPYRAMIDAL SIDE EFFECTS
Simpson, G. M., B., M., B., G., Angus, J. W. S., P., F. R. C., & M., D. P. (1970) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.1970.tb02066.x · Cited by 3,265 · see citing works
A Rating Scale for Drug-Induced Akathisia
Barnes, T. R. E. (1989) · The British Journal of Psychiatry · doi:10.1192/bjp.154.5.672 · Cited by 2,179 · see citing works
Lingjærde, O., Ahlfors, U. G., Bech, P., Dencker, S. J., & Elgen, K. (1987) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.1987.tb10566.x · Cited by 1,705 · see citing works
D’Souza, D. C., Abi-Saab, W. M., Madonick, S., Forselius-Bielen, K., Doersch, A., Braley, G., Gueorguieva, R., Cooper, T. B., & Krystal, J. H. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.12.006 · Cited by 617 · see citing works
Action of cannabidiol on the anxiety and other effects produced by ?9-THC in normal subjects
Zuardi, A. W., Shirakawa, I., Finkelfarb, E., & Karniol, I. G. (1982) · Psychopharmacology · doi:10.1007/bf00432554 · Cited by 608 · see citing works
Self-citationChronic Administration of Cannabidiol to Healthy Volunteers and Epileptic Patients
Cunha, J. M., Carlini, E. A., Pereira, A. E., Ramos, O. L., Pimentel, C., Gagliardi, R. J., Sanvito, W. L., Lander, N., & Mechoulam, R. (2008) · Pharmacology · doi:10.1159/000137430 · Cited by 570 · see citing works
Cannabidiol: An Overview of Some Pharmacological Aspects
Mechoulam, R., Parker, L. A., & Gallily, R. (2002) · The Journal of Clinical Pharmacology · doi:10.1002/j.1552-4604.2002.tb05998.x · Cited by 511 · see citing works
Giuffrida, A., Leweke, F. M., Gerth, C. W., Schreiber, D., Koethe, D., Faulhaber, J., Klosterkötter, J., & Piomelli, D. (2004) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300558 · Cited by 481 · see citing works
Bech, P., Kastrup, M., & Rafaelsen, O. J. (1986) · PubMed · Cited by 466 · see citing works
Elevated endogenous cannabinoids in schizophrenia
Leweke, F. M., Giuffrida, A., Wurster, U., Emrich, H. M., & Piomelli, D. (1999) · Neuroreport · doi:10.1097/00001756-199906030-00008 · Cited by 431 · see citing works
Del-Ben, C. M., Vilela, J. A. A., Crippa, J. A. D. S., Hallak, J. E. C., Labate, C. M., & Zuardi, A. W. (2001) · Revista Brasileira de Psiquiatria · doi:10.1590/s1516-44462001000300008 · Cited by 386 · see citing works
Self-citationActa Psychiatrica Scandinavica
Read, J., van Os, J., Morrison, A. P., & Ross, C. A. (2010) · Acta Psychiatrica Scandinavica · doi:10.1111/(issn)1600-0447 · Cited by 385 · see citing works
Meltzer, H. Y., Arvanitis, L. A., Bauer, D., Rein, W., & Meta-Trial Study Group (2004) · American Journal of Psychiatry · doi:10.1176/appi.ajp.161.6.975 · Cited by 330 · see citing works
Controlled clinical trial of cannabidiol in Huntington's disease
Consroe, P. F., Laguna, J., Allender, J. R., Snider, S. R., Stern, L. Z., Sandyk, R., Kennedy, K., & Schram, K. H. (1991) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(91)90386-g · Cited by 324 · see citing works
Cannabis and cannabinoids: pharmacology, toxicology, and therapeutic potential
(2003) · Choice Reviews Online · doi:10.5860/choice.40-3432 · Cited by 293 · see citing works
Antipsychotic effect of cannabidiol.
Zuardi, A. W., Morais, S. L., Guimarães, F. S., & Mechoulam, R. (1995) · PubMed · Cited by 264 · see citing works
Self-citationCannabidiol inhibits the hyperlocomotion induced by psychotomimetic drugs in mice
Moreira, F. A., & Guimarães, F. S. (2005) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2005.02.040 · Cited by 206 · see citing works
Cannabis use and the risk of later schizophrenia: a review
Smit, F., Bolier, L., & Cuijpers, P. J. (2004) · Addiction · doi:10.1111/j.1360-0443.2004.00683.x · Cited by 203 · see citing works
Effects of cannabidiol in animal models predictive of antipsychotic activity
Zuardi, A. W., Antunes Rodrigues, J., & Cunha, J. M. (1991) · Psychopharmacology · doi:10.1007/bf02244189 · Cited by 191 · see citing works
Self-citationPharmacological interaction between cannabidiol and ?9-tetrahydrocannabinol
Karniol, I. G., & Carlini, E. A. (1973) · Psychopharmacology · doi:10.1007/bf00428793 · Cited by 182 · see citing works
Different Effects of Nabilone and Cannabidiol on Binocular Depth Inversion in Man
Leweke, F. M., Schneider, U., Radwan, M., Schmidt, E., & Emrich, H. M. (2000) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(00)00201-x · Cited by 150 · see citing works
Carlini, E. A., Santos, M., Claussen, U., Bieniek, D., & KORTE, F. (1970) · Psychopharmacology · doi:10.1007/bf00402387 · Cited by 81 · see citing works
Effect of cannabidiol on plasma prolactin, growth hormone and cortisol in human volunteers.
Zuardi, A. W., Guimarães, F. S., & Moreira, A. C. (1993) · PubMed · Cited by 76 · see citing works
Self-citationCannabidiol increases Fos expression in the nucleus accumbens but not in the dorsal striatum
Guimaraes, V. H. (2004) · Life Sciences · doi:10.1016/j.lfs.2004.01.015 · Cited by 75 · see citing works
Characterization of cannabidiol-mediated cytochrome P450 inactivation
Bornheim, L. M., Everhart, E. T., Li, J., et al. (1993) · Biochemical Pharmacology · doi:10.1016/0006-2952(93)90286-6 · Cited by 64 · see citing works
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Cited by
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Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia
Leweke, F. M., Piomelli, D., Pahlisch, F., Muhl, D., Gerth, C. W., Hoyer, C., Klosterkötter, J., Hellmich, M., & Koethe, D. (2012) · Translational Psychiatry · doi:10.1038/tp.2012.15 · Cited by 1,059 · see citing works
Bhattacharyya, S., Morrison, P. D., Fusar-Poli, P., Martin-Santos, R., Borgwardt, S., Winton-Brown, T., Nosarti, C., O' Carroll, C. M., Seal, M., Allen, P., et al. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.184 · Cited by 680 · see citing works
Self-citationMcGuire, P., Robson, P., Cubala, W. J., Vasile, D., Morrison, P. D., Barron, R., Taylor, A., & Wright, S. (2018) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2017.17030325 · Cited by 617 · see citing works
Black, N., Stockings, E., Campbell, G., Tran, L. T., Zagic, D., Hall, W. D., Farrell, M., & Degenhardt, L. (2019) · The Lancet Psychiatry · doi:10.1016/s2215-0366(19)30401-8 · Cited by 564 · see citing works
Safety and side effects of cannabidiol, a Cannabis sativa constituent
Machado Bergamaschi, M., Helena Costa Queiroz, R., Waldo Zuardi, A., & Alexandre S. Crippa, J. (2011) · Current Drug Safety · doi:10.2174/157488611798280924 · Cited by 558 · see citing works
Campos, A. C., Moreira, F. A., Gomes, F. V., Del Bel, E. A., & Guimarães, F. S. (2012) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2011.0389 · Cited by 475 · see citing works
Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action
Zuardi, A. W. (2008) · Revista Brasileira de Psiquiatria · doi:10.1590/s1516-44462008000300015 · Cited by 421 · see citing works
Cannabidiol for the treatment of psychosis in Parkinson's disease
Zuardi, A., Crippa, J., Hallak, J., Pinto, J., Chagas, M., Rodrigues, G., Dursun, S., & Tumas, V. (2009) · Journal of Psychopharmacology · doi:10.1177/0269881108096519 · Cited by 355 · see citing works
Self-citationTranslational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age
Crippa, J. A., Guimarães, F. S., Campos, A. C., & Zuardi, A. W. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02009 · Cited by 308 · see citing works
Self-citationCannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes
Oláh, A., Tóth, B. I., Borbíró, I., Sugawara, K., Szöllõsi, A. G., Czifra, G., Pál, B., Ambrus, L., Kloepper, J., Camera, E., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci64628 · Cited by 268 · see citing works
A systematic review of the antipsychotic properties of cannabidiol in humans
Iseger, T. A., & Bossong, M. G. (2015) · Schizophrenia Research · doi:10.1016/j.schres.2015.01.033 · Cited by 261 · see citing works
The direct actions of cannabidiol and 2-arachidonoyl glycerol at GABA A receptors
Bakas, T., van Nieuwenhuijzen, P. S., Devenish, S. O., McGregor, I. S., Arnold, J. C., & Chebib, M. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2017.02.022 · Cited by 246 · see citing works
The adverse health effects of synthetic cannabinoids with emphasis on psychosis-like effects
van Amsterdam, J., Brunt, T., & van den Brink, W. (2015) · Journal of Psychopharmacology · doi:10.1177/0269881114565142 · Cited by 244 · see citing works
Waldo Zuardi, A., Alexandre S. Crippa, J., E.C. Hallak, J., Bhattacharyya, S., Atakan, Z., Martin-Santos, R., K. McGuire, P., & Silveira Guimaraes, F. (2012) · Current Pharmaceutical Design · doi:10.2174/138161212802884681 · Cited by 222 · see citing works
Wolf, S. A., Bick-Sander, A., Fabel, K., Leal-Galicia, P., Tauber, S., Ramirez-Rodriguez, G., Müller, A., Melnik, A., Waltinger, T. P., Ullrich, O., et al. (2010) · Cell Communication and Signaling · doi:10.1186/1478-811x-8-12 · Cited by 208 · see citing works
Decreased glial reactivity could be involved in the antipsychotic-like effect of cannabidiol
Gomes, F. V., Llorente, R., Del Bel, E. A., Viveros, M.-P., López-Gallardo, M., & Guimarães, F. S. (2015) · Schizophrenia Research · doi:10.1016/j.schres.2015.01.015 · Cited by 147 · see citing works
Schiavon, A. P., Bonato, J. M., Milani, H., Guimarães, F. S., & Weffort de Oliveira, R. M. (2016) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2015.06.017 · Cited by 135 · see citing works
Gomes, F. V., Issy, A. C., Ferreira, F. R., Viveros, M.-P., Del Bel, E. A., & Guimarães, F. S. (2015) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyu041 · Cited by 89 · see citing works
Hallak, J. E. C., Dursun, S. M., Bosi, D. C., de Macedo, L. R. H., Machado-de-Sousa, J. P., Abrão, J., Crippa, J. A. S., McGuire, P., Krystal, J. H., Baker, G. B., et al. (2011) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2010.11.002 · Cited by 83 · see citing works
Self-citationValvassori, S. S., Elias, G., de Souza, B., Petronilho, F., Dal-Pizzol, F., Kapczinski, F., Trzesniak, C., Tumas, V., Dursun, S., Nisihara Chagas, M. H., et al. (2011) · Journal of Psychopharmacology · doi:10.1177/0269881109106925 · Cited by 80 · see citing works
Cannabidiol was ineffective for manic episode of bipolar affective disorder
Zuardi, A., Crippa, J., Dursun, S., Morais, S., Vilela, J., Sanches, R., & Hallak, J. (2010) · Journal of Psychopharmacology · doi:10.1177/0269881108096521 · Cited by 72 · see citing works
Cannabidiol (CBD) as a novel treatment in the early phases of psychosis
Chesney, E., Oliver, D., & McGuire, P. (2022) · Psychopharmacology · doi:10.1007/s00213-021-05905-9 · Cited by 40 · see citing works
Rømer Thomsen, K., Callesen, M. B., & Feldstein Ewing, S. W. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.05.025 · Cited by 24 · see citing works
The Changing Legal Landscape of Cannabis Use and Its Role in Youth-onset Psychosis
Wright, A., Cather, C., Gilman, J., & Evins, A. E. (2020) · Child and Adolescent Psychiatric Clinics of North America · doi:10.1016/j.chc.2019.08.016 · Cited by 16 · see citing works
- Authors
- Zuardi, A. W., Hallak, J. E. C., Dursun, S. M., Morais, S. L., Sanches, R. F., Musty, R. E., & Crippa, J. A. S.
- Affiliations
- Universidade de São Paulo (BR)
- University of Manchester (GB)
- University of Vermont (US)
- Venue
- Journal of Psychopharmacology
- Publisher
- SAGE Publications
- Published
- 2006-09
- Volume
- 20
- Issue
- 5
- Pages
- 683-686
- ISSN
- 0269-8811 (ISSN-L)
- 1461-7285
- OpenAlex
- W2046058705
- Cited by
- 192
- References
- 27
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 8 · 2023: 6 · 2022: 4 · 2021: 18 · 2020: 19 · 2019: 17 · 2018: 13 · 2017: 19 · 2016: 13 · 2015: 16 · 2014: 3 · 2013: 8 · 2012: 13
- FWCI
- 3.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Keywords
- cannabidiol, treatment-resistant schizophrenia, monotherapy, antipsychotic efficacy, tolerability, olanzapine
- MeSH terms
- Adult, Aggression, Behavior, Cannabidiol, Drug Resistance, Humans, Male, Psychiatric Status Rating Scales, Schizophrenia, Schizophrenic Psychology, Substance Withdrawal Syndrome, Antipsychotic Agents
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