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Is cannabidiol the ideal drug to treat non-motor Parkinson’s disease symptoms?

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Abstract

Parkinson’s disease (PD) is a chronic neurodegenerative disorder characterized by motor symptoms such as bradykinesia, rest tremor, postural disturbances, and rigidity. PD is also characterized by non-motor symptoms such as sleep disturbances, cognitive deficits, and psychiatric disorders such as psychosis, depression, and anxiety. The pharmacological treatment for these symptoms is limited in efficacy and induce significant adverse reactions, highlighting the need for better treatment options. Cannabidiol (CBD) is a phytocannabinoid devoid of the euphoriant and cognitive effects of tetrahydrocannabinol, and preclinical and preliminary clinical studies suggest that this compound has therapeutic effect in non-motor symptoms of PD. In the present text, we review the clinical studies of cannabinoids in PD and the preclinical and clinical studies specifically on CBD. We found four randomized controlled trials (RCTs) involving the administration of agonists/antagonists of the cannabinoid 1 receptor, showing that these compounds were well tolerated, but only one study found positive results (reductions on levodopa-induced dyskinesia). We found seven preclinical models of PD using CBD, with six studies showing a neuroprotective effect of CBD. We found three trials involving CBD and PD: an open-label study, a case series, and an RCT. CBD was well tolerated, and all three studies reported significant therapeutic effects in non-motor symptoms (psychosis, rapid eye movement sleep behaviour disorder, daily activities, and stigma). However, sample sizes were small and CBD treatment was short (up to 6 weeks). Large-scale RCTs are needed to try to replicate these results and to assess the long-term safety of CBD.

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Acknowledgements

The authors are thankful to Dr. José Diogo de Souza and Mr. Luíz Avanzo for the preparation of the Figure. JAC, JEH, AWZ, and FSG are recipients of Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil) 1A productivity fellowships. Research was supported in part by Grants from (1) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); (2) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); (3) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); (4) Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (FAEPA, Brazil); (5) Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, São Paulo, Brazil (NAPNA); and (6) National Institute for Translational Medicine (INCT-TM; CNPq/FAPESP, Brazil).

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Authors and Affiliations

  1. Department of Neurosciences and Behavior, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil

    José Alexandre S. Crippa, Jaime E. C. Hallak, Antônio W. Zuardi, Vitor Tumas & Rafael G. dos Santos

  2. National Institute of Science and Technology-Translational Medicine, Ribeirão Preto, Brazil

    José Alexandre S. Crippa, Jaime E. C. Hallak, Antônio W. Zuardi, Francisco S. Guimarães, Vitor Tumas & Rafael G. dos Santos

  3. Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil

    Francisco S. Guimarães

  4. Hospital das Clínicas, Terceiro Andar, Av. Bandeirantes, 3900, Ribeirão Preto, São Paulo, CEP-14049-900, Brazil

    José Alexandre S. Crippa

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  1. José Alexandre S. Crippa
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  2. Jaime E. C. Hallak
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Correspondence to José Alexandre S. Crippa.

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Conflict of interest

JAC, JH, FSG, and AWZ are co-inventors (Mechoulam R, Crippa JA, Guimaraes FS, Zuardi A, Hallak, JE, and Breuer A) of the patent “Fluorinated CBD compounds, compositions and uses thereof. Pub. No.: WO/2014/108899. International Application No.: PCT/IL2014/050023” Def. US no. Reg. 62193296; 29/07/2015; INPI on 19/08/2015 (BR1120150164927). The University of São Paulo has licensed the patent to Phytecs Pharm (USP Resolution No. 15.1.130002.1.1). The University of São Paulo has an agreement with Prati-Donaduzzi (Toledo, Brazil) to “develop a pharmaceutical product containing synthetic cannabidiol and prove its safety and therapeutic efficacy in the treatment of epilepsy, schizophrenia, Parkinson’s disease, and anxiety disorders”. JAC and JEH have received travel support from and are medical advisors of BSPG-Pharm. JAC has a Grant from University Global Partnership Network (UGPN)—Global priorities in cannabinoid research excellence. The other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Crippa, J.A.S., Hallak, J.E.C., Zuardi, A.W. et al. Is cannabidiol the ideal drug to treat non-motor Parkinson’s disease symptoms?. Eur Arch Psychiatry Clin Neurosci 269, 121–133 (2019). https://doi.org/10.1007/s00406-019-00982-6

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