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Neuropharmacological Effects of the Main Phytocannabinoids: A Narrative Review

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Book cover Cannabinoids and Neuropsychiatric Disorders

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1264))

Abstract

Cannabis can synthetize more than 400 compounds, including terpenes, flavonoids, and more than 100 phytocannabinoids. The main phytocannabinoids are Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Cannabis-based products are used as medicines in several countries. In this text, we present an overview of the main neurochemical mechanisms of action of the phytocannabinoids, especially THC and CBD. We also reviewed the indications and adverse effects of the main cannabis-based medicinal products. THC acts as a partial agonist at cannabinoid 1/2 receptors (CB1/2). It is responsible for the characteristic effects of cannabis, such as euphoria, relaxation, and changes in perceptions. THC can also produce dysphoria, anxiety, and psychotic symptoms. THC is used therapeutically in nausea and vomiting due to chemotherapy, as an appetite stimulant, and in chronic pain. CBD acts as a noncompetitive negative allosteric modulator of the CB1 receptor, as an inverse agonist of the CB2 receptor, and as an inhibitor of the reuptake of the endocannabinoid anandamide. Moreover, CBD also activates 5-HT1A serotonergic receptors and vanilloid receptors. Its use in treatment-resistant epilepsy syndromes is approved in some countries. CBD does not produce the typical effects associated with THC and has anxiolytic and antipsychotic effects. Some of the most common adverse effects of CBD are diarrhea, somnolence, nausea, and transaminase elevations (with concomitant use of antiepileptics). The mechanisms of action involved in both the therapeutic and adverse effects of the phytocannabinoids are not fully understood, involving not only the endocannabinoid system. This “promiscuous” pharmacology could be responsible for their wide therapeutic spectrum.

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Acknowledgements

RGS is Fellow of the Programa Nacional de Pós-Doutorado, Brazil (PNPD/CAPES). JECH and JAC are recipients of fellowship awards from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil). This review was supported by the Brazilian fund INCT-TM/CNPq/FAPESP (465458/2014-9).

Funding

Research was supported in part by grants from (i) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Brazil); (ii) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil); (iii) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brazil); and (iv) National Institute for Translational Medicine (INCTTM; CNPq, Brazil; INCT-TM/CNPq/FAPESP: 465458/2014–9). JECH and JAC are recipients of fellowship awards from CNPq. JC has a grant from University Global Partnership Network (UGPN)—Global priorities in cannabinoid research excellence.

Conflict of Interest

JECH and JAC are coinventors 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. 62,193,296; 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.” JECH and JAC have received travel support from and are medical advisors of BSPG-Pharm. RGS declares no conflicts of interest.

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Authors and Affiliations

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

    Rafael G. dos Santos, Jaime E. C. Hallak & José Alexandre S. Crippa

  2. National Institute of Science and Technology–Translational Medicine, Ribeirão Preto, São Paulo, Brazil

    Rafael G. dos Santos, Jaime E. C. Hallak & José Alexandre S. Crippa

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  1. Rafael G. dos Santos
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  2. Jaime E. C. Hallak
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  3. José Alexandre S. Crippa
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Correspondence to José Alexandre S. Crippa .

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  1. División Ciencias de la Salud, Univ Anahuac Mayab, Merida, Yucatán, Mexico

    Eric Murillo-Rodriguez

  2. Somnogen Canada Inc., Toronto, ON, Canada

    S. R. Pandi-Perumal

  3. Clinics Hospital, Montevideo, Uruguay

    Jaime M. Monti

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dos Santos, R.G., Hallak, J.E.C., Crippa, J.A.S. (2021). Neuropharmacological Effects of the Main Phytocannabinoids: A Narrative Review. In: Murillo-Rodriguez, E., Pandi-Perumal, S.R., Monti, J.M. (eds) Cannabinoids and Neuropsychiatric Disorders. Advances in Experimental Medicine and Biology, vol 1264. Springer, Cham. https://doi.org/10.1007/978-3-030-57369-0_3

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