doi: 10.1016/j.pnpbp.2021.110352.
- PMID: 34015384
- DOI: 10.1016/j.pnpbp.2021.110352
Abstract
Cannabidiol (CBD), a major non-psychotomimetic component of the Cannabis sativa plant, shows therapeutic potential in several psychiatric disorders, including schizophrenia. The molecular mechanisms underlying the antipsychotic-like effects of CBD are not fully understood. Schizophrenia and antipsychotic treatment can modulate DNA methylation in the blood and brain, resulting in altered expression of diverse genes associated with this complex disorder. However, to date, the possible involvement of DNA methylation in the antipsychotic-like effects of CBD has not been investigated. Therefore, this study aimed at evaluating in mice submitted to the prepulse inhibition (PPI) model: i) the effects of a single injection of CBD or clozapine followed by AMPH or MK-801 on PPI and global DNA methylation changes in the ventral striatum and prefrontal cortex (PFC); and ii). if the acute antipsychotic-like effects of CBD would last for 24-h. AMPH (5 mg/kg) and MK-801 (0.5 mg/kg) impaired PPI. CBD (30 and 60 mg/kg), similar to clozapine (5 mg/kg), attenuated AMPH- and MK801-induced PPI disruption. AMPH, but not MK-801, increased global DNA methylation in the ventral striatum, an effect prevented by CBD. CBD and clozapine increased, by themselves, DNA methylation in the prefrontal cortex. The acute effects of CBD (30 or 60 mg/kg) on the PPI impairment induced by AMPH or MK-801 was also detectable 24 h later. Altogether, the results show that CBD induces acute antipsychotic-like effects that last for 24-h. It also modulates DNA methylation in the ventral striatum, suggesting a new potential mechanism for its antipsychotic-like effects.
Keywords: Amphetamine, Antipsychotic effect, Global DNA methylation, Prepulse inhibition, Schizophrenia
Copyright © 2018. Published by Elsevier Inc.
Conflict of interest statement
Declaration of Competing Interest F.S.G., and J.A.C. 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 number Reg. 62193296; July 29, 2015; INPI on August 19, 2015 (BR1120150164927; Mechoulam R, Zuardi A.W., Kapczinski F, Hallak J.E.C, Guimarâes F.S., Crippa J.A.S., Breuer A). The University of São Paulo has licensed this patent to Phytecs Pharm (USP Resolution No. 15.1.130002.1.1). The University of São Paulo has an agreement with Prati-Donaduzzi Pharm to “develop a pharmaceutical product containing synthetic CBD and prove its safety and therapeutic efficacy in the treatment of epilepsy, schizophrenia, Parkinson’s disease, and anxiety disorders.” J.A.C ans F.S.G. are coinventors of the patent “Cannabinoid-containing oral pharmaceutical composition, method for preparing and using same”, INPI on September 16, 2016 (BR 112018005423-2). J.A.C. is a member of the International Advisory Board of the Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE) – National Health and Medical Research Council (NHMRC). J.A.C. have received travel support to scientific meetings and personal consultation fees from BSPG-Pharm. J.A.C. is recipient of Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) productivity fellowships (1 A). J.A.C. received a grant from the University Global Partnership Network (UGPN)— Global priorities in cannabinoid research excellence program. J.A.S.C. is a member of the International Advisory Board of the Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE – National Health and Medical Research Council, NHMRC).
