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Mechanisms involved in the cannabidiol antipsychotic profile

Grant number: 15/06515-8
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): August 01, 2015
Effective date (End): July 31, 2018
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal researcher:Elaine Aparecida Del Bel Belluz Guimarães
Grantee:João Francisco Cordeiro Pedrazzi
Home Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil


Schizophrenia is a highly disabling disorder that affects about 1% of the population, involving imbalance of dopaminergic neurotransmission and a glutamatergic hypofunction. Patients with this disease have a deficiency of sensory-motor gating, characterized by disruption in prepulse inhibition test (PPI). This condition can be reproduced in experimental models, by treatment with psychostimulants such as amphetamine and attenuated / reversed by treatment with antipsychotics. Cannabidiol (CBD) a component of Cannabis sativa is devoid of psychotomimetic properties. Clinical and pre-clinical studies suggest that CBD has an antipsychotic profile, yet its mechanism of action has been little investigated to date. Recently, epigenetic mechanisms such as DNA methylation, have been linked to the schizophrenia pathophysiology. However, there is no investigation of the involvement of DNA methylation regulated by CBD on the behavioral responses induced by amphetamine. The aim of this study is to investigate the mechanisms of action of CBD in predictive models for antipsychotic action. Therefore, we will investigate: (I) the involvement of TRPV1 receptors, serotonin (5-HT1A) receptors and increased anandamide signaling in the PPI test and locomotor activity. (II) the participation of the prefrontal cortex as a possible neural substrates for the CBD antipsychotic profile on PPI test. (III) the global DNA methylation in brain structures (prefrontal cortex, hippocampus, striatum and ventral) after acute treatment with amphetamine. If changes will found we will investigate if pretreatment with clozapine or CBD modifies that condition. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
PEDRAZZI, JOAO F. C.; SALES, AMANDA J.; GUIMARAES, FRANCISCO S.; JOCA, SAMIA R. L.; CRIPPA, JOSE A. S.; DEL BEL, ELAINE. annabidiol prevents disruptions in sensorimotor gating induced by psychotomimetic drugs that last for 24-h with probable involvement of epigenetic changes in the ventral striatu. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, v. 111, . (17/24304-0, 15/06515-8, 14/25029-4)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
PEDRAZZI, João Francisco Cordeiro. Mechanisms involved in cannabidiol antipsychotic profile. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.

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