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New perspectives in the use of drugs that modify atypical neurotransmitters in the treatment of neuropsychiatric disorders

Grant number: 17/24304-0
Support type:Research Projects - Thematic Grants
Duration: February 01, 2019 - January 31, 2024
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal Investigator:Francisco Silveira Guimaraes
Grantee:Francisco Silveira Guimaraes
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Co-Principal Investigators:Elaine Aparecida Del Bel Belluz Guimarães ; Leonardo Resstel Barbosa Moraes ; Sâmia Regiane Lourenço Joca
Assoc. researchers:Alline Cristina de Campos ; Ana Carolina de Castro Issy Pereira ; Ana Luisa Bernardes Terzian ; Antonio Cardozo dos Santos ; Ariandra Guerini Sartim ; Claudia Maria de Castro Batista ; Cristina Aparecida Jark Stern ; Daniele Cristina de Aguiar ; Elaine Aparecida Del Bel Belluz Guimarães ; Fabricio de Araujo Moreira ; Fernanda Grecco Grano ; Fernando Morgan de Aguiar Correa ; Frederico Rogério Ferreira ; Glauce Crivelaro Do Nascimento ; Leandro José Bertoglio ; Mariza Bortolanza ; Maurício dos Santos Pereira ; Nilson Carlos Ferreira Junior ; Pedro Henrique Gobira Nunes ; Rúbia Maria Monteiro Weffort de Oliveira ; Sabrina Francesca de Souza Lisboa
Associated scholarship(s):20/02297-4 - Conditioned and unconditioned stimulus send at fixed or randomized intervals: possible behavioral differences for the expression and extinction of conditioned fear memory, BP.IC
20/04145-7 - Investigation of the possible involvement of adenosinergic receptors in the behavioral effects induced by cannabidiol in mice using different animal models, BP.IC
19/26351-0 - Evaluation of paclitaxel-induced cognitive deficits in a 4T-1 murine mammary carcinoma model and possible protective effect of concomitant cannabidiol treatment, BP.IC
+ associated scholarships 19/24591-4 - Mechanisms of cannabidiol antipsychotics effects in schizophrenia model based in neurodevelopment variation, BP.DR
19/18846-0 - Role of the endocannabinoid system in orofacial muscular pain related to Parkinson's Disease, BP.IC
19/26810-5 - Extracellular vesicles as signals of the hippocampal neurogenic niche: participation in the behavioral effects of cannabinoid and antidepressant drugs, BP.PD
18/15896-3 - Participation of DNA methylation in rapid and sustained antidepressant-like effects induced by Cannabidiol and Ketamine, BP.PD
18/20433-2 - Neuroprotective and behavioral effects of the PPAR³ agonist pioglitazone in a neurodevelopmental model of schizophrenia, BP.PD
17/14207-7 - THE ACTION OF CANNABINOID DRUGS IN L-DOPA-INDUCED DISCINESIA: ANALYSIS OF NEUROINFLAMATION AND GLUTAMATE RELEASE IN GLIAL CELLS, BP.PD - associated scholarships

Abstract

The need to develop new therapeutic targets for the treatment of neuropsychiatric disorders is a consensus in the scientific literature. Endocannabinoids (eCBs) and nitric oxide (NO) have been proposed as two of these possible targets. Studies from our group have disclosed the therapeutic potential of drugs that interfere with these two atypical neurotransmitters in anxiety, depressive, psychotic disorders, Parkinson's disease, aggressive behavior and neurodegeneration/neurotoxicity. Cannabidiol (CBD), a non-psychotomimetic phytocannabinoid, which, among other effects, can increase the levels of the eCB anandamide, is already undergoing clinical trials to test its efficacy in some of these disorders. However, several important questions still remain related to the therapeutic potential of these drugs in other specific disorders as well as to the mechanisms involved. In the last few years our studies have indicated new possibilities, including facilitation of adult hippocampal neurogenesis and autophagy and the possible involvement of neuroinflammatory/neuroimmune mechanisms. The present project aimed at continuing this research line, trying to investigate 1. Which is the involvement and mechanisms of the anti-inflammatory effects of CBD and drugs that modify the NO and eCB system in their potential therapeutic effects?; 2. Which other neuropsychiatric disorders could benefice from these drugs?; 3. In case of co-morbities such as metabolic syndrome and anxiety disorders, in which an inflammatory component is present, would these new therapies be effective?; 4. Which other intra-cellular pathways would be involved?; 5. Which is the specific eCB involvement in the modulation of rewarding and aversive responses?; 6. Which specific epigenetic mechanisms are involved with these effects? (AU)

Matéria(s) publicada(s) na Agência FAPESP sobre o auxílio:
Cannabidiol reduces aggressiveness, study concludes 
Articles published in other media outlets (70 total):
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UOL: Medicamentos que vêm da cannabis são alvo de pesquisa intensa (16/Apr/2020)
Gazeta do Povo: O que já sabemos sobre o uso terapêutico do canabidiol (31/Aug/2019)
UOL: Canabidiol diminui agressividade, conclui estudo (22/Jul/2019)
Portal Exame: Canabidiol diminui agressividade, diz estudo da USP (22/Jul/2019)
Sechat: Medicamentos que vêm da Cannabis são alvo de pesquisa intensa (17/Apr/2020)
Central das Notícias: Medicamentos que vêm da cannabis são alvo de pesquisa intensa (16/Apr/2020)
Scientific Inquirer (EUA): Cannabis appears to reduce aggressiveness, study (09/Sep/2019)
Santé blog (França): Cannabis : Le cannabidiol pour réduire l'agressivité (06/Sep/2019)
Paperblog (France): CANNABIS : Le cannabidiol pour réduire l'agressivité (06/Sep/2019)
Clear Critique: Cannabidiol Attenuates Aggressiveness: Study (05/Sep/2019)
Santé blog (França): CANNABIS : Le cannabidiol pour réduire l'agressivité (05/Sep/2019)
The 1ml Store (Reino Unido): Cannabidiol Attenuates Aggressiveness: Study (05/Sep/2019)
CBD Olie: Cannabidiol vermindert de agressiviteit, concludeert de studi (05/Sep/2019)
Birnith Mining & Construction (China): Cannabidiol vermindert de agressiviteit, concludeert de studi (05/Sep/2019)
Gazeta do Povo online: O que já sabemos sobre o uso terapêutico do canabidiol (04/Sep/2019)
All My Family Care: In test with rats, cannabidiol showed sustained effects against depression for seven days (31/Aug/2019)
HealthMedicinentral: Cannabidiol reduces aggressiveness, study concludes (26/Aug/2019)
Dr. Soler Cannabis (Porto Rico): Cannabidiol reduces aggressiveness, study concludes (26/Aug/2019)
David Icke: Cannabidiol reduces aggressiveness, study concludes (26/Aug/2019)
Science and Technology Research News (EUA): Cannabidiol Reduces Aggressiveness, Study Concludes (23/Aug/2019)
Gold Voice: Canabindol reduces aggressiveness, study concludes (12/Aug/2019)
The Daily Leaf (EUA): Study Shows CBD Reduces Aggressive Behavior (05/Aug/2019)
Business Standard (Índia) online: Study finds cannabidiol can reduce isolation-induced aggression (04/Aug/2019)
Sify (Índia): Study finds cannabidiol can reduce isolation-induced aggression (04/Aug/2019)
Revista Ecociencias (Chile) online: El cannabidiol disminuye la agresividad, de acuerdo con un estudio (01/Aug/2019)
Genetic Engineering & Biotechnology News (EUA): CBD Mellows Out Aggressive Shut-Ins (31/Jul/2019)
Nutrition Insight (Holanda): Could CBD reduce aggression? CBD-dosed mice half as likely to attack intruders (31/Jul/2019)
Global Health News Wire (EUA): Cannabidiol Reduces Aggressiveness, Study Concludes (31/Jul/2019)
Green Rush Daily: CBD Can Reduce Isolation-Induced Aggression, Study Finds (31/Jul/2019)
International Business Times (EUA): CBD Compound In Marijuana Can Reduce Aggressiveness Induced By Isolation (30/Jul/2019)
Medical Xpress (Reino Unido): Cannabidiol reduces aggressiveness, study concludes (30/Jul/2019)
ScienceBlog: Cannabidiol reduces aggressiveness, study concludes (30/Jul/2019)
Before It's News (EUA): Cannabidiol Reduces Aggressiveness, Study Concludes (30/Jul/2019)
Medindia (Índia): Cannabidiol Attenuates Aggressiveness: Study (30/Jul/2019)
Steemit: Cannabidiol reduces aggressiveness, study concludes (30/Jul/2019)
Natural Blaze: Cannabidiol Reduces Aggressiveness, Study Concludes (30/Jul/2019)
ScienceBeta: Cannabidiol Mitigates Isolation-Induced Aggression (30/Jul/2019)
W3 live news (Austrália): Cannabidiol Reduces Aggressiveness, Study Concludes (30/Jul/2019)
Tech Deeps: Cannabidiol Reduces Aggressiveness, Study Concludes (30/Jul/2019)
GDS Noticias (Argentina): Cannabidiol Reduces Aggressiveness, Study Concludes (30/Jul/2019)
Busy.org: Cannabidiol Reduces Aggressiveness, Study Concludes (30/Jul/2019)
SteemPeak: Cannabidiol Reduces Aggressiveness, Study Concludes (30/Jul/2019)
New Republic Liberia (Libéria): Cannabidiol Reduces Aggressiveness, Study Concludes (30/Jul/2019)
Science Codex: Cannabidiol reduces aggressiveness, study concludes (29/Jul/2019)
Scienmag Science Magazine (Reino Unido): Cannabidiol reduces aggressiveness, study concludes (29/Jul/2019)
Neuroscience News (EUA): Cannabidiol reduces aggressiveness (29/Jul/2019)
Agenparl (Itália): Cannabidiol reduces aggressiveness, study concludes (29/Jul/2019)
7thSpace: Cannabidiol reduces aggressiveness, study concludes (29/Jul/2019)
CBD Olie: Cannabidiol vermindert de agressiviteit, concludeert de studi (29/Jul/2019)
MH BioShop (Holanda): Cannabidiol vermindert de agressiviteit, concludeert de studi (29/Jul/2019)
Hempadão: Canabidiol diminui agressividade, diz estudo da USP (28/Jul/2019)
O Estado (MS) online: Estudo conclui que Canabidiol diminui agressividade (25/Jul/2019)
Algomais online: Canabidiol diminui agressividade, conclui estudo (25/Jul/2019)
Revide: Canabidiol diminui agressividade, conclui estudo feito na USP de Ribeirão Preto (24/Jul/2019)
The Rio Times: Cannabidiol has Reduced Aggressiveness, According to Researchers From the University of São Paulo (24/Jul/2019)
Smoke Buddies: Estudo da USP conclui que CBD reduz agressividade (23/Jul/2019)
Sociedade Científica: Canabidiol diminui agressividade, conclui estudo (23/Jul/2019)
Zero Hora online: Canabidiol reduz a agressividade, aponta estudo (22/Jul/2019)
Espaço Ecológico no Ar: Canabidiol diminui agressividade, conclui estudo feito na USP em Ribeirão Preto (22/Jul/2019)
Esteta : Canabidiol diminui agressividade, conclui estudo (22/Jul/2019)
Metropóles: Canabidiol diminuiu agressividade, concluem pesquisadores da USP (22/Jul/2019)
RM Consult: Canabidiol - artigo brasileiro publicado na Science Direct mostra redução de agressividade (22/Jul/2019)
Os Cabeças da Notícia: Canabidiol diminuiu agressividade, concluem pesquisadores da USP (22/Jul/2019)
Nossa vida de cada dia: Canabidiol diminui agressividade, diz estudo da USP – Exame (22/Jul/2019)
W Rádio Brasil: Canabidiol diminui agressividade, conclui estudo (22/Jul/2019)
Jornal Notícias: Canabidiol diminui agressividade, conclui estudo (22/Jul/2019)
Portal da Enfermagem: Canabidiol diminui agressividade, conclui estudo (22/Jul/2019)
Maryjuana: Canabidiol diminui agressividade, conclui estudo (23/Jul/2019)
Maryjuana: Canabidiol diminui agressividade, conclui estudo (23/Jul/2019)
Olhar Capital: Canabidiol diminui agressividade, diz estudo da USP (22/Jul/2019)

Scientific publications (11)
(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)
HEIMANN, ANDREA S.; DALE, CAMILA S.; GUIMARAES, FRANCISCO S.; REIS, RICARDO A. M.; NAVON, AMI; SHMUELOV, MICHAL A.; RIOLI, VANESSA; GOMES, IVONE; DEVI, LAKSHMI L.; FERRO, EMER S. Hemopressin as a breakthrough for the cannabinoid field. Neuropharmacology, v. 183, FEB 1 2021. Web of Science Citations: 0.
DOS SANTOS PEREIRA, MAURICIO; ABREU, GABRIEL HENRIQUE DIAS; ROCCA, JEREMY; HAMADAT, SABAH; RAISMAN-VOZARI, RITA; MICHEL, PATRICK PIERRE; DEL BEL, ELAINE. Contributive Role of TNF-alpha to L-DOPA-Induced Dyskinesia in a Unilateral 6-OHDA Lesion Model of Parkinson's Disease. FRONTIERS IN PHARMACOLOGY, v. 11, JAN 11 2021. Web of Science Citations: 0.
ASTH, LAILA; IGLESIAS, LIA P.; BRIANIS, RAYSSA C.; MARCAL, ANNA P.; SOARES, NICIA P.; AGUIAR, DANIELE C.; MOREIRA, FABRICIO A. Effects of the monoamine stabilizer, (-)-OSU6162, on cocaine-induced locomotion and conditioned place preference in mice. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, JAN 2021. Web of Science Citations: 0.
MACIEL, IZAQUE DE SOUSA; SALES, AMANDA J.; CASAROTTO, PLINIO C.; CASTREN, EERO; BIOJONE, CAROLINE; JOCA, SAMIA R. L. Nitric Oxide Synthase inhibition counteracts the stress-induced DNA methyltransferase 3b expression in the hippocampus of rats. European Journal of Neuroscience, DEC 2020. Web of Science Citations: 0.
GONZALEZ-LIZARRAGA, FLORENCIA L.; PLOPER, DIEGO; AVILA, CESAR L.; SOCIAS, SERGIO B.; DOS-SANTOS-PEREIRA, MAURICIO; MACHIN, BELEN; DEL-BEL, ELAINE; MICHEL, PATRICK PIERRE; PIETRASANTA, I, LIA; RAISMAN-VOZARI, RITA; CHEHIN, ROSANA. CMT-3 targets different alpha-synuclein aggregates mitigating their toxic and inflammogenic effects. SCIENTIFIC REPORTS, v. 10, n. 1 NOV 20 2020. Web of Science Citations: 0.
CORTEZ, ISADORA L.; RODRIGUES DA SILVA, NAIELLY; GUIMARAES, FRANCISCO S.; GOMES, FELIPE V. Are CB2 Receptors a New Target for Schizophrenia Treatment?. FRONTIERS IN PSYCHIATRY, v. 11, OCT 30 2020. Web of Science Citations: 0.
ULIANA, DANIELA L.; ANTERO, LEANDRO S.; BORGES-ASSIS, ANNA B.; ROSA, JESSICA; VILA-VERDE, CARLA; LISBOA, SABRINA F.; RESSTEL, LEONARDO B. M. Differential modulation of the contextual conditioned emotional response by CB1 and TRPV1 receptors in the ventromedial prefrontal cortex: Possible involvement of NMDA/nitric oxide-related mechanisms. JOURNAL OF PSYCHOPHARMACOLOGY, v. 34, n. 9 JUL 2020. Web of Science Citations: 0.
DA SILVA, NAIELLY RODRIGUES; GOMES, FELIPE VILLELA; SONEGO, ANDREZA BUZOLIN; DA SILVA, NICOLE RODRIGUES; GUIMARAES, FRANCISCO SILVEIRA. Cannabidiol attenuates behavioral changes in a rodent model of schizophrenia through 5-HT1A, but not CB1 and CB2 receptors. PHARMACOLOGICAL RESEARCH, v. 156, JUN 2020. Web of Science Citations: 0.
RAYMUNDI, ANA MARIA; DA SILVA, THIAGO R.; ZAMPRONIO, ALEKSANDER R.; GUIMARAES, FRANCISCO S.; BERTOGLIO, LEANDRO J.; STERN, CRISTINA A. J. A time-dependent contribution of hippocampal CB1, CB2 and PPAR gamma receptors to cannabidiol-induced disruption of fear memory consolidation. British Journal of Pharmacology, v. 177, n. 4, SI JAN 2020. Web of Science Citations: 0.
LOPES, JADNA B.; BASTOS, JULIANA R.; COSTA, RAYSSA B.; AGUIAR, DANIELE C.; MOREIRA, FABRICIO A. The roles of cannabinoid CB1 and CB2 receptors in cocaine-induced behavioral sensitization and conditioned place preference in mice. Psychopharmacology, OCT 2019. Web of Science Citations: 0.
HARTMANN, ALICE; LISBOA, SABRINA FRANCESCA; SONEGO, ANDREZA BUZOLIN; COUTINHO, DEBORA; GOMES, FELIPE VILLELA; GUIMARAES, FRANCISCO SILVEIRA. Cannabidiol attenuates aggressive behavior induced by social isolation in mice: Involvement of 5-HT1A and CB1 receptors. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, v. 94, AUG 30 2019. Web of Science Citations: 0.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.