Cannabidiol in the treatment of neuropsychiatric disorders: new paths

• Grant number: 23/16182-2
• Support Opportunities: Research Projects - Thematic Grants
• Start date: January 01, 2025
• End date: December 31, 2029
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Francisco Silveira Guimaraes
• Grantee: Francisco Silveira Guimaraes
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Pesquisadores principais: Elaine Aparecida Del Bel Belluz Guimarães
• Associated researchers: Cristina Aparecida Jark Stern ; Daniele Cristina de Aguiar ; Fabricio de Araujo Moreira ; Felipe Villela Gomes ; Frederico Rogério Ferreira ; Glauce Crivelaro Do Nascimento ; Leandro José Bertoglio ; Rúbia Maria Monteiro Weffort de Oliveira ; Sabrina Francesca de Souza Lisboa
• Associated research grant(s): 25/13560-1 - Neuroprotective and anti-inflammatory effects of cannabidiol in a model of Parkinson's disease, with or without concomitant periodontitis, AP.R
• Associated scholarship(s): 25/14274-2 - Investigation of the Effect of Cannabidiol on PV+ Interneuron Maturation and the Response to Adolescent Stress: Potential Involvement of OTX2, BP.DR; 25/07600-0 - Impact of typical antipsychotic on parvalbumin-positive interneurons and perineuronal nets: motor and cognitive effects, BP.DR; 25/13329-8 - Cannabinoid Modulation of Parkinsonism-Induced Orofacial Manifestations: An Integrated Approach to Pain and Muscle Bioenergetics, BP.IC; + associated scholarships 25/07827-5 - Effects of Cannabidiol Associated with Physical Exercise on Trigeminal Neuralgia, BP.IC; 25/03137-4 - Training in immunohistochemistry, microscopy, and cell culture., BP.TT; 22/01192-0 - Investigation of the participation of the ADAM10-NEGR1-FGFR2 pathway in vitro and in vivo effects of Cannabidiol in stress conditions, BP.PD - associated scholarships

Abstract

Among the more than 200 phytocannabinoids present in the Cannabis sativa plant, the one that has received the most attention regarding therapeutic potential is cannabidiol (CBD). The number of scientific works aimed at investigating this potential has been increasing exponentially. Results obtained in recent decades suggest that CBD may be useful in a large number of neuropsychiatric disorders, including schizophrenia, mood and anxiety disorders, substance dependence, autism, epilepsy, and neurodegenerative diseases such as Parkinson's and Alzheimer's. The contribution of our research group to this investigation is significant and widely recognized in the global literature. Nevertheless, several aspects of CBD pharmacology and similar molecules remain obscure. The most significant one concerns the mechanism of action. Our group's work has been pioneering in demonstrating that CBD acts, in vivo, through various mechanisms that depend, at least in part, on the condition for which it is being employed. As over 60 molecular targets of CBD have already been described by in vitro studies, the involvement of several of these targets in the observed in vivo effects still needs to be investigated. Another aspect of CBD pharmacology that remains relatively unexplored is its use as a complementary treatment (add-on) to well-established drugs to enhance efficacy and/or reduce adverse effects. Finally, pharmacokinetic aspects are recognized as limiting factors for the clinical use of CBD. In view of this, this project aims to continue the research on the pharmacological properties of CBD and similar molecules developed by our group, seeking to investigate, as specific objectives: 1. the involvement of still little explored in vivo mechanisms of CBD, such as the influence and interaction between neurotrophic factors and inflammatory mechanisms with alterations in enteric microbiota in its therapeutic and preventive effects (another understudied point); and 2. the potential of CBD use as an "add-on" therapy in neuropsychiatric disorders. (AU)

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)

HASSIB, LUCAS; KANASHIRO, ALEXANDRE; PEDRAZZI, JOAO FRANCISCO CORDEIRO; VERCESI, BARBARA FERREIRA; HIGA, SAYURI; ARRUDA, IRIS; SOARES, YAGO; DE SOUZA, ADRIANA DE JESUS; JORDAO, ALCEU AFONSO; GUIMARAES, FRANCISCO SILVEIRA; et al. Should we consider microbiota-based interventions as a novel therapeutic strategy for schizophrenia? A systematic review and meta-analysis. BRAIN, BEHAVIOR, & IMMUNITY - HEALTH, v. 43, p. 15-pg., 2025-02-01. (23/16182-2, 23/16731-6)

ANDREOTTI, JULIA P.; IGLESIAS, LIA P.; BRIANIS, RAYSSA C.; BARRA, WALACE C. P.; DUARTE, IGOR D. G.; STERN, CRISTINA A. J.; BERTOGLIO, LEANDRO J.; CRIPPA, JOSE A.; AGUIAR, DANIELE C.; MOREIRA, FABRICIO A.. Cannabigerol does not affect contextual fear memory in mice but modulates nociception in a sex-dependent manner. Pharmacology Biochemistry and Behavior, v. 254, p. 10-pg., 2025-09-01. (23/16182-2)

PONCIANO, R.; HALLAK, J. E. C.; CRIPPA, J. A.; GUIMARAES, F. S.; DEL BEL, ELAINE AP.. Cannabigerol Mitigates Haloperidol-Induced Vacuous Chewing Movements in Mice. NEUROTOXICITY RESEARCH, v. 43, n. 1, p. 12-pg., 2025-02-01. (21/02873-8, 23/16182-2)