Investigation of the molecular targets of cannabidiol and its possible interaction with the adenosinergic system

• Grant number: 23/07647-1
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Effective date (Start): November 12, 2023
• Effective date (End): May 10, 2024
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Francisco Silveira Guimaraes
• Grantee: João Raphael Campos Alves da Silveira
• Supervisor: Francisco Ciruela
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Research place: Universitat de Barcelona (UB), Spain
• Associated to the scholarship: 22/09348-9 - Investigation of the involvement of adenosinergic neurotransmission in the behavioral effects of cannabidiol: participation of serotoninergic 5-HT1A and CB1 cannabinoid receptors., BP.MS

Abstract

Cannabidiol (CBD), a non-psychotomimetic constituent of Cannabis sativa, has been shown to have various therapeutical effects on neuropsychiatric disorders, including anxiety and depression. However, the molecular mechanisms responsible for these effects have not been fully elucidated. These disorders are associated with alterations in the endocannabinoid system (ECS), which comprises cannabinoid receptors (CB1R and CB2R), endogenous ligands (2-AG and AEA), and enzymes responsible for their regulation. CBD interacts with ECS by inhibiting the uptake and degradation of endocannabinoids and indirectly facilitating their actions on CB1R, CB2R and other associated receptors. Furthermore, CBD interacts with non-ECS targets, such as the 5-HT1A receptor, contributing to its therapeutic effects. The adenosinergic system, which includes adenosine receptors (A1R, A2AR, A2BR and A3R), has also been implicated in the neuropsychiatric conditions cited above. Activation of A1R has shown antidepressant-like effects, while A2AR receptors play a role in modulation of anxiety. CBD can indirectly activate adenosinergic receptors by inhibiting adenosine uptake and potentially interacting with CB1R and adenosine receptor heteromers. These interactions between CBD, ECS, and the adenosinergic system could contribute to the modulation of neurotransmission and the therapeutic effects of CBD in psychiatric disorders. Therefore, we propose to investigate the hypothesis that CBD modulates the adenosinergic system by direct interactions with adenosinergic receptors and/or controlling adenosine extracellular levels. (AU)