Neuroprotective and anti-inflammatory effects of cannabidiol in a model of Parkinson's disease, with or without concomitant periodontitis

• Grant number: 25/13560-1
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2025
• End date: September 30, 2026
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Principal Investigator: Elaine Aparecida Del Bel Belluz Guimarães
• Grantee: Elaine Aparecida Del Bel Belluz Guimarães
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 23/16182-2 - Cannabidiol in the treatment of neuropsychiatric disorders: new paths, AP.TEM

Abstract

Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra, leading to both motor and non-motor symptoms that impair quality of life (Jankovic, 2008). Periodontitis is a source of peripheral inflammation that induces the release of pro-inflammatory cytokines (TNF-¿, IL-1¿), which can cross the blood-brain barrier, activate microglia, and exacerbate neurodegeneration (Holmes & Butchart, 2011). Jacob et al. (2024) demonstrated in rats that dopaminergic lesions combined with periodontitis result in increased motor deficits and striatal neuroinflammation compared to ligature-free controls. Among therapeutic strategies, the endocannabinoid system has emerged as a promising target for treating neurodegenerative diseases such as Parkinson's and Alzheimer's (Fernández-Ruiz et al., 2009). Cannabidiol (CBD), a non-psychoactive phytocannabinoid, modulates the TLR4/NF-¿B and NLRP3 pathways, reducing pro-inflammatory cytokines and oxidative stress, thereby exerting neuroprotective effects (Silvestro et al., 2023; Zuardi et al., 2017). CBD also modulates inflammation in periodontal tissues by reducing the expression of pro-inflammatory cytokines in both in vitro and in vivo models, partly through inhibition of the RANKL/RANK inflammatory pathway and neutrophil migration, as well as activation of antioxidant pathways (Jirasek et al., 2024; Chen et al., 2023; Napimoga et al., 2009). In animal models of Parkinson's disease, CBD reduced markers of neuroinflammation, including pro-inflammatory cytokines and glial activation, increased anti-inflammatory cytokines, and attenuated dopaminergic neuron degeneration, leading to improvements in motor impairments (Santos et al., 2024; Wang et al., 2022; Giuliano et al., 2021; Mattos et al., 2024). In experimental models of periodontitis, CBD treatment significantly reduced alveolar bone loss and pro-inflammatory cytokine levels (Guimarães et al., 2008). This is a novel project that will evaluate, in rats, the impact of CBD treatment on the severity of dopaminergic neuron/terminal damage (Parkinsonism induced by 6-OHDA infusion in the striatum), when combined with peripheral oral inflammation (periodontitis). Motor behavior, anti-inflammatory and neuroprotective effects will be analyzed in the striatum, substantia nigra, alveolar bone loss, and bone resorption. (AU)