Can cannabidiol be effective in modulating inflammation and enhancing oral healing in diabetes mellitus?Diabetes mellitus is a chronic metabolic condition characterized by persistent hyperglycemia, which, over the long term, leads to various microvascular and macrovascular complications (Antar et al. 2023). Among the microvascular complications are aphthous ulcerations of the oral mucosa, which have a prevalence of approximately 5% to 66% in the global population. These ulcers cause patients pain and discomfort during daily activities, directly impacting their quality of life (Thomes et al. 2021).
A key mechanism involved in this damage is the accumulation of advanced glycation end-products (AGEs), which result from the glycation reaction between glucose and proteins or lipids (Tang et al. 2025). These compounds promote irreversible structural modifications, leading to tissue stiffness and triggering critical intracellular inflammatory signaling pathways, such as the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. This inflammatory activation dysregulates the wound healing process, the formation of inflammatory infiltrate, and the synthesis of type III collagen (Marques et al. 2025).
Cannabidiol (CBD), the primary non-psychoactive component of Cannabis sativa, has been investigated for its anti-inflammatory, wound-healing, antioxidant, and immunomodulatory properties. These characteristics position it as a novel candidate for the treatment of oral lesions (Klein et al. 2018). In a study conducted by Klein et al. (2018), standardized 5 mm aphthous ulcers were induced on the tongues of Wistar rats and subsequently treated with CBD administered intraperitoneally at doses of 5 and 10 mg/kg. Clinical and histological evaluations on days 3 and 7 post-lesion revealed a significant reduction in inflammatory infiltrate, decreased cytokine levels, and enhanced healing. The authors concluded that CBD possesses anti-inflammatory potential (Klein et al. 2018).
Furthermore, the study by Qi et al. (2022) evaluated the topical application of CBD in a murine model of oral ulcers, observing effects on inflammation reduction and tissue healing (Qi et al. 2022). The treatment resulted in diminished of inflammatory cells, increased collagen deposition, and promotion of re-epithelialization (Qi et al. 2022). At the molecular level, CBD downregulated the CMPK2-mediated NLRP3 inflammasome, reducing caspase-1 activation and the release of IL-1β, a potent pro-inflammatory mediator (Bauer et al. 2024). CBD positively influenced the PPARγ signaling pathway, decreasing oxidative stress and stimulating fibroblast proliferation. These findings suggest its potential as an adjuvant therapeutic agent for slow-healing oral lesions (Qi et al. 2022).
Randomized clinical trials corroborate these findings, showing that 0.1% topical CBD formulations can significantly reduce ulcer size and inflammation in cases of recurrent aphthous ulcers, with no relevant adverse events (Umpreecha et al. 2023). CBD acts by regulating the expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), inhibiting the NF-κB signaling pathway, and stimulating angiogenesis and fibroblast proliferation, processes essential for tissue repair that are impaired in the context of chronic hyperglycemia (Tang et al. 2025).
This evidence indicates that the use of CBD as an adjunctive therapy for inflammatory and difficult-to-heal oral lesions, such as those in individuals with diabetes, may be of clinical interest. However, further studies are necessary to evaluate the safety, efficacy, and effectiveness of CBD, particularly in comparison to corticosteroids, which are the first-line treatment for aphthous ulcerations in people with diabetes, while respecting the current regulations for the use of Cannabis derivatives in Brazil.
References
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