The Role of Different Types of Cannabinoids in Periodontal Disease: An Integrative Review

Abstract

This integrative review addresses the potential of the Endocannabinoid System (ES) and cannabinoids in the pathogenesis and treatment of periodontal disease (PD). Cannabinoid receptors are expressed in healthy and inflamed periodontal tissues, indicating a potential regulatory role for SEC in oral homeostasis. Healthy periodontal cells express more CB1 receptors, while inflamed sites show increased CB2 receptors. This suggests a dynamic involvement of the SEC in the inflammatory response associated with PD. Cannabinoids such as cannabidiol (CBD) and cannabinoid receptor agonists such as HU-308, anandamide (AEA), and methanamide (Meta-AEA) have demonstrated promising therapeutic potential in studies. CBD has been associated with the control of bone resorption, antibacterial activity, and increased production of gingival fibroblasts, indicating effects in mitigating the progression of PD. HU-308 demonstrated preventive effects against alveolar bone loss, and anti-inflammatory, osteoprotective, and pro-homeostatic properties in animal models of periodontitis. AEA and Meta-AEA have anti-inflammatory effects by reducing pro-inflammatory mediators such as IL-1, IL-6, and TNF-α. The activation of cannabinoid receptors attenuates inflammatory processes, inhibits alveolar bone loss, exerts antibacterial effects, and promotes tissue repair. However, clinical trials are especially needed to validate these results and explore the therapeutic potential of cannabinoids in the treatment of PD in humans.

Keywords: cannabinoids; inflammation; periodontal diseases; treatment.

Figure 1

Flow diagram of the selected studies.

Figure 2

Representation of the main cannabinoid molecules and their respective effects on periodontal disease. Cannabinoids comprise a diverse group of molecules that can be endogenous (anandamide (AEA), synthetic (methanandamide (Meta-AEA), and CB₂-specific agonist (HU-308)) or derived from plants (phytocannabinoids; Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabichromene (CBC), cannabinol (CBN)).

Figure 3

Illustrates the possible mechanisms described in the literature on the effects of cannabinoids and their derivatives on periodontal disease. (1) Anti-inflammatory effect: AEA and HU-308 act to reduce the levels of cytokines involved in the inflammatory cascade (IL-1β, TNF-α, PGE₂, IL-6, IL-8, NF-κB, MCP-1). (2) Antibacterial effect: CBD, CBN, and THC have an inhibitory effect on the growth of periodontopathogenic bacteria, such as Porphyromonas gingivalis and Filifactor alocis. (3) Prevention of bone resorption: HU-308, META-AEA, and CBD demonstrate the ability to reduce alveolar bone loss by reducing levels of mediators (IL-1β, TNF-α, iNOS, PGE₂, RANKL, RANK) that induce bone resorption. (4) Tissue repair: AEA demonstrates an increase in tissue repair capacity due to its action on the proliferation of periodontal ligament cells. Legend: AEA: anandamide; HU-308: CB2-specific agonist; CBD: Cannabidiol; CBN: Cannabinol; THC: Δ9-Tetrahydrocannabinol; META-AEA: methanandamide; IL-1β: interleukin-1β; TNF-α: tumor necrosis factor alpha; PGE₂: Prostaglandin E2; IL-6: interleukin 6; IL-8: interleukin 8; NF-κB: Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells; MCP-1: Monocyte Chemoattractant Protein-1; iNOS: Inducible Nitric Oxide Synthase; RANK: Receptor Activator of Nuclear Factor Kappa B; RANKL: Receptor Activator of Nuclear Factor Kappa B Ligand.

Figure 4

Schematic representation of the differential expression of cannabinoid receptors (CB1 and CB2) in healthy and diseased periodontal tissues. In healthy periodontal tissues, CB1 receptor expression predominates, while inflamed tissues exhibit a higher tendency for CB2 receptor expression. This shift in receptor expression suggests a potential regulatory role of the Endocannabinoid System in the pathogenesis and progression of periodontal disease.