Cannabinoids in Periodontology: Where Are We Now?

Abstract

Introduction: Cannabinoids are a well-documented treatment modality for various immune and inflammatory diseases, including asthma, chronic obstructive pulmonary disease, Crohn's disease, arthritis, multiple sclerosis, and a range of neurodegenerative conditions. However, limited information is available regarding the therapeutic potential of cannabinoids in treating periodontal disease.

Objective: The objective of this study is to analyze the current evidence on the antibacterial and immunomodulatory effects of cannabis and its role in the healing and regeneration processes within periodontal tissues.

Results: This review discusses the potential role of cannabinoids in restoring periodontal tissue homeostasis.

Conclusions: The examination of the endocannabinoid system and the physiological effects of cannabinoids in the periodontium suggests that they possess immunomodulatory and antibacterial properties, which could potentially promote proper tissue healing and regeneration.

Keywords: cannabinoids; cannabis; periodontitis; regeneration.

Figure 1

Cannabinoids derived from the cannabis sativa plant are known as phytocannabinoids, including the psychoactive component Δ9-tetrahydrocannabinol (Δ9-THC), cannabidiol (CBD), cannabigerol (CBG), cannabinol (CBN), and cannabichromene (CBC), which lack such effects. Flavonoids and terpenoids constitute other bioactive molecules contained in the plant; terpenoids are secondary metabolites with organoleptic properties that give them differential properties (A). Endocannabinoids (compounds produced naturally by the human body) belong to the eicosanoid group, and its two main representatives are anandamide (arachidonoyl ethanolamide-AEA), and 2-arachidonoylglycerol (2-AG), which act as cannabinoid receptor agonists. Both phytocannabinoids and endocannabinoids act on the cannabinoid receptors CB1 and CB2. CB1 receptors are widely distributed in the human body, with high expression in the central nervous system, while CB2 receptors are mainly found in the cells of the immune system (B).

Figure 2

Both endocannabinoids and exo-cannabinoids influence various facets of the immune system. Effects on effector cells of both innate immunity (PMNn, macrophages, and NK cells) and acquired immunity (CD4+ and CD8+ T cells, and B lymphocytes) have been described, influencing cell proliferation and the release of pro-inflammatory cytokines (IL-12, IL-6, TNFa, and IFNg) and regulators (IL.10 and TGFb); the levels of effector enzymes are also affected (A). In relation to the effects on the microbiota, cannabinoids have shown antibacterial activity both in planktonic Gram+ and Gram- bacteria and in preventing the formation of certain biofilms, in addition to clear fungicide activity (B). * Antimicrobial effects of cannabinoids correlate to the presence of different terpene profiles related to different cultivars of C. sativa and the extraction method.

Figure 3

Potential effects of cannabinoids in the control of periodontal inflammation. The expression of CB1 and CB2 cannabinoid receptors in periodontal tissues (junctional epithelium, immune response cells, gingival and periodontal ligament fibroblasts, osteoblasts, and osteoclasts) and the increase in their expression in the presence of inflammation are a clear indication of a possible role in modulating the host response (A). Through their activation, cannabinoids mediate anti-inflammatory and regulatory responses, decreasing mediators of inflammation in periodontal tissues and inducing the blocking of pro-inflammatory pathways (B). The modulation of these responses goes hand in hand with a range of actions that promote the repair and regeneration of tissues, which include the promotion of the proliferation and survival of stem cells, the increase in the production of metalloproteinases, hand in hand with the proliferation of gingival fibroblasts (hGFs) and anabolic functions of bone metabolism mediated by their activity in the RANK–RANKL–Osteoprotegerin (OPG) system, which results in an increase in osteogenic differentiation and a decrease in bone resorption (C).