Cannabidiol in Periodontal Therapy—Is There Hope or Just a Bias? A Systematic Review

Background: Periodontitis is a chronic inflammatory disease characterized by dysbiotic biofilm formation, progressive destruction of periodontal tissues, and alveolar bone resorption. Conventional periodontal therapy primarily focuses on mechanical biofilm removal; however, adjunctive therapeutic approaches targeting host inflammatory responses and microbial activity have gained increasing attention. Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from Cannabis sativa, has demonstrated anti-inflammatory, antimicrobial, and immunomodulatory properties that may be relevant in periodontal disease management. Objective: This systematic review aimed to evaluate the available evidence regarding the potential role of CBD in modulating periodontal inflammation, microbial biofilms, and bone resorption processes. Methods: A systematic literature search was conducted in Web of Science, Cochrane, PubMed, Scopus, and Google Scholar. The review was conducted in accordance with PRISMA guidelines. Studies investigating the effects of CBD on periodontal inflammation, oral biofilms, or bone remodeling were included. Both preclinical (in vitro and animal) and clinical studies were considered. Results: Evidence from experimental studies consistently demonstrated that CBD modulates inflammatory signaling pathways, including inhibition of the TLR4/NF-κB pathway and a reduction in pro-inflammatory cytokine expression, but some results are contradictory. Animal studies reported reduced alveolar bone loss and decreased osteoclast activity following CBD administration. Several studies also demonstrated antimicrobial and antibiofilm effects of CBD against oral microorganisms. Conclusions: While preclinical evidence is promising, the current body of clinical data remains limited. Further well-designed randomized clinical trials are required to determine the efficacy, type of formulation, optimal dosing, and long-term safety of CBD as an adjunctive therapy in periodontal treatment.