# The Potential of Cannabidiol in the Management of Oral Infections
## 3 Overview of Pharmacokinetics Relevant to Oral Tissues  
While the systemic pharmacokinetics of CBD have been studied in various formulations and routes of administration, its behavior within the oral cavity, including absorption, distribution, metabolism, and elimination (ADME), requires special consideration due to the unique anatomy and physiology of oral tissues [34; 35].  
CBD can be administered via multiple routes, including oral ingestion, sublingual application, buccal sprays, and topical formulations. Among these, sublingual and buccal delivery systems are of particular relevance for oral health applications, as they allow direct absorption into the oral mucosa, bypassing first-pass metabolism in the liver and improving systemic bioavailability [36]. In sublingual administration, CBD is placed under the tongue and absorbed through the highly vascularized mucosa. The onset of action typically occurs within 15-45 min, with bioavailability ranging from 13% to 35%, depending on the formulation and individual variability [37]. Buccal absorption offers a slower but sustained route through the inner cheek, which can be advantageous for prolonged local exposure to oral tissues, especially in the management of localized infections or inflammation. These mucosal routes allow CBD to reach oral tissues directly, potentially achieving higher local concentrations compared to systemic administration [38].  
Due to its lipophilic nature, CBD readily diffuses through cell membranes once absorbed and accumulates in lipid-rich tissues. Studies suggest that following mucosal absorption, CBD may distribute effectively to the gingival epithelium, periodontal ligament, and alveolar bone, where it can exert antimicrobial and anti-inflammatory effects. In periodontal disease, where tissue penetration and modulation of the host immune response are critical, localized delivery systems (e.g., CBD-loaded gels or nanoparticles) may further enhance tissue-specific bioavailability and therapeutic efficacy [39; 40].  
While hepatic metabolism (via CYP450 enzymes) is dominant in systemic CBD processing, enzymatic activity in the oral cavity may contribute to local metabolism. Salivary enzymes, along with microbial enzymes in the oral microbiota, can potentially alter CBD structure or activity before systemic absorption. However, the extent and clinical relevance of these local metabolic transformations remain underexplored [41]. CBD and its metabolites are ultimately eliminated through urine and feces after systemic absorption. However, in oral applications, particularly topical or intraoral slow-release systems, CBD may remain in contact with mucosal surfaces or within biofilms for extended periods, enhancing local retention and efficacy. Salivary flow, pH, and formulation viscosity are key factors influencing residence time. Formulations such as mucoadhesive films, mouth rinses, or biodegradable inserts are being explored to maximize retention and minimize washout by saliva or swallowing [27].  
Given its pharmacokinetic profile, CBD offers several advantages for oral health applications, as follows: (i) rapid onset and localized action via sublingual or buccal routes; (ii) bypassing first-pass metabolism, improving systemic and local bioavailability; and (iii) potential for site-specific delivery in periodontal pockets or mucosal lesions. Novel delivery systems such as CBD-infused dental gels, mucoadhesive patches, nanocarriers, and biodegradable strips are being investigated to optimize both pharmacokinetic properties and therapeutic outcomes in oral health [38].