# The Potential of Cannabidiol in the Management of Oral Infections
## 1 Introduction
### Management of Oral Infections
The search for novel therapeutic agents to address the limitations of conventional antimicrobial therapies has led to increased scientific interest in phytochemicals, particularly cannabinoids. Among these, CBD, a non-psychoactive compound derived from _Cannabis sativa_, has gained attention for its broad-spectrum antimicrobial, anti-inflammatory, and immunomodulatory properties. While historically studied for its neuroprotective and anxiolytic effects, recent preclinical and _in vitro_ studies have highlighted CBD's potential as a therapeutic compound in preventing and treating oral infections [18; 19]. CBD interacts with multiple molecular targets, including cannabinoid receptors (CB1, CB2), transient receptor potential (TRP) channels, adenosine receptors, and per-oxisome proliferator-activated receptors (PPARs). These interactions contribute to its anti-inflammatory, analgesic, and antimicrobial activities, making it a promising candidate for managing oral cavity infections, where inflammation and polymicrobial biofilms play central roles. Emerging evidence suggests that CBD exhibits direct antimicrobial effects against a range of Gram-positive bacteria, including _Streptococcus mutans_, a key contributor to dental caries [20; 21; 22], and _Enterococcus faecalis_, commonly associated with endodontic failures [19]. Studies have demonstrated that CBD disrupts bacterial membrane integrity, leading to cell lysis, and can inhibit biofilm formation, a critical component of oral pathogenicity [23]. Moreover, CBD has shown activity against fungal pathogens such as _Candida albicans_, suggesting potential for use in oral candidiasis [19; 24]. Oral infectionsare characterized not only by microbial invasion but also by a dysregulated host immune response [25]. CBD modulates key inflammatory pathways by reducing the production of pro-inflammatory cytokines such as TNF-\(\alpha\), IL-1\(\beta\), and IL-6. It also appears to suppress reactive oxygen species (ROS) production and inhibit NF-\(\kappa\)B signaling, thereby limiting tissue destruction and promoting the resolution of inflammation. These effects are particularly relevant in periodontal disease, where chronic inflammation leads to progressive bone and soft tissue loss [26]. \"Clinical antimicrobials\" will be used throughout to specifically denote antimicrobial agents that are employed in clinical settings for the treatment of human infections. This usage is intended to distinguish such therapeutically applied substances from the broader category of antimicrobials, including any chemical, natural, or synthetic agent that acts against microorganisms, regardless of context or application. This terminology aims to avoid ambiguity and clearly differentiate the substances used in medical practice from those used in non-clinical settings such as agriculture, industry, or disinfection. In that sense, studies suggest that CBD may act synergistically with clinical antimicrobials, potentially enhancing their efficacy and reducing the required dose. This could be advantageous in combating antimicrobial-resistant strains and minimizing the adverse effects associated with high-dose antibiotic use. Additionally, its incorporation into topical formulations such as mouthwashes, gels, or slow-release strips could provide localized, sustained delivery in the oral cavity [21]. CBD also shows benefits for bone and soft tissue regeneration following oral infections. This review aims to explore the potential of CBD, which exhibits promising antimicrobial, anti-inflammatory, and immunomodulatory properties in oral infections. By integrating recent preclinical findings, the review assesses CBD's role in modulating oral microbiota, inhibiting biofilm formation, and alleviating inflammation, offering a novel perspective on adjunctive therapy for oral infections. Ultimately, this review aims to bridge current therapeutic gaps and inform future research directions in the development of safer, more effective treatments for oral infectious diseases.