# The Potential of Cannabidiol in the Management of Oral Infections
## 4 Antimicrobial Properties of Cannabidiol
### Preclinical and Clinical Studies  
The therapeutic application of CBD in oral infections has garnered increasing interest, supported by a growing body of preclinical research. These studies have evaluated CBD's efficacy in reducing microbial burden, alleviating pain, and modulating inflammatory responses. Although promising, the current findings are derived from diverse models, ranging from _in vitro_ and _ex vivo_ tissue cultures to animal experiments and preliminary human trials, each contributing distinct insights into CBD's potential as an adjunctive treatment in dentistry.  
Rodent models of oral disease, particularly ligature-induced periodontitis and oral mucositis, have been widely used to assess CBD's therapeutic impact [57]. Periodontitis models in rats demonstrated that both systemic and local CBD administration reduced inflammatory infiltrates, decreased alveolar bone loss, and downregulated pro-inflammatory cytokines such as IL-18 and TNF-\(\alpha\). Bone preservation was confirmed by micro-CT and histological analyses [56; 57].  
CBD has been tested on human gingival fibroblasts (HGFs), periodontal ligament cells, and oral epithelial cells, often stimulated with _Porphyomonas gingivalis_ LPS or pro-inflammatory cytokines. The outcomes consistently show reduced expression of COX-2, IL-6, IL-8, and MMPs after CBD treatment. In ex vivo models using extracted human gingival tissue, topical CBD application reduced inflammatory cytokine release and preserved epithelial integrity [52].  
Clinical data remain limited; few studies mainly focus on the following: (i) Topical CBD in Oral Pain and Inflammation: a randomized controlled trial (RCT) reported that topical CBD oil applied to aphthous ulcers resulted in reduced pain intensity and faster healing compared to placebo [58]. (ii) CBD Mouthwash: pilot studies evaluating CBD-infused oral rinses demonstrated significant reductions in plaque indices and gingival inflammation, with efficacy comparable to chlorhexidine and fewer side effects [45; 59]. (iii) Systemic CBD in Mucositis: a case series in oncology patients undergoing chemotherapy suggested that systemic CBD could reduce the severity and duration of oral mucositis, although larger trials are needed [60].  
CBD treatment across various models has yielded consistent therapeutic outcomes, as follows: (i) Infection reduction and antibacterial and antifungal effects were observed _in vitro_ and _in vivo_, especially against _S. mutans_, _E. faecalis_, and _Candida albicans_. While few human studies directly quantify pathogen load, plaque and biofilm reduction has been noted [19; 20; 28; 43]. (ii) Pain relief: both animal models and small clinical trials suggest analgesic effects, attributed to CBD's interaction with TRPV1 and adenosine receptors, reducing nociceptive signaling and peripheral sensitization [61; 62]. (iii) Reduction in inflammatory markers: CBD downregulated key inflammatory mediators, including TNF-\(\alpha\), IL-18, IL-6, and COX-2, while also modulating oxidative stress markers such as nitric oxide and ROS [55]. Table 1 summarizes the effects of CBD in several studies on oral infections.