Fibrogenic Effects of Cannabidiol on Human Gingival Fibroblasts

Marijuana (Cannabis) use may be associated with gingival enlargement, which can resemble that caused by the anticonvulsant agent phenytoin. Cannabidiol (CBD), a nonpsychotropic derivative of cannabis, is structurally similar to phenytoin and has also been used as an anticonvulsant. While there are many reports on effects of phenytoin on human gingival fibroblasts, there is no information on effects of Cannabis on these cells. Objective: To determine fibrogenic effects of CBD, on human gingival fibroblasts. Methods: Fibroblasts were incubated with CBD (30µM – 10nM) in serum-free medium for 1-6 days. CBD effect on cell viability was determined by measuring activity of the mitochondrial enzyme MTT. Transforming growth factor ß (TGFß), which promotes tissue healing and fibrosis, and the extracellular matrix (ECM) molecule fibronectin were measured in culture supernatants by ELISA. Data were analyzed using ANOVA. Results: CBD had little or no significant effect on cell viability. Low CBD concentrations (10-50nM) increased TGFß by as much as 40% over control (P<0.001), while higher concentrations (2-20µM) decreased it by as much as 40% (P<0.0001). CBD (0.025-30µM) increased fibronectin production by more than 100% (P<0.001) over control. Conclusion: The data suggest that the effects of CBD on human gingival fibroblasts may promote fibrotic gingival enlargement by increasing their production of the fibrogenic growth factor TGFß, as well as specific ECM molecules such as fibronectin. (Supported by UT College of Dentistry Alumni Endowment Fund).