Investigation of the effect of cannabidiol, tetrahydrocannabinol, and vancomycin combination on cariogenic bacterial retention due to microleakage under prosthetic restorations

Aims: Oral and dental infections develop due to many different bacterial activities, and with the increasing resistance mechanism against conventional antimicrobial agents, the formation of biofilms in the microleakage under prosthetic restorations, which cause dental caries, has become a major clinical challenge to overcome. This study aims to reveal the antibiofilm effect of vancomycin (VAN) combined with cannabidiol (CBD) and tetrahydrocannabinol (THC) against biofilm formation caused by Streptococcus mutans (S. mutans) and Staphylococcus aureus (S. aureus) on dental dentin under prosthetic restorations. Methods: Freshly extracted human teeth without caries, resorption, or fracture were collected and obtained by slicing 2 mm dentin discs. A total of 64 dentin discs were inoculated with S. mutans and S. aureus and randomly allocated into control and five experimental groups consisting of CBD, THC, CBD+VAN, THC+VAN, and CBD+THC+VAN. Antibiofilm activity and combination index were analyzed by the MTT viability test and the Chou–Talalay method, respectively. Biofilm structure was assessed by scanning electron microscopy. Analysis of variance and post hoc Tukey tests were applied for comparisons. Results: CBD and VAN showed antimicrobial effects against S. aureus and S. mutans bacteria in unary combinations, while THC was ineffective. However, no apparent synergistic interaction was observed in the binary combinations of VAN. Interestingly, a high synergistic effect (CI<1) occurred in the triple combination against both bacterial species. When this effect in the triple combination was examined, it was seen that VAN exhibited a suitable dose reduction index (DRI>1). When these synergistic and dose reduction results are evaluated together with SEM image analysis, it can be said that the triple combination of VAN+CBD+THC probably causes the most optimum antibiofilm effect on dental caries bacteria. Conclusion: Combining VAN with CBD and THC may offer a new approach to combat microleakage-induced bacterial retention in dental dentin under prosthetic restorations.