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

Year 2025, Volume: 6 Issue: 4, 298 - 304, 31.08.2025
https://doi.org/10.47582/jompac.1703800

Abstract

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.

Ethical Statement

This study received approval from the ethics committee of the Faculty of Medicine at Yozgat Bozok University (2025-GOKAEK-257_2025.04.09_443), and all experiments were conducted in accordance with the ethical guidelines of the Helsinki Declaration.

Supporting Institution

not applicable

Project Number

2025-GOKAEK-257_2025.04.09_443

Thanks

not applicable

References

  • Koo H, Falsetta ML, Klein MI. The exopolysaccharide matrix: a virulence determinant of cariogenic biofilm. J Dent Res. 2013;92(12):1065-1073. doi:10.1177/0022034513504218
  • Haralur SB, Ghaseb GAAL, Alqahtani NA, Alqahtani B. Comparison of microleakage between different restorative materials to restore marginal gap at crown margin. PeerJ. 2021;9:e10823. doi:10.7717/peerj.10823
  • Shao Q, Feng D, Yu Z, et al. The role of microbial interactions in dental caries: dental plaque microbiota analysis. Microbial Pathogenesis. 2023; 185:106390. doi:10.1016/j.micpath.2023.106390
  • Hajishengallis G. Illuminating the oral microbiome and its host interactions: animal models of disease. FEMS Microbiol Rev. 2023;47(3): fuad018. doi:10.1093/femsre/fuad018
  • Hayran Y, Sarikaya I, Aydin A, Tekin YH. Determination of the effective anticandidal concentration of denture cleanser tablets on some denture base resins. J Appl Oral Sci. 2018;26:e20170077. doi:10.1590/1678-7757-2017-0077
  • Abidi AH, Alghamdi SS, Derefinko K. A critical review of cannabis in medicine and dentistry: a look back and the path forward. Clin Exp Dent Res. 2022;8(3):613-631. doi:10.1002/cre2.564
  • Hayran Y, Aydin A. Evaluation of the time-dependent effect of an enzymatic denture cleanser tablet against six microbial species. Ann Med Res. 2019;26(8):1556-1564. doi:10.5455/annalsmedres.2019.05.297
  • Zeckel ML, Woodworth JR. Vancomycin: a clinical overview. Glycopeptide Antibiotics. 1st Edition. CRC Press. 2020.
  • Roy S, Kc HR, Roberts J, et al. Development and antibacterial properties of 4-[4-(anilinomethyl)-3-phenylpyrazol-1-yl]benzoic acid derivatives as fatty acid biosynthesis inhibitors. J Med Chemistry. 2023;66(19):13622-13645. doi:10.1021/acs.jmedchem.3c00969
  • Esteban P, Redrado S, Comas L, et al. In Vitro and in vivo antibacterial activity of gliotoxin alone and in combination with antibiotics against Staphylococcus aureus. Toxins (Basel). 2021;13(2):85. doi:10.3390/toxins 13020085
  • Kim JH. Anti-bacterial action of onion (Allium cepa L.) extracts against oral pathogenic bacteria. J Nihon Univ Sch Dent. 1997;39(3):136-141. doi: 10.2334/josnusd1959.39.136
  • Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65(1-2):55-63. doi:10.1016/0022-1759(83)90303-4
  • Chou TC. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev. 2006;58(3):621-681. doi:10.1124/pr.58.3.10
  • Chou TC, Talalay P. Analysis of combined drug effects: a new look at a very old problem. Trends Pharmacol Sci. 1983;4:450-454. doi:10.1016/ 0165-6147(83)90490-X
  • Hayran Y, Kuşcu S, Aydın A. Determination of Streptococcus mutans retention in acidic and neutral pH artificial saliva environment of all-ceramic materials with different surface treatment. BMC Oral Health. 2025;25(1):7. doi:10.1186/s12903-024-05386-0
  • Smith AJ, Jackson MS, Bagg J. The ecology of Staphylococcus species in the oral cavity. J Med Microbiol. 2001;50(11):940-946. doi:10.1099/0022-1317-50-11-940
  • Schofs L, Sparo MD, Sanchez Bruni SF. The antimicrobial effect behind Cannabis sativa. Pharmacol Res Perspect. 2021;9(2):e00761. doi:10.1002/prp2.761
  • Zeng H, Wang X, Tang J, et al. Proteomic and metabolomic analyses reveal the antibacterial mechanism of Cannabidiol against gram-positive bacteria. J Proteomics. 2025;315:105411. doi:10.1016/j.jprot.2025. 105411
  • Barak T, Sharon E, Steinberg D, Feldman M, Sionov RV, Shalish M. Anti-bacterial effect of cannabidiol against the cariogenic Streptococcus mutans bacterium: an in vitro study. Int J Mol Sci. 2022;23(24):15878. doi:10.3390/ijms232415878
  • Pena-Miller R, Laehnemann D, Jansen G, et al. When the most potent combination of antibiotics selects for the greatest bacterial load: the smile-frown transition. PLoS Biol. 2013;11(4):e1001540. doi:10.1371/journal.pbio.1001540
  • Fischbach MA. Combination therapies for combating antimicrobial resistance. Curr Opin Microbiol. 2011;14(5):519-23. doi:10.1016/j.mib. 2011.08.003
  • Woods RJ, Read AF. Combination antimicrobial therapy to manage resistance. Evol Med Public Health. 2023;11(1):185-6. doi:10.1093/emph/eoad005
  • More PR, Pandit S, Filippis AD, Franci G, Mijakovic I, Galdiero M. Silver nanoparticles: bactericidal and mechanistic approach against drug resistant pathogens. Microorganisms. 2023;11(2):369. doi:10.3390/microorganisms11020369

Protez restorasyonları altında mikrosızıntıya bağlı kariyojenik bakteriyel tutunma üzerine kanabidiol, tetrahidrokanabinol ve vankomisin kombinasyonunun etkisinin araştırılması

Year 2025, Volume: 6 Issue: 4, 298 - 304, 31.08.2025
https://doi.org/10.47582/jompac.1703800

Abstract

Amaç: Ağız ve diş enfeksiyonları birçok farklı bakteri aktivitesi nedeniyle gelişir ve geleneksel antimikrobiyal ajanlara karşı artan direnç mekanizmasıyla birlikte, protez restorasyonların altındaki mikrosızıntıda diş çürüğüne neden olan biyofilm oluşumu, üstesinden gelinmesi gereken önemli bir klinik zorluk haline gelmiştir. Bu çalışma, vankomisinin (VAN) kanabidiol (CBD) ve tetrahidrokanabinol (THC) ile kombinasyonunun, protez restorasyonların altındaki diş dentini üzerinde Streptococcus mutans ve Staphylococcus aureus'un neden olduğu biyofilm oluşumuna karşı antibiyofilm etkisini ortaya koymayı amaçlamaktadır.
Materyal ve Yöntem: Çürük, rezorpsiyon veya kırık olmayan yeni çekilmiş insan dişleri toplandı ve 2 mm dentin diskleri kesilerek elde edildi. Toplam 64 dentin diski S. mutans ve S. aureus ile aşılandı ve rastgele kontrol ve CBD, THC, CBD+VAN, THC+VAN ve CBD+THC+VAN'dan oluşan beş deney grubuna ayrıldı. Antibiyofilm aktivitesi ve kombinasyon indeksi sırasıyla MTT canlılık testi ve Chou-Talalay yöntemi ile analiz edildi. Biyofilm yapısı taramalı elektron mikroskobu ile değerlendirildi. Karşılaştırmalar için varyans analizi ve post hoc Tukey testleri uygulandı.
Sonuçlar: CBD ve VAN, tekli kombinasyonlarda S. aureus ve S. mutans bakterilerine karşı antimikrobiyal etki gösterirken, THC etkisizdi. Ancak, VAN'ın ikili kombinasyonlarında belirgin bir sinerjistik etkileşim gözlenmedi. İlginç bir şekilde, üçlü kombinasyonda her iki bakteri türüne karşı yüksek bir sinerjistik etki (CI < 1) meydana geldi. Üçlü kombinasyondaki bu etki incelendiğinde, VAN'ın uygun bir doz azaltma indeksi (DRI>1) sergilediği görüldü. Bu sinerjistik ve doz azaltma sonuçları SEM görüntü analizi ile birlikte değerlendirildiğinde, VAN+CBD+THC üçlü kombinasyonunun muhtemelen diş çürüğü bakterileri üzerinde en optimum antibiyofilm etkisine neden olduğu söylenebilir.
Sonuç: VAN'ın CBD ve THC ile kombinasyonu, protetik restorasyonlar altında dental dentinlerde mikrosızıntıya bağlı bakteriyel retansiyonla mücadelede yeni bir yaklaşım sunabilir.

Project Number

2025-GOKAEK-257_2025.04.09_443

References

  • Koo H, Falsetta ML, Klein MI. The exopolysaccharide matrix: a virulence determinant of cariogenic biofilm. J Dent Res. 2013;92(12):1065-1073. doi:10.1177/0022034513504218
  • Haralur SB, Ghaseb GAAL, Alqahtani NA, Alqahtani B. Comparison of microleakage between different restorative materials to restore marginal gap at crown margin. PeerJ. 2021;9:e10823. doi:10.7717/peerj.10823
  • Shao Q, Feng D, Yu Z, et al. The role of microbial interactions in dental caries: dental plaque microbiota analysis. Microbial Pathogenesis. 2023; 185:106390. doi:10.1016/j.micpath.2023.106390
  • Hajishengallis G. Illuminating the oral microbiome and its host interactions: animal models of disease. FEMS Microbiol Rev. 2023;47(3): fuad018. doi:10.1093/femsre/fuad018
  • Hayran Y, Sarikaya I, Aydin A, Tekin YH. Determination of the effective anticandidal concentration of denture cleanser tablets on some denture base resins. J Appl Oral Sci. 2018;26:e20170077. doi:10.1590/1678-7757-2017-0077
  • Abidi AH, Alghamdi SS, Derefinko K. A critical review of cannabis in medicine and dentistry: a look back and the path forward. Clin Exp Dent Res. 2022;8(3):613-631. doi:10.1002/cre2.564
  • Hayran Y, Aydin A. Evaluation of the time-dependent effect of an enzymatic denture cleanser tablet against six microbial species. Ann Med Res. 2019;26(8):1556-1564. doi:10.5455/annalsmedres.2019.05.297
  • Zeckel ML, Woodworth JR. Vancomycin: a clinical overview. Glycopeptide Antibiotics. 1st Edition. CRC Press. 2020.
  • Roy S, Kc HR, Roberts J, et al. Development and antibacterial properties of 4-[4-(anilinomethyl)-3-phenylpyrazol-1-yl]benzoic acid derivatives as fatty acid biosynthesis inhibitors. J Med Chemistry. 2023;66(19):13622-13645. doi:10.1021/acs.jmedchem.3c00969
  • Esteban P, Redrado S, Comas L, et al. In Vitro and in vivo antibacterial activity of gliotoxin alone and in combination with antibiotics against Staphylococcus aureus. Toxins (Basel). 2021;13(2):85. doi:10.3390/toxins 13020085
  • Kim JH. Anti-bacterial action of onion (Allium cepa L.) extracts against oral pathogenic bacteria. J Nihon Univ Sch Dent. 1997;39(3):136-141. doi: 10.2334/josnusd1959.39.136
  • Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65(1-2):55-63. doi:10.1016/0022-1759(83)90303-4
  • Chou TC. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev. 2006;58(3):621-681. doi:10.1124/pr.58.3.10
  • Chou TC, Talalay P. Analysis of combined drug effects: a new look at a very old problem. Trends Pharmacol Sci. 1983;4:450-454. doi:10.1016/ 0165-6147(83)90490-X
  • Hayran Y, Kuşcu S, Aydın A. Determination of Streptococcus mutans retention in acidic and neutral pH artificial saliva environment of all-ceramic materials with different surface treatment. BMC Oral Health. 2025;25(1):7. doi:10.1186/s12903-024-05386-0
  • Smith AJ, Jackson MS, Bagg J. The ecology of Staphylococcus species in the oral cavity. J Med Microbiol. 2001;50(11):940-946. doi:10.1099/0022-1317-50-11-940
  • Schofs L, Sparo MD, Sanchez Bruni SF. The antimicrobial effect behind Cannabis sativa. Pharmacol Res Perspect. 2021;9(2):e00761. doi:10.1002/prp2.761
  • Zeng H, Wang X, Tang J, et al. Proteomic and metabolomic analyses reveal the antibacterial mechanism of Cannabidiol against gram-positive bacteria. J Proteomics. 2025;315:105411. doi:10.1016/j.jprot.2025. 105411
  • Barak T, Sharon E, Steinberg D, Feldman M, Sionov RV, Shalish M. Anti-bacterial effect of cannabidiol against the cariogenic Streptococcus mutans bacterium: an in vitro study. Int J Mol Sci. 2022;23(24):15878. doi:10.3390/ijms232415878
  • Pena-Miller R, Laehnemann D, Jansen G, et al. When the most potent combination of antibiotics selects for the greatest bacterial load: the smile-frown transition. PLoS Biol. 2013;11(4):e1001540. doi:10.1371/journal.pbio.1001540
  • Fischbach MA. Combination therapies for combating antimicrobial resistance. Curr Opin Microbiol. 2011;14(5):519-23. doi:10.1016/j.mib. 2011.08.003
  • Woods RJ, Read AF. Combination antimicrobial therapy to manage resistance. Evol Med Public Health. 2023;11(1):185-6. doi:10.1093/emph/eoad005
  • More PR, Pandit S, Filippis AD, Franci G, Mijakovic I, Galdiero M. Silver nanoparticles: bactericidal and mechanistic approach against drug resistant pathogens. Microorganisms. 2023;11(2):369. doi:10.3390/microorganisms11020369
There are 23 citations in total.

Details

Primary Language English
Subjects Dental Therapeutics, Pharmacology and Toxicology, Prosthodontics, Dental Materials
Journal Section Research Articles [en] Araştırma Makaleleri [tr]
Authors

Süha Kuşçu 0000-0002-0805-5888

Yeliz Hayran 0000-0002-8664-9083

Ali Aydın 0000-0002-9550-9111

Project Number 2025-GOKAEK-257_2025.04.09_443
Early Pub Date August 30, 2025
Publication Date August 31, 2025
Submission Date May 21, 2025
Acceptance Date June 20, 2025
Published in Issue Year 2025 Volume: 6 Issue: 4

Cite

AMA Kuşçu S, Hayran Y, Aydın A. Investigation of the effect of cannabidiol, tetrahydrocannabinol, and vancomycin combination on cariogenic bacterial retention due to microleakage under prosthetic restorations. J Med Palliat Care / JOMPAC / jompac. August 2025;6(4):298-304. doi:10.47582/jompac.1703800

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Interuniversity Board (UAK) Equivalency: Article published in Ulakbim TR Index journal [10 POINTS], and Article published in other (excuding 1a, b, c) international indexed journal (1d) [5 POINTS]



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