Čes. stomatol. Prakt. zub. lék. (Czech Dental Journal) 2023; 123(2): 33-39 | DOI: 10.51479/cspzl.2023.004
EFFECTS OF NON-PSYCHOTROPIC PHYTOCANNABINOIDS ON ORAL BACTERIA – IN VITRO STUDY
- 1 Klinika zubního lékařství, Lékařská fakulta Univerzity Palackého v Olomouci, a Fakultní nemocnice Olomouc
- 2 Mikrobiologický ústav, Masarykova univerzita, Lékařská fakulta, a Fakultní nemocnice u sv. Anny v Brně
- 3 Oddělení pokročilých materiálů a organické syntézy, Ústav chemických procesů AV ČR, v. v. i., Praha
- 4 Ústav lékařské chemie a biochemie, Lékařská fakulta Univerzity Palackého v Olomouci
Introduction, aim: Maintaining homeostasis of the oral cavity is associated not only with the immune response and soft tissue metabolism but also the action of commensal and pathogenic bacteria. In the development of dental remedies against pathogenic forms, new/alternative antibiotic agents are being sought. One of the currently studied groups of these substances are the phytocannabinoids, in particular cannabidiol (CBD). The aim of the presented study was to evaluate the antimicrobial effects of four non- psychotropic phytocannabinoids on selected oral bacteria.
Methods: The antimicrobial effects (MIC – minimal inhibition concentrations) of phytocannabinoids were determined in vitro using a standard microdilution technique. The effect of CBD, cannabigerol (CBG), cannabichromene (CBC), cannabinol (CBN) and selected phytocannabinoid extracts composed of 50% CBD or CBG was evaluated on Streptococcus mutans CCM 7409 and Porphyromonas gingivalis CCM 3985. The effect of CBD was further tested on Lactobacillus acidophilus CCM 4833, Lactobacillus casei CCM 1825, Aggregatibacter actinomycetemcomitans CCM 4688, and Eikenella corrodens CCM 5985. Chlorhexidine digluconate (CHX) was used as an active comparator.
Results: The MIC values of CBD in P. gingivalis were similar to those for CHX (1–2 μg/ml). In case of S. mutans, the lowest MIC was found for CBG (8 μg/ml). For L. casei and L. acidophilus, MIC for CBD was close to MIC for CHX. Specifically for L. casei, CBD was as effective as CHX (MIC 2–4 μg/ml). In L. acidophilus, MICs were determined for CBD (4–8 μg/ml) and for CHX (2–4 μg/ml). For other microbes, the efficacy of CBD was lower than that for CHX. A. actinomycetemcomitans growth was significantly more inhibited by CHX (MIC = 4 μg/ml) than by CBD (MIC > 128 μg/ml). Similar effects were observed for E. corrodens with the following antimicrobial activity for CBD (MIC 16–32 μg/ml) and CHX (MIC 2–4 μg/ml). The tested complex mixtures showed no superior antimicrobial effects than individual phytocannabinoids.
Conclusion: The results show that non-psychotropic phytocannabinoids (predominantly CBD) inhibit some oral bacteria. At the same time, they are able to inhibit the growth of periodontopathogens such as P. gingivalis, and in case of CBD also E. corrodens, which suggests the possibility of further research and application in dentistry.
Keywords: phytocannabinoid, cannabidiol, inflammation, periodontium, microbiome
Received: December 21, 2022; Revised: March 6, 2023; Accepted: March 7, 2023; Prepublished online: June 7, 2023; Published: June 12, 2023 Show citation
ACS | AIP | APA | ASA | Harvard | Chicago | Chicago Notes | IEEE | ISO690 | MLA | NLM | Turabian | Vancouver |
References
- Caton JG, Armitage G, Berglundh T, Chapple ILC, Jepsen S, Kornman KS, et al. A new classification scheme for periodontal and peri-implant diseases and conditions - Introduction and key changes from the 1999 classification. J Clin Periodontol. 2018; 45(Suppl 20): S1-S8.
Go to original source...
- Nazir M, Al-Ansari A, Al-Khalifa K, Alhareky M, Gaffar B, Almas K. Global prevalence of periodontal disease and lack of its surveillance. Sci World J. 2020; 2020: 2146160.
Go to original source...
- Kassebaum NJ, Bernabé E, Dahiya M, Bhandari B, Murray CJ, Marcenes W. Global burden of severe tooth loss: A systematic review and meta-analysis. J Dent Res. 2014; 93(Suppl 7): 20s-28s.
Go to original source...
Go to PubMed...
- Mark Welch JL, Rossetti BJ, Rieken CW, Dewhirst FE, Borisy GG. Biogeography of a human oral microbiome at the micron scale. Proc Natl Acad Sci USA. 2016; 113(6): E791-800.
Go to original source...
- Deo PN, Deshmukh R. Oral microbiome: Unveiling the fundamentals. J Oral Maxillofac Pathol. 2019; 23(1): 122-128.
Go to original source...
- Jia G, Zhi A, Lai PFH, Wang G, Xia Y, Xiong Z, et al. The oral microbiota - a mechanistic role for systemic diseases. Br Dent J. 2018; 224(6): 447-455.
Go to original source...
- Nazir MA. Prevalence of periodontal disease, its association with systemic diseases and prevention. Int J Health Sci (Qassim). 2017; 11(2): 72-80.
- Socransky SS, Haffajee AD, Cugini MA, Smith C, Kent RL Jr. Microbial complexes in subgingival plaque. J Clin Periodontol. 1998; 25(2): 134-144.
Go to original source...
- Slots J. Periodontitis: facts, fallacies and the future. Periodontology 2000. 2017; 75(1): 7-23.
Go to original source...
- Madianos PN, Bobetsis YA, Kinane DF. Generation of inflammatory stimuli: how bacteria set up inflammatory responses in the gingiva. J Clin Periodontol. 2005; 32(Suppl 6): 57-71.
Go to original source...
- Gaoni Y, Mechoulam R. Isolation, structure, and partial synthesis of an active constituent of Hashish. J Am Chem Soc. 1964; 86(8): 1646-1647.
Go to original source...
- Mechoulam R, Shvo Y. Hashish I. The structure of cannabidiol. Tetrahedron. 1963; 19(12): 2073-2078.
Go to original source...
Go to PubMed...
- Santavy F. Notes on the structure of cannabidiol compounds. Acta Univ Palacki Olomuc Fac Med. 1964; 35: 5-9.
- Lowe H, Toyang N, Steele B, Bryant J, Ngwa W, Nedamat K. The current and potential application of medicinal cannabis products in dentistry. Dent J (Basel). 2021; 9: 106.
Go to original source...
- Booz GW. Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress. Free Radic Biol Med. 2011; 51(5): 1054-1061.
Go to original source...
- O'Sullivan SE. An update on PPAR activation by cannabinoids. Br J Pharmacol. 2016; 173(12): 1899-1910.
Go to original source...
- Atalay Ekiner S, Gęgotek A, Skrzydlewska E. The molecular activity of cannabidiol in the regulation of Nrf2 system interacting with NF-κB pathway under oxidative stress. Redox Biol. 2022; 57: 102489.
Go to original source...
- Konermann A, Jäger A, Held SAE, Brossart P, Schmöle A. In vivo and in vitro identification of endocannabinoid signaling in periodontal tissues and their potential role in local pathophysiology. Cell Mol Neurobiol. 2017; 37(8): 1511-1520.
Go to original source...
- Jirasek P, Jusku A, Simanek V, Frankova J, Storch J, Vacek J. Cannabidiol and periodontal inflammatory disease: A critical assessment. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2022; 166(2): 155-160.
Go to original source...
Go to PubMed...
- Blaskovich MAT, Kavanagh AM, Elliott AG, Zhang B, Ramu S, Amado M, et al. The antimicrobial potential of cannabidiol. Commun Biol. 2021; 4(1): 7.
Go to original source...
- Karas JA, Wong LJM, Paulin OKA, Mazeh AC, Hussein MH, Li J, et al. The antimicrobial activity of cannabinoids. Antibiotics. 2020; 9(7): 1-10.
Go to original source...
- Gu Z, Singh S, Niyogi RG, Lamont GJ, Wang H, Lamont RJ, et al. Marijuana-derived cannabinoids trigger a CB2/PI3K axis of suppression of the innate response to oral pathogens. Front Immunol. 2019; 10: 2288.
Go to original source...
Go to PubMed...
- Kosgodage US, Matewele P, Awamaria B, Kraev I, Warde P, Mastroianni G, et al. Cannabidiol is a novel modulator of bacterial membrane vesicles. Front Cell Infect Microbiol. 2019; 9: 324.
Go to original source...
Go to PubMed...
- Napimoga MH, Benatti BB, Lima FO, Alves PM, Campos AC, Pena-dos-Santos DR, et al. Cannabidiol decreases bone resorption by inhibiting RANK/RANKL expression and pro-inflammatory cytokines during experimental periodontitis in rats. Int Immunopharmacol. 2009; 9(2): 216-222.
Go to original source...
Go to PubMed...
- Abidi AH, Abhyankar V, Alghamdi SS, Tipton DA, Dabbous M. Phytocannabinoids regulate inflammation in IL-1β-stimulated human gingival fibroblasts. J Periodontal Res. 2022; 57: 1127-1138.
Go to original source...
Go to PubMed...
- Hobbs JM, Vazquez AR, Remijan ND, Trotter RE, McMillan TV, Freedman KE, et al. Evaluation of pharmacokinetics and acute anti-inflammatory potential of two oral cannabidiol preparations in healthy adults. Phytother Res. 2020; 34(7): 1696-1703.
Go to original source...
- Muthumalage T, Rahman I. Cannabidiol differentially regulates basal and LPS-induced inflammatory responses in macrophages, lung epithelial cells, and fibroblasts. Toxicol Appl Pharmacol. 2019; 382: 114713.
Go to original source...
- Rajan TS, Giacoppo S, Iori R, De Nicola GR, Grassi G, Pollastro F, et al. Anti-inflammatory and antioxidant effects of a combination of cannabidiol and moringin in LPS-stimulated macrophages. Fitoterapia. 2016; 112: 104-115.
Go to original source...
Go to PubMed...
- Ruhl T, Kim BS, Beier JP. Cannabidiol restores differentiation capacity of LPS exposed adipose tissue mesenchymal stromal cells. Exp Cell Res. 2018; 370(2): 653-662.
Go to original source...
- Sermet S, Li J, Bach A, Crawford RB, Kaminski NE. Cannabidiol selectively modulates interleukin (IL)-1β and IL-6 production in toll-like receptor activated human peripheral blood monocytes. Toxicology. 2021; 464: 153016.
Go to original source...
- Silva RL, Silveira GT, Wanderlei CW, Cecilio NT, Maganin AGM, Franchin M, et al. DMH-CBD, a cannabidiol analog with reduced cytotoxicity, inhibits TNF production by targeting NF-κB activity dependent on A(2A) receptor. Toxicol Appl Pharmacol. 2019; 368: 63-71.
Go to original source...
- Vacek J, Vostalova J, Papouskova B, Skarupova D, Kos M, Kabelac M, et al. Antioxidant function of phytocannabinoids: Molecular basis of their stability and cytoprotective properties under UV-irradiation. Free Radic Biol Med. 2021; 164: 258-270.
Go to original source...
- CLSI. Methods for antimicrobial susceptibility testing of anaerobic bacteria 9th ed CLSI standard M11 Wayne PA: Clinical and Laboratory Standards Institute. 2018.
- Takahashi N. Oral microbiome metabolism: From "who are they?" to "what are they doing?". J Dent Res. 2015; 94(12): 1628-1637.
Go to original source...
Go to PubMed...
- Rezaei T, Mehramouz B, Gholizadeh P, Yousefi L, Ganbarov K, Ghotaslou R, et al. Factors associated with Streptococcus mutans pathogenicity in the oral cavity. Biointerface Res Appl Chem. 2023; 13(4): 368.
Go to original source...
- Stahl V, Vasudevan K. Comparison of efficacy of cannabinoids versus commercial oral care products in reducing bacterial content from dental plaque: A preliminary observation. Cureus. 2020; 12(1): e6809.
Go to original source...
Go to PubMed...
- Vasudevan K, Stahl V. Cannabinoids infused mouthwash products are as effective as chlorhexidine on inhibition of total-culturable bacterial content in dental plaque samples. J Cannabis Res. 2020; 2(1): 20.
Go to original source...
- Haffajee AD, Yaskell T, Socransky SS. Antimicrobial effectiveness of an herbal mouthrinse compared with an essential oil and a chlorhexidine mouthrinse. J Am Dental Assoc. 2008; 139(5): 606-611.
Go to original source...
- Vacek J. CBD effects on periodontal health of patients with chronic Periodontitis (Stoma-CBD) 2022 August 11 In: ClinicalTrialsgov [Internet] Bethesda (MD): US National Library of Medicine Available from: https://clinicaltrialsgov/ct2/show/NCT05498012 ClinicalTrialsgov Identifier: NCT05498012.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0), which permits non-comercial use, distribution, and reproduction in any medium, provided the original publication is properly cited. No use, distribution or reproduction is permitted which does not comply with these terms.