Cannabidiol and periodontal inflammatory disease: A critical assessment

Petr Jirasek, Alexandr Jusku, Vilim Simanek, Jana Frankova, Jan Storch, Jan Vacek, Petr Jirasek, Alexandr Jusku, Vilim Simanek, Jana Frankova, Jan Storch, Jan Vacek

Abstract

Cannabidiol (CBD), a non-psychotropic cannabinoid produced by the genus Cannabis, is a phytoceutical that activates the endocannabinoid system (ECS) through binding to CB1 and CB2 receptors. The ECS is involved in cellular homeostasis and regulates metabolic processes in virtually all mammalian tissues. Published studies on CBD focus, inter alia, on its use in prophylaxis and as an anti-inflammatory agent. Here the authors present a critical assessment of the effects of CBD on inflammatory periodontal diseases caused by bacterial virulence factors, and evaluate critically the possible benefits and drawbacks of CBD use in dentistry. Particular attention is paid to the interaction of CBD with microbially colonized oral tissues, the inflammatory response in relation to the immune response, and the destruction/regeneration of hard and soft tissues of the periodontium.

Keywords: CB1/2 receptors; bacterial virulence; cannabidiol; endocannabinoid system; gingivitis; immune system; microbial colonisation; periodontitis.

Conflict of interest statement

The authors report no conflicts of interest in this work.

References

    1. Nazir MA. Prevalence of periodontal disease, its association with systemic diseases and prevention. Int J Health Sci (Qassim) 2017;11:72-80.
    1. Guggenheim B, Shapiro SE. Oral biology at the turn of the century: Misconceptions, truths, challenges and prospects, S Karger AG Basel 1998.
    1. Priyanka T, Shalini G, Nymphea P, Radha C, Deepika B. Porphyromonas gingivalis: Its virulence and vaccine. J Int Clin Dent Res Organ 2015;7:51-8.
    1. Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. Lancet 2005;366:1809-20.
    1. Walterova D, Ulrichova J, Valka I, Vicar J, Vavreckova C, Taborska E, Harjrader RJ, Meyer DL, Cerna H, Simanek V. Benzo[c]phenanthridine alkaloids sanguinarine and chelerythrine: biological activities and dental care applications. Acta Univ Palacki Olomuc Fac Med 1995;139:7-16.
    1. Groppo FC, De Cassia Bergamaschi C, Cogo K, Franz-Montan M, Motta RHL, De Andrade ED. Use of phytotherapy in dentistry. Phytother Res 2008;22:993-98.
    1. He Z, Zhang X, Song Z, Li L, Chang H, Li S, Zhou W. Quercetin inhibits virulence properties of Porphyromas gingivalis in periodontal disease. Sci Rep 2020;10:18313.
    1. Petti S, Scully C. Polyphenols, oral health and disease: A review. J Dent 2009;37:413-23.
    1. Shapiro S, Guggenheim B. Chemoprophylaxis in the oral cavity: "plus on change les choses, plus elles devraient rester les memes" Oral Biology at the Turn of the Century. Eds. Guggenheim B, Shapiro S. S. Karger AG. p. 226-238. Zurich. 1998.
    1. Gaoni Y, Mechoulam R. Isolation, Structure, and Partial Synthesis of an Active Constituent of Hashish. J Am Chem Soc 1964;86:1646-47.
    1. Santavy F. Notes on the structure of cannabidiol compounds. Acta Univ Palacki Olomuc Fac Med 1964;35:5-9.
    1. ElSohly MA, Radwan MM, Gul W, Chandra S, Galal A. Phytochemistry of Cannabis sativa L. Prog Chem Org Nat Prod 2017;103:1-36.
    1. White CM. A Review of Human Studies Assessing Cannabidiol's (CBD) Therapeutic Actions and Potential. J Clin Pharmacol 2019;59:923-34.
    1. 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(9):106. doi: 10.3390/dj9090106
    1. Izzo AA, Borrelli F, Capasso R, Di Marzo V, Mechoulam R. Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Trends Pharmacol Sci 2009;30:515-27.
    1. Ye L, Cao Z, Wang W, Zhou N. New Insights in Cannabinoid Receptor Structure and Signaling. Curr Mol Pharmacol 2019;12:239-48.
    1. Silver RJ. The Endocannabinoid System of Animals. Animals (Basel) 2019;9:686.
    1. Navarro G, Gonzalez A, Sánchez-Morales A, Casajuana-Martin N, Gómez-Ventura M, Cordomí A, Busqué F, Alibés R, Pardo L, Franco R. Design of Negative and Positive Allosteric Modulators of the Cannabinoid CB(2) Receptor Derived from the Natural Product Cannabidiol. J Med Chem 2021;64:9354-64.
    1. Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, Gibson D, Mandelbaum A, Etinger A, Mechoulam R. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 1992;258:1946-49.
    1. Mechoulam R, Hanus LO, Pertwee R, Howlett AC. Early phytocannabinoid chemistry to endocannabinoids and beyond. Nat Rev Neurosci 2014;15:757-64.
    1. Di Marzo V. The endocannabinoid system: its general strategy of action, tools for its pharmacological manipulation and potential therapeutic exploitation. Pharmacol Res 2009;60:77-84.
    1. 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;37:1511-20.
    1. Jäger A, Setiawan M, Beins E, Schmidt-Wolf I, Konermann A. Analogous modulation of inflammatory responses by the endocannabinoid system in periodontal ligament cells and microglia. Head Face Med 2020;16:26.
    1. O'Sullivan SE. An update on PPAR activation by cannabinoids. Br J Pharmacol 2016;173:1899-910.
    1. Taskan MM, Gevrek F. PPAR-γ, RXR, VDR, and COX-2 Expressions in gingival tissue samples of healthy individuals, periodontitis and peri-implantitis patients. Niger J Clin Pract 2020;23:46-53.
    1. Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther 2017;2:17023.
    1. Chiu AV, Saigh MA, McCulloch CA, Glogauer M. The Role of NrF2 in the Regulation of Periodontal Health and Disease. J Dent Res 2017;96:975-83.
    1. Atalay S, Jarocka-Karpowicz I, Skrzydlewska E. Antioxidative and Anti-Inflammatory Properties of Cannabidiol. Antioxidants (Basel) 2019;9(1):21. doi: 10.3390/antiox9010021.
    1. Vacek J, Vostalova J, Papouskova B, Skarupova D, Kos M, Kabelac M, Storch J. Antioxidant function of phytocannabinoids: Molecular basis of their stability and cytoprotective properties under UV-irradiation. Free Radic Biol Med 2021;164:258-70.
    1. Rodriguez Mesa XM, Moreno Vergara AF, Contreras Bolanos LA, Guevara Moriones N, Mejia Pineros AL, Santander Gonzalez SP. Therapeutic Prospects of Cannabinoids in the Immunomodulation of Prevalent Autoimmune Diseases. Cannabis Cannabinoid Res 2021;6:196-210.
    1. Gu Z, Singh S, Niyogi RG, Lamont GJ, Wang H, Lamont RJ, Scott DA. Marijuana-Derived Cannabinoids Trigger a CB2/PI3K Axis of Suppression of the Innate Response to Oral Pathogens. Front Immunol 2019;10:2288.
    1. Sing S. Cannabidiol alters the immune response to P. gingivalis in mice. Electronic Theses and Dissertations 2018; Paper 3008. doi: 10.18297/etd/3008
    1. Tolker-Nielsen T. Biofilm Development. Microbiol Spectr 2015;3:Mb-0001-2014.
    1. Zhang Y, Wang X, Li H, Ni C, Du Z, Yan F. Human oral microbiota and its modulation for oral health. Biomed Pharmacother 2018;99:883-93.
    1. Karas JA, Wong LJM, Paulin OKA, Mazeh AC, Hussein MH, Li J, Velkov T. The antimicrobial activity of cannabinoids. Antibiotics 2020;9:1-10.
    1. Appendino G, Gibbons S, Giana A, Pagani A, Grassi G, Stavri M, Smith E, Rahman MM. Antibacterial cannabinoids from Cannabis sativa: a structure-activity study. J Nat Prod 2008;71:1427-30.
    1. Martinenghi LD, Jønsson R, Lund T, Jenssen H. Isolation, Purification, and Antimicrobial Characterization of Cannabidiolic Acid and Cannabidiol from Cannabis sativa L. Biomolecules 2020;10:900.
    1. Blaskovich MAT, Kavanagh AM, Elliott AG, Zhang B, Ramu S, Amado M, Lowe GJ, Hinton AO, Pham DMT, Zuegg J, Beare N, Quach D, Sharp MD, Pogliano J, Rogers AP, Lyras D, Tan L, West NP, Crawford DW, Peterson ML, Callahan M, Thurn M. The antimicrobial potential of cannabidiol. Commun Biol 2021;4:7.
    1. Kosgodage US, Matewele P, Awamaria B, Kraev I, Warde P, Mastroianni G, Nunn AV, Guy GW, Bell JD, Inal JM, Lange S. Cannabidiol Is a Novel Modulator of Bacterial Membrane Vesicles. Front Cell Infect Microbiol 2019;9:324.
    1. Rawal SY, Dabbous MK, Tipton DA. Effect of cannabidiol on human gingival fibroblast extracellular matrix metabolism: MMP production and activity, and production of fibronectin and transforming growth factor β. J Periodont Res 2012;47:320-29.
    1. Hobbs JM, Vazquez AR, Remijan ND, Trotter RE, McMillan TV, Freedman KE, Wei Y, Woelfel KA, Arnold OR, Wolfe LM, Johnson SA, Weir TL. Evaluation of pharmacokinetics and acute anti-inflammatory potential of two oral cannabidiol preparations in healthy adults. Phytother Res 2020;34:1696-703.
    1. 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.
    1. Rajan TS, Giacoppo S, Iori R, De Nicola GR, Grassi G, Pollastro F, Bramanti P, Mazzon E. Anti-inflammatory and antioxidant effects of a combination of cannabidiol and moringin in LPS-stimulated macrophages. Fitoterapia 2016;112:104-15.
    1. Ruhl T, Kim BS, Beier JP. Cannabidiol restores differentiation capacity of LPS exposed adipose tissue mesenchymal stromal cells. Exp Cell Res 2018;370:653-62.
    1. 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.
    1. Silva RL, Silveira GT, Wanderlei CW, Cecilio NT, Maganin AGM, Franchin M, Marques LMM, Lopes NP, Crippa JA, Guimarães FS, Alves-Filho JCF, Cunha FQ, Cunha TM. DMH-CBD, a cannabidiol analog with reduced cytotoxicity, inhibits TNF production by targeting NF-kB activity dependent on A(2A) receptor. Toxicol Appl Pharmacol 2019;368:63-71.
    1. Graves DT, Kang J, Andriankaja O, Wada K, Rossa C, Jr. Animal models to study host-bacteria interactions involved in periodontitis. Front Oral Biol 2012;15:117-32.
    1. Napimoga MH, Benatti BB, Lima FO, Alves PM, Campos AC, Pena-dos-Santos DR, Severino FP, Cunha FQ, Guimarães FS. Cannabidiol decreases bone resorption by inhibiting RANK/RANKL expression and pro-inflammatory cytokines during experimental periodontitis in rats. Int Immunopharmacol 2009;9:216-22.
    1. Klein M, Salum FG, Cherubini K, de Figueiredo MAZ. Cannabidiol as a novel therapeutic strategy for oral inflammatory diseases: A review of current knowledge and future perspectives. Altern Ther Health Med 2020;26:12-16.
    1. 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:e6809-e09.
    1. 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;2:20.
    1. Libro R, Scionti D, Diomede F, Marchisio M, Grassi G, Pollastro F, Piattelli A, Bramanti P, Mazzon E, Trubiani O. Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol 2016;7:559.

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