Effects and clinical application of cannabinoids for the treatment of periodontal disease: a systematic review
DOI:
https://doi.org/10.17533/udea.rfo.v36n1a7Keywords:
cannabis, cannabinoids, cannabidiol, periodontitis, periodontal diseasesAbstract
Introduction: cannabinoids have a wide range of biological effects and are currently used for therapeutic purposes in modern medicine. The objective was to determine the effects and clinical application of cannabinoids as a therapeutic alternative for periodontal disease. Methods: we conducted a systematic review following the Cochrane manual for systematic reviews' recommendations to address the following inquiries: 1) What is the impact of non-surgical therapy with cannabidiol compared to conventional non-surgical therapy on the level of insertion in patients with periodontal disease? 2) What are the potential biological and microbiological effects of cannabinoids in the treatment of periodontal disease? The primary outcome was changes in the periodontal attachment level (CAL) and secondary outcomes included changes in probing depth (PD), changes in bleeding on probing (BoP), report of adverse effects and microbiological and biological effects. Results: out of 59 potential studies, 26 were excluded in the initial screening, and 33 full-text studies underwent further review. Among these, 13 were excluded for not meeting the selection criteria, resulting in 20 studies included in the qualitative synthesis. Notably, only one highly biased human clinical study was identified. In vitro and animal studies demonstrated that cannabinoids possess bactericidal properties, anti-inflammatory potential, and modulating activity on periodontal bone resorption. Conclusions: the available scientific evidence is scarce to recommend the use of cannabis derivatives for the treatment of periodontal disease. Despite promising findings in preclinical studies indicating therapeutic potential, further investigation is required to assess its application in human subjects.
Downloads
References
Un alto porcentaje de la población mundial padece la enfermedad periodontal [Website]. México: ANUIES – Asociación Nacional de Universidades e Instituciones de Educación Superior; 2005. Available in: https://bit.ly/49zmqzd
Trindade D, Carvalho R, Machado V, Chambrone L, Mendes JJ, Botelho J. Prevalence of periodontitis in dentate people between 2011 and 2020: a systematic review and meta-analysis of epidemiological studies. J Clin Periodontol. 2023; 50(5): 604-26. DOI: https://doi.org/10.1111/jcpe.13769
FDI World Dental Federation. Salud y enfermedades periodontales: guía práctica para reducir la carga mundial de morbilidad para las enfermedades periodontales. FDI World Dental Federation; 2018. Available in: https://www.fdiworlddental.org/sites/default/files/2020-11/gphp-2018-toolkit-es.pdf
Marcenes W, Kassebaum NJ, Bernabé E, Flaxman A, Naghavi M, Lopez A et al. Global burden of oral conditions in 1990-2010: a systematic analysis. J Dent Res. 2013; 92(7): 592–7. https://doi.org/10.1177/0022034513490168
Ángeles Lopez GE, Brindis F, Niizawa SC, Ventura Martínez R. Cannabis sativa L., a singular plant. Rev mex cienc farm. 2014; 45(4).
Jones É, Vlachou S. A critical review of the role of the cannabinoid compounds Δ9-Tetrahydrocannabinol (Δ9-THC) and Cannabidiol (CBD) and their combination in multiple sclerosis treatment. Molecules. 2020; 25(21): 4930. DOI: https://doi.org/10.3390/molecules25214930
Appendino G, Gibbons S, Giana A, Pagani A, Grassi G, Stavri M et al. Antibacterial cannabinoids from Cannabis sativa: a structure-activity study. J Nat Prod. 2008; 71(8): 1427–30. DOI: https://doi.org/10.1021/np8002673
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. cellular and molecular neurobiology. Cell Mol Neurobiol. 2017. 37: 1511–20. https://doi.org/10.1007/s10571-017-0482-4
Ossola CA, Balcarcel NB, Astrauskas JI, Bozzini C, Elverdin JC, Fernández-Solari J. A new target to ameliorate the damage of periodontal disease: the role of transient receptor potential vanilloid type-1 in contrast to that of specific cannabinoid receptors in rats. J Periodontol. 2019; 90(11): 1325–35. DOI: https://doi.org/10.1002/JPER.18-0766
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. DOI: https://doi.org/10.3389/fimmu.2019.02288
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. DOI: https://doi.org/10.1186/s13005-020-00244-0
Alvarez X, Sestak K, Byrareddy SN, Mohan M. Long term Delta-9-tetrahydrocannabinol administration inhibits proinflammatory responses in minor salivary glands of chronically simian immunodeficieny virus infected rhesus macaques. Viruses. 2020; 12(7), 713. DOI: https://doi.org/10.3390/v12070713
Lowe H, Toyang N, Steele B, Bryant J, Ngwa W, Nedamat K. The current and potential application of medicinal cannabis products in dentistry. Denti J. 2021; 9(9): 106 DOI: https://doi.org/10.3390/dj9090106
Lowe H, SteeleB, Bryant J, Toyang N, Ngwa W. Non-Cannabinoid Metabolites of Cannabis sativa L. with Therapeutic potential. Plants (Basel). 2021; 10(2): 400. DOI: https://doi.org/10.3390/plants10020400
Lowe H, Toyang N, Steele B, Bryant J, Ngwa W. The Endocannabinoid system: a potential target for the treatment of various diseases. Int J Mol Sci. 2021; 22(17): 9472. DOI: https://doi.org/10.3390/ijms22179472
Blaskovich MAT, Kavanagh AM, Elliott AG, Zhang B, Ramu S, Amado M et al. The antimicrobial potential of cannabidiol. Commun Biol. 2021; 4: 7. DOI: https://doi.org/10.1038/s42003-020-01530-y
Qi X, Liu C, Li G, Al-Alfe D, Paurazas S, Askar M et al. Evaluation of Cannabinoids on the odonto/osteogenesis in human dental pulp cells in vitro. J Endod. 2021; 47(3): 444–50. DOI: https://doi.org/10.1016/j.joen.2020.12.005
Aqawi M, Sionov RV, Gallily R, Friedman M, Steinberg D. Anti-Biofilm activity of cannabigerol against streptococcus mutans. Microorganisms. 2021; 9(10): 2031. DOI: https://doi.org/10.3390/microorganisms9102031
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. DOI: https://doi.org/10.5507/bp.2022.012
Yan W, Li L, Ge L, Zhang F, Fan Z, Hu L. The cannabinoid receptor I (CB1) enhanced the osteogenic differentiation of BMSCs by rescue impaired mitochondrial metabolism function under inflammatory condition. Stem Cell Res Ther. 2022; 13: 22. DOI: https://doi.org/10.1186/s13287-022-02702-9
Vasudevan K, Stahl V. CBD-supplemented polishing powder enhances tooth polishing by inhibiting dental plaque bacteria. J Int Soc Prev Community Dent. 2020; 10(6): 766–70. DOI: https://doi.org/10.4103/jispcd.JISPCD_351_20
Nakajima Y, Furuichi Y, Biswas KK, Hashiguchi T, Kawahara K, Yamaji K et al. Endocannabinoid, anandamide in gingival tissue regulates the periodontal inflammation through NF-kappaB pathway inhibition. FEBS lett. 2006; 580(2): 613–9. DOI: https://doi.org/10.1016/j.febslet.2005.12.079
Özdemir B, Shi B, Bantleon HP, Moritz A, Rausch-Fan X, Andrukhov O. Endocannabinoids and inflammatory response in periodontal ligament cells. PloS One. 2014; 9(9): e107407. DOI: https://doi.org/10.1371/journal.pone.0107407
Abidi AH, Presley CS, Dabbous M, Tipton DA, Mustafa SM, Moore BM. Anti-inflammatory activity of cannabinoid receptor 2 ligands in primary hPDL fibroblasts. Arch Oral Biol. 201; 87: 79–85. DOI: https://doi.org/10.1016/j.archoralbio.2017.12.005
Abidi AH, Alghamdi SS, Dabbous MK, Tipton DA, Mustafa SM, Moore BM. Cannabinoid type-2 receptor agonist, inverse agonist, and anandamide regulation of inflammatory responses in IL-1β stimulated primary human periodontal ligament fibroblasts. J Periodontal Res. 2020; 55(5): 762–83. DOI: https://doi.org/10.1111/jre.12765
Zhang F, Özdemir B, Nguyen PQ, Andrukhov O, Rausch-Fan X. Methanandamide diminish the Porphyromonas gingivalis lipopolysaccharide induced response in human periodontal ligament cells. BMC oral health. 2020; 20(1): 107. DOI: https://doi.org/10.1186/s12903-020-01087-6
Qian H, Zhao Y, Peng Y, Han C, Li S, Huo N et al. Activation of cannabinoid receptor CB2 regulates osteogenic and osteoclastogenic gene expression in human periodontal ligament cells. J Periodontal Res. 2010; 45(4): 504–11. DOI: https://doi.org/10.1111/j.1600-0765.2009.01265.x
Yan W, Cao Y, Yang H, Han N, Zhu X, Fan Z et al. CB1 enhanced the osteo/dentinogenic differentiation ability of periodontal ligament stem cells via p38 MAPK and JNK in an inflammatory environment. Cell Prolif. 2019; 52(6): e12691. DOI: https://doi.org/10.1111/cpr.12691
Kozono S, Matsuyama T, Biwasa KK, Kawahara K, Nakajima Y, Yoshimoto T, et al. Involvement of the endocannabinoid system in periodontal healing. Biochem Biophys Res Commun. 2010; 394(4): 928-33. DOI: https://doi.org/10.1016/j.bbrc.2010.03.080
Lanza Cariccio V, Scionti D, Raffa A, Iori R, Pollastro F, Diomede F et al. Treatment of periodontal ligament stem cells with MOR and CBD Promotes cell survival and neuronal differentiation via the PI3K/Akt/mTOR pathway. Int J Mol Sci. 2018; 19(8): 2341. DOI: https://doi.org/10.3390/ijms19082341
Rawal SY, Dabbous MKh, 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 Periodontal Res. 2011; 47(3): 320–9. DOI: https://doi.org/10.1111/j.1600-0765.2011.01435.x
Liu C, Qi X, Alhabeil J, Lu H, Zhou Z. Activation of cannabinoid receptors promote periodontal cell adhesion and migration. J Clin Periodontol. 2019; 46(12): 1264–72. DOI: https://doi.org/10.1111/jcpe.13190
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. DOI: https://doi.org/10.7759/cureus.6809
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. DOI: https://doi.org/10.1186/s42238-020-00027-z
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): 216–22. DOI: https://doi.org/10.1016/j.intimp.2008.11.010
Ossola CA, Surkin PN, Pugnaloni A, Mohn CE, Elverdin JC, Fernandez-Solari J. Long-term treatment with methanandamide attenuates LPS-induced periodontitis in rats. Inflamm Res. 2012; 61: 941–8. DOI: https://doi.org/10.1007/s00011-012-0485-z
Ossola CA, Surkin PN, Mohn CE, Elverdin JC, Fernández-Solari J. Anti-Inflammatory and osteoprotective effects of Cannabinoid-2 receptor agonist HU-308 in a rat model of lipopolysaccharide-induced periodontitis. J Periodontol. 2016; 87(6): 725–34. DOI: https://doi.org/10.1902/jop.2016.150612
Ossola CA, Rodas JA, Balcarcel NB, Astrauskas JI, Elverdin JC, Fernández-Solari J. Signs of alveolar bone damage in early stages of periodontitis and its prevention by stimulation of cannabinoid receptor 2: model in rats. Acta Odontol Latinoam. 2020; 33(2): 143–52.
Klein KP, Guastaldi FPS, Pereira HSG, He Y, Lukas SE. Dronabinol inhibits alveolar bone remodeling in tooth movement of rats. Am J Orthod Dentofacial Orthop. 2022; 161(3): e215–22. DOI: https://doi.org/10.1016/j.ajodo.2021.07.012
McDew-White M, Lee E, Alvarez X, Sestak K, Ling BJ, Byrareddy SN et al. Cannabinoid control of gingival immune activation in chronically SIV-infected rhesus macaques involves modulation of the indoleamine-2,3-dioxygenase-1 pathway and salivary microbiome. EBioMedicine. 2022; 75: 103769. DOI: https://doi.org/10.1016/j.ebiom.2021.103769
Downloads
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2024 Revista Facultad de Odontología Universidad de Antioquia
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Copyright Notice
Copyright comprises moral and patrimonial rights.
1. Moral rights: are born at the moment of the creation of the work, without the need to register it. They belong to the author in a personal and unrelinquishable manner; also, they are imprescriptible, unalienable and non negotiable. Moral rights are the right to paternity of the work, the right to integrity of the work, the right to maintain the work unedited or to publish it under a pseudonym or anonymously, the right to modify the work, the right to repent and, the right to be mentioned, in accordance with the definitions established in article 40 of Intellectual property bylaws of the Universidad (RECTORAL RESOLUTION 21231 of 2005).
2. Patrimonial rights: they consist of the capacity of financially dispose and benefit from the work trough any mean. Also, the patrimonial rights are relinquishable, attachable, prescriptive, temporary and transmissible, and they are caused with the publication or divulgation of the work. To the effect of publication of articles in the journal Revista de la Facultad de Odontología, it is understood that Universidad de Antioquia is the owner of the patrimonial rights of the contents of the publication.
The content of the publications is the exclusive responsibility of the authors. Neither the printing press, nor the editors, nor the Editorial Board will be responsible for the use of the information contained in the articles.
I, we, the author(s), and through me (us), the Entity for which I, am (are) working, hereby transfer in a total and definitive manner and without any limitation, to the Revista Facultad de Odontología Universidad de Antioquia, the patrimonial rights corresponding to the article presented for physical and digital publication. I also declare that neither this article, nor part of it has been published in another journal.
Open Access Policy
The articles published in our Journal are fully open access, as we consider that providing the public with free access to research contributes to a greater global exchange of knowledge.
Creative Commons License
The Journal offers its content to third parties without any kind of economic compensation or embargo on the articles. Articles are published under the terms of a Creative Commons license, known as Attribution – NonCommercial – Share Alike (BY-NC-SA), which permits use, distribution and reproduction in any medium, provided that the original work is properly cited and that the new productions are licensed under the same conditions.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.