PERİODONTOLOJİDE KANNABİONİDLERİN ROLÜ

Abstract

İnsanlık tarihi boyunca çeşitli özelliklerinden yararlanılan kenevir, dioik, çiçekli ve otsu bir bitki türüdür. Kenevir tekstil alanında, otomotiv sektöründe, uzay sanayisinde, ilaç ve gıda desteği üretimi gibi alanlarda olmak üzere geniş bir kullanım alanına sahiptir. Milattan önceki döneme kadar dayanan medikal kenevir kullanımı 1940’lı yıllara kadar devam etmiş; ancak daha sonraki yıllarda psikoaktif içeriğinin suistimal edilmesi nedeniyle birçok ülkede yasaklanmaya başlamıştır. Nükleer manyetik rezonans spektroskopisinin geliştirilmesi ile kenevirin öforik etkisinden sorumlu ana bileşen olarak tetrahidrokannabiolün kimyasal yapısı ve içeriği sonrasında ise kannabionid reseptörler ve endokannabionidler ile endokannabionid enzimlerin yapısı ve içeriği keşfedilmiştir. Kannabionid terimi insan vücudunda yer alan kannabionid reseptörlerine bağlanabilen, kenevirden üretilen fitokannabionidleri, insan vücudunda üretilen endokannabionidleri ve sentetik olarak elde edilen kannabionidleri kapsayan bir terimdir. Endokannabionid sistem ise transmembran endokannabionid reseptörleri, endojen ligandları, spesifik alım mekanizmalarını, biyosentezi ve yıkımı ile ilgili enzimatik sistemleri içeren karmaşık bir hücre sinyalizasyon sistemi olarak tanımlanmıştır. Endokannabionid sistem ve kannabionidler arasındaki etkileşimlerin incelenmesi periodontal hastalıkların terapötik tedavisinde ve önlenmesinde yeni fikirlerin ortaya çıkmasını sağlamıştır. Sonuç olarak yapılan çalışmalar endokannabionid sistemin ve kannabionid türlerinin oral dokuları ve hücreleri etkileyen durumların patogenezinde ve tedavisinde önemli bir role sahip olduğunu kanıtlamaktadır. Endokannabinoid sistemin enflamatuar yanıtı düzenleyebileceği ve enflamasyon ilerlemesini durdurabileceği ortaya konmuştur. Mevcut veriler periodontitis hastalarında terapötik uygulamalar için bir seçenek olarak kannabionidlerin kullanımını desteklemektedir.

Keywords

• Kenevir
• Periodontitis
• HU-308
• Kannabidiol
• Endokannabionid Sistem

THE ROLE OF CANNABIONIDES IN PERIODONTOLOGY

Abstract

Hemp is a dioecious, flowering, and herbaceous plant species that has been utilized throughout human history for various properties and has a wide range of applications including the textile industry, automotive sector, aerospace, pharmaceuticals, and food supplements. The medical use of hemp dates back to the pre-Christian era and continued until the 1940s. However, due to the abuse of its psychoactive components, it has been banned in many countries. With the development of nuclear magnetic resonance spectroscopy, the chemical structure and composition of tetrahydrocannabinol, the primary component responsible for the euphoric effect of hemp, were identified. Subsequently, cannabinoid receptors, endocannabinoids, and enzymes involved in the endocannabinoid system were discovered. The term cannabinoid encompasses phytocannabinoids derived from hemp, endocannabinoids produced in the human body, and synthetic cannabinoids, all of which can bind to cannabinoid receptors in the human body. The endocannabinoid system is defined as a complex cellular signaling system comprising transmembrane cannabinoid receptors, endogenous ligands, specific uptake mechanisms, biosynthesis, and enzymatic degradation systems. The study of the interaction between the endocannabinoid system and cannabinoids has inspired new perspectives for the treatment and prevention of periodontal diseases. As a result, current research demonstrates that the endocannabinoid system and various types of cannabinoids play a significant role in the pathogenesis and treatment of conditions affecting oral tissues and cells. It has been shown that the endocannabinoid system may regulate inflammatory responses and halt the inflammation progression. Existing data support the therapeutic use of cannabinoids as a potential option for patients with periodontitis.

Keywords

• Hemp
• Periodontitis
• HU-308
• Cannnabidiol

Supporting Institution

Bulunmamaktadır

Ethical Statement

Literatürden alınan tüm bilgilerin, kaynakça göstererek kaynaklar bölümüne eklendiğini ve etik ilkelere uygun hazırlandığını taahhüt ederiz.

Thanks

Bulunmamaktadır

References

1. 1. Anderson LC. Leaf variation among Cannabis species from a controlled garden. Botanical Museum Leaflets, Harvard University. 1980;28(1):61-69.
2. 2. Schultes RE, Klein WM, Plowman T, Lockwood TE. Cannabis: an example of taxonomic neglect. Botanical Museum Leaflets, Harvard University. 1974;23(9):337-367.
3. 3. Visković J, Zheljazkov VD, Sikora V, Noller J, Latković D, Ocamb CM, et al. Industrial Hemp (Cannabis sativa) Agronomy and Utilization: A Review. Agronomy. 2023;13(3):931. doi:10.3390/agronomy13030931.
4. 4. Khan BA, Wang J, Warner P, Wang H. Antibacterial properties of hemp hurd powder against E coli. J Appl Polym Sci. 2015;132:41588. doi:10.1002/app.41588.
5. 5. Ryz NR, Remillard DJ, Russo EB. Cannabis Roots: A Traditional Therapy with Future Potential for Treating Inflammation and Pain. Cannabis Cannabinoid Res. 2017;1;2(1):210-216. doi:10.1089/can.2017.0028. PMID: 29082318.
6. 6. Ulugöl A. Kannabis bitkisi ve kannabinoidlere giriş. Turkiye Klinikleri Pharmacology Special Topics. 2018;6(1):1-5.
7. 7. Gaoni Y, Mechoulam R. Isolation, structure, and partial synthesis of an active constituent of hashish. Journal of the American chemical society. 1964;86(8):1646-1647. doi:10.1021/ja01062a046
8. 8. Elias R, Raheb M, Istasy M, Mekhaiel D, Sidhu G, Warren D, et al. Knowledge of cannabinoids among patients, physicians, and pharmacists. Archives of Psychiatry and Behavioral Sciences. 2019;2(1):25-28.

9. 9. Holdman R, Vigil D, Robinson K, Shah P, Contreras AE. Safety and Efficacy of Medical Cannabis in Autism Spectrum Disorder Compared with Commonly Used Medications. Cannabis Cannabinoid Res. 2022;7(4):451-463. doi:10.1089/can.2020.0154. PMID: 34432543.
10. 10. Chen Q, Liu X, Wang D, Zheng J, Chen L, Xie Q, et al. Periodontal Inflammation-Triggered by Periodontal Ligament Stem Cell Pyroptosis Exacerbates Periodontitis. Front Cell Dev Biol. 2021;1(9):663037. doi:10.3389/fcell.2021.663037. PMID: 33869229.
11. 11. 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(6):1127- 1138. doi:10.1111/jre.13050. PMID: 36070347.
12. 12. Karas JA, Wong LJM, Paulin OKA, Mazeh AC, Hussein MH, Li J, et al. The Antimicrobial Activity of Cannabinoids. Antibiotics. 2020;9(7):406. doi: 10.3390/antibiotics9070406. PMID: 32668669.
13. 13. Haney A, Kutscheid BB. Quantitative variation in the chemical constituents of marihuana from stands of naturalized Cannabis sativa L. in East-Central Illinois. Economic Botany. 1973;27(2):193- 203.
14. 14. Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9- tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol. 2008;153(2):199-215. doi:10.1038/sj.bjp.0707442. PMID: 17828291.
15. 15. Le Boisselier R, Alexandre J, Lelong-Boulouard V, Debruyne D. Focus on cannabinoids and synthetic cannabinoids. Clin Pharmacol Ther. 2017;101(2):220-229. doi:10.1002/cpt.563. PMID: 27861784.
16. 16. 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;1;33(2):143-152. PMID: 32920617.
17. 17. Smeriglio A, Giofrè SV, Galati EM, Monforte MT, Cicero N, D'Angelo V, et al. Inhibition of aldose reductase activity by Cannabis sativa chemotypes extracts with high content of cannabidiol or cannabigerol. Fitoterapia. 2018;127:101-108. doi:10.1016/j.fitote.2018.02.002. PMID: 29427593.
18. 18. Romano B, Borrelli F, Fasolino I, Capasso R, Piscitelli F, Cascio M, et al. The cannabinoid TRPA1 agonist cannabichromene inhibits nitric oxide production in macrophages and ameliorates murine colitis. Br J Pharmacol. 2013;169(1):213-29. doi:10.1111/bph.12120. PMID: 23373571.
19. 19. Consroe P, Sandyk R, Snider SR. Open label evaluation of cannabidiol in dystonic movement disorders. Int J Neurosci. 1986;30(4):277-82. doi:10.3109/00207458608985678. PMID: 3793381.
20. 20. Abu-Sawwa R, Scutt B, Park Y. Emerging Use of Epidiolex (Cannabidiol) in Epilepsy. J Pediatr Pharmacol Ther. 2020;25(6):485-499. doi:10.5863/1551-6776-25.6.485. PMID: 32839652.
21. 21. Abi-Jaoude E, Chen L, Cheung P, Bhikram T, Sandor P. Preliminary Evidence on Cannabis Effectiveness and Tolerability for Adults With Tourette Syndrome. J Neuropsychiatry Clin Neurosci. 2017;29(4):391-400. doi:10.1176/appi.neuropsych.16110310. PMID: 28464701.
22. 22. Romano B, Pagano E, Orlando P, Capasso R, Cascio MG, Pertwee R, et al. Pure Δ 9-tetrahydrocannabivarin and a Cannabis sativa extract with high content in Δ9-tetrahydrocannabivarin inhibit nitrite production in murine peritoneal macrophages. Pharmacol Res. 2016;113(PtA):199-208. doi:10.1016/j.phrs.2016.07.045. PMID: 27498155.
23. 23. Kisková T, Mungenast F, Suváková M, Jäger W, Thalhammer T. Future Aspects for Cannabinoids in Breast Cancer Therapy. Int J Mol Sci. 2019;3;20(7):1673. doi:10.3390/ijms20071673. PMID: 30987191.
24. 24. Patil AS, Mahajan UB, Agrawal YO, Patil KR, Patil CR, Ojha S, et al. Plant-derived natural therapeutics targeting cannabinoid receptors in metabolic syndrome and its complications: A review. Biomed Pharmacother. 2020;132:110889. doi:10.1016/j.biopha.2020.110889. PMID: 33113429.
25. 25. Ryberg E, Larsson N, Sjögren S, Hjorth S, Hermansson NO, Leonova J, et al. The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol. 2007;152(7):1092-101. doi:10.1038/sj.bjp.0707460. PMID: 17876302.
26. 26. Battista N, Di Tommaso M, Bari M, Maccarrone M. The endocannabinoid system: an overview. Front Behav Neurosci. 2012;14;6:9. doi: 10.3389/fnbeh.2012.00009. PMID: 22457644.
27. 27. Di Marzo V, De Petrocellis L. Why do cannabinoid receptors have more than one endogenous ligand? Philos Trans R Soc Lond B Biol Sci. 2012;5;367(1607):3216-28. doi:10.1098/rstb.2011.0382. PMID: 23108541.
28. 28. Greineisen WE, Turner H. Immunoactive effects of cannabinoids: considerations for the therapeutic use of cannabinoid receptor agonists and antagonists. Int Immunopharmacol. 2010;10(5):547-55. doi:10.1016/j.intimp.2010.02.012. PMID: 20219697.
29. 29. Ribeiro A, Almeida VI, Costola-de-Souza C, Ferraz-de-Paula V, Pinheiro ML, Vitoretti LB, et al. Cannabidiol improves lung function and inflammation in mice submitted to LPS-induced acute lung injury. Immunopharmacol Immunotoxicol. 2015;37(1):35-41. doi:10.3109/08923973.2014.976794. PMID: 25356537.
30. 30. Vuolo F, Petronilho F, Sonai B, Ritter C, Hallak JE, Zuardi AW, et al. Evaluation of Serum Cytokines Levels and the Role of Cannabidiol Treatment in Animal Model of Asthma. Mediators Inflamm. 2015;2015:538670. doi:10.1155/2015/538670. PMID: 26101464.
31. 31. Demuth DG, Molleman A. Cannabinoid signalling. Life Sci. 2006;2;78(6):549-63. doi:10.1016/j.lfs.2005.05.055. PMID: 16109430.
32. 32. Kozela E, Lev N, Kaushansky N, Eilam R, Rimmerman N, Levy R, et al. Cannabidiol inhibits pathogenic T cells, decreases spinal microglial activation and ameliorates multiple sclerosis-like disease in C57BL/6 mice. Br J Pharmacol. 2011;163(7):1507-19. doi:10.1111/j.1476- 5381.2011.01379.x. PMID: 21449980.
33. 33. Maccarrone M, Di Rienzo M, Battista N, Gasperi V, Guerrieri P, Rossi A, et al. The endocannabinoid system in human keratinocytes. Evidence that anandamide inhibits epidermal differentiation through CB1 receptor-dependent inhibition of protein kinase C, activation protein-1, and transglutaminase. J Biol Chem. 2003;5;278(36):33896-903. doi:10.1074/jbc.M303994200. PMID: 12815050.
34. 34. Theocharis S, Giaginis C, Alexandrou P, Rodriguez J, Tasoulas J, Danas E, et al. Evaluation of cannabinoid CB1 and CB2 receptors expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients' survival. Tumour Biol. 2016;37(3):3647-56. doi:10.1007/s13277-015-4182-8. PMID: 26459312.
35. 35. Pereira SR, Tello Velasquez J, Duggan S, Ivanisevic B, McKenna JP, McCreary C, et al. Recent advances in the understanding of the aetiology and therapeutic strategies in burning mouth syndrome: Focus on the actions of cannabinoids. Eur J Neurosci. 2022;55(4):1032-1050. doi:10.1111/ejn.14712. PMID: 32091630.
36. 36. Zamith Cunha R, Grilli E, Piva A, Delprete C, Franciosi C, Caprini M, et al. The Expression of Cannabinoid and Cannabinoid-Related Receptors on the Gustatory Cells of the Piglet Tongue. Molecules. 2024;28;29(19):4613. doi:10.3390/molecules29194613. PMID: 39407543.
37. 37. Pertwee RG, Howlett AC, Abood ME, Alexander SP, Di Marzo V, Elphick MR, et al. International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB₁ and CB₂. Pharmacol Rev. 2010;62(4):588-631. doi:10.1124/pr.110.003004. PMID: 21079038.
38. 38. Pirino C, Cappai MG, Maranesi M, Tomassoni D, Giontella A, Pinna W, et al. The presence and distribution of cannabinoid type 1 and 2 receptors in the mandibular gland: The influence of different physical forms of diets on their expression in piglets. J Anim Physiol Anim Nutr (Berl). 2018;102(2):870-876. doi:10.1111/jpn.12848. PMID: 29218862.
39. 39. 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;16;394(4):928-33. doi:10.1016/j.bbrc.2010.03.080. PMID: 20233580.
40. 40. 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. doi:10.1007/s10571-017-0482-4. PMID: 28289947.
41. 41. 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:10.1902/jop.2016.150612. PMID: 26846967.
42. 42. Özdemir B, Shi B, Bantleon HP, Moritz A, Rausch-Fan X, Andrukhov O. Endocannabinoids and inflammatory response in periodontal ligament cells. PLoS One. 2014;16;9(9):107407. doi:10.1371/journal.pone.0107407. PMID: 25226300.
43. 43. 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;15;10:2288. doi:10.3389/fimmu.2019.02288. PMID: 31681262.
44. 44. Feldman M, Sionov RV, Mechoulam R, Steinberg D. Anti-Biofilm Activity of Cannabidiol against Candida albicans. Microorganisms. 2021;20;9(2):441. doi:10.3390/microorganisms9020441. PMID: 33672633.
45. 45. 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;29;12(1):6809. doi:10.7759/cureus.6809. PMID: 32038896.
46. 46. 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;23;2(1):20. doi:10.1186/s42238-020-00027-z. PMID: 33526124.
47. 47. Blaskovich MAT, Kavanagh AM, Elliott AG, Zhang B, Ramu S, Amado M, et al. The antimicrobial potential of cannabidiol. Commun Biol. 2021;19;4(1):7. doi:10.1038/s42003-020-01530-y. PMID: 33469147.
48. 48. Abidi AH, Presley CS, Dabbous M, Tipton DA, Mustafa SM, Moore BM 2nd. Anti-inflammatory activity of cannabinoid receptor 2 ligands in primary hPDL fibroblasts. Arch Oral Biol. 2018;87:79- 85. doi:10.1016/j.archoralbio.2017.12.005. PMID: 29274621.
49. 49. 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):1264-1272. doi:10.1111/jcpe.13190. PMID: 31461164.
50. 50. 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:10.1016/j.ebiom.2021.103769. PMID: 34954656.
51. 51. Chen H, Liu Y, Yu S, Li C, Gao B, Zhou X. Cannabidiol attenuates periodontal inflammation through inhibiting TLR4/NF-κB pathway. J Periodontal Res. 2023;58(4):697-707. doi:10.1111/jre.13118. PMID: 37143211.
52. 52. Garcia-Ovejero D, Arevalo-Martin A, Petrosino S, Docagne F, Hagen C, Bisogno T, et al. The endocannabinoid system is modulated in response to spinal cord injury in rats. Neurobiol Dis. 2009;33(1):57-71. doi:10.1016/j.nbd.2008.09.015. PMID: 18930143.
53. 53. 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 proinflammatory cytokines during experimental periodontitis in rats. Int Immunopharmacol. 2009;9(2):216-22. doi:10.1016/j.intimp.2008.11.010. PMID: 19070683.
54. 54. Ofek O, Karsak M, Leclerc N, Fogel M, Frenkel B, Wright K, et al. Peripheral cannabinoid receptor, CB2, regulates bone mass. Proc Natl Acad Sci USA. 2006;17;103(3):696-701. doi:10.1073/pnas.0504187103. PMID:16407142;
55. 55. 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- 1335. doi:10.1002/JPER.18-0766. PMID: 31077362.
56. 56. 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;21;13(1):22. doi: 10.1186/s13287-022-02702-9. PMID: 35063024.
57. 57. Petrescu NB, Jurj A, Sorițău O, Lucaciu OP, Dirzu N, Raduly L, et al. Cannabidiol and Vitamin D3 Impact on Osteogenic Differentiation of Human Dental Mesenchymal Stem Cells. Medicina (Kaunas). 2020;12;56(11):607. doi:10.3390/medicina56110607. PMID: 33198232.
58. 58. Libro R, Scionti D, Diomede F, Marchisio M, Grassi G, Pollastro F, et al. Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016;24(7):559. doi:10.3389/fphys.2016.00559. PMID: 27932991
59. 59. 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. 2012;47(3):320-9. doi:10.1111/j.1600- 0765.2011.01435.x. PMID: 22092062.
60. 60. 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):215-222. doi:10.1016/j.ajodo.2021.07.012. PMID: 34924285.