Abstract
The study was evaluated the impact of cannabidiol (CBD) on thyroid hormones by modulation cannabinoid receptor-2 (CB2) and vitamin D receptor (VDR) in rats fed with vitamin D3 deficiency diet (VDD). CB2-receptors were analyzed by RT-PCR method and others biomarkers by ELISA. The relative expression of CB2 (thyroid ~ 4 folds), VDR protein (liver, 151.72%), and (kidney, 66%) was significantly increased in CBD-60 compared to VDD. Vitamin D3 metabolites were significantly increased serum (189.42%), kidney (73.84%), and liver (58.11%) in CBD-60 than VDD. Increased thyroxine (59.9%) and calcitonin (213.59%); while decreased thyroid-stimulating hormone (36.15%) and parathyroid hormone (38.64%) was observed CBD treatment in VDD rats. In conclusion, CBD treatment improves CB2 and VDR expression and the level of vitamin D3 metabolites, along with improved thyroid hormones, including calcitonin. This is the first report with an improved CB2 and VDR expression after CBD treatment in VDD induced animals. Thus, CBD can be considered to use in hypothyroidism conditions and to maintain bone health.
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The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
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Abbreviations
- CBD:
-
Cannabidiol
- ECS:
-
Endocannabinoid system
- VDR:
-
Vitamin D3 receptor
- CB1R:
-
Cannabinoid receptor
- VDD:
-
Vitamin D3 deficiency diet
- RQ:
-
Relative quantification
- CT :
-
Threshold cycle
- T4:
-
Thyroxine
- TSH:
-
Thyroid stimulating hormone
- PTH:
-
Parathyroid hormone
- CKD:
-
Chronic kidney disease
- MBD:
-
Mineral and bone disorders
- CGRP:
-
Calcitonin gene-related protein
References
Avraham Y, Grigoriadis N, Poutahidis T, Vorobiev L, Magen I, Ilan Y, Mechoulam R, Berry E (2011) Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice. Br J Pharmacol 162(7):1650–1658. https://doi.org/10.1111/j.1476-5381.2010.01179.x
Boggs DL, Surti T, Gupta A, Gupta S, Niciu M, Pittman B, Schnakenberg Martin AM, Thurnauer H, Davies A, D’Souza DC, Ranganathan M (2018) The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia a randomized placebo controlled trial. Psychopharmacology 235(7):1923–1932. https://doi.org/10.1007/s00213-018-4885-9
Borrelli F, Aviello G, Romano B, Orlando P, Capasso R, Maiello F, Guadagno F, Petrosino S, Capasso F, Di Marzo V, Izzo AA (2009) Cannabidiol, a safe and non-psychotropic ingredient of the marijuana plant Cannabis sativa, is protective in a murine model of colitis. J Mol Med (berl) 87(11):1111–1121. https://doi.org/10.1007/s00109-009-0512-x
Bosworth C, de Boer IH (2013) Impaired vitamin D metabolism in CKD. Semin Nephrol 33(2):158–168. https://doi.org/10.1016/j.semnephrol.2012.12.016
Carriba P, Ortiz O, Patkar K, Justinova Z, Stroik J, Themann A, Müller C, Woods AS, Hope BT, Ciruela F, Casadó V, Canela EI, Lluis C, Goldberg SR, Moratalla R, Franco R, Ferré S (2007) Striatal adenosine A2A and cannabinoid CB1 receptors form functional heteromeric complexes that mediate the motor effects of cannabinoids. Neuropsychopharmacology 32(11):2249–2259. https://doi.org/10.1038/sj.npp.1301375
Castillo A, Tolón MR, Fernández-Ruiz J, Romero J, Martinez-Orgado J (2010) The neuroprotective effect of cannabidiol in an in vitro model of newborn hypoxic-ischemic brain damage in mice is mediated by CB(2) and adenosine receptors. Neurobiol Dis 37(2):434–440. https://doi.org/10.1016/j.nbd.2009.10.023
Chacar FC, Kogika MM, Zafalon RVA, Brunetto MA (2020) Vitamin D metabolism and its role in mineral and bone disorders in chronic kidney disease in humans, dogs and cats. Metabolites 10(12):499. https://doi.org/10.3390/metabo10120499
Hammell DC, Zhang LP, Ma F, Abshire SM, McIlwrath SL, Stinchcomb AL, Westlund KN (2016) Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis. Eur J Pain 20(6):936–948. https://doi.org/10.1002/ejp.818
Kamali A, Oryan A, Hosseini S, Ghanian MH, Alizadeh M, Baghaban Eslaminejad M, Baharvand H (2019) Corrigendum to "Cannabidiol-loaded microspheres incorporated into osteoconductive scaffold enhance mesenchymal stem cell recruitment and regeneration of critical-sized bone defects" [Mater. Sci. Eng. C. 101C (2019) pages 64–75]. Mater Sci Eng C Mater Biol Appl 126:112179. doi:https://doi.org/10.1016/j.msec.2021.112179
Komorowski J, Stepień H (2007) The role of the endocannabinoid system in the regulation of endocrine function and in the control of energy balance in humans. Postepy Hig Med Dosw (online) 61:99–105
Lakiotaki E, Giaginis C, Tolia M, Alexandrou P, Delladetsima I, Giannopoulou I, Kyrgias G, Patsouris E, Theocharis S (2015) Clinical significance of cannabinoid receptors CB1 and CB2 expression in human malignant and benign thyroid lesions. Biomed Res Int 2015:839403. https://doi.org/10.1155/2015/839403
Ligresti A, De Petrocellis L, Di Marzo V (2016) From phytocannabinoids to cannabinoid receptors and endocannabinoids: pleiotropic physiological and pathological roles through complex pharmacology. Physiol Rev 96(4):1593–1659. https://doi.org/10.1152/physrev.00002.2016
Lu HC, Mackie K (2016) An introduction to the endogenous cannabinoid system. Biol Psychiat 79(7):516–525. https://doi.org/10.1016/j.biopsych.2015.07.028
Malhotra S, Heptulla RA, Homel P, Motaghedi R (2017) Effect of marijuana use on thyroid function and autoimmunity. Thyroid 27(2):167–173. https://doi.org/10.1089/thy.2016.0197
Navarrete F, García-Gutiérrez MS, Aracil-Fernández A, Lanciego JL, Manzanares J (2018) Cannabinoid CB1 and CB2 receptors, and monoacylglycerol lipase gene expression alterations in the basal ganglia of patients with Parkinson’s disease. Neurotherapeutics 15(2):459–469. https://doi.org/10.1007/s13311-018-0603-x
Navarro G, Carriba P, Gandı´a J, Ciruela F, Casado´ V, Corte´ s A, Mallol J, Canela EI, Lluis C, and Franco R. (2008) Detection of heteromers formed by cannabinoid CB1, dopamine D2, and adenosine A2A G-protein-coupled receptors by combining bimolecular fluorescence complementation and bioluminescence energy transfer. Sci World J 8: 1088-1097. doi:https://doi.org/10.1100/tsw.2008.136
Petrescu NB, Jurj A, Sorițău O, Lucaciu OP, Dirzu N, Raduly L, Berindan-Neagoe I, Cenariu M, Boșca BA, Campian RS, Ilea A (2020) Cannabidiol and vitamin D3 impact on osteogenic differentiation of human dental mesenchymal stem cells. Medicina (kaunas) 56(11):607. https://doi.org/10.3390/medicina56110607
Porcella A, Marchese G, Casu MA, Rocchitta A, Lai ML, Gessa GL, Pani L (2002) Evidence for functional CB1 cannabinoid receptor expressed in the rat thyroid [published correction appears in Eur J Endocrinol 2002 Sep; 147(3):434]. Eur J Endocrinol 147(2):255–261. https://doi.org/10.1530/eje.0.1470255
Ritter JK, Li G, Xia M, Boini K (2016) Anandamide and its metabolites: what are their roles in the kidney? Front Biosci (schol Ed) 8:264–277. https://doi.org/10.2741/s461
Saponaro F, Ferrisi R, Gado F, Polini B, Saba A, Manera C, Chiellini G (2021) The role of cannabinoids in bone metabolism: a new perspective for bone disorders. Int J Mol Sci 22(22):12374. https://doi.org/10.3390/ijms222212374
Shahid MA, Ashraf MA, Sharma S. (2021) Physiology, Thyroid Hormone. [Updated 2021 May 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK500006/
Soderstrom K, Soliman E, Van Dross R (2017) Cannabinoids modulate neuronal activity and cancer by CB1 and CB2 receptor-independent mechanisms. Front Pharmacol 8:720. https://doi.org/10.3389/fphar.2017.00720
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The authors extend their sincere thanks and gratitude to Dabur Research Foundation, India, for providing the facilities and support that enabled the successful completion of the work.
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MKT: Conceptualization, Project administration, Resources, SM: Writing—review & editing, Formal analysis; Software, Methodology, SJ: Conceptualization, Project administration, Supervision, Writing—review & editing, Validation.
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Trivedi, M.K., Mondal, S. & Jana, S. Cannabidiol improves thyroid function via modulating vitamin D3 receptor in vitamin D3 deficiency diet-induced rat model. J Food Sci Technol 59, 3237–3244 (2022). https://doi.org/10.1007/s13197-022-05492-3
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DOI: https://doi.org/10.1007/s13197-022-05492-3