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A Review of the Cardioprotective Effects of Plant Derived and Synthetic Derivatives Targeting the Cannabinoid Receptors

Shailaja Shashikant Shirsat, Sameer N. Goyal

Abstract


Cannabinoids are chemicals that were discovered in the Cannabis sativa plant for the first time. They've been used to treat a variety of ailments for thousands of years. The endocannabinoid system is made up of cannabinoid receptors, endocannabinoids, and the enzymes that catalyse their synthesis and breakdown. It plays a vital role in cardiovascular system function. The findings so far point to endocannabinoids playing a role in the pathogenesis of a variety of cardiovascular illnesses, including myocardial infarction, hypertension, and hypotension linked to hemorrhagic, endotoxic, and cardiogenic shock. The cardioprotective effects of endocannabinoids, as well as the dilatation of coronary arteries caused by them, require special attention. It is impossible to rule out the possibility that a greater understanding of the cannabis system would enable the development of new techniques for the treatment of cardiovascular disorders in the future. This article aims to review the role of cannabinoids to pave a future in the treatment and prevention of cardiovascular disorders.


Keywords


Endocannabinoids Cannabinoid receptors Plant-derived cannabinoids

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References


Mechoulam R. The Pharmacohistory of Cannabis sativa, in Cannabis as Therapeutic Agent. CRC Press; Boca Raton, FL, USA: 1986.

Iversen LL. The science of marijuana. Oxford University Press; 2001 Oct 25.

Pacher P. Batkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev. 2006; 58: 389–462.

Gaoni Y., Mechoulam R. Isolation, structure, and partial synthesis of an active constituent of hashish. J. Am. Chem. Soc. 1964; 86: 1646–1647.

Matsuda L.A., Lolait S.J., Brownstein M.J., Young A.C., Bonner T.I. Structure of a cannabinoid receptor and functional expression of the cloned cdna. Nature. 1990; 346: 561–564.

Devane W.A., Dysarz F.A., 3rd, Johnson M.R., Melvin L.S., Howlett A.C. Determination and characterization of a cannabinoid receptor in rat brain. Mol. Pharmacol. 1988; 34: 605–613.

Pacher P, Bátkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev. 2006 Sep; 58 (3): 389–462.

Felder CC, Joyce KE, Briley EM, Glass M, Mackie KP, Fahey KJ, Cullinan GJ, Hunden DC, Johnson DW, Chaney MO, et al. (1998) LY320135, a novel cannabinoid CB1 receptor antagonist, unmasks coupling of the CB1 receptor to stimulation of cAMP accumulation. J Pharmacol Exp Ther 284: 291–297.

Felder CC, Joyce KE, Briley EM, Mansouri J, Mackie K, Blond O, Lai Y, Ma AL, and MitchellRL(1995)Comparisonofthepharmacologyandsignaltransductionofthe human cannabinoid CB1 and CB2 receptors. Mol Pharmacol 48: 443–450.

Mechoulam R, Parker LA, and Gallily R (2002c) Cannabidiol: an overview of some pharmacological aspects. J Clin Pharmacol 42: 11S–19S.

Huang YC, Wang SJ, Chiou LC, and Gean PW (2003) Mediation of amphetamineinduced long-term depression of synaptic transmission by CB1 cannabinoid receptors in the rat amygdala. J Neurosci 23: 10311–10320.

Rhee MH, Beywitch M, Avidor-Reiss T, Levy R, and Vogel Z (1998) Cannabinoid receptor activation differentially regulates the various adenylyl cyclase isozymes. J Neurochem 71:1525–1534.

Rhee MH, Vogel Z, Barg J, Bayewitch M, Levy R, Hanus L, Breuer A, and Mechoulam R (1997) Cannabinol derivatives: binding to cannabinoid receptors and inhibition of adenylyl cyclase. J Med Chem 40: 3228–3233.

Howlett AC (2004) Efficacy in CB1 receptor-mediated signal transduction. Br J Pharmacol 142: 1209–1218.

Howlett AC, Barth F, Bonner TI, Cabral G, Casellas P, Devane WA, Felder CC, Herkenham M, Mackie K, Martin BR, et al. (2002) International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev 54: 161–202.

Howlett AC, Breivogel CS, Childers SR, Deadwyler SA, Hampson RE, and Porrino LJ (2004) Cannabinoid physiology and pharmacology: 30 years of progress. Neuropharmacology 47 (Suppl 1): 345–358.

RANDALL, M.D. & KENDALL, D. A. (1997). Involvement of a cannabinoid in endothelium-derived hyperpolarizing factormediated coronary vasorelaxation. European Journal of Pharmacology 335, 205–209.

DEUTSCH, D.G., GOLIGORSKY, M.S., SCHMID, P.C., KREBSBACH, R.J., SCHMID, H. H. O., DAS, S.K., DEY, S.K., ARREAZA, G., THORUP, C., STEFANO, G. & MOORE, L.C. (1997). Production and physiological actions of anandamide in the vasculature of the rat kidney. Journal of Clinical Investigation 100, 1538–1546.

VARGA, K., LAKE, K. D., HUANGFU, D., GUYENET, P.G. & KUNOS, G. (1996). Mechanism of the hypotensive action of anandamidein anesthetized rats. Hypertension 28, 682–686.

VARGA, K., LAKE, K.D., MARTIN, B.R. & KUNOS, G. (1995). Novel antagonist implicates the CB1 cannabinoid receptor in the hypotensive action of anandamide. European Journal of Pharmacology 278, 279–283.

VARGA, K., WAGNER, J.A., BRIDGEN, T.D. & KUNOS, G. (1998). Platelet-and macrophage-derived endogenous cannabinoids are involved in endotoxin-induced hypotension. FASEB Journal12, 1035–1044.

Iversen L. The Science of Marijuana. Oxford University Press; Oxford, UK: 2000.

Pacher P., Batkai S., Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol. Rev. 2006; 58: 389–462.

Gaoni Y., Mechoulam R. Isolation, structure, and partial synthesis of an active constituent of hashish. J. Am. Chem. Soc. 1964; 86:1646–1647.

Ashwani S. Patil, Umesh B. Mahajan, Yogeeta O. Agrawal, Kalpesh R. Patil, Chandragouda R. Patil, Shreesh Ojha, Charu Sharma, Sameer N. Goyal Plant-derived natural therapeutics targeting cannabinoid receptors in metabolic syndrome and its complications: A review

S. Zou, U. Kumar, Cannabinoid receptors and the endocannabinoid system: signaling and function in the central nervous system, Int. J. Mol. Sci. 19 (2018) 833.

C.J. Hillard, Circulating endocannabinoids: from whence do they come and where are they going? Neuropsychopharmacology 43 (2018) 155–172.

V. Chiurchiù, M. van der Stelt, D. Centonze, M. Maccarrone, The endocannabinoid system and its therapeutic exploitation in multiple sclerosis:clues for other neuroinflammatory diseases, Prog. Neurobiol. 160 (2018) 82–100.

Matias I, Di Marzo V. Endocannabinoid and the control of energybalance. Trends Endocrinol Metab 2007; 18: 27–37. 11.

G. Torre-Amione, S. Kapadia, J. Lee et al., “Tumor necrosis factor-α and tumor necrosis factor receptors in the failing human heart,” Circulation, vol. 93, no. 4, pp. 704–711, 1996.

M. Rajesh, P. Mukhopadhyay, S. Bátkai et al., “Cannabidiol attenuates cardiac dysfunction, oxidative stress, fibrosis, and inflammatory and cell death signaling pathways in diabetic cardiomyopathy,” Journal of the American College of Cardiology, vol. 56, no. 25, pp. 2115–2125.

G. Solaini, A. Baracca, G. Lenaz, and G. Sgarbi, “Hypoxia and mitochondrial oxidative metabolism,” Biochimica et Biophysica Acta-Bioenergetics, vol. 1797, no. 6–7, pp. 1171–1177, 2010.

Y. Oropeza-Almazán, E. Vázquez-Garza, H. Chapoy-Villanueva, G. Torre-Amione, and G. García-Rivas, “Small interfering RNA targeting mitochondrial calcium uniporter improves cardiomyocyte cell viability in hypoxia/reoxygenation injury by reducing calcium overload,” Oxidative Medicine and Cellular Longevity, vol. 2017, 13 pages, 2017.

O. Lozano, A. Lázaro-Alfaro, C. Silva-Platas et al., “Nanoencapsulated quercetin improves cardioprotection during hypoxia-reoxygenation injury through preservation of mitochondrial function,” Oxidative Medicine and Cellular Longevity, vol. 2019, 14 pages, 2019.

R.P. Lifton, A.G. Gharavi, and D.S. Geller, “Molecular mechanisms of human hypertension,” Cell, vol. 104, no. 4, pp. 545–556, 2001.

A.C. Montezano and R.M. Touyz, “Molecular mechanisms of hypertension-reactive oxygen species and antioxidants: a basic science update for the clinician,” Canadian Journal of Cardiology, vol. 28, no. 3, pp. 288–295, 2012.

A. P. Landstrom, D. Dobrev, and X.H.T. Wehrens, “Calcium signaling and cardiac arrhythmias,” Circulation Research, vol. 120, no. 12, pp. 1969–1993, 2017.

M. Schwartz, S. Böckmann, and B. Hinz, “Up-regulation of heme oxygenase-1 expression and inhibition of diseaseassociated features by cannabidiol in vascular smooth muscle cells,” Oncotarget, vol. 9, no. 77, pp. 34595–34616, 2018.

C.P. Stanley, W.H. Hind, C. Tufarelli, and S.E. O'Sullivan, “Cannabidiol causes endothelium-dependent vasorelaxation of human mesenteric arteries via CB1activation,” Cardiovascular Research, vol. 107, no. 4, pp. 568–578, 201.

Joyeux M, Arnaud C, Godin-Ribuot D, Demenge P, Lamontagne D, Ribuot C. Endocannabinoids are implicated in the infarct size-reducing effect conferred by heat stress preconditioning in isolated rat hearts. Cardiovasc Res 2002; 55 (3): 619–25.

Lagneux C, Lamontagne D. Involvement of cannabinoids in the cardioprotection induced by lipopolysaccharide. Br J Pharmacol 2001; 132 (4): 793–6.

Bouchard JF, Lepicier P, Lamontagne D. Contribution of endocannabinoids in the endothelial protection afforded by ischemic preconditioning in the isolated rat heart. Life Sci 2003; 72 (16): 1859–70.

Lepicier P, Bouchard JF, Lagneux C, Lamontagne D. Endocannabinoids protect the rat isolated heart against ischaemia. Br J Pharmacol 2003; 139 (4): 805–15.

Underdown NJ, Hiley CR, Ford WR. Anandamide reduces infarct size in rat isolated hearts subjected to ischaemia–reperfusion by a novel cannabinoid mechanism. Br J Pharmacol 2005; 146 (6):809–16.

Krylatov AV, Ugdyzhekova DS, Bernatskaya NA, Maslov LN, Mekhoulam R, Pertwee RG, Stephano GB. Activation of type II cannabinoid receptors improves myocardial tolerance to arrhythmogenic effects of coronary occlusion and reperfusion. Bull Exp Biol Med 131: 523–525, 2001.

Ugdyzhekova DS, Bernatskaya NA, Stefano JB, Graier VF, Tam SW, Mekhoulam R. Endogenous cannabinoid anandamide increases heart resistance to arrhythmogenic effects of epinephrine: role of CB1 and CB2 receptors. Bull Exp Biol Med 131: 251–253,

Ugdyzhekova DS, Krylatov AV, Bernatskaya NA, Maslov LN, Mechoulam R, Pertwee RG. Activation of cannabinoid receptors decreases the area of ischemic myocardial necrosis. Bull Exp Biol Med 133: 125–126, 2002.

Bouchard JF, Lepicier P, Lamontagne D. Contribution of endocannabinoids in the endothelial protection afforded by ischemic preconditioning in the isolated rat heart. Life Sci 72: 1859–1870, 2003.

Joyeux M, Arnaud C, Godin-Ribuot D, Demenge P, Lamontagne D, Ribuot C. Endocannabinoids are implicated in the infarct size-reducing effect conferred by heat stress preconditioning in isolated rat hearts. Cardiovasc Res 55: 619–625, 2002.

N.D. Volkow, The Biology and Potential Therapeutic Effects of Cannabidiol, Testimony Before the US Senate Caucus on International Narcotics Control “Cannabidiol: Barriers to Research and Potential Medical Benefits, 2015.

Y.L. Hurd, S. Spriggs, J. Alishayev, G. Winkel, K. Gurgov, C. Kudrich, A.M. Oprescu, E. Salsitz, Cannabidiol for the reduction of cue-induced craving and anxiety in drug-abstinent individuals with heroin use disorder: a double-blind randomized placebo-controlled trial, Am. J. Psychiatr. 176 (11) (2019) 911–922.

K. Iffland, F. Grotenhermen, An update on safety and side effects of cannabidiol: a review of clinical data and relevant animal studies, Cannabis Cannabinoid Res. 2 (2017) 139–154.

N.D. Volkow, The Biology and Potential Therapeutic Effects of Cannabidiol, Testimony Before the US Senate Caucus on International Narcotics Control “Cannabidiol: Barriers to Research and Potential Medical Benefits, 2015.

A.A. Izzo, R. Capasso, G. Aviello, F. Borrelli, B. Romano, F. Piscitelli, L. Gallo, F. Capasso, P. Orlando, V. Di Marzo, Inhibitory effect of cannabichromene, a major non-psychotropic cannabinoid extracted from Cannabis sativa, on inflammationinduced hypermotility in mice, Br. J. Pharmacol. 166 (2012) 1444–1460.

S. Maione, F. Piscitelli, L. Gatta, D. Vita, L. De Petrocellis, E. Palazzo, V. De Novellis, V. Di Marzo, Non-psychoactive cannabinoids modulate the descending pathway of antinociception in anaesthetized rats through several mechanisms of action, Br. J. Pharmacol. 162 (2011) 584–596.

N.D. Volkow, The Biology and Potential Therapeutic Effects of Cannabidiol, Testimony Before the US Senate Caucus on International Narcotics Control “Cannabidiol: Barriers to Research and Potential Medical Benefits, 2015.

M. Schwartz, S. Böckmann, and B. Hinz, “Up-regulation of heme oxygenase-1 expression and inhibition of diseaseassociated features by cannabidiol in vascular smooth muscle cells,” Oncotarget, vol. 9, no. 77, pp. 34595–34616, 2018.

C.P. Stanley, W.H. Hind, C. Tufarelli, and S.E. O'Sullivan, “Cannabidiol causes endothelium-dependent vasorelaxation of human mesenteric arteries via CB1activation,” Cardiovascular Research, vol. 107, no. 4, pp. 568–578, 2015.

P. Remiszewski, I. Jarocka-Karpowicz, M. Biernacki et al., “Chronic cannabidiol administration fails to diminish blood pressure in rats with primary and secondary hypertension despite its effects on cardiac and plasma endocannabinoid system, oxidative stress and lipid metabolism,” International Journal of Molecular Sciences, vol. 21, no. 4, p. 1295, 2020. sympathomimetic effects in spontaneously hypertensive and normotensive rats,” Frontiers in Pharmacology, vol. 10, 2019.

M. Rajesh, P. Mukhopadhyay, S. Bátkai et al., “Cannabidiol attenuates cardiac dysfunction, oxidative stress, fibrosis, and inflammatory and cell death signaling pathways in diabetic cardiomyopathy,” Journal of the American College of Cardiology, vol. 56, no. 25, pp. 2115–2125, 201.

W.-S. Lee, K. Erdelyi, C. Matyas et al., “Cannabidiol limits T cell-mediated chronic autoimmune myocarditis: implications to autoimmune disorders and organ transplantation,” Molecular Medicine, vol. 22, no. 1, pp. 136–146, 2016.

Amin M.R., Ali D.W. Pharmacology of Medical Cannabis. In: Cohen I.R., Lajtha A., Lambris J.D., Paoletti R., Rezaei N., editors. Advances in Experimental Medicine and Biology. Volume 1162. Springer Nature; Cham, Switzerland: 2019. pp. 151–165.

Howlett A.C., Abood M.E. CB(1) and CB(2) receptor pharmacology. Adv. Pharmacol. 2017; 80: 169–206.

Hervás E.S. Synthetic cannabinoids: Characteristics, use and clinical implications. Arch. Psychiatry Psychother. 2017; 19: 42–48.

Morales P., Hernandez-folgado L., Goya P., Jagerovic N. Cannabinoid receptor 2 (CB 2) agonists and antagonists: A patent update. Expert Opin. Ther. Pat. 2016; 26: 843–856.

Badal S., Smith K.N., Rajnarayanan R. Analysis of natural product regulation of cannabinoid receptors in the treatment of human disease. Pharmacol. Ther. 2017; 180: 24–48.

FDA and Cannabis: Research and Drug Approval Process. [(accessed on 29 June 2020)]; Available online: https://www.fda.gov/news-events/public-health-focus/fda-and-cannabis-res earch-and-drug-approval-process.

R. Durst, H. Danenberg, R. Gallily et al., “Cannabidiol, a nonpsychoactiveCannabisconstituent, protects against myocardial ischemic reperfusion injury,” American Journal of Physiology-Heart and Circulatory Physiology, vol. 293, no. 6, pp. H3602–H3607, 2007.

L.B.M. Resstel, S.R.L. Joca, F.A. Moreira, F.M.A. Corrêa, and F.S. Guimarães, “Effects of cannabidiol and diazepam on behavioral and cardiovascular responses induced by contextual conditioned fear in rats,” Behavioural Brain Research, vol. 172, no. 2, pp. 294–298, 2006.

L.BM. Resstel, R.F. Tavares, S.F.S. Lisboa, S.R.L. Joca, F.M.A. Corrêa, and F.S. Guimarães, “5-HT1Areceptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats,” British Journal of Pharmacology, vol. 156, no. 1, pp. 181–188, 2009.

F.V. Gomes, F.H.F. Alves, F.S. Guimarães, FM.A. Correa, L.B.M. Resstel, and C.C. Crestani, “Cannabidiol administration into the bed nucleus of the stria terminalis alters cardiovascular responses induced by acute restraint stress through 5-HT1A receptor,” European Neuropsychopharmacology, vol. 23, no. 9, pp. 1096–1104, 2013.

É.M. Granjeiro, F.V. Gomes, F.S. Guimarães, F.M.A. Corrêa, and L.B.M. Resstel, “Effects of intracisternal administration of cannabidiol on the cardiovascular and behavioral responses to acute restraint stress,” Pharmacology, Biochemistry, and Behavior, vol. 99, no. 4, pp. 743–748, 2011.

D.S. Ugdyzhekova, N.A. Bernatskaya, J.B. Stefano, V.F. Graier, S.W. Tam, and R. Mekhoulam, “Endogenous Cannabinoid Anandamide Increases Heart Resistance to Arrhythmogenic Effects of Epinephrine: Role of CB(1) and CB(2) Receptors,” Bulletin of Experimental Biology and Medicine, vol. 131, no. 3, pp. 251–253, 2001.

D.S. Ugdyzhekova, Y.G. Davydova, L.A. Maimeskulova, and R. Mechoulam, “Involvement of central and peripheral cannabinoid receptors in the regulation of heart resistance to arrhythmogenic effects of epinephrine,” Bulletin of Experimental Biology and Medicine, vol. 130, no. 11, pp. 1087–1089, 2000. [60] A.V. Krylatov, R.V. Uzhachenko, L. N. Maslov et al.

W.C. Schrottmaier, M. Mussbacher, M. Salzmann, and A. Assinger, “Platelet-leukocyte interplay during vascular disease,” Atherosclerosis, vol. 307, pp. 109–120, 2.

National Institute on Drug Abuse (NIDA), Laboratory Study of Cannabidiol on the Effects of Smoked Marijuana, 2013, Jun. 2020.

G.C.’s. S. Healthcare, The Effects of Cannabidiol (CBD) on Electrical and Autonomic Cardiac Function in Children with Severe Epilepsy, 2016, Jun. 2020.

P.N. Ainslie, Cannabinoid Supplementation on Vascular and Cognitive Function, 2017, Jun. 2020.

L. Sánchez-Trujillo, E. Vázquez-Garza, E.C. Castillo, G. García-Rivas, and G. Torre-Amione, “Role of Adaptive Immunity in the Development and Progression of Heart Failure: New Evidence,” Archives of Medical Research, vol. 48, no. 1, pp. 1–11, 2017.

G. García-Rivas, E.C. Castillo, A.M. Gonzalez-Gil et al., “The role of B cells in heart failure and implications for future immunomodulatory treatment strategies,” ESC Heart Failure, vol. 7, no. 4, pp. 1387–1399, 2020.

E.C. Castillo, E. Vázquez-Garza, D. Yee-Trejo, G. GarcíaRivas, and G. Torre-Amione, “What is the role of the inflammation in the pathogenesis of heart failure?,” Current Cardiology Reports, vol. 22, no. 11, 2020.

C.P. Stanley, W.H. Hind, and S.E. O'Sullivan, “Is the cardiovascular system a therapeutic target for cannabidiol?,” British Journal of Clinical Pharmacology, vol. 75, no. 2, pp. 313–322, 2013.




DOI: https://doi.org/10.37591/tdd.v9i1.1164

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