Cannabidiol: main mechanisms of action and therapeutic targets
DOI:
https://doi.org/10.12775/JEHS.2023.38.01.020Keywords
cannabidiol, CBD, CBD therapeutic targets, CBD's mechanism of action, endocannabinoid systemAbstract
Introduction: Over the past few years, multiple publications have proven many beneficial properties associated with CBD. Currently, its use in the treatment of inflammatory and autoimmune diseases is suggested. Also, very often the use of CBD in the treatment of anxiety disorders, schizophrenia and depression, as well as Parkinson's disease and Alzheimer's disease is the subject of scientific research. CBD could be also used in treatment of the chronic pain in cancer patients or in people with diabetic complications. So far, it has been proven that CBD has anti-inflammatory, anticonvulsant, antioxidant, anti-arthritic, procognitive, cardio- and neuroprotective effects. The potential of cannabidiol in the prevention and treatment of many diseases is seen in its complex and multidirectional mechanisms of action. CBD has low affinity for cannabinoid receptors and acts as an inverse agonist of type 2 cannabinoid receptors (CB2-R). Additionally, CBD exerts its effects through many other molecular targets.
Aim of the study: The aim of this review is to present mechanisms of action of cannabidiol and its possible therapeutic targets.
Materials and methods: The literature available in the PubMed and Google Scholar data bases was reviewed, using the following keywords: "cannabidiol", "CBD", "CBD's mechanism of action", "CBD therapeutic targets", "endocannabinoid system".
Conclusions: Cannabidiol is a promising candidate in the treatment of many common diseases. Furthermore, research is needed to confirm its beneficial effects and turn it into an effective drug that supports therapy with other drugs.
References
Lu HC, Mackie K. Review of the Endocannabinoid System. Vol. 6, Biol Psychiatry Cognitive Neuroscience and Neuroimaging. 2021;6(6):607-615. doi:10.1016/j.bpsc.2020.07.016
Crocq MA. History of cannabis and the endocannabinoid system. Dialogues Clin Neurosci. 2020 Sep 1;22(3):223–228. doi:10.31887/DCNS.2020.22.3/mcrocq
Karabowicz P, Grzęda E, Baranowska-Kuczko M, Malinowska B. Znaczenie endokannabinoidu 2-arachidonyloglicerolu w fizjologii i patofizjologii układu krążenia [Role of endocannabinoid 2-arachidonoylglycerol in the physiology and pathophysiology of the cardiovascular system]. Postepy Hig Med Dosw (Online). 2014;68:814-827. Published 2014 Jun 12. doi:10.5604/17322693.1108875
Di Marzo V, Piscitelli F. The Endocannabinoid System and its Modulation by Phytocannabinoids. Neurotherapeutics. 2015;12(4):692-698. doi:10.1007/s13311-015-0374-6
Thomas A, Baillie GL, Phillips AM, Razdan RK, Ross RA, Pertwee RG. Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro. Br J Pharmacol. 2007;150(5):613-623. doi:10.1038/sj.bjp.0707133
Lunn CA, Fine JS, Rojas-Triana A, et al. A novel cannabinoid peripheral cannabinoid receptor-selective inverse agonist blocks leukocyte recruitment in vivo. J Pharmacol Exp Ther. 2006;316(2):780-788. doi:10.1124/jpet.105.093500
Booz GW. Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress. Vol. 51, Free Radical Biology and Medicine. 2011. p. 1054–61; doi:10.1016/j.freeradbiomed.2011.01.007.
Tanasescu R, Constantinescu CS. Cannabinoids and the immune system: An overview. Immunobiology. 2010 Aug;215(8):588–97; DOI: 10.1016/j.imbio.2009.12.005.
Castillo A, Tolón MR, Fernández-Ruiz J, Romero J, Martinez-Orgado J. The neuroprotective effect of cannabidiol in an in vitro model of newborn hypoxic-ischemic brain damage in mice is mediated by CB2 and adenosine receptors. Neurobiol Dis. 2010 Feb;37(2):434–40; DOI: 10.1016/j.nbd.2009.10.023.
Durst R, Danenberg H, Gallily R, Mechoulam R, Meir K, Grad E, et al. Cannabidiol, a nonpsychoactive Cannabis constituent, protects against myocardial ischemic reperfusion injury. Am J Physiol Heart Circ Phys-iol [Internet]. 2007;293:3602–7; DOI: 10.1152/ajpheart.00098.2007.
Gonca E, Darici F. The Effect of Cannabidiol on ischemia/reperfusion-induced ventricular arrhythmias: The role of adenosine a1 receptors. J Cardiovasc Pharmacol Ther. 2015 Jan 12;20(1):76–83; DOI: 10.1177/1074248414532013.
Polska E, med Katarzyna Winczyk hab, Neuroendokrynologii Z, Endokrynologii K. PRACE POGLĄDOWE/REWIEVS. Vol. 59, Polish Journal of Endocrinology Tom. 2008.
Vanden Berghe W, Vermeulen L, Delerive # P, De Bosscher K, Staels # B, Haegeman G. A Paradigm for Gene Regulation: Inflammation, NF-KB and PPAR; DOI: 10.1007/978-1-4419-9072-3_22.
Delerive P, Fruchart JC, Staels B. EUROSTERONE MEETING Peroxisome proliferator-activated receptors in inflammation control [Internet]. Vol. 169, Journal of Endocrinology. 2001; DOI: 10.1677/joe.0.1690453.
Delerive P, De Bosscher K, Besnard S, Vanden Berghe W, Peters JM, Gonzalez FJ, et al. Peroxisome proliferator-activated receptor α negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factors NF-κB and AP-1. Journal of Biological Chemistry. 1999 Nov 5;274(45):32048–54; DOI: 10.1074/jbc.274.45.32048.
Delerive P, Gervois P, Fruchart JC, Staels B. Induction of IκBα expression as a mechanism contributing to the anti-inflammatory activities of peroxisome proliferator-activated receptor-α activators. Journal of Biological Chemistry. 2000 Nov 24;275(47):36703–7, DOI: 10.1074/jbc.M004045200.
O’Sullivan SE, Kendall DA. Cannabinoid activation of peroxisome proliferator-activated receptors: Potential for modulation of inflammatory disease. Immunobiology. 2010 Aug;215(8):611–6; DOI: 10.1016/j.imbio.2009.09.007.
Esposito G, Pesce M, Seguella L, Sanseverino W, Lu J, Corpetti C, et al. The potential of cannabidiol in the COVID-19 pandemic. Br J Pharmacol. 2020 Nov 1;177(21):4967–70; DOI: 10.1111/bph.15157.
Milam JE, Keshamouni VG, Phan SH, Hu B, Gangireddy SR, Hogaboam CM, et al. PPAR-agonists inhibit profibrotic phenotypes in human lung fibroblasts and bleomycin-induced pulmonary fibrosis. 2008; DOI: 10.1152/ajplung.00333.2007.
Vuolo F, Abreu SC, Michels M, Xisto DG, Blanco NG, Hallak JE, et al. Cannabidiol reduces airway inflammation and fibrosis in experimental allergic asthma. Eur J Pharmacol. 2019 Jan 15;843:251–9; DOI: 10.1016/j.ejphar.2018.11.029.
Huang S, Zhu B, Cheon IS, Goplen NP, Jiang L, Zhang R, et al. PPAR-γ in Macrophages Limits Pulmonary Inflammation and Promotes Host Recovery following Respiratory Viral Infection. J Virol. 2019 May;93(9); DOI: 10.1128/JVI.00030-19.
O'Sullivan SE, Stevenson CW, Laviolette SR. Could Cannabidiol Be a Treatment for Coronavirus Disease-19-Related Anxiety Disorders?. Cannabis Cannabinoid Res. 2021;6(1):7-18. Published 2021 Feb 12; DOI:10.1089/can.2020.0102.
Russo EB, Burnett A, Hall B, Parker KK. Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochem Res. 2005 Aug;30(8):1037–43; DOI: 10.1007/s11064-005-6978-1.
Mishima K, Hayakawa K, Abe K, Ikeda T, Egashira N, Iwasaki K, et al. Cannabidiol prevents cerebral infarction via a serotonergic 5-hydroxytryptamine1A receptor-dependent mechanism. Stroke. 2005 May;36(5):1071–6; DOI: 10.1161/01.STR.0000163083.59201.34.
Campos AC, Guimarães FS. Involvement of 5HT1A receptors in the anxiolytic-like effects of cannabidiol injected into the dorsolateral periaqueductal gray of rats. Psychopharmacology (Berl). 2008 Aug;199(2):223–30; DOI: 10.1007/s00213-008-1168-x.
de Almeida DL, Devi LA. Diversity of molecular targets and signaling pathways for CBD. Pharmacol Res Perspect. 2020;8(6):e00682. doi:10.1002/prp2.682.
Xiong W, Koo BN, Morton R, Zhang L. Psychotropic and nonpsychotropic cannabis derivatives inhibit human h5-HT3A receptors through a receptor desensitization-dependent mechanism. Neuroscience. 2011 Jun 16;184:28–37; DOI: 10.1016/j.neuroscience.2011.03.066.
Scichilone N, Caponetto C, Fagone E, Benfante A, Paternò A, Heffler E, et al. The Arg/Arg polymorphism of the ADRB2 is associated with the severity of allergic asthma. J Allergy Clin Immunol Pract [Internet]. 2016 Nov 1 [cited 2022 Apr 5];4(6):1251–2; DOI: 10.1016/j.ctarc.2020.100278.
Booz GW. PARP inhibitors and heart failure--translational medicine caught in the act. Congest Heart Fail. 2007;13(2):105-112. doi:10.1111/j.1527-5299.2007.06595.x.
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