Canna~Fangled Abstracts

Hepatic Cannabinoid Signaling in the Regulation of Alcohol-Associated Liver Disease

By September 23, 2021October 17th, 2021No Comments
Review

doi: 10.35946/arcr.v41.1.12. eCollection 2021.

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Free PMC article

Abstract

Purpose: The endocannabinoid system has emerged as a key regulatory signaling pathway in the pathophysiology of alcohol-associated liver disease (ALD). More than 30 years of research have established different roles of endocannabinoids and their receptors in various aspects of liver diseases, such as steatosis, inflammation, and fibrosis. However, pharmacological applications of the endocannabinoid system for the treatment of ALD have not been successful because of psychoactive side effects, despite some beneficial effects. Thus, a more delicate and detailed elucidation of the mechanism linking the endocannabinoid system and ALD may be of paramount significance in efforts to apply the system to the treatment of ALD.

Search methods: Three electronic databases (PubMed, MEDLINE, and Cochrane Library) were used for literature search from November 1988 to April 2021. Major keywords used for literature searches were “cannabinoid,” “cannabinoid receptor,” “ALD,” “steatosis,” and “fibrosis.”

Search results: According to the inclusion and exclusion criteria, the authors selected 47 eligible full-text articles out of 2,691 searched initially. Studies in the past 3 decades revealed the opposite effects of cannabinoid receptors CB1R and CB2R on steatosis, inflammation, and fibrosis in ALD.

Discussion and conclusions: This review summarizes the endocannabinoid signaling in the general physiology of the liver, the pathogenesis of ALD, and some of the potential therapeutic implications of cannabinoid-based treatments for ALD.

 

Keywords: CB1R, CB2R, alcohol, cell communication, endocannabinoid, fatty liver, metabotropic glutamate receptor 5, xCT

Conflict of interest statement

Disclosures The authors declare no competing financial or nonfinancial interests.

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References

    1. Witkiewitz K, Litten R, Leggio L. Advances in the science and treatment of alcohol use disorder. Sci Adv. 2019;5(9):eaax4043. doi: 10.1126/sciadv.aax4043. – DOI – PMC – PubMed
    1. Grant BF, Chou SP, Saha TD, et al. Prevalence of 12-month alcohol use, high-risk drinking, and DSM-IV alcohol use disorder in the United States, 2001–2002 to 2012–2013: Results from the National Epidemiologic Survey on Alcohol and Related Conditions. JAMA Psychiatry. 2017;74(9):911–923. doi: 10.1001/jamapsychiatry.2017.2161. – DOI – PMC – PubMed
    1. Xi B, Veeranki SP, Zhao M, Ma C, Yan Y, Mi J. Relationship of alcohol consumption to all-cause, cardiovascular, and cancer-related mortality in US adults. J Am Coll Cardiol. 2017;70(8):913–922. doi: 10.1016/j.jacc.2017.06.054. – DOI – PubMed
    1. Stickel F, Datz C, Hampe J, Bataller R. Pathophysiology and management of alcoholic liver disease: Update 2016. Gut Liver. 2017;11(2):173–188. doi: 10.5009/gnl16477. – DOI – PMC – PubMed
    1. Kim HH, Choi SE, Jeong WI. Oxidative stress and glutamate excretion in alcoholic steatosis: Metabolic synapse between hepatocyte and stellate cell. Clin Mol Hepatol. 2020;26(4):697–704. doi: 10.3350/cmh.2020.0152. – DOI – PMC – PubMed

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