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Medicines 2018, 5(2), 47; https://doi.org/10.3390/medicines5020047

Mechanistic Potential and Therapeutic Implications of Cannabinoids in Nonalcoholic Fatty Liver Disease

1
Division of Gastroenterology, Women & Infants Hospital/Warren Alpert School of Medicine, Brown University, Providence, RI 02905, USA
2
Department of Medicine, Stanford University School of Medicine, Stanford, CA 94304, USA
3
Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94304, USA
4
Department of Medicine, Mary Imogene Bassett Hospital, Cooperstown, NY 13326, USA
5
Division of Gastroenterology and Hepatology, University of Tennessee Health Science Center, Memphis, TN 38163, USA
*
Author to whom correspondence should be addressed.
Received: 17 May 2018 / Revised: 23 May 2018 / Accepted: 24 May 2018 / Published: 28 May 2018
(This article belongs to the Special Issue Cannabinoids for Medical Use)
Full-Text   |   PDF [280 KB, uploaded 28 May 2018]

Abstract

Nonalcoholic fatty liver disease (NAFLD) is comprised of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). It is defined by histologic or radiographic evidence of steatosis in the absence of alternative etiologies, including significant alcohol consumption, steatogenic medication use, or hereditary disorders. NAFLD is now the most common liver disease, and when NASH is present it can progress to fibrosis and hepatocellular carcinoma. Different mechanisms have been identified as contributors to the physiology of NAFLD; insulin resistance and related metabolic derangements have been the hallmark of physiology associated with NAFLD. The mainstay of treatment has classically involved lifestyle modifications focused on the reduction of insulin resistance. However, emerging evidence suggests that the endocannabinoid system and its associated cannabinoid receptors and ligands have mechanistic and therapeutic implications in metabolic derangements and specifically in NAFLD. Cannabinoid receptor 1 antagonism has demonstrated promising effects with increased resistance to hepatic steatosis, reversal of hepatic steatosis, and improvements in glycemic control, insulin resistance, and dyslipidemia. Literature regarding the role of cannabinoid receptor 2 in NAFLD is controversial. Exocannabinoids and endocannabinoids have demonstrated some therapeutic impact on metabolic derangements associated with NAFLD, although literature regarding direct therapeutic use in NAFLD is limited. Nonetheless, the properties of the endocannabinoid system, its receptors, substrates, and ligands remain a significant arena warranting further research, with potential for a pharmacologic intervention for a disease with an anticipated increase in economic and clinical burden. View Full-Text
Keywords: nonalcoholic fatty liver disease; NAFLD; nonalcoholic steatohepatitis; NASH; cannabinoids; endocannabinoid system; endocannabinoid; exocannabinoid nonalcoholic fatty liver disease; NAFLD; nonalcoholic steatohepatitis; NASH; cannabinoids; endocannabinoid system; endocannabinoid; exocannabinoid
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Dibba, P.; Li, A.; Cholankeril, G.; Iqbal, U.; Gadiparthi, C.; Khan, M.A.; Kim, D.; Ahmed, A. Mechanistic Potential and Therapeutic Implications of Cannabinoids in Nonalcoholic Fatty Liver Disease. Medicines 2018, 5, 47.

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