Endocannabinoids and Liver Disease. II. Endocannabinoids in the pathogenesis and treatment of liver fibrosis

“Plant-derived cannabinoids such as delta-9-tetrahydrocannabinol (THC) have been used for medicinal purposes for thousands of years. Two G protein-coupled receptors termed CB1 and CB2 were identified in the early 1990s as receptors for cannabinoids…”

“Hepatic fibrosis is the response of the liver to chronic injury and is associated with portal hypertension, progression to hepatic cirrhosis, liver failure, and high incidence of hepatocellular carcinoma. On a molecular level, a large number of signaling pathways have been shown to contribute to the activation of fibrogenic cell types and the subsequent accumulation of extracellular matrix in the liver. Recent evidence suggests that the endocannabinoid system is an important part of this complex signaling network. In the injured liver, the endocannabinoid system is upregulated both at the level of endocannabinoids and at the endocannabinoid receptors CB1 and CB2. The hepatic endocannabinoid system mediates both pro- and antifibrogenic effects by activating distinct signaling pathways that differentially affect proliferation and death of fibrogenic cell types. Here we will summarize current findings on the role of the hepatic endocannabinoid system in liver fibrosis and discuss emerging options for its therapeutic exploitation.”

“There is overwhelming evidence that the endocannabinoid system plays a major role in the pathophysiology of chronic liver injury and wound healing responses and that modulation of the endocannabinoid system may be exploited for the treatment of liver fibrosis. Among all candidates, CB1 represents the most promising target for antifibrotic therapies. In addition to the antifibrogenic effects of CB1 blockade, one can expect positive effects on other complications such as portal hypertension, ascites formation, hepatic encephalopathy, and cardiomyopathy. Moreover, CB1 antagonism appears to have beneficial effects on hepatic steatosis…”

http://ajpgi.physiology.org/content/294/2/G357.long

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