The cannabinoid system (CS) works for regulating hepatic fibrosis, steatosis and inflammation, with cannabinoid receptors 1 and 2 (CB1 and CB2) causing regulation of pro- and antifibrogenic effects. 

Everyday smoking of cannabis is an independent risk factor for advancing fibrosis to chronic hepatitis C and mediates experimental alcoholic steatosis. But the role and function of CS in alcoholic liver fibrosis (ALF) remains unclear. Thus, a study investigated human liver samples from patients with alcoholic liver disease (ALD) for analyzing CB1 expression. 

Hepatic stellate cells (HSC) were treated with acetaldehyde, H2O2, endo- and exocannabinoids (2-arachidonoylglycerol (2-AG) and Δ9-tetrahydrocannabinol [THC]), and CB1 antagonist SR141716 (rimonabant) in-vitro. 

CB1 knockout (KO) mice were administered thioacetamide (TAA)/ethanol (EtOH) to induce fibrosis, in-vivo. Thus, in human ALD, CB1 expression was confined to advanced fibrosis areas only. 

• In vitro, acetaldehyde, H2O2, as well as 2-AG and THC, alone or in combination with acetaldehyde, generated CB1 mRNA expression, while CB1 blockage with SR141716 dose-dependently impeded HSC proliferation and diminished mRNA expression of fibrosis-mediated genes PCα1(I), MMP-13 and TIMP-1. 
• This was backed up by considerable cytotoxicity of SR141716 at high doses (5–10 µmol/L). 
• In vivo, CB1 knockout mice exhibited substantial resistance to alcoholic liver fibrosis. 

Thus, CB1 expression is increased in human ALF, which is to some degree provoked by acetaldehyde (AA) and oxidative stress. Impeding CB1 by SR141716, or via genetic knock-out can protect against alcoholic-induced fibrosis both in vitro as well as in vivo.

Source- Patsenker E, Stoll M, Millonig G. et al. Cannabinoid Receptor Type I Modulates Alcohol-Induced Liver Fibrosis. Mol Med, 2011;17, 1285–1294. https://doi.org/10.2119/molmed.2011.00149