Cannabinoids and Chronic Liver Diseases

Abstract

Nonalcoholic fatty liver disease (NAFLD), alcohol-induced liver disease (ALD), and viral hepatitis are the main causes of morbidity and mortality related to chronic liver diseases (CLDs) worldwide. New therapeutic approaches to prevent or reverse these liver disorders are thus emerging. Although their etiologies differ, these CLDs all have in common a significant dysregulation of liver metabolism that is closely linked to the perturbation of the hepatic endocannabinoid system (eCBS) and inflammatory pathways. Therefore, targeting the hepatic eCBS might have promising therapeutic potential to overcome CLDs. Experimental models of CLDs and observational studies in humans suggest that cannabis and its derivatives may exert hepatoprotective effects against CLDs through diverse pathways. However, these promising therapeutic benefits are not yet fully validated, as the few completed clinical trials on phytocannabinoids, which are thought to hold the most promising therapeutic potential (cannabidiol or tetrahydrocannabivarin), remained inconclusive. Therefore, expanding research on less studied phytocannabinoids and their derivatives, with a focus on their mode of action on liver metabolism, might provide promising advances in the development of new and original therapeutics for the management of CLDs, such as NAFLD, ALD, or even hepatitis C-induced liver disorders.

Beta-Caryophyllene Modifies Intracellular Lipid Composition in a Cell Model of Hepatic Steatosis by Acting through CB2 and PPAR Receptors

“…The binding of BCP to the CB2 receptor has been well characterized [ 11 ], and the role of the endocannabinoid system (ECS) in the liver has been widely studied since it may be a therapeutic target for chronic liver disease [ 41 ], characterized by dysregulation of hepatic lipid metabolism and also perturbation of the hepatic endocannabinoid system [ 42 ]. Although CB2 expression in the liver is moderate, its role has been demonstrated in both physiological (regulating liver development in zebrafish embryos [ 43 ]) and pathological conditions.…”

Nutritional and Lifestyle Therapy for NAFLD in People with HIV

“…Therefore, these risks should be carefully considered before suggesting the use of cannabinoids. In addition, despite preclinical studies that have focused on isolated phytocannabinoids as therapeutic options for NAFLD showing promising results, preliminary human trials have failed to confirm them [74]. We believe that further evidence on safety and tolerability is needed before conducting large-scale efficacy human trials.…”

“…Evidence from pre-clinical models shows that a cannabinoid receptors 1 overexpression leads to de novo hepatic lipogenesis, along with an intrahepatic monounsaturated FAs accumulation. Oppositely, a cannabinoid receptors 1 blockage inhibits insulin resistance and hepatic steatosis [74]. Similarly, cannabinoid receptors 2 are known to contribute both directly-by inducing liver inflammation-and indirectlyby increasing the hepatic cannabinoid receptors 1 expression-to NAFLD, NASH, and liver fibrosis [74].…”

“…Oppositely, a cannabinoid receptors 1 blockage inhibits insulin resistance and hepatic steatosis [74]. Similarly, cannabinoid receptors 2 are known to contribute both directly-by inducing liver inflammation-and indirectlyby increasing the hepatic cannabinoid receptors 1 expression-to NAFLD, NASH, and liver fibrosis [74]. Aligned with these findings, human studies have confirmed an inverse association of cannabis consumption with NAFLD [75,76], as well as with its metabolic risk factors, namely obesity [77], diabetes [78], and metabolic syndrome [79].…”

"Cannabinoids as Potential Therapeutic Agents for Kidney and Liver Toxicity: A Review"

“…Furthermore, its anti-inflammatory properties reduce the release of stellate cells and inhibit the activation of immune cells in the liver [44], thereby limiting the progression of liver diseases [44]. Moreover, the antioxidant effects of cannabinoids act as scavengers of free radicals and inhibit the production of reactive oxygen species known to cause oxidative damage to liver cells, which helps to preserve healthy liver function [46]. Although the aforementioned research was preclinical, an increasing number of clinical investigations and human trials have lately offered insightful data.…”