Department of Biological Sciences and CERMO-FC Research Centre, Université du Québec à Montréal, Montreal, QC H2X 1Y4, Canada.
Infectious Diseases and Immunity in Global Health Program, Research Institute of McGill University Health Centre, Montreal, QC H3A 3J1, Canada.
Int J Mol Sci. 2022 Aug 20;23(16):9423. doi: 10.3390/ijms23169423.
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.
非酒精性脂肪性肝病（NAFLD）、酒精性肝病（ALD）和病毒性肝炎是全球与慢性肝病（CLD）相关发病率和死亡率的主要原因。因此，新的治疗方法正在出现，以预防或逆转这些肝脏疾病。尽管它们的病因不同，但这些 CLD 都有一个共同的特点，即肝脏代谢的显著失调，这与肝内大麻素系统（eCBS）和炎症途径的紊乱密切相关。因此，靶向肝内 eCBS 可能具有治疗 CLD 的巨大潜力。CLD 的实验模型和人类的观察性研究表明，大麻及其衍生物可能通过多种途径对 CLD 发挥保肝作用。然而，这些有希望的治疗益处尚未得到充分验证，因为少数关于植物大麻素的已完成临床试验（被认为具有最有前途的治疗潜力的大麻二酚或四氢大麻酚）仍未得出结论。因此，扩大对研究较少的植物大麻素及其衍生物的研究，重点研究它们对肝脏代谢的作用模式，可能会为开发新的和原创的治疗方法提供有希望的进展，以管理 CLD，如非酒精性脂肪性肝病、酒精性肝病，甚至丙型肝炎引起的肝脏疾病。
