title: Review article: the endocannabinoid system in liver disease, a potential therapeutic target.
abstract: BACKGROUND
  Endocannabinoids are a family of potent lipid-soluble molecules, acting on the cannabinoid (CB) receptors that mediate the effects of marijuana. The CB receptors, endocannabinoids and the enzymes involved in their synthesis and degradation are located in the brain and peripheral tissues, including the liver.
  
  
  OBJECTIVE
  To review the current understanding of the role of the endocannabinoid system in liver disease-associated pathophysiological conditions, and drugs targeting the endocannabinoid system as therapy for liver disease.
  
  
  METHODS
  Original articles and reviews were used to summarise the relevant pre-clinical and clinical research findings relating to this topic.
  
  
  RESULTS
  The endocannabinoid system as a whole plays an important role in liver diseases (i.e. non-alcoholic liver disease, alcoholic liver disease, hepatic encephalopathy and autoimmune hepatitis) and related pathophysiological conditions (i.e. altered hepatic haemodynamics, cirrhotic cardiomyopathy, metabolic syndrome and ischaemia/reperfusion disease). Pharmacological targeting of the endocannabinoid system has had success as treatment for patients with liver disease, but adverse events led to withdrawal of marketing approval. However, there is optimism over novel therapeutics targeting the endocannabinoid system currently in the pre-clinical stage of development.
  
  
  CONCLUSIONS
  The endocannabinoid system plays an important role in the pathophysiology of liver disease and its associated conditions. While some drugs targeting the endocannabinoid system have deleterious neurological adverse events, there is promise for a newer generation of therapies that do not cross the blood-brain barrier.
authors.affiliation: Division of Digestive and Liver Diseases and Center for Liver Disease and Transplantation, Columbia University Medical Center, NY, USA; King's County Hospital Medical Center, Brooklyn, NY, USA.
authors.forename: P P
authors.initials: PP
authors.lastname: Basu
authors.forename: M M
authors.initials: MM
authors.lastname: Aloysius
authors.forename: N J
authors.initials: NJ
authors.lastname: Shah
authors.forename: R S
authors.initials: RS
authors.lastname: Brown
mesh_terms: D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D063388:Endocannabinoids / Q000378:metabolism*; D006801:Humans; D008107:Liver Diseases / Q000188:drug therapy* / Q000503:physiopathology; D058990:Molecular Targeted Therapy; D043882:Receptors, Cannabinoid / Q000187:drug effects / Q000378:metabolism
chemical_list: D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D043882:Receptors, Cannabinoid