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. AIMS: 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.
Subject(s)
Cannabinoid Receptor Modulators/therapeutic use , Endocannabinoids/metabolism , Liver Diseases/drug therapy , Animals , Cannabinoid Receptor Modulators/adverse effects , Cannabinoid Receptor Modulators/pharmacology , Drug Design , Drug Evaluation, Preclinical , Humans , Liver Diseases/physiopathology , Molecular Targeted Therapy , Receptors, Cannabinoid/drug effects , Receptors, Cannabinoid/metabolismABSTRACT
Twenty-one patients with corrosive esophageal strictures underwent contrast-enhanced CT of the chest to determine (1) the esophageal wall thickness at the stricture site and (2) its correlation with number of sessions required for adequate dilation. Average esophageal wall thickness was defined as the mean thickness of all four walls at the site of the stricture, whereas the size of the thickest wall was taken as maximal esophageal wall thickness. Average esophageal wall thickness (8.52 +/- 0.61 mm; range, 5.4 to 13.5 mm) and maximal esophageal wall thickness (11.63 +/- 0.83 mm; range, 5.4 to 20 mm) were significantly higher in patients with corrosive esophageal strictures than normal esophageal wall thickness (2.70 +/- 0.04 mm, p < .01). These patients required a mean of 5.70 +/- 1.42 sessions for achieving adequate dilation. Age, sex, grade of dysphagia, and cause and site of the stricture did not influence the number of sessions required for adequate dilation. On multivariate analysis, maximal esophageal wall thickness (p < .01) but not average esophageal wall thickness or stricture length was independently associated with the number of sessions required for adequate dilation. Patients with maximal esophageal wall thickness of 9 mm or more required a significantly higher number of sessions for adequate dilation than did those with wall thickness of less than 9 mm (7.57 +/- 1.80 versus 1.42 +/- 0.27, p < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
