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Role of Cannabinoids in Gastrointestinal Mucosal Defense and Inflammation
Modulating the activity of the endocannabinoid system influences various gastrointestinal physiological and pathophysiological processes, and cannabinoid receptors as well as regulatory enzymes responsible for the synthesis or degradation of endocannabinoids representing potential targets to reduce...
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Published in: | Current neuropharmacology 2016-01, Vol.14 (8), p.935-951 |
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Main Authors: | , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that cite this one |
Online Access: | Get full text |
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Summary: | Modulating the activity of the endocannabinoid system influences various
gastrointestinal physiological and pathophysiological processes, and cannabinoid
receptors as well as regulatory enzymes responsible for the synthesis or degradation
of endocannabinoids representing potential targets to reduce the development of
gastrointestinal mucosal lesions, hemorrhage and inflammation. Direct activation of
CB1 receptors by plant-derived, endogenous or synthetic cannabinoids effectively
reduces both gastric acid secretion and gastric motor activity, and decreases the
formation of gastric mucosal lesions induced by stress, pylorus ligation, nonsteroidal
anti-inflammatory drugs (NSAIDs) or alcohol, partly by peripheral, partly by central
mechanisms. Similarly, indirect activation of cannabinoid receptors through elevation
of endocannabinoid levels by globally acting or peripherally restricted inhibitors of their metabolizing
enzymes (FAAH, MAGL) or by inhibitors of their cellular uptake reduces the gastric mucosal lesions
induced by NSAIDs in a CB1 receptor-dependent fashion. Dual inhibition of FAAH and cyclooxygenase
enzymes induces protection against both NSAID-induced gastrointestinal damage and intestinal
inflammation. Moreover, in intestinal inflammation direct or indirect activation of CB1 and CB2 receptors
exerts also multiple beneficial effects. Namely, activation of both CB receptors was shown to ameliorate
intestinal inflammation in various murine colitis models, to decrease visceral hypersensitivity and
abdominal pain, as well as to reduce colitis-associated hypermotility and diarrhea. In addition, CB1
receptors suppress secretory processes and also modulate intestinal epithelial barrier functions. Thus,
experimental data suggest that the endocannabinoid system represents a promising target in the treatment
of inflammatory bowel diseases, and this assumption is also confirmed by preliminary clinical studies. |
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ISSN: | 1570-159X 1875-6190 |
DOI: | 10.2174/1570159X14666160303110150 |