Targeting the Endocannabinoid System for Gastrointestinal Diseases: Future Therapeutic Strategies

Rudolf Schicho; Martin Storr


Expert Rev Clin Pharmacol. 2010;3(2):193-207. 

In This Article

Effects of Ligands on CBs in GI Physiology

Cannabinoids that act via central and peripheral CB1s influence fundamental features of gut physiology (i.e., food intake, motility and mucosal homeostasis). Agonists of CB1 increase food intake and inhibit vomiting, while antagonists inhibit food intake and induce vomiting.[25,82–87] Regulation of motility is a prominent task of CB1, and any pharmacological manipulation has an impact on its effect. CB1 agonism inhibits gastric fundus contractions,[88] emptying of the stomach, lower esophageal sphincter relaxation and contractions of the ileum and colon, and slows down intestinal and colonic transit (reviewed in[89]). Conversely, CB1 antagonism increases gastric emptying and intestinal motility.[89] The effects on GI motility seen in rodents also apply to human tissue. In vitro experiments in human ileum and colon confirm that CB1 ligands inhibit muscle contractility.[47,90–92] Control of motility via CB1 can also be induced indirectly through inhibition of FAAH and an increase in endocannabinoid levels.[93,94] CB2s are not involved in the physiological regulation of GI motility; however, they could come into play in pathophysiological conditions.[30] CB1 not only inhibits motility but also gastric and intestinal secretion.[15,44,95] A study by MacNaughton et al. in the guinea pig ileum has addressed how CB1 may be integrated in this inhibitory mechanism, which involves activation of capsaicin-sensitive neurons.[16] The capsaicin receptor, TRPV1, which plays a significant importance in visceral hypersensitivity,[96] is mainly expressed in extrinsic primary afferent fibers in the GI tract, where it colocalizes with CB1.[16]


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