Our findings show that i.c.v. semapimod reduces manipulation-induced intestinal inflammation and prevented post-operative ileus. This anti-inflammatory effect depends on central activation of the vagus nerve.

Background and purpose: Transient lower oesophageal sphincter relaxations (TLESRs) are the main mechanism underlying gastro-oesophageal reflux and are a potential pharmacological treatment target. We evaluated the effect of the CB1/CB2 receptor agonist D -THC significantly reduced the number of TLESRs and caused a non-significant reduction of acid reflux episodes in the first postprandial hour. In addition, lower oesophageal sphincter pressure and swallowing were significantly reduced by D 9 -THC. After intake of 20 mg, half of the subjects experienced nausea and vomiting leading to premature termination of the study. Other side-effects were hypotension, tachycardia and central effects. Conclusions and implications: D 9-THC significantly inhibited the increase in meal-induced TLESRs and reduced spontaneous swallowing in both dogs and humans. In humans, D 9-THC significantly reduced basal lower oesophageal sphincter pressure. These findings confirm previous observations in dogs and indicate that cannabinoid receptors are also involved in the triggering of TLESRs in humans.

Loxiglumide significantly reduces the number of TLESRs triggered by gastric distension without interfering with swallow-related relaxation of the lower esophageal sphincter, suggesting the involvement of CCKA receptors in the reflex pathway mediating TLESRs.