EXPRESS: Plasma endocannabinoids and cannabimimetic fatty acid derivatives are altered in cyclic vomiting syndrome: The effects of sham feeding.

Abstract

Cyclic vomiting syndrome (CVS) is an underdiagnosed disorder of the gut-brain interaction. Our understanding of the pathophysiology of CVS is evolving. Here, we tested the hypotheses that: (1) the levels of endocannabinoids and related lipids are altered in CVS, and (2) cephalic-vagal stimulation drive changes in endolipid levels. Ten adult patients with CVS and 8 healthy controls were included. Indirect measurements of parasympathetic (RFa) functions were performed with spectral analysis of heart rate variability and respiratory activity. Plasma levels of endocannabinoids and related lipids were measured at baseline and during a sham feeding. Values are reported as mean ± SEM and compared using t-test or ANONA. CVS patients had a lower parasympathetic tone and response to Valsalva maneuver and deep breathing than the controls. The baseline 2-Arachidonoylglycerol (2-AG) had a significantly higher concentration in CVS (5.9e-008 ± 3.7e-008 mole/L) than control (3.7e-008 ± 1.3e-008 mole/; p<0.05). Sham feeding did not change the concentration of 2-AG. 2-linoleoylglycerol and 2-oleoylglycerol were significantly higher in CVS than control and did not change with sham feeding. Levels of N-acyl ethanolamines, including Anandamide (AEA), were not different in CVS vs. control. After sham feeding, AEA showed a trend toward increasing (P=0.08) in CVS, but not in control. With sham feeding, palmitoyl ethanolamine significantly increased in both CVS and control groups; oleoyl ethanolamine in CVS only, and stearoyl ethanolamine in the control group. Levels of endocannabinoids and related lipids are altered in CVS patients. Sham feeding affects endogenous signaling lipids in a disease and time-dependent manner.