Endocannabinoid-related lipids are increased during an episode of cyclic vomiting syndrome

Background The endocannabinoid system and the hypothalamic-pituitary-adrenal axis are important neuromodulators of nausea and vomiting. This led us to hypothesize that patients with cyclic vomiting syndrome (CVS) have lower serum endocannabinoids (eCBs) and higher salivary cortisol and alpha amylase. Methods Serum eCBs and related lipids, N-oleoylethanolamine (OEA) and N-palmitoylethanolamide (PEA), and salivary cortisol, and alpha amylase (index of sympathetic nervous system activity) were measured in 22 CVS patients (age 40 +/- 11, female = 17) in the well and sick phases and 12 matched controls (age 37 +/- 12, female = 10). Key Results Contrary to our hypothesis, serum concentrations of the eCBs were not different among the study groups. However, serum concentrations of OEA and PEA were significantly higher during the sick than well phase in CVS patients (p = 0.001 and p = 0.04). There were positive correlations between serum PEA and nausea scores in the sick phase (Pearson's rho = 0.48, p = 0.036) and between serum OEA and poor sleep quality in patients (Pearson's rho = 0.7, p = 0.0005). Salivary cortisol and alpha amylase were not different between patients and controls, but subgroup analysis revealed that both were significantly higher in marijuana users compared to non-users during the sick phase (p = 0.04 and 0.03, respectively). Conclusions& Inferences These data demonstrate that eCB-related lipids, OEA and PEA, are mobilized in the sick phase of CVS and are positively correlated with several of the symptoms of a CVS episode. These data also suggest the hypothesis that chronic marijuana use results in enhanced stress responses during CVS.