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Endocannabinoid signaling system alterations The endocannabinoid signaling system plays an important role in CVS.21,22 This system is formed by endogenous ligands, N-arachidonoylethanolamide, 2-arachidonylglycerol (endocannabinoids), and two cannabinoid G-protein coupled receptors (cannabinoid receptor type 1 [CNR1] and type 2 [CNR2]), which regulate gastrointestinal motility.23,24 The CNR1 and CNR2 receptor agonists prevent vomiting, and in contrast, the CNR1 receptor antagonists cause vomiting