Recent work in the field of gastrointestinal pharmacology of cannabinoids has focused on enteric endocannabinoid and endovanilloid systems and their modulation in pathophysiological conditions. CB(1) receptor immunoreactivity was detected on enteric cholinergic neurones and vasoactive intestinal peptide-containing submucosal ganglion cells, on discrete nuclei of the dorsovagal complex (involved in emesis) and on central and peripheral vagal terminals, thus controlling gastroesophageal reflux and gastrointestinal motility. CB(1) receptor activation by endocannabinoids inhibited induced fluid secretion and inflammation in animal models and reduced proliferation of cultured colorectal cancer cells. Endocannabinoids also activate cannabinoid CB(2) and vanilloid VR1 receptors in certain inflammatory states. Thus endocannabinoid metabolism could provide a useful therapeutic target for many gastrointestinal disorders.