This chapter briefly describes the physiological neural mechanisms by which diverse
neurotransmitter receptor systems control several aspects of gastrointestinal functions such as motility, secretion, feeding, and
emesis. The current techniques used to study the effects of
cannabinoids on these gastrointestinal functions are then sequentially described, starting with isolated gastrointestinal muscle preparations and ultimately evolving to whole animal models. Both delta9-tetrahydrocannibinol (delta9-THC) and well-studied representatives of other classes of exogenous
cannabinoid CB1/
CB2 receptor agonists inhibit gastrointestinal motility, peristalsis, defecation, and secretions via
cannabinoid CB1 receptors since the CB1 (SR141716A)- and not the CB2 (SR144528)-receptor antagonist reverses these effects in a dose-dependent manner. In addition, exogenous
cannabinoids inhibit
vomiting produced by diverse
emetic stimuli in a SR141716A-sensitive manner in different animal models of
emesis. Often these
cannabinoids produce hyperphagic effects under laboratory conditions in most human and animal models of feeding. Administration of
SR141716A by itself can produce effects opposite to
cannabinoid agonists (e.g., increases in gastrointestinal motility and secretions,
hyperphagia and
vomiting), which suggests an important role for
endocannabinoids in these gastrointestinal functions. Indeed, the presence of
cannabinoid CB1 receptor markers,
endocannabinoids such as
anandamide and
2-arachidonoylglycerol (2-AG), their metabolic
enzymes, and an
endocannabinoid reuptake system have been confirmed in the gastrointestinal tract (GIT). The well-studied
endocannabinoid anandamide also seems to reduce both gastrointestinal motility and secretion while producing
hyperphagia. On the other hand, while the less well-investigated
endocannabinoid 2-AG is a potent emetogen,
anandamide may possess weak
antiemetic activity.