Methods Evaluating Cannabinoid and Endocannabinoid Effects on Gastrointestinal Functions

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 Δ⁹ -tetrahydrocannibinol (Δ⁹ -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.