The endocannabinoid-CB receptor system: a new player in the brain-gut-adipose field

The 1990's have witnessed the discovery of the 'endocannabinoid-cannabinoid (CB) receptor (ECBR) system' consisting of specific receptors (CB1 and CB2), at least 3 endogenous ligands (anandamide, 2-arachidonyl glycerol and noladin ether) and their enzymes. Subsequently, a series of discoveries were made on the involvement of the ECBR system in many physiological functions including immunity, inflammation, neurotoxicity and neurotrauma, epilepsy, depression and stress, appetite, food intake and energy homeostasis, cardiovascular regulation, reproduction, and bone remodeling. The brain-gut-adipose axis regulates digestive processes, food ingestion and energy balance and is closely associated with hormonal regulation by the hypothalamic-pituitary-adrenal stress axis and by the mesolimbic reward system. It is proposed to call these interfacing systems the "alimentary control system". ECBR presence in brain, gastrointestinal as well as adipose tissue explains its role in food intake, digestion and the regulation of adipose tissue mass. Moreover, the ECBR system's involvement in stress and emotional processing, makes it eminently suited to be (one of) the principle players in the alimentary control system. The ECBR system is present during the early embryonal and postnatal stages and we have discovered endocannabinoids in maternal milk. The ECBR system seems to be of critical value for newborn milk ingestion and suckling. Ghrelin, an orexigenic gastric hormone, exerts many effects similar to those of endocannabinoids. Therefore this review will compare some of the functions and anatomy of ghrelin and endocannabinoids. It is concluded that (i) the ECBR system is a major mediator between the brain and the alimentary system, and possibly, the adipose tissue, (ii) the role of the ECBR system in adult regulation of food processing is a remnant of its critical role for the initiation of feeding in the newborn, and (iii) the pervasive influence of the ECBR system in alimentary control make it a highly suitable target for therapeutic developments for pathophysiological conditions such as inflammatory bowel disease, irritable bowel syndrome, gastric ulcers, nausea, anorexia and failure-to-thrive.Biomedical Reviews 2006; 17: 23-42