The endogenous cannabinoid system: a new player in the brain-gut-adipose axis

The 'endocannabinoid (CB) receptor (ECBR) system', consists of specific receptors and several endogenous ligands. The ECBR system is involved 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 and gastrointestinal system interact bidirectionally in the regulation of digestive processes, food ingestion and energy balance (hence the 'brain-gut axis'). Emotional stress and and the 'reward' center in the brain modulate the brain-gut axis. ECBR presence in brain, gastrointestinal as well as adipose (fat) tissue as well as its involvement in stress and emotional processing, provide it with a major role in food intake, digestion and the regulation of adipose tissue mass and adipocyte endocrine function. With cannabinoid receptors and endocannabinoids present from the early embryonic stages and in maternal milk, the ECBR system seems of critical value for newborn milk ingestion. It is concluded that (i) the ECBR system is a major mediator between the brain and the digestive system, (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 conditions such as inflammatory bowel disease, irritable bowel syndrome, gastric ulcers, nausea, obesity, anorexia and failure-to-thrive.