The endocannabinoid system: function in survival of the embryo, the newborn and the neuron

Since the identification and cloning of the first cannabinoid (CBI) receptor and the subsequent discovery of the endogenous cannabinoid ligands (endocannabinoids), anandamide, 2-arachidonoyl glycerol (2-AG) and noladin ether, a intensive search for their function in health and disease has been launched. The endocannabinoids in the central nervous system bind Gi/o coupled CBI receptors that modulate adenylyl cyclase, ion channels and extracellular signal-regulated kinases. The present review discusses the nature of endocannabinoid (anandamide and 2-AG) neurotransmission, the in vivo activity of cannabinoids and the possibility that some of these activities are mediated via a receptor, yet to be discovered, which is distinct from the brain specific CBI receptor. Three physiological functions in which the endocannabinoids play a critical role are also discussed: embryonal implantation, feeding and appetite, and neuroprotection.