Identification of brain receptors that interact with natural or synthetic cannabinoids in the 1980s stimulated the quest for the brain’s endogenous cannabis-like molecule .  From the abundance of cannabinoid (CB)  receptors, it was inferred that there must be an endogenous ligand that activates those receptors. Following many years of research, the elusive endogenous CB was identified as arachidonolyl ethanolamide (AEA) and named anandamide.  The molecule is found in nearly all tissues in many animals. Anandamide binds to both types of CB receptors, the CB1 receptor found in the central nervous system and the CB2 receptors distributed in peripheral tissues, immune cells, but also is found in some neurons of the brain stem (dorsal motor nucleus of the vagus, spinal trigeminal nucleus and nucleus ambiguous). Anandamide (AEA) and 2-arachidonoylgylcerol (2-AG) are derived from fatty acid metabolism and serve as a bi-lipid messengers that activate the CB receptors on nearby cells. Although their pharmacological properties are similar to THC, their  chemical structure is very different than the phytocannabinoids THC and CBD.

Mechoulam et al., (2014) Early phytocannabinoid chemistry to endocannabinoids  and beyond Nat Rev Neurosci.  Vol 14, Issue 11, pp 757-764


Schematic representation of the endocannabinoid system in pre- and postsynaptic neurons. The presynaptic terminal is located in the top, whereas the postsynaptic neuron is located in the bottom. EMT, endocannabinoid membrane transporter; MAGL, monoacylglyceride lipase; DAGL, DAG lipase; AEA, anandamide; NArPE, N-arachidonyl phosphatidylethanolamine; NAT, N-acyltransferase. Figure from Pacher et al.(2006) Pharmacological Reviews September  58 (3) 389-46