ENDOGENOUS CANNABINOID LIGANDS - CHEMICAL AND BIOLOGICAL STUDIES

Arachidonic acid ethanolamide (anandamide) is a brain constituent that binds to the brain cannabinoid receptor (CB1). It produces many of th e pharmacological effects caused by Delta(9)-tetrahydrocannabinol (Del ta(9)-THC) in mice. Anandamide parallels Delta(9)-THC in its specific interaction with the cannabinoid receptor and in inhibition of adenyla te cyclase. Two additional fatty acid ethanolamides that bind to the c annabinoid receptor, homo-gamma-linolenylethanolamide and docostetraen ylethanolamide, have been identified in the brain. We believe that the anandamides are involved in the coordination of movement and short te rm memory. Depression of ambulation in an open field and the analgetic response to anandamide are not fully developed until adulthood, possi bly due to an age-related increase in the CB1 receptor concentration. This observation has clinical implications in pediatrics. A second can nabinoid receptor (CB2) is present in the spleen. A monoglyceride, 2-a rachidonyl-glycerol which binds to both CB1 and CB2 in transfected cel ls and inhibits andenylate cyclase in spleen cells was found in the gu t. Its role is apparently associated with the immune system. These fat ty acids amides and esters represent a new family of chemical modulato rs in the body.