Molecular model of anandamide docked with the CB1 cannabinoid receptor. The endocannabinoid anandamide (space-filling molecule mostly in gray) assumes an extended conformation in the lipid bilayer (green) with its polar group at the same level as the polar phospholipid head groups. It diffuses laterally to the binding site of the CB1 receptor (shown as 7 multicolored helices) and interacts with a hydrophobic groove formed by helices 3, 5 and 6 (purple, cyan and blue helices). The multicolored dots represent water molecules on the intracellular (bottom) and extracellular (top) sides of the membrane bilayer.

Image: Drs. A. Makriyannis and X. Tian