Chemistry/structural biology of psychedelic drugs and their receptor(s)

This brief review highlights some of the structure-activity relationships of classic serotonergic psychedelics. In particular, we discuss structural features of three chemotypes: phenethylamines, ergolines, and certain tryptamines, which possess psychedelic activity in humans. Where it is known, we point out the underlying molecular mechanisms utilized by each of the three chemotypes of psychedelic molecules. With a focus on the serotonin 5-HT2A receptor subtype, a G-protein coupled receptor known to be the primary target of psychedelics, we reference several x-ray and cryoEM structures with various ligands bound to illustrate the underlying atomistic basis for some of the known pharmacological observations of psychedelic drug actions.