This talk will begin with a brief review of the natural sources of psychedelics that have been used for millennia.  That will be followed by a discussion of the 5-HT2A receptors that are the targets for the classic psychedelics; where they are located and very brief comments on the nature and function of G protein-coupled receptors.  There will be brief discussion of some preclinical studies from the Nichols lab, focused on elucidation of the conformation of the diethylamide function of LSD.  In particular, Leucine 229, in extracellular loop 2 of the receptor was shown to be a critical residue in the receptor kinetics of LSD binding to the receptor.  A few of the groundbreaking projects supported by the Heffter Research Institute, founded by the speaker in 1993, will be mentioned.  Finally, unpublished structures of several molecules bound to the human 5-HT2A receptor will be shown and very briefly noted.