MDMA has an apparently novel therapeutic mechanism that is distinct from classical psychedelics and that may offer benefits in a wide range of CNS disorders. Beginning with Shulgin's pioneering research in the 1970s, scientists and psychonauts have explored how changing MDMA's chemical structure modifies the drug's effects. This presentation will describe the history of attempts to modify and improve on MDMA, including novel compounds and drug combinations, and will discuss what this history can teach us about the mechanisms of MDMA's therapeutic magic.