In 1973, the federal government classified psychedelics as schedule I substances, rendering possession illegal, even for research purposes except under tightly regulated circumstances. Although these restrictions have hindered research on the therapeutic uses of psychedelics for decades, recent studies have brought increasing attention and enthusiasm to the potential benefits of psychedelic treatment.1 Accompanying this revival of psychedelic research have been initiatives by states and localities to legalize psychedelic possession and use. Two of the most ambitious measures, in Oregon and California, take different paths to legalization. This Viewpoint reviews these initiatives and the concerns they raise by looking to the cautionary precedents involving the legalization and commercialization of other controlled substances.