The major limitations of the current evidence for psychedelic drugs are interconnected. In the absence of pharmaceutical industry interest, limited support from philanthropic sources has funded the research, restricting trials to relatively small samples of patients because of the cost of doing larger studies. The persons who have done the research believe in the therapeutic value of psychedelic drugs. This is to be expected, given the history of psychedelics and the reputational challenges in conducting clinical research on them. If psychedelic drugs are introduced in clinical practice, there is a risk that their use will get ahead of the evidence on their safety and efficacy, in much the same way that “medical cannabis” has done. If the criteria for who is a qualified therapist are relaxed, MDMA may be used to treat unhappiness, anxiety and existential angst. The evidence may be used to argue for compassionate access to other psychedelic drugs, such as LSD, mescaline and DMT. It is uncertain if the use of psychedelics will remain under medical supervision for approved disorders, or whether their use will be advocated for spiritual and other nonmedical purposes. A combination of libertarian and utilitarian arguments may be used to justify the legalization of adult use of these drugs for any purpose, because they cause little harm to users and have a low abuse potential. There may also be demands for compassionate access to plant-based psychedelic drugs in advance of any research evidence. US states may pass citizen-initiated referenda to legalize the medical use of psychedelic mushrooms and plants, such as ibogaine and ayahuasca, by appealing to the putative “entourage” effects of whole plants and the misconception that medicines derived from plants are safer than “synthetic” pharmaceuticals. For all these reasons, we need public funding of independent evaluations of the efficacy of psychedelic drugs. Trials should involve larger numbers of patients who are representative of those clinical disorders for which these drugs may be used, and should include longer-term follow-up evaluations of safety and sustainability of favorable outcomes.