In this issue of JAMA Psychiatry, Davis and colleagues1 at the Johns Hopkins Center for Psychedelic and Consciousness Research have contributed a timely and important proof-of-concept randomized clinical trial on the effects of psilocybin-assisted supportive psychotherapy for the treatment of major depression. The authors reported rapid relief of depressive symptoms and high rates of response and remission that were sustained for more than 4 weeks in a sample of 24 midlife adults, many of whom had chronic depression. The research, supported by crowd-sourced funding, was carried out rigorously, with attention to experimental bias through the use of both immediate and delayed treatment conditions, single-blind and self-reported outcome assessments across many domains, and urn randomization to yield comparable groups of participants in both immediate and delayed treatment conditions. In addition to assessing efficacy, the investigators carefully documented potentially adverse (medical and psychological) effects of psilocybin use. Because of this attention to efficacy and tolerability as well as high rates of retention, treatment completion, and follow-up, the data from this trial are clinically informative and have heuristic value for further research.