FDA Recommends Expanding Psilocybin Depression Research

The FDA’s request in early 2017 transformed a plan to study psilocybin in cancer patients into a proposal to investigate depression across the general population. It was a striking change in scale and regulatory interest: officials saw enough promise in the existing data to ask for a larger question, while leaving that question to be answered by further trials.

The Evidence That Reached Regulators

In December 2016, a front-page New York Times story announced results from the New York University and Johns Hopkins University psilocybin cancer studies. Published together in a special issue of the Journal of Psychopharmacology, the studies drew nearly a dozen commentaries from prominent figures in mental health, including two former presidents of the American Psychiatric Association.

Across the two trials, about 80 percent of cancer patients showed clinically significant reductions in anxiety and depression. The improvement lasted at least six months after a psilocybin session, and the intensity of participants’ reported mystical experiences closely tracked the extent of symptom relief. The findings were notable for the size and persistence of the reported effects, though they came from small studies rather than definitive large-scale trials.

The combined number of subjects was only eighty. The results would need replication on a larger scale before the government could consider rescheduling psilocybin or approving the treatment. Still, the findings had already begun to change the research climate: medical schools sought to participate in future trials, funders offered support, and New York University moved Stephen Ross’s treatment room from its dental college into the main hospital.

The FDA Broadens the Question

Early in 2017, Roland Griffiths and Stephen Ross brought the cancer-trial results to the FDA hoping to obtain approval for a larger, phase 3 study of psilocybin for cancer patients. They had chosen that population partly because they believed it would be easier to secure permission to study a controlled substance among people who were seriously ill or dying.

Instead, FDA staff asked them to expand the proposed research and test whether psilocybin could treat depression in the general population. The regulators viewed the data as a sufficiently strong signal of possible antidepressant benefit to warrant investigation, given the scale of need and the limits of existing therapies. Ross later described the meeting as surreal, recalling that he had been stunned by both the response and its implications.

The request was not an approval of a treatment or proof that psilocybin worked for depression. It proposed a new research direction. Nor was the meeting’s account independently confirmed by the agency: when asked, the FDA declined to confirm or deny it, saying it did not comment on drugs in development or under regulatory review.

A European Parallel

The shift in ambition had a parallel in Europe. In 2016, researchers approached the European Medicines Agency seeking permission to study psilocybin for anxiety and depression in people facing life-changing diagnoses. Regulators noted that existential distress was not an official DSM diagnosis and therefore was not covered by national health services. They nevertheless pointed to a possible depression signal and encouraged a large, multisite trial.

That response reflected, in part, an early feasibility study led by Robin Carhart-Harris in David Nutt’s laboratory at Imperial College London. The initial study gave psilocybin to twelve people with treatment-resistant depression—six men and six women, all of whom had already tried at least two treatments without success. It had no control group, and participants knew they were receiving psilocybin. After one week, all showed symptom improvement; two-thirds were depression-free, in some cases for the first time in years. Seven still showed substantial benefit three months later.

The study later expanded to twenty participants. At six months, six remained in remission, while the others had relapsed to varying degrees, suggesting that treatment might need to be repeated. The researchers reported that psilocybin was well tolerated and that there were no adverse events, but the study’s modest size and lack of randomization limited what it could establish. The European agency’s response, like the FDA staff’s, treated the results as grounds for a larger test, not as settled evidence.

Promise, Method, and Uncertainty

The FDA’s request mattered because it took the research beyond the narrower case the investigators had initially chosen. It also exposed the difficult questions that larger trials would have to address: psychedelic studies are hard to blind; the effects of a drug session are intertwined with the therapy surrounding it; and psilocybin remained illegal. A positive signal therefore had to be tested within a research design capable of distinguishing the drug’s effects from expectations, therapeutic attention, and other influences.

The book’s account places this moment against a longer record of both promise and methodological dispute. Earlier LSD trials for alcohol dependence appeared highly successful in Saskatchewan, but a Toronto replication conducted in neutral rooms, with little engagement from clinicians and, for some participants, restraints or blindfolds, produced worse results and frightening experiences. The contrast showed how much the conditions of a session could matter. In another case, a later reconstruction of the Concord Prison Experiment found no statistically significant difference in recidivism, despite Timothy Leary’s much more dramatic reported figures. These histories do not determine what psilocybin can do for depression, but they underscore why initial results cannot stand in for careful replication.

The FDA’s move was thus consequential without being conclusive. It signaled that regulators considered the depression hypothesis worth testing, even amid unusual scientific and legal obstacles. The small cancer trials and early depression study supplied reasons to ask a larger question; they did not yet supply its answer.