Evidence versus expectancy: the development of psilocybin therapy

Psilocybin therapy, which combines drug dosing with psychological support and integration, has been studied for 25 years. Early clinical trials show promise for treatment-resistant depression, but masking (blinding) likely fails, and expectancy effects may contribute to the therapeutic mechanism. Distinguishing drug effects from expectancy is necessary yet difficult when masking fails. Masking and expectancy have not been routinely measured in psilocybin or other medication trials; doing so could improve research and influence psychiatry. This opinion piece reviews the development, hope, hype, challenges, and opportunities of psilocybin therapy.

Study at a glance

Abstract

Summary Although the development of psilocybin therapy has come as a surprise to many, modern research with the drug has been ongoing for 25 years. Psilocybin therapy is composed of psilocybin dosing sessions embedded within a wider process of psychoeducation, psychological support and integration. Early phase clinical trial evidence is promising, particularly for treatment-resistant depression. However, masking probably fails and expectancy effects may be a part of the mechanism of change. Disambiguating between drug and expectancy effects is a necessary part of the development process, yet this is difficult if masking fails. Hitherto, masking and expectancy have not been routinely measured in psilocybin or other medication trials. Doing so represents an opportunity for research and may influence psychiatry more widely. In this opinion piece I summarise the clinical development process of psilocybin therapy thus far, discussing the hope, the hype, the challenges and the opportunities along the way.