Has psilocybin's depression benefit been overestimated?

Psilocybin for treatment-resistant depression may be less effective than earlier trials suggested. A new study compares psilocybin to other depression treatments by focusing on the control groups and the placebo effect. The discussion argues that disappointment and expectancy differences can make placebo controls for psilocybin trials worse, widening the apparent drug-to-control gap. The guest, Associate Professor Fredrik Hieronymus, explains that control group quality is a longstanding issue in depression trials and that effect sizes may decline as psilocybin moves from highly selected, motivated participants to broader patient groups. The episode also compares these dynamics to earlier ketamine research, where early trial controls looked worse than later real-world or market conditions.