Does psilocybin treat depression? What the COMP360 trials found and why they are debated
A 2022 trial in the New England Journal of Medicine and a 2025 phase 3 result both beat a comparison group, yet critics say a trial where everyone can tell what they took cannot be fully trusted.
Possibly, in some people, but the evidence is early and contested. Trials of psilocybin, the active compound of "magic mushrooms", have found that a single dose with psychological support can reduce depression scores more than a comparison treatment. Whether the benefit is large, lasting or truly caused by the drug is still debated.
The best-known early result came in 2022 in the New England Journal of Medicine. In this phase 2 trial, adults with were randomly given one of three doses of a synthetic psilocybin formulation known as COMP360, with the lowest dose acting as the control. The authors concluded that the highest dose, but not the middle dose, reduced depression scores significantly more than the control over 3 weeks. The authors wrote that larger and longer trials are needed. The study was funded by the company COMPASS Pathfinder.
In June 2025 the company announced a trial that met its primary : at 6 weeks there was a 3.6-point greater reduction on the depression scale (MADRS) than with placebo. That is small: an advantage of at least 5 points had been expected. As of October 2026, a second phase 3 trial had also met its endpoint, but the effect was modest.
Why do critics urge caution? In a psychedelic trial most people can tell whether they got the drug. This "functional unblinding", together with strong expectations, is described as a major limitation and source of bias.
June 2025 phase 3: advantage over placebo at 6 weeks
points on the MADRS depression scale
| MADRS points better than placebo | |
|---|---|
| Minimum advantage that had been expected | 5 points on the MADRS depression scale |
| Advantage observed | 3.6 points on the MADRS depression scale |
What the trials found
- A single dose with support beat a comparison in the 2022 phase 2 trial at 3 weeks
- (June 2025) met its main , but the gain was small
- Adverse events were common
Why caution is urged
- People can feel the drug, so blinding fails
- Expectations can raise scores for any treatment
- Most trials had financial conflicts and risk of bias
Quiz me
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Recap
Psilocybin trials show early, modest benefit, but unblinding and expectation make the size of the effect uncertain.
💡 A trick to remember it · A trial you can feel is a trial you cannot fully blind: the drug gives itself away.
Surprising fact · The 2025 phase 3 advantage over placebo was 3.6 points on the MADRS scale, below the 5 points expected.
Connects to
- 🔬 How did Johns Hopkins and Imperial College restart psychedelic research?
- 🧠 Why did the FDA turn down MDMA-assisted therapy for PTSD in 2024?
- ⚖️ Talk therapy or medication for depression: what is the evidence fight actually about?
- 🎲 How does a trial keep hope from fooling everyone?
- 💊 Can a sugar pill really make you feel better?
Sources (3)
No source, no claim. Every fact in this lesson (16 claims) cites at least one of these.