Magic mushroom mystery: can psilocybin fight depression without the trip?

NCT ID NCT05710237

First seen Jun 25, 2026 · Last updated Jun 27, 2026 · Updated 1 time

Summary

This study tested whether psilocybin, the active ingredient in magic mushrooms, can treat depression even when its psychedelic effects are blocked by another drug (risperidone). Forty-one adults with treatment-resistant depression received either psilocybin alone, psilocybin plus risperidone, or placebo plus risperidone. The goal was to see if blocking the 'trip' would still allow antidepressant benefits, helping researchers understand how psilocybin works.

What this could mean

Our plain-language read of the trial. This is informational only — not medical advice or a prediction.

Active substance
psilocybin (the active ingredient in magic mushrooms) and risperidone (a drug that blocks psychedelic effects)
What this could lead to
If it works, this could help researchers understand whether psilocybin's antidepressant benefits come from the psychedelic experience itself or from other brain effects.
What could go wrong
This is a very small, early proof-of-concept trial with only 41 participants. It is designed to test feasibility, not to prove effectiveness. Results may not apply to larger populations.

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Conditions

The condition(s) this trial relates to.

Depressive Disorder, Treatment-Resistant

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Contacts and locations

Locations

  • Centre for Addiction and Mental Health

    Toronto, Ontario, M6J1H4, Canada

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