Reappraisal of the hype and hope offered by psilocybin treatment of depression

N Z Med J. 2025 Sep 19;138(1622):94-97. doi: 10.26635/6965.7138.

Abstract

Aim: To provide a balanced account of psilocybin treatment of depression for expectations to be appropriately set.

Method: Review and discussion of key psilocybin efficacy studies. Reporting of side effects and risk of harm with psychedelic treatments. Comparisons and contrasts with ketamine studies of treatment-resistant depression (TRD).

Result: Early psilocybin studies offer promise but expectation bias and functional unblinding are factors in the treatment response. Psilocybin is generally well tolerated but side effects are often not systematically reported, and some recipients may experience harm. The ketamine research has similar methodological considerations, but the weight of positive evidence is stronger for a treatment-resistant group.

Conclusion: The evidence for psilocybin treatment of depression is insufficient to press for wider availability and use.

Publication types

  • Review

MeSH terms

  • Depression* / drug therapy
  • Depressive Disorder, Treatment-Resistant* / drug therapy
  • Hallucinogens* / adverse effects
  • Hallucinogens* / therapeutic use
  • Hope
  • Humans
  • Ketamine / therapeutic use
  • Psilocybin* / adverse effects
  • Psilocybin* / therapeutic use
  • Treatment Outcome

Substances

  • Psilocybin
  • Hallucinogens
  • Ketamine