Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up

J Psychopharmacol. 2022 Feb;36(2):151-158. doi: 10.1177/02698811211073759.


Background: Preliminary data suggest that psilocybin-assisted treatment produces substantial and rapid antidepressant effects in patients with major depressive disorder (MDD), but little is known about long-term outcomes.

Aims: This study sought to examine the efficacy and safety of psilocybin through 12 months in participants with moderate to severe MDD who received psilocybin.

Methods: This randomized, waiting-list controlled study enrolled 27 patients aged 21-75 with moderate to severe unipolar depression (GRID-Hamilton Depression Rating Scale (GRID-HAMD) ⩾ 17). Participants were randomized to an immediate or delayed (8 weeks) treatment condition in which they received two doses of psilocybin with supportive psychotherapy. Twenty-four participants completed both psilocybin sessions and were followed through 12 months following their second dose.

Results: All 24 participants attended all follow-up visits through the 12-month timepoint. Large decreases from baseline in GRID-HAMD scores were observed at 1-, 3-, 6-, and 12-month follow-up (Cohen d = 2.3, 2.0, 2.6, and 2.4, respectively). Treatment response (⩾50% reduction in GRID-HAMD score from baseline) and remission were 75% and 58%, respectively, at 12 months. There were no serious adverse events judged to be related to psilocybin in the long-term follow-up period, and no participants reported psilocybin use outside of the context of the study. Participant ratings of personal meaning, spiritual experience, and mystical experience after sessions predicted increased well-being at 12 months, but did not predict improvement in depression.

Conclusions: These findings demonstrate that the substantial antidepressant effects of psilocybin-assisted therapy may be durable at least through 12 months following acute intervention in some patients.

Keywords: Insight; long-term effects; major depressive disorder; mystical experience; psilocybin.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / pharmacology*
  • Combined Modality Therapy
  • Depressive Disorder, Major / physiopathology
  • Depressive Disorder, Major / therapy*
  • Female
  • Follow-Up Studies
  • Hallucinogens / administration & dosage
  • Hallucinogens / adverse effects
  • Hallucinogens / pharmacology*
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Psilocybin / administration & dosage
  • Psilocybin / adverse effects
  • Psilocybin / pharmacology*
  • Psychiatric Status Rating Scales
  • Psychotherapy / methods
  • Time Factors
  • Treatment Outcome
  • Young Adult


  • Antidepressive Agents
  • Hallucinogens
  • Psilocybin