The therapeutic potential of psilocybin: a systematic review

Expert Opin Drug Saf. 2022 Jun;21(6):833-840. doi: 10.1080/14740338.2022.2047929. Epub 2022 Mar 2.


Introduction: Psychedelic drugs were used quite extensively before their prohibition in 1968 which delayed research. However, since the 1990s, studies on the potential therapeutic benefits of psychedelics have rapidly increased.

Areas covered: This systematic review provides an overview of the clinical effects of psilocybin in the treatment of a variety of mental disorders. Only (randomized) clinical trials were selected. A total of 11 studies (15 publications) were selected, including seven randomized controlled trials (eight publications) and four single arm open-label studies (seven publications). In total, 488 patients were included in the selected studies: 333 patients treated with psilocybin and 155 patients treated with (active) placebo. In nine studies, psychotherapeutic support was provided as an integral part of the psilocybin treatment. The findings of these studies collectively show that psilocybin has a positive benefit-risk balance in the treatment of various mental disorders with an immediate and prolonged effect following 1-3 doses of psilocybin and a few (serious) adverse events.

Expert opinion: Psilocybin - mostly combined with psychotherapy or psychotherapeutic support - shows a promise as a treatment for various (treatment-resistant) mental disorders. Larger double-blind RCTs with objective (long-term) outcomes are needed to confirm these findings before standard clinical use of psilocybin can be considered.

Keywords: Psilocybin; anxiety; depression; psychedelic agents.

Publication types

  • Systematic Review

MeSH terms

  • Double-Blind Method
  • Hallucinogens* / adverse effects
  • Humans
  • Mental Disorders* / chemically induced
  • Mental Disorders* / drug therapy
  • Psilocybin / adverse effects
  • Randomized Controlled Trials as Topic


  • Hallucinogens
  • Psilocybin