Psilocybin-assisted psychotherapy for depression: Emerging research on a psychedelic compound with a rich history

J Neurol Sci. 2022 Mar 15;434:120096. doi: 10.1016/j.jns.2021.120096. Epub 2021 Dec 16.


There is a serious need for novel therapies that treat individuals with depression, including major depressive disorder (MDD) and treatment-resistant depression (TRD). An emerging body of research has demonstrated that psychedelic drugs such as psilocybin, combined with supportive psychotherapy, exert rapid and sustained antidepressant effects. The use of psychedelics is not new: they have a rich history with evidence of their use in ritual and medical settings. However, due to political, social, and cultural pressures, their use was limited until modern clinical trials began to emerge in the 2010s. This review provides a comprehensive look at the potential use of psilocybin in the treatment of depression and TRD. It includes an overview of the history, pharmacology, and proposed mechanism of psilocybin, and describes several published studies in the last decade which have provided evidence of the efficacy and safety of psilocybin-assisted psychotherapy for individuals with depression. It also includes a discussion of the limitations and barriers of current research on psychedelics. The results of these studies are contextualized within the current treatment landscape through an overview of the pathophysiology of depression and the treatments currently in use, as well as the clinical needs these novel therapies have the promise to fulfill.

Keywords: Depression; Psilocybin; Psychedelics; Treatment-resistant depression.

Publication types

  • Review

MeSH terms

  • Depression
  • Depressive Disorder, Major* / drug therapy
  • Hallucinogens* / pharmacology
  • Hallucinogens* / therapeutic use
  • Humans
  • Psilocybin / pharmacology
  • Psilocybin / therapeutic use
  • Psychotherapy / methods


  • Hallucinogens
  • Psilocybin