Psilocybin-assisted therapy for the treatment of resistant major depressive disorder (PsiDeR): protocol for a randomised, placebo-controlled feasibility trial

BMJ Open. 2021 Dec 1;11(12):e056091. doi: 10.1136/bmjopen-2021-056091.


Introduction: Psilocybin-assisted therapy may be a new treatment for major depressive disorder (MDD), with encouraging data from pilot trials. In this trial (short name: PsiDeR) we aimed to test the feasibility of a parallel-group, randomised, placebo-controlled design. The primary outcomes in this trial are measures of feasibility: recruitment rates, dropout rates and the variance of the primary outcome measure of depression.

Methods and analysis: We are recruiting up to 60 participants at a single centre in London, UK who are unresponsive to, or intolerant of, at least two evidence-based treatments for MDD. Participants are randomised to receive a single dosing session of 25 mg psilocybin or a placebo. All participants receive a package of psychological therapy. The primary outcome measure for depression is the Montgomery Asberg Depression Rating Scale collected by blinded, independent raters. The primary endpoint is at 3 weeks, and the total follow-up is 6 weeks. With further informed consent, this study collects neuroimaging and omics data for mechanism and biomarker analyses and offers participants an open label extension consisting of a further, open label dose of 25 mg of psilocybin.

Ethics and dissemination: All participants will be required to provide written informed consent. The trial has been authorised by the National Research Ethics Committee (20-LO/0206), Health Research Authority (252750) and Medicine's and Healthcare Products Regulatory Agency (CTA 14523/0284/001-0001) in the UK. Dissemination of results will occur via a peer-reviewed publication and other relevant media.

Trial registration numbers: EUDRACT2018-003573-97; NCT04959253.

Keywords: adult psychiatry; clinical trials; depression & mood disorders.

Publication types

  • Clinical Trial Protocol
  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19*
  • Depressive Disorder, Major* / drug therapy
  • Feasibility Studies
  • Humans
  • Psilocybin / therapeutic use
  • Randomized Controlled Trials as Topic
  • SARS-CoV-2
  • Treatment Outcome


  • Psilocybin

Associated data