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

This paper (2021) lays out the protocol for a randomized, placebo-controlled trial exploring the safety and efficacy of using psilocybin-assisted therapy for the treatment of treatment-resistant major depressive disorder (MDD). Up to 60 participants will be selected and randomized to a single dosing session of 25mg psilocybin or placebo.


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.”

Authors: James Rucker, Hassan Jafari, Tim Mantingh, Catherine Bird, Nadav Liam Modlin, Gemma Knight, Frederick Reinholdt, Camilia Day, Ben Carter & Allan Young

Study details

Compounds studied

Topics studied
Treatment-Resistant Depression Depression

Study characteristics
Double-Blind Randomized

60 Humans


Authors associated with this publication with profiles on Blossom

James Rucker
James Rucker is a Senior Clinical Lecturer at The Institute of Psychiatry, Psychology & Neuroscience in King's College London.


Institutes associated with this publication

King's College London
KCL is home to the Psychedleic Trials Group.

Linked Clinical Trial

Psilocybin in Depression Resistant to Standard Treatments
A single centre clinical trial to evaluate the feasibility, safety and efficacy of psilocybin, given under supportive conditions, in a randomised, blinded design in adult participants with treatment resistant major depressive disorder.

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