Moving through the phases of clinical trials in psilocybin research

The therapeutic potential of psilocybin – the psychoactive component in magic mushrooms – has been of interest since the 1960’s in psychotherapy but there was little rigorous evaluation as to its benefit at the time. When the drug was designated Schedule 1 in 1970, any funding there was for research in this area petered out but, since 2000, there has been a resurgence of interest in this field with a more scientific focus.

Academic and consultant psychiatrist, Dr James Rucker was awarded a NIHR Clinician Scientist Fellowship to research the use of psilocybin therapy for people with treatment resistant depression (TRD). His career as an academic clinician started in earnest ten years earlier when, as a junior doctor, he was awarded one of the first preparatory fellowships from the NIHR Maudsley Biomedical Research Centre (BRC).
The NIHR Clinician Scientist fellowship allowed Dr Rucker to build a small research team under the mentorship of Professor Allan Young, who has twice been appointed NIHR Senior Investigator and was part of the NIHR Maudsley BRC for several years, leading the Translational Therapeutics Cluster from 2018 – 2022.

The group launched the NIHR funded phase 2 PsiDeR trial to investigate the use of psilocybin to treat TRD. As well as evaluating the safety and effectiveness of psilocybin, the study collected brain scanning data and blood-based measures with the aim of understanding the mechanisms underlying positive effect and identifying those who may benefit the most from psilocybin therapy.

The launch of the PSiDeR trial attracted interest from industry and triggered the start of a long-term partnership with Compass Pathways - a biotechnology company that accelerates patient access to evidence-based innovation in mental health.

Supported by the NIHR Maudsley BRC and funded by Compass Pathways Dr Rucker led a phase 1 trial with 89 healthy volunteers. The trial took place in the NIHR King’s Clinical Research Facility after receiving Home Office approval for the use of psilocybin in research. It was at the NIHR King’s CRF that the team developed the model for psilocybin therapy with a trained therapist sitting with the participant in a specially designed room to talk through their experiences after psilocybin administration. As well as demonstrating the safety of psilocybin, the phase 1 trial showed it was possible to treat at least six people at the same time with this approach. An important aspect to demonstrate early on so as to provide insight into the potential for this approach to be scaled up.

The launch of NIHR funded PSiDeR trial and the healthy volunteer trial demonstrated a successful model for both the therapy itself and how to conduct research in this area. Compass Pathways launched a phase 2b multi-centre trial for TRD with King’s leading the European arm and achieving the highest recruitment figures amongst the different sites. Dr Rucker’s team was central in developing the delivery of the therapy and standardising its approach through training and materials. The trial was completed in 2022 with positive results that received a wide range of media coverage.

Looking to the future

The initial research team has now developed into the Psychoactive Trials Group at King’s College London, also running trials and associated mechanism and therapy research with MDMA and dimethyltryptamine. Alongside the work on psilocybin and TRD, the team are working with Compass Pathways on a psilocybin clinical trial for PTSD and NIHR Maudsley BRC researchers are leading the European arm of a multi-centre trial for anorexia and the first study of psilocybin for adults with autism.

In March 2023 Compass Pathways launched their phase 3 trial for people with TRD in which the King’s team will lead the European arm and in November 2023 the UK component of phase 3 trial started with the official opening of the new Centre for Mental Health Research and Innovation. The Centre is a partnership between King’s College London, South London and Maudsley NHS Foundation Trust and Compass Pathways and initially will support the current psilocybin trials and studies. It will contain four dedicated therapy rooms for research, alongside training rooms and a small laboratory space with a team of employees from across the partnership.

Through the support, expertise and facilities of the NIHR Maudsley BRC and NIHR King’s CRF, researchers have developed and evaluated psilocybin therapy for efficacy and safety whilst also keeping in mind the feasibility to translate the therapy into the NHS and other healthcare settings. By bringing together clinical, academic and lived experience expertise the group have worked in partnership with Compass Pathways to develop an effective and testable model of the delivery of psilocybin therapy that has the potential to be implemented at scale.

Please note image shows therapy room at NIHR King’s Clinical Research Facility.