Probing the functional magnetic resonance imaging response to psilocybin in functional neurological disorder (PsiFUND): study protocol.
Matt Butler, Catherine Bird, Carolina Maggio, Amy Durden, Nadav L. Modlin, Kete Campbell‐coker, Mark J. Edwards, Susannah Pick, L S Merritt Millman, Emily Lowery, Chiranth Bhagavan, Richard Kanaan, Dawn Golder, Bridget Mildon, Mitul A. Mehta, James Rucker, Timothy R. Nicholson
Wellcome Open Research 2024 DOI: 10.12688/wellcomeopenres.22543.1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label neuroimaging study Peer reviewed |
|---|---|
| Sample size | 24 |
| Population | People with chronic functional neurological disorder |
| Intervention | Psilocybin |
| Dose | 25 mg |
| Duration | Three-month follow-up |
| Topics | Psilocybin |
| Keywords | Psychedelic medicine Neurological disorders Brain imaging Clinical research FMRI Functional neurological disorder Psychedelics |
| Citations | 4 |
| Key points | This study will probe mechanisms of FND and assess whether psilocybin with psychological support is safe and feasible in people with chronic FND. |
Abstract
Functional neurological disorder (FND) is a common cause of neurological symptoms including seizures and movement disorders. It can be debilitating, is associated with high health and social care costs, and can have a poor prognosis. Functional magnetic resonance imaging (fMRI) has suggested FND is a multi-network disorder. Converging evidence suggests that other mechanisms including dissociation, interoception, and motor agency may be abnormal in people with FND. Psychedelics are currently under investigation for numerous neuropsychiatric disorders and have been shown to disrupt functional brain networks. Administering psychedelics to people with FND will help us to probe mechanistic theories of the disorder. In this open-label neuroimaging study, we will administer 25mg oral psilocybin with psychological support to people with chronic FND (target n = 24). Participants will undergo resting-state and task-based (Libet's clock, a measure of motor agency) fMRI sequences which will be compared in a pre-post manner. Additional mechanistic outcomes including measures of interoception (heartbeat tracking task), somatisation, illness perceptions, suggestibility, and dissociation will be collected. Data on expectancy, preparedness, and subjective experience of the psychedelic experience will also be gathered. Participants will be followed up for three months following psilocybin administration. fMRI changes in networks will be analysed using seed-based approaches, and additional exploratory analysis of resting-state imaging will take place. The study will help us to probe the mechanisms thought to potentially underpin FND. As the first modern study of psychedelics in FND, it will also help us to understand whether psychedelic administration alongside psychological support might be safe and feasible in this patient population.
Comparable studies
Other non-randomized and open-label trials on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Patients with moderate-to-severe, unipolar, treatment-resistant major depression | 2016 | Open-label feasibility trial | n = 12 |
| Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Patients with severe, unipolar, treatment-resistant major depression | 2017 | Open-label trial | n = 20 |
| Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction Psychiatrically healthy nicotine-dependent smokers | 2014 | Open-label pilot study | n = 15 |
| Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression Patients with treatment-resistant depression | 2018 | Clinical trial | n = 20 |
| Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder Subjects with obsessive-compulsive disorder (OCD) | 2006 | Controlled clinical trial |
Citations in the library
Cited by 6
- Narrating the psychoneuroimmunomodulatory properties of serotonin 5-HT2A receptor psychedelics from a transdiagnostic perspective. Acta Neuropsychiatrica July 25, 2025
- How to set up a psychedelic study: Unique considerations for research involving human participants. Neuroscience & Biobehavioral Reviews July 1, 2026
- Psychedelics in functional disorders: A scoping review Progress in Neuro-Psychopharmacology and Biological Psychiatry February 10, 2026
- A Randomised, Triple-Blind, Dose-Finding Study of the Impact of Psilocybin on Motor Function in Healthy Participants medRxiv December 23, 2025
- Impact of Psilocybin on Motor Function in Healthy Participants: A Phase 1, Randomised, Triple-Blind, Dose-Finding Study CNS Drugs August 7, 2026
and 1 more in the library
Cites 49
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology November 8, 2017
- Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Psychopharmacology December 1, 2011
- Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences April 11, 2016
and 44 more in the library