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Psilocybin-assisted physiotherapy for refractory motor functional neurological disorder: protocol for a randomised dose-comparison pilot study

Chiranth Bhagavan, Alexander Bryson, Olivia Carter, Glenn Nielsen, David J. Berlowitz, Sara Issak, Sabine Braat, Sophie Zaloumis, Zachary Attard, Dina Eleftheriadis, Georgina Oliver, Deanne Mayne, Greg Roebuck, James Rucker, Matthew Butler, Richard Kanaan

Acta Neuropsychiatrica November 4, 2025 DOI: 10.1017/neu.2025.10042 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Pilot study Peer reviewed
Sample size 24
Population People with refractory motor functional neurological disorder
Intervention Psilocybin-assisted physiotherapy
Dose 15 mg or 25 mg
Duration Two physiotherapy sessions pre-dosing, six sessions post-dosing, follow-up at one week and four weeks after final physiotherapy
Topics Psilocybin
Keywords Protocol science Refractory planetary science Pilot trial Randomized controlled trial Motor activity Clinical trial Treatment protocol Functional training Physical therapy Functional movement Motor symptoms
Citations 4
Key findings The protocol tests whether two regimens of psilocybin-assisted physiotherapy are tolerable and feasible for refractory motor FND, with results intended to guide a larger efficacy trial.

Abstract

Abstract

Background: Motor functional neurological disorder (FND) is a common illness associated with significant functional impairment. There are no effective pharmacotherapies, and despite the early promise of physiotherapy studies, many suffer disabling symptoms in the long term. There is a theoretical rationale for combining psychedelics with physiotherapy; however, the potential benefit of this approach and optimal treatment model remains unexplored. Here, we present the protocol for the first study investigating the tolerability, feasibility, and potential efficacy of two distinct treatment regimens of psilocybin-assisted physiotherapy for refractory motor FND: a moderate dose that incorporates movement tasks during the acute drug effects versus a standard dose alone.

Methods: Twenty-four participants with refractory motor FND will be randomised in a 1:1 ratio to either (1) psilocybin 15 mg, with movement tasks conducted during the acute drug effects, or (2) psilocybin 25 mg alone. All participants will receive two sessions of FND-specific physiotherapy pre-dosing, six sessions of physiotherapy post-dosing, and undergo follow-up visits one week and four weeks following their final physiotherapy session. A battery of outcome measures will be completed as scheduled, assessing tolerability, feasibility, motor FND symptom severity, psychiatric and physical symptoms, quality of life, treatment expectations, intensity of the acute drug effects, personality, motor function, force-matching performance, resting-state and task-based brain imaging, and subjective experiences of the study treatment.

Discussion: These findings will assist the design of an adequately powered randomised controlled trial in this cohort. The findings may also inform the feasibility of psychedelic treatment in related functional and neuropsychiatric disorders.