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

Acta Neuropsychiatrica  – November 04, 2025

Source: OpenAlex

Summary

A novel approach is being tested to address motor functional neurological disorder (FND), a common and disabling condition currently lacking effective drug treatments. Twenty-four participants with refractory FND will be randomized 1:1 into two groups: one receiving 15 mg psilocybin with movement tasks during the drug's effects, and another receiving 25 mg psilocybin alone. All participants receive eight physiotherapy sessions. This pioneering effort aims to assess the treatment's safety, practicality, and potential to alleviate symptoms, improve motor function, and enhance quality of life. Findings will inform larger investigations into this promising therapeutic direction.

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.

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