Probing the functional magnetic resonance imaging response to psilocybin in functional neurological disorder (PsiFUND): study protocol

Background 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. Protocol 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. Discussion 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.