5-HT2A Agonists: A Novel Therapy for Functional Neurological Disorders?

Introduction

Functional neurological disorders (FNDs) are common conditions at the interface of neurology and psychiatry that are associated with a poor prognosis and limited, inconsistently effective treatments. Bryson and colleagues describe prevailing theoretical accounts that implicate a disturbance of somatic self-representation and an excessive top-down cognitive influence on sensorimotor processes as central to FND pathophysiology. These models—supported by behavioural studies and functional neuroimaging—help explain clinical features such as loss of motor agency and symptom variability with attentional focus. This paper sets out to synthesise evidence from cellular, neurophysiological and neuroimaging studies of 5-HT2A agonists and to argue that these agents may have unique therapeutic potential in FNDs. The authors propose that because 5-HT2A agonists perturb hierarchical brain dynamics and modulate networks involved in self-related processing, they could weaken pathological higher-order priors and restore more adaptive sensorimotor integration; on that basis the paper argues a clinical trial is warranted.