Abstract
Rationale Clinical interest in psilocybin-assisted rehabilitation for motor disorders is growing. However, psilocybin’s motor effects are under-researched, and quantifying them is essential for assessing treatment risks and outcomes. Objectives This study aims to clarify whether acute effects of psilocybin disrupt established patterns of manual dexterity and coordination. Specifically, we evaluate the impact of psilocybin on velocity, smoothness and kinematic manifold stability. Methods In a randomised, blinded trial, healthy participants received three doses of psilocybin (5–20 mg) administered one week apart. Manual dexterity was assessed using the Box and Block Test (BBT) at baseline and 1.5, 3, and 4.5 hours post-drug administration. Task performance was analysed using a Bayesian mixed-effects model. For kinematic analysis, 21 hand landmarks were tracked from video recordings obtained at baseline and 1.5 hours post-administration. Principal component analysis (PCA) was the basis for evaluating the stability and dimensionality of latent structure. Results BBT performance showed a modest biphasic dose–response pattern at higher doses (10–20 mg), with slight impairment during peak effects and slight improvement 4.5 hours post-administration relative to baseline. Effect sizes were small compared to inter-individual baseline variability. Kinematic analyses revealed no substantial changes in movement smoothness or velocity. Dimensionality metrics indicated a stable coordination structure, although finger movements showed a subtle increase in complexity. Conclusions Low to moderate doses of psilocybin did not meaningfully disrupt manual dexterity or the latent structure of hand coordination. These findings support the feasibility of combining psilocybin administration with active motor rehabilitation.