Psilocybin's kinematic effect on manual dexterity

Psilocybin is a classic serotonergic psychedelic with established effects on consciousness, emotion and cognition, and it has shown promise in studies of depression, anxiety and addiction. However, its direct effects on motor function remain poorly characterised. The authors note that most psilocybin studies are conducted in settings that minimise movement, so existing evidence does not adequately address whether the drug alters manual dexterity, hand coordination, or the underlying kinematic organisation of movement. They also highlight that prior motor research has been sparse and often limited to screen-based tasks rather than real-world manipulation. Klintefors and colleagues set out to test whether acute psilocybin disrupts manual dexterity and whether it changes the latent coordination structure of the hand during a standardised motor task. Specifically, they aimed to assess effects on movement velocity, smoothness, dimensionality and kinematic manifold stability during the peak drug period. The study is presented as a preparatory step towards evaluating psilocybin-assisted motor rehabilitation, particularly for functional neurological and other motor disorders.

The study used data from a larger protocol in healthy volunteers who were recruited by advertisement. Participants received psilocybin on three occasions separated by at least one week. The dose order was randomised and both participants and the physiotherapist were blinded to the dose. The first six participants received 5 mg, 10 mg and 15 mg; the second six received 10 mg, 15 mg and 20 mg. The dose escalation was designed to explore whether a threshold existed at which participants could no longer complete the motor task. Before the first dosing session, participants completed the motor tasks to establish individual baselines. On each dosing day, they performed multiple motor tests at 1.5, 3 and 4.5 hours after administration. A subset of tasks was video recorded using an iPhone 11 mounted on a tripod. The extracted text states that the study focus here was manual dexterity. Gross manual dexterity was measured using the Box and Block Test (BBT), in which participants move as many 25 mm wooden blocks as possible from one box to another in 60 seconds. Behavioural performance was analysed with a Bayesian mixed linear model that included participant-specific baselines and dose responses, plus a fixed effect for session number to account for practice effects. The model was fitted in PyMC using NUTS sampling. For the kinematic analysis, 21 anatomical landmarks of the grasping hand were manually annotated for the first 350 frames of the baseline and 1.5-hour post-dose videos at the highest dose condition (15 mg or 20 mg), corresponding to roughly 12 seconds of movement. Landmark coordinates were converted from pixel to real-world space using the known box dimensions and a reprojection pipeline based on depth estimation and a Perspective-n-Point solver. Kinematic outcomes included centroid velocity, time spent in different movement phases, and smoothness measured with Spectral Arc Length (SPARC). Dimensionality and coordination structure were examined with principal component analysis in both world-centric and hand-centric reference frames, using measures such as the Krzanowski similarity factor, RMSIP, participation ratio and variance accounted for. Bayesian comparisons were used for smoothness, complexity and manifold stability, with a region of practical equivalence defined for dimensionality differences.

Twelve participants were included in the study: six in the 5/10/15 mg sequence and six in the 10/15/20 mg sequence. One participant in the second group could not complete the BBT at the 3-hour time point after 20 mg, but completed other time points. Eleven participants contributed to the behavioural analysis, and ten participants were included in the kinematic and dimensionality analyses. The cohort had a mean age of 33 years, with seven men and four women. For BBT performance, the Bayesian model converged well. The estimated baseline mean was 64.81 blocks in 60 seconds, and the practice effect from session number was negligible. Psilocybin produced a modest dose-related pattern. At the lower 5 mg dose, mean performance was slightly better than baseline across time points, with the largest positive deviation at 4.5 hours post-dose. At 10 mg, 15 mg and 20 mg, performance dipped slightly at 1.5 hours, which coincided with peak effects, and then rose again by 4.5 hours. However, the highest density intervals were broad and overlapped substantially with baseline, so the estimated effects were small and uncertain. Between-participant variability in baseline performance was large (σparticipant = 7.09), exceeding the size of the drug effects, whereas variability in treatment response was low and fairly consistent across doses. The kinematic analysis found negligible differences between baseline and dose sessions for mean velocity, peak velocity, timing measures and smoothness. For smoothness, there was a probable decrease in variability during the dose session, but the overall mean changes were small. In the dimensionality analysis, the coordination subspaces were highly similar between baseline and dose conditions. RMSIP was 0.95 in the world frame and 0.93 in the hand frame, indicating strong overlap. Participation ratio changed little overall, with differences of 0.02 in the world frame and 0.054 in the hand frame when comparing baseline with dose. Variance accounted for was also high, at 0.94 in the world frame and 0.92 in the hand frame, and the Bayesian comparison did not show clear divergence from baseline. The authors note a slight increase in finger-movement complexity in the hand-centred frame, with a posterior increase in participation ratio of 0.23 and limited overlap with the region of practical equivalence, but this was not accompanied by evidence of major manifold disruption.

Klintefors and colleagues interpret the findings as the first quantitative assessment of psilocybin’s acute effects on manual dexterity and hand kinematics. They conclude that the drug caused, at most, minor transient changes in BBT performance: slight impairment at peak effects for 10-20 mg and slight improvement at 5 mg, but with substantial uncertainty because the intervals overlapped baseline and the sample was small. The authors emphasise that baseline variability among participants was much larger than the drug-related change, which made the performance estimates imprecise, whereas the treatment effect itself appeared relatively consistent. They place the kinematic results in the context of earlier research that found slower hand-eye coordination under psilocybin in a computer-based task. By contrast, their own results suggest that the basic mechanics of physical movement were largely preserved during the BBT. The authors argue that the difference may reflect the distinct demands of the tasks: the earlier study relied on visual-motor response tracking, whereas the BBT assesses physical manipulation and simpler sensorimotor integration. They interpret the unchanged world-centred dimensionality and high manifold overlap as evidence that psilocybin did not substantially disrupt established low-dimensional coordination strategies, although the slight rise in hand-centred complexity might indicate a subtle effect on grasping mechanics. They also caution that this inference is limited by the resolution of the video data. The main limitations acknowledged are the small sample size, which led to wide posterior distributions, and the use of 2D video with single-camera depth estimation rather than high-fidelity 3D motion capture. The BBT itself may also have been too simple to detect subtle fine-motor effects, and the kinematic analysis covered only the first 12 seconds of each 60-second trial. The authors further note that their manifold approach assessed linear subspace alignment rather than task-relevant versus task-irrelevant variance, and that methods such as uncontrolled manifold or goal equivalent manifold analysis would require object tracking that was not available in this study. In terms of implications, they state that moderate doses of psilocybin left manual dexterity intact and did not substantially alter grasping coordination, supporting the feasibility of psilocybin-assisted trials involving motor rehabilitation. They frame the work as preliminary evidence that psilocybin may be integrated into physiotherapy or motor-rehabilitation protocols without obvious disruption of gross motor task performance, while stressing the need for replication and higher-resolution motion capture before stronger conclusions are drawn.

The authors conclude that quantitative motor assessment is feasible during moderate-dose psilocybin exposure and that participants preserved BBT performance and the basic intrinsic structure of hand coordination. They state that 5-20 mg of psilocybin did not appear to disrupt access to established motor strategies, but that larger studies using higher-fidelity 3D motion capture are needed to rule out more subtle deficits. Overall, they present the findings as preliminary support for the safety of incorporating psilocybin into motor rehabilitation protocols.