Cross-Species Evidence for Psilocin-Induced Visual Distortions: Apparent Motion Is Perceived by Both Humans and Rats

Vejmola and colleagues situate their study within evidence that psychedelics, particularly psilocybin/psilocin, produce visual hallucinations and distortions such as apparent motion, contour undulation and geometric transformations. They note that 5-HT2A receptor agonism is central to these effects, that these receptors are abundant in visual pathways, and that altered 5-HT2A signalling has been implicated in visual hallucinations in clinical conditions such as Parkinson's disease and schizophrenia. Prior animal observations (disorganised behaviour, abnormal tracking or reaching at nonexistent objects across species) suggest cross-species effects, but until now no systematic, objective measurement of psychedelic-induced visual distortions in animals has been reported. To address this gap, the investigators developed a 2-choice visual discrimination paradigm applied in parallel to humans and rats. They hypothesised that psilocin would impair the capacity to distinguish static from dynamic images, yielding a tendency to misclassify static stimuli as moving. In humans, the design linked behavioural performance to self-reported hallucination intensity and plasma psilocin; in rats, decision time was used as an additional objective marker. The study aimed to provide the first objective, cross-species comparison of drug-induced apparent motion and to establish a preclinical model for studying the neurobiology of visual hallucinations.

Human experiment: The clinical component was embedded in a double-blind, placebo-controlled, crossover trial approved by local ethics bodies. Twenty-one healthy volunteers (10 women), aged 28–53 years (mean 37 ± 6.1), gave informed consent; psilocybin was administered orally at 0.26 mg/kg (capsules) and matched placebo capsules were used. The minimum washout was 28 days (mean 49 days). Participants performed a 6-minute visual discrimination task at 65, 165 and 265 minutes after ingestion, deciding whether 8-second grayscale stimuli (human faces or an ellipsoid) were "moving" or "not moving"; dynamic stimuli were created by applying visual effects while keeping luminance constant. Self-reported effects were measured retrospectively at 380 minutes using the Altered States of Consciousness (ASC) scale, and participants also provided a continuous time-course of hallucination intensity (0–7 hours). Blood samples for psilocin quantification were drawn at 1, 2, 4, 6 and 24 hours and analysed by liquid chromatography–tandem mass spectrometry; detailed pharmacokinetic procedures are reported in the supplement. Rat experiment: Ten male Long–Evans rats were housed under standard conditions and food restricted to maintain motivation. Psilocin (0.3 mg/kg) or saline was administered subcutaneously (2 mL/kg) 30 minutes prior to testing. Rats were trained in a PVC maze on a 2-choice visual discrimination protocol that progressed from a luminance-based task to a motion-based task. Static cues were vertical square-wave gratings; dynamic cues used six different smooth visual-effect distortions that preserved average luminance. Training continued until rats achieved an 85% accuracy threshold over three consecutive sessions. Testing used a 3-day protocol: baseline (training then testing), saline day, and psilocin day, with incorrect responses rewarded during testing to avoid discouraging animals and to ensure impairments reflect perceptual changes rather than motivational decline. A posttreatment training session checked retention; after a one-week washout, rats were retrained on the luminance task and retested. Data analysis: For both species, the primary behavioural metric was the correct ratio (proportion of correct trials per session). Discrimination impairment was operationalised as the absolute difference in correct ratios between placebo/saline and psilocybin/psilocin conditions. In rats, decision time (time spent in a predefined decision area) was extracted from overhead video using EthoVision Pro (version not fully reported). Areas under the curve (AUCs) for hallucination intensity and serum psilocin were computed; summary statistics included mean ± SEM or median (Q1/Q3) as appropriate. The supplement is cited for the full statistical protocol; the main text reports Wilcoxon tests, Friedman's ANOVA and paired t-tests for key comparisons.

Human results: Fifteen participants completed all three measurements and were included in the behavioural analyses; six were excluded because they could not perform the task during peak drug effect. Overall accuracy differed markedly between placebo and psilocybin sessions (Wilcoxon signed-rank, n = 15, W = 0, z = 3.408, p < .001). Mean correct ratios were 98.7 ± 2.0% under placebo and 76.0 ± 10.8% under psilocybin. Discrimination impairment varied with cue type and time (Friedman's ANOVA χ2(2) = 14.550, p < .001), with the largest deficit at 65 minutes post‑ingestion. At 65 minutes participants significantly misclassified static stimuli as dynamic (Wilcoxon, n = 15, W = 1, z = 3.350, p < .001); facial stimuli produced a stronger effect than ellipsoids (Wilcoxon, n = 15, W = 0, z = 2.934, p < .010). Discrimination impairment at the 65-minute point correlated with ASC subscales for oceanic boundlessness (OSE, r = 0.652, p < .05) and visionary restructuralization (VUS, r = 0.623, p < .05), and with measured psilocin serum levels (r = 0.585, p < .05). The AUC of fitted psilocin levels correlated with retrospective hallucination intensity (r = 0.547, p < .05). Psilocybin markedly increased ASC scores versus placebo across subscales (Bonferroni-corrected p < .001): OSE rose from 2.5 ± 0.4% to 60.6 ± 3.3%, AIA from 1.1 ± 0.3% to 30.3 ± 2.0%, VUS from 2.2 ± 0.4% to 64.7 ± 2.7%, and the global G‑ASC from 2.0 ± 0.4% to 50.6 ± 3.0%. Rat results: Six rats were reported as tested in both tasks (the Methods note ten animals were housed; the extracted text does not clearly reconcile this difference). Across the sample, correct ratios were significantly lower after psilocin than after saline (paired t-test, t11 = 4.693, p < .001), with mean accuracy 93.3 ± 5.7% for saline and 72.7 ± 1.8% for psilocin. Decision time was inversely correlated with correct ratio (Pearson r = -0.440, p < .05), indicating faster choices were associated with greater impairment. Discrimination impairment was larger in the motion-based task than in the luminance-based task (paired t-test, t5 = 4.067, p < .001). The authors further report that particular visual-effect manipulations (wavewarp, ripple, fisheye) produced the highest error rates, and that rats tended to perform faster and with higher accuracy on the luminance task, consistent with greater intrinsic difficulty of the motion-based discrimination.

The investigators interpret their findings as cross-species evidence that psilocin induces apparent-motion visual distortions. In humans, impaired discrimination between static and dynamic images peaked early (around 65 minutes), closely tracking psilocin plasma levels and self-reported hallucination intensity; volunteers more often perceived static stimuli as moving, and complex stimuli (faces) were particularly prone to apparent motion. The rat data showed a selective deficit in the motion-based task while luminance discrimination remained largely intact, supporting a perceptual rather than global motivational or cognitive explanation. An inverse relation between decision time and accuracy in rats suggested that rapid decisions under psilocin reflected misperception rather than careful discrimination. The authors place these results alongside prior human and animal literature, noting consistency with pharmacokinetic correlations reported elsewhere and with demonstrations that psychedelics can differentially affect aspects of motion processing. They argue that the rodent visual system's organisation into clusters analogous to primate ventral and dorsal streams makes rats a viable model for mechanistic work, including mapping stimulus propagation through the visual pathway to localise where distortions emerge. Several limitations are acknowledged. The tasks probed apparent motion but did not capture other common psychedelic visual alterations such as colour and pattern changes. Small sample size in rats and reliance on correct ratios and decision times may have limited sensitivity to subtle perceptual changes. In humans, excluding six participants who could not complete the task at peak effects could bias results toward those with less severe intoxication. Dose-equivalency across species remains challenging; the authors note previous reports of locomotor disruption at higher rodent doses and defend their choice of 0.3 mg/kg as producing perceptual effects without gross motor impairment. They recommend further studies with broader stimulus sets, larger samples, and real-time neural measurements to clarify mechanisms and locus of disruption in the visual pathway.

Vejmola and colleagues conclude that psilocin impairs static–dynamic visual discrimination in both humans and rats, and that rats exhibit motion-like visual distortions comparable in nature to those reported by humans. The human behavioural impairment correlated with psilocin plasma levels and subjective hallucination intensity. Establishing an objective, cross-species behavioural paradigm provides a preclinical platform to investigate the neurobiology of visual hallucinations and may aid development of interventions for disorders in which visual hallucinations are prevalent.