Cross-Species Evidence for Psilocin-Induced Visual Distortions: Apparent Motion Is Perceived by Both Humans and Rats
Status PubMed-not-MEDLINE Language English Country United States Media electronic-ecollection
Document type Journal Article
PubMed
40599633
PubMed Central
PMC12209919
DOI
10.1016/j.bpsgos.2025.100524
PII: S2667-1743(25)00078-3
Knihovny.cz E-resources
- Keywords
- Human, Psilocin, Psychedelics, Rat, Vision, Visual hallucinations,
- Publication type
- Journal Article MeSH
BACKGROUND: Psychedelics, particularly psilocin, are increasingly being studied for their mind-altering effects and potential therapeutic applications in psychiatry. Visual hallucinations, especially the illusion of motion in static images, are a hallmark of their action. Despite growing interest, the underlying mechanisms remain poorly understood, as their systematic evaluation in both humans and animals is challenging. METHODS: To investigate psilocin-induced visual distortions, we designed a 2-choice visual discrimination task. Human participants and male rats indicated whether an image appeared static or moving while the image either actually moved or did not. In humans, performance was compared with self-reported hallucination intensity, Altered States of Consciousness scale scores, and psilocin plasma levels. Rats were tested in 2 distinct tasks, a luminance-based task and a motion-based task. Their performance was evaluated alongside decision time. RESULTS: Both species exhibited significant impairment in distinguishing static from dynamic visual stimuli while under psilocin's influence. In humans, this impairment followed the time course of psilocin plasma levels and hallucination intensity. In rats, psilocin selectively impaired performance in the motion-based task, while performance in the luminance-based task remained intact, indicating a specific effect on visual perception. Decision time was linked to discrimination impairment. CONCLUSIONS: Psilocin impaired static-dynamic discrimination in both species, providing the first evidence that rats experience visual distortions similar to those reported by humans. The correlations between discrimination impairment, psilocin levels, and hallucination intensity in humans reinforce psilocin's effects on visual perception. This approach provides a valuable tool for investigating the neurobiology of altered visual perception in drug-induced states and psychiatric conditions.
In this study, we explored how psilocin, a compound derived from psilocybin in magic mushrooms, alters visual perception in humans and rats. Using a visual discrimination task, both species were tested on their ability to distinguish static from dynamic images. Psilocin caused humans to misclassify static images as dynamic and induced similar visual distortions in rats. This is the first study to demonstrate that rats experience psilocin-induced visual distortions comparable to those reported by humans, thereby providing a valuable foundation for further research on visual alterations across species.
3rd Faculty of Medicine Charles University Prague Czechia
Clinical Research Program National Institute of Mental Health Klecany Czechia
Faculty of Science Charles University Prague Czechia
Psychedelic Research Center National Institute of Mental Health Klecany Czechia
Sleep and Chronobiology Research Center National Institute of Mental Health Klecany Czechia
See more in PubMed
Tylš F., Páleníček T., Horáček J. Psilocybin - Summary of knowledge and new perspectives. Eur Neuropsychopharmacol. 2014;24:342–356. PubMed
Hasler F., Bourquin D., Brenneisen R., Bär T., Vollenweider F.X. Determination of psilocin and 4-hydroxyindole-3-acetic acid in plasma by HPLC-ECD and pharmacokinetic profiles of oral and intravenous psilocybin in man. Pharm Acta Helv. 1997;72:175–184. PubMed
Vollenweider F.X., Vollenweider-Scherpenhuyzen M.F., Bäbler A., Vogel H., Hell D. Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. Neuroreport. 1998;9:3897–3902. PubMed
Kometer M., Schmidt A., Jäncke L., Vollenweider F.X. Activation of serotonin 2A receptors underlies the psilocybin-induced effects on α oscillations, N170 visual-evoked potentials, and visual hallucinations. J Neurosci. 2013;33:10544–10551. PubMed PMC
Jakab R.L., Goldman-Rakic P.S. 5-Hydroxytryptamine 2A serotonin receptors in the primate cerebral cortex: Possible site of action of hallucinogenic and antipsychotic drugs in pyramidal cell apical dendrites. Proc Natl Acad Sci U S A. 1998;95:735–740. PubMed PMC
Watakabe A., Komatsu Y., Sadakane O., Shimegi S., Takahata T., Higo N., et al. Enriched expression of serotonin 1B and 2A receptor genes in macaque visual cortex and their bidirectional modulatory effects on neuronal responses. Cereb Cortex. 2009;19:1915–1928. PubMed PMC
Gerstl F., Windischberger C., Mitterhauser M., Wadsak W., Holik A., Kletter K., et al. Multimodal imaging of human early visual cortex by combining functional and molecular measurements with fMRI and PET. Neuroimage. 2008;41:204–211. PubMed
Moreau A.W., Amar M., Le Roux N., Morel N., Fossier P. Serotoninergic fine-tuning of the excitation-inhibition balance in rat visual cortical networks. Cereb Cortex. 2010;20:456–467. PubMed
Masson J. Serotonin in retina. Biochimie. 2019;161:51–55. PubMed
Teeple R.C., Caplan J.P., Stern T.A. Visual hallucinations: Differential diagnosis and treatment. Prim Care Companion J Clin Psychiatry. 2009;11:26–32. PubMed PMC
Ballanger B., Strafella A.P., Van Eimeren T., Zurowski M., Rusjan P.M., Houle S., Fox S.H. Serotonin 2A receptors and visual hallucinations in Parkinson disease. Arch Neurol. 2010;67:416–421. PubMed
Huot P., Johnston T.H., Darr T., Hazrati L.N., Visanji N.P., Pires D., et al. Increased 5-HT2A receptors in the temporal cortex of Parkinsonian patients with visual hallucinations. Mov Disord. 2010;25:1399–1408. PubMed
González-maeso J., Ang R.L., Yuen T., Chan P., Weisstaub N.V., López-giménez J.F., et al. Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature. 2008;452:93–97. PubMed PMC
Meltzer H.Y., Mills R., Revell S., Williams H., Johnson A., Bahr D., Friedman J.H. Pimavanserin, a serotonin(2A) receptor inverse agonist, for the treatment of Parkinson’s disease psychosis. Neuropsychopharmacology. 2010;35:881–892. PubMed PMC
Sommer I.E.C., Kleijer H., Visser L., Van Laar T. Successful treatment of intractable visual hallucinations with 5-HT 2A antagonist ketanserin. BMJ Case Rep 2018. 2018 PubMed PMC
Díaz J.L. Sacred plants and visionary consciousness. Phenomenol Cogn Sci. 2010;9:159–170.
Grinspoon L., Bakalar J.B. Psychedelic Reflections. New York, NY: Human Sciences Press, Incorporated. 1983. http://www.scribd.com/doc/19720797/Psychedelic-Reflections Available at:
Mescal K.H. Kegan, Paul, Trench, Trubner and Co; London, United Kingdom: 1928. The ‘Divine’ Plant and Its Psychological Effects.
Klüver H. University of Chicago Press; Chicago, IL: 1966. Mescal and Mechanisms of Hallucinations.
Kometer M., Vollenweider F.X. Serotonergic hallucinogen-induced visual perceptual alterations. Curr Top Behav Neurosci. 2018;36:257–282. PubMed
Shanon B. Ayahuasca visualizations: A structural typology. J Conscious Stud. 2002;9:3–30.
Siegel R.K., Jarvik M.E. Hallucinations: Behavior, Experience and Theory. John Wiley & Sons, Inc.; New York, NY: 1975. Drug-induced hallucinations in animals and man; pp. 163–195.
Oster G. Moiré patterns and visual hallucinations. Psychedel Rev. 1965;7:33–40.
Studerus E., Gamma A., Vollenweider F.X. Psychometric evaluation of the altered states of consciousness rating scale (OAV) PLoS One. 2010;5 PubMed PMC
Dittrich A. The standardized psychometric assessment of altered states of consciousness (ASCs) in humans. Pharmacopsychiatry. 1998;31(suppl 2):80–84. PubMed
Strassman R.J., Qualls C.R., Uhlenhuth E.H., Kellner R. Dose-response study of N,N-Dimethyltryptamine in humans. II. Subjective effects and preliminary results of a new rating scale. Arch Gen Psychiatry. 1994;51:98–108. PubMed
Studerus E., Kometer M., Hasler F., Vollenweider F.X. Acute, subacute and long-term subjective effects of psilocybin in healthy humans: A pooled analysis of experimental studies. J Psychopharmacol. 2011;25:1434–1452. PubMed
Vollenweider F.X., Kometer M. The neurobiology of psychedelic drugs: Implications for the treatment of mood disorders. Nat Rev Neurosci. 2010;11:642–651. PubMed
Christiansen A., Baum R., Witt P.N. Changes in spider webs brought about by mescaline, psilocybin and an increase in body weight. J Pharmacol Exp Ther. 1962;136:31–37. PubMed
Witt P.N. Vol. 7. 1951. D-lysergic acid diethylamide (LSD 25) in the Spider test; pp. 310–311. PubMed
Abramson H.A., Evans L.T. Lysergic acid diethylamide (LSD 25). II. Psychobiological effects on the Siamese fighting fish. Science. 1954;120:990–991. PubMed
Turner W.J. The effect of lysergic acid diethylamide on Betta splendens: I. Dis Nerv Syst. 1956;17:198. PubMed
Evans L.T., Geronimus L.H., Kornetsky C., Abramson H.A. Effect of ergot drugs on Betta splendens. Science. 1956;123:26. PubMed
Chessick R.D., Kronholm J., Beck M., Maier G. Effect of pretreatment with tryptamine, tryptophan and DOPA on LSD reaction in tropical fish. Psychopharmacologia. 1964;5:390–392. PubMed
Siegel R.K. Studies of hallucinogens in fish, birds, mice and men: The behavior of “psychedelic” populations. Adv Neuropsychopharmacol. 1971:311–318.
Tirri M., Ponzoni L., Bilel S., Arfè R., Braida D., Sala M., Marti M. Acute DOB and PMA administration impairs motor and sensorimotor responses in mice and causes hallucinogenic effects in adult zebrafish. Brain Sci. 2020;10:586. PubMed PMC
Boulton C.S., Handley S.L. Factors modifying the head-twitch response to 5-hydroxytryptophan. Psychopharmacologia. 1973;31:205–214. PubMed
Corne S.J., Pickering R.W. A possible correlation between drug-induced hallucinations in man and a behavioural response in mice. Psychopharmacologia. 1967;11:65–78. PubMed
Hanks J.B., González-Maeso J. Animal models of serotonergic psychedelics. ACS Chem Neurosci. 2013;4:33–42. PubMed PMC
Halberstadt A.L., Chatha M., Klein A.K., Wallach J., Brandt S.D. Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. Neuropharmacology. 2020;167 PubMed PMC
Alexander L., Anderson D., Baxter L., Claydon M., Rucker J., Robinson E.S.J. Preclinical models for evaluating psychedelics in the treatment of major depressive disorder. Br J Pharmacol. 2024 [published online Oct 28]. Br J Pharmacol. PubMed
Apter J.T., Pfeiffer C.C. The effect of the hallucinogenic drugs LSD-25 and mescaline on the electroretinogram. Ann N Y Acad Sci. 1957;66:508–514. PubMed
Schneider J.A., Sigg E.B. Neuropharmacological studies on ibogaine, an indole alkaloid with central-stimulant properties. Ann N Y Acad Sci. 1957;66:765–776. PubMed
Florio V., Fuentes J.A., Ziegler H., Longo V.G. EEG and behavioral effects in animals of some amphetamine derivatives with hallucinogenic properties. Behav Biol. 1972;7:401–414. PubMed
Jacobs B.L., Trulson M.E., Stark A.D., Christoph G.R. Comparative effects of hallucinogenic drugs on behavior of the cat. Commun Psychopharmacol. 1977;3:243–254. PubMed
Hardman H.F., Haavik C.O., Seevers M.H. Relationship of the structure of mescaline and seven analogs to toxicity and behavior in five species of laboratory animals. Toxicol Appl Pharmacol. 1973;25:299–309. PubMed
Davis W.M., Bedford J.A., Buelke J.L., Guinn M.M., Hatoum H.T., Waters I.W., et al. Acute toxicity and gross behavioral effects of amphetamine, four methoxyamphetamines, and mescaline in rodents, dogs, and monkeys. Toxicol Appl Pharmacol. 1978;45:49–62. PubMed
Donovan L.L., Johansen J.V., Ros N.F., Jaberi E., Linnet K., Johansen S.S., et al. Effects of a single dose of psilocybin on behaviour, brain 5-HT2A receptor occupancy and gene expression in the pig. Eur Neuropsychopharmacol. 2021;42:1–11. PubMed
Siegel R.K., Brewster J.M., Jarvik M.E. An observational study of hallucinogen-induced behavior in unrestrained Macaca mulatta. Psychopharmacologia. 1974;40:211–223. PubMed
Fantegrossi W.E., Woods J.H., Winger G. Transient reinforcing effects of phenylisopropylamine and indolealkylamine hallucinogens in rhesus monkeys. Behav Pharmacol. 2004;15:149–157. PubMed
Zoccolan D. Invariant visual object recognition and shape processing in rats. Behav Brain Res. 2015;285:10–33. PubMed PMC
Bossens C., Op de Beeck H.P. Linear and non-linear visual feature learning in rat and humans. Front Behav Neurosci. 2016;10:235. PubMed PMC
Leinonen H., Tanila H. Vision in laboratory rodents-Tools to measure it and implications for behavioral research. Behav Brain Res. 2018;352:172–182. PubMed
Vinken K., Vermaercke B., Op de Beeck H.P. Visual categorization of natural movies by rats. J Neurosci. 2014;34:10645–10658. PubMed PMC
Wang Q., Sporns O., Burkhalter A. Network analysis of corticocortical connections reveals ventral and dorsal processing streams in mouse visual cortex. J Neurosci. 2012;32:4386–4399. PubMed PMC
Wang Q., Gao E., Burkhalter A. Gateways of ventral and dorsal streams in mouse visual cortex. J Neurosci. 2011;31:1905–1918. PubMed PMC
Tafazoli S., Safaai H., De Franceschi G., Rosselli F.B., Vanzella W., Riggi M., et al. Emergence of transformation-tolerant representations of visual objects in rat lateral extrastriate cortex. Elife. 2017;6 PubMed PMC
Denman D.J., Contreras D. On parallel streams through the mouse dorsal lateral geniculate nucleus. Front Neural Circuits. 2016;10:20. PubMed PMC
Juavinett A.L., Callaway E.M. Pattern and component motion responses in mouse visual cortical areas. Curr Biol. 2015;25:1759–1764. PubMed PMC
Nishio N., Tsukano H., Hishida R., Abe M., Nakai J., Kawamura M., et al. Higher visual responses in the temporal cortex of mice. Sci Rep. 2018;8 PubMed PMC
Rasmussen R., Yonehara K. Circuit mechanisms governing local vs. global motion processing in mouse visual cortex. Front Neural Circuits. 2017;11:109. PubMed PMC
Reinagel P. Using rats for vision research. Neuroscience. 2015;296:75–79. PubMed
Rambousek L., Palenicek T., Vales K., Stuchlik A. The effect of psilocin on memory acquisition, retrieval, and consolidation in the rat. Front Behav Neurosci. 2014;8:180. PubMed PMC
Tylš F., Páleníček T., Kadeřábek L., Lipski M., Kubešová A., Horáček J. Sex differences and serotonergic mechanisms in the behavioural effects of psilocin. Behav Pharmacol. 2016;27:309–320. PubMed
Gaffan E.A., Eacott M.J. A computer-controlled maze environment for testing visual memory in the rat. J Neurosci Methods. 1995;60:23–37. PubMed
Kumar G., Talpos J., Steckler T. Strain-dependent effects on acquisition and reversal of visual and spatial tasks in a rat touchscreen battery of cognition. Physiol Behav. 2015;144:26–36. PubMed
Sutherland N.S. Visual discrimination of horizontal and vertical rectangles by rats on a new discrimination training apparatus. Q J Exp Psychol. 1961;13:117–121.
Wiesenfeld Z., Branchek T. Refractive and visual acuity in the hooded rat. Vision Res. 1976;16:823–827. PubMed
Bravermanová A., Viktorinová M., Tylš F., Novák T., Androvičová R., Korčák J., et al. Psilocybin disrupts sensory and higher order cognitive processing but not pre-attentive cognitive processing-Study on P300 and mismatch negativity in healthy volunteers. Psychopharmacology (Berl) 2018;235:491–503. PubMed
Marin F., Rohatgi A., Charlot S. WebPlotDigitizer, a polyvalent and free software to extract spectra from old astronomical publications: Application to ultraviolet spectropolarimetry. arXiv. 2017 doi: 10.48550/arXiv.1708.02025. DOI
Rohatgi A. Webplotdigitizer. 2022. https://automeris.io/WebPlotDigitizer Available at:
Madsen M.K., Fisher P.M., Burmester D., Dyssegaard A., Stenbæk D.S., Kristiansen S., et al. Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels. Neuropsychopharmacology. 2019;44:1328–1334. PubMed PMC
Reinagel P. Speed and accuracy of visual motion discrimination by rats. PLoS One. 2013;8 PubMed PMC
Schmack K., Bosc M., Ott T., Sturgill J.F., Kepecs A. Striatal dopamine mediates hallucination-like perception in mice. Science. 2021;372 PubMed
Geyer M.A., Light R.K., Rose G.J., Petersen L.R., Horwitt D.D., Adams L.M., Hawkins R.L. A characteristic effect of hallucinogens on investigatory responding in rats. Psychopharmacology (Berl) 1979;65:35–40. PubMed
Harris R.T., Balster R.L. In: Pickens R., editor. Vol. 183. Appleton-Century Crofts; New York, NY: 1971. pp. 111–132. (An analysis of the function of drugs in the stimulus control of operant behavior: Stimulus Properties of Drugs Thompson T).
Schechter M.D., Rosecrans J.A. Lysergic acid diethylamide (LSD) as a discriminative cue: Drugs with similar stimulus properties. Psychopharmacologia. 1972;26:313–316. PubMed
Winter J.C., Rice K.C., Amorosi D.J., Rabin R.A. Psilocybin-induced stimulus control in the rat. Pharmacol Biochem Behav. 2007;87:472–480. PubMed PMC
Reagan-Shaw S., Nihal M., Ahmad N. Dose translation from animal to human studies revisited. FASEB J. 2008;22:659–661. PubMed
Blanchard O.L., Smoliga J.M. Translating dosages from animal models to human clinical trials-revisiting body surface area scaling. FASEB J. 2015;29:1629–1634. PubMed
Carter O.L., Pettigrew J.D., Burr D.C., Alais D., Hasler F., Vollenweider F.X. Psilocybin impairs high-level but not low-level motion perception. NeuroReport. 2004;15:1947–1951. PubMed
Douglas R.M., Neve A., Quittenbaum J.P., Alam N.M., Prusky G.T. Perception of visual motion coherence by rats and mice. Vision Res. 2006;46:2842–2847. PubMed
Hupfeld D., Hoffmann K.P. Motion perception in rats (Rattus norvegicus sp.): Deficits in albino Wistar rats compared to pigmented Long-Evans rats. Behav Brain Res. 2006;170:29–33. PubMed
Van Ommen M.M., Van Beilen M., Cornelissen F.W., Smid H.G.O.M., Knegtering H., Aleman A., et al. The prevalence of visual hallucinations in non-affective psychosis, and the role of perception and attention. Psychol Med. 2016;46:1735–1747. PubMed
Eversfield C.L., Orton L.D. Auditory and visual hallucination prevalence in Parkinson’s disease and dementia with Lewy bodies: A systematic review and meta-analysis. Psychol Med. 2019;49:2342–2353. PubMed PMC
Holroyd S., Shepherd M.L., Downs J.H. Associated with visual hallucinations in Alzheimer’s disease. J Neuropsychiatry Clin Neurosci. 2000;12:25–28. PubMed
Waters F., Collerton D., Ffytche D.H., Jardri R., Pins D., Dudley R., et al. Visual hallucinations in the psychosis spectrum and comparative information from neurodegenerative disorders and eye disease. Schizophr Bull. 2014;40(suppl 4):S233–S245. PubMed PMC
Langova V., Vales K., Horka P., Horacek J. The role of zebrafish and laboratory rodents in schizophrenia research. Front Psychiatry. 2020;11:703. PubMed PMC