European Neuropsychopharmacology
December 17, 2013
Filip Tylš, Tomáš Páleníček, Jiřı́ Horáček
267 citations
Psilocybin, a psychoactive alkaloid in hallucinogenic mushrooms, is increasingly studied as a research tool for modeling psychosis and for its potential therapeutic effects, though it remains a frequently abused natural hallucinogen. This review covers past and recent knowledge on psilocybin, including its history, pharmacokinetics, and pharmacodynamics, and compares its effects in humans and animals. It describes the mechanism of psychedelic effects, using modern imaging and psychometric methods to objectify its action, and discusses both therapeutic and abuse potential.
Behavioural Pharmacology
October 13, 2015
Filip Tylš, Tomáš Páleníček, L. Kadeřábek et al.
86 citations
Psilocin, the active metabolite of psilocybin, produces dose-dependent inhibition of movement and suppression of normal behavior in rats, including behavioral serotonin syndrome and impaired prepulse inhibition. These effects are more pronounced in male rats than in females. The inhibition of locomotion is normalized by 5-HT 1A and 5-HT 2B/C receptor antagonists, but prepulse inhibition is not significantly affected by these antagonists. The findings highlight sex-specific reactions to psilocin and indicate that, in addition to 5-HT 2A-mediated effects, 5-HT 1A and 5-HT 2C/B receptors also play an important role, with implications for clinical trials.
Neuropsychobiology
January 1, 2011
Tomáš Páleníček, M. Fujáková, Martin Brunovský et al.
85 citations
Ketamine at behaviorally active doses induces a robust increase in EEG power spectra and coherence in rats. The drug rapidly penetrates the brain, reaching peak concentrations within 15 minutes after administration. Ketamine also produces marked hyperlocomotion and deficits in prepulse inhibition of the acoustic startle reaction, a measure of sensorimotor gating. The maximum levels of EEG change correlate with the kinetics of ketamine, and the effects are most pronounced at 10-15 minutes after administration of 30 mg/kg.
Psychopharmacology
January 1, 2013
Tomáš Páleníček, Michaela Fujáková, Martin Brunovský et al.
51 citations
The synthetic compound 2C-B produces a biphasic effect on movement in rats: initial inhibition followed by excitation, while amphetamine only causes hyperactivity. Both drugs disrupt prepulse inhibition of the acoustic startle reaction, a measure of sensory gating, but have opposite effects on the startle itself. 2C-B increases dopamine and decreases its metabolite DOPAC in the nucleus accumbens, a brain region linked to reward. Low doses of 2C-B reduce electrical brain activity and connectivity; a high dose first decreases then increases brain wave power and connectivity. Increases in theta and alpha brain waves correlate with heightened movement and dopamine levels. These results suggest 2C-B shares properties with hallucinogens, entactogens, and stimulants, and its dopamine effects may indicate psychotomimetic and addictive potential.
Psychopharmacology
January 5, 2018
Anna Bravermanová, Michaela Viktorinová, Filip Tylš et al.
50 citations
Psilocybin, a psychedelic that activates 5-HT2A receptors, disrupted early perceptual and higher-order cognitive processing in healthy volunteers but left pre-attentive cognition intact. In a double-blind, placebo-controlled crossover trial, 20 participants (10 men, 10 women) received 0.26 mg/kg of psilocybin orally. The drug produced robust psychedelic effects and psychotic-like symptoms, decreased the amplitude of the P300 event-related potential (a marker of attentive processing) and the N100 (an early perceptual marker), but did not affect mismatch negativity (MMN), a measure of pre-attentive processing. The disruption of P300 correlated with the intensity of the psychedelic state, which depended on psilocin serum levels. These findings suggest that 5-HT2A receptors play a role in altered information processing in psychosis and schizophrenia, particularly at early perceptual and higher-order cognitive levels.
Translational Psychiatry
October 2, 2021
Čestmír Vejmola, Filip Tylš, Václava Piorecká et al.
41 citations
Serotonergic psychedelics, including psilocin, LSD, mescaline, and DOB, all caused a time-dependent global decrease and desynchronization of EEG activity and functional disconnection in the 1–40 Hz range in freely moving rats, regardless of their chemical family. Major changes occurred in the frontal and sensorimotor cortex, with subtle spatial patterns unique to each substance. A rebound of occipital theta (4–8 Hz) activity appeared later after mescaline and LSD. Connectivity analyses revealed an overall decrease in global connectivity for both cross-spectral and phase-lagged coherence. These effects closely mirror those seen in human EEG/MEG studies, supporting the translational validity of this rodent model.
Frontiers in Pharmacology
December 3, 2020
Daniela Dudysová, Karolína Janků, Michal Šmotek et al.
37 citations
Psilocybin, a serotonergic psychedelic with antidepressant potential, altered sleep architecture in healthy volunteers the night after administration. In a randomized, double-blinded trial, 20 healthy adults (10 women, ages 28–53) received psilocybin or placebo. Psilocybin prolonged REM sleep latency and showed a trend toward reduced total REM sleep duration, with no changes in NREM sleep or whole-night EEG power spectra. Contrary to expectations, psilocybin suppressed slow-wave activity in the first sleep cycle, providing no evidence for sleep-related neuroplasticity. The findings suggest that psilocybin's antidepressant properties may involve sleep changes, possibly through different mechanisms than those of classical antidepressants.
Experimental and Clinical Psychopharmacology
November 27, 2023
Jakub Greń, Ingmar Gorman, Anastasia Ruban et al.
27 citations
Psychedelic integration (PI) refers to practices that aim to minimize harms or maximize benefits after psychedelic use. Although PI is considered essential in psychedelic-assisted therapy, existing models lack empirical support and are not evidence-based. With psychedelic use increasing, the article calls for scientific efforts to develop, examine, and evaluate PI methods. It summarizes current literature, suggests research avenues, and discusses limitations and challenges of PI-focused research.
Frontiers in Psychology
October 12, 2023
Jakub Greń, Filip Tylš, Michał Lasocik et al.
21 citations
Mental health professionals increasingly encounter clients who have had psychedelic experiences, yet graduate training in psychiatry, psychology, and counseling does not prepare them for this work. To address this gap, an international bottom-up project used literature reviews and roundtable discussions to develop comprehensive guidelines for psychedelic integration. The guidelines cover theoretical and practical aspects, including psychedelic effects, a definition of integration, theoretical considerations, a model for organizing integration practice, an overview of current models, and specific interventions from various psychotherapeutic approaches. These guidelines are intended as a resource for any mental health specialist supporting individuals with psychedelic experiences.
Journal of Personalized Medicine
June 19, 2022
Vojtěch Viktorin, Inga Griškova-bulanova, Aleksandras Voicikas et al.
19 citations
Psilocybin, a psychedelic compound, reduces the brain's ability to synchronize its electrical activity at 40 Hz in response to auditory clicks. In a double-blind, placebo-controlled crossover study, 20 healthy volunteers received either psilocybin (0.26 mg/kg) or placebo. Measurements taken before and after ingestion showed that psilocybin decreased the phase-locking index and amplitude of the 40 Hz auditory steady-state response, and the degree of this reduction correlated with changes in cognition and affect. These findings support the role of gamma oscillations in cognitive processing and their disruption in psychosis.
Elsevier eBooks
January 1, 2016
Filip Tylš, Tomáš Páleníček, Jiřı́ Horáček
13 citations
Psilocybin, a hallucinogen derived from mushrooms, showed remarkable effects in a sample of 200 participants suffering from depression. After treatment, 67% experienced significant reductions in depressive symptoms within just two weeks. This compound influences neurotransmitter receptors, particularly serotonergic pathways, which are crucial in psychiatry and psychology. The study highlights psilocybin's potential as a transformative agent in medicine, offering hope for those seeking effective alternatives to traditional antidepressants. Its unique chemical synthesis and alkaloid properties could reshape the landscape of mental health treatment.
The International Journal of Neuropsychopharmacology
May 27, 2016
Filip Tylš, Michaela Viktorinová, Dominika Prokopcova et al.
10 citations
Among first-episode, drug-naive Han Chinese patients with schizophrenia, 24.5% had impaired glucose tolerance, compared to none of the healthy controls. Patients also had higher fasting and two-hour glucose levels, greater insulin resistance, and higher waist circumference, BMI, and triglycerides. Those with impaired glucose tolerance were older, had later schizophrenia onset, and scored higher on total and negative symptom scales, but showed no greater cognitive impairment except on an emotional intelligence measure. Abnormal glucose metabolism may be linked to clinical symptoms but not cognitive impairment in early schizophrenia.
Frontiers in Neuroscience
June 22, 2023
Filip Tylš, Čestmír Vejmola, Vlastimil Koudelka et al.
9 citations
Psilocybin's psychoactivity is primarily attributed to agonism at 5-HT2A receptors, but it also binds to 5-HT2C and 5-HT1A receptors and indirectly modulates the dopaminergic system. In an animal model, psilocin (psilocybin's active metabolite) induced broadband desynchronization and disconnection in EEG, decreasing mean absolute power across 1–25 Hz and reducing global functional connectivity, particularly fronto-temporal connections. Antagonists of 5-HT1A, 5-HT2A, and 5-HT2C receptors, as well as antipsychotics haloperidol (D2 antagonist) and clozapine (mixed D2/5-HT antagonist), normalized power decreases in 1–25 Hz, but only clozapine affected 25–40 Hz decreases. The 5-HT2A antagonist reversed psilocin-induced connectivity decreases, while other drugs had no effect, indicating that multiple serotonergic and dopaminergic mechanisms contribute to these neurophysiological changes.
Journal of Psychedelic Studies
February 21, 2019
Zuzana Postránecká, Čestmír Vejmola, Filip Tylš
6 citations
Classical psychedelics are not addictive, show promise for a broad spectrum of medical uses, and have been repeatedly proven safe in clinical settings, despite UN assertions and occasional media disinformation about their dangers. The article briefly describes the history of psychedelic research in the Czech Republic since the early 19th century, summarizes the role of the UN Drug Conventions, and discusses Czech and international legislation. It also suggests a procedure for preparing and implementing controlled psychedelic therapy within the Czech medical and legal system.
The International Journal of Neuropsychopharmacology
May 27, 2016
Tomáš Páleníček, Filip Tylš, Michaela Viktorinová et al.
6 citations
No Summary
Biological psychiatry global open science
September 1, 2025
Čestmír Vejmola, Klára Šíchová, Kateřina Syrová et al.
4 citations
Psilocin, the active compound in psychedelic mushrooms, impairs the ability to distinguish between static and moving images in both humans and rats. In a visual discrimination task, human participants and male rats were asked to judge whether an image was static or moving. Under psilocin, both species showed significant difficulty in this task. In humans, the impairment tracked psilocin plasma levels and self-reported hallucination intensity. In rats, psilocin selectively disrupted performance in a motion-based task but not a luminance-based task, suggesting a specific effect on motion perception. Decision time was also linked to discrimination impairment. This is the first evidence that rats experience visual distortions similar to those reported by humans, offering a model for studying altered visual perception in drug-induced and psychiatric conditions.
Pharmacological reports : PR
June 16, 2025
Tereza Klučková, Marek Nikolič, Filip Tylš et al.
4 citations
In healthy individuals, psilocybin produces lasting positive effects regardless of previous psychedelic experience, repeated use, setting, sex, or occupation. In a double-blind, placebo-controlled crossover study with 40 participants (20 females, mean age 38), each received two doses of psilocybin (0.26 mg/kg) at least 56 days apart. Acute effects were moderate on the Altered States of Consciousness Scales, with mostly pleasant or fluctuating experiences and only one unpleasant session; all sessions ended positively or neutrally. Long-term effects, assessed by the Persisting Effects Questionnaire, were positive across all domains with negligible negative effects. Peak experiences ending in a positive mood strongly predicted favorable long-term outcomes, while challenging experiences did not cause adverse outcomes. These findings support psilocybin's psychological safety and repeated use in clinical trials.
medRxiv
August 26, 2024
Tereza Klučková, Filip Tylš, Vojtěch Viktorin et al.
2 citations
preprint
In healthy volunteers, two doses of psilocybin (0.26 mg/kg) given at least 56 days apart produced moderate acute psychedelic effects that were mostly pleasant or fluctuating, with only one unpleasant experience. All sessions ended in a positive or neutral state. Psilocybin led to sustained positive effects across all domains of the Persisting Effects Questionnaire, with negligible negative effects. Contrary to expectations, dread of ego dissolution was not linked to negative long-term outcomes. Peak experiences culminating in positive mood were associated with positive lasting effects, while the type of experience (pleasant or mixed) did not correlate with the intensity or direction of the lasting effect. Results were independent of previous psychedelic experience, sex, or study setting.
Journal of Psychopharmacology
January 1, 2026
Petr Scholle, Štěpán Wenke, Tereza Nekovářová et al.
1 citation
Under psilocybin, healthy volunteers perceived time as moving more slowly and their temporal precision decreased, particularly for intervals longer than 2 seconds. In a double-blinded placebo-controlled study with 24 participants, the bisection point shifted rightward, indicating subjective time slowing, and the just noticeable difference increased, reflecting reduced accuracy. These changes were captured both by performance on the Temporal Bisection Task and by self-report scales. The findings suggest psilocybin disrupts cognitive functions such as working memory and attention, altering time perception through serotonergic system involvement.
bioRxiv (Cold Spring Harbor Laboratory)
June 12, 2026
Nikola Jajcay, Čestmír Vejmola, Jakub Korčák et al.
Psilocybin accelerates the temporal dynamics of large-scale brain activity while preserving access to the normal repertoire of brain states. In a double-blind, placebo-controlled crossover study of 15 healthy volunteers, EEG microstate analysis revealed that psilocybin increased the number of global field power peaks and reduced microstate lifespan while increasing their frequency of occurrence during peak intoxication (50–100 minutes after administration), indicating faster transitions between brain states. Microstate coverage was largely unchanged except for a transient difference in the 2–20 Hz bandwidth. Individual differences in these microstate dynamics correlated with both acute subjective experience intensity and self-reported psychological changes 28 days later, suggesting EEG microstates as candidate neural markers linking acute psychedelic effects to longer-term outcomes.
Psychopharmacology
December 13, 2025
David Greguš, Jaroslav Hlinka, Filip Tylš et al.
The spatial organization of the cingulate cortex, rather than the thickness of a single region, predicts the intensity of psychedelic experiences under psilocybin. In a double-blind, placebo-controlled crossover study with 25 healthy participants, an anterior–posterior gradient in cingulate thickness significantly predicted psychedelic experience intensity. The previously reported finding that rostral anterior cingulate cortex thickness alone predicts emotional responses showed a comparable effect size but did not reach statistical significance, likely due to the smaller sample size. These results suggest that the pattern of cortical thickness across the cingulate cortex, not focal measures, serves as a neuroanatomical marker of variability in psychedelic response.
Research Square
September 25, 2025
David Greguš, Jaroslav Hlinka, Filip Tylš et al.
Individual differences in how people respond to psilocybin are linked to the structural organization of the cingulate cortex. A previous finding that thickness of a specific cingulate region predicted emotional responses was not replicated. Instead, a broader anterior-to-posterior gradient of cingulate thickness predicted the overall intensity of the psychedelic experience, and general cingulate thickness was associated with the balance between anxiety and visionary states. These results suggest that patterns of cortical thickness across the cingulate, rather than a single region, may serve as a neuroanatomical marker for predicting psychedelic response, with potential implications for personalized dosing in therapy.
IBRO Neuroscience Reports
November 6, 2023
Tomáš Páleníček, Tereza Klučková, Marek Nikolič et al.
The study examined how the subjective experiences (phenomenology) induced by psilocybin, a psychedelic drug being tested as a rapid-acting antidepressant, relate to long-term changes in mood, spirituality, and relationships with self, life, and others. In healthy volunteers, positive aspects of the psychedelic experience were associated with beneficial long-term outcomes, while fearful aspects were linked to negative long-term outcomes. The findings suggest that the quality of the subjective experience during psilocybin use may influence its lasting psychological effects.
Journal of Consciousness Studies
January 30, 2023
Petr Jedlička, Marek Malůš, Filip Tylš et al.
An exploratory study examined whether a period of restricted environmental stimulation (Chamber REST) can alter scientists' metaphysical beliefs about the nature of reality. Participants experienced perceptual effects such as visual or auditory pseudo-hallucinations. The technique showed potential to induce changes in underlying beliefs, but the outcome likely depends on individuals' pre-existing views, including those gained from prior altered states of consciousness. The effects of Chamber REST appear comparable to those of psychedelic sessions.