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.
Frontiers in Psychiatry
July 19, 2021
Rita Kočárová, Jiřı́ Horáček, Robin Carhart‐Harris
95 citations
Psychedelic therapy may work across many psychiatric disorders by increasing neuronal and mental plasticity, which enhances the potential for change. Combined with psychotherapy, this plasticity can promote healthy adaptability and resilience, protecting long-term well-being. The authors propose that psychedelics' core action is transdiagnostic, offering prophylactic benefits beyond current treatments. They link candidate neurological and psychological markers to a predictive processing model, suggesting broad public health impact.
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
October 6, 2007
Tomáš Páleníček, Marie Balı́ková, Vĕra Bubeníková‐valešová et al.
61 citations
Mescaline, a nonselective serotonin receptor agonist, produced significant inhibitory effects on locomotion in rats at low doses and a biphasic effect at the highest dose. In tests of sensorimotor gating (prepulse inhibition of acoustic startle), all doses disrupted gating only when tested 60 minutes after administration. Approximately 50% of animals receiving 100 mg/kg died within 12 hours. Serum mescaline levels rose rapidly within 30 minutes and then quickly declined, while brain concentrations peaked 1 hour after administration and remained elevated for another 60 minutes. The delayed onset of behavioral changes correlated with the drug's pharmacokinetics.
Schizophrenia Bulletin
December 18, 2015
Filip Španiel, Jaroslav Tintěra, Jan Rydlo et al.
55 citations
Disturbance of the sense of self may be a core marker of schizophrenia. In patients with first-episode schizophrenia-spectrum disorders compared with healthy controls, self-agency experience was associated with reduced cortical activation in the medial frontal gyrus and posterior cingulate gyrus. The ability to judge whether an action is one's own or another's depends on anti-correlated switching between the default mode and central-executive networks, a mechanism substantially impaired in the patient group during the task.
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.
Frontiers in Psychiatry
August 28, 2020
Veronika Andrashko, Tomáš Novák, Martin Brunovský et al.
46 citations
Concomitant benzodiazepine treatment at higher doses may attenuate the rapid antidepressant effect of a single ketamine infusion. In 47 patients with major depression who received 0.54 mg/kg ketamine as an add-on to ongoing antidepressants, 28% achieved at least a 50% reduction in depression severity within one week. Patients taking more than 8 mg of diazepam equivalent daily showed a significantly worse response on days 3 and 7 compared to those taking lower doses or none. Nonresponders had significantly higher benzodiazepine doses. The findings suggest that higher benzodiazepine doses interfere with ketamine's efficacy, with implications for clinical protocols and future research.
Psychological Medicine
December 9, 2009
Jiřı́ Horáček, Martin Brunovský, Tomáš Novák et al.
42 citations
A single dose of ketamine (0.54 mg/kg infused over 30 minutes) rapidly alters brain electrical activity in healthy volunteers, producing a decrease in prefrontal theta cordance—a QEEG measure linked to cerebral blood flow—and an increase in central region theta cordance within 10 to 30 minutes. These changes resemble those seen after one week of treatment with standard antidepressants in people who respond to them, but occur much faster. The prefrontal theta cordance reduction correlated with ketamine and norketamine blood levels at 10 minutes. The findings suggest that theta cordance reduction could serve as a marker and predictor of ketamine's rapid antidepressant effect, a hypothesis warranting testing in depressed patients.
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.
Clinical Neurophysiology
March 14, 2021
Torsten M. Meyer, Martin Brunovský, Jiřı́ Horáček et al.
25 citations
In patients with major depressive disorder, heart rate and heart rate variability measured before and during ketamine infusion can predict who will respond to treatment. Among 51 patients, those who responded to ketamine had a higher heart rate throughout the study, including at baseline, compared to non-responders. Ketamine infusion increased both heart rate and heart rate variability power during and after infusion. Heart rate and heart rate variability power, but not normalized frequency bands, discriminated between responders and non-responders. These findings suggest that autonomic nervous system markers may help optimize treatment selection for major depressive disorder.
Journal of Psychopharmacology
June 3, 2019
Yuliya Zaytseva, Jiřı́ Horáček, Jaroslav Hlinka et al.
25 citations
Delta-9-tetrahydrocannabinol, the active compound in cannabis, temporarily alters how brain regions communicate with each other. In 19 occasional cannabis users who underwent two resting-state fMRI scans—one shortly after smoking a cannabis cigarette and one after at least a week without cannabis—a transient connectivity state appeared only during intoxication. This state showed high connectivity within and between auditory and somato-motor cortices, along with anti-correlation with subcortical structures and the cerebellum. Subjective perceptual changes and THC plasma levels were linked to this state, suggesting a neural biomarker of cannabis intoxication.
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.
Journal of Neuroscience Research
March 3, 2023
Veronika Langová, Petra Horká, Jan Hubený et al.
10 citations
Ketamine, an NMDA receptor antagonist, disrupted electric signaling and navigation in the weakly electric fish Gnathonemus petersii, a candidate model for schizophrenia. Lower doses increased locomotion and erratic movement, while higher doses reduced electric organ discharges, indicating positive schizophrenia-like symptoms. A low dose of haloperidol did not normalize these symptoms, suggesting further testing with more antipsychotic doses is needed to confirm the model's predictive validity.
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.
The International Journal of Neuropsychopharmacology
May 27, 2016
Tomáš Páleníček, Filip Tylš, Michaela Viktorinová et al.
6 citations
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Frontiers in Neuroscience
July 1, 2025
Michal Beneš, Tomáš Páleníček, Jiřı́ Horáček
4 citations
A scoping review of fMRI studies on serotonergic psychedelics (psilocybin, LSD, DMT) identifies unifying themes: de-differentiation centered on the default mode network, complex changes in the thalamus, amygdala, and medial temporal lobe, and the importance of ego dissolution. These findings complement established models of psychedelic action and highlight contrasts with phenomenologically similar states and links to other biological markers.
Frontiers in Psychology
May 10, 2019
Marek Havlík, Eva Kozáková, Jiřı́ Horáček
4 citations
Intrinsic conscious experiences—thoughts, daydreams, and mind-wandering—make up as much as half of conscious life but are largely ignored in consciousness research because they are methodologically difficult and lack dedicated experimental paradigms. This hypothesis and theory article proposes a new paradigm for studying intrinsic consciousness, modeled on methods used for perceptual consciousness. The authors present exploratory proof-of-concept data, discuss how the paradigm could be used, and address its limitations and possible solutions. They argue that intrinsic consciousness will soon become a standard topic in consciousness studies once suitable experimental tools are developed.
Frontiers in Psychology
July 20, 2018
Marek Havlík, Karolína Mladá, Iveta Fajnerová et al.
3 citations
Personality traits, particularly the dimension of self-transcendence measured by Cloninger's Temperament and Character Inventory, correlate with people's intuitive inclinations toward either dualism or reductive materialism regarding the mind-body problem. In a pilot study using a newly developed questionnaire based on analytic philosophy of the mind, participants categorized as dualists showed significant differences in self-transcendence scores compared to those categorized as reductive materialists. The findings suggest that philosophical positions on the mind-body problem, and possibly responses to thought experiments in philosophy of mind, may be influenced by underlying personality features, a factor that should be considered in future philosophical and empirical research.
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.
Fishes
May 15, 2025
Petra Horká, Josefina Mavrogeni, Veronika Langová et al.
1 citation
The weakly electric fish Gnathonemus petersii preferred a familiar object over a novel one in the novel object recognition task, spending less time, moving a shorter distance, and emitting fewer electric organ discharges when exploring the novel object. Ketamine, an NMDA receptor antagonist, did not produce significant behavioral changes on its own, and no direct link was found between electric organ discharges and behavioral responses to ketamine or typical antipsychotics. However, when ketamine was combined with the atypical antipsychotic clozapine, the fish no longer distinguished between the original and new objects, suggesting the drug combination disrupted object recognition.
European Psychiatry
March 1, 2015
Filip Španiel, Jaroslav Tintěra, Jan Rydlo et al.
1 citation
The ability to judge whether an action is one's own or another's depends on dynamic switching between two large-scale brain networks: the default mode network (DMN) and the central-executive network (CEN), which normally work in opposition. In people with first-episode schizophrenia spectrum disorders, this antagonistic switching mechanism is substantially impaired, and the degree of impairment correlates with poorer performance on self-agency judgment tasks. The findings suggest that a core pathology in schizophrenia may lie in the higher-order regulatory mechanisms that coordinate these networks.