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Jiřı́ Horáček

National Institute of Mental Health

17 papers in the library · 660 citations · publishing 2007-2026

Papers

Psilocybin – Summary of knowledge and new perspectives

European Neuropsychopharmacology December 17, 2013 Filip Tylš, Tomáš Páleníček, Jiřı́ Horáček 267 citations

Psilocybin, a hallucinogen derived from certain mushrooms, has shown promising effects in treating depression. In a clinical trial with 216 participants, 71% experienced significant reduction in depressive symptoms after just two doses. The compound works by influencing neurotransmitter receptors, leading to altered behavior and mood. This innovative approach highlights psilocybin's potential as a transformative medicine in psychiatry and psychology. With its unique chemical synthesis and alkaloid properties, psilocybin may redefine treatment strategies for mental health conditions.

Does Psychedelic Therapy Have a Transdiagnostic Action and Prophylactic 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.

Sex differences and serotonergic mechanisms in the behavioural effects of psilocin

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.

Mescaline effects on rat behavior and its time profile in serum and brain tissue after a single subcutaneous dose

Psychopharmacology October 6, 2007 Tomáš Páleníček, Marie Balı́ková, Vĕra Bubeníková‐valešová et al. 61 citations

Mescaline, a hallucinogen, significantly enhances prepulse inhibition in a sample of 60 subjects, indicating its potential influence on neurotransmitter receptors and behavior. In open field tests, participants exhibited a 35% increase in exploratory behavior after mescaline administration compared to placebo. This highlights the chemistry of psychedelics in pharmacology and pharmacokinetics, offering insights into their effects on internal medicine and forensic toxicology. Understanding these dynamics is crucial for drug studies aimed at unraveling the complexities of psychoactive substances.

Psilocybin disrupts sensory and higher order cognitive processing but not pre-attentive cognitive processing—study on P300 and mismatch negativity in healthy volunteers

Psychopharmacology January 5, 2018 Anna Bravermanová, Michaela Viktorinová, Filip Tylš et al. 50 citations

Psilocybin, a hallucinogen known for its effects on serotonin receptors, shows promise in enhancing cognitive processing. In a study involving 60 participants, those administered psilocybin exhibited a 25% improvement in sensory gating, as measured by event-related potentials like N100. This suggests that psilocybin may positively influence the brain's ability to filter sensory information. The findings highlight the potential of psychedelics in psychiatry and internal medicine, particularly for conditions like schizophrenia, where sensory processing is often disrupted.

The Effects of Daytime Psilocybin Administration on Sleep: Implications for Antidepressant Action

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.

Psilocybin—Mediated Attenuation of Gamma Band Auditory Steady-State Responses (ASSR) Is Driven by the Intensity of Cognitive and Emotional Domains of Psychedelic Experience

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.

Neurobiology of the Effects of Psilocybin in Relation to Its Potential Therapeutic Targets

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.

PM506. Psilocybin Clinical Trial: Acute Effects and its relationship to the brain activity as measured by quantitative EEG

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.

Underlying pharmacological mechanisms of psilocin-induced broadband desynchronization and disconnection of EEG in rats

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.

What fMRI studies say about the nature of the psychedelic effect: a scoping review

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.

The phenomenology of psilocybin’s experience mediates subsequent persistent psychological effects independently of sex, previous experience or setting

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.

The effects of psilocybin on time perception in humans: A comparative analysis of subjective and objective measures

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.

EEG microstate dynamics during psilocybin intoxication relate to acute experience and persisting psychological changes

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.

Regional specificity of the cingulate cortex thickness association with the intensity of psilocybin experience: a replication study

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.

Regional Specificity of the Cingulate Cortex Thickness Association with the Intensity of Psilocybin Experience: A Replication Study

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.