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 Psychiatry
January 10, 2018
Klára Šíchová, Nikola Pinterová, Monika Židková et al.
28 citations
Mephedrone (MEPH) and its primary metabolite nor-mephedrone (nor-MEPH) were detected in the serum, brain, lungs, and liver of male Wistar rats, with the highest levels found in lungs. Maximum concentrations occurred at 30 minutes, and nor-MEPH levels exceeded those of the parent drug at 2 and 4 hours. Both drugs increased locomotion and altered its spatial distribution in a dose-dependent, rapid, and short-lasting manner, without disrupting prepulse inhibition. Behavioral effects disappeared within 40 minutes, but MEPH-induced rectal temperature elevations persisted for 3 hours even in singly housed rats, suggesting a dissociation between behavioral and hyperthermic effects that may contribute to prolonged somatic toxicity.
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.
Addiction Biology
August 4, 2022
Klára Šíchová, Kateřina Syrová, Edita Kofroňová et al.
8 citations
25CN-NBOMe, a substance related to LSD, readily crosses the blood-brain barrier in rats. After a 5 mg/kg dose, drug concentration peaked in blood and brain at 1 hour, with half-lives of 1.88 and 2.28 hours. The drug is classified as toxicity category 3, with a lethal dose of 300 mg/kg and an estimated LD50 of 200 mg/kg. Histological findings suggest acute cardiovascular arrest from malignant arrhythmia at lethal doses. A 5 mg/kg dose reduced body temperature in individually housed rats. Lower doses (0.2 and 1 mg/kg) reduced locomotor activity and increased anxiety, while 5 mg/kg also impaired sensorimotor gating. The drug's behavioral effects are comparable to other NBOMes.
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.
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.
Frontiers in pharmacology
January 1, 2023
Kateřina Syrová, Klára Šíchová, Hynek Danda et al.
4 citations
2C-B-Fly-NBOMe, a new psychoactive substance related to the psychedelic entactogen 2C-B, was studied in adult male Wistar rats. After injection, peak drug levels in blood serum occurred at 30 minutes (28 ng/ml) and in brain tissue at 60 minutes (171 ng/g), with the compound still detectable in the brain after 8 hours. The drug dose-dependently reduced locomotor activity and strongly disrupted the acoustic startle response, with a weaker effect on prepulse inhibition. It did not cause significant changes in body temperature. The overall profile resembles that of 2C-B and other NBOMe substances, suggesting slow brain penetration and inhibitory effects on motor performance and sensorimotor gating.
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 international journal of neuropsychopharmacology
August 1, 2025
Klára Šíchová, Barbara Mallarino, Lucie Janeckova et al.
1 citation
Hexahydrocannabinol (HHC), a new psychoactive substance used as a legal alternative to ∆9-tetrahydrocannabinol, crosses the blood-brain barrier, exhibits mild toxicity, and induces behavioral effects similar to tetrahydrocannabinol in male Wistar rats. A 1:1 mixture of (9R)-HHC and (9S)-HHC was given at doses of 1, 5, and 10 mg/kg. Two hours after the highest dose, peak concentrations appeared in blood and brain tissue. The OECD 423 test classified HHC as Category 4, with an estimated lethal dose of 1000 mg/kg. Compared to controls, 10 mg/kg HHC reduced movement, increased anxiety, and impaired sensory processing, highlighting dose-dependent anxiogenic properties and impact on information processing.
Journal of pharmaceutical and biomedical analysis
August 1, 2026
Magdaléna Vágnerová, Petr Palivec, Monika Mrňavá et al.
The metabolism of the recreational drug 25E-NBOH was investigated in human liver microsomes, rat urine, and Cunninghamella elegans fungus. Using untargeted LC-HRMS/MS, 56 metabolites were annotated, many as isomers. Primary metabolic pathways included hydroxylation, O-demethylation, and N-debenzylation, followed by conjugation. Ten reference substances were synthesized; seven matched detected metabolites by retention time and MS/MS spectra, enabling structural assignment. The known psychoactive substance 2C-E was confirmed as a metabolite. Three main biomarkers are proposed. This work provides the first comprehensive metabolic profile of 25E-NBOH, supporting future pharmacological and toxicological studies and aiding clinical diagnosis of intoxication.
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.
October 2, 2024
Klára Šíchová, Barbara Mallarino, Lucie Janeckova et al.
Hexahydrocannabinol (HHC), a psychoactive cannabinoid used as a legal alternative to THC, readily crosses the blood-brain barrier in male Wistar rats. After oral administration, both HHC epimers peaked in blood and brain tissue at two hours. The estimated lethal dose was 1000 mg/kg, classifying HHC as a Category 4 substance with mild toxicity. At the highest dose (10 mg/kg), HHC reduced locomotor activity, increased anxiety, and impaired sensorimotor gating, producing behavioral effects similar to THC-like cannabinoids.
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.
IBRO Neuroscience Reports
October 1, 2023
Čestmír Vejmola, Kateřina Syrová, Klára Šíchová et al.
GABAB receptors, which are part of the brain's inhibitory system, are modulated by accessory proteins called KCTD16. In experiments using mice lacking the KCTD16 gene, baseline pain sensitivity and nerve cell activity in the spinal cord were similar to normal mice. However, when treated with the GABAB receptor agonist baclofen, normal mice showed greater pain relief (higher thresholds for heat and touch) than mice lacking KCTD16. In a model of peripheral inflammation, KCTD16-deficient mice tended to have higher pain thresholds, and baclofen's inhibitory effect on nerve signals was reduced. The findings suggest KCTD16 may be important for pain modulation during pathological conditions when GABAB receptors are activated, but further research is needed.
Journal of neurophysiology
April 1, 2026
Inga Griškova-bulanova, Čestmír Vejmola, Tomáš Páleníček
Psilocin, the active metabolite of psilocybin, selectively disrupts auditory neural synchronization in rats in a frequency- and region-specific manner. In eight adult male Wistar rats implanted with cortical electrodes, psilocin (4 mg/kg) reduced phase-locking at 40 Hz stimulation in the right temporal cortex, with no significant changes in frontal or left temporal regions or at 80 Hz stimulation. Spectral power was globally reduced at 80 Hz after psilocin, but not consistently at 40 Hz. These results indicate that low-gamma oscillations are sensitive to serotonergic modulation via 5-HT2A receptor signaling, supporting auditory steady-state responses as translational biomarkers for altered perceptual states.