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.
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.
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 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.
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.
Therapeutic advances in psychopharmacology
January 1, 2026
Veronika Andrashko, Tomáš Novák, Miloslav Kopecek et al.
Higher blood pressure during ketamine infusion was associated with better antidepressant response in people with depression. Among 39 patients who received a single intravenous dose of ketamine, those who responded at day 7 had significantly higher systolic and diastolic blood pressure during the infusion than nonresponders. Dissociation and psychotomimetic symptoms did not differ between responders and nonresponders. Concomitant antipsychotic medication was linked to worse antidepressant outcome and lower infusion-related blood pressure. Plasma levels of ketamine or norketamine did not correlate with blood pressure, dissociative symptoms, or psychotomimetic effects.