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.
Frontiers in Psychiatry
November 17, 2017
Kristýna Štefková, Monika Židková, Rachel R. Horsley et al.
82 citations
Methylone, a synthetic cathinone analog of ecstasy, is marketed as relatively safe but has caused fatalities from hyperthermia, serotonin syndrome, and multi-organ failure. In adolescent male Wistar rats, methylone (5, 10, 20 mg/kg subcutaneously) dose-dependently increased locomotion, reduced time in the open field center at 20 mg/kg, and induced stereotyped circling; its metabolite nor-methylone showed similar behavioral potency. Both drugs peaked in serum and brain at 30 minutes, with a serum-to-brain ratio of 1:7.97. Methylone also caused hyperthermia, more pronounced in group-housed rats, and 40 mg/kg was lethal to some animals. The findings suggest methylone acts like MDMA or amphetamine but with higher toxicity, posing risks of serotonin syndrome, especially in crowded settings.
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.
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.
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 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.
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.
Addiction Biology
May 7, 2020
Nikola Pinterová, Rachel R. Horsley, Hynek Danda et al.
13 citations
Naphyrone, a synthetic cathinone similar to pyrovalerone, potently blocks monoamine transporters and produces stimulant and entactogen-like effects. In male Wistar rats, a single subcutaneous dose of 1 mg/kg reached peak concentrations in blood and tissues within 30 minutes, with prolonged elevation in the brain relative to serum. A higher dose of 20 mg/kg caused modest increases in body temperature and lasting hyperactivity in an open field test, while transiently improving sensorimotor gating as measured by prepulse inhibition. No acute toxicity was observed. The drug crosses the blood-brain barrier rapidly and is eliminated slowly, with effects matching its pharmacokinetics. Harm-reduction guidance should follow that for other stimulants and cathinones.
Xenobiotica
July 12, 2016
Monika Židková, Igor Linhart, Marie Balı́ková et al.
6 citations
The drug 5,6-Methylenedioxy-2-aminoindane (MDAI), a serotoninergic aminoindane sold as a substitute for banned stimulants and entactogens, is metabolized in rats primarily through oxidative demethylenation followed by O-methylation and N-acetylation, producing five main metabolites found as glucuronides and sulphates. Most of the administered MDAI was excreted unchanged. Minor metabolites formed by hydroxylation include cis- and trans-1-hydroxy- and 4-hydroxy derivatives. Identification of most metabolites was confirmed with synthesized reference standards.
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.