The New England journal of medicine
November 3, 2022
Guy M Goodwin, Scott T Aaronson, Oscar Alvarez et al.
1,095 citations
A single 25 mg dose of psilocybin, but not 10 mg, reduced depression scores more than a 1 mg control dose over three weeks in adults with treatment-resistant depression. In this phase 2 trial, 233 participants were randomly assigned to 25 mg, 10 mg, or 1 mg of synthetic psilocybin with psychological support. The 25 mg group showed an average 12-point drop on the MADRS depression scale versus a 5.4-point drop in the 1 mg group, a significant difference. The 10 mg group did not differ significantly from control. Response and remission rates at three weeks supported the primary result, but sustained response at 12 weeks was not significantly different.
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.
European Neuropsychopharmacology
March 4, 2020
M. Madsen, Patrick M. Fisher, Dea Siggaard Stenbæk et al.
189 citations
A single dose of the serotonin 2A receptor agonist psilocybin can produce lasting beneficial effects on mood and personality, and potentially on mindfulness, but the underlying mechanisms are unclear. In ten healthy, psychedelic-naïve volunteers, psilocybin (0.2-0.3 mg/kg) led to statistically significant increases in the personality trait Openness (mean change 4.2) and in mindfulness (mean change 0.5) at three months. Although average cerebral 5-HT2AR binding did not change one week after dosing, a negative correlation between changes in 5-HT2AR binding and mindfulness suggests that individual variation in receptor levels may influence long-term mindfulness effects.
Journal of Affective Disorders
February 3, 2023
Guy M Goodwin, Scott T Aaronson, Oscar Alvarez et al.
168 citations
Three weeks after a single dose, 25 mg of psilocybin, and to a lesser extent 10 mg, improved patient-reported measures of depression severity, anxiety, affect, and functioning in people with treatment-resistant depression. These findings extend the primary results from the largest randomized clinical trial of psilocybin for TRD, highlighting outcomes that matter to patients.
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.
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.
Frontiers in Behavioral Neuroscience
May 16, 2014
Lukáš Rambousek, Tomáš Páleníček, Karel Valeš et al.
55 citations
Psilocin, the main metabolite of psilocybin and an agonist at 5-HT2A receptors, dose-dependently impaired spatial learning and memory retrieval in rats but did not affect memory consolidation. In the Carousel maze, both 1 and 4 mg/kg doses significantly impaired acquisition, with the higher dose blocking learning even in a subsequent saline session. In the Morris water maze, only the 4 mg/kg dose disrupted reinforced retrieval; the lower dose had no effect. Neither dose impaired memory consolidation when injected post-training. These findings suggest that 5-HT2A receptor activation disrupts certain cognitive processes relevant to schizophrenia models, though the validity of such animal models remains questioned due to the complexity of human cognition.
Behavioural Pharmacology
March 13, 2018
Rachel R. Horsley, Tomáš Páleníček, Jan Kolin et al.
52 citations
Microdosing with hallucinogens such as ketamine and psilocin may produce mild anxiety-like effects rather than relief, according to a rat study. Over six days, rats received low or moderate doses of ketamine, psilocin, or saline on three occasions. Forty-eight hours after the final treatment, an elevated plus-maze test measured anxiety-related behaviors. Statistical effects were modest or borderline, but the pattern was most consistent with a mildly anxiogenic profile, significant at lower doses. Lower doses of both drugs produced comparable effects, as did higher doses, suggesting a possible common mechanism. The authors conclude that microdosing for therapeutic purposes might be counter-productive, though more research is needed.
Psychopharmacology
January 1, 2013
Tomáš Páleníček, Michaela Fujáková, Martin Brunovský et al.
51 citations
The synthetic compound 2C-B produces a biphasic effect on movement in rats: initial inhibition followed by excitation, while amphetamine only causes hyperactivity. Both drugs disrupt prepulse inhibition of the acoustic startle reaction, a measure of sensory gating, but have opposite effects on the startle itself. 2C-B increases dopamine and decreases its metabolite DOPAC in the nucleus accumbens, a brain region linked to reward. Low doses of 2C-B reduce electrical brain activity and connectivity; a high dose first decreases then increases brain wave power and connectivity. Increases in theta and alpha brain waves correlate with heightened movement and dopamine levels. These results suggest 2C-B shares properties with hallucinogens, entactogens, and stimulants, and its dopamine effects may indicate psychotomimetic and addictive potential.
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.
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.
Brain Research Bulletin
May 4, 2016
Rachel R. Horsley, Eva Lhotková, Kateřina Hájková et al.
38 citations
Methoxetamine (MXE), a novel psychoactive compound used as a substitute for ketamine, was tested in Wistar rats across a series of behavioral tasks. At lower doses (5 and 10 mg/kg), MXE stimulated locomotion, increased thigmotaxis, and decreased time spent in the center of an open field, indicating anxiogenic effects. At a higher dose (40 mg/kg), it reduced locomotion and increased time in the center, suggesting sedation or anesthesia. MXE disrupted prepulse inhibition (PPI) and reduced habituation. The drug accumulated in the brain, with brain-to-serum ratios between 2.06 and 2.93, and its effects lasted at least 60–90 minutes.
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.
Frontiers in Psychiatry
November 17, 2017
Nikola Pinterová, Rachel R. Horsley, Tomáš Páleníček
37 citations
Aminoindanes, a class of novel psychoactive substances often sold as "bath salts," gained popularity on the recreational drug market after mephedrone and other synthetic cathinones were banned in the UK in 2010. Originally developed for medical uses such as anti-Parkinsonian drugs and potential psychotherapy aids, they are now widely substituted for ecstasy. Their primary mechanism of action involves serotonin, which poses a significant risk of serotonin syndrome at high doses or when combined with other drugs. Fatally toxic effects have been observed in animal studies and in clinical cases, with reported deaths. Greater knowledge and appropriate legislation are urgently needed to reduce risks of fatal intoxication while not impeding research.
Journal of affective disorders
March 1, 2025
Guy M Goodwin, Scott T Aaronson, Oscar Alvarez et al.
35 citations
In treatment-resistant depression, a single dose of 25 mg of psilocybin produced stronger correlations between certain psychedelic experiences and depression improvement three weeks later than lower doses. The intensity of psychedelic effects was dose-related, but scores for different doses overlapped considerably. At the 25 mg dose, dimensions of oceanic boundlessness and visual restructuralization, along with emotional breakthrough, showed the strongest correlations with reduced depression scores. The study does not establish causation and requires replication. The overlap in experience intensity across doses suggests unblinding to dose is less likely. Correlations between psychedelic experience and outcome indicate specificity in psilocybin's mechanism of action.
Toxicology letters
April 21, 2008
Miroslava Rohanová, Tomáš Páleníček, Marie Balíková
33 citations
The psychedelic compound 2C-B, involved in human drug abuse and overdose cases, was studied in rats to determine its distribution and kinetics after subcutaneous injection. The drug had an estimated half-life of 1.1 hours and a volume of distribution of 16 L/kg. 2C-B entered the brain without significant delay, and its brain-to-serum ratio peaked at 13.9, remaining above 6.5 for six hours. The lungs showed a tendency to retain the drug and release it gradually over time, similar to the brain. The major metabolite 2H5M-BPEA was found in lung, brain, and liver tissues but distributed less efficiently into the brain than the parent compound. These findings help assess the drug's psychotropic and toxic effects.
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.
Analytical and Bioanalytical Chemistry
December 11, 2015
Kateřina Hájková, Bronislav Jurásek, David Sýkora et al.
26 citations
A new sample preparation and detection method for the designer drug methoxetamine (MXE) and five of its metabolites in rat brain, liver, and lung tissues was developed. The procedure uses salting-out-assisted liquid-liquid extraction followed by liquid chromatography-tandem mass spectrometry. Calibration curves were linear from 2.5 to 250 ng/g, with limits of quantification of 2.5 and 5 ng/g. Recovery ranged from 80% to 117% and matrix effects from 94% to 110%. The method was successfully applied to real samples from toxicological trials on rats.
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.
Frontiers in Psychiatry
April 24, 2018
Rachel R. Horsley, Eva Lhotková, Kateřina Hájková et al.
20 citations
MDPV, a potent synthetic cathinone, is rapidly absorbed after subcutaneous injection in male Wistar rats, reaching peak concentrations in serum, brain, and lungs within 30 minutes. It readily crosses the blood-brain barrier, with a brain-to-serum ratio of about 2 lasting for roughly 120 minutes. The drug is primarily excreted as metabolites, with demethylenyl-MDPV and demethylenyl-methyl-MDPV levels three to four times higher than the parent drug in urine. MDPV acts as a typical stimulant, producing locomotor activation, disrupted spatial behavior, moderate hyperthermia (exacerbated in group-housed animals), and transient disruption of prepulse inhibition at 4 mg/kg, consistent with a dopaminergic mechanism. No specific signs of acute toxicity were observed at the doses used.
Neuroscience of consciousness
January 1, 2025
Christopher Timmermann, James W Sanders, David Reydellet et al.
19 citations
The psychedelic 5-MeO-DMT can, in its most extreme cases, produce a complete absence of self-experience and other perceptual content while preserving a quality of aroused, waking awareness. In an exploratory observational study in naturalistic ceremonial settings, micro-phenomenological interviews, questionnaires, and EEG recordings revealed a dynamic progression of effects, including variable disruptions of bodily and narrative self, reduced phenomenal distinctions, and visual imagery. EEG showed global alpha and posterior beta power reductions, suggesting inhibition of top-down brain models. The findings indicate 5-MeO-DMT's potential as a pharmacological model for deconstructed consciousness, though retrospective questionnaires have limitations.
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.