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 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.
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.
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.
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 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.
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 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.
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.
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.
Metabolites
November 12, 2021
Jitka Nykodemová, Anna Šuláková, Petr Palivec et al.
14 citations
The metabolism of the psychoactive compound 2C-B-Fly-NBOMe was investigated using three systems: human liver microsomes, the fungus Cunninghamella elegans, and live rats. Thirty-five phase I and nine phase II metabolites were identified. Major metabolic pathways include hydroxylation, O-demethylation, oxidative debromination, and N-demethoxybenzylation, followed by glucuronidation or N-acetylation. Human liver microsomes produced the most metabolites at highest concentrations. Two poly-hydroxylated metabolites appeared only in rat urine, while the fungus generated dehydrogenated, N-oxygenated, and dibrominated metabolites. These findings clarify how the body processes this substance, aiding understanding of its effects and potential toxicity.
British journal of pharmacology
January 1, 2022
Kristýna Štefková-mazochová, Hynek Danda, Wim Dehaen et al.
13 citations
Deschloroketamine (DCK), a structural analogue of ketamine sold as a recreational drug, was tested in Wistar rats to examine its pharmacokinetics, acute effects, and addictive potential. DCK rapidly entered the brain, with peak levels at 30 minutes and sustained high levels for 2 hours. It blocks NMDA receptors similarly to ketamine, with the S-enantiomer more potent. DCK stimulated locomotion, induced place preference (a sign of reward), and strongly disrupted prepulse inhibition (PPI). Locomotor stimulation faded faster than PPI disruption. S-DCK had stronger stimulatory effects than R-DCK, but both equally disrupted PPI. DCK's behavioral and addictive profiles resemble ketamine's, with a slightly slower clearance, matching its reported longer duration. These findings clarify risks of illicit DCK use.
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.
Journal of Fungi
January 28, 2025
Eyal Kurzbaum, Tomáš Páleníček, Amiel Shrchaton et al.
11 citations
The psychoactive mushroom Psilocybe cubensis, known for its historical and modern therapeutic roles, shows substantial variability in its psychoactive compounds, psilocybin and psilocin, due to genetic diversity, strain differences, and environmental factors. Advances in cultivation, such as submerged fermentation of mycelium, and improved analytical methods now allow more precise compound quantification and extraction. Despite nearly four decades of regulatory restrictions limiting scientific information, recent genetic and biochemical studies are beginning to reveal insights into its therapeutic potential. The review identifies key knowledge gaps and suggests future research directions to improve cultivation, document strain diversity, and address regulatory and therapeutic uses.
Journal of Neurochemistry
February 28, 2025
Aneta Petrušková, Debarpan Guhathakurta, Enes Yağız Akdaş et al.
8 citations
Serotonergic psychedelics like psilocybin, LSD, and DMT rapidly alter how neurons communicate at synapses. Using live-cell imaging in rat cortical neurons, the drugs reduced the fraction of synaptic vesicles that fuse in response to electrical stimulation within minutes, an effect that faded within 24 hours. DMT only reduced the total recycling pool of vesicles, while LSD and psilocin also shrank the readily releasable pool. Psilocin and DMT increased evoked glutamate release, yet LSD and psilocin lowered presynaptic calcium levels. Psilocin further depressed responses to paired stimuli. These drug-specific modulations of glutamatergic transmission may help explain their distinct therapeutic properties.
medRxiv
September 11, 2024
M. Nikolič, Pedro A. M. Mediano, Tom Froese et al.
6 citations
preprint
Psilocybin, a classic psychedelic, alters perception, cognition, and emotion by activating 5-HT2A receptors and reducing serotonin reuptake. In a placebo-controlled crossover study with 20 healthy individuals, electroencephalography tracked brain activity changes over 24 hours after oral psilocybin (0.26 mg/kg). Acutely, absolute power decreased in alpha and beta bands but increased in delta and gamma frequencies; alpha power decreased occipitally between 1 and 3 hours, and beta decreased frontally at 3 hours. Global functional connectivity in the alpha band dropped acutely, while Lempel-Ziv complexity increased at 1 and 1.5 hours.
The International Journal of Neuropsychopharmacology
May 27, 2016
Tomáš Páleníček, Filip Tylš, Michaela Viktorinová et al.
6 citations
No Summary
Journal of Psychopharmacology
September 12, 2025
Stephan Tap, Kelan Thomas, Tomáš Páleníček et al.
5 citations
Classic psychedelics like psilocybin are being studied for psychiatric disorders. Current protocols typically require patients to stop antidepressants (ADs) for at least two weeks before psychedelic use to avoid serotonin syndrome and preserve efficacy, but discontinuation can worsen depression and increase suicidal ideation. This scoping review of 18 studies found that using ADs alongside classic psychedelics is generally safe and tolerable, with no increased risk of serotonin syndrome, especially with psilocybin. Some studies showed significant improvements in depression and other symptoms. Although some evidence suggests a potential reduction in acute subjective psychedelic effects, this was not consistent. The authors conclude that maintaining ADs may improve patient access and avoid discontinuation risks.
Pharmacology, biochemistry, and behavior
December 1, 2024
Lucie Olejníková-Ladislavová, Michaela Fujáková-Lipski, Klára Šíchová et al.
5 citations
Mescaline, a classical psychedelic, primarily acts on serotonin 5-HT2A/C receptors but also binds to 5-HT1A and 5-HT2B receptors. In adult male rats, the highest dose (100 mg/kg) caused hyperlocomotion, which was reversed by almost all antagonists tested. Sensorimotor gating deficits, measured as prepulse inhibition of acoustic startle, were selectively normalized by a 5-HT2A antagonist, while a 5-HT2C antagonist partially reversed deficits from lower doses. These findings indicate that mescaline's behavioral effects are mainly mediated by the 5-HT2A receptor subtype, with a lesser role for 5-HT2C receptors, and limited involvement of other subtypes.
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.
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.