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.
JAMA Psychiatry
March 25, 2026
Wiesław Jerzy Cubała, Malek Bajbouj, Michael Bauer et al.
3 citations
A single day of treatment with an inhaled synthetic formulation of mebufotenin (GH001) significantly reduced depression symptoms in adults with treatment-resistant depression compared to placebo. In a randomized, double-blind trial of 81 patients, those receiving up to three escalating doses of GH001 showed an average 15.5-point greater improvement on the Montgomery-Åsberg Depression Rating Scale by day 8 than those on placebo. Remission rates were 57.5% for GH001 and 0% for placebo. No severe or serious adverse events occurred. The findings suggest GH001 may be a rapid-acting, well-tolerated treatment option for treatment-resistant depression.
Progress in neuro-psychopharmacology & biological psychiatry
March 20, 2025
Kristýna Štefková-mazochová, Hynek Danda, Vladimír Mazoch et al.
3 citations
Methoxphenidine (MXP), a new psychoactive substance, rapidly crosses the blood-brain barrier in Wistar rats, reaching peak concentrations in serum and brain 30 minutes after injection, with a half-life of 2.15 hours. Low to moderate doses (10-20 mg/kg) increase locomotor activity in an open field test, while a higher dose (40 mg/kg) decreases it. All doses disrupt sensorimotor gating (prepulse inhibition), an effect linked to psychosis. MXP shows moderate acute toxicity with an estimated LD50 of 500 mg/kg subcutaneously. The drug exhibits a profile similar to dissociative anesthetics, producing stimulant and anxiogenic effects at lower doses and sedative effects at higher doses, indicating risks of serious adverse health outcomes from recreational use.
Journal of affective disorders
August 1, 2026
Guy M Goodwin, Scott T Aaronson, Oscar Alvarez et al.
2 citations
In people with treatment-resistant depression receiving 25 mg psilocybin with monitoring and support, the therapeutic alliance before dosing had only weak correlations with improvement in depression scores at three weeks. Stronger correlations were seen with the intensity of the psychedelic experience itself, particularly emotional breakthrough and visual restructuring. Path analysis suggested that therapeutic alliance helped facilitate the psychedelic experience, but it was the psychedelic experience—not the alliance—that had stronger direct effects on clinical outcomes. The alliance's direct effect on antidepressant response was limited or absent.
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 Janečková 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.
Progress in neuro-psychopharmacology & biological psychiatry
July 5, 2025
Hynek Danda, Kristýna Mazochová, Klára Šíchová et al.
1 citation
Baeocystin, a compound found in psychoactive mushrooms, has minimal to no behavioral effects in rats, likely because it poorly crosses the blood-brain barrier. After subcutaneous doses of 1.25 or 5 mg/kg, baeocystin and its metabolite norpsilocin showed very limited brain penetration. Consistent with this, the compound had no significant effects on locomotor activity, exploratory behavior, anxiety-like responses, or sensorimotor gating in Wistar rats. The findings suggest baeocystin's negligible neurobiological and psychedelic activity is due to its poor permeability across the blood-brain barrier.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
June 1, 2025
Natalie Paškanová, Magdaléna Vágnerová, Bronislav Jurásek et al.
1 citation
Methoxphenidine (MXP), a dissociative anaesthetic derivative, is increasingly abused, but forensic and clinical data on its metabolism and enantiomers are limited. Researchers developed and validated achiral LC-MS/MS and chiral SFC-MS methods to quantify MXP and its primary metabolite, O-desmethyl-methoxphenidine (dmMXP), in rat serum and brain after a single subcutaneous dose of racemic MXP. Serum MXP peaked at 1600 ng/mL at 0.5 hours and decreased to 5.87 ng/mL at 24 hours; brain MXP peaked at 13200 ng/g at 0.5 hours and fell to 36.1 ng/g at 24 hours. (S)-MXP concentrations in brain appeared higher than (R)-enantiomer concentrations. The methods enable pharmacokinetic studies and provide tools for forensic and clinical toxicology.
Journal of psychopharmacology (Oxford, England)
May 28, 2025
Yana Vella, Kateřina Syrová, Aneta Petrušková et al.
1 citation
Psilocin, the active compound in magic mushrooms, promotes the formation of new synapses in rat brain cells, an effect comparable to ketamine and lithium. In laboratory experiments on rat cortical cultures, psilocin increased the number of synaptic puncta and boosted expression of the immediate early gene Arc after acute treatment. Lysergic acid diethylamide (LSD) and N,N-dimethyltryptamine (DMT) did not produce significant synaptogenic effects. Fluoxetine, a common antidepressant, had no effect on synapse formation but upregulated other immediate early genes. These findings add evidence that psilocin may be a promising therapeutic agent for psychiatric conditions.
bioRxiv Preprint Server
August 7, 2024
Yana Vella, Kateřina Syrová, Aneta Petrušková et al.
1 citation
preprint
Psychedelics can produce rapid and lasting antidepressant effects, likely through neuroplasticity, though the precise molecular mechanisms are not yet understood.
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.
Journal of Fungi
July 2, 2026
Amiel Sharchaton, Shilat Parsha, Sara P. Azerrad et al.
Even when grown under identical conditions, different strains of the same mushroom species, Psilocybe cubensis, vary dramatically in their psychedelic compound content. Total tryptamine concentrations ranged more than 7.8-fold across 14 strains, from 2.62 to 20.65 mg per gram of dried mushroom. Psilocybin was always the most abundant compound. Individual mushrooms from the same strain also showed substantial variation, with psilocybin levels differing by 12.81% to 23.39% between fruiting bodies. This biochemical variability, both between strains and within a single strain, makes it difficult to standardize whole mushroom preparations for research or therapeutic use, emphasizing the need for careful strain selection, chemical profiling, and precise dosing.
Pharmacology, biochemistry, and behavior
June 30, 2026
Lucie Ladislavová, Viera Kútná, Kristýna Mazochová et al.
Chronic microdosing of psilocin (0.05 or 0.075 mg/kg) in adult male Wistar rats over five weeks did not alter locomotor activity, depressive-like behavior, sociability, or novelty seeking, and did not increase cell proliferation in the dentate gyrus of the hippocampus. A small anxiogenic effect was detected in the Elevated Plus Maze. The findings suggest that, under this dosing schedule, psilocin microdosing produces limited behavioral effects and does not enhance hippocampal progenitor proliferation.
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.
Journal of Psychedelic Studies
June 12, 2026
Zuzana Postránecká, Matyáš Lucký, Viktor Mravčík et al.
Psychedelic-assisted psychotherapy (PAP) shows cautious clinical potential for treating substance use disorders, but the evidence remains heterogeneous and largely from observational, open-label, or historical studies rather than strong randomized controlled trials. In the Czech Republic, recent developments include ketamine-assisted psychotherapy initiatives, inclusion of PAP in national addictology guidance, publication of national psychiatry guidelines for psilocybin-assisted psychotherapy, and a 2025 legislative reform introducing psilocybin for medical use from January 2026. Broader integration will require clearer indications, accredited training, longitudinal outcome monitoring, and transparent communication of benefits and risks.
Journal of Fungi
April 7, 2026
Eyal Kurzbaum, Tomáš Páleníček, Amiel Sharchaton et al.
correction
The text is a correction notice for an earlier publication and provides no substantive findings, arguments, or data to summarize.
Addiction Biology
March 1, 2026
Isis Koutrouli, Vojtěch Brejtr, Marek Schwendt et al.
Psilocybin and ibogaine, given in a dose-escalation protocol, facilitated extinction learning in male rats that had self-administered cocaine. Psilocybin reduced active lever pressing one day after the second dose, with a nonsignificant reduction after the first dose; ibogaine significantly reduced pressing even after the first administration. Neither drug significantly altered cue-induced reinstatement of drug-seeking, though psilocybin showed a trend toward attenuation. The treatments had no side effects on general locomotor activity or anxiety-like behavior in the open field test. These results suggest psilocybin and ibogaine may support extinction learning and possibly protect against relapse, warranting further research into their antiaddictive potential.
Psychopharmacology
December 13, 2025
David Greguš, Jaroslav Hlinka, Filip Tylš et al.
The spatial organization of the cingulate cortex, rather than the thickness of a single region, predicts the intensity of psychedelic experiences under psilocybin. In a double-blind, placebo-controlled crossover study with 25 healthy participants, an anterior–posterior gradient in cingulate thickness significantly predicted psychedelic experience intensity. The previously reported finding that rostral anterior cingulate cortex thickness alone predicts emotional responses showed a comparable effect size but did not reach statistical significance, likely due to the smaller sample size. These results suggest that the pattern of cortical thickness across the cingulate cortex, not focal measures, serves as a neuroanatomical marker of variability in psychedelic response.
Research Square
September 25, 2025
David Greguš, Jaroslav Hlinka, Filip Tylš et al.
Individual differences in how people respond to psilocybin are linked to the structural organization of the cingulate cortex. A previous finding that thickness of a specific cingulate region predicted emotional responses was not replicated. Instead, a broader anterior-to-posterior gradient of cingulate thickness predicted the overall intensity of the psychedelic experience, and general cingulate thickness was associated with the balance between anxiety and visionary states. These results suggest that patterns of cortical thickness across the cingulate, rather than a single region, may serve as a neuroanatomical marker for predicting psychedelic response, with potential implications for personalized dosing in therapy.
bioRxiv Preprint Server
August 28, 2024
Lucie Olejníková-Ladislavová, Michaela Fujáková-Lipski, Klára Šíchová et al.
preprint
Mescaline, a classical psychedelic with a phenylethylamine structure, primarily acts on serotonin 5-HT2A/C receptors but also binds to 5-HT1A and 5-HT2B receptors. Although it was the first psychedelic ever isolated and synthesized, the precise role of these different serotonin receptor subtypes in its behavioral pharmacology remains not fully understood.
IBRO Neuroscience Reports
November 6, 2023
Tomáš Páleníček, Tereza Kluckova, Marek Nikolic 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.