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.
Pharmaceuticals
November 30, 2022
Martin Paškan, Silvie Rimpelová, Vladimíra Svobodová Pavlíčková et al.
9 citations
A novel synthetic cathinone, 4-isobutylmethcathinone, was synthesized and its properties characterized. The substance showed significantly higher cytotoxicity compared to other synthetic cathinones, with IC50 values reaching 18–65 µM after 72 hours in human bladder, neuroblastoma, microglia, and liver cancer cells. Chiral separation enabled study of individual enantiomers, which exhibited different agonistic effects on dopamine and adrenergic receptors. The compound lacked binding affinity for serotonin receptors, placing it among monoamine drugs like MDMA.
Addiction Biology
August 4, 2022
Klára Šíchová, Kateřina Syrová, Edita Kofroňová et al.
8 citations
25CN-NBOMe, a substance related to LSD, readily crosses the blood-brain barrier in rats. After a 5 mg/kg dose, drug concentration peaked in blood and brain at 1 hour, with half-lives of 1.88 and 2.28 hours. The drug is classified as toxicity category 3, with a lethal dose of 300 mg/kg and an estimated LD50 of 200 mg/kg. Histological findings suggest acute cardiovascular arrest from malignant arrhythmia at lethal doses. A 5 mg/kg dose reduced body temperature in individually housed rats. Lower doses (0.2 and 1 mg/kg) reduced locomotor activity and increased anxiety, while 5 mg/kg also impaired sensorimotor gating. The drug's behavioral effects are comparable to other NBOMes.
bioRxiv (Cold Spring Harbor Laboratory)
December 7, 2021
Federico Cavanna, Stephanie Müller, Laura Alethia de la Fuente et al.
8 citations
preprint
A double-blind placebo-controlled trial tested the effects of a low (0.5 g) sub-hallucinogenic dose of dried psilocybin mushrooms in 34 individuals planning to microdose. Acute subjective effects were significantly stronger with the active dose than with placebo, possibly due to unblinding. For other measures—including creativity, perception, cognition, and brain activity—the results were null or showed a trend toward cognitive impairment and, in electroencephalography, reduced theta band spectral power. These findings suggest that expectation effects may account for some of the anecdotal benefits people report from microdosing psilocybin.
Scientific Reports
April 22, 2024
Oleh Durydivka, Petr Palivec, Matej Gazdarica et al.
7 citations
Hexahydrocannabinol (HHC) activates cannabinoid receptor 1 (CB1R) in ways only broadly comparable to Δ9-tetrahydrocannabinol (Δ9-THC), with each HHC epimer showing unique signaling properties. HHC's greater chemical stability than Δ9-THC makes it a potential candidate for modern medicine. The study examined the pharmacodynamics of HHC epimers and their activation of CB1R-mediated signaling pathways, comparing them to those activated by Δ9-THC.
International Journal of Molecular Sciences
February 14, 2022
Bronislav Jurásek, Silvie Rimpelová, Martin Babor et al.
7 citations
A sample of the dissociative anesthetic methoxphenidine from the black market contained an unusual bromo- and chloro-zincate anion impurity. In vitro cytotoxicity tests on kidney, liver, and bladder cell lines showed that the street sample was markedly more toxic than a pure methoxphenidine standard, suggesting the impurity caused the increased toxicity. A method using X-ray powder diffraction (XRPD) was developed to identify such anions and distinguish different crystalline forms of methoxphenidine, providing additional data not captured by routine analysis.
Translational psychiatry
December 5, 2024
Bettina Habelt, Dzmitry Afanasenkau, Cindy Schwarz et al.
6 citations
Alcohol use disorder (AUD) impairs prefrontal control mechanisms, leading to reduced inhibitory control and increased relapse risk. Using a biocompatible neuroprosthesis in a rat model of alcohol addiction, researchers measured neural oscillations and event-related potentials during abstinence. Alcohol-dependent rats showed reduced amplitudes of P1N1 and N1P2 components and attenuated event-related oscillatory activity, along with a dominance in higher beta frequencies indicating hyperarousal prone to relapse. Treatment with psilocybin or LY379268 restored these electrophysiological impairments, with psilocybin particularly counteracting the hyperarousal state. These prefrontal markers may serve as indicators of relapse vulnerability and treatment response, especially for psychedelic drugs.
New Journal of Chemistry
January 1, 2023
Bronislav Jurásek, Patrik Fagan, Bohumil Dolenský et al.
6 citations
Methoxphenidine, a dissociative anesthetic related to phencyclidine, was originally patented for its potential to treat neurotoxic injury. The abstract indicates that the compound was developed with therapeutic applications in mind, specifically for addressing damage to the nervous system. No further details about its efficacy, mechanism, or clinical use are provided in this text.
Powder Diffraction
June 21, 2017
J. Maixner, Bronislav Jurásek, Michal Kohout et al.
5 citations
The crystal structure of S-2-(methylamino)-2-phenylcyclohexan-1-one hydrochloride (C13H18ClNO) was determined using X-ray powder diffraction. The compound crystallizes in the monoclinic space group P21 with unit-cell parameters a = 6.578 Å, b = 13.250 Å, c = 15.096 Å, β = 91.619°, and a unit-cell volume of 1315 ų, with four formula units per cell. All measured diffraction lines were indexed and are consistent with the assigned space group, and no detectable impurities were observed in the sample.
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.
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.
June 14, 2021
Luisa Prochazkova, Michiel van Elk, Josephine Marschall et al.
4 citations
preprint
Microdosing psychedelic truffles increased the quality of divergent thinking, measured as the ratio of original responses to total responses on the Alternative Uses Task, in a pooled analysis of three double-blind placebo-controlled trials with 175 participants. The unadjusted originality score was significantly higher only when relative dosage (dose per body weight) was considered. No effects were found on convergent thinking or other divergent-thinking scores. The effects were subtle and persisted after controlling for expectation and demographic biases. The findings underscore the importance of controlling for placebo effects and prior psychedelic experience in microdosing research.
Neuropharmacology
October 17, 2025
Luisa Prochazkova, Josephine Marschall, Dominique P. Lippelt et al.
3 citations
Microdosing psilocybin truffles does not reliably enhance cognitive or emotional functioning beyond a placebo. In two randomized, double-blind, placebo-controlled trials conducted in semi-naturalistic settings, microdosing did not significantly affect behavioral or subjective measures compared to placebo. Some initial effects on social cognition, mood, and self-reported cognitive flexibility were observed but did not remain significant after correcting for multiple comparisons. Participants predominantly reported positive subjective experiences regardless of condition, though negative bodily feelings were enhanced in the active condition. Participants remained effectively blinded throughout the trials.
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.
Neuroscience
November 1, 2024
Veronika Pohořalá, Martin Kuchař, Rainer Spanagel et al.
3 citations
Psilocybin administered immediately after extinction training did not reduce cue-induced cocaine-seeking in male and female mice or rats. In mice (16 female, 19 male) and rats (24 female, 23 male) that had learned to self-administer cocaine, psilocybin injections (1.0 mg/kg in mice; 1.0 or 2.5 mg/kg in rats) following extinction trials failed to attenuate reinstatement of drug-seeking when cues were presented. Both species and sexes showed significant cue-induced reinstatement regardless of psilocybin treatment. The findings indicate that psilocybin, at the doses and regimen tested, is ineffective in altering cocaine-seeking behavior in these animal models, leaving open whether other conditions might prove useful.
Neuropharmacology
November 2, 2025
Luisa Prochazkova, Josephine Marschall, Michiel van Elk et al.
2 citations
Microdosing psilocybin from truffles modestly improved the quality of divergent thinking—specifically the ratio of original responses to total responses—in a pooled analysis of three double-blind, placebo-controlled trials with 171 participants. The effect on unadjusted originality was significant only when dosage relative to body weight was considered, and it remained after controlling for dose guess and demographic biases. No effects were found on other measures of divergent thinking or on convergent thinking. The findings underscore the need to account for placebo effects and prior psychedelic experience when evaluating microdosing claims.
Scientific Reports
March 24, 2025
Lisa Höfert, Benjamin Franz, Cedric Groß et al.
2 citations
After oral (25 mg fruit gum) or inhalative (three puffs from a vape) consumption of the semi-synthetic cannabinoid hexahydrocannabinol (HHC), its pharmacokinetics and psychoactive effects are comparable to those of tetrahydrocannabinol (THC). The route of administration and inter-individual factors strongly influence maximum concentrations, pharmacokinetic profiles, and the subjective 'high' feeling. Serum, urine, and saliva samples were analyzed for HHC and its metabolites. Three commercially available immunological tests were also evaluated for detectability.
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.
Powder Diffraction
August 22, 2017
J. Maixner, Bronislav Jurásek, Michal Himl et al.
2 citations
The X-ray powder diffraction pattern of 2-(ethylamino)-2-(3-methoxyphenyl)cyclohexan-1-one hydrochloride is reported, providing its unit-cell parameters and space group. The compound crystallizes in the monoclinic space group P21 with two molecules per unit cell. All observed diffraction lines were indexed and matched this space group, and no impurities were detected.
Journal of Psychopharmacology
January 1, 2026
Petr Scholle, Štěpán Wenke, Tereza Nekovářová et al.
1 citation
Under psilocybin, healthy volunteers perceived time as moving more slowly and their temporal precision decreased, particularly for intervals longer than 2 seconds. In a double-blinded placebo-controlled study with 24 participants, the bisection point shifted rightward, indicating subjective time slowing, and the just noticeable difference increased, reflecting reduced accuracy. These changes were captured both by performance on the Temporal Bisection Task and by self-report scales. The findings suggest psilocybin disrupts cognitive functions such as working memory and attention, altering time perception through serotonergic system involvement.
The international journal of neuropsychopharmacology
August 1, 2025
Klára Šíchová, Barbara Mallarino, Lucie Janeckova 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.