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.
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.
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.
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.
Metabolites
March 31, 2021
Anna Šuláková, Jitka Nykodemová, Petr Palivec et al.
11 citations
N-Benzylphenethylamines, including 25CN-NBOMe, are novel psychedelic substances with limited metabolism data. This study investigated the metabolic profile of 25CN-NBOMe in rats in vivo and in human liver microsomes and Cunninghamella elegans mycelium in vitro. Major metabolic pathways include mono- and bis-O-demethylation, hydroxylation, and combinations, followed by glucuronidation, sulfation, or N-acetylation of primary metabolites. The cyano group was either hydrolyzed to an amide or carboxylic acid or remained unchanged. Differences between species should be considered in metabolism studies of novel substances.
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.
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 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.
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.
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 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.
Pharmacology, biochemistry, and behavior
June 30, 2026
Lucie Ladislavová, Viera Kútna, 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.
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.
October 2, 2024
Klára Šíchová, Barbara Mallarino, Lucie Janeckova et al.
Hexahydrocannabinol (HHC), a psychoactive cannabinoid used as a legal alternative to THC, readily crosses the blood-brain barrier in male Wistar rats. After oral administration, both HHC epimers peaked in blood and brain tissue at two hours. The estimated lethal dose was 1000 mg/kg, classifying HHC as a Category 4 substance with mild toxicity. At the highest dose (10 mg/kg), HHC reduced locomotor activity, increased anxiety, and impaired sensorimotor gating, producing behavioral effects similar to THC-like cannabinoids.
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
October 1, 2023
Čestmír Vejmola, Kateřina Syrová, Klára Šíchová et al.
GABAB receptors, which are part of the brain's inhibitory system, are modulated by accessory proteins called KCTD16. In experiments using mice lacking the KCTD16 gene, baseline pain sensitivity and nerve cell activity in the spinal cord were similar to normal mice. However, when treated with the GABAB receptor agonist baclofen, normal mice showed greater pain relief (higher thresholds for heat and touch) than mice lacking KCTD16. In a model of peripheral inflammation, KCTD16-deficient mice tended to have higher pain thresholds, and baclofen's inhibitory effect on nerve signals was reduced. The findings suggest KCTD16 may be important for pain modulation during pathological conditions when GABAB receptors are activated, but further research is needed.