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.
Psychopharmacology
October 24, 2018
Luisa Prochazkova, Dominique P. Lippelt, Lorenza S. Colzato et al.
181 citations
Microdosing psychedelics may enhance cognitive performance by improving the balance between cognitive persistence and flexibility, according to preliminary quantitative findings. The authors speculate that psychedelics affect cognitive metacontrol policies, optimizing this balance. However, they emphasize that future research with rigorous placebo-controlled designs is needed to confirm these initial results. The study provides support for cognitive-enhancing properties but remains preliminary.
Translational Psychiatry
August 2, 2022
Federico Cavanna, Stephanie Müller, Laura Alethia de la Fuente et al.
130 citations
A double-blind placebo-controlled trial tested the effects of a low (0.5 g) dose of dried psilocybin mushrooms on 34 individuals beginning a microdosing protocol. The active dose produced more intense acute subjective effects than placebo, but only among participants who correctly guessed their condition. These effects coincided with reduced EEG theta-band power and preserved Lempel-Ziv broadband signal complexity. No evidence was found for enhanced well-being, creativity, or cognitive function; instead, small changes toward cognitive impairment appeared. The findings suggest that expectation, not the drug itself, accounts for many anecdotal benefits attributed to psilocybin microdosing.
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.
Journal of Psychopharmacology
December 17, 2021
Josephine Marschall, George Fejer, Pascal Lempe et al.
69 citations
In a double-blind, placebo-controlled, within-subject crossover study, psilocybin microdosing (a sub-hallucinogenic dose taken every third day) did not alter emotion processing, symptoms of anxiety or depression, or self-reported interoceptive awareness compared with placebo. Exploratory analyses showed that symptoms of depression and stress were significantly reduced in the first block compared with baseline, but participants broke blind in the second block, and there was no effect of expectations. The authors call for further research in a substance-naïve population with clinical-range anxiety and depressive symptoms to substantiate potential beneficial effects.
Drug Testing and Analysis
October 29, 2020
Klára Gotvaldová, Kateřina Hájková, Jan Borovička et al.
69 citations
Psilocybin, psilocin, baeocystin, norbaeocystin, and aeruginascin are tryptamines structurally similar to serotonin. Psilocybin and its active metabolite psilocin are known for psychoactive effects and occur in most Psilocybe fungi. Freshly cultivated Psilocybe cubensis fruit bodies were used to monitor stability under various storage and processing conditions. Mycelium and individual parts (caps, stipes, basidiospores) were examined via ultra-high-performance liquid chromatography-mass spectrometry. No tryptamines were detected in basidiospores; only psilocin was present at 0.47 wt.% in mycelium. Stipes contained about half the tryptamine alkaloids (0.52 wt.%) compared to caps (1.03 wt.%), but results were not statistically significant due to high variability. Highest degradation occurred in fresh mushrooms stored at -80°C; lowest decay in dried biomass stored in dark at room temperature.
Psychopharmacology
April 30, 2021
Michiel van Elk, George Fejer, Pascal Lempe et al.
53 citations
People who take small, non-hallucinogenic doses of psilocybin (microdosing) report feeling more awe when watching videos of funny animals and moving objects compared to when they take a placebo. However, about two-thirds of participants correctly guessed whether they had received psilocybin or placebo, suggesting that expectancy effects—rather than the drug itself—may explain the subjective benefits of microdosing. The study used a double-blind, placebo-controlled crossover design with a microdosing workshop and lab visits over several weeks.
International Journal of Molecular Sciences
November 15, 2022
Klára Gotvaldová, Jan Borovička, Kateřina Hájková et al.
50 citations
Wild mushrooms that contain psilocybin also carry several other tryptamine alkaloids in highly variable concentrations, making their effects unpredictable compared to pure psilocybin. Using ultra-high performance liquid chromatography with tandem mass spectrometry, researchers measured psilocybin, psilocin, baeocystin, norbaeocystin, and aeruginascin in 226 fruiting bodies from 82 collections across seven genera. Psilocybe species had the highest psilocybin and psilocin levels, but no tryptamines were detected in Psilocybe fuscofulva or Psilocybe fimetaria. For many species, concentrations of baeocystin, norbaeocystin, and aeruginascin were reported for the first time. The extreme variability in tryptamine content poses a risk of overdose for consumers and complicates interpretation of medicinal effects compared to chemically pure psilocybin.
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.
Translational Psychiatry
December 14, 2023
Ivan Skorodumov, Rainer Spanagel, Jonathan Reinwald et al.
25 citations
Psilocybin, a psychedelic compound, may help treat alcohol use disorder (AUD), but its brain effects in AUD are not well understood. In a placebo-controlled crossover study with healthy rats and a rat model of alcohol relapse, psilocybin broadly decreased functional connectivity across the brain while increasing connectivity between serotonin-related core regions and cortical areas. It also reduced connectivity within the default mode network (DMN), mirroring human findings. However, in rats with a history of alcohol relapse, this DMN hypoconnectivity was blunted, and the blunting correlated with relapse intensity. The results suggest that a standard psilocybin dose may be insufficient for severe AUD, a consideration for future clinical trials.
International Journal of Molecular Sciences
February 15, 2023
Martina di Bartolomeo, Tibor Stark, Serena di Martino et al.
23 citations
Rats exposed to the toxin methylazoxymethanol acetate (MAM) before birth or to THC shortly after birth showed adult behaviors resembling schizophrenia, such as social withdrawal and memory problems, along with increased expression of cannabinoid and dopamine receptor genes in the prefrontal cortex linked to DNA methylation changes. Giving THC during adolescence impaired social behavior in otherwise healthy rats but did not worsen the schizophrenia-like traits in rats already exposed to THC after birth. In rats exposed to MAM before birth, adolescent THC paradoxically reversed their memory deficit by altering dopamine receptor gene expression. The effects of adolescent THC exposure appear to depend on individual differences in dopamine signaling.
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.
Phytotherapy Research
July 31, 2023
Giuseppe Tringali, Gianluca Lavanco, Valentina Castelli et al.
17 citations
Adolescent rats that binge drink alcohol show reduced levels of the neuropeptide CGRP in brain regions involved in emotion and reward (medial prefrontal cortex, nucleus accumbens, amygdala) and increased CGRP in the brainstem. These rats also display heightened responses to rewarding and painful stimuli, reduced social drive, and lower corticosterone levels. Treatment with cannabidiol (40 mg/kg) before each drinking session reduced alcohol consumption and preference, normalized CGRP expression in corticolimbic areas, and corrected the abnormal reward and aversion responses as well as glucocorticoid levels. CGRP may mediate and be a target of alcohol binge drinking, and cannabidiol shows promise for limiting adolescent binge drinking and its behavioral and neuroendocrine consequences.
New Journal of Chemistry
January 1, 2018
Bronislav Jurásek, František Králík, Silvie Rimpelová et al.
15 citations
The dissociative drug deschloroketamine was synthesized, and the absolute configuration of its enantiomers was determined. The in vitro cytotoxicity of each enantiomer was tested across nine different cell lines, providing data on their relative toxicities.
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.
RSC Advances
January 1, 2017
Bronislav Jurásek, Michal Himl, Radek Jurok et al.
13 citations
Methoxetamine, a designer drug sold as a substitute for the dissociative anesthetic ketamine, has been linked to numerous hospital intoxications and deaths across Europe.
Drug Testing and Analysis
October 31, 2019
Kateřina Hájková, Bronislav Jurásek, Jan Čejka et al.
12 citations
Deschloroketamine, a ketamine analog sold illicitly since 2015 and sometimes misrepresented as ketamine, has potential antidepressant properties. A metabolomics study used liquid chromatography–high-resolution mass spectrometry and a validated multiple reaction monitoring method to track its metabolites in urine, serum, and brain tissue. Key metabolites—trans-dihydrodeschloroketamine, cis- and trans-dihydronordeschloroketamine, and nordeschloroketamine—were synthesized and used as standards. In serum, nordeschloroketamine and deschloroketamine concentrations ranged from 0.5 to 860 ng/mL; in brain tissue, they ranged from 0.5 to 4700 ng/g. The quantification methods showed intra-day accuracy of 80–125% and precision averaging 3–7%.
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.
Journal of pharmacological and toxicological methods
January 1, 2019
Anna Šuláková, Lucie Fojtíková, Barbora Holubová et al.
11 citations
Two new immunoassays, a lateral flow immunoassay (LFIA) and an enzyme-linked immunosorbent assay (ELISA), were developed to detect the hallucinogenic phenethylamine 2C-B and related drugs in urine. The LFIA provides rapid on-site screening with a detection limit of 15 ± 7 ng mL⁻¹, suitable for identifying recent exposure. The ELISA offers much higher sensitivity, with a detection limit of 6 ± 3 pg mL⁻¹, and its results closely match those from established UHPLC-MS-MS analysis, making it reliable for quantitative confirmation in toxicology. Both methods address the need for simple, cost-effective tools to monitor these dangerous substances.
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.