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 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.
Psychedelics
June 28, 2026
Joost J. Breeksema, Ulf Bremberg, Jens H. van Dalfsen et al.
Psychedelic therapies face layered complexity from interactions between pharmacological and extra-pharmacological factors, and their embeddedness in societal, legal, and regulatory systems. This is compounded by epistemic fragmentation: dominant biomedical paradigms often clash with knowledge from social sciences, humanities, or Indigenous traditions. Though interdisciplinary engagement is increasingly recognized as necessary, existing calls rarely specify structural or pedagogical conditions for operationalizing it. Addressing these complexities requires moving beyond superficial collaboration; genuine interdisciplinary progress needs researchers capable of productive friction across epistemic cultures. The authors propose cultivating T-shaped competencies and intersectoral training as a structural response to these systemic challenges.
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.
J Affect Disord
October 10, 2025
Guy M. Goodwin, Scott T. Aaronson, Oscar Alvarez et al.
correction
No Summary
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.
Klinická farmakologie a farmacie
April 29, 2025
Michal Židó, Tomáš Páleníček, Ivana Štětkářová
Psychedelics are psychoactive substances that typically induce changes in perception, thinking, emotionality, and cognitive processes immediately after use. Their antidepressant and anxiolytic effects are being intensively studied. A main advantage is rapid onset of action with long-lasting effects after one or only a few doses, along with a good safety profile. These substances may also have potential in treating chronic pain from neuropathy and primary headaches, such as cluster headache. Cluster headache is a rare disorder with episodes of intense pain and autonomic symptoms that can severely limit patients. Although conventional treatment is sufficiently effective and safe for most patients, a subgroup does not respond well. Based on recent data, tryptamine and ergoline psychedelics like psilocybin and LSD and some derivatives represent a new potential therapeutic source, though still experimental.
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
November 6, 2023
Tomáš Páleníček, Tereza Klučková, Marek Nikolič 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.
IBRO Neuroscience Reports
October 1, 2023
Aneta Petrušková, Eva‐maria Weiss, Debarpan Guhathakurta et al.
Serotonergic psychedelics like psilocybin, LSD, and DMT may offer new treatments for depression, PTSD, and addiction, but better understanding of their cellular and molecular mechanisms is needed. Imaging studies in humans and animal studies have shown acute changes in neuronal activity and connectivity, though findings are sometimes contradictory.
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.
Journal of neurophysiology
April 1, 2026
Inga Griškova-bulanova, Čestmír Vejmola, Tomáš Páleníček
Psilocin, the active metabolite of psilocybin, selectively disrupts auditory neural synchronization in rats in a frequency- and region-specific manner. In eight adult male Wistar rats implanted with cortical electrodes, psilocin (4 mg/kg) reduced phase-locking at 40 Hz stimulation in the right temporal cortex, with no significant changes in frontal or left temporal regions or at 80 Hz stimulation. Spectral power was globally reduced at 80 Hz after psilocin, but not consistently at 40 Hz. These results indicate that low-gamma oscillations are sensitive to serotonergic modulation via 5-HT2A receptor signaling, supporting auditory steady-state responses as translational biomarkers for altered perceptual states.