International Journal of Molecular Sciences
June 16, 2022
Adam Wojtas, Agnieszka Bysiek, Agnieszka Wawrzczak‐bargieła et al.
110 citations
Ketamine and psilocybin, both fast-acting antidepressants in clinical studies, increase extracellular levels of dopamine, serotonin, glutamate, and GABA in the rat frontal cortex. Psilocybin also raises GABA in the reticular nucleus of the thalamus. However, both drugs cause oxidative DNA damage—psilocybin in the frontal cortex and both drugs in the hippocampus. Psilocybin at 10 mg/kg increases NR2A glutamate receptor subunit levels. Behavioral tests 24 hours after administration show no antidepressant or anxiolytic effects; only ketamine reduces locomotor activity. The observed neurotransmitter changes may lead to genotoxicity and altered receptor levels without markedly affecting behavior.
Pharmacological reports : PR
December 1, 2024
Izabela Szpręgiel, Agnieszka Bysiek
18 citations
Psilocybin, a 5-HT2A receptor agonist on cortical pyramidal cells, increases glutamate release in the frontal cortex and hippocampus. This elevated glutamate boosts activity of GABAergic interneurons, raising GABA levels, which appears to promote antidepressant effects. Psilocybin also interacts with glutamatergic pathways to support neuroplasticity. This mini-review discusses how psilocybin affects glutamatergic neurotransmission and its therapeutic potential for depression and other nervous system disorders.
International Journal of Molecular Sciences
December 20, 2023
Adam Wojtas, Agnieszka Bysiek, Marzena Maćkowiak et al.
16 citations
Depression involves reduced volume of the hippocampus and amygdala and enlargement of the nucleus accumbens. Ketamine, a fast-acting antidepressant, reverses these volume reductions. This study tested whether the psychedelic psilocybin similarly affects limbic system neurotransmission in rats. Using microdialysis, both psilocybin and ketamine increased dopamine and serotonin release in the nucleus accumbens, influenced glutamate and GABA release in the nucleus accumbens, hippocampus, and amygdala, and raised acetylcholine levels in the hippocampus. Long-lasting changes in D2, 5-HT1A, and 5-HT2A receptor density occurred in the nucleus accumbens and hippocampus. Psilocybin showed a marked anxiolytic effect acutely and 24 hours later in the open field test, providing a neurobiological basis for its antidepressant and anti-stress effects.
Scientific reports
February 21, 2022
Monika Herian, Adam Wojtas, Marzena Maćkowiak et al.
15 citations
The synthetic hallucinogen 25I-NBOMe crosses the blood-brain barrier easily and accumulates in the brain after repeated doses. In rats, chronic treatment caused DNA damage in brain tissue 72 hours later, but no signs of apoptosis. The number of glial cells decreased in the frontal and medial prefrontal cortex, while neural cells were unaffected. These findings suggest that oxidative DNA damage from 25I-NBOMe may lead to glial cell death, indicating potential brain toxicity from recreational use.
Progress in neuro-psychopharmacology & biological psychiatry
April 2, 2025
Agnieszka Bysiek, Adam Wojtas, Izabela Szpręgiel et al.
10 citations
Psilocybin increased the release of dopamine, noradrenaline, serotonin, and acetylcholine in the frontal cortex of rats, with the 0.3 mg/kg dose producing the weakest effect. Glutamate release rose only for the first two hours after injection then fell, while γ-aminobutyric acid release increased. Unlike the 5-HT2A receptor agonist 25I-NBOMe, psilocybin did not cause hallucinogenic wet dog shakes or disrupt sensorimotor gating. It showed an anxiolytic effect in the light dark box test one hour after administration, transiently raised serum corticosterone, altered hypothalamic neurotransmitter turnover, and did not produce oxidative DNA damage in the frontal cortex or hippocampus.
Neuropharmacology
December 1, 2023
Adam Wojtas, Monika Herian, Marzena Maćkowiak et al.
6 citations
Repeated administration of the hallucinogenic drug 25B-NBOMe (0.3 mg/kg for 7 days) in rats rapidly produced tolerance to its effects on neurotransmitter release and hallucinogenic behavior, as measured by the Wet Dog Shake test. The drug reduced dopamine, serotonin, and glutamate responses in the frontal cortex, striatum, and nucleus accumbens after a challenge dose. Genotoxicity, indicated by DNA damage, was found in the frontal cortex and hippocampus, with increased glial cells in cortical regions but no neuronal loss. Anxiety effects depended on treatment and environmental context, with anxiogenic effects observed after both single and repeated dosing.
Pharmacological reports : PR
February 1, 2026
Zuzanna Kościuk, Izabela Szpręgiel, Agnieszka Bysiek et al.
2 citations
Psilocin and 25I-NBOMe, two serotonergic psychedelics, both altered neurotransmitter levels in the rat claustrum but produced distinct neurochemical profiles. Psilocin elevated noradrenaline and acetylcholine, yielding a balanced excitatory–inhibitory pattern, while 25I-NBOMe induced a stronger excitatory shift with the largest increase in serotonin release. These differences reflect psilocin's engagement of both 5-HT2A and 5-HT1A receptors versus 25I-NBOMe's selective, high-affinity 5-HT2A agonism. The claustrum is highlighted as a convergence point for psychedelic action, and the contrasting profiles suggest fundamentally different therapeutic and toxicological potentials.
Progress in neuro-psychopharmacology & biological psychiatry
June 20, 2026
Agnieszka Bysiek, Izabela Szpręgiel, Adam Wojtas et al.
Two doses of psilocybin (0.6 mg/kg, given subcutaneously seven days apart) reversed anhedonia, produced antidepressant-like effects in the forced swim test, and reduced anxiety in the light/dark box, elevated plus maze, and open field tests in rats exposed to chronic unpredictable mild stress. Psilocybin also increased hippocampal neurogenesis, shown by higher numbers of BrdU-positive, DCX-positive, and Ki-67-positive cells in stressed animals. Stress-induced reductions in brain-derived neurotrophic factor (BDNF) expression appeared linked to normalization of hypothalamic-pituitary-adrenal (HPA) axis activity. The findings highlight psilocybin-induced neuroplasticity as a key mechanism for its antidepressant and anxiolytic effects.
Journal of Psychopharmacology
April 17, 2025
Artur Pałasz, Marta Pukowiec, Katarzyna Bogus et al.
A single high dose of psilocybin (10 mg/kg) increased the gene expression of most noncanonical neuropeptides in the hypothalamus of male rats, while decreasing expression of neuromedin U. Psilocybin also raised expression of serotonin receptors 5-HT1A, 5-HT2A, and 5-HT2B, but not 5-HT2C. Ketamine had a more limited effect, increasing only NUCB2, GPR173, and POMC transcripts. These findings suggest psychedelics may alter neuropeptide signaling and serotonin transmission in the hypothalamus, contributing to understanding their brain actions.
Kosmos
August 8, 2024
Agnieszka Bysiek
MDMA, first synthesized in 1912, was rediscovered in the 1970s for its empathogenic and anti-anxiety qualities, leading to its use as a psychotherapy adjunct for anxiety disorders and trauma. Despite being outlawed in 1985 due to recreational overuse, its positive effects and lack of negative side effects kept it in psychiatric underground use. Current research and clinical trials in many countries aim to confirm its efficacy as an adjunct therapy for Post-Traumatic Stress Disorder with relatively small side effects. As of 2023, only Australia has legalized MDMA for psychotherapy in patients with severe PTSD.