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.
Experimental Neurology
October 1, 2021
Giulia Costa, Krystyna Gołembiowska
64 citations
MDMA, also known as ecstasy, can cause acute and lasting abnormalities in the brain, as shown in both animal and human studies. Neurotoxic effects have been demonstrated in experimental animals, raising concerns about serious harm to health, especially since MDMA is used recreationally by young and adult people. This review summarizes recent findings on MDMA's central effects and the mechanisms behind its neurotoxicity.
Neurotoxicity Research
April 15, 2019
Monika Herian, Adam Wojtas, Katarzyna Kamińska et al.
44 citations
25I-NBOMe, a synthetic hallucinogen related to the 2C family, increases extracellular levels of dopamine, serotonin, and glutamate in the rat frontal cortex, as measured by microdialysis in freely moving animals. It also raises tissue content of serotonin and its metabolite 5-HIAA but does not affect tissue dopamine or its metabolites. The drug elicits head-twitch response in rats, a behavioral marker of hallucinogenic effect in humans. Dose-response curves were inverted U-shaped for dopamine and serotonin release, but U-shaped for glutamate release and head-twitch response. The findings suggest that the hallucinogenic activity of 25I-NBOMe is linked to increased extracellular glutamate mediated by cortical 5-HT2A receptors, with modulation by 5-HT2C and 5-HT1A receptors.
Neurotoxicity Research
November 13, 2014
Anna Górska, Krystyna Gołembiowska
36 citations
Caffeine worsens the increase in dopamine and serotonin release caused by MDMA (ecstasy) in the mouse striatum. Blocking adenosine A1 or A2A receptors with selective antagonists mimics caffeine's effect, with the A2A antagonist being more potent. This suggests that caffeine exacerbates MDMA's neurochemical effects and potential toxicity through adenosine receptor blockade, not through monoamine oxidase inhibition.
Neurotoxicity Research
December 18, 2020
Adam Wojtas, Monika Herian, Mateusz Skawski et al.
33 citations
The hallucinogen 25B-NBOMe, which binds strongly to serotonin receptors, increased dopamine, serotonin, and glutamate release in the rat frontal cortex, striatum, and nucleus accumbens. It induced hallucinogenic activity, impaired short-term memory as measured by the novel object recognition test, and reduced locomotor activity in the open field test. In the light/dark box, rats spent more time in the dark zone, suggesting an anxiogenic effect. Scopolamine blocked the memory impairment. Unlike MDMA, 25B-NBOMe showed a subtle genotoxic effect in the comet assay. The changes in neurotransmitter levels may stem from its affinity for the 5-HT2A receptor.
Psychopharmacology
May 25, 2021
Monika Herian, Mateusz Skawski, Adam Wojtas et al.
29 citations
Repeated daily injections of the hallucinogenic drug 25I-NBOMe for seven days in rats reduced the brain's release of dopamine, serotonin, and glutamate in the frontal cortex and weakened hallucinogenic behavior compared to a single dose. In contrast, dopamine and serotonin release increased in the striatum and nucleus accumbens, and acetylcholine release rose across all brain regions. Chronic treatment also reduced motor activity, impaired short-term memory, and induced anxiety. These findings indicate that repeated use of 25I-NBOMe produces tolerance to its hallucinogenic effects while altering multiple neurotransmitter systems, with complex effects on memory, movement, and anxiety.
Neurotoxicity Research
July 26, 2016
Karolina Noworyta, Katarzyna Kamińska, Grzegorz Kreiner et al.
26 citations
The hallucinogen 5-MeO-DIPT ('foxy') increases dopamine, serotonin, and glutamate release in rat brain regions including the striatum, nucleus accumbens, and frontal cortex, with varying potency. It raises serotonin and lowers its metabolite 5-HIAA in tissue, likely by inhibiting the serotonin transporter. Decreases in dopamine and its metabolites suggest possible damage to dopamine terminals or adaptive changes in turnover. DNA strand breaks persisted for up to 60 days, indicating marked neurotoxicity. The drug also induced head-twitch responses and potentiated forepaw treading, suggesting its hallucinogenic effects involve stimulation of 5-HT2A and 5-HT1A receptors.
Pharmacological reports : PR
December 1, 2020
Monika Herian, Adam Wojtas, Małgorzata Katarzyna Sobocińska et al.
19 citations
The hallucinogenic compound 25I-NBOMe acts through specific serotonin receptors to produce its effects. In rats, blocking the 5-HT2A or 5-HT2C receptors with selective antagonists reduced both the hallucinogenic-like behavior (wet dog shakes) and the release of glutamate, dopamine, and serotonin in the frontal cortex caused by 25I-NBOMe. Blocking the 5-HT1A receptor did not affect the behavior or glutamate release but did decrease dopamine and serotonin release, likely by disinhibiting GABA neurons. These findings indicate that 5-HT2A and 5-HT2C receptors are key mediators of 25I-NBOMe's hallucinogenic activity and its effects on neurotransmitter release in the frontal cortex.
International Journal of Molecular Sciences
December 23, 2023
Adam Wojtas, Krystyna Gołembiowska
16 citations
Psychedelics, among the oldest psychoactive drugs, are gaining renewed interest for treating depression, substance use disorders, anxiety, and obsessive-compulsive disorder. This review summarizes preclinical research on the mechanisms, neurotoxicity, and behavioral effects of psychedelics, focusing on the selective 5-HT2A receptor agonists 25I- and 25B-NBOMe compared to the less selective drug psilocybin. NBOMes significantly increased glutamatergic, dopaminergic, serotonergic, and cholinergic neurotransmission in the frontal cortex, striatum, and nucleus accumbens, though not dose-dependently, likely due to 5-HT2A and subsequent 5-HT2C receptor activation.
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
October 1, 2018
Karolina Noworyta-Sokołowska, Anna Maria Górska, Krystyna Gołembiowska
5 citations
Repeated intermittent exposure to the hallucinogenic novel psychoactive substance 5-MeO-DIPT during adolescence impaired adult rats' exploratory activity in the open field test, reducing the number of crossings, and impaired learning in the serial pattern learning test, suggesting deficits in long-term memory and cognitive flexibility. No change was observed in the novel object recognition test. The findings indicate that adolescent exposure to 5-MeO-DIPT can cause long-lasting behavioral changes that persist into adulthood.
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.
Pharmacological Reports
January 20, 2026
Piotr Olejnik, Katarzyna Kamińska, Krystyna Gołembiowska et al.
Psilocybin, a hallucinogen known for its effects on serotonin receptors, significantly reduced inflammation in a study involving 40 participants. The treatment lowered levels of tumor necrosis factor alpha by 30% and decreased hyperalgesia—a heightened pain response—by 25%. Utilizing both ex vivo and in vivo models, findings showed that psilocybin modulates microglial activity, impacting the immune system's response. These results suggest potential applications in internal medicine for managing neuroinflammation and pain mechanisms, highlighting the promise of psychedelics in pharmacology and analgesic therapies.
The International Journal of Neuropsychopharmacology
August 1, 2025
Yana Babii, C. Barbara, Dorota Bederska‐łojewska et al.
Hallucinogens from different classes, such as scopolamine and psilocybin, show rapid antidepressant effects that are enhanced by blocking group II metabotropic glutamate (mGlu2/3) receptors. In mice, scopolamine reversed depressive-like behaviors induced by chronic mild stress, and a selective M1 muscarinic antagonist produced dose-dependent antidepressant effects potentiated by an mGlu2 receptor negative allosteric modulator. Scopolamine increased extracellular dopamine, serotonin, and glutamate in the frontal cortex, while the mGlu2 modulator had opposite effects on glutamate. A low dose of the mGlu2/3 antagonist LY341495 boosted the antidepressant effect of low-dose psilocybin in the tail suspension test, with rapid onset and long duration, while also reducing hallucinogenic-like head twitch responses. Combined targeting of these systems may allow lower doses and fewer side effects while maintaining antidepressant efficacy.
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
Krystyna Gołembiowska
No Summary
Kosmos
August 8, 2024
Krystyna Gołembiowska, K. Kamińska
Classic psychedelics such as psilocybin, mescaline, DMT, and LSD alter consciousness, perception, and produce hallucinations through serotonergic pharmacodynamic effects. These compounds profoundly affect neuroplasticity—altering neuronal structure and function. Their psychoplastogenic properties suggest potential for treating depression, neurodegenerative disorders like Alzheimer's disease, recovery after stroke, and schizophrenia. The role of microdosing, defined as 10% of the dose that elicits psychedelic effects, requires extensive further investigation.
Handbook of Neurotoxicity
January 1, 2021
Krystyna Gołembiowska
The psychedelic drug 5-MeO-DIPT (street name 'foxy') acts as a serotonin transporter inhibitor and agonist at serotonin receptors, producing hallucinogenic effects and increasing release of dopamine, serotonin, and glutamate in rat brain regions. In cell lines, it shows potent cytotoxicity. Repeated intermittent doses during adolescence in rats reduced the response to a subsequent challenge dose in some brain regions and caused oxidative DNA damage in the cortex. Exposed rats showed stronger neurotransmitter responses to MDMA and performed worse on cognitive tasks, with impairments in long-term memory and cognitive flexibility, suggesting that adolescent exposure may lead to neurological problems in adulthood.