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.
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
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.
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.
Pharmacological reports : PR
December 1, 2023
Adam Wojtas
10 citations
The serotonergic theory of depression, which emerged in the 1960s, led to many antidepressant drugs that have helped millions, but recent studies question their effectiveness compared to placebo, noting slow onset and side effects. Research now focuses on rapid-acting antidepressants like ketamine, an NMDA receptor antagonist that quickly alleviates depression symptoms, though its effects last only about two weeks and it has severe side effects. A safer, more efficient approach may involve hallucinogenic 5-HT2A receptor agonists—psychedelics—which are being reconsidered in clinical practice after their 1970s stigma. This review examines current literature and recent clinical studies on the antidepressant potential of LSD, psilocybin, DMT, and 5-MeO-DMT, along with other applications.
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.
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.