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Paweł Orłowski1,2, Justyna Hobot3, Anastasia Ruban4, Jan Szczypiński5, Michał Bola1
1Centre for Brain Research, Jagiellonian University, Kraków, Poland
2Doctoral School in the Social Sciences, Jagiellonian University, Kraków, Poland
3Consciousness Lab, Psychology Institute, Jagiellonian University, Kraków, Poland
4Department of Psychology, SWPS University of Social Sciences and Humanities, Warsaw, Poland
5Department of Psychiatry, Medical University of Warsaw, Warsaw, Poland
Psychedelics lead to acute experience of ego dissolution – the blurring of the distinction between representations of self and the external world. However, whether repeated use of psychedelics is associated with prolonged or permanent modifications to the concept of self remains to be investigated. Therefore, we conducted a preregistered, cross-sectional study in which experienced psychedelics users (15 or more lifetime experiences with psychedelics; N = 56) were compared to non-users (N = 57) in terms of neural reactivity to a Self-name (i.e., each participant’s own name) stimulus. Two control stimuli were additionally used: an Other-name stimulus, as a passive control condition in which no reaction was required; and a Target-name stimulus, to which participants provided a manual response. Analysis of the amplitude of the P300 ERP component evoked by the Self-name revealed no difference between the psychedelics users and non-users. However, in comparison to non-users, psychedelics users exhibited a smaller increase in P300 amplitude when processing the task-relevant Target-name (in relation to both Self- and Other-names). Therefore, our data suggests that regular naturalistic use of psychedelics may not be related to long-term changes in the representation of self, but it might potentially affect allocation of attentional resources to task-relevant stimuli.
Funding: This study was funded by a National Science Center Poland grant (2020/39/O/HS6/01545).
Anastasia Ruban1,2, Mikołaj Magnuski1, Justyna Hobot3, Paweł Orłowski4, Aleksandra Kołodziej1, Michał Bola4, Aneta Brzezicka1
1Neurocognitive Research Center, Institute of Psychology, University SWPS, Warsaw, Poland
2Jan Dlugosz University, Częstochowa, Poland
3Consciousness Lab, Psychology Institute, Jagiellonian University, Krakow, Poland
4Center for Brain Research, Jagiellonian University, Krakow, Poland
Psychedelics have gained increasing interest in scientific research due to their ability to induce profound alterations in perception, emotional processing and self-consciousness. However, the research regarding the short- and long-term impact of using psychedelics in non-controlled, naturalistic contexts remains limited. Here we aim to fill this gap and explore differences between naturalistic psychedelics users and non-users during processing of self-related thoughts, using behavioural testing combined with electroencephalography (EEG) with source localisation. To ensure robustness of our results, we included two datasets collected at two different laboratories. The results from Dataset I (N = 70) suggest that during self-related thoughts psychedelics users exhibit weaker increases in alpha and beta power in comparison to non-users, primarily in brain regions linked to processing of self-related information and memory. However, analysis of Dataset II (N = 38) did not replicate between-group effects, possibly due to the smaller sample size and spatial resolution limitations. While non-replicability restricts interpretation of our findings, this study contributes to understanding the relationship between the use of psychedelics, self-related thoughts, and well-being, which is crucial for assessing mental health impact of psychedelic substances.
Funding: This study was funded by the National Science Center Poland PRELUDIUM (grant no. 2020/37/N/HS6/02086) and PRELUDIUM BIS (2020/39/O/HS6/01545) grants.
Maja Wójcik1, Agata Chrobak1, Arkadiusz Dudek2, Aleksandra Bolek2, Paweł Kubicki1, Lucyna Pomierny-Chamioło3, Michał Wierzchoń1, Justyna Hobot1, Maciej Pilecki2,4, Grzegorz Kazek5
1Institute of Psychology, Jagiellonian University, Kraków, Poland
2Psychiatry Department for Adults, Children and Youth of the University Hospital in Kraków, Poland
3Chair of Toxicology, Jagiellonian University Medical College, Kraków, Poland
4Chair of Psychiatry, Jagiellonian University Medical College, Kraków, Poland
5Chair of Pharmacodynamics, Jagiellonian University Medical College, Kraków, Poland
The need to research the long-term influence of psychedelics on neurobiological and cognitive functioning of their users stems from their increasingly widespread use and significant gaps in knowledge about their effects. Psychedelics act mainly as agonists for the 5-HT2A receptors, affecting serotonergic transmission and therefore - numerous biological processes. The serotonergic system plays a crucial role in various cognitive aspects such as memory, attention, spatial navigation, and decision-making. The influence of psychedelics on various proteins that are of essential importance in neurobiological functions and their links to cognitive functioning remain unclarified, especially in naturalistic users (outside of the laboratory context). Accordingly, the aim of the study was to examine the cognitive functions of psychedelic users and the levels of selected neural proteins, along with analyzing their interrelations. Cognitive functions were measured in 46 psychedelics users using the Cogstate battery of behavioral tests (GML, GMR, IDN, OCL, SETS, TWOB, DET). Protein analyses were performed in blood plasma using xMAP technology with simultaneous quantitative determination of multiple proteins in a single sample. Some cognitive function parameters showed significant correlations with the protein concentration: GMR with BDNF, PDGF-AB, and NRG1B1, SETS corelated with BDNF and PDGF-AB, and OCL with BDNF. This study is the first to demonstrate the links between these proteins and the cognitive tests of the Cogstate battery. No statistically significant differences were found between the users and non-users group in terms of the results of cognitive function tests. The number of lifetime psychedelics uses correlated only with BDNF levels. The results might indicate that psychedelics are relatively safe in terms of long term changes in cognitive functioning, but further research is required to confirm these findings.
Funding: Projekt nr U1C/P04/NO/02.06 realizowany w ramach konkursu "Interdyscyplinarna współpraca między dziedzinami nauk medycznych, nauk o zdrowiu i nauk społecznych - Priorytetowe Obszary Badawcze Uniwersytetu Jagiellońskiego: FutureSoc i POB qLIFE.
Č. Vejmola1,2, J. Hubený3, V. Koudelka3, K. Šíchová1, T. Páleníček1,2
1National Institute of Mental Health, Psychedelic Research Center, Klecany, Czech Republic
2Charles University, Third Faculty of Medicine, Praha, Czech Republic
3National Institute of Mental Health, Clinical Research Program, Klecany, Czech Republic
Hallucinations are a distinctive feature of the action of 5-HT2A agonist psilocin. Despite growing interest, the underlying mechanisms remain poorly understood. In this study, we employed a series of various visual stimuli evoking EEG potentials to study the functional processing pathways. Three different visual stimuli, each targeting specific cell types and neural pathways involved, were used: the motion-onset, pattern-reversal and flickers to test magnocellular, parvocellular and general multiple pathways, respectively. To disentangle the contribution of 5-HT2A receptors, subjects were also pretreated with the selective 5-HT2A receptor antagonist MDL 100907. Psilocin dose-dependently decreased P1 peak of motion-onset stimuli as well as decrease the P1 peak of flashes. However, did not affect P1 peak of pattern-reversal stimuli. The response showed to be region-specific, corresponding to the functional areas involved. Surprisingly, effects were not blocked by pretreatment with the MDL 100907 as expected. The findings indicate a pivotal role of 5-HT2A receptors in modulating visual processing during psilocin effects, particularly in the magnocellular pathway, crucial for perceiving motion. These insights may contribute to understanding hallucinatory states in psychiatric disorders like schizophrenia and Parkinson’s disease.
Funding: Projekt nr U1C/P04/NO/02.06 realizowany w ramach konkursu "Interdyscyplinarna współpraca między dziedzinami nauk medycznych, nauk o zdrowiu i nauk społecznych - Priorytetowe Obszary Badawcze Uniwersytetu Jagiellońskiego: FutureSoc i POB qLIFE.
Adam Wojtas1, Agnieszka Bysiek1, Izabela Szpręgiel1, Agnieszka Wawrzczak-Bargieła2, Marzena Maćkowiak2, Krystyna Gołembiowska1
1Department of Pharmacology, Unit II, Maj Institute of Pharmacology of the Polish Academy of Sciences, Poland
2Department of Pharmacology, Laboratory of Pharmacology and Brain Biostructure, Maj Institute of Pharmacology of the Polish Academy of Sciences, Krakow, Poland
Clinical studies provide evidence that psilocybin might be used as a fast-acting antidepressant, however, it’s mechanisms and toxicity are still not fully understood. Moreover, via the activation of the 5-HT2A receptor, this drug can potentially induce a psychotic episode in treated individuals. The aim of this study was to determine the effects of low doses of psilocybin on rat cortical neurotransmission. Moreover, its effects on psychosis-associated behavior and molecular changes were assessed in comparison to selected reference drugs. The study was conducted on male Wistar-Han rats. The animals were treated with single doses of ketamine (10 mg/kg), psilocybin (0.1, 0.3, or 0.6 mg/kg), 25I-NBOMe (1 mg/kg), or MDMA (10 mg/kg). The cortical levels of dopamine, serotonin, glutamate, GABA, and acetylcholine were measured using microdialysis in freely moving animals. The effect on sensorimotor gating was assessed with the prepulse inhibition test (PPI), while the relative activation of the 5-HT2A receptor was examined with the wet-dog shake (WDS) test. The genotoxic effect in the frontal cortex (FCX) and hippocampus (HP) was assessed with comet assay. Psilocybin dose-dependently increased extracellular levels of examined neurotransmitters (except for the glutamate). Moreover, it dose-dependently shifted the GABA/Glutamate ratio in comparison to both control and group treated with selective 5-HT2A agonist, 25I-NBOMe. It induced a significant, but not numerous number of WDS episodes in rats. The highest dose of psilocybin didn’t affect the startle response in the PPI test and didn’t induce oxidative damage in the FCX and HP.
Funding: This research was funded by National Science Centre grant no. 2020/37/B/NZ7/03753.
