Psilocybin disrupts sensory and higher order cognitive processing but not pre-attentive cognitive processing—study on P300 and mismatch negativity in healthy volunteers

• Published in: Psychopharmacology Vol. 235; no. 2; pp. 491 - 503
• Main Authors: Bravermanová, Anna, Viktorinová, Michaela, Tylš, Filip, Novák, Tomáš, Androvičová, Renáta, Korčák, Jakub, Horáček, Jiří, Balíková, Marie, Griškova-Bulanova, Inga, Danielová, Dominika, Vlček, Přemysl, Mohr, Pavel, Brunovský, Martin, Koudelka, Vlastimil, Páleníček, Tomáš
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.02.2018; Springer; Springer Nature B.V
• Subjects: Acoustic Stimulation - methods; Adult; Aged; Attention - drug effects; Attention - physiology; Auditory evoked potentials; Biomedical and Life Sciences; Biomedicine; Cognition & reasoning; Cognition - drug effects; Cognition - physiology; Cognitive ability; Complications and side effects; Cross-Over Studies; Development and progression; Diagnosis; Double-Blind Method; Electroencephalography - drug effects; Electroencephalography - methods; Event-related potentials; Event-Related Potentials, P300 - drug effects; Event-Related Potentials, P300 - physiology; Female; Glutamatergic transmission; Hallucinogenic drugs; Hallucinogens - pharmacology; Healthy Volunteers; Humans; Information processing; Intoxication; Male; Mental disorders; Middle Aged; Mismatch negativity; Neurosciences; Original Investigation; Perceptual distortion; Pharmacology/Toxicology; Psilocybin; Psilocybin - adverse effects; Psilocybin - pharmacology; Psychedelic drugs; Psychiatry; Psychopharmacology; Psychosis; Risk factors; Schizophrenia; Serotonin receptors; Serotonin S2 receptors; Serum levels; Human; ERP; Psilocybin; Model of psychosis; P300; MMN
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-017-4807-2

Rationale Disruption of auditory event-related evoked potentials (ERPs) P300 and mismatch negativity (MMN), electrophysiological markers of attentive and pre-attentive cognitive processing, is repeatedly described in psychosis and schizophrenia. Similar findings were observed in a glutamatergic model of psychosis, but the role of serotonergic 5-HT 2A receptors in information processing is less clear. Objectives We studied ERPs in a serotonergic model of psychosis, induced by psilocybin, a psychedelic with 5-HT 2A/C agonistic properties, in healthy volunteers. Methods Twenty subjects (10M/10F) were given 0.26 mg/kg of psilocybin orally in a placebo-controlled, double-blind, cross-over design. ERPs (P300, MMN) were registered during the peak of intoxication. Correlations between measured electrophysiological variables and psilocin serum levels and neuropsychological effects were also analyzed. Results Psilocybin induced robust psychedelic effects and psychotic-like symptoms, decreased P300 amplitude ( p  = 0.009) but did not affect the MMN. Psilocybin’s disruptive effect on P300 correlated with the intensity of the psychedelic state, which was dependent on the psilocin serum levels. We also observed a decrease in N100 amplitude ( p  = 0.039) in the P300 paradigm and a negative correlation between P300 and MMN amplitude ( p  = 0.014). Conclusions Even though pre-attentive cognition (MMN) was not affected, processing at the early perceptual level (N100) and in higher-order cognition (P300) was significantly disrupted by psilocybin. Our results have implications for the role of 5-HT 2A receptors in altered information processing in psychosis and schizophrenia.