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-HT2A receptors in information processing is less clear. OBJECTIVES: We studied ERPs in a serotonergic model of psychosis, induced by psilocybin, a psychedelic with 5-HT2A/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-HT2A receptors in altered information processing in psychosis and schizophrenia.

1st Faculty of Medicine Charles University Prague Kateřinská 32 121 08 Prague 2 Czech Republic

3rd Faculty of Medicine Charles University Prague Ruská 87 100 00 Praha 10 Czech Republic

Institute of Biosciences Vilnius University Sauletekio ave 7 102 57 Vilnius Lithuania

National Institute of Mental Health Topolová 748 250 67 Klecany Czech Republic

Zobrazit více v PubMed

J Neurosci. 2013 Sep 18;33(38):15171-83 PubMed

Arch Gen Psychiatry. 1994 Feb;51(2):98-108 PubMed

Int J Neurosci. 1995;80(1-4):317-37 PubMed

Proc Natl Acad Sci U S A. 2016 Apr 26;113(17 ):4853-8 PubMed

Nat Rev Neurosci. 2008 Sep;9(9):696-709 PubMed

Trends Pharmacol Sci. 2008 Sep;29(9):445-53 PubMed

Psychiatry Res. 2015 Feb 28;231(2):126-33 PubMed

Biol Psychiatry. 2012 Jun 1;71(11):969-77 PubMed

Pharmacopsychiatry. 2009 Jul;42(4):129-34 PubMed

Brain Topogr. 2014 Jul;27(4):451-66 PubMed

Biol Psychiatry. 2015 Oct 15;78(8):572-81 PubMed

Biol Psychiatry. 2016 Jun 15;79(12 ):980-7 PubMed

Neuropharmacology. 2017 Nov 20;:null PubMed

Clin Neurophysiol. 2007 Oct;118(10):2128-48 PubMed

Neuropsychopharmacology. 2003 Jan;28(1):170-81 PubMed

Prog Neuropsychopharmacol Biol Psychiatry. 2010 May 30;34(4):588-96 PubMed

J Forensic Sci. 2005 Mar;50(2):336-40 PubMed

Clin Neurophysiol. 2016 Feb;127(2):1387-1394 PubMed

Int J Psychophysiol. 2006 May;60(2):172-85 PubMed

Pharmacopsychiatry. 1998 Jul;31 Suppl 2:80-4 PubMed

Front Hum Neurosci. 2014 Feb 03;8:20 PubMed

Clin EEG Neurosci. 2017 Jan;48(1):3-10 PubMed

Prog Neuropsychopharmacol Biol Psychiatry. 2010 May 30;34(4):674-80 PubMed

Conscious Cogn. 2015 Dec 15;38:172-81 PubMed

Eur Neuropsychopharmacol. 2014 Mar;24(3):342-56 PubMed

J Clin Psychiatry. 1998;59 Suppl 20:22-33;quiz 34-57 PubMed

J Psychopharmacol. 2011 Dec;25(12):1623-31 PubMed

Front Behav Neurosci. 2013 Oct 16;7:140 PubMed

Biol Psychiatry. 2015 Oct 15;78(8):516-8 PubMed

J Pers Assess. 1991 Oct;57(2):203-4 PubMed

PLoS One. 2014 Feb 13;9(2):e87347 PubMed

Ind Psychiatry J. 2009 Jan;18(1):70-3 PubMed

J Psychopharmacol. 2014 Apr;28(4):287-302 PubMed

Brain Res. 2008 Apr 8;1203:97-102 PubMed

Pharmacol Rev. 2016 Apr;68(2):264-355 PubMed

Biol Psychiatry. 2008 Sep 1;64(5):376-84 PubMed

Biol Psychiatry. 2012 Dec 1;72 (11):898-906 PubMed

Schizophr Res. 2010 Aug;121(1-3):139-45 PubMed

Eur Neuropsychopharmacol. 2012 Jul;22(7):492-500 PubMed

J Pharmacol Exp Ther. 1968 Jan;159(1):216-21 PubMed

Mol Psychiatry. 2017 Nov;22(11):1585-1593 PubMed

J Cogn Neurosci. 2005 Oct;17 (10 ):1497-508 PubMed

Neuroreport. 1998 Dec 1;9(17 ):3897-902 PubMed

Schizophr Bull. 2016 Nov;42(6):1504-1516 PubMed

Psychiatry Res. 2008 Dec 15;161(3):259-74 PubMed

Arch Gen Psychiatry. 2000 Dec;57(12):1139-47 PubMed

Neuroimage. 2011 Sep 15;58(2):508-25 PubMed

Front Psychol. 2011 Nov 25;2:327 PubMed

J Psychopharmacol. 2008 Aug;22(6):603-20 PubMed

Psychophysiology. 2003 Sep;40(5):684-701 PubMed

Schizophr Bull. 2017 Mar 1;43(2):407-416 PubMed

Schizophr Bull. 2013 Nov;39(6):1343-51 PubMed

Trends Neurosci. 2004 Nov;27(11):683-90 PubMed

Arch Gen Psychiatry. 2005 Feb;62(2):127-36 PubMed

Psychopharmacology (Berl). 2008 Jul;199(1):77-88 PubMed

Biol Psychol. 1987 Aug;25(1):61-71 PubMed

Psychopharmacology (Berl). 2004 Mar;172(2):145-56 PubMed

CNS Drugs. 2006;20(5):389-409 PubMed

Psychopharmacology (Berl). 2005 Jul;180(3):427-35 PubMed

J Neurosci. 2013 Jun 19;33(25):10544-51 PubMed

Arch Gen Psychiatry. 1967 Feb;16(2):146-51 PubMed

Biol Psychol. 1995 Oct;41(2):103-46 PubMed

Schizophr Res. 2004 Oct 1;70(2-3):315-29 PubMed

Front Behav Neurosci. 2014 May 16;8:180 PubMed

Neuropsychopharmacology. 2012 Mar;37(4):865-75 PubMed

Science. 1965 Nov 26;150(3700):1187-8 PubMed

Neuropsychopharmacology. 2001 Oct;25(4):498-504 PubMed

Behav Pharmacol. 2016 Jun;27(4):309-20 PubMed

J Cogn Neurosci. 2008 Aug;20(8):1403-14 PubMed

Schizophr Res. 2005 Jul 1;76(1):1-23 PubMed

Forensic Sci Int. 2000 Sep 11;113(1-3):403-7 PubMed

Neuropsychopharmacology. 2012 Feb;37(3):630-40 PubMed

Psychopharmacology (Berl). 2008 Jan;196(1):51-62 PubMed

PLoS One. 2014 Jun 16;9(6):e97794 PubMed

Neuropsychopharmacology. 2000 Mar;22(3):293-302 PubMed

Nat Rev Neurosci. 2015 Sep;16(9):535-50 PubMed

Psychopharmacology (Berl). 2011 Dec;218(4):649-65 PubMed

Neuropsychopharmacology. 1999 Jun;20(6):565-81 PubMed

Front Behav Neurosci. 2014 May 30;8:171 PubMed

Psilocybin-Mediated Attenuation of Gamma Band Auditory Steady-State Responses (ASSR) Is Driven by the Intensity of Cognitive and Emotional Domains of Psychedelic Experience

The Effects of Daytime Psilocybin Administration on Sleep: Implications for Antidepressant Action