1. ¹Psychiatric University Hospital of Zurich Department of Research, Zurich, Switzerland
2. ²Psychiatric University Hospital of Zurich, Zurich, Switzerland
3. ³University of Zurich Medical School, Zurich, Switzerland

Correspondence: Dr D Umbricht, Psychiatric University Hospital of Zurich Department of Research, PO Box 68, CH-8029 Zurich, Switzerland. Tel: +41-1-384-2555; Fax: +41-1-384-3396; E-mail: umbricht@bli.unizh.ch

Received 23 October 2001; Revised 12 March 2002; Accepted 8 May 2002.

Abstract

Previously the NMDA (N-methyl-D-aspartate) receptor (NMDAR) antagonist ketamine was shown to disrupt generation of the auditory event-related potential (ERP) mismatch negativity (MMN) and the performance of an 'AX'-type continuous performance test (AX-CPT)—measures of auditory and visual context-dependent information processing—in a similar manner as observed in schizophrenia. This placebo-controlled study investigated effects of the 5-HT_2A receptor agonist psilocybin on the same measures in 18 healthy volunteers. Psilocybin administration induced significant performance deficits in the AX-CPT, but failed to reduce MMN generation significantly. These results indirectly support evidence that deficient MMN generation in schizophrenia may be a relatively distinct manifestation of deficient NMDAR functioning. In contrast, secondary pharmacological effects shared by NMDAR antagonists and the 5-HT_2A agonist (ie disruption of glutamatergic neurotransmission) may be the mechanism underlying impairments in AX-CPT performance observed during both psilocybin and ketamine administration. Comparable deficits in schizophrenia may result from independent dysfunctions of 5-HT_2A and NMDAR-related neurotransmission.