Effects of the 5-HT2A Agonist Psilocybin on Mismatch Negativity Generation and AX-Continuous Performance Task: Implications for the Neuropharmacology of Cognitive Deficits in Schizophrenia
Daniel Umbricht, Franz X. Vollenweider, Liselotte Schmid, Claudia Grübel, Anja Skrabo, Theo Huber, Rene Koller
Neuropsychopharmacology 2003 DOI: 10.1038/sj.npp.1300005 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Placebo-controlled study Peer reviewed |
|---|---|
| Sample size | 18 |
| Population | Healthy volunteers |
| Intervention | Psilocybin |
| Topics | Psilocybin |
| Keywords | Mismatch negativity Nmda receptor Schizophrenia object-oriented programming Agonist Psychosis Psychotomimetic Electroencephalography Hallucinogen |
| Citations | 192 |
| Key points | Psilocybin induced significant performance deficits in the AX-CPT but failed to reduce MMN generation significantly. |
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.