Archives of General Psychiatry
December 1, 2000
Daniel Umbricht, Liselotte Schmid, Rene Koller et al.
590 citations
In healthy volunteers, the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine significantly reduced the amplitude of mismatch negativity (MMN) brain responses to pitch and duration changes by 27% and 21%, respectively. Ketamine also impaired performance on a continuous performance test, decreasing hit rates and increasing specific context-dependent errors (BX errors), indicating a failure to form and use transient memory traces. These findings suggest that NMDARs are critically involved in generating MMN and that NMDAR dysfunction may underlie deficits in transient memory at different levels of information processing in schizophrenia.
Neuropsychopharmacology
January 1, 2003
Daniel Umbricht, Franz X. Vollenweider, Liselotte Schmid et al.
192 citations
The NMDA receptor antagonist ketamine disrupts auditory mismatch negativity (MMN) and performance on an AX-type continuous performance test (AX-CPT), similar to deficits seen in schizophrenia. This placebo-controlled study tested the 5-HT(2A) receptor agonist psilocybin on the same measures in 18 healthy volunteers. Psilocybin caused significant performance deficits on the AX-CPT but did not significantly reduce MMN generation. These results suggest that deficient MMN generation in schizophrenia may specifically reflect NMDA receptor dysfunction, while impairments in AX-CPT performance during both psilocybin and ketamine administration may stem from shared disruption of glutamatergic neurotransmission. Comparable deficits in schizophrenia may arise from independent dysfunctions of 5-HT(2A) and NMDA receptor-related neurotransmission.
Journal of Psychopharmacology
October 16, 2025
Gerard J. Marek, Soma Makai‐bölöni, Daniel Umbricht et al.
2 citations
A single intravenous dose of GM-2505, a novel 5-HT2A receptor agonist, was safe and well tolerated in 48 healthy volunteers at doses up to 20 mg. The drug produced mild, transient increases in blood pressure and pulse, no significant electrocardiograph changes, and a half-life of 40–50 minutes. Dose-dependent effects appeared on neuroendocrine hormones, neuropsychological and neurophysiological measures, subjective drug effects, and resting-state electroencephalography, with decreased theta and alpha power and increased slow and fast gamma power. These pharmacodynamic effects resembled those of other 5-HT2A agonists, but GM-2505's shorter duration of cardiovascular and subjective effects than psilocybin and longer than DMT suggests a more practical temporal profile for supervised clinical use, with an optimal dose range of 10–15 mg IV.