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 Serotonin |
| 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.
Comparable studies
Other randomized controlled trials on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose?effect study Healthy human subjects | 2004 | Randomized controlled trial | n = 8 |
| Dose-Response Study of N,N-Dimethyltryptamine in Humans Experienced hallucinogen users | 1994 | Double-blind, saline placebo-controlled, randomized study | n = 12 |
| Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects Healthy subjects (8 women, 8 men) | 2014 | Double-blind, randomized, placebo-controlled, crossover study | n = 16 |
| Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor Healthy human participants | 2018 | Double-blind, randomized, counterbalanced, cross-over study | n = 24 |
| Activation of Serotonin 2A Receptors Underlies the Psilocybin-Induced Effects on Oscillations, N170 Visual-Evoked Potentials, and Visual Hallucinations Healthy human subjects | 2013 | Randomized controlled trial |
Citations in the library
Cited by 68
- Human hallucinogen research: guidelines for safety. Journal of Psychopharmacology July 1, 2008
- Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies Journal of Psychopharmacology September 20, 2010
- The paradoxical psychological effects of lysergic acid diethylamide (LSD) Psychological Medicine February 5, 2016
- Phenomenology, Structure, and Dynamic of Psychedelic States Current Topics in Behavioral Neurosciences 2016
- Peak experiences and the afterglow phenomenon: When and how do therapeutic effects of hallucinogens depend on psychedelic experiences? Journal of Psychopharmacology February 9, 2015
and 63 more in the library
Cites 14
- Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Journal of Neuroscience April 15, 1997
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- Reversal of Phencyclidine Effects by a Group II Metabotropic Glutamate Receptor Agonist in Rats Science August 28, 1998
- Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers Archives of General Psychiatry December 1, 2000
- Attenuation of the Neuropsychiatric Effects of Ketamine With Lamotrigine Archives of General Psychiatry March 1, 2000
and 9 more in the library