The NMDA antagonist ketamine and the 5-HT agonist psilocybin produce dissociable effects on structural encoding of emotional face expressions
André Schmidt, Michael Kometer, Rosilla Bachmann, Erich Seifritz, Franz X. Vollenweider
Psychopharmacology July 26, 2012 DOI: 10.1007/s00213-012-2811-0 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind within-subject placebo-controlled design Peer reviewed |
|---|---|
| Population | Healthy subjects |
| Interventions | S-ketamine psilocybin |
| Topics | Ketamine Psilocybin Esketamine Serotonin |
| Keywords | Nmda receptor Agonist |
| Citations | 94 |
| Key points | Both S-ketamine and psilocybin impaired the encoding of fearful faces, but only S-ketamine impaired encoding of happy faces, indicating differential contributions of NMDA and 5-HT receptor systems to emotional face processing. |
Abstract
RationaleBoth glutamate and serotonin (5-HT) play a key role in the pathophysiology of emotional biases. Recent studies indicate that the glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine and the 5-HT receptor agonist psilocybin are implicated in emotion processing. However, as yet, no study has systematically compared their contribution to emotional biases.ObjectivesThis study used event-related potentials (ERPs) and signal detection theory to compare the effects of the NMDA (via S-ketamine) and 5-HT (via psilocybin) receptor system on non-conscious or conscious emotional face processing biases.MethodsS-ketamine or psilocybin was administrated to two groups of healthy subjects in a double-blind within-subject placebo-controlled design. We behaviorally assessed objective thresholds for non-conscious discrimination in all drug conditions. Electrophysiological responses to fearful, happy, and neutral faces were subsequently recorded with the face-specific P100 and N170 ERP.ResultsBoth S-ketamine and psilocybin impaired the encoding of fearful faces as expressed by a reduced N170 over parieto-occipital brain regions. In contrast, while S-ketamine also impaired the encoding of happy facial expressions, psilocybin had no effect on the N170 in response to happy faces.ConclusionThis study demonstrates that the NMDA and 5-HT receptor systems differentially contribute to the structural encoding of emotional face expressions as expressed by the N170. These findings suggest that the assessment of early visual evoked responses might allow detecting pharmacologically induced changes in emotional processing biases and thus provides a framework to study the pathophysiology of dysfunctional emotional biases.
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 72
- Emotions and brain function are altered up to one month after a single high dose of psilocybin. Scientific Reports February 10, 2020
- Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers Biological Psychiatry April 26, 2014
- Phenomenology, Structure, and Dynamic of Psychedelic States Current Topics in Behavioral Neurosciences 2016
- Psilocybin – Summary of knowledge and new perspectives European Neuropsychopharmacology December 17, 2013
- Effect of Psilocybin on Empathy and Moral Decision-Making The International Journal of Neuropsychopharmacology June 14, 2017
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Cites 17
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
- Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) PLoS One August 31, 2010
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