Modulatory Effects of Ketamine and Lamotrigine on Cognition: Emotion Interaction in the Brain.
Matti Gärtner, Anne Weigand, Christian Keicher, Marvin Sören Meiering, David Weigner, Luisa Carstens, Rita Hertrampf, Christian Beckmann, Maarten Mennes, Andreas Wunder, Simone Grimm
Neuropsychobiology 2023 DOI: 10.1159/000528315 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, placebo-controlled, randomized, single-dose, parallel-group study Peer reviewed |
|---|---|
| Sample size | 75 |
| Population | Healthy subjects |
| Interventions | Ketamine Lamotrigine |
| Duration | Single dose, with scanning sessions acutely and 24 hours post-administration |
| Topics | Ketamine Esketamine |
| Keywords | Cognition Emotion Lamotrigine FMRI |
| Key points | Acute ketamine increased dissociative, psychotomimetic, and cognitive effects and neural activity during working memory for positive stimuli compared with placebo. Lamotrigine pretreatment did not alter ketamine's subjective effects but significantly attenuated its impact on emotional working memory and associated neural activity. No effects on these measures were present 24 hours after ketamine administration. |
Abstract
Cognition and emotion are fundamentally integrated in the brain and mutually contribute to behavior. The relation between working memory (WM) and emotion is particularly suited to investigate cognition-emotion interaction since WM is an essential component of many higher cognitive functions. Ketamine affects not only WM but also has a profound impact on emotional processing. Effects of acute ketamine challenge are sensitive to modulation by pretreatment with lamotrigine, which inhibits glutamate release. Accordingly, a combination of these approaches should be particularly suited to investigate cognition-emotion interaction. Seventy five healthy subjects were investigated in a double-blind, placebo-controlled, randomized, single-dose, parallel-group study with three treatment conditions. All subjects underwent two scanning sessions (acute/post 24 h). Compared to placebo, acute ketamine administration induced significant dissociative, psychotomimetic, and cognitive effects, as well as an increase in neural activity during WM for positive stimuli. Inhibition of glutamate release by pretreatment with lamotrigine did not influence ketamine's subjective effects, but significantly attenuated its impact on emotional WM and associated neural activity. There was no effect on these measures 24 h after ketamine administration. Our results demonstrate differential acute effects of modulated glutamate release and a swift restoration of disturbed neurobehavioral homeostasis in healthy subjects.
Comparable studies
Other randomized controlled trials on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Healthy human subjects recruited from the community | 1994 | Randomized controlled trial | n = 19 |
| Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode | 2013 | Randomized controlled trial | n = 73 |
| Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine Patients undergoing major abdominal surgery | 2005 | Randomized controlled trial | n = 75 |
| Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder Patients with chronic PTSD related to a range of trauma exposures | 2014 | Randomized controlled trial | n = 41 |
| Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers Healthy volunteers | 2000 | Single-blind placebo-controlled study | n = 20 |
Citations in the library
Cited by 5
- Functional activity and connectivity signatures of ketamine and lamotrigine during negative emotional processing: a double-blind randomized controlled fMRI study. Translational Psychiatry October 14, 2024
- Negative emotionality shapes the modulatory effects of ketamine and lamotrigine in subregions of the anterior cingulate cortex. Translational Psychiatry June 18, 2024
- Ketamine’s impact on rumination-related brain dynamics: insights from a randomized controlled fMRI trial Translational Psychiatry August 18, 2026
- Functional connectivity alterations of the pregenual anterior cingulate cortex by ketamine and the modulation by lamotrigine. Journal of Psychopharmacology June 19, 2025
- Region- and time- specific effects of ketamine on cerebral blood flow: a randomized controlled trial. Neuropsychopharmacology May 25, 2023
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