S‐ketamine and GABA‐A‐receptor interaction in humans: an exploratory study with I‐123‐iomazenil SPECT
Alexander Heinzel, Rainer Steinke, Thorsten Dirk Poeppel, Oliver S. Großer, Bernhard Bogerts, H J Otto, Georg Northoff
Human Psychopharmacology Clinical and Experimental June 11, 2008 DOI: 10.1002/hup.960 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Blinded placebo-controlled study Peer reviewed |
|---|---|
| Sample size | 24 |
| Population | Healthy human subjects |
| Intervention | S-ketamine |
| Measures | I-123-iomazenil SPECT, Brief Psychiatric Rating Scale (BPRS), cortisol, prolactin |
| Topics | Esketamine Ketamine |
| Citations | 22 |
| Key points | S-ketamine administration was associated with significantly decreased I-123-iomazenil binding in the bilateral dorsomedial prefrontal cortex compared with placebo, along with positive and negative symptoms on the BPRS and increased cortisol and prolactin. The authors present this as preliminary evidence for an in vivo interaction between S-ketamine and GABA-A receptors in human dorsomedial prefrontal cortex. |
Abstract
Objective: We aimed to probe for regional cerebral effects of S-ketamine on in vivo GABA-A-receptor binding in healthy human subjects.
Methods: We investigated I-123-iomazenil SPECT before, during and after administration of S-ketamine in a blinded placebo-controlled study design (n = 12 in both groups). Analyses of SPECT were performed with voxel-based statistical parametric mapping (SPM), and statistical comparisons were made between the groups. We also assessed biochemical and behavioural changes during S-ketamine infusion.
Results: S-ketamine induced positive and negative symptoms measured by the Brief Psychiatric Rating scale (BPRS). It increased the cortisol and prolactin levels. Image analysis revealed significantly decreased I-123-iomazenil binding in bilateral dorsomedial prefrontal cortex during S-ketamine administration when compared to placebo.
Conclusion: Our study delivers preliminary evidence for an in vivo interaction of S-ketamine with GABA-A-receptors in human dorsomedial prefrontal cortex.
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 4
- The neurophysiology of ketamine: an integrative review Reviews in the Neurosciences May 5, 2020
- Effects of ketamine on GABAergic and glutamatergic activity in the mPFC: biphasic recruitment of GABA function in antidepressant-like responses. Neuropsychopharmacology March 1, 2025
- Pharmacological modulation of anxiety-like behavior by flumazenil, midazolam, and ketamine in rats: Evidence from aversive ultrasonic vocalizations and elevated plus maze. Pharmacology, Biochemistry, and Behavior May 25, 2026
- Prolonged blockade of NMDA receptors and positive modulation of a5 GABA A receptors: No changes in depressive-like behavior, while the former slightly increased emotional reactivity in unstressed rats Medicinska istrazivanja 2025
Cites 5
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Effects of different subanaesthetic doses of (S)-ketamine on psychopathology and binocular depth inversion in man Journal of Psychopharmacology 2003
- Inhibition of return in the human 5HT2A agonist and NMDA antagonist model of psychosis. Neuropsychopharmacology February 2006
- NMDA hypofunction in the posterior cingulate as a model for schizophrenia: an exploratory ketamine administration study in fMRI. Schizophrenia Research January 1, 2005
- A systems model of altered consciousness: integrating natural and drug-induced psychoses. Brain Research Bulletin November 15, 2001