Ketamine reduces the neural distinction between self- and other-produced affective touch: a randomized double-blind placebo-controlled study.
Reinoud Kaldewaij, Paula C Salamone, Adam Enmalm, Lars Östman, Michal Pietrzak, Hanna Karlsson, Andreas Löfberg, Emelie Gauffin, Martin Samuelsson, Sarah Gustavson, Andrea J Capusan, Håkan Olausson, Markus Heilig, Rebecca Boehme
Neuropsychopharmacology October 1, 2024 DOI: 10.1038/s41386-024-01906-2 (opens in new tab)
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Study at a glance
AI-extracted from the abstract| Characteristics | Randomized double-blind placebo-controlled cross-over study Peer reviewed |
|---|---|
| Sample size | 30 |
| Population | Healthy participants (15 females/15 males, age 19-39) |
| Intervention | intravenous ketamine |
| Duration | Single session (no follow-up reported) |
| Topics | Esketamine Ketamine |
| Keywords | Self-perception Psychopharmacology Sensory-processing Consciousness |
| Citations | 19 |
| Key points | Ketamine reduces neural activity associated with self-other-differentiation in the right temporoparietal cortex, particularly during touch by someone else, and this reduction correlates with decreased interoceptive awareness. |
Abstract
A coherent sense of self is crucial for social functioning and mental health. The N-methyl-D-aspartate antagonist ketamine induces short-term dissociative experiences and has therefore been used to model an altered state of self-perception. This randomized double-blind placebo-controlled cross-over study investigated the mechanisms for ketamine's effects on the bodily sense of self in the context of affective touch. Thirty healthy participants (15 females/15 males, age 19-39) received intravenous ketamine or placebo while performing self-touch and receiving touch by someone else during functional MRI - a previously established neural measure of tactile self-other-differentiation. Afterwards, tactile detection thresholds during self- and other-touch were assessed, as well as dissociative states, interoceptive awareness, and social touch attitudes. Compared to placebo, ketamine administration elicited dissociation and reduced neural activity associated with self-other-differentiation in the right temporoparietal cortex, which was most pronounced during other-touch. This reduction correlated with ketamine-induced reductions in interoceptive awareness. The temporoparietal cortex showed higher connectivity to somatosensory cortex and insula during other- compared to self-touch. This difference was augmented by ketamine, and correlated with dissociation strength for somatosensory cortex. These results demonstrate that disrupting the self-experience through ketamine administration affects neural activity associated with self-other-differentiation in a region involved in touch perception and social cognition, especially with regard to social touch by someone else. This process may be driven by ketamine-induced effects on top-down signaling, rendering the processing of predictable self-generated and unpredictable other-generated touch more similar. These findings provide further evidence for the intricate relationship of the bodily self with the tactile sense.
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
- Minimal self-consciousness and the flying man argument. Frontiers in Psychology 2023
- Can ketamine and other glutamate receptor modulators be considered entactogens? Psychiatry Research July 1, 2025
- Sex, drugs, and arousal-two randomized trials on the effects of ketamine on sexual arousal and calcarine gyrus activity. Therapeutic Advances in Psychopharmacology 2026
- Ketamine and α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid (AMPA) Receptor Potentiation in the Somatosensory Cortex: A Comprehensive Review. Cureus September 1, 2024
- (Es)ketamine in functional neurological disorder: a systematic review Frontiers in Psychiatry July 20, 2026
Cites 24
- 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
- The Predictive Coding Account of Psychosis. Biological Psychiatry May 25, 2018
- Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study American Journal of Psychiatry May 21, 2019
- Ketamine for chronic pain: risks and benefits British Journal of Clinical Pharmacology February 21, 2013
and 19 more in the library