Ketamine disrupts consciousness in healthy participants in relation with psychotic-like symptoms.
Lucie Berkovitch, Alexandre Salvador, Thomas Andrillon, Stanislas Dehaene, Raphaël Gaillard
bioRxiv : the preprint server for biology November 8, 2025 preprint DOI: 10.1101/2025.11.06.687042 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Double-blind |
|---|---|
| Sample size | 21 |
| Population | Healthy volunteers |
| Intervention | Ketamine |
| Dose | low doses |
| Topics | Ketamine Esketamine |
| Keywords | Drug Conscious perception Visual information Visual awareness Conscious access Brain activity Early brain responses Psychotic experiences Psychotic-like experiences Symptoms |
| Key findings | Ketamine disrupts conscious access by attenuating early visual brain responses, and this impairment correlates with its psychotic-like effects. |
Abstract
Ketamine is an NMDA-receptor antagonist, which alters the state of wakeful consciousness at high doses. At lower doses, it induces reversible psychotic-like symptoms and has been used as a pharmacological model of psychosis. In this study, we explore whether low doses of ketamine disrupt conscious access in relation with its psychotomimetic effects, and investigate the neural correlates of its action. We administered ketamine and placebo to 21 healthy volunteers following a double-blind within-subject randomized design and recorded brain activity with high-density electroencephalography during a perceptual task. Participants had to categorize a sound and a masked digit, and to report the digit visibility. To manipulate visibility, the delays between the sound, the digit, and the mask were varied. Principal component analysis was used to decompose ketamine-induced psychiatric symptoms and to examine their relationships with conscious access measures. Under ketamine, participants had an increased visual masking effect, more interference between the sound and the digit, and a reduced ability to consciously perceive the digit. The N1 component, a EEG marker of visual processing, correlated with conscious access and was significantly reduced under ketamine. Ketamine induced manic-like and psychotic-like symptoms but only the psychotic-like dimension correlated with conscious access impairments. Overall, our results suggest that ketamine disrupts conscious access in healthy subjects through an attenuation of early visual responses, and in relation with its psychotomimetic effects. Interestingly, these changes differed in part from those observed in patients with schizophrenia, opening new perspectives on the mechanisms of psychotic symptoms.
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
Cites 27
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- Neural correlates of consciousness: progress and problems Nature Reviews Neuroscience April 20, 2016
- Measurement of dissociative states with the Clinician‐Administered Dissociative States Scale (CADSS) Journal of Traumatic Stress 1998
- From drugs to deprivation: a Bayesian framework for understanding models of psychosis Psychopharmacology May 27, 2009
- The NMDA antagonist ketamine and the 5-HT agonist psilocybin produce dissociable effects on structural encoding of emotional face expressions Psychopharmacology July 26, 2012
and 22 more in the library