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Ketamine-induced changes in accumbal glutamate and their association with altered states of consciousness.

Ladina Philomena Gubser, Anna Stefania Trippel, Niklaus Zoelch, Etna Jennifer Elektra Engeli, Marcus Herdener

Brain Research Bulletin May 1, 2026 DOI: 10.1016/j.brainresbull.2026.111842 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Within-subjects experimental study Peer reviewed
Sample size 10
Population Healthy volunteers
Interventions R S-ketamine
Dose 0.71 mg/kg bodyweight
Duration 40-minute infusion
Topics Ketamine Altered states of consciousness Esketamine
Keywords Altered Consciousness Glutamate Nucleus accumbens Spectroscopy
Key findings Ketamine did not significantly increase mean glutamate levels in the NAc, but individual glutamate changes were positively associated with anxious ego dissolution and reductions in vigilance.

Abstract

Ketamine has been shown to modulate glutamate signaling in animals and may therefore have the potential to restore glutamate imbalances in the brain. Impaired glutamate homeostasis has been implicated in mental health disorders such as substance use disorders (SUDs). Thus, we investigated ketamine's potential to increase glutamate levels in the nucleus accumbens (NAc), a key region for the development and maintenance of SUD. We further examined whether glutamate changes are associated with ketamine's potential to induce altered states of consciousness. A single intravenous dose of R,S-ketamine (0.71 mg/kg bodyweight) was administered to 10 healthy volunteers over 40 min. Glutamate levels were measured by using a tailored proton magnetic resonance spectroscopy (1H-MRS) sequence in the left NAc on a 3 T scanner, before and during the infusion. Subjective effects were measured by using the Five-Dimensional Altered States of Consciousness (5D-ASC) questionnaire. Glutamate levels were considered from the overall spectrum average (22 min) as well as three shorter, overlapping sub-blocks (each 10 min), to capture the progression of glutamate over time. Mean glutamate levels in the NAc were not significantly altered between baseline and ketamine 1H-MRS measurement. However, glutamate changes were positively associated with anxious ego dissolution and reductions in vigilance. In conclusion, ketamine did not significantly increase glutamate levels across our sample of 10 healthy volunteers, but individual glutamate changes induced by ketamine correlate with anxious ego dissolution and reductions in vigilance, indicating that ketamine-induced glutamate alterations in the NAc underly specific alterations in perception and consciousness.

Comparable studies

Other experimental studies on altered states of consciousness, most cited first.

Study Year Design Participants
The Standardized Psychometric Assessment of Altered States of Consciousness (ASCs) in Humans Healthy subjects in six countries 1998 Experimental and field study n = 1,133
TMS-EEG and resting-state EEG applied to altered states of consciousness: oscillations, complexity, and phenomenology. 2023 Experimental study
A Test of the Psychedelic Model of Altered States of Consciousness 1976 Experimental study with comparison groups
Neural Correlates of Non-ordinary States of Consciousness in Pranayama Practitioners: The Role of Slow Nasal Breathing Experienced meditators 2022 Within-subjects comparison n = 12
Increased spontaneous EEG signal diversity during stroboscopically-induced altered states of consciousness Healthy adults 2019 Experimental study

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Ketamine Altered states of consciousness Esketamine Addiction Ego dissolution