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Detecting neuroplastic effects induced by ketamine in healthy human subjects: A multimodal approach.

Claudio Agnorelli, Joseph Peill, Gabriela Sawicka, Danielle Kurtin, Ekaterina Shatalina, Kirran Ahmad, Matthew B. Wall, Catarina Rua, Kate Godfrey, Natalie Ertl, Graham Searle, Katie Zhou, Martin Osugo, Brandon Weiss, Kyle T. Greenway, Andrea Fagiolini, Robin Carhart-Harris, Paul Matthews, Eugenii A Rabiner, David Nutt, David Erritzøe

Journal of Cerebral Blood Flow & Metabolism March 21, 2026 DOI: 10.1177/0271678x261431447 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Observational cohort Peer reviewed
Sample size 11
Population Healthy male human subjects
Intervention Ketamine
Dose 1 mg/kg, intravenous
Duration 1-8 days after administration
Topics Default mode network Ketamine Neuroplasticity Esketamine
Keywords MRI PET
Key findings Ketamine increased ACC glutamate levels and altered ACC functional connectivity with dlPFC and amygdala, with DMN activity changes linked to synaptic plasticity.

Abstract

We investigated ketamine's neuroplastic effects in healthy human subjects using integrated Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI) measures before and 1-8 days after a single psychedelic dose of ketamine (1 mg/kg, intravenous). Eleven male participants underwent two PET/MRI scans with [11C]-UCBJ (synaptic density/plasticity), 1H-MRS (glutamate and GABA) and resting-state fMRI (intrinsic brain activity, functional connectivity), before and after ketamine. While group-level analyses showed no significant increases in PET synaptic markers, ketamine administration resulted in significantly elevated glutamate levels within the anterior cingulate cortex (ACC). Functional connectivity analyses revealed reduced coupling between the ACC and the dorsolateral prefrontal cortex (dlPFC) and increased coupling between the ACC and the amygdala in the days following ketamine administration. Our multimodal analysis revealed that participants showing an increase in [11C]-UCBJ volume distribution (VT), a putative index of synaptic plasticity, showed a correlated reduction in intrinsic activity within regions belonging to the default mode network (DMN). By linking molecular, cellular and network-level changes, our results point to the DMN as a central hub where ketamine may reshape brain hierarchies in the long term, providing new directions for understanding its therapeutic mechanisms and developing targeted treatments.

Comparable studies

Other observational and cohort studies on ketamine, most cited first.

Study Year Design Participants
Taming the Ketamine Tiger Volunteers from a prison population 2010 Observational study n = 20
Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin Humans 2017 Observational study
Disruption of Frontal–Parietal Communication by Ketamine, Propofol, and Sevoflurane Surgical patients undergoing induction of anesthesia with intravenous ketamine 2013 Observational cohort n = 30
Do the dissociative side effects of ketamine mediate its antidepressant effects? Treatment-resistant inpatients with major depressive disorder or bipolar disorder 2014 Observational cohort n = 108
Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder 2012 Observational cohort n = 30

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Default mode network Ketamine Neuroplasticity Esketamine