Skip to content

Concurrent assessment of neurometabolism and brain hemodynamics to characterize the functional brain response to psychotropic drugs: An S-ketamine study.

Daphne E Boucherie, Liesbeth Reneman, Jan Booij, Rogier Immink, Markus W Hollmann, Anouk Schrantee

Journal of Cerebral Blood Flow & Metabolism April 1, 2026 DOI: 10.1177/0271678x251399023 (opens in new tab)

Read Full Text
Relevant Not relevant

Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial, crossover design Placebo-controlled Peer reviewed
Sample size 32
Population Healthy controls
Intervention S-ketamine
Dose double-dose, low or high S-ketamine dose
Topics Esketamine Ketamine
Keywords Dissociation Functional mrs Pharmacological MRI Psychopharmacology
Key findings Concurrent phMRI and phMRS assessments provide complementary insights into the functional brain response to S-ketamine, with hemodynamic changes paralleling increases in glutamate and lactate.

Abstract

Neuroimaging techniques offer valuable insights for understanding pharmacological treatment effects in neuropsychiatric disorders. Here, we present a novel approach that simultaneously assesses hemodynamic and neurometabolic brain responses to psychotropic drugs using interleaved pharmacological magnetic resonance imaging (phMRI) and pharmacological magnetic resonance spectroscopy (phMRS). This method was tested using a double-dose, placebo-controlled, randomized, crossover design using S-ketamine as the pharmacological agent. We acquired 7 Tesla phMRI and phMRS data to evaluate time- and dose-dependent effects of S-ketamine in 32 healthy controls. S-ketamine elicited robust phMRI responses in the dorsofrontal, cingulate, and insular cortices, which correlated with glutamate and opioid receptor maps and subjective dissociation scores. These hemodynamic changes were paralleled by increases in glutamate and lactate, especially at higher doses. Furthermore, accuracy in predicting received condition (placebo, a low, or a high S-ketamine dose) increased when combining both techniques. Here, we show for the first time that concurrent phMRI and phMRS assessments provide important complementary insights into the functional brain response to pharmacological interventions.

Comparable studies

Other randomized controlled trials on esketamine, most cited first.

Study Year Design Participants
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 Adults with moderate to severe nonpsychotic depression and a history of nonresponse to... 2019 Phase 3, double-blind, active-controlled, multicenter randomized controlled trial n = 227
Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression Adults with treatment-resistant depression who achieved stable remission or stable... 2019 Phase 3, multicenter, double-blind, randomized withdrawal study n = 297
Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression Adults with DSM-IV-TR diagnosis of major depressive disorder and history of inadequate... 2017 Phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study n = 67
Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study Depressed patients at imminent risk for suicide 2018 Randomized controlled trial n = 68
Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1) Adults with moderate-to-severe depression and nonresponse to at least two... 2019 Randomized controlled trial n = 346

Citations in the library

Cites 16

and 11 more in the library

Related reading

Explore topics

Esketamine Ketamine Addiction