Regional Blood Flow Signatures of Opioidergic Modulation of Ketamine in Major Depressive Disorder: A Randomized Crossover Study

American Journal of Psychiatry 2026 Open access

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Authors: Luke A. Jelen, Owen O’Daly, Fernando O. Zelaya, James M. Stone, Allan H. Young, Mitul A Mehta
DOI: 10.1176/appi.ajp.20250903
Cited by: 2
References: 46

Abstract

OBJECTIVE: Accumulating evidence suggests that the opioid system may modulate ketamine's rapid antidepressant effects. The objective of this study was to test whether opioid system modulation via naltrexone alters ketamine's acute effects on regional cerebral blood flow (rCBF) in major depressive disorder (MDD), and whether these changes relate to symptom measures and map onto receptor density profiles. METHODS: α5), correcting for spatial autocorrelation. RESULTS: α5. CONCLUSIONS: The results suggest that ketamine's effects on CBF in MDD are influenced by complex interactions between glutamatergic, opioidergic, and GABAergic systems. These findings provide mechanistic insights with potential implications for optimizing ketamine-based treatments.

Fields of Study & Subjects

Treatment of Major Depression Functional Brain Connectivity Studies Neurotransmitter Receptor Influence on Behavior

Publication details

Journal / source
American Journal of Psychiatry
Publisher
American Psychiatric Association Publishing
Volume
183
Issue
6
Pages
420–430
Publication date
2 April 2026
Language
EN