Glutamate and Opioid Mechanisms of Antidepressant Response to Ketamine

This randomised, double-blind, crossover trial (n=27) investigated the acute effects of ketamine (35mg/70kg) on brain glutamate, functional connectivity, and cerebral blood flow in individuals with treatment-resistant depression (TRD).

Conducted by King’s College London, participants underwent two imaging sessions on separate days, receiving either oral placebo or oral naltrexone preceding ketamine infusion during neuroimaging. Each participant received a dose of ketamine (IV infusion, 0.5 mg/kg over 40 minutes) during each scan, preceded by either oral placebo or naltrexone 50 mg, 45 minutes before the initiation of the ketamine infusions.

The study aimed to determine if the effects of ketamine on brain functioning were attenuated by the opioid receptor antagonist naltrexone, and how these findings related to antidepressant response. The primary purpose of the study was to explore basic science, with a crossover assignment design and quadruple masking.

The study focused on individuals aged 18 to 50 with treatment-resistant depression. The primary outcome measure was the change in glutamate during ketamine infusion, with secondary outcomes including changes in resting state functional connectivity and cerebral blood flow. The study commenced in September 2021 and concluded in February 2023.

Topic Treatment-Resistant Depression Depression
Compound Ketamine Placebo
Country United Kingdom
Visit trial
Status Completed
Results Published No
Start date 27 September 2021
End date 20 February 2023
Phase Phase I
Design Blinded
Type Interventional
Generation First
Participants 27
Sex All
Age 18- 650
Therapy No

Trial Details

The overarching aim of this research is to determine the acute effects of ketamine on brain glutamate, functional connectivity and cerebral blood flow in treatment-resistant depression, explore whether the effects are attenuated by the opioid receptor antagonist naltrexone and relate these findings to antidepressant response.

NCT Number NCT04977674

Sponsors & Collaborators

King's College London
The Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King's College London is one of Europe's top centres for mental health and related neurosciences research.

Data attribution

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