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Glutamatergic Adaptation to Stress as a Mechanism for Anhedonia and Treatment Response With Ketamine

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Early Phase I, randomized, triple-blind, placebo-controlled trial (n=250 MDD; +60 healthy controls) testing a single sub‑anesthetic IV ketamine infusion (0.5 mg/kg) versus saline to assess glutamate stress response, anhedonia, decision-making, and emotion processing.

Details

This study evaluates the glutamate stress response and its relation to motivation, valuation, and anhedonia in people with Major Depressive Disorder using multimodal neuroimaging, behavioural tasks, and questionnaires.

MDD participants are randomized to a single IV ketamine infusion (0.5 mg/kg) or saline placebo administered over 40–100 minutes; behavioural and imaging assessments are collected to measure acute and downstream effects.

A separate healthy control cohort (n≈60) completes a behavioural session and one neuroimaging session for baseline comparison and does not receive any intervention.

Topics:Major Depressive Disorder (MDD)

Registry

Registry linkNCT05327699