Subacute effects of ketamine on neural correlates of reward processing
Elisa Briem, Peter Stöhrmann, Gregor Dörl, Christian Milz, Gabriel Schlosser, Manfred Klöbl, M. Reed, M. Atger, Claudia M Schmidt, Samantha Graf, Maximilian Kathofer, Godber Mathis Godbersen, JS Crone, Rupert Lanzenberger, Marie Spies
Translational Psychiatry September 24, 2026 DOI: 10.1038/s41398-026-04485-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Single-blind, placebo-controlled, crossover study Peer reviewed |
|---|---|
| Sample size | 28 |
| Population | Healthy participants |
| Interventions | Ketamine placebo |
| Dose | 0.5 mg/kg racemic ketamine |
| Duration | 40 min intravenous infusion; fMRI approximately 5 h post-infusion |
| Measures | Monetary Incentive Delay (MID) task, functional magnetic resonance imaging, plasma concentrations of ketamine and norketamine, psychometric measures |
| Topics | Esketamine Ketamine |
| Key points | At approximately 5 hours after a 0.5 mg/kg intravenous ketamine infusion, ketamine did not significantly modulate brain activation during the Monetary Incentive Delay task in ROI-based or whole-brain analyses, despite measurable subjective drug effects. Neither individual drug exposure nor psychometric measures showed robust associations with task-related neural activation. The authors suggest ketamine's effects on reward circuitry may be time-sensitive, possibly more prominent acutely or in clinical populations with pre-existing reward dysfunction. |
Abstract
Abstract Ketamine induces a sequence of temporally distinct effects on brain function, yet its impact on reward processing beyond the acute post-administration phase remains unclear. In this single-blind, placebo-controlled, crossover study, 28 healthy participants received 0.5 mg/kg racemic ketamine or placebo via a 40 min intravenous infusion. Functional magnetic resonance imaging was acquired approximately 5 h post-infusion during the Monetary Incentive Delay (MID) task, targeting the subacute phase after resolution of acute dissociative effects. Plasma concentrations of ketamine and norketamine were obtained for pharmacokinetic modeling and area under the curve estimation. At 5 h post-administration, ketamine did not significantly modulate brain activation during the MID task in either ROI-based or whole-brain analyses, despite measurable subjective drug effects. Pharmacokinetic modeling yielded ketamine and norketamine concentration-time profiles consistent with expected pharmacokinetic patterns, however, neither individual drug exposure nor psychometric measures showed robust associations with MID task-related neural activation. These findings suggest an absence of detectable task-evoked effects under the present methodological conditions. When considered alongside prior work, they are consistent with the possibility that ketamine’s effects on reward circuitry are time-sensitive and may be more prominent during the acute post-administration phase or in clinical populations with pre-existing reward dysfunction.
Comparable studies
Other randomized controlled trials on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Healthy human subjects recruited from the community | 1994 | Randomized controlled trial | n = 19 |
| Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode | 2013 | Randomized controlled trial | n = 73 |
| Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine Patients undergoing major abdominal surgery | 2005 | Randomized controlled trial | n = 75 |
| Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder Patients with chronic PTSD related to a range of trauma exposures | 2014 | Randomized controlled trial | n = 41 |
| Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers Healthy volunteers | 2000 | Single-blind placebo-controlled study | n = 20 |