Evidence map›Paper›PMID 40707608›Full record

Trial reportNature medicine2025

Effect of naltrexone pretreatment on ketamine-induced glutamatergic activity and symptoms of depression: a randomized crossover study.

Luke A Jelen, David J Lythgoe, James M Stone, Allan H Young, Mitul A Mehta

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Is the antidepressant efficacy of ketamine and esketamine mediated via opioid mechanisms?European psychiatry : the journal of the Association of European Psychiatrists · 2026
    Pooled it
  2. Modulation of early non-rapid eye movement slow wave activity by ketamine in treatment-resistant depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Trial
  3. Modulation of GABA and glutamate by ketamine in depression: A systematic review and meta-analysis of magnetic resonance spectroscopy studies.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article
  4. Article
  5. Molecular snapshots confirm ketamine's opioid nature.Nature structural & molecular biology · 2026
    Article
  6. Review
  7. Treatment-resistant Depression in the Post-ketamine Era: Unmet Needs beyond Rapid Response.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2026
    Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Methodological considerations for interpreting ketamine-naltrexone trials in depression.The international journal of neuropsychopharmacology · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Luke A JelenThe Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. luke.jelen@kcl.ac.uk.ORCID http://orcid.org/0000-0001-6398-5239
David J LythgoeThe Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.ORCID http://orcid.org/0000-0002-5078-9025
James M StoneBrighton and Sussex Medical School (BSMS), University of Sussex, Brighton, UK.ORCID http://orcid.org/0000-0003-3051-0135
Allan H YoungThe Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.ORCID http://orcid.org/0000-0003-2291-6952
Mitul A MehtaThe Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.ORCID http://orcid.org/0000-0003-1152-5323

Funding

RCUK | Medical Research Council (MRC) MR/T028084/1
6 · The paper itself

Abstract

We investigated the potential role of the opioid system in modulating glutamatergic effects of ketamine administration in major depressive disorder. Twenty-six adults with major depressive disorder participated in a double-blind crossover study, receiving oral placebo or 50 mg naltrexone before an intravenous infusion of 0.5 mg per kg ketamine. Brain glutamatergic activity in the anterior cingulate cortex was measured using functional magnetic resonance spectroscopy and depressive symptoms were assessed with the Montgomery-Åsberg Depression Rating Scale. Naltrexone attenuated the increase in glutamate + glutamine to total N-acetylaspartate ratio during ketamine infusion compared to placebo (F

Indexed as

DepressionGlutamic AcidKetamineMajor Depressive DisorderNaltrexoneAdultAntidepressive AgentsCross-Over StudiesDouble-Blind MethodFemaleGlutamineGyrus CinguliHumansMaleMiddle AgedNarcotic AntagonistsAntidepressive AgentsGlutamic AcidGlutamineKetamineNaltrexoneNarcotic Antagonists

Identifiers

PMID40707608
PMCPMC12443602

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.