ReviewCurrent pain and headache reports2021
Ketamine in the Past, Present, and Future: Mechanisms, Metabolites, and Toxicity.
Review in Current pain and headache reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 25 papers, 2 of them syntheses that pooled 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.
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.
Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 41 citations in OpenAlex.
- Molecular pathways of ketamine: A systematic review of immediate and sustained effects on PTSD.Psychopharmacology · 2025Pooled it
- Ketamine treatment for refractory anxiety: A systematic review.British journal of clinical pharmacology · 2022Pooled it
- A Randomized Controlled Trial of Intraoperative Ketamine for Acute Postsurgical Pain after Breast Cancer Surgery: The Moderating Effect of Baseline Temporal Summation of Pain.Anesthesiology · 2025Trial
- Nitrous oxide for the treatment of complex regional pain syndrome: a randomized blinded trial.Regional anesthesia and pain medicine · 2024Trial
- Intraoperative Non-Opiate Anesthesia for Patients Undergoing Arthroscopic Temporomandibular Joint Surgery: A Randomized Controlled Trial.Drug design, development and therapy · 2024Trial
- Ketamine abuse also affects sexual health.Sexual medicine · 2026Article
- Ketamine attenuates anxiety-like behavior and oxidative imbalance in the maternal immune activation model: emphasis on the cerebellum.Psychopharmacology · 2026Article
- Review
- Long-term relief of CRPS-associated limb dystonia with ketamine infusion.BMJ case reports · 2026Article
- Progress in the Application of Esketamine During the Perioperative Period.Drug design, development and therapy · 2026Review
- Clinical research progress of esketamine in perioperative neuroprotection: from mechanisms to therapeutic neuroprotection.Frontiers in pharmacology · 2026Review
- Repeated ketamine exposure induces psychotic-like behaviors in mice via DRD1-mediated phosphorylation of p-Thr34 DARPP-32 and p-Ser10 histone H3.Cell biology and toxicology · 2025Article
- Multiday intravenous ketamine infusion therapy for the management of central sensitisation syndrome secondary to chronic chemotherapy-induced peripheral neuropathic pain.BMJ case reports · 2025Article
- Article
- Determination of drugs of abuse in oral fluid using dried oral fluid spot assisted by 24-well plate and LC-MS/MS.Bioanalysis · 2025Review
- Esketamine reduces postoperative depression in breast cancer through TREK-1 channel inhibition and neurotransmitter modulation.Cancer cell international · 2025Article
- Drug substitutes - Insights on benefits, risks, detection methods, and management strategies: a systematic review.Frontiers in psychiatry · 2025Review
- Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms.Biomedicines · 2024Review
- The metabolic clock of ketamine abuse in rats by a machine learning model.Scientific reports · 2024Article
- Ketamine, an Old-New Drug: Uses and Abuses.Pharmaceuticals (Basel, Switzerland) · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purpose of reviewWhile ketamine's analgesia has mostly been attributed to antagonism of N-methyl-D-aspartate receptors, evidence suggests multiple other pathways are involved in its antidepressant and possibly analgesic activity. These mechanisms and ketamine's role in the nociplastic pain paradigm are discussed. Animal studies demonstrating ketamine's neurotoxicity have unclear human translatability and findings from key rodent and human studies are presented. RECENT
findingsKetamine's metabolites, and (2R,6R)-hydroxynorketamine in particular, may play a greater role in its clinical activity than previously believed. The activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and the mammalian target of rapamycin by ketamine are mechanisms that are still being elucidated. Ketamine might work best in nociplastic pain, which involves altered pain processing. While much is known about ketamine, new studies will continue to define its role in clinical medicine. Evidence supporting ketamine's neurotoxicity in humans is lacking and should not impede future ketamine clinical trials.
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What OpenQuestion holds
Registered trials
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 OpenQuestion graph.