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Benchmark validation hit Hypothesis #5385 Benchmark case

ketamine NMDA receptor pain

Cross-domain hypothesis: Depression drug → ALS outcome

Figure 1. Hypothesis chain: ketamine (inhibits) NMDA receptor (associated with) pain.
Benchmark validation case
Outreach score
0.101
Evidence A → B
8
papers
Evidence B → C
1
papers
Direct A → C
1
papers

Evidence network

The full set of scientific papers supporting this hypothesis, visualized as a force-directed graph. Each gray node is one paper; hover for the extracted claim, click to open it on PubMed.

Figure 2. Evidence network for ketamine → NMDA receptor → pain. Each gray node represents a scientific paper from the Robertium extraction. A→B edges show ketamine → NMDA receptor claims; B→C edges show NMDA receptor → pain claims. Hover for details, click a paper to open PubMed. Sparse evidence — 9 papers total. See Limitations section for context.
View as text list

A→B papers (8)

  • PMID 41765199 — Ketamine pharmacotherapy for major depressive disorder: A narrative review (2026) · mechanism of action conf 0.95
  • PMID 41656677 — Comparative Efficacy and Safety of Ketamine Versus Midazolam for Suicidality: A GRADE‐Assessed Systematic Review and Meta‐Analysis of Randomized Controlled Trials (2026) · general conf 0.90
  • PMID 41690063 — Ketamine combined with psychotherapy for treatment-resistant depression: Real-world outcomes and the role of subjective experience (2026) · general conf 0.95
  • PMID 35783539 — Ketamine use disorder: preclinical, clinical, and neuroimaging evidence to support proposed mechanisms of actions (2022) · mechanism of action conf 0.95
  • PMID 32209965 — Ketamine in Major Depressive Disorder: Mechanisms and Future Perspectives (2020) · sub-anesthetic doses conf 0.95
  • PMID 31579184 — Efficacy of ketamine therapy in the treatment of depression (2019) · in vitro conf 0.90
  • PMID 31617335 — Effects of ketamine on circadian rhythm and synaptic homeostasis in patients with treatment‐resistant depression: A protocol for mechanistic studies of its rapid and sustained antidepressant actions in humans (2019) · in vitro or in vivo (general) conf 0.95
  • PMID 29722313 — Ketamine enhances structural plasticity in human dopaminergic neurons: possible relevance for treatment-resistant depression (2018) · as non-competitive antagonist conf 0.90

B→C papers (1)

  • PMID 33467407 — Delayed Onset Muscle Soreness (DOMS): The Repeated Bout Effect and Chemotherapy-Induced Axonopathy May Help Explain the Dying-Back Mechanism in Amyotrophic Lateral Sclerosis and Other Neurodegenerative Diseases (2021) · in DOMS and ALS according to gate control theory conf 0.60

Clinical trials

0 registered trials for ketamine in pain

Source: ClinicalTrials.gov

No registered trials found on ClinicalTrials.gov. This could indicate either an unexplored indication or a gap in registry coverage.

Search ClinicalTrials.gov →

Provenance trace

Full audit trail of how this hypothesis was generated: source papers, extracted claims, bridging logic, embedding model, and scoring. Every step is recorded and reproducible.

Provenance trace not available for hypothesis 5385.

The drug — ketamine

Source domain: Depression · entity type: drug

The mediator — NMDA receptor

Entity type: protein

The outcome — pain

Target domain: ALS · entity type: phenotype

Evidence

Limited evidence base in our current extraction. Treat this hypothesis as a starting point for further literature review, not a settled conclusion.

A → B evidence: ketamine inhibits NMDA receptor

  • PMID 41765199 Ketamine pharmacotherapy for major depressive disorder: A narrative review (2026)
  • PMID 41656677 Comparative Efficacy and Safety of Ketamine Versus Midazolam for Suicidality: A GRADE‐Assessed Systematic Review and Meta‐Analysis of Randomized Controlled Trials (2026)
  • PMID 41690063 Ketamine combined with psychotherapy for treatment-resistant depression: Real-world outcomes and the role of subjective experience (2026)
  • PMID 35783539 Ketamine use disorder: preclinical, clinical, and neuroimaging evidence to support proposed mechanisms of actions (2022)
  • PMID 32209965 Ketamine in Major Depressive Disorder: Mechanisms and Future Perspectives (2020)
  • PMID 31579184 Efficacy of ketamine therapy in the treatment of depression (2019)
  • PMID 31617335 Effects of ketamine on circadian rhythm and synaptic homeostasis in patients with treatment‐resistant depression: A protocol for mechanistic studies of its rapid and sustained antidepressant actions in humans (2019)
  • PMID 29722313 Ketamine enhances structural plasticity in human dopaminergic neurons: possible relevance for treatment-resistant depression (2018)

B → C evidence: NMDA receptor associated with pain

  • PMID 33467407 Delayed Onset Muscle Soreness (DOMS): The Repeated Bout Effect and Chemotherapy-Induced Axonopathy May Help Explain the Dying-Back Mechanism in Amyotrophic Lateral Sclerosis and Other Neurodegenerative Diseases (2021)

References

All PMID-linked papers cited in the evidence network above, deduplicated and sorted by publication year.

  1. PMID 41765199 Ketamine pharmacotherapy for major depressive disorder: A narrative review (2026) A→B
  2. PMID 41656677 Comparative Efficacy and Safety of Ketamine Versus Midazolam for Suicidality: A GRADE‐Assessed Systematic Review and Meta‐Analysis of Randomized Controlled Trials (2026) A→B
  3. PMID 41690063 Ketamine combined with psychotherapy for treatment-resistant depression: Real-world outcomes and the role of subjective experience (2026) A→B
  4. PMID 35783539 Ketamine use disorder: preclinical, clinical, and neuroimaging evidence to support proposed mechanisms of actions (2022) A→B
  5. PMID 33467407 Delayed Onset Muscle Soreness (DOMS): The Repeated Bout Effect and Chemotherapy-Induced Axonopathy May Help Explain the Dying-Back Mechanism in Amyotrophic Lateral Sclerosis and Other Neurodegenerative Diseases (2021) B→C
  6. PMID 32209965 Ketamine in Major Depressive Disorder: Mechanisms and Future Perspectives (2020) A→B
  7. PMID 31579184 Efficacy of ketamine therapy in the treatment of depression (2019) A→B
  8. PMID 31617335 Effects of ketamine on circadian rhythm and synaptic homeostasis in patients with treatment‐resistant depression: A protocol for mechanistic studies of its rapid and sustained antidepressant actions in humans (2019) A→B
  9. PMID 29722313 Ketamine enhances structural plasticity in human dopaminergic neurons: possible relevance for treatment-resistant depression (2018) A→B

Limitations & disclaimer

This hypothesis was generated algorithmically through cross-domain literature analysis and has not been experimentally validated. Treat it as a starting point for further investigation, not a therapeutic recommendation. For established knowledge about each entity, refer to the authoritative sources linked above (Wikipedia, DrugBank, UniProt, MeSH).