Trial reportTranslational psychiatry2023
The novel uncompetitive NMDA receptor antagonist esmethadone (REL-1017) has no meaningful abuse potential in recreational drug users.
Trial report in Translational psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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
12 citing papers in PubMed, 18 citations in OpenAlex.
- Novel approaches in depression treatment: from rapid-acting antidepressants to personalized interventions.Molecular psychiatry · 2026Review
- Article
- Cancer neuroscience: signaling pathways and new therapeutic strategies for cancer.Signal transduction and targeted therapy · 2026Review
- New advances in small molecule drugs targeting NMDA receptors.Acta pharmacologica Sinica · 2026Review
- Methadone and morphine have equivalent analgesic but not reward potency in female mice.Addiction neuroscience · 2025Article
- Distinctive biochemical properties of the μ-opioid receptor-corticotropin- releasing factor CRFPharmacological research · 2025Article
- Navigating the intersection of mental health and kidney health: a systematic review of antidepressant safety in renal impairment.Discover mental health · 2025Review
- New Synthesis and Pharmacological Evaluation of Enantiomerically Pure (Journal of medicinal chemistry · 2025Article
- Letter to the Editor regarding 'Unique pharmacodynamic properties and low abuse liability of the µ-opioid receptor ligand (S)-methadone'.Molecular psychiatry · 2024Article
- N-methyl-D-aspartate Receptors and Depression: Linking Psychopharmacology, Pathology and Physiology in a Unifying Hypothesis for the Epigenetic Code of Neural Plasticity.Pharmaceuticals (Basel, Switzerland) · 2024Review
- NMDA Receptor Antagonists: Emerging Insights into Molecular Mechanisms and Clinical Applications in Neurological Disorders.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Sex-dependent effects of the uncompetitive N-methyl-D-aspartate receptor antagonist REL-1017 in G93A-SOD1 amyotrophic lateral sclerosis mice.Frontiers in neurology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Esmethadone (REL-1017) is the opioid-inactive dextro-isomer of methadone and a low-affinity, low-potency uncompetitive NMDA receptor antagonist. In a Phase 2, randomized, double-blind, placebo-controlled trial, esmethadone showed rapid, robust, and sustained antidepressant effects. Two studies were conducted to evaluate the abuse potential of esmethadone. Each study utilized a randomized, double-blind, active-, and placebo-controlled crossover design to assess esmethadone compared with oxycodone (Oxycodone Study) or ketamine (Ketamine Study) in healthy recreational drug users. Esmethadone 25 mg (proposed therapeutic daily dose), 75 mg (loading dose), and 150 mg (Maximum Tolerated Dose) were evaluated in each study. Positive controls were oral oxycodone 40 mg and intravenous ketamine 0.5 mg/kg infused over 40 min. The Ketamine study included oral dextromethorphan 300 mg as an exploratory comparator. The primary endpoint was maximum effect (E
Indexed as
Identifiers
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.