ArticleThe Journal of clinical investigation2019
Opioid-galanin receptor heteromers mediate the dopaminergic effects of opioids.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02941809 (Open-labeled Dose-extending Placebos as an Adjunct to Methadone Treatment), which is not on this map. Cited by 44 papers, 1 of them a synthesis 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.
Open-labeled Dose-extending Placebos as an Adjunct to Methadone Treatment: A Pilot Study
Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
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- OPRM1/MRGPRX1 heterodimers drive opioid-induced itch through a peripheral mechanism.Journal of biomedical science · 2026Article
- Galanin Receptors: G Protein-Dependent Signaling and Beyond.Biomolecules · 2026Review
- Early socially isolated rats of both sexes reduce alcohol consumption and seeking by the Galanin (1-15) and naltrexone combination.Frontiers in pharmacology · 2026Article
- Levomethadone Selectively Reduces Emotional Impulsivity in ASRS-Positive ADHD-OUD Patients, Independent of Dose Escalation.Journal of clinical medicine · 2025Article
- Association of Galanin and Its Receptor Gene Polymorphism with Opioid Dependence: Preliminary Findings from India.Indian journal of psychological medicine · 2025Article
- Methadone and morphine have equivalent analgesic but not reward potency in female mice.Addiction neuroscience · 2025Article
- Functional significance of opioid receptor homomers and heteromers.Nature communications · 2025Article
- Distinctive biochemical properties of the μ-opioid receptor-corticotropin- releasing factor CRFPharmacological research · 2025Article
- Development of a HiBiT Peptide-Based NanoBRET Ligand Binding Assay for Galanin Receptor 1 in Live Cells.ACS chemical biology · 2025Article
- Reply to "Letter to the Editor regarding 'Unique pharmacodynamic properties and low abuse liability of the μ-opioid receptor ligand (S)-methadone'".Molecular psychiatry · 2025Article
- Mu opioid receptor activation in microglia enhances HIV-1 infection and HIV-infection-induced inflammatory responses.Frontiers in immunology · 2025Article
- A Comprehensive Collection of Pain and Opioid Use Disorder Compounds for High-Throughput Screening and Artificial Intelligence-Driven Drug Discovery.ACS pharmacology & translational science · 2024Article
- Genetic or pharmacological GHSR blockade has sexually dimorphic effects in rodents on a high-fat diet.Communications biology · 2024Article
- Unique pharmacodynamic properties and low abuse liability of the µ-opioid receptor ligand (S)-methadone.Molecular psychiatry · 2024Article
- In Vitro Functional Profiling of Fentanyl and Nitazene Analogs at the μ-Opioid Receptor Reveals High Efficacy for Gi Protein Signaling.ACS chemical neuroscience · 2024Article
- Article
- Alkoxy chain length governs the potency of 2-benzylbenzimidazole 'nitazene' opioids associated with human overdose.Psychopharmacology · 2023Article
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Authors and funding
26 authors at 8 institutions in 4 countries.
Funding
Abstract
Identifying non-addictive opioid medications is a high priority in medical sciences, but μ-opioid receptors mediate both the analgesic and addictive effects of opioids. We found a significant pharmacodynamic difference between morphine and methadone that is determined entirely by heteromerization of μ-opioid receptors with galanin Gal1 receptors, rendering a profound decrease in the potency of methadone. This was explained by methadone's weaker proficiency to activate the dopaminergic system as compared to morphine and predicted a dissociation of therapeutic versus euphoric effects of methadone, which was corroborated by a significantly lower incidence of self-report of "high" in methadone-maintained patients. These results suggest that μ-opioid-Gal1 receptor heteromers mediate the dopaminergic effects of opioids that may lead to a lower addictive liability of opioids with selective low potency for the μ-opioid-Gal1 receptor heteromer, exemplified by methadone.
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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.