Evidence map›Paper›PMID 41535481›Full record

ArticleCommunications medicine2026

Nalmefene and naltrexone reduce alcohol intake via selective efficacy in subpopulations distinguished by behavioral and blood-based biomarkers.

Zahra Z Farahbakhsh, Alex R Brown, Suzanne O Nolan, Snigdha Mukerjee, Cody A Siciliano

Abstract read
In one paragraph

Article in Communications medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–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

1 citing paper in PubMed.

  1. Review
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.

Zahra Z Farahbakhsh *Vanderbilt University, Department of Pharmacology, Vanderbilt Brain Institute, Vanderbilt Center for Addiction Research, Nashville, TN, USA.
Alex R Brown *Vanderbilt University, Department of Pharmacology, Vanderbilt Brain Institute, Vanderbilt Center for Addiction Research, Nashville, TN, USA.ORCID http://orcid.org/0000-0001-8585-5953
Suzanne O NolanVanderbilt University, Department of Pharmacology, Vanderbilt Brain Institute, Vanderbilt Center for Addiction Research, Nashville, TN, USA.
Snigdha MukerjeeVanderbilt University, Department of Pharmacology, Vanderbilt Brain Institute, Vanderbilt Center for Addiction Research, Nashville, TN, USA.
Cody A SicilianoVanderbilt University, Department of Pharmacology, Vanderbilt Brain Institute, Vanderbilt Center for Addiction Research, Nashville, TN, USA. Cody.Siciliano@Vanderbilt.Edu.ORCID http://orcid.org/0000-0001-9871-2089

Funding

Training in Fundamental NeuroscienceT32MH064913 · NIMH · VANDERBILT UNIVERSITY · PI IHRIE, REBECCA A, WINDER, DANNY G. · 2001 to 2022
$7.6M
VAREC Research CoreP60AA031124 · NIAAA · VANDERBILT UNIVERSITY · PI Erin Calipari · 2024 to 2026
$7.1M
Mesocortical neuromodulation in punishment-resistant alcohol drinkingR01AA030115 · NIAAA · VANDERBILT UNIVERSITY · PI Cody Siciliano · 2022 to 2026
$2.1M
8/8: INIA Stress and Chronic Alcohol Interactions: Cross-species plasticity signatures of alcohol and stressU01AA029971 · NIAAA · VANDERBILT UNIVERSITY · PI Cody Siciliano · 2022 to 2026
$2.0M
Defining the role of compartment-specific dopamine dynamics in reinforcement learningF32DA051136 · NIDA · VANDERBILT UNIVERSITY · PI NOLAN, SUZANNE OLIVIA · 2020 to 2022
$136k
Role of the kappa opioid receptor system in learning and substance use disordersF31DA056196 · NIDA · VANDERBILT UNIVERSITY · PI FARAHBAKHSH, ZAHRA · 2023 to 2024
$56k
NIAAA NIH HHS P60 AA031124NIAAA NIH HHS R01 AA030115NIAAA NIH HHS U01 AA029971NIDA NIH HHS F31 DA056196NIDA NIH HHS F32 DA051136NIMH NIH HHS T32 MH064913U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) MH064913U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA) AA029971U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA) AA030115U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA) AA031124U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) DA051136U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) DA056196
6 · The paper itself

Abstract

backgroundThe relative efficacies of nalmefene versus naltrexone for alcohol use disorder is the subject of intense and ongoing debate. The two pan-opioid receptor ligands differ primarily in actions at the kappa opioid receptor, where naltrexone acts as an antagonist and nalmefene acts as a partial agonist. Parallel clinical trials for nalmefene or naltrexone have produced widely disparate outcomes and a marked lack of consensus regarding which of the compounds should be used for the treatment of alcohol use disorder.

methodsHere we leveraged a mouse model (n = 56 male C57BL/6 J) to directly compare the efficacy of nalmefene and naltrexone within-subject. After acquiring operant responding for ethanol, each subject underwent four treatment block conditions: nalmefene (0.1 mg/kg i.p.), naltrexone (1.0 mg/kg i.p.), the selective kappa opioid receptor agonist U50,488 (1.0 mg/kg i.p.) and placebo (saline 10 ml/kg i.p.). Each treatment block consisted of an ethanol self-administration session followed by two subsequent sessions of punished (quinine adulterated) ethanol self-administration sessions with treatment given 30 min prior to each session.

resultsWe show that nalmefene and naltrexone have similar efficacy in reducing ethanol consumption, whereas U50,488 increases ethanol consumption. Despite similar effects in aggregate analyses, nalmefene- and naltrexone-induced reductions in drinking are driven by fully separate subpopulations which do not show any beneficial response to the non-preferred compound and display markedly different behavioral phenotypes prior to treatment. A predictive model based on circulating biogenic amines allows for high accuracy classification of nalmefene- versus naltrexone-responders.

conclusionTogether, these results provide a roadmap for improving alcohol use disorder treatment outcomes via precision application of existing compounds.

Identifiers

PMID41535481
PMCPMC12894949

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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.