Evidence map›Paper›PMID 42090839›Full record

ArticleDrug and alcohol dependence2026

GHSR antagonist LEAP2 concentrations negatively correlate with alcohol craving and are modulated by alcohol exposure: Evidence from human and rat studies.

Andras H Leko, Mehdi Farokhnia, Elizabeth H Tressler, Janaina C M Vendruscolo, Lindsay A Kryszak, Shelley N Jackson, Lisa A Farinelli, Olivia Jennings, Zhihong Yang, Carolina L Haass-Koffler and 3 more

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In one paragraph

Article in Drug and alcohol dependence, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

13 authors.

Andras H LekoClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA; National Institute on Alcohol Abuse and Alcoholism, Division of Intramural Clinical and Biological Research, National Institutes of Health, Bethesda, MD, USA; Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary.
Mehdi FarokhniaClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA; National Institute on Alcohol Abuse and Alcoholism, Division of Intramural Clinical and Biological Research, National Institutes of Health, Bethesda, MD, USA; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Elizabeth H TresslerClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA; National Institute on Alcohol Abuse and Alcoholism, Division of Intramural Clinical and Biological Research, National Institutes of Health, Bethesda, MD, USA; Stress and Addiction Neuroscience Unit, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA; Neurobiology of Addiction Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
Janaina C M VendruscoloNeurobiology of Addiction Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
Lindsay A KryszakTranslational Analytical Core, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
Shelley N JacksonTranslational Analytical Core, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
Lisa A FarinelliOffice of the Clinical Director, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
Olivia JenningsClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA; National Institute on Alcohol Abuse and Alcoholism, Division of Intramural Clinical and Biological Research, National Institutes of Health, Bethesda, MD, USA.
Zhihong YangDivision of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Carolina L Haass-KofflerCenter for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, School of Public Health, Brown University, Providence, RI, USA; Department of Psychiatry and Human Behavior, The Warren Alpert Medical School, Brown University, Providence, RI, USA; Carney Institute for Brain Science, Brown University, Providence, RI, USA.
Leandro F VendruscoloNational Institute on Alcohol Abuse and Alcoholism, Division of Intramural Clinical and Biological Research, National Institutes of Health, Bethesda, MD, USA; Stress and Addiction Neuroscience Unit, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
Suthat LiangpunsakulDivision of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, ID, USA; Roudebush Veterans Administration Medical Center, Indianapolis, ID, USA.
Lorenzo LeggioClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA; National Institute on Alcohol Abuse and Alcoholism, Division of Intramural Clinical and Biological Research, National Institutes of Health, Bethesda, MD, USA; Translational Analytical Core, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA; Office of the Clinical Director, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA; Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, School of Public Health, Brown University, Providence, RI, USA; Division of Addiction Medicine, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA. Electronic address: lorenzo.leggio@nih.gov.

Funding

Clinical Psychoneuroendocrinology and Neuropsychopharmacology (CPN)ZIADA000635 · NATIONAL INSTITUTE ON DRUG ABUSE · 2025 to 2025
$2.7M
Intramural NIH HHS ZIA DA000635
6 · The paper itself

Abstract

backgroundDespite its clinical significance, pharmacological treatment options for alcohol use disorder (AUD) remained limited, which highlights the need for novel therapeutic targets. The ghrelin system has emerged as an important regulator of alcohol craving and intake. Liver-expressed antimicrobial peptide 2 (LEAP2) has recently been identified as an endogenous ghrelin receptor (GHSR) antagonist that influences metabolic and reward-related pathways.

methodsAs a secondary analysis of five different clinical trials, we measured LEAP2 concentrations in the collected blood samples and examined their association with alcohol craving and the effects of both acute and chronic alcohol use on LEAP2. In addition, we complemented these clinical trial analyses by conducting preclinical experiments in wild-type and GHSR-KO Wistar rats to investigate the effects of alcohol and ghrelin on LEAP2 concentrations.

resultsIn humans, LEAP2 concentrations negatively correlated with both priming- and cue-induced alcohol craving. Acute alcohol administration reduced LEAP2 concentrations 90min after oral alcohol intake, a response that was attenuated by co-administration of the GHSR inverse agonist PF-5190457. An intraperitoneal alcohol administration after a pre-treatment with ghrelin reduced LEAP2 concentrations in wild-type but not GHSR-KO Wistar rats. In contrast to acute alcohol administration, LEAP2 concentrations did not differ between people with alcohol use disorder and healthy controls and were unaffected by evidence of hepatocyte injury and alcohol abstinence.

conclusionsThese results enhance our understanding of the ghrelin system, particularly LEAP2, with regard to alcohol craving and consumption. This work may inform the development of novel interventions for alcohol use disorder.

Indexed as

Alcohol DrinkingAlcoholismAntimicrobial Cationic PeptidesCravingEthanolReceptors, GhrelinAdultAnimalsAzetidinesBlood ProteinsFemaleGhrelinHumansMaleMiddle AgedRatsAntimicrobial Cationic PeptidesAzetidinesBlood ProteinsEthanolGhrelinliver-expressed antimicrobial peptide 2, humanPF-5190457Receptors, GhrelinSpiro CompoundsAlcohol Use DisorderCravingEndocrinologyGhrelinGut-Brain AxisLiver-expressed antimicrobial peptide 2Psychoneuroendocrinology

Identifiers

PMID42090839
PMCPMC13342706

What Socratic holds

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Registered trials

None linked

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 Socratic graph.