Evidence map›Paper›PMID 40451996›Full record

Trial reportAlcohol, clinical & experimental research2025

Inflammatory endotoxin challenge in individuals with alcohol use disorder and controls.

Kaitlin R McManus, Erica N Grodin, Elizabeth Burnette, Yenashi Castillo, Karen Miotto, Michael R Irwin, Naomi Eisenberger, Lara A Ray

Abstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Alcohol, clinical & experimental research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
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

8 authors.

Kaitlin R McManusDepartment of Psychology, University of California, Los Angeles, Los Angeles, California, USA.ORCID https://orcid.org/0000-0002-1594-7796
Erica N GrodinDepartment of Psychology, University of California, Los Angeles, Los Angeles, California, USA.ORCID https://orcid.org/0000-0001-5528-4918
Elizabeth BurnetteNeuroscience Interdepartmental Program, University of California, Los Angeles, Los Angeles, California, USA.
Yenashi CastilloDepartment of Psychology, University of California, Los Angeles, Los Angeles, California, USA.
Karen MiottoDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California, USA.
Michael R IrwinDepartment of Psychology, University of California, Los Angeles, Los Angeles, California, USA.
Naomi EisenbergerDepartment of Psychology, University of California, Los Angeles, Los Angeles, California, USA.
Lara A RayDepartment of Psychology, University of California, Los Angeles, Los Angeles, California, USA.ORCID https://orcid.org/0000-0002-5734-9444

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
Clinical Neuroscience of Alcoholism: Integrating Neuroscience and Clinical TrialsK24AA025704 · NIAAA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LARA A. RAY · 2018 to 2026
$1.3M
Characterizing the Microbiome-Gut-Brain Axis in Individuals with Alcohol Use DisorderK01AA029712 · NIAAA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Erica N Grodin · 2022 to 2026
$819k
Probing Inflammation and Reward Sensitivity in Alcohol Use DisorderF31AA028976 · NIAAA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BURNETTE, ELIZABETH · 2020 to 2022
$103k
Clinical and Translational Science Institute, University of California, Los Angeles UL1TR001881Friends of the Semel Institute Research Scholar ProgramNCATS NIH HHS UL1 TR001881NIAAA NIH HHS F31 AA028976NIAAA NIH HHS F31AA028976NIAAA NIH HHS K01 AA029712NIAAA NIH HHS K01AA029712NIAAA NIH HHS K24 AA025704NIAAA NIH HHS K24AA025704Norman Cousins Center for Psychoneuroimmunology
6 · The paper itself

Abstract

backgroundPreclinical and clinical research reveal associations between chronic alcohol use, increases in proinflammatory cytokines (interleukin [IL]-6, IL-8, tumor necrosis factor alpha [TNF-α]), and increases in alcohol consumption, alcohol craving, and negative mood. However, these findings remain largely correlational in clinical samples. Therefore, we conducted a preliminary inflammatory challenge using endotoxin in individuals with alcohol use disorder (AUD) to investigate the immune, behavioral, and brain responses to the inflammatory challenge.

methodsParticipants were randomly assigned to receive a bolus intravenous injection of either low-dose endotoxin (0.8 ng/kg of body weight) or placebo (same volume of 0.9% saline). Blood samples, sickness symptoms, physiology, mood, and alcohol craving were collected at baseline and hourly for 4 h postbaseline, with a neuroimaging scan occurring at 3 h postbaseline. Matched control data were used to validate the endotoxin challenge in comparison to the AUD sample.

resultsEndotoxin led to an acute blunted pro-inflammatory (i.e., TNF-α, IL-6, and IL-8) response in individuals with AUD compared to controls (all p's < 0.039). Endotoxin led to decreased cue-induced craving in both the behavioral human laboratory (p = 0.03) and neuroimaging (p's < 0.01) assays. Moreover, higher levels of endotoxin-induced IL-6 were most negatively associated with decreased self-reported craving following baseline (p < 0.05) in comparison with lower levels of endotoxin-induced IL-6.

conclusionsThis preliminary study provides an acute experimental manipulation of inflammatory processes associated with AUD and suggests that the short-term effects of inflammation in AUD phenomenology are multifaceted and dose-dependent.

Indexed as

AlcoholismEndotoxinsInflammationAdultCravingFemaleHumansInterleukin-6Interleukin-8MaleMiddle AgedTumor Necrosis Factor-alphaYoung AdultEndotoxinsInterleukin-6Interleukin-8Tumor Necrosis Factor-alphaalcohol cravingalcohol use disordercytokinesendotoxininflammation

Identifiers

PMID40451996
PMCPMC13037421

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

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.