The effect of neuroimmune modulation on subjective response to alcohol in the natural environment
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BACKGROUND: Despite the promising implications for novel immune therapeutics, few clinical trials have tested these therapies to date. An understanding of how immune pharmacotherapies influence complex alcohol use disorder (AUD) profiles, including subjective response to alcohol, is very limited. Initial findings show that ibudilast, a neuroimmune modulator, reduces rates of heavy drinking and measures of alcohol craving. METHODS: This study is a secondary analysis of a 2-week clinical trial of ibudilast that enrolled a nontreatment-seeking sample with AUD. Eligible participants (N = 52) were randomized to receive ibudilast or matched placebo and completed daily diary assessments (DDAs) during the 2-week period. Each morning, participants reported on their mood and craving levels both before and during the previous day's drinking episode, as well as stimulation and sedation levels during the previous day's drinking episode. Multilevel models were used to compare the effects of ibudilast and placebo on subjective alcohol response. Exploratory analyses tested whether ibudilast moderated the relationship between daily stimulation/sedation and alcohol intake and whether withdrawal-related dysphoria moderated ibudilast's effects on subjective response. RESULTS: Ibudilast did not significantly alter mean levels of stimulation or sedation (p's > 0.05). It did, however, moderate the effect of daily stimulation on drinking (p = 0.045). Ibudilast attenuated alcohol-induced increases in craving compared with placebo (p = 0.047), but not other subjective response measures. Ibudilast significantly tempered daily alcohol-induced changes in urge to drink and positive mood only among individuals without withdrawal-related dysphoria. CONCLUSIONS: Ibudilast's effects on subjective alcohol responses appear to be nuanced and perhaps most salient for individuals drinking for positive reinforcement as distinguished from those who drink to feel normal. Consistent with previous findings, reductions in alcohol craving may represent a primary mechanism of ibudilast's effects on drinking. The ecologically valid nature of DDAs provide a clinically useful window into how individuals experience alcohol's effects while taking ibudilast.
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In an RCT of 52 patients, ibudilast did not significantly impact stimulation or sedation levels but moderated the influence of daily stimulation on drinking and reduced alcohol-induced cravings, particularly in individuals without withdrawal-related dysphoria.
“While ibudilast did not significantly impact stimulation or sedation levels, it did moderate the influence of daily stimulation on drinking. Additionally, it reduced alcohol-induced cravings, particularly in individuals without withdrawal-related dysphoria, where it also tempered changes in the urge to drink and positive mood [41].”
From A Narrative Review of Current and Emerging Trends in the Treatment of Alcohol Use Disorder (2024) · cites this paper as [41]
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Self-citation
- Authors
- Meredith, L. R., Grodin, E. N., Montoya, A. K., Miranda, R., Squeglia, L. M., Towns, B., Evans, C., & Ray, L. A.
- Affiliations
- University of California, Los Angeles (US)
- Brown University (US)
- Medical University of South Carolina (US)
- Corresponding author
- Ray, Lara A.
- ORCID
- Venue
- Alcoholism: Clinical and Experimental Research
- Publisher
- Wiley
- Published
- 2022-04-11
- Volume
- 46
- Issue
- 5
- Pages
- 876-890
- ISSN
- 0145-6008 (ISSN-L)
- 1530-0277
- PMC
- PMC10460619
- OpenAlex
- W4220995211
- Cited by
- 12
- References
- 78
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 3 · 2022: 1
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alcoholism Clinical and Experimental Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (F32AA027699, K24AA025704)
- National Institute on Drug Abuse (P50 DA005010‐33)
- Topics
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- ibudilast, neuroimmunomodulation, alcoholism, subjective response to alcohol, alcohol craving, positive mood
- MeSH terms
- Affect, Alcohol Drinking, Ethanol, Alcoholism, Humans, Craving
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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