Effects of ibudilast on central and peripheral markers of inflammation in alcohol use disorder: A randomized clinical trial
Open accessAbstract
Ibudilast, a neuroimmune modulator, shows promise as a pharmacotherapy for alcohol use disorder (AUD). In vivo administration of ibudilast reduces the expression of pro‐inflammatory cytokines in animal models, but its effects on markers of inflammation in humans are unknown. This preliminary study examined the effect of ibudilast on peripheral and potential central markers of inflammation in individuals with AUD. This study also explored the predictive relationship of neurometabolite markers with subsequent drinking in the trial. Non‐treatment‐seeking individuals with an AUD (n = 52) were randomized to receive oral ibudilast (n = 24) or placebo (n = 28) for 2 weeks. Plasma levels of peripheral inflammatory markers were measured at baseline and after 1 and 2 weeks of medication. At study mid‐point, proton magnetic resonance spectroscopy was performed to measure potential neurometabolite markers of inflammation: choline‐compounds (Cho),myo‐inositol (MI) and creatine + phosphocreatine (Cr) in frontal and cingulate cortices from 43 participants (ibudilast:n = 20; placebo:n = 23). The treatment groups were compared on peripheral and central markers. Ibudilast‐treated participants had lower Cho in superior frontal white matter and nominally lower MI in pregenual anterior cingulate cortex. Ibudilast‐treated participants had nominally lower C‐reactive protein levels at visit 2 and nominally lower TNF‐α/IL‐10 ratios, relative to placebo. C‐reactive protein and Cho levels were correlated, controlling for medication. Superior frontal white matter Cho predicted drinking in the following week. Micro‐longitudinal ibudilast treatment may induce peripheral and putative central anti‐inflammatory responses in patients with AUD. The neurometabolite responses may be associated with reduction in drinking, suggesting an anti‐inflammatory component to the therapeutic action of ibudilast.
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In an RCT, the ibudilast group exhibited lower inflammation markers in their brains and bodies.
“The ibudilast group exhibited lower inflammation markers in their brains and bodies.”
From A Narrative Review of Current and Emerging Trends in the Treatment of Alcohol Use Disorder (2024) · cites this paper as [87]
The Results (MRS Metabolites; Inflammatory Markers) report lower levels of a putative brain inflammation marker in the ibudilast group and lower levels of two peripheral markers relative to placebo. The claim omits that the peripheral differences were only trend-level and that the brain measures were putative markers of inflammation; the Discussion also says the peripheral findings were not consistent across all markers. (LLM, conf=0.85)
Experimental — accuracy not yet measuredIn that RCT, a link was observed between C-reactive protein and choline compound (Cho) levels, and Cho levels in the brain predicted drinking behavior in the following week.
“Interestingly, a link was observed between C-reactive protein and choline compound (Cho) levels, and Cho levels in the brain predicted drinking behavior in the following week”
From A Narrative Review of Current and Emerging Trends in the Treatment of Alcohol Use Disorder (2024) · cites this paper as [87]
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A Narrative Review of Current and Emerging Trends in the Treatment of Alcohol Use Disorder
Celik, M., Gold, M. S., & Fuehrlein, B. (2024) · Brain Sciences · doi:10.3390/brainsci14030294 · Cited by 25 · see citing works
- Authors
- Grodin, E. N., Nieto, S. J., Meredith, L. R., Burnette, E., O'Neill, J., Alger, J., London, E. D., Miotto, K., Evans, C. J., Irwin, M. R., & Ray, L. A.
- Affiliations
- University of California, Los Angeles (US)
- Jane and Terry Semel Institute for Neuroscience and Human Behavior University of California Los Angeles California USA
- Corresponding author
- Ray, Lara A.
- ORCID
- Venue
- Addiction Biology
- Publisher
- Wiley
- Published
- 2022-05-11
- Volume
- 27
- Issue
- 4
- Pages
- e13182-e13182
- ISSN
- 1355-6215 (ISSN-L)
- 1369-1600
- PMC
- PMC9888600
- OpenAlex
- W4280653262
- Cited by
- 25
- References
- 72
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 7 · 2023: 5 · 2022: 1
- FWCI
- 3.97
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Addiction Biology (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 › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- ibudilast, alcoholism, neuroimmunomodulation, inflammation, C-reactive protein, TNF-α/IL-10 ratio, choline-containing compounds, myo-inositol, creatine, frontal white matter, anterior cingulate cortex, neurometabolites, drinking behavior, anti-inflammatory pharmacotherapy
- MeSH terms
- Alcohol Drinking, Alcoholism, Animals, Aspartic Acid, C-Reactive Protein, Choline, Creatine, Humans, Indolizines, Inflammation, Inositol, Pyrazoles, Pyridines
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