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Effects of ibudilast on central and peripheral markers of inflammation in alcohol use disorder: A randomized clinical trial
- Source :
- Addiction biology, vol 27, iss 4, Addict Biol
- Publication Year :
- 2022
- Publisher :
- eScholarship, University of California, 2022.
-
Abstract
- 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 2weeks 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.
- Subjects :
- Alcohol Drinking
Pyridines
Clinical Trials and Supportive Activities
Medicine (miscellaneous)
alcohol use disorder
Medical and Health Sciences
Article
Oral and gastrointestinal
Choline
Alcohol Use and Health
Substance Misuse
Clinical Research
Behavioral and Social Science
cytokine
Animals
Humans
anti-inflammatory
Pharmacology
Inflammation
Aspartic Acid
Psychology and Cognitive Sciences
Neurosciences
Substance Abuse
Evaluation of treatments and therapeutic interventions
Creatine
magnetic resonance spectroscopy
Brain Disorders
Psychiatry and Mental health
Alcoholism
C-Reactive Protein
Good Health and Well Being
6.1 Pharmaceuticals
Inositol
ibudilast
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Addiction biology, vol 27, iss 4, Addict Biol
- Accession number :
- edsair.doi.dedup.....1665678db566ba1c12769a75c33bbbb0