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.