Ibudilast attenuates alcohol cue-elicited frontostriatal functional connectivity in alcohol use disorder

Alcohol Clin Exp Res. 2021 Oct;45(10):2017-2028. doi: 10.1111/acer.14696. Epub 2021 Sep 29.


Background: Ibudilast, a novel neuroimmune modulator being studied to treat alcohol use disorder (AUD), was shown in a randomized controlled trial (NCT03489850) to reduce ventral striatum (VS) activation in response to visual alcohol cues. The present study extended this finding by probing the effects of ibudilast on alcohol cue-elicited functional connectivity (i.e., temporally correlated activation) with the VS seed. The study also tests the association between functional connectivity and alcohol use during the trial.

Methods: Non-treatment-seeking participants (n = 45) with current alcohol use disorder were randomized to receive twice-daily dosing with either ibudilast (50 mg; n = 20) or placebo (n = 25). Upon reaching the target dosagee of the medication or placebo, participants completed a functional neuroimaging alcohol cue reactivity paradigm. Drinks per drinking day were assessed at baseline and daily during the 2-week trial.

Results: Ibudilast reduced alcohol cue-elicited functional connectivity between the VS seed and reward-processing regions including the orbitofrontal and anterior cingulate cortices compared with placebo (p < 0.05). Cue-elicited functional connectivity was correlated with drinks per drinking day (R2 = 0.5351, p < 0.001), and ibudilast reduced this association in similar reward-processing regions compared with placebo.

Conclusions: Ibudilast's effects on drinking outcomes may be related to the attenuation of functional connectivity in frontostriatal circuits related to reward processing. These results provide an important proof of concept for this novel pharmacotherapy and support the clinical utility of incorporating neuroimaging-and especially functional connectivity-analyses into medication development.

Keywords: AUD; fMRI; functional connectivity; ibudilast.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Alcoholism / drug therapy*
  • Brain / diagnostic imaging
  • Brain / drug effects*
  • Connectome
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Phosphodiesterase Inhibitors / pharmacology
  • Phosphodiesterase Inhibitors / therapeutic use*
  • Pyridines / pharmacology
  • Pyridines / therapeutic use*
  • Young Adult


  • Phosphodiesterase Inhibitors
  • Pyridines
  • ibudilast

Associated data

  • ClinicalTrials.gov/NCT03489850