Neuroinflammation is implicated in the development and maintenance of alcohol use disorder (AUD) and neuroimmune therapeutics show promise in treating AUD. Proinflammatory signaling contributes to progressive elevations in the dysfunction of mood and alcohol craving. The current study sought to examine potential biobehavioral mechanisms of neuroimmune modulation in AUD under experimental conditions. In a community sample of individuals with AUD who completed a placebo-controlled crossover trial of ibudilast, we tested the effect of ibudilast on the relationship between mood states and alcohol craving. Multilevel modeling analyses tested the hypothesis that ibudilast would moderate the effect of positive and negative mood states on alcohol craving during stress and cue exposures. Results revealed that after stress-induction, participants’ feelings of depression and happiness were more strongly predictive of their craving for alcohol while taking ibudilast as compared with placebo (ps<. 03). These results suggest that with neuroimmune modulation, positive and negative mood states may have a stronger influence on one’s desire to drink, such that craving may be more mood dependent. No moderating effect of ibudilast on mood states and craving were observed after alcohol cue exposure. Given the potential of anti-inflammatory treatments to reduce depressive symptomatology, this strengthened relationship between mood and craving under ibudilast might reduce the likelihood of stress-related craving and subsequent drinking over time. Moreover, ibudilast may enhance the benefits of happiness, such that maintaining positive mood in the face of acute stress may attenuate craving. Future trials directly testing the clinical implications of these mechanistic findings are warranted.(PsycInfo Database Record (c) 2022 APA, all rights reserved)