"New drug in the town": Ibudilast for booze dependence.

Alcohol use disorder (AUD) is a chronic relapsing disorder with a major public health impact. Ibudilast, a neuroimmune modulator which selectively inhibits phosphodiesterases (PDE)-3, -4, -10, and -11, and macrophage migration inhibitory factor (MIF), shows promise as a novel pharmacotherapy for alcohol use disorder (AUD) in a recent study published in Translational Psychiatry Journal.

Grodin et al examined the efficacy of ibudilast to improve negative mood, reduce heavy drinking, and attenuate neural reward signals in individuals with AUD. Their findings extend preclinical and human laboratory studies of the utility of ibudilast to treat AUD and suggest a biobehavioral mechanism through which ibudilast acts by reducing the rewarding response to alcohol cues in the brain leading to a reduction in heavy drinking.

Alcohol use disorder (AUD) is a chronic relapsing disorder with a major public health impact. Over 14 million adults in the United States have an AUD; however, only 8% of adults with current AUD received treatment.

Only four pharmacotherapies are currently approved by the FDA for the treatment of AUD, - disulfiram (Antabuse), acamprosate, oral naltrexone, and extended-release injectable naltrexone. These medications are only modestly effective. Therefore, there is a clear need to develop more efficacious treatments, particularly those with novel molecular targets. To that end, the modulation of neuroimmune signaling is a promising AUD treatment target.

This was a 2-week clinical study of ibudilast for negative mood improvement and drinking reduction in non-treatment-seeking individuals with an AUD. Eligible participant were randomized to ibudilast or matched placebo. Participants completed three in-person visits and daily online diary assessments to report on their drinking, craving, and mood from the previous day.

Fifty-two nontreatment-seeking individuals with AUD were randomized to receive ibudilast (n = 24) or placebo (n = 28). Participants completed a 2-week daily diary study during which they filled out daily reports of their past day drinking, mood, and craving. Participants completed a functional magnetic resonance imaging (fMRI) alcohol cue-reactivity paradigm half-way through the study.

It was found that, ibudilast did not have a significant effect on negative mood on drinking or non-drinking days. However, ibudilast significantly reduced the probability of heavy drinking compared to placebo.

Ibudilast also significantly attenuated alcohol cue-elicited activation in the bilateral ventral striatum. Regarding the drinking outcomes in this study, IBUD significantly reduced the probability of heavy drinking compared to placebo. Specifically, individuals treated with IBUD were 45.3% less likely (OR = 0.547) to drink heavily compared to individuals treated with placebo. Importantly, the drinking results combined with the adverse effects report indicate that ibudilast is a safe medication for individuals who are still drinking and may want to reduce their drinking. IBUD also reduced craving on non-drinking days, at trend level, as compared to placebo.

In conclusion, Ibudilast did not have a significant effect on negative mood. However, ibudilast, relative to placebo, reduced the odds of heavy drinking across time by 45%. Ibudilast also attenuated alcohol cue-elicited activation in the ventral striatum (VS) compared to placebo, such that individuals who had attenuated ventral striatal activation and took ibudilast had the fewest number of drinks per drinking day in the week following the scan. 

Source: Translational Psychiatry (2021) 11:355 ; https://doi.org/10.1038/s41398-021-01478-5