The Effect of Neuroimmune Modulation on Subjective Response to Alcohol in the Natural Environment

Background: Despite the promising implications for novel immune therapeutics, few clinical trials have tested these therapies to date. An understanding of how immune pharmacotherapies influence complex alcohol use disorder (AUD) profiles, including subjective response to alcohol, is very limited. Initial findings show that ibudilast, a neuroimmune modulator, reduces rates of heavy drinking and measures of alcohol craving.

Methods: This study is a secondary analysis of a 2-week clinical trial of ibudilast that enrolled a nontreatment-seeking sample with AUD. Eligible participants (N = 52) were randomized to receive ibudilast or matched placebo and completed daily diary assessments (DDAs) during the 2-week period. Each morning, participants reported on their mood and craving levels both before and during the previous day's drinking episode, as well as stimulation and sedation levels during the previous day's drinking episode. Multilevel models were used to compare the effects of ibudilast and placebo on subjective alcohol response. Exploratory analyses tested whether ibudilast moderated the relationship between daily stimulation/sedation and alcohol intake and whether withdrawal-related dysphoria moderated ibudilast's effects on subjective response.

Results: Ibudilast did not significantly alter mean levels of stimulation or sedation (p's > 0.05). It did, however, moderate the effect of daily stimulation on drinking (p = 0.045). Ibudilast attenuated alcohol-induced increases in craving compared with placebo (p = 0.047), but not other subjective response measures. Ibudilast significantly tempered daily alcohol-induced changes in urge to drink and positive mood only among individuals without withdrawal-related dysphoria.

Conclusions: Ibudilast's effects on subjective alcohol responses appear to be nuanced and perhaps most salient for individuals drinking for positive reinforcement as distinguished from those who drink to feel normal. Consistent with previous findings, reductions in alcohol craving may represent a primary mechanism of ibudilast's effects on drinking. The ecologically valid nature of DDAs provide a clinically useful window into how individuals experience alcohol's effects while taking ibudilast.