Effect of N‐acetylcysteine on neural alcohol cue reactivity and craving in adolescents who drink heavily: A preliminary randomized clinical trial

Abstract

AbstractBackgroundAlcohol craving is related to problematic alcohol use; therefore, pharmacotherapies that modulate alcohol craving are of interest. N‐acetylcysteine, an over‐the‐counter antioxidant, is a candidate pharmacotherapy for adolescent alcohol use with the potential to impact craving. Cue‐reactivity paradigms using functional magnetic resonance imaging (fMRI) can identify neural regions implicated in craving and serve as a screening tool for novel pharmacotherapy options.MethodsThis preliminary study examined the effect of N‐acetylcysteine on neural reactivity to alcohol cues and subjective craving among 31 non‐treatment‐seeking adolescents (17.6–19.9 years old, 55% female) who use alcohol heavily. In a randomized cross‐over design, participants completed three fMRI sessions: baseline and after a 10‐day course of N‐acetylcysteine (1200 mg twice daily) and matched placebo. The primary outcome was neural response to alcohol versus non‐alcohol beverage cues after N‐acetylcysteine versus placebo, with a secondary outcome of self‐reported subjective craving.ResultsIn the full sample (n = 31), there was no effect of N‐acetylcysteine versus placebo on neural alcohol reactivity (ps ≥ 0.49; s = 0.00–0.07) or self‐reported acute alcohol craving (p = 0.18,  = 0.06). However, N‐acetylcysteine did reduce self‐reported generalized alcohol craving (p = 0.03,  = 0.15). In a subsample of youth who met criteria for past‐year alcohol use disorder (n = 19), results remained unchanged.ConclusionsN‐acetylcysteine may not alter neural reactivity to alcohol cues or acute craving; however, it may reduce general subjective alcohol craving among adolescents who consume alcohol heavily.