Oxytocin increases neural cue-reactivity but modulates cue-induced craving differently in males and females with alcohol use disorder - results of a randomized controlled cross-over trial

BackgroundCraving and altered reactivity to alcohol cues are central features of alcohol use disorder (AUD). Approved medications yield only limited effects on these facets. Oxytocin (OXY) might be a promising candidate, due to its anti-craving effects. MethodsWe conducted a randomized double-blind placebo-controlled crossover study to investigate the effects of 24 IU intranasal OXY compared to a matched Placebo (PLC) on the neural response to alcohol stimuli (primary outcome) and cue-induced alcohol craving (secondary outcome) in a validated functional magnetic resonance imaging cue-reactivity task in N=24 individuals with AUD. ResultsOXY compared to PLC increased alcohol cue-induced activation in parts of the frontal gyrus, supplementary motor area, hippocampus, parts of the temporal gyrus, fusiform gyrus, parahippocampal gyrus, precuneus, the superior parietal gyrus on a whole brain cluster-level. After OXY versus PLC administration, cue-induced craving during fMRI was rated higher after OXY application (F(1,691) = 4.370, p = .037). Interestingly, sex interacted with the treatment effect on cue-induced craving, i.e., female participants reported higher craving while males reported lower craving after OXY compared to PLC (F(1,691) = 8.914, p = .003). ConclusionsThe results provide evidence that OXY increases cue-induced neural response to alcohol stimuli in brain areas that are associated with cognitive control, context processing and social perception sensory processing and motor control. OXY increases cue-induced craving in female and reduces cue-induced craving in male non-treatment seeking individuals with AUD.Further well-powered studies are needed to investigate OXY effects on the mechanisms underlying AUD and sex-specific effects.