Work

Glucose intake reduces alcohol craving and amplifies habituation to cue-induced brain activation in male patients with alcohol use disorder: A randomized, placebo-controlled crossover study examining male and female patients with AUD

Year: 2025

Type: article

Abstract: Evidence suggests a role of appetite-regulating hormones in alcohol use disorder. Reductions in acylated ghrelin levels are associated with reductions in craving and cue-induced brain activity. Ghrelin levels can be physiologically decreased by glucose intake, which therefore could be a treatment reducing craving and cue-induced brain activity in patients with alcohol use disorder, potentially mediated by acylated ghrelin. 80 males and females with alcohol use disorder participated in the randomized placebo-controlled crossover study, examining glucose intake as acute treatment to reduce craving. Changes in craving and ghrelin levels were assessed at eight time points. Of these, 43 participants attended fMRI measurements examining habituation to cue-induced brain activation over time. Craving and hormone levels over time were analyzed using linear mixed modeling, brain activation habituation over time using flexible factorial models. Models revealed a significant interaction effect (F(1,474.607)= 13.563, p < .001) between sex and treatment on craving, with lower craving values in males (difference in means=-.540, p = .016, 95 %CI: −.976, −.103) and higher craving in females (difference in means=.815, p = .005, 95 %CI:.243, 1.387) in the glucose compared to the placebo condition. In males, we found a significant effect of treatment (F(1,313.602)= 7.811, p = .006) and a trend, but no significant effect of acylated ghrelin (F(1,301.568)= 3.574, p = .060) on craving as well as greater habituation to cue-induced brain activation after glucose compared to placebo intake in right putamen (T(1,35)= 4.77, p = .019). Individual habituation slopes significantly predicted the difference in craving before and after the alcohol task (F(2,36)= 5.234, p = .010; B= -36.018, p = .027) in males. Glucose intake could be a short-term treatment for males with alcohol use disorder to reduce alcohol craving and cue-induced brain activation. Sex-specific differences should be considered to gain a better understanding of the underlying mechanisms and develop treatment options for females. • There is a significant interaction effect between sex and treatment on craving. • The interaction shows lower craving values in males and higher craving values in females after glucose compared to placebo. • In males, a significant greater habituation to brain activation after glucose compared to placebo was found. • There was a strong trend with regard of the effect of acylated ghrelin levels on craving. • Glucose intake is a potential short-term treatment for males with AUD to reduce craving and cue-induced brain activation.

Source: Psychoneuroendocrinology

DOI: 10.1016/j.psyneuen.2025.107456