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

Introduction - 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...

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Main Authors: Wetzel, Lea (Author) , Hoffmann, Sabine (Author) , Reinhard, Iris (Author) , Riegler, Alisa (Author) , Pourbaix, Madeleine (Author) , Ardern, Isabel (Author) , Link, Tobias (Author) , Vollstädt-Klein, Sabine (Author) , Lenz, Bernd (Author) , Kiefer, Falk (Author) , Bach, Patrick (Author) , Koopmann, Anne (Author)
Format: Article (Journal)
Language:English
Published: July 2025
In: Psychoneuroendocrinology
Year: 2025, Volume: 177, Pages: 1-11
ISSN:1873-3360
DOI:10.1016/j.psyneuen.2025.107456
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.psyneuen.2025.107456
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0306453025001799
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Author Notes:Lea Wetzel, Sabine Hoffmann, Iris Reinhard, Alisa Riegler, Madeleine Pourbaix, Isabel Ardern, Tobias Link, Sabine Vollstädt-Klein, Bernd Lenz, Falk Kiefer, Patrick Bach, Anne Koopmann

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520 |a Introduction - 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. - Material and methods - 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. - Results - 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. - Conclusions - 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. 
650 4 |a Alcohol use disorder 
650 4 |a Brain activation 
650 4 |a Craving 
650 4 |a Ghrelin 
650 4 |a Glucose 
650 4 |a Habituation 
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