Acute cannabidiol administration reduces alcohol craving and cue-induced nucleus accumbens activation in individuals with alcohol use disorder: the double-blind randomized controlled ICONIC trial

Although alcohol use disorder (AUD) is highly prevalent, only a few medications are approved for its treatment leaving much room for improvement. Cannabidiol (CBD) might be a particularly promising candidate, with preclinical data suggesting that CBD is effective in targeting AUD symptoms and diseas...

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Main Authors: Vetter, Sina (Author) , Teetzmann, Anton (Author) , Baeßler, Joscha (Author) , Schreckenberger, Lena (Author) , Zaiser, Judith (Author) , Pfisterer, Marlen (Author) , Stenger, Manuel (Author) , Bach, Patrick (Author)
Format: Article (Journal)
Language:English
Published: 12 December 2024
In: Molecular psychiatry
Year: 2025, Volume: 30, Issue: 6, Pages: 2612-2619
ISSN:1476-5578
DOI:10.1038/s41380-024-02869-y
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41380-024-02869-y
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41380-024-02869-y
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Author Notes:Sina Zimmermann, Anton Teetzmann, Joscha Baeßler, Lena Schreckenberger, Judith Zaiser, Marlen Pfisterer, Manuel Stenger and Patrick Bach

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520 |a Although alcohol use disorder (AUD) is highly prevalent, only a few medications are approved for its treatment leaving much room for improvement. Cannabidiol (CBD) might be a particularly promising candidate, with preclinical data suggesting that CBD is effective in targeting AUD symptoms and disease processes that drive alcohol use and relapse, due to its anti-craving, stress-reducing, and anti-compulsive effects. Here we report data from the double-blind randomized controlled ICONIC trial that compared the effects of a single dose of 800 mg cannabidiol against placebo (PLC) in N = 28 individuals with AUD. Cue-induced nucleus accumbens (NAc) activation, alcohol craving during a combined stress- and alcohol cue exposure session, as well as craving during an fMRI alcohol cue-reactivity task and CBD plasma levels served as outcomes. Individuals receiving CBD showed lower bilateral cue-induced NAc activation (tleft_NAc(23) = 4.906, p < 0.001, d = 1.15; tright_NAc (23) = 4.873, p < 0.001, d = 1.13) and reported significantly lower alcohol craving after a combined stress- and alcohol cue exposure session (Fgroup(1,26) = 4.516, p = 0.043, eta2 = 0.15) and during the fMRI cue-reactivity task (Fgroup(1,24) = 6.665, p = 0.015, eta2 = 0.23). CBD levels were significantly higher in the CBD group (t(25) = 3.808, p < 0.001, d = 1.47) and showed a significant negative association with alcohol craving during the cue exposure experiment (r = −0.394, pFDR = 0.030) and during fMRI (r = −0.389, pFDR = 0.030), and with left and right NAc activation (rleft_NAc = −0.459, pFDR = 0.030; rright_NAc = −0.405, pFDR = 0.030). CBD’s capacity to reduce stress- and cue-induced alcohol craving and to normalize NAc activation - a region critical to the pathophysiology of AUD - contribute to understanding the neurobiological basis of its clinical effects and support its potential as a treatment option for AUD. Clinical Trials Registry: DRKS00029993. 
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