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Journal Article Randomized Controlled Trial Ppublish 1 citation

PubMed: 39668256 DOI: 10.1038/s41380-024-02869-y

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.

Mol Psychiatry 30(6):2612-2619

Authors: Sina Zimmermann, Anton Teetzmann, Joscha Baeßler, Lena Schreckenberger, Judith Zaiser, Marlen Pfisterer, Manuel Stenger, Patrick Bach

Affiliations

  • Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim/ University of Heidelberg, Heidelberg, Germany. German Center for Mental Health (DZPG), Mannheim, Germany.
  • Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim/ University of Heidelberg, Heidelberg, Germany. German Center for Mental Health (DZPG), Mannheim, Germany.
  • Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim/ University of Heidelberg, Heidelberg, Germany.
  • German Center for Mental Health (DZPG), Mannheim, Germany.
  • Feuerlein Center on Translational Addiction Medicine (FCTS), University of Heidelberg, Heidelberg, Germany.
  • Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Abstract

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 (t left_NAc(23) = 4.906, p < 0.001, d = 1.15; t right_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 (F group(1,26) = 4.516, p = 0.043, eta 2 = 0.15) and during the fMRI cue-reactivity task (F group(1,24) = 6.665, p = 0.015, eta 2 = 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, p FDR = 0.030) and during fMRI (r = -0.389, p FDR = 0.030), and with left and right NAc activation (r left_ NAc = -0.459, p FDR = 0.030; r right_ NAc = -0.405, p FDR = 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.

MeSH

Nucleus Accumbens, Molecular Biology, Alcoholism, Craving, Mental Disorders, Stress, Physiological, Neurosciences, Therapeutics, Cannabidiol

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