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The neural and psychophysiological effects of cannabidiol in youth with alcohol use disorder: A randomized controlled clinical trial.

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Title: The neural and psychophysiological effects of cannabidiol in youth with alcohol use disorder: A randomized controlled clinical trial.
Authors: Kirkland AE; Medical University of South Carolina, Department of Psychiatry and Behavioral Sciences, Charleston, SC, USA. kirklaan@musc.edu., Browning BD; Medical University of South Carolina, Department of Psychiatry and Behavioral Sciences, Charleston, SC, USA., Meredith LR; Medical University of South Carolina, Department of Psychiatry and Behavioral Sciences, Charleston, SC, USA., Robertson E; Medical University of South Carolina, Department of Psychiatry and Behavioral Sciences, Charleston, SC, USA., Herring C; Medical University of South Carolina, Department of Psychiatry and Behavioral Sciences, Charleston, SC, USA., Tomko RL; Medical University of South Carolina, Department of Psychiatry and Behavioral Sciences, Charleston, SC, USA., Gray KM; Medical University of South Carolina, Department of Psychiatry and Behavioral Sciences, Charleston, SC, USA., Squeglia LM; Medical University of South Carolina, Department of Psychiatry and Behavioral Sciences, Charleston, SC, USA.
Source: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2025 Sep; Vol. 50 (10), pp. 1482-1492. Date of Electronic Publication: 2025 Jun 11.
Publication Type: Journal Article; Randomized Controlled Trial
Language: English
Journal Info: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8904907 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1740-634X (Electronic) Linking ISSN: 0893133X NLM ISO Abbreviation: Neuropsychopharmacology Subsets: MEDLINE
Imprint Name(s): Publication: 2003- : London : Nature Publishing Group
Original Publication: [New York, NY] : Elsevier, [c1987-
MeSH Terms: Cannabidiol*/pharmacology , Cannabidiol*/therapeutic use , Alcoholism*/drug therapy , Alcoholism*/physiopathology , Alcoholism*/diagnostic imaging , Alcoholism*/metabolism , Alcoholism*/psychology , Gyrus Cinguli*/drug effects , Gyrus Cinguli*/diagnostic imaging , Gyrus Cinguli*/metabolism , Brain*/drug effects , Brain*/diagnostic imaging , Brain*/metabolism, Glutamic Acid/metabolism ; gamma-Aminobutyric Acid/metabolism ; Glutamine/metabolism ; Craving/drug effects ; Heart Rate/drug effects ; Humans ; Female ; Double-Blind Method ; Adolescent ; Male ; Young Adult ; Magnetic Resonance Imaging
Abstract: Novel treatment evaluation for youth with alcohol use disorder (AUD) is needed. Cannabidiol (CBD), a constituent of the Cannabis sativa plant, may be a promising candidate pharmacotherapy due to its potential therapeutic properties and preclinical research suggesting it decreases alcohol use. Due to limited data in humans, rigorous screening of the acute neural, psychophysiological, and alcohol-related effects of CBD is indicated to assess its viability as a potential treatment for youth AUD. Using a within-subjects, randomized, double-blind, placebo-controlled design, we tested acute multi-modal effects of CBD (600 mg) in non-treatment seeking youth with AUD (N = 36; ages 17-22; 69% female). Outcomes included (1) glutamate+glutamine (Glx) and GABA levels in the anterior cingulate cortex measured with proton magnetic resonance spectroscopy; (2) whole-brain and a priori region-of-interest neural alcohol cue-reactivity measured with functional MRI; (3) psychophysiological response to alcohol olfactory cues measured by self-reported acute alcohol craving, heart rate variability, and skin conductance; and (4) alcohol use. No CBD-associated adverse events were observed. There were no effects of acute CBD administration, compared to placebo, on any outcomes of interest. This is the first adequately powered medication screening study for the use of CBD in youth with AUD. We did not detect significant effects of CBD on neurometabolic, neurobehavioral, psychophysiological, or alcohol use outcomes in this sample. Future studies may benefit from chronic administration to better understand substance-related effects.Clinicaltrials.gov NCT05317546 https://clinicaltrials.gov/study/NCT05317546.
(© 2025. The Author(s).)
Competing Interests: Competing interests: Dr. Kevin Gray reports having received consultation fees from Achieve Life Sciences and Indivior, and research support from Aelis Farma. All other authors report no potential competing interests.
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Grant Information: T32 DA007288 United States DA NIDA NIH HHS; K01 AA031745 United States AA NIAAA NIH HHS; R21 AA030114 United States AA NIAAA NIH HHS; DA007288 U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA); K01AA031745 U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA); K24AA031052 U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA); K24 AA031052 United States AA NIAAA NIH HHS; R21AA030114 U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Molecular Sequence: ClinicalTrials.gov NCT05317546
Substance Nomenclature: 19GBJ60SN5 (Cannabidiol)
3KX376GY7L (Glutamic Acid)
56-12-2 (gamma-Aminobutyric Acid)
0RH81L854J (Glutamine)
Entry Date(s): Date Created: 20250611 Date Completed: 20250812 Latest Revision: 20250814
Update Code: 20260130
PubMed Central ID: PMC12339998
DOI: 10.1038/s41386-025-02141-z
PMID: 40500407
Database: MEDLINE
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  Data: The neural and psychophysiological effects of cannabidiol in youth with alcohol use disorder: A randomized controlled clinical trial.
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  Data: <searchLink fieldCode="AU" term="%22Kirkland+AE%22">Kirkland AE</searchLink>; Medical University of South Carolina, Department of Psychiatry and Behavioral Sciences, Charleston, SC, USA. kirklaan@musc.edu.<br /><searchLink fieldCode="AU" term="%22Browning+BD%22">Browning BD</searchLink>; Medical University of South Carolina, Department of Psychiatry and Behavioral Sciences, Charleston, SC, USA.<br /><searchLink fieldCode="AU" term="%22Meredith+LR%22">Meredith LR</searchLink>; Medical University of South Carolina, Department of Psychiatry and Behavioral Sciences, Charleston, SC, USA.<br /><searchLink fieldCode="AU" term="%22Robertson+E%22">Robertson E</searchLink>; Medical University of South Carolina, Department of Psychiatry and Behavioral Sciences, Charleston, SC, USA.<br /><searchLink fieldCode="AU" term="%22Herring+C%22">Herring C</searchLink>; Medical University of South Carolina, Department of Psychiatry and Behavioral Sciences, Charleston, SC, USA.<br /><searchLink fieldCode="AU" term="%22Tomko+RL%22">Tomko RL</searchLink>; Medical University of South Carolina, Department of Psychiatry and Behavioral Sciences, Charleston, SC, USA.<br /><searchLink fieldCode="AU" term="%22Gray+KM%22">Gray KM</searchLink>; Medical University of South Carolina, Department of Psychiatry and Behavioral Sciences, Charleston, SC, USA.<br /><searchLink fieldCode="AU" term="%22Squeglia+LM%22">Squeglia LM</searchLink>; Medical University of South Carolina, Department of Psychiatry and Behavioral Sciences, Charleston, SC, USA.
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– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Novel treatment evaluation for youth with alcohol use disorder (AUD) is needed. Cannabidiol (CBD), a constituent of the Cannabis sativa plant, may be a promising candidate pharmacotherapy due to its potential therapeutic properties and preclinical research suggesting it decreases alcohol use. Due to limited data in humans, rigorous screening of the acute neural, psychophysiological, and alcohol-related effects of CBD is indicated to assess its viability as a potential treatment for youth AUD. Using a within-subjects, randomized, double-blind, placebo-controlled design, we tested acute multi-modal effects of CBD (600 mg) in non-treatment seeking youth with AUD (N = 36; ages 17-22; 69% female). Outcomes included (1) glutamate+glutamine (Glx) and GABA levels in the anterior cingulate cortex measured with proton magnetic resonance spectroscopy; (2) whole-brain and a priori region-of-interest neural alcohol cue-reactivity measured with functional MRI; (3) psychophysiological response to alcohol olfactory cues measured by self-reported acute alcohol craving, heart rate variability, and skin conductance; and (4) alcohol use. No CBD-associated adverse events were observed. There were no effects of acute CBD administration, compared to placebo, on any outcomes of interest. This is the first adequately powered medication screening study for the use of CBD in youth with AUD. We did not detect significant effects of CBD on neurometabolic, neurobehavioral, psychophysiological, or alcohol use outcomes in this sample. Future studies may benefit from chronic administration to better understand substance-related effects.Clinicaltrials.gov NCT05317546 https://clinicaltrials.gov/study/NCT05317546.<br /> (© 2025. The Author(s).)
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: Competing interests: Dr. Kevin Gray reports having received consultation fees from Achieve Life Sciences and Indivior, and research support from Aelis Farma. All other authors report no potential competing interests.
– Name: Ref
  Label: References
  Group: RefInfo
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        Type: general
      – SubjectFull: Young Adult
        Type: general
      – SubjectFull: Magnetic Resonance Imaging
        Type: general
      – SubjectFull: Cannabidiol pharmacology
        Type: general
      – SubjectFull: Cannabidiol therapeutic use
        Type: general
      – SubjectFull: Alcoholism drug therapy
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        Type: general
      – SubjectFull: Alcoholism diagnostic imaging
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      – SubjectFull: Alcoholism metabolism
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      – SubjectFull: Gyrus Cinguli drug effects
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      – TitleFull: The neural and psychophysiological effects of cannabidiol in youth with alcohol use disorder: A randomized controlled clinical trial.
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              M: 09
              Text: 2025 Sep
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              Y: 2025
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