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Hugh Myrick, MD; Raymond F. Anton, MD; Xingbao Li, MD; Scott Henderson, BA; Patrick K. Randall, PhD; Konstantin Voronin, MD, PhD

Arch Gen Psychiatry. 2008;65(4):466-475.

Context  Medication for the treatment of alcoholism is currently not particularly robust. Neuroimaging techniques might predict which medications could be useful in the treatment of alcohol dependence.

Objective  To explore the effect of naltrexone, ondansetron hydrochloride, or the combination of these medications on cue-induced craving and ventral striatum activation.

Design  Functional brain imaging was conducted during alcohol cue presentation.

Setting  Participants were recruited from the general community following media advertisement. Experimental procedures were performed in the magnetic resonance imaging suite of a major training hospital and medical research institute.

Patients  Ninety non–treatment-seeking alcohol-dependent (by DSM-IV criteria) and 17 social drinking (< 14 drinks per week) paid volunteers recruited through advertisements at an academic center.

Interventions  A taste of alcohol and a series of alcohol-related pictures, neutral beverage pictures, and visual control images were provided to volunteers after 7 days of double-blind randomly assigned daily dosing with 50 mg of naltrexone (n = 23), 0.50 mg of ondansetron hydrochloride (n = 23), the combination of the 2 medications (n = 20), or matching placebos (n = 24).

Main Outcome Measures  Difference in brain blood oxygen level–dependent magnetic resonance when viewing alcohol pictures vs neutral beverage pictures with a particular focus on ventral striatum activity comparison across medication groups. Self-ratings of alcohol craving.

Results  The combination treatment decreased craving for alcohol. Naltrexone with (P = .02) or without (P = .049) ondansetron decreased alcohol cue–induced activation of the ventral striatum. Ondansetron by itself was similar to naltrexone and the combination in the overall analysis but intermediate in a region-specific analysis.

Conclusions  Consistent with animal data that suggest that both naltrexone and ondansetron reduce alcohol-stimulated dopamine output in the ventral striatum, the current study found evidence that these medications, alone or in combination, could decrease alcohol cue–induced activation of the ventral striatum, consistent with their putative treatment efficacy.

Author Affiliations: Research and Development Service, Ralph H. Johnson Department of Veterans Affairs Medical Center (Dr Myrick and Mr Henderson), and Alcohol Research Center, Department of Psychiatry and Behavioral Sciences (Drs Myrick, Anton, Li, Randall, and Voronin and Mr Henderson), and Center for Advanced Imaging Research (Drs Myrick and Li and Mr Henderson), Medical University of South Carolina, Charleston, South Carolina.

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