Effect of naltrexone and ondansetron on alcohol cue–induced activation of the ventral striatum in alcohol-dependent people
Open accessAbstract
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.
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In that RCT, both naltrexone and ondansetron, alone or in combination, decreased activation of the ventral striatum in response to alcohol cues.
“Furthermore, both medications, whether administered alone or in combination, decreased activation of the ventral striatum in response to alcohol cues”
From A Narrative Review of Current and Emerging Trends in the Treatment of Alcohol Use Disorder (2024) · cites this paper as [71]
In an RCT of 107 patients, the combination of naltrexone and ondansetron effectively reduced alcohol craving when participants were exposed to alcohol-related cues.
“When exposed to alcohol-related cues, the combination of naltrexone and ondansetron effectively reduced alcohol craving.”
From A Narrative Review of Current and Emerging Trends in the Treatment of Alcohol Use Disorder (2024) · cites this paper as [71]
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References 79 · Cited by 258
- Authors
- Myrick, H., Anton, R. F., Li, X., Henderson, S., Randall, P. K., & Voronin, K.
- Affiliations
- Ralph H. Johnson VA Medical Center (US)
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2008-04-01
- Volume
- 65
- Issue
- 4
- Pages
- 466
- ISSN
- 0003-990X (ISSN-L)
- PMC
- PMC2504413
- OpenAlex
- W1970015881
- Cited by
- 258
- References
- 79
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 4 · 2023: 9 · 2022: 6 · 2021: 12 · 2020: 12 · 2019: 17 · 2018: 14 · 2017: 12 · 2016: 23 · 2015: 12 · 2014: 18 · 2013: 18 · 2012: 23
- FWCI
- 16.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (K23 AA00314, K23AA000314, P50AA010761)
- Topics
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- naltrexone, ondansetron, alcoholism, alcohol craving, alcohol cue reactivity, ventral striatum, dopamine, combination therapy
- MeSH terms
- Adult, Alcoholism, Basal Ganglia, Cerebrovascular Circulation, Cues, Female, Humans, Magnetic Resonance Imaging, Male, Naltrexone, Narcotics, Oxygen, Photic Stimulation, Serotonin Antagonists, Severity of Illness Index, Ondansetron, Diagnostic and Statistical Manual of Mental Disorders
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