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Combining ondansetron and naltrexone reduces craving among biologically predisposed alcoholics: preliminary clinical
N Ait-Daoud1, B A Johnson, T J Prihoda
1Treatment Research Center, Department of Psychiatry, University of Texas, Health Science Center at San Antonio, 78229-3900, USA. tiouririne@uthscsa.edu
Rationale:
Previously, we have reported that the combination of ondansetron (a 5-HT3 antagonist) and naltrexone (a mu opioid antagonist) appears to act synergistically at improving the drinking outcomes of early onset alcoholics (EOA). a subtype of alcoholic characterized by developing problem-drinking earlier, antisocial behaviors, high familial loading, and biological disease predisposition. Presumably, this medication combination counteracts the interaction between activated central 5-HT3 receptors and the endogenous opioid system during the mediation of alcohol-induced reward. We now hypothesize further that an important mechanism by which the combination diminishes alcohol consumption is through a reduction in craving.
Objective:
To determine whether the combination of naltrexone and ondansetron is superior to a placebo at reducing craving among EOA, and the relationship between craving and drinking behavior in both treatment groups.
Methods:
We conducted an 8-week double-blind placebo-controlled clinical trial in which 10 EOA were randomized to receive ondansetron (4 microg/kg b.i.d.) + naltrexone (25 mg b.i.d.) and 10 EOA had a placebo (total n=20) as an adjunct to weekly standardized group cognitive behavioral therapy. Craving was measured by using the obsessive compulsive drinking scale (OCDS).
Results:
Craving ratings were scored on four subscales which where derived empirically by principal component structure analysis of the OCDS. EOA who received the medication combination, compared with the placebo, had significantly lower scores on "automaticity of drinking" and "alcohol consumption ". Reduction in automaticity of drinking was correlated with self-reported drinking for only the medication combination group.
Conclusions:
By reducing automaticity of drinking, the medication combination presumably decreased drinking salience and intensity. Larger scale studies testing these medications, both alone and together, among alcoholic subtypes are needed to establish and extend these promising findings.
Insights
This study found that combining ondansetron and naltrexone significantly reduced alcohol craving and automaticity of drinking in early onset alcoholics (EOA). These findings suggest a promising new treatment approach for alcoholism.
Area of Science:
- Neuroscience
- Pharmacology
- Addiction Medicine
Background:
- Early onset alcoholics (EOA) exhibit specific characteristics including early problem drinking, antisocial behaviors, and genetic predisposition.
- Previous research indicated synergistic effects of ondansetron (5-HT3 antagonist) and naltrexone (mu opioid antagonist) in improving drinking outcomes for EOA.
- The combination is hypothesized to counteract the interaction between central 5-HT3 receptors and the endogenous opioid system in alcohol reward pathways.
Purpose of the Study:
- To evaluate if naltrexone and ondansetron combination is more effective than placebo in reducing craving among EOA.
- To examine the relationship between craving and drinking behavior in both treatment groups.
Main Methods:
- An 8-week double-blind, placebo-controlled clinical trial was conducted with 20 EOA.
- Participants were randomized to receive either ondansetron + naltrexone or a placebo.
- Craving was assessed using the Obsessive Compulsive Drinking Scale (OCDS).
Main Results:
- The medication combination group showed significantly lower scores on "automaticity of drinking" and "alcohol consumption" compared to the placebo group.
- Reduced automaticity of drinking was correlated with self-reported drinking exclusively in the medication combination group.
- The study identified four empirically derived subscales from the OCDS for craving ratings.
Conclusions:
- The medication combination likely reduces drinking salience and intensity by decreasing the automaticity of drinking.
- These findings support the potential of ondansetron and naltrexone as a treatment for EOA.
- Further large-scale studies are recommended to validate these medications, alone and in combination, across different alcoholic subtypes.
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