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Ondansetron alters human alcohol intoxication
R M Swift1, D Davidson, W Whelihan
1Department of Psychiatry and Human Behavior, Brown University Medical School, Providence, Rhode Island, USA.
Abstract:
There is considerable evidence that serotonin-3 (5-HT3) receptor antagonists modulate some of the behavioral effects of alcohol, and may decrease alcohol consumption. To better clarify the mechanism of action of 5-HT3 antagonists on these behaviors, we investigated the effects of the 5-HT3 antagonist, ondansetron, on several subjective and objective measures of alcohol intoxication in social drinkers. Twelve nonalcoholic, social drinkers received either 8 mg ondansetron, p.o., or placebo during one of two test sessions in a crossover, double-blind protocol. Both conditions were followed by a standard, intoxicating dose of alcohol. Subjective and objective measures of intoxication including mood, physical sensations, performance changes, and alcohol pharmacokinetics were determined. To control for ondansetron effects, 10 additional subjects received either ondansetron or placebo, followed by a nonintoxicating, "placebo" dose of alcohol during a second crossover double-blind protocol. Ondansetron was found to augment certain stimulant, sedative, and discriminant effects of alcohol, without affecting psychomotor performance or alcohol pharmacokinetics. Ondansetron had minimal effects on subjects receiving placebo alcohol. These data suggest that the reductions in alcohol consumption observed in animals and humans treated with ondansetron may be mediated by increases in subjective intoxication, and/or increases in the aversive effects of alcohol.
Insights
The serotonin-3 (5-HT3) antagonist ondansetron increased subjective alcohol intoxication effects in social drinkers. This may explain how ondansetron reduces alcohol consumption by enhancing intoxication and aversive responses.
Area of Science:
- Neuropharmacology
- Behavioral Science
Background:
- Serotonin-3 (5-HT3) receptor antagonists are known to influence alcohol's behavioral effects and potentially reduce alcohol consumption.
- The precise mechanisms by which 5-HT3 antagonists affect alcohol-related behaviors require further elucidation.
Purpose of the Study:
- To investigate the effects of the 5-HT3 antagonist ondansetron on subjective and objective measures of alcohol intoxication in social drinkers.
- To clarify the mechanism of action of 5-HT3 antagonists in modulating alcohol's effects.
Main Methods:
- A crossover, double-blind protocol was employed with 12 nonalcoholic social drinkers receiving either 8 mg ondansetron or placebo, followed by an intoxicating alcohol dose.
- Subjective and objective intoxication measures, including mood, physical sensations, and performance, were assessed.
- A separate protocol with 10 subjects examined ondansetron's effects with a placebo alcohol dose to control for its direct effects.
Main Results:
- Ondansetron augmented specific stimulant, sedative, and discriminant effects of alcohol.
- No significant impact was observed on psychomotor performance or alcohol pharmacokinetics.
- Ondansetron demonstrated minimal effects when subjects received a placebo alcohol dose.
Conclusions:
- The observed reductions in alcohol consumption with ondansetron may be linked to heightened subjective intoxication.
- Increased aversive effects of alcohol, potentially mediated by ondansetron, could also contribute to reduced consumption.
- These findings provide insight into the neurobiological pathways influenced by 5-HT3 antagonism in the context of alcohol use.