Effects of 5-hydroxytryptamine3 antagonist, ondansetron, on cigarette smoking, smoke exposure, and mood in humans

Recent studies in the animal laboratory indicate that 5-hydroxytryptamine3 (5-HT3) antagonists reduce the reinforcing effects of several psychoactive drugs, including nicotine. The purpose of our study was to determine if ondansetron, a selective 5-HT3 antagonist, affected tobacco cigarette consumption in smokers. In the first experiment, a prospective, crossover, placebo-controlled trial was used in which subjects (N = 7) were exposed in an inpatient research unit to 0, 0.15, 0.3, or 0.45 mg/kg ondansetron in three equally divided doses given 4 h apart. In the second experiment, seven different subjects were exposed to the same trial except the dose range was reduced to about 10%: 0, 0.01, 0.02, or 0.04 mg/kg. In each experiment, order of dosing conditions was determined by a Latin square design. Dependent measures included number of cigarettes smoked during the 24-h session, biologic exposure levels (carbon monoxide and plasma nicotine levels), and mood. Number of cigarettes smoked and biologic exposure levels did not differ across drug conditions in either experiment. There were also no effects of ondansetron on mood. From our study results, we conclude that acute administration of ondansetron, at doses appropriate for antiemesis or at markedly lower doses, does not alter tobacco consumption or smoke exposure in humans.