5-HT₃ receptor antagonism and psychoactivity

The purpose of this study was to assess the acute psychoactive and physiological properties of 5-HT₃ antagonism using ondansetron as a probe. Ondansetron is used clinically as an anti-emetic but is also under treatment consideration for a range of psychiatric disorders including drug abuse. A 15 min infusion of 40 mg ondansetron, a 1 min infusion of 25 mg of cocaine (positive control) and their respective placebos were tested intravenously in eight volunteers with histories of drug abuse in a blinded cross-over study. Ondansetron responses could not be distinguished from the placebo. Cocaine produced typical subjective and physiological effects. These findings indicate that the prototypic 5-HT₃ receptor antagonist ondansetron does not produce acute psychoactive effects when infused at doses of up to 40 mg and has no rewarding effects with this regime.