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5-HT3 receptor antagonism and psychoactivity

Department of Medicine, Johns Hopkins University School of Medicine and Johns Hopkins Bayview Medical Center, Baltimore, MD, USA

Kenzie L. Preston

Department of Medicine, Johns Hopkins University School of Medicine and Johns Hopkins Bayview Medical Center, Baltimore, MD, USA

Margaret P. Testa

Department of Medicine, Johns Hopkins University School of Medicine and Johns Hopkins Bayview Medical Center, Baltimore, MD, USA

Joanne Bell

Department of Medicine, Johns Hopkins University School of Medicine and Johns Hopkins Bayview Medical Center, Baltimore, MD, USA

Donald R. Jasinski

Department of Medicine, Johns Hopkins University School of Medicine and Johns Hopkins Bayview Medical Center, Baltimore, MD, USA

The purpose of this study was to assess the acute psychoactive and physiological properties of 5-HT ₃ 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-HT ₃ 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.

Key Words: ondansetron • cocaine • psychoactivity • subjective effects • 5-HT3 antagonism

Journal of Psychopharmacology, Vol. 10, No. 3, 182-187 (1996)
DOI: 10.1177/026988119601000302


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