The most likely outcome of smoking cessation attempts is relapse, underscoring the need to
advance novel treatments. Preclinical research shows that the noradrenergic system is
critical for modulating drug-seeking behavior and recent findings indicate that the
α1-adrenergic antagonist prazosin reduces nicotine self-administration and reinstatement.
Presently, data on prazosin's effects on nicotine-related behaviour in humans is lacking. An
efficient method for screening novel smoking cessation medications is to integrate human
laboratory paradigms in the context of brief, randomized trials of smoking cessation that
include smokers motivated to quit. This study aims to provide an initial test of prazosin for
smoking cessation by implementing a brief, randomized trial that will include both human
laboratory and clinical phenotypes. This approach will allow an efficient but sensitive
method for medication screening that maximizes clinical validity.