Atomoxetine Attenuates Dextroamphetamine Effects in Humans

Background: Although preclinical studies support the contribution of the noradrenergic system activation in mediating the acute effects of amphetamines, these findings have not been followed up in clinical studies. Objectives: To examine the effects of atomoxetine, a norepinephrine transporter inhibitor, on subjective, physiological, and plasma cortisol responses to dextroamphetamine in 10 healthy volunteers. Methods: Subjects were randomly assigned to a sequence of atomoxetine (40 mg/day) or placebo treatments each lasting for 4 days. On Day 4 of each treatment period, responses to a single 20 mg/70 kg dose of dextroamphetamine were assessed. Results: Atomoxetine treatment attenuated dextroamphetamine-induced increases in systolic and diastolic blood pressure and plasma cortisol as well as the self-report ratings of stimulated, high, and good drug effects. Conclusions: These findings are consistent with previous preclinical studies supporting the role of the noradrenergic system in mediating acute amphetamine responses. Scientific significance: Atomoxetine's capacity to attenuate some of the physiological and subjective responses to dextroamphetamine supports its potential use for stimulant addiction.