Mehmet Sofuoglu1, James Poling, Kevin Hill, Thomas Kosten. 1. Yale University, School of Medicine, Department of Psychiatry and VA Connecticut Healthcare System, West Haven, CT 06516, USA. Mehmet.Sofuoglu@yale.edu
Abstract
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.
RCT Entities:
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.
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