Atomoxetine attenuates dextroamphetamine effects in humans

Am J Drug Alcohol Abuse. 2009;35(6):412-6. doi: 10.3109/00952990903383961.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Uptake Inhibitors / pharmacology*
  • Adult
  • Affect / drug effects
  • Atomoxetine Hydrochloride
  • Blood Pressure / drug effects
  • Central Nervous System Stimulants / antagonists & inhibitors*
  • Central Nervous System Stimulants / pharmacology
  • Dextroamphetamine / antagonists & inhibitors*
  • Dextroamphetamine / pharmacology
  • Drug Interactions
  • Female
  • Heart Rate / drug effects
  • Humans
  • Hydrocortisone / blood
  • Male
  • Norepinephrine Plasma Membrane Transport Proteins / antagonists & inhibitors*
  • Propylamines / pharmacology*


  • Adrenergic Uptake Inhibitors
  • Central Nervous System Stimulants
  • Norepinephrine Plasma Membrane Transport Proteins
  • Propylamines
  • Atomoxetine Hydrochloride
  • Dextroamphetamine
  • Hydrocortisone