Safety of atomoxetine in combination with intravenous cocaine in cocaine-experienced participants

J Addict Med. 2012 Dec;6(4):265-73. doi: 10.1097/ADM.0b013e31826b767f.


Objectives: Atomoxetine has been considered as an agonist replacement therapy for cocaine. We investigated the safety of the interaction of atomoxetine with cocaine and also whether cognitive function was affected by atomoxetine during short-term administration.

Methods: In a double-blind placebo-controlled inpatient study of 20 cocaine-dependent volunteers, participants received atomoxetine 80 mg daily followed by 100 mg daily for 5 days each. On the fourth and fifth day at each dose, cocaine (20 and 40 mg) was infused intravenously in sequential daily sessions.

Results: Preinfusion mean systolic pressures showed a small but statistically significant difference between placebo and both doses of atomoxetine. Preinfusion mean diastolic pressures were significant between placebo and atomoxetine 80 mg only. The diastolic pressure response to 40 mg cocaine was statistically significant only between the 80- and 100-mg atomoxetine doses. All electrocardiogram parameters were unchanged. Visual Analog Scale (VAS) scores for "bad effect" in the atomoxetine group were significantly higher at baseline, then declined, and for "likely to use" declined with atomoxetine treatment. On the Addiction Research Center Inventory, the atomoxetine group scored significantly lower on amphetamine, euphoria, and energy subscales (P < 0.0001). Other VAS descriptors, Brief Substance Craving Scale, Profile of Moods State, and Brief Psychiatric Rating Scale showed no differences. Atomoxetine did not affect cocaine pharmacokinetics. In tests of working memory, sustained attention, cognitive flexibility, and decision-making, atomoxetine improved performance on the visual n-back task. There were no differences in any pharmacokinetic parameters for cocaine with atomoxetine.

Conclusions: Atomoxetine was tolerated safely by all participants. Certain cognitive improvements and a dampening effect on VAS scores after cocaine were observed, but should be weighed against small but significant differences in hemodynamic responses after atomoxetine.

Trial registration: NCT00265265.

Publication types

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

MeSH terms

  • Adrenergic Uptake Inhibitors / administration & dosage*
  • Adrenergic Uptake Inhibitors / adverse effects*
  • Adrenergic Uptake Inhibitors / pharmacokinetics
  • Adult
  • Affect / drug effects
  • Atomoxetine Hydrochloride
  • Attention Deficit Disorder with Hyperactivity / blood
  • Attention Deficit Disorder with Hyperactivity / rehabilitation
  • Blood Pressure / drug effects
  • Cocaine / adverse effects*
  • Cocaine / agonists
  • Cocaine / pharmacokinetics
  • Cocaine-Related Disorders / blood
  • Cocaine-Related Disorders / complications*
  • Cocaine-Related Disorders / rehabilitation*
  • Cognition / drug effects*
  • Comorbidity
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Interactions
  • Electrocardiography / drug effects
  • Heart Rate / drug effects
  • Humans
  • Male
  • Middle Aged
  • Motivation / drug effects
  • Neuropsychological Tests
  • Opiate Substitution Treatment / adverse effects*
  • Opiate Substitution Treatment / methods
  • Propylamines / administration & dosage*
  • Propylamines / adverse effects*
  • Propylamines / pharmacokinetics
  • Substance Abuse, Intravenous / blood
  • Substance Abuse, Intravenous / rehabilitation*
  • Young Adult


  • Adrenergic Uptake Inhibitors
  • Propylamines
  • Atomoxetine Hydrochloride
  • Cocaine

Associated data