title: Physiological and subjective effects of acute intranasal methamphetamine during atomoxetine maintenance.
abstract: BACKGROUND
  Methamphetamine abuse and dependence are significant public-health concerns. Behavioral therapies are effective for reducing methamphetamine use. However, many patients enrolled in behavioral therapies are unable to achieve significant periods of abstinence suggesting other strategies like pharmacotherapy are needed.
  
  
  OBJECTIVE
  This experiment determined the physiological and subjective effects of acutely administered intranasal methamphetamine during atomoxetine maintenance in seven non-treatment seeking stimulant-dependent participants. Atomoxetine was chosen for study because it blocks reuptake at the norepinephrine transporter and increases extracellular dopamine levels in the prefrontal cortex. In this way, atomoxetine might function as an agonist replacement therapy for stimulant-dependent patients.
  
  
  METHODS
  After at least 7 days of maintenance on atomoxetine (0 and 80 mg/day), participants were administered ascending doses of intranasal methamphetamine (0, 5, 10, 20 and 30 mg) across two experimental sessions. Intranasal methamphetamine doses were separated by 90 min.
  
  
  RESULTS
  Intranasal methamphetamine produced prototypical physiological and subjective effects (e.g., increased heart rate, blood pressure, temperature and subjective ratings of Good Effects). Atomoxetine maintenance augmented the heart rate-increasing effects of methamphetamine, but attenuated the pressor effects. The subjective effects of intranasal methamphetamine were similar during atomoxetine and placebo maintenance.
  
  
  CONCLUSIONS
  These results suggest that methamphetamine can be safely administered to participants maintained on atomoxetine, but whether it might be an effective pharmacotherapy for methamphetamine dependence remains to be determined.
authors.affiliation: Department of Behavioral Science, University of Kentucky College of Medicine, College of Medicine Office Building, Lexington, KY 40536-0086, USA. crush2@email.uky.edu
authors.forename: Craig R
authors.initials: CR
authors.lastname: Rush
authors.forename: William W
authors.initials: WW
authors.lastname: Stoops
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Lile
authors.forename: Paul E A
authors.initials: PE
authors.lastname: Glaser
authors.forename: Lon R
authors.initials: LR
authors.lastname: Hays
mesh_terms: D000281:Administration, Intranasal; D000069445:Atomoxetine Hydrochloride; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008694:Methamphetamine / Q000008:administration & dosage*; D011437:Propylamines / Q000008:administration & dosage*; D011597:Psychomotor Performance / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
chemical_list: D011437:Propylamines; D008694:Methamphetamine; D000069445:Atomoxetine Hydrochloride