title: Subjective and physiological effects of acute intranasal methamphetamine during d-amphetamine 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 subjective and physiological effects of intranasal methamphetamine during D: -amphetamine maintenance in eight non-treatment-seeking stimulant-dependent participants. We predicted D: -amphetamine maintenance would attenuate the acute subjective effects of intranasal methamphetamine. We also predicted intranasal methamphetamine would be well tolerated during D: -amphetamine maintenance.
  
  
  METHODS
  After at least 7 days of maintenance on sustained-release D: -amphetamine (0 and 45 mg/day), participants were administered ascending doses of intranasal methamphetamine (0, 2.5, 5, 10, and 20 mg) across two experimental sessions. Intranasal methamphetamine doses were separated by 90 min.
  
  
  RESULTS
  Intranasal methamphetamine produced prototypical subjective and physiological effects (e.g., increased ratings of Like Drug; increased heart rate, blood pressure, and body temperature). The acute effects of intranasal methamphetamine were significantly diminished during D: -amphetamine maintenance relative to placebo maintenance.
  
  
  CONCLUSIONS
  These results are concordant with those of clinical trials and provide further support for the use of agonist replacement therapy to manage methamphetamine dependence. Additional research in humans is needed to determine the effectiveness of D: -amphetamine under different experimental conditions that more closely reflect use in the natural environment (e.g., higher methamphetamine doses) and behavioral arrangements that are predictive of pharmacotherapy effectiveness (e.g., drug self-administration).
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; D000328:Adult; D000661:Amphetamine / Q000009:adverse effects*; D019969:Amphetamine-Related Disorders / Q000188:drug therapy* / Q000503:physiopathology*; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D008875:Middle Aged; D009483:Neuropsychological Tests; D011795:Surveys and Questionnaires; D013997:Time Factors; D055815:Young Adult
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D000661:Amphetamine