title: Physiological and subjective effects of acute intranasal methamphetamine during extended-release alprazolam maintenance.
abstract: BACKGROUND
  Medications development for methamphetamine dependence is ongoing, but no widely accepted, effective pharmacotherapy has been identified. Previous studies have demonstrated neurobiological perturbations to central GABA(A) activity following chronic stimulant use, and that positive modulation of GABA(A) receptors attenuates the neurochemical and behavioral response to stimulant drugs such as methamphetamine. Therefore, GABA(A) modulators could be useful as pharmacotherapies for stimulant-use disorders.
  
  
  METHODS
  This study tested the hypothesis that intranasal methamphetamine would be safe and well tolerated during maintenance on extended-release alprazolam (XR), and that the effects of methamphetamine would be attenuated. Eight non-treatment-seeking, stimulant-dependent individuals completed an inpatient experiment in which ascending doses of intranasal methamphetamine (0, 5, 10, 20 and 30 mg) were administered after four days of alprazolam XR maintenance (0 and 1mg/day).
  
  
  RESULTS
  Intranasal methamphetamine produced prototypical effects (e.g., increased positive subjective ratings and elevated cardiovascular signs). The combination of intranasal methamphetamine and alprazolam XR was safe and well tolerated. Alprazolam XR produced small, but orderly, reductions in some of the subjective effects of methamphetamine, and performance impairment.
  
  
  CONCLUSIONS
  The present results demonstrate that methamphetamine use during alprazolam XR treatment would not pose a significant safety risk. Given the potential of GABA(A) positive modulators to manage certain aspects of stimulant abuse and dependence (i.e., drug-induced seizures, anxiety and stress), but the relatively small impact on the acute abuse-related effects of methamphetamine observed here, additional research with GABA(A) positive modulators is warranted, but should consider their use as an adjunct component of combination behavioral and/or drug treatment.
authors: Department of Behavioral Science, University of Kentucky College of Medicine, Medical Behavioral Sciences Building, Lexington, KY 40536-0086, USA.
authors: Joshua A
authors: JA
authors: Lile
authors: William W
authors: WW
authors: Stoops
authors: Paul E A
authors: PE
authors: Glaser
authors: Lon R
authors: LR
authors: Hays
authors: Craig R
authors: CR
authors: Rush
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000339:Affect / Q000187:drug effects* / Q000502:physiology; D000525:Alprazolam / Q000008:administration & dosage*; D019969:Amphetamine-Related Disorders / Q000188:drug therapy* / Q000523:psychology; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D008875:Middle Aged; D011597:Psychomotor Performance / Q000187:drug effects* / Q000502:physiology
chemical_list: D003692:Delayed-Action Preparations; D008694:Methamphetamine; D000525:Alprazolam