title: Alprazolam absorption kinetics affects abuse liability.
abstract: OBJECTIVE
  To evaluate the behavioral, subjective, and reinforcing effects of immediate-release (IR) alprazolam and extended-release (XR) alprazolam to assess the effect of release rate on laboratory measures of abuse liability.
  
  
  METHODS
  Fourteen healthy men with histories of sedative abuse participated as subjects in a double-blind crossover study. All subjects received placebo, 1 and 2 mg immediate-release alprazolam, and 2 and 3 mg extended-release alprazolam in random order. Behavioral performance, subjective effects, and alprazolam plasma concentrations were assessed repeatedly 1/2 hour before and 1/2, 1, 3, 5, 7, 9, 12, and 24 hours after drug administration.
  
  
  RESULTS
  Mean peak alprazolam plasma concentrations occurred 1.7 and 9.2 hours after immediate-release alprazolam and extended-release alprazolam, respectively. Compared to placebo, 2 mg immediate-release alprazolam impaired all measures of psychomotor and cognitive performance (Digit Symbol Substitution Test), motor coordination (circular lights and balance), and memory (digit entry and recall); 2 mg extended-release alprazolam did not affect any of these measures and 3 mg extended-release alprazolam impaired circular lights only. Immediate-release alprazolam, 2 mg, increased all six measures of positive drug effects (e.g., ratings of liking or good effects); none of these measures were increased by 2 mg extended-release alprazolam and only three of the six measures were increased by 3 mg extended-release alprazolam. A drug versus money multiple-choice procedure designed to assess the relative reinforcing effects of each condition was administered 24 hour after the drug. The amount of money subjects were willing to "pay" to take the drug was significantly greater than placebo for both doses of immediate-release alprazolam but for neither dose of extended-release alprazolam.
  
  
  CONCLUSIONS
  These data indicate that extended-release alprazolam has less potential for abuse than immediate-release alprazolam.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Md., USA.
authors.forename: G K
authors.initials: GK
authors.lastname: Mumford
authors.forename: S M
authors.initials: SM
authors.lastname: Evans
authors.forename: J C
authors.initials: JC
authors.lastname: Fleishaker
authors.forename: R R
authors.initials: RR
authors.lastname: Griffiths
mesh_terms: D000328:Adult; D000525:Alprazolam / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000704:Analysis of Variance; D003071:Cognition / Q000187:drug effects; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects; D012016:Reference Values; D019966:Substance-Related Disorders / Q000378:metabolism* / Q000523:psychology*; D011795:Surveys and Questionnaires; D013997:Time Factors
chemical_list: D003692:Delayed-Action Preparations; D000525:Alprazolam