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Alprazolam absorption kinetics affects abuse liability

G K Mumford1, S M Evans, J C Fleishaker

  • 1Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Md., USA.

Clinical Pharmacology and Therapeutics
|March 1, 1995
PubMed
Summary
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Extended-release alprazolam showed less abuse potential than immediate-release alprazolam. This study evaluated behavioral and subjective effects, finding XR formulations had reduced impact on performance and reinforcing properties.

Area of Science:

  • Pharmacology
  • Neuroscience
  • Clinical Psychology

Background:

  • Alprazolam is a commonly prescribed benzodiazepine with abuse potential.
  • Understanding the impact of drug formulation on abuse liability is crucial for clinical practice.
  • Immediate-release (IR) and extended-release (XR) formulations may differ in their abuse potential.

Purpose of the Study:

  • To compare the abuse liability of immediate-release (IR) alprazolam and extended-release (XR) alprazolam.
  • To assess the influence of drug release rate on behavioral, subjective, and reinforcing effects.

Main Methods:

  • A double-blind, crossover study involving 14 healthy men with a history of sedative abuse.
  • Participants received placebo, IR alprazolam (1 and 2 mg), and XR alprazolam (2 and 3 mg) in random order.

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  • Evaluations included behavioral performance, subjective effects, and plasma concentrations over 24 hours.

    • Main Results:

    • Immediate-release alprazolam (2 mg) significantly impaired cognitive, psychomotor, and memory performance.
    • Extended-release alprazolam (2 mg) did not affect these measures; 3 mg XR only affected motor coordination.
    • IR alprazolam increased positive subjective drug effects and reinforcing value (drug vs. money choice) more than XR formulations.

    Conclusions:

    • Extended-release alprazolam demonstrates a lower abuse potential compared to immediate-release alprazolam.
    • The release rate significantly influences the subjective and behavioral effects associated with alprazolam abuse liability.