¹Department of Psychiatry and Behavioral Sciences, and the Department of Neuroscience, Johns Hopkins University School of Medicine, Behavioral Biology Research Center, and the Clinical Pharmacology Branch National Institute on Drug Abuse, Addiction Research Center, Baltimore, and the Clinical Pharmacokinetics Unit, The Upjohn Company, Kalamazoo, Mich., USA

Correspondence: Roland R. Griffiths, PhD, 5510 Nathan Shock Dr., Baltimore, MD 21224.

^aPresent address: Columbia University, College of Physicians and Surgeons and The New York State Psychiatric Institute, 722 West 168th St., Unit 66, New York, NY 10032.

^*Supported in part by National Institute on Drug Abuse grant DA-03889 and by The Upjohn Company (Kalamazoo, Mich.).

Preliminary results of this work were presented at the Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics, New Orleans, La., March 30–April 1, 1994.

Received 17 June 1994; Accepted 19 September 1994.

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 ½ hour before and ½, 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.