Relative Abuse Liability of γ-Hydroxybutyric Acid, Flunitrazepam, and Ethanol in Club Drug Users

Summary

A single oral dose of gamma-hydroxybutyric acid (GHB) at 40 or 60 mg/kg produces euphoria and pleasurable effects with slightly higher ratings than those from flunitrazepam (1.25 mg) or ethanol (0.7 g/kg) in healthy male recreational club drug users. GHB shows a biphasic time profile: an initial stimulant-like effect as plasma concentrations rise, followed by a later sedative effect unrelated to its kinetics. GHB increases blood pressure and pupil diameter, while flunitrazepam produces marked sedation. Both GHB and flunitrazepam impair psychomotor performance, including digit symbol substitution and balance tasks, whereas ethanol only mildly affects balance. The findings suggest a high abuse liability of GHB and flunitrazepam in this population.

Study at a glance

Abstract

OBJECTIVES: Despite the increasing concern about gamma-hydroxybutyric acid (GHB) toxicity, there are few studies examining the clinical pharmacology of GHB and its abuse potential. To evaluate GHB-induced subjective and physiological effects, its relative abuse liability and its impact on psychomotor performance in club drug users. MATERIALS AND METHODS: Twelve healthy male recreational users of GHB participated in 5 experimental sessions in the framework of a clinical trial. The study was randomized, double-blind, double-dummy, and crossover. Drug conditions were a single oral dose of GHB (40 or 60 mg/kg), ethanol (0.7 g/kg), flunitrazepam (1.25 mg), and placebo. Study variables included vital signs (blood pressure, heart rate, oral temperature, pupil diameter), psychomotor performance (digit symbol substitution test, balance, Maddox-Wing), subjective effects (a set of 13 visual analogue scales, Addiction Research Center Inventory-49 items, and Evaluation of the Subjective Effects of Substances with Potential of Abuse questionnaires), and pharmacokinetics. RESULTS: All active conditions induced positive effects related to their abuse potential. The administration of GHB produced euphoria and pleasurable effects with slightly higher ratings than those observed for flunitrazepam and ethanol. Gamma-hydroxybutyric acid induced a biphasic time profile with an initial stimulant-like effect related to the simultaneous rise of plasma concentrations and a latter sedative effect not related to GHB kinetics. Gamma-hydroxybutyric acid increased blood pressure and pupil diameter. Ethanol induced its prototypical effects, and flunitrazepam produced marked sedation. Gamma-hydroxybutyric acid and flunitrazepam impaired psychomotor performance, digit symbol substitution test, and balance task, whereas ethanol, at the dose tested, induced only mild effects exclusively affecting the balance task. CONCLUSIONS: Our results suggest a high abuse liability of GHB and flunitrazepam in club drug users.