Gamma-hydroxybutyrate (GHB) in humans: pharmacodynamics and pharmacokinetics

Ann N Y Acad Sci. 2006 Aug;1074:559-76. doi: 10.1196/annals.1369.065.


Despite gamma-hydroxybutyrate (GHB) therapeutic uses and the increasing concern about its toxicity, few studies have addressed GHB dose-related effects under controlled administration and their relationship with its pharmacokinetics. The study design was double-blind, randomized, crossover, and controlled. As a pilot pharmacology phase I study, increasing doses of GHB were given. Single oral sodium GHB doses (40, 50, 60, and 72 mg/kg) were administered to eight volunteers. Plasma and urine were analyzed for GHB by gas chromatography-mass spectrometry. Physiological effects, psychomotor performance, and subjective effects were examined simultaneously. GHB produced dose-related changes in subjective effects as measured by questionnaires and VAS. GHB showed a mixed stimulant-sedative pattern, with initially increased scores in subjective feeling of euphoria, high, and liking followed by mild-moderate symptoms of sedation with impairment of performance and balance. Mean peak GHB plasma concentrations were 79.1, 83.1, 113.5, and 130.1 mug/L for 40, 50, 60, and 72 mg/kg, respectively. GHB-mediated physiological and subjective effects were dose dependent and related to GHB plasma concentrations. GHB urinary excretion was mainly related to administered doses. GHB-mediated subjective and physiological effects seem dose dependent and related to GHB plasma concentrations. Results suggest a high abuse liability of GHB in the range of dose usually consumed.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Humans
  • Male
  • Pilot Projects
  • Psychomotor Disorders / metabolism
  • Sodium Oxybate / administration & dosage
  • Sodium Oxybate / pharmacokinetics*
  • Sodium Oxybate / pharmacology*
  • Substance-Related Disorders / metabolism*
  • Time Factors


  • Sodium Oxybate