Comparative abuse liability of GHB and ethanol in humans

Gamma-hydroxybutyric acid (GHB; sodium oxybate) is approved for narcolepsy symptom treatment, and it is also abused. This study compared the participant-rated, observer-rated effects, motor/cognitive, physiological, and reinforcing effects of GHB and ethanol in participants with histories of sedative (including alcohol) abuse. Fourteen participants lived on a residential unit for ∼1 month. Sessions were conducted Monday through Friday. Measures were taken before and repeatedly up to 24 hours after drug administration. Participants were administered GHB (1, 2, 4, 6, 8, and 10 g/70 kg), ethanol (12, 24, 48, 72, 96, and 120 g/70 kg), or placebo in a double-blind, within-subjects design. For safety, GHB and ethanol were administered in an ascending dose sequence, with placebos and both drugs intermixed across sessions. The sequence for each drug was stopped if significant impairment or intolerable effects occurred. Only 9 and 10 participants received the full dose range for GHB and ethanol, respectively. The highest doses of GHB and ethanol showed onset within 30 minutes, with peak effects at 60 minutes. GHB effects dissipated between 4 and 6 hours, whereas ethanol effects dissipated between 6 and 8 hours. Dose-related effects were observed for both drugs on a variety of measures assessing sedative drug effects, abuse liability, performance impairment, and physiological effects. Within-session measures of abuse liability were similar between the two drugs. However, postsession measures of abuse liability, including a direct preference test between the highest tolerated doses of each drug, suggested somewhat greater abuse liability for GHB, most likely as a result of the delayed aversive ethanol effects (e.g., headache).