Effect of [gamma]-hydroxybutyrate on driving as measured by a driving simulator

Rationale Gamma-hydroxybutyrate acid (GHB), a GABA.sub.B receptor agonist approved for treatment of narcolepsy, impairs driving ability, but little is known about doses and plasma concentrations associated with impairment and time course of recovery. Objective To assess effects of oral GHB (Xyrem®)...

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Bibliographic Details
Published in:Psychopharmacology 2018-11, Vol.235 (11), p.3223
Main Authors: Liakoni, Evangelia, Dempsey, Delia A, Meyers, Matthew, Murphy, Nancy G, Fiorentino, Dary, Havel, Christopher, Haller, Christine
Format: Article
Language:English
Subjects:
Dosage and administration
Drug therapy
GABA agonists
Gamma hydroxybutyrate
Narcolepsy
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Summary:Rationale Gamma-hydroxybutyrate acid (GHB), a GABA.sub.B receptor agonist approved for treatment of narcolepsy, impairs driving ability, but little is known about doses and plasma concentrations associated with impairment and time course of recovery. Objective To assess effects of oral GHB (Xyrem®) upon driving as measured by a driving simulator, and to determine plasma concentrations associated with impairment and the time course of recovery. Methods Randomized, double-blind, two-arm crossover study, during which 16 participants received GHB 50 mg/kg orally or placebo. GHB blood samples were collected prior to and at 1, 3, and 6 h post dosing. Driving simulator sessions occurred immediately after blood sampling. Results Plasma GHB was not detectable at baseline or 6 h post dosing. Median GHB concentrations at 1 and 3 h were 83.1 mg/L (range 54-110) and 24.4 mg/L (range 7.2-49.7), respectively. Compared to placebo, at 1 h post GHB dosing, significant differences were seen for the life-threatening outcome collisions (p < 0.001) and off-road accidents (p = 0.018). Although driving was not faster, there was significantly more weaving and erratic driving with GHB as measured by speed deviation (p = 0.002) and lane position deviation (p = 0.004). No significant impairment regarding driving outcomes was found in the GHB group at 3 and 6 h post dose. Conclusion GHB in doses used to treat narcolepsy resulted in severe driving impairment at 1 h post dosing. After 3 to 6 h, there was full recovery indicating that safe driving is expected the next morning after bedtime therapeutic GHB use in the absence of other substances.
ISSN:0033-3158
DOI:10.1007/s00213-018-5025-2