The drug-drug interaction between gamma-hydroxybutyric acid (GHB) and cobicistat was evaluated in a randomized, double-blind, placebo-controlled, crossover clinical trial. Ten participants underwent two 5-day treatment periods with at least 1-week washout period in between treatments. In each treatment period, the participants received cobicistat (150 mg once daily orally) or placebo. On day 5 of each treatment period, the participants were given a single oral dose of GHB (25 mg/kg). Plasma concentrations of GHB, subjective effects, blood pressure, heart rate and oxygen saturation were monitored for 5 hours after dosing. GHB pharmacokinetic and pharmacodynamics parameters were calculated for each participant for each study period. The pharmacokinetics of GHB were not substantially changed by cobicistat coadministration. Geometric mean ratios (90% CI) for GHB with and without cobicistat were 0.95 (0.89-1.03) for AUC0-5, and 0.95 (0.85-1.06) for Cmax. No drug-related adverse events necessitating subject withdrawal or medical intervention occurred during the study. Furthermore, no differences in subjective or physiological effects were observed when GHB was administered alone or with cobicistat.