Cognitive, psychomotor, and subjective effects of sodium oxybate and triazolam in healthy volunteers

Abstract

Rationale: Illicit gamma-hydroxybutyrate (GHB) has received attention as a "date rape drug" that produces robust amnesia; however, there is little experimental evidence in support of GHB's amnestic effects.

Objectives: This study compared the cognitive effects of GHB (sodium oxybate) with those of triazolam in healthy volunteers.

Materials and methods: Doses of sodium oxybate (1.125, 2.25, and 4.5 g/70 kg), triazolam (0.125, 0.25, and 0.5 mg/70 kg), and placebo were administered to 15 volunteers under repeated measures, counterbalanced, double-blind, double-dummy conditions. The time course and peak physiological, psychomotor, subjective, and cognitive effects were examined.

Results: Sodium oxybate and triazolam produced similar increases in participant ratings of drug effects. Performance on psychomotor, working memory, and episodic memory tasks was impaired to a greater extent after triazolam than sodium oxybate.

Conclusions: Together, these data suggest that sodium oxybate produces less psychomotor and cognitive impairment than triazolam at doses that produce equivalent participant-rated subjective effects in healthy volunteers.

Fig. 1

Time course of effects of triazolam (left panels) and sodium oxybate (right panels) on participant-rated drug effect, balance, and circular lights. Y-axes: rating on a visual analog scale in millimeters, time balanced on one foot (summed across both feet; 60 s total) in seconds, and number of correct responses, respectively. X-axes: time after drug administration in minutes (0 indicates pre-drug; measures were assessed approximately 35, 110, and 230 min after administration). Data points show means (N=15), brackets show + or −1 SEM, and the absence of brackets indicates that 1 SEM fell within the area of the data symbol. Filled symbols indicate values that are significantly different from the corresponding placebo value at the same time point (p<0.05)

Fig. 2

Peak participant-rated subjective effects of triazolam and sodium oxybate. Y-axes: rating expressed as peak effect, which is the mean of the maximum value for individual participants across the 4-h session (measures were assessed approximately 35, 110, and 230 min after administration). X-axes: dose in milligrams (triazolam) or grams (sodium oxybate) per 70 kg (log scale). PL designates placebo. Data points show means (N=15), brackets show ±1 SEM, and the absence of brackets indicates that 1 SEM fell within the area of the data symbol. Filled symbols indicate values that are significantly different from placebo; the letter “t” above 4.5 g/70 kg sodium oxybate indicates that that data point is significantly different from 0.5 mg/70 kg triazolam (p<0.05)

Fig. 3

Peak effects of triazolam and sodium oxybate on working memory. Y-axes: number of trials correct expressed as peak effect, which is the mean of the minimum value for individual participants across the 4-h session (measures were assessed approximately 35, 110, and 230 min after administration). X-axes: dose in milligrams (triazolam) or grams (sodium oxybate) per 70 kg (log scale); PL designates placebo. Data points show means (N=15), brackets show ±1 SEM, and the absence of brackets indicates that 1 SEM fell within the area of the data symbol. Filled symbols indicate values that are significantly different from placebo; the letter “t” above 4.5 g/70 kg sodium oxybate indicates that that data point is significantly different from 0.5 mg/70 kg triazolam (p<0.05)

Fig. 4

Effects of triazolam and sodium oxybate on episodic memory. Y-axes: number of words recalled (top panels) or discriminative index (d’, bottom panels) for words studied before drug or placebo administration (list 1, left panels) or during the period of drug effect (100 min after administration; list 2, right panels). X-axes: dose in milligrams (triazolam) or grams (sodium oxybate) per 70 kg (log scale). PL designates placebo. Data points show means (N=15), brackets show ±1 SEM, and the absence of brackets indicates that 1 SEM fell within the area of the data symbol. Filled symbols indicate values that are significantly different from placebo; the letter “t” above 2.25 or 4.5 g/70 kg sodium oxybate indicates that that data point is significantly different from 0.25 or 0.5 mg/70 kg triazolam, respectively (p<0.05)