Relative Abuse Liability of GHB in Humans: A Comparison of Psychomotor, Subjective, and Cognitive Effects of Supratherapeutic Doses of Triazolam, Pentobarbital, and GHB

Abstract

Although preclinical studies suggest that GHB has low likelihood for abuse, case reports indicate that GHB is abused. This study evaluated the relative abuse liability of GHB in 14 volunteers with histories of drug abuse. Psychomotor, subjective, and cognitive effects of a broad range of GHB doses (2-18 g/70 kg), up to a dose that produced severe behavioral impairment in each participant, were compared to placebo and two abused sedative/hypnotic drugs, triazolam (0.5 and 1 mg/70 kg) and pentobarbital (200 and 400 mg/70 kg), under double-blind, double-dummy conditions at a residential research facility. In general, GHB produced effects similar to triazolam and pentobarbital, although GHB was not identified as a benzodiazepine or barbiturate by participants that correctly identified triazolam and pentobarbital as such. On most measures of likelihood of abuse (eg ratings of liking, reinforcing effects), effects of pentobarbital were significantly greater than those of triazolam, with GHB being intermediate. GHB produced significantly greater negative subjective effects, including nausea, than the other drugs. Memory impairment after GHB was less than that after triazolam and pentobarbital. Within participants, the dose-effect function for sedation was steeper for GHB than for triazolam and pentobarbital. Also, at higher doses, GHB was associated with greater sedation and more variability across participants in sedation. Taken together, these data suggest that the profile of effects of GHB only partially overlaps with that of triazolam and pentobarbital. Although the likelihood for GHB to be abused is intermediate to triazolam and pentobarbital, the possibility of accidental overdose (ie greater sedation than intended) with GHB appears to be greater.

Pharmacodynamic interactions of a solid formulation of sodium oxybate and ethanol in healthy volunteers

“…Benzodiazepine use has been associated with a wide range of cognitive side effects [46,77,78]. Few studies have compared SO and benzodiazepines on cognitive tasks [76][77][78][79], and due to differences in study populations and in cognitive tasks, the data of this study cannot be compared with Carter's data [76,79]. Nevertheless, the present results showed that sedation induced by SMO.IR remained mainly subjective and was less frequently observed in performance tasks.…”

“…First, the subjects had no history of alcohol use/abuse and therefore did not reflect the targeted population. However, in subjects with histories of abuse of sedative/hypnotic drugs, a great variability in sedation ratings was demonstrated [79] and most of them remained awake and alert after an administration of 2 or 4 g 70 kg -1 GHB. Moreover, only one dose of SMO.IR and one dose of alcohol were tested.…”

Non-medical use, abuse and dependence on sedatives and tranquilizers among U.S. adults: Psychiatric and socio-demographic correlates

“…In addition to covariates related to socio-demographics and co-occurring substance use, we included in our analysis independent variables related to anxiety and mood disorders (listed in the next section) since sedatives and tranquilizers have well-described anxiolytic effects (Carter et al, 2006;Helmus et al, 2005;Jackson et al, 2005;Zawertailo et al, 2003).…”

Residual social, memory and oxytocin-related changes in rats following repeated exposure to γ-hydroxybutyrate (GHB), 3,4-methylenedioxymethamphetamine (MDMA) or their combination

“…In rodent models, GHB caused acute impairment in working memory (Kueh et al 2008) and spatial learning (Pedraza et al 2009;Sircar et al 2008). GHB can also cause acute cognitive disturbance in human users, although this can be difficult to dissociate from the strong sedative effects of the drug (Carter et al 2006). To date, it is unclear whether there are lasting cognitive deficits arising from GHB use and addressing this issue was a major aim of the present study.…”