Gamma-hydroxybutyrate (GHB) has been used as a recreational drug since the 1990s and over the last few years there has been increasing use of its analogues gamma-butyrolactone (GBL) and to a lesser extent 1,4-butanediol (1,4BD). This review will summarize the literature on the pharmacology of these compounds; the patterns and management of acute toxicity associated with their use; and the clinical patterns of presentation and management of chronic dependency associated with GHB and its analogues.

Over the last 10-15 years, γ-hydroxybutyrate (GHB) and γ-butyrolactone have become increasingly popular "club drugs", but they have also gained attention as potential agents of drug-facilitated sexual assault (DFSA). Several studies have attempted to characterize GHB's pharmacokinetic properties in humans, and the aim of this paper is to build on this research with an emphasis on DFSA cases. A 25 mg/kg dose of GHB was given to 12 GHB-naïve volunteers (6 men and 6 women). Urine and blood samples (serum and whole blood) were collected and analyzed by gas chromatography-mass spectrometry following liquid-liquid extraction. The urinary T(max) was 1 h in 11 volunteers with a mean C(max) of 67.6 mg/L (32.6-161.3 mg/L). Urinary concentrations rapidly decreased to < 10 mg/L (interpretive limit) for 11 volunteers after just 4 h. Data derived from whole blood (mean C(max) = 48.0 mg/L, T(max) = 24.6 min) closely matched that from serum (mean C(max) = 59.4 mg/L, T(max) = 23.3 min), suggesting GHB is distributed into erythrocytes. All 12 volunteers had GHB concentrations of less than 5 mg/L in both whole blood and serum after 3 h. Results verify the rapid elimination of GHB and the limited retrospective power of a concentration-based approach to prove GHB administration in blood and urine and confirm that, in DFSA cases, samples should be collected as soon as possible.

This study aimed to replicate a previous study which showed that endogenous opioid release, following an oral dose of amphetamine, can be detected in the living human brain using [11C]carfentanil positron emission tomography (PET) imaging. Nine healthy volunteers underwent two [11C]carfentanil PET scans, one before and one 3 h following oral amphetamine administration (0.5 mg/kg). Regional changes in [11C]carfentanil BPND from pre- to post-amphetamine were assessed. The amphetamine challenge led to significant reductions in [11C]carfentanil BPND in the putamen, thalamus, frontal lobe, nucleus accumbens, anterior cingulate, cerebellum and insula cortices, replicating our earlier findings. None of the participants experienced significant euphoria/'high', supporting the use of oral amphetamine to characterize in vivo endogenous opioid release following a pharmacological challenge. [11C]carfentanil PET is able to detect changes in binding following an oral amphetamine challenge that reflects endogenous opioid release and is suitable to characterize the opioid system in neuropsychiatric disorders.

Pathological gambling is a psychiatric disorder and the first recognized behavioral addiction, with similarities to substance use disorders but without the confounding effects of drug-related brain changes. Pathophysiology within the opioid receptor system is increasingly recognized in substance dependence, with higher mu-opioid receptor (MOR) availability reported in alcohol, cocaine and opiate addiction. Impulsivity, a risk factor across the addictions, has also been found to be associated with higher MOR availability. The aim of this study was to characterize baseline MOR availability and endogenous opioid release in pathological gamblers (PG) using [11C]carfentanil PET with an oral amphetamine challenge. Fourteen PG and 15 healthy volunteers (HV) underwent two [11C]carfentanil PET scans, before and after an oral administration of 0.5 mg/kg of d-amphetamine. The change in [11C]carfentanil binding between baseline and post-amphetamine scans (ΔBPND) was assessed in 10 regions of interest (ROI). MOR availability did not differ between PG and HV groups. As seen previously, oral amphetamine challenge led to significant reductions in [11C]carfentanil BPND in 8/10 ROI in HV. PG demonstrated significant blunting of opioid release compared with HV. PG also showed blunted amphetamine-induced euphoria and alertness compared with HV. Exploratory analysis revealed that impulsivity positively correlated with caudate baseline BPND in PG only. This study provides the first evidence of blunted endogenous opioid release in PG. Our findings are consistent with growing evidence that dysregulation of endogenous opioids may have an important role in the pathophysiology of addictions.

ABSTRACTγ-Hydroxybutyric acid (GHB) is a popular drug increasingly associated to cases of drug-facilitated sexual assault (DFSA). Currently, expanding procedures of analysis and having forensic evidence of GHB intake at a long term are mandatory. Up to now, most studies have been performed using GC-MS and LC-MS as analytical platforms, which 25 involve significant manipulation of the sample and, often, indirect measurements. In this work, procedures used in NMR-based metabolomics were applied to a GHB clinical trial on urine and serum. Detection, identification and quantification of the drug by NMR methods were surveyed, as well as the use of NMR-based metabolomics for the search of potential surrogate biomarkers of GHB consumption. Results demonstrated the suitability of NMR 30 spectroscopy, as a robust nondestructive technique, to monitor (detect, identify and quantify) fast and directly exogenous GHB in almost intact body fluids, and its high potential in the search for metabolites associated to GHB intake.