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.
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.
A series of molecularly imprinted polymers have been prepared and investigated as stationary phases in high performance liquid chromatography for the separation of testosterone and epitestosterone using non-polar mobile phases. The polymers were imprinted using 5?-dihydrotestosterone as template, and all retain testosterone more strongly than its 17?-OH epimer. The best polymer was prepared using trifluoromethylacrylic acid as functional monomer (interacting with the template via hydrogen bonds), divinylbenzene as inert cross-linker, and chloroform as porogen. It also included a steroid-based cross-linker, which may interact with the template via van der Waals interactions to lend additional shape selectivity. A 250×4.6mm column packed with this polymer gave baseline resolution of testosterone and epitestosterone (15 ?g each) in under 20 min. Preparation of the steroid based cross-linker included the selective reduction of 5?-dihydrotestosterone (17?-hydroxy-5?-androstan-3-one) to the 3?,17?-diol using K-selectride.
?-Hydroxybutyrate (GHB) and its metabolic precursor ?-butyrolactone (GBL) are often implicated in cases of drug-facilitated sexual assault (DFSA), although definitive confirmation of GHB/GBL ingestion is complicated by GHBs endogenous nature and rapid elimination following ingestion. Multiple studies have attempted to establish a discriminant limit (generally 10 mg/L) above which urinary GHB concentrations can be considered consistent with GHB/GBL consumption. To supplement the currently available data, a rapid gas chromatography-mass spectrometry method was developed and validated for the analysis of GHB (following acidic conversion to GBL) and used to analyze urine samples collected from 1126 women (mean = 0.84 mg/L, median = 0.68 mg/L, range = 0.00-5.5 mg/L). GHB concentrations were shown to be independent of urinary pH (within the range 4.6-9.3), age (within the range 18-35 years), body mass index (within the range 13.8-36.3), and race. Adjusting GHB concentrations with respect to urinary specific gravity had little effect on the mean value (0.91 mg/L) and range (0.0-7.76 mg/L), although a statistically significant trend of increasing GHB concentration with specific gravity could be observed. Our results can be taken to offer further support for the 10 mg/L discriminant limit for GHB administration in antemortem urine samples.
Reported incidences of drug-facilitated sexual assault (DFSA) are on the increase worldwide. These cases represent a particular challenge for the forensic toxicologist due to the difficulty in obtaining adequate evidence of drug administration. Primarily, this is due to the nature and diversity of the drugs involved, their pharmacology and sampling timescales. Evaluating whether a drug has been administered to a victim for the purpose of sexual assault can often be difficult, if not impossible. This review draws attention to this burgeoning crime and focuses on the unique challenges DFSA cases present in terms of evidential analysis. Current analytical methodologies for investigating DFSA are highlighted and discussed along with developments in improving analytical procedures. In particular, enlarging detection windows by adopting emerging LC-MS techniques is also discussed. This review also highlights the use of cutting-edge technologies such as ultra-HPLC and the use of alternative matrices for addressing the problem of improved retrospective drug detection.
Over the last 10-15 years, ?-hydroxybutyrate (GHB) and ?-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 GHBs 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.
Related JoVE Video
Journal of Visualized Experiments
What is Visualize?
JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.
How does it work?
We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.
Video X seems to be unrelated to Abstract Y...
In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.