Etizolam and Its Major Metabolites: A Short Review.

Etizolam is a benzodiazepine (BZD). Etizolam is structurally different from BZDs as a thiophene replaces the benzene ring and a triazole ring is fused to the diazepine ring, but etizolam's pharmacological profile is similar. Etizolam has been used to treat anxiety and panic disorders, to reduce depressive and somatization symptoms and to induce muscle relaxation. Etizolam is used recreationally due to its reinforcing and sedative effects. Etizolam is available in tablet or powder form or administered on blotter paper that can be placed on the tongue for oral absorption. Etizolam metabolizes into two major metabolites: α-hydroxyetizolam and 8-hydroxyetizolam, and all three compounds can be detected in different biological specimens using various common analytical techniques such as immunoassay, chromatography and mass spectrometry. Etizolam is a controlled drug in many countries around the globe but is approved for medical use in some countries, such as Japan, South Korea and Italy. This work is a collation and review of available literature on etizolam to help improve the fundamental understanding of its toxicology, outline best analytical practice, and aid interpretation of toxicology results.

The First Fatal Intoxication with 3-MeO-PCP in the UK and a Review of the Literature.

The phencyclidine derivative 3-methoxyphencyclidine (3-MeO-PCP) is a potent dissociative hallucinogen. Sought for recreational use as a novel psychoactive substance, it can also induce acute psychological agitation and pathophysiological cardiorespiratory effects. Due to the harms associated with its use, 3-MeO-PCP was added to the "Green List" of materials covered by the 1971 Convention on Psychotropic Substances as a Schedule II substance by the United Nations Commission on Narcotic Drugs in April 2021. There have been 15 previous reports of fatal intoxications following 3-MeO-PCP use, but only one was attributable to 3-MeO-PCP intoxication alone. In this report, we detail the first fatality due to 3-MeO-PCP intoxication to be reported in the UK, along with a review of the surrounding literature. While the blood concentrations associated with 3-MeO-PCP toxicity and fatality remain unclear, by providing details of sample collection and storage conditions, this case will aid in future interpretations. Furthermore, this case suggests that 3-MeO-PCP toxicity may be exacerbated by exercise. Users of 3-MeO-PCP should be cautioned against its use as a "club drug" or in a similar setting where elevations in heart rate, body temperature and blood pressure may occur.

Deaths from novel psychoactive substances in England, Wales and Northern Ireland: Evaluating the impact of the UK psychoactive substances act 2016.

BACKGROUND: 'Legal highs' began appearing in the UK in the mid-2000s. Whilst many of these substances were controlled under the 1971 Misuse of Drugs Act, novel compounds and new variants of controlled compounds were continuously being introduced to the recreational drug market. The Psychoactive Substances Act (PSA) was therefore implemented in 2016 as a blanket ban on all novel psychoactive substances (NPS). AIM: To evaluate the impact of the PSA on deaths following NPS use in England, Wales and Northern Ireland. METHODS: Cases reported to the National Programme on Substance Abuse Deaths where death had occurred 3 years pre- or post-implementation of the PSA were extracted. Cases with NPS detected at post-mortem were analysed and compared against cases non-NPS cases. RESULTS: 293 deaths with NPS detected were identified; 91 occurring before the PSA and 202 afterwards, indicating an 222.0% post-PSA increase. Contrastingly, non-NPS drug-related death case reporting increased by only 8.0%. Synthetic cannabinoid, anxiolytic/sedative and stimulant NPS were detected in the largest proportions of deaths pre-PSA; post-PSA stimulant NPS detections reduced whilst synthetic cannabinoid and anxiolytic/sedative detections increased.Post-PSA, average decedent age increased significantly (mean age pre-PSA 34.4 ± 10.8 vs post-PSA 38.3 ± 9.4), and they were significantly more likely to have been living in deprived areas (pre-PSA 50.0% vs post-PSA 65.9%). CONCLUSIONS: Reporting of deaths following NPS use has risen despite introduction of the PSA. Whilst deaths amongst younger individuals and those living in more affluent areas has reduced, additional approaches to prohibition are needed to curb their persistence in deprived demographics.

The effect of contextual information on decision-making in forensic toxicology.

The impact of cognitive bias on decisions in forensic science has been demonstrated in numerous disciplines such as DNA and fingerprints, but has not been empirically investigated in the more objective domains, such as forensic toxicology. In the first experiment, participants (n = 58) were affected by irrelevant case information when analysing data from an immunoassay test for opiate-type drugs. In the second experiment, participants (n = 53) were biased in their choice of tests, for example, the age of the deceased impacted testing strategy: for older people, medicinal drugs were commonly chosen, whereas for younger people drugs of abuse were selected. Based on the results that examiners analyzing case data may have biases if they are given access to case context, we propose that examiners analysing presumptive test data are blind to irrelevant contextual information. Furthermore, that forensic toxicology laboratories use a consistent protocol for selecting tests, and that any deviations are documented and justified.

Chemical and physical variations of cannabis smoke from a variety of cannabis samples in New Zealand.

Studies have compared the chemical properties of tobacco smoke to those of cannabis smoke, with the objective of identifying the chemical attributes responsible for the mutagenicity and carcinogenicity of cannabis smoke. Comparative studies have included small sample sizes and produced conflicting results. The aim of this study was to assess the major chemical and physical variations of cannabis smoke across a range of cannabis samples of different potencies and origins, sourced from the illegal market in New Zealand. Twelve cannabis samples were studied ranging from 1.0% to 13.4% delta-9-tetrahydrocannabinol (Δ9THC) content. A smoking machine was used to smoke "joints" (cannabis cigarettes) and the chemical/physical properties of the smoke assessed. The chemical constituents of the smoke extracts were analysed by gas chromatography/mass spectrometry. A range of different chemical constituents (in addition to Δ9THC) were identified and their concentrations estimated. Terpenoids were identified as the major variable in cannabis smoke, showing a 40-fold range in total terpenoid content. Analysis of the total particulate matter showed that significantly different levels of particulate matter were produced between the different cannabis samples, ranging from 14.6 to 66.3 mg/g of cannabis smoked. The Δ9THC delivery efficiency during smoking was also investigated and produced consistent results showing a mean and median of 12.6% and 10.8%, respectively, of the theoretically available Δ9THC (ranging from 7.2% to 28.0%).

The use of contextual information in forensic toxicology: An international survey of toxicologists' experiences.

Cognitive bias is a well-documented automatic process that can have serious negative consequences in a variety of settings. For example, cognitive bias within a forensic science setting can lead to examiners' judgements being swayed by details that they have learned while working on the case, and which go beyond the physical evidence being examined. Although cognitive bias has been studied in many forensic disciplines, such as fingerprints, bullet comparison, and document examination, knowledge of cognitive bias within forensic toxicology is lacking. Here, we address this knowledge gap by assessing the reported use of contextual information by an international group of forensic toxicologists attending the 54th conference of The International Association of Forensic Toxicologists (TIAFT) in Brisbane in 2016. In a first study, participants read a set of simple post-mortem toxicology results (two drug concentrations in blood) and then indicated what information they would normally use when interpreting these results in their day-to-day casework. Using a questionnaire, we then surveyed the familiarity of toxicologists with contextual bias and captured any suggested bias-minimizing procedures for use in forensic toxicology laboratories. Thirty-six participants from 23 different countries and with a range of 1-35 years' forensic toxicology reporting experience volunteered. Analysis of their responses showed that the majority of participants reported using some contextual information in their interpretation of these post-mortem toxicology results (range = 3-15 pieces of information, median ±â€¯SD = 11 ±â€¯3), the most common being the deceased's history of prescription or illicit drug use. More than three-quarters of participants reported being familiar with the concept of contextual bias, although few (n = 9) worked in laboratories that had a formal policy covering it. Over half of participants knew of at least one bias-minimizing procedure specifically for forensic toxicology casework, but only a quarter (overall) reported using bias-minimizing procedures in their laboratories. Our results provide substantial evidence that although practising forensic toxicologists are familiar with contextual bias, many report that they still engage in behaviours that could lead to cognitive bias (e.g., through the use of contextual information, through lack of explicit policies or bias-minimizing procedures). We anticipate that our work will form the basis of further research involving a larger sample of participants and examining other potentially relevant factors such as sex/gender, country and accreditation of laboratories.

Epidemiological Study of Carbon Monoxide Deaths in Scotland 2007-2016.

Carbon monoxide (CO) intoxications are quite frequent in forensic toxicology. Using a sample of 209 CO-positive deaths in Scotland from 2007 to 2016, this study provides ranges of percentage CO saturations (%COHb) according to the CO source and examines any correlation with age, gender, alcohol, and preexisting disease. It also reports the full toxicological findings, including drug concentrations, in CO-positive cases. The highest numbers of fatalities involved males, occurred during autumn/winter, and the main source of CO was fire. The median %COHb in fire-related cases was significantly lower than in non-fire-related cases such as those involving exhausts, generators and gas supply systems, and portable BBQs. There was no relationship between %COHb and age, blood alcohol concentration, or the presence of preexisting cardiovascular and/or respiratory disease. Toxicology results revealed that prescription medications were the most commonly detected drug group and that the number of cases positive for controlled drugs was small.

The Effect of Lowering the Legal Drink-Drive Limit on the Toxicological Findings in Driver Fatalities: A Comparison of Two Jurisdictions.

In December 2014, the legal blood alcohol limit for drivers in both Scotland and New Zealand was reduced from 80 to 50 mg/100 mL. This paper reports a retrospective study comparing changes in the toxicological findings in deceased drivers and motorcyclists before and after the limit change in both jurisdictions. A year of fatal motor vehicle crashes prior to and following the limit change is examined for both countries. In Scotland, there was an increase in drug prevalence among fatally injured drivers and motorcyclists, with the use of all drug groups increasing after the limit change, with the exception of cannabinoids. In New Zealand, there was a reduction in cases involving drugs only, but increases in the numbers of deceased drivers and motorcyclists positive for alcohol only and co-using alcohol and drugs.

Toxicological findings in driver and motorcyclist fatalities in Scotland 2012-2015.

Fatal motor vehicle crashes (MVCs) continue to be a common occurrence worldwide. This paper presents a retrospective analysis of the toxicological investigation of drivers and motorcyclists fatally injured in MVCs in Scotland from 2012 to 2015. One hundred and eighteen cases with full toxicological analysis, i.e., alcohol, drugs of abuse and prescription drugs, were examined. Of those 118 MVC cases, 74 (63%) were car drivers, 32 (27%) were motorcyclists and the remaining were drivers of other vehicles such as large goods vehicles. The majority of deceased drivers and motorcyclists were male (N=104, 88%). For the toxicological findings, 51 (43%) of the cases were negative, and of the 67 (57%) positive cases, alcohol and cannabinoids were the most frequently detected substances, followed by opioids and benzodiazepines. Fifteen percent of all drivers and motorcyclists were over the prescribed blood alcohol limit at the time of analysis. In comparison to previous reports of drug use by drivers in Scotland, benzodiazepines and new psychoactive substances were less common findings in fatally injured drivers and motorcyclists than in drivers suspected of being impaired.