title: Detection of designer Benzodiazepines in Scottish sub-populations
Creators: name: O'Connor, Lauren
Publisher: name: University of Glasgow
Year: 2020
Subjects: subject: Designer benzodiazepines, toxicology, research chemicals, post-mortem toxicology.

description: Designer benzodiazepine is the term used when referring to benzodiazepines, which have been available for recreational use since the late 2000s. Some designer benzodiazepines are prescribed in other countries and became popular in the UK as a drug of abuse, others were investigated as medicines in the 1960s and 1970s but were never brought to market. A few designer benzodiazepines are novel drugs created solely for the recreational market. Originally sold as “research chemicals” or “legal highs” they circumvented the law by having small structural differences to the traditional benzodiazepines and sold in packages containing the disclaimer “Not for Human Consumption.” The introduction of the Psychoactive Substances Act 2016 (PSA) put new UK legislation in place to control the distribution and manufacture of any compound that is “capable of producing a psychoactive effect,” this captured the designer benzodiazepines as well as other “legal highs”. This legislation works in conjunction with the current Misuse of Drugs Act 1971 (MoDA), thereby legislating against a distinct list of drugs in the MoDA and any drug producing a psychoactive effect in the PSA. While there is now clarity of the legal status of these drugs, the scale of use in different sub-populations in Scotland, before and after, this legislation is unknown. There is little literature exploring how commonly designer benzodiazepines are detected in post-mortem cases from both drug related and non-drug related deaths. It has been demonstrated that etizolam is a common finding in drug-related deaths in Scotland but there is a lack of data regarding the designer benzodiazepines that emerged after etizolam. This makes toxicological interpretation and the decision to include the drug in the cause of death very difficult for toxicologists and pathologists, respectively, as there is a lack reference ranges to consult. Similarly the scale of use in living populations who are required to abstain from drugs for reason such as treatment or incarceration is unknown. The initial legality and the belief they may evade detection by simple screening tests make the designer benzodiazepines an attractive option. Two Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) methods were developed in order to test the different sub-populations. The urine method developed was a qualitative screen and was validated for use. The blood method developed was used to quantify the designer benzodiazepines and was validated for use. A total of 2,582 samples were analysed from the different sub-populations. Of these, 893 were urine samples from living participants and 1691 were blood samples from deceased individuals. All blood samples were from the post-mortem (PM) cohort and 369 (22%) of the cases were positive for the designer benzodiazepines tested. Diclazepam was detected in 212 cases and gave a median concentration of 0.017 mg/L (n=157, 0.005 – 0.211 mg/L), Delorazepam was detected in 339 cases and gave a median concentration of 0.043 mg/L (n=311, 0.005 – 1.50 mg/L), Lormetazepam was detected in 144 cases and gave a median concentration of 0.010 mg/L (n=85, 0.005 – 0.18 mg/L), Flubromazepam was detected in 18 cases and gave a median concentration of 0.66 mg/L (n=15, 0.01 – 2.30 mg/L), Pyrazolam was detected in 9 cases and gave a median concentration of 0.033 mg/L (n=6, 0.008 – 1.10 mg/L). These concentrations can assist in the toxicological interpretation of these drugs. The urine samples, which were screened for a wider range of benzodiazepines, were from three different cohorts. These were made up of individuals being admitted to or liberated from one of the seven Scottish Prison Service (SPS) facilities included in this study, individuals under the supervision of a Drug Treatment and Testing Order (DTTO) through the Scottish Drug Court (SDC) system in Glasgow and patients undergoing psychiatric treatment from NHS Greater Glasgow and Clyde Forensic Directorate (NHS GGC FD). The analysis found that 55% of the 73 urine samples from the SDC were positive, 41% of the 725 SPS urine samples were positive and there were no positive samples found in the 95 NHS GGC FD urine samples. The results of the studies show that benzodiazepines and designer benzodiazepines are widely used in the Scottish population. The individuals from the SDC and NHS GGC FD were able to refuse to take part in the study or able to abstain before their known drug test date. The SPS samples only gives a snapshot of those being admitted to or liberated from prison, which is not a reflection of the general inmate population and not every post-mortem case was tested for designer benzodiazepines. However despite these limitations, key information about the scale, nature and blood concentrations of the designer benzodiazepines being abused in Scotland was gained.