Synthetic Cannabinoid Receptor Agonists in Scottish sub-populations

The term Synthetic Cannabinoid Receptor Agonists (SCRAs) describes a group of hundreds of compounds which are not derived from the Cannabis plant but bind at the cannabinoid receptors. These compounds have been available for recreational use since the late 2000s and have been linked to a variety of adverse effects and death. Due to the number of compounds available, and their novel nature, controlling the manufacture, sale and possession of SCRAs has proved challenging under current legislative structure. The introduction of the Psychoactive Substances Act 2016 brought under control the manufacture, distribution and possession in a custodial facility of any SCRA which had not already been controlled by the Misuse of Drugs Act 1971. Whilst clarification has been brought to the legal status of these drugs, what remains largely unknown is the scale of use within Scotland, and different sub-populations. Simple and quick protocols were developed for the extraction of 40 SCRAs (comprising parent compounds and metabolites) from blood and urine. Sensitive Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) methods were developed to detect and quantify the most commonly encountered compounds at realistic blood and urine concentrations. Depending on the timing of cohort sample receipt, one of these methods was then applied to cohorts of individuals from various sub-populations within Scotland. Optimised methods for detection and quantitation in blood and urine then underwent validation. Overall, in 1177 cases tested, SCRA prevalence was found to be low, relative to the prevalence of more ‘traditional’ drugs of abuse such as opiates/opioids or benzodiazepines. The detection of SCRAs was highest in the cohort of individuals presenting at an Emergency Department (ED) with suspected drug toxicity, with 56% of cases tested positive. Second highest was the cohort of deceased individuals undergoing post-mortem (PM) examination, with SCRAs found in 11% of cases tested. It should be noted, though, that samples from both these cohorts were only tested if SCRA use had been suspected. Samples collected from individuals undergoing admission to or liberation from Scottish Prison Service (SPS) facilities were found to contain SCRAs at a rate of 3% for all samples. All of the positive samples in this cohort were admission samples (except one which was not labeled admission or liberation), thus 5% of admission samples were positive for SCRAs. Out of 73 samples collected from individuals under the jurisdiction of the Glasgow Drug Court (GDC), only 1 sample was positive (1.4%). All 95 samples collected from individuals being treated by the NHS Greater Glasgow and Clyde Forensic Directorate (FD) were negative for all SCRAs included in the panel. These results indicate that SCRAs are having negative effects on the health of users and that they are being used by the offending community, both of which have been reported in mainstream media. Another suspected aspect of SCRA use was the intention of avoiding detection by mandatory drug tests. Both the GDC and FD cohorts were aware of their required compliance with drug abstinence and mandatory drug testing regime, but the low findings of SCRAs in these groups suggest this is not the case. It is acknowledged that the numbers of individuals tested in the cohorts were relatively low, and that the studies were not a true calculation of prevalence. In addition to this, not all SCRAs were included in the analytical method, and those not included would not be identified in samples. Nonetheless, important information was gained about the scale and nature of SCRA use within Scotland

Analysis and clinical findings of cases positive for the novel synthetic cannabinoid receptor agonist MDMB-CHMICA

Context: MDMB-CHMICA is a synthetic cannabinoid receptor agonist which has caused concern due to its presence in cases of adverse reaction and death. Method: 43 cases of suspected synthetic cannabinoid ingestion were identified from patients presenting at an Emergency Department and from post-mortem casework. These were subjected to liquid-liquid extraction using tertiary-butyl methyl ether and quantitatively analysed by Electospray Ionisation Liquid Chromatography – tandem Mass Spectrometry. For positive samples, case and clinical details were sought and interrogated. Results: 11 samples were found positive for MDMB-CHMICA. Concentrations found ranged from <1 – 22 ng/mL (mean: 6 ng/mL, median: 3 ng/mL). The age range was 15 – 44 years (mean: 26 years, median: 21 years), with the majority (82%) of positive results found in males. Clinical presentations included hypothermia, hypoglycaemia, syncope, recurrent vomiting, altered mental state and serotonin toxicity, with corresponding concentrations of MDMB-CHMICA as low as <1 ng/mL. Duration of hospitalisation ranged from 3 – 24 hours (mean: 12 hours, median: 8 hours). Discussion: The concentration range presented in this case series is indicative of MDMB-CHMICA having a high potency, as is known to be the case for other synthetic cannabinoid receptor agonists. The age range and gender representation were consistent with that reported for users of other drugs of this type. The clinical presentations observed were typical of synthetic cannabinoid receptor agonists and show the difficulties in identifying reactions potentially associated with drugs of this type. Conclusion: The range of MDMB-CHMICA concentrations in Emergency Department presentations (n=9) and post-mortem cases (n=2) was reported. No correlation between the concentration of this drug and clinical presentation or cause of death was reported in this sample. However, the potential for harm associated with low concentrations of MDMB-CHMICA and the symptoms of toxicity being non-specific was highlighted

Synthetic cannabinoid receptor agonists in postmortem casework in Scotland

Synthetic cannabinoid receptor agonists (SCRAs) have been a concern to forensic toxicologists since their emergence as drugs of abuse in the mid-late 2000s. The extent of their use in Scotland appears to be low especially when compared to other drug groups such as opioids and benzodiazepines. There is a concern, however, that the use is widespread in prison populations in particular. In this work, samples of blood and urine collected during routine postmortem examination between April 2017 and March 2019 were subjected to analysis of SCRA compounds. Circumstantial and demographic information was collected on positive cases to build up a body of evidence for where SCRAs may be most likely to contribute to the cause of death. Thirteen out of 133 cases (10%) tested were positive for one or more compound in one or more matrix. Overall, the detection of 5F-MDMB-PINACA or its O-desmethyl acid metabolite was most common, followed by the metabolite shared by AB-FUBINACA and MMB-FUBINACA. SCRA-positive cases were predominantly males (92%), and the age range of all decedents was 21–49 years old (median 36 years). The majority of cases were certified as drug-related deaths (DRDs, 38%), natural/medical (31%) or suicide (23%), and two of the DRDs mentioned SCRAs specifically in the cause of death. The concentrations of SCRAs detected did not seem to be as important to the determination of the cause of death as their mere presence, but quantitative results were reported (where possible) in order to build up a body of evidence for SCRA concentrations in different case types