“Spice”-related deaths in and around Munich, Germany: A retrospective look at the role of synthetic cannabinoids in our postmortem cases over a seven-year period (2014–2020)

Abstract

The synthetic cannabinoid receptor agonists (SCRAs, “Spice”) are a diverse group of recreational drugs, with their structural and pharmacological differences still evolving. Due to limited data on their pharmacokinetics and pharmacodynamics in humans, the assessment of their role in fatal cases remains challenging. Forensic toxicologists thus often rely on previous reports of intoxication cases. This work provides detailed information on forensic cases for which SCRAs could be detected in postmortem specimens. All cases included underwent an autopsy at the Institute of Forensic Medicine in Munich between 2014 and 2020, followed by routine toxicological analyses, including analysis for alcohol. Pharmaceutical substances and classical drugs of abuse were detected and quantified in postmortem femoral venous blood (or liver where not available) by liquid chromatography-tandem mass spectrometry (LC-MS/MS) at the Forensic Toxicological Centre Munich. Based on circumstantial data and case histories, additional targeted analyses for the detection of SCRAs and other new psychoactive substances were performed on those cases for which a prior consumption was indicated or suspected. Synthetic cannabinoids were detected and quantified in femoral venous blood (81 cases), cardiac blood (12 cases), liver tissue (2 cases), antemortem blood (2 cases) and urine (1 case) by LC-MS/MS at the Institute of Forensic Medicine in Freiburg, Germany. The cause of death and the roles of the SCRAs in the individual fatalities were assessed based on the concentrations detected, the presence and concentrations of other drugs, pathological findings at autopsy and case histories. Furthermore, the total number of SCRAs detected and how these substances were scattered over the investigated period (i.e. how often a particular substance was detected each year) were determined. The latter was correlated with the number of SCRAs detected in police seizures analysed at the Bavarian State Criminal Police Office (BLKA), as well as the change in their legal status in Germany. The concentration range for each SCRA detected in femoral venous blood was defined and correlated with the estimated interval between death and sample collection. We were able to identify 98 “Spice”-related fatalities among our autopsy cases from 2014 to 2020. Most of the deceased were male (91.8%), with a median age of 36 years. SCRAs played a causative role in 51%, a contributory role in 26% and no significant role in 23% of cases. The most common cause of death was polydrug intoxications that include synthetic cannabinoids. Altogether 41 different synthetic cannabinoids could be detected during the investigated period. 5F-ADB was the most prevalent SCRA among our cases ( n = 25), at median and maximum concentrations in femoral venous blood of 0.22 μg/L and 14 μg/L, respectively, followed by 5F-MDMB-PICA (0.64 μg/L; 7.2 μg/L) and AB-CHMINACA (3.95 μg/L; 28 μg/L). Cumyl-CBMICA and 5F-MDMB-P7AICA were two of the least frequently detected synthetic cannabinoids. These results correlate with the number of SCRAs detected in local police seizures. No direct correlation between synthetic cannabinoid concentrations and postmortem interval was evident from our results. Our awareness of the importance of SCRAs in fatal intoxication cases has clearly increased since 2014, as is evident from our numbers in toxicological analyses for their postmortem detection. Nonetheless, the number of identified “Spice”-related fatalities has significantly decreased in our cohort of cases after the New Psychoactive Substances Act was implemented in Germany. Furthermore, the causative role of SCRAs in these fatalities has since also diminished in significance. Considering the continuing evolvement of SCRAs and the limited knowledge about their pharmacology, postmortem distribution and stability in humans, forensic toxicologists will undoubtedly benefit from more detailed postmortem case studies to assess their role in fatal intoxication cases.