Post-Mortem Toxicology: A Systematic Review of Death Cases Involving Synthetic Cannabinoid Receptor Agonists

Abstract

Background: Synthetic cannabinoid receptor agonists (SCRAs) have become the largest group of new psychoactive substances monitored by the European Union Early Warning System. Despite the wide diffusion on the market, data regarding effects, toxicities, and mechanisms as well as toxic/lethal doses are still scarce. Methods: A comprehensive literature search for articles published up to January 2019 was performed in multiple electronic databases. Only cases of death in which toxicological analyses revealed the presence of SCRAs in blood or urine and at least an external examination was performed, including those occurred in emergency departments, were included. Results: Of 380 studies identified, 354 were excluded, while 8 additional manuscripts were included through the screening of relevant references cited in the selected articles. A total number of 34 manuscripts (8 case series and 26 case reports) were included. Conclusions: Typical toxic ranges for SCRAs have not been so far identified, and the results of toxicological analyses should be interpreted with caution. In death cases involving SCRAs, a thorough post-mortem examination is a prerequisite to assess the role of the substance use in the deceased and to identify a probable mechanism of death. Even after a comprehensive analysis of clinical, circumstantial, toxicological, and autoptic data, the cause and manner of death remain unclear in some cases.

An outbreak of deaths associated with AMB-FUBINACA in Auckland NZ

“…Giorgetti et al. [15] also noted a significant prevalence of cardiovascular disease in their review of the published literature on deaths involving synthetic cannabinoids. Cardiovascular disease was certified as either the primary or a contributory cause of death in 27 (47%) of our cases, with hypertensive and atherosclerotic disease the most common diagnosis (52%).…”

“…“Typical blood concentrations” of synthetic cannabinoids are described as 0·1–10 ng/mL, while autopsy concentrations have been reported as high as 68–200 ng/mL [27] . Reported concentrations in fatalities have varied considerably with different synthetic cannabinoids [15] . In a death associated with AMB-FUBINACA in combination with EMB-FUBINACA, blood concentrations of both compounds were below detection limit (0·1 ng/mL), although various solid tissue concentrations ranged from 0·2 to 0·9 ng/g and 0·2 to 3·5 ng/g, respectively [13] .…”

“…In a survey of American medical examiner/coroner offices between 2010 and 2014, 25 deaths were reported in which synthetic cannabinoids were toxicologically confirmed and may have contributed to death [4] . Since 2014 an increasing number of deaths associated with a variety of synthetic cannabinoids has been reported [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] . A recent review of Australian coronial deaths between 2000 and 2017 revealed 55 cases in which synthetic cannabinoid use was considered a contributory mechanism to death [16] .…”

UHPLC-HRMS and GC-MS Screening of a Selection of Synthetic Cannabinoids and Metabolites in Urine of Consumers

“…The limited availability of screening tests for the detection of synthetic cannabinoids and/or metabolites in urine of consumers [9,14] prompted us to propose a screening method for urinalysis of JWH-122, JWH-210, UR-144 and their metabolites. The method can be applied to other compounds of the JWH family and successfully coupled UHPLC-HRMS and GC/MS assays.…”

“…Differently from cannabis products, synthetic cannabinoids can cause severe toxicity in active consumers and the offspring of pregnant or breastfeeding mothers [5,6], causing outbreaks of intoxication and fatalities [7,8]. Therefore, the analytical challenge involves not only the large range of different compounds and/or metabolites to identify, but also the variety of biological matrices to investigate including non-conventional matrices, which have gained major interest in recent years for information provided, detection window and minimal sample collection invasiveness [9].…”