Four cases of death involving the novel synthetic cannabinoid 5F-Cumyl-PEGACLONE

Abstract

Purpose Cumyl-PEGACLONE was the first synthetic cannabinoid (SC) with a γ-carbolinone core structure detected in forensic casework and, since then, it has dominated the German SC-market. Here the first four cases of death involving its fluorinated analog, 5F-Cumyl-PEGACLONE, a recently emerged γ-carbolinone derived SC, are reported. Methods Complete postmortem examinations were performed. Postmortem samples were screened by immunoassay, gas chromatography mass spectrometry (GC-MS) or liquid chromatography tandem mass spectrometry. For quantification of SCs, the standard addition method was employed. Herbal blends were analyzed by GC-MS. In each case of death, the Toxicological Significance Score (TSS) was assigned to the compound. Results 5F-Cumyl-PEGACLONE was identified at concentrations ranging 0.09-0.45 ng/mL in postmortem femoral blood. In case 1, signs of hypothermia and kidney bleedings were noted. Despite a possible tolerance due to long term SC use, a TSS of 3 was assigned. In case 2, an acute heroin intoxication occurred and a contributory role (TSS = 1) of 5F-Cumyl-PEGACLONE was suggested. In case 3, a prisoner was found dead. GC-MS analysis of herbal blends, retrieved in his cell together with paraphernalia, confirmed the presence of 5F-Cumyl-PEGACLONE and a causative role was deemed probable (TSS = 2). In case 4, the aspiration of gastric content due to a SC-induced coma was observed (TSS = 3). Conclusions 5F-Cumyl-PEGACLONE is an emerging and extremely potent SC which raises serious public health concerns. A comprehensive analysis of circumstantial, clinical, and postmortem findings, as well as an in-depth toxicological analysis is necessary for a valid interpretation and for the assessment of the toxicological significance.

In vitro activity profiling of Cumyl‐PEGACLONE variants at the CB1 receptor: Fluorination versus isomer exploration

“…However, contrasting with these reports are a number of fatalities reported in Australia, in which even sub‐nanogram per millilitre concentrations of Cumyl‐PEGACLONE in blood were considered as highly probable to have contributed to death 13 . Similarly, for 5F‐Cumyl‐PEGACLONE, low blood concentrations have been linked to fatalities 10,13 . Therefore, whether there is a difference in toxicity between Cumyl‐PEGACLONE and 5F‐Cumyl‐PEGACLONE is currently not clear.…”

“…Reported concentrations of Cumyl‐PEGACLONE ranged from 0.38 to 34.9 nM (0.14–13 ng/mL) in serum from clinical samples and from 0.32 to 24.2 nM (0.12–9 ng/mL) in femoral post‐mortem blood samples 6,13 . Cases of 5F‐Cumyl‐PEGACLONE included a concentration range of 0.24–1.2 nM (0.09–0.45 ng/mL) 10,13 . The latter concentrations, derived from post‐mortem samples, should be interpreted with caution for different reasons, among which are post‐mortem redistribution and non‐availability of the exact methods that were applied for quantification.…”

“…Following the identification of this compound in November 2017, the EU Early Warning System of the EMCDDA sent out a formal notification for this compound late 2017. Not surprisingly, identification and case reports for both Cumyl‐PEGACLONE and 5F‐Cumyl‐PEGACLONE have emerged since then 6,8–12 . Initially, SCRAs containing a γ‐carbolinone core structure were hypothesized to be relatively safe, as no lethalities were observed in cases with (over)consumption of Cumyl‐PEGACLONE.…”

“…However, several fatalities have been reported during the past few years 13 . Also for 5F‐Cumyl‐PEGACLONE several fatalities have been reported 10,13 . Therefore, the relative ‘safety’ of γ‐carbolinones can be questioned 6,10,13 .…”

“…Also for 5F‐Cumyl‐PEGACLONE several fatalities have been reported 10,13 . Therefore, the relative ‘safety’ of γ‐carbolinones can be questioned 6,10,13 . As fluorination can have a beneficial effect on a compound's activity, resulting in a higher potency, it could be hypothesized that this would lead to a higher toxicity of 5F‐Cumyl‐PEGACLONE 7,14,15 .…”