A Review of Synthetic Cathinone–Related Fatalities From 2017 to 2020

Abstract

Background: Synthetic cathinones (SCs) are designer analogs of the natural active principle of khat. Since their appearance on the black market in 2003, their popularity has increased annually, and they have become the most seized class of new psychoactive substances reported to the UNODC Early Warning Advisory system. The constant introduction of newly synthesized molecules makes this issue difficult to monitor. The authors reviewed the most recent SC-related fatalities worldwide to highlight new trends of consumption, reporting acute pharmacological and toxicological symptoms, scene investigations, analytical methods, and reported SC concentrations in diverse biological matrices. Methods: A literature search was performed using scientific databases such as PubMed, Scopus, Science Direct, Web of Science, and Research Gate to identify relevant scientific publications from 2017 to 2020. In addition, a search was conducted through the EU EWS. Results: From 2017 to 2020, 31 different SCs were identified in 75 reported fatal intoxications in the literature, alone or in combination with other substances. The most abused SCs were N-ethylpentylone, N-ethylhexedrone, and 4-chloromethcathinone. The EU EWS included less detail on 72 additional SC-related fatalities from 2017 to 2020. Conclusions: New SCs continuously replace older natural and synthetic stimulant drugs, making determining the cause of death difficult. Analytical methods and high-performance mass spectrometry instruments are essential to detect the low concentrations of these potent new SCs. Little data are available on the pharmacology of these new drugs; the evaluation of toxicological antemortem and postmortem findings provides critical data on the drug's pharmacology and toxicology and for the interpretation of new SC cases.

Determination of the Synthetic Cannabinoids JWH-122, JWH-210, UR-144 in Oral Fluid of Consumers by GC-MS and Quantification of Parent Compounds and Metabolites by UHPLC-MS/MS

“…SCs along with synthetic cathinones remain the most consumed new psychoactive substances (NPS) accounting for 28 and 36% seizures along Europe according to the European Monitoring Centre for Drugs and Drug Addiction [ 3 ]. Both classes of compounds present potent and long-lasting effects but also severe acute and chronic toxicity possibly leading to fatalities [ 4 , 10 , 30 , 31 ]. Hence, due to their potential health hazard, identification and quantification in conventional and non-conventional biological samples of consumers can be strictly important.…”

Pyrrolidinyl Synthetic Cathinones α-PHP and 4F-α-PVP Metabolite Profiling Using Human Hepatocyte Incubations

“…SCs inhibit the transport of monoamines in the central nervous system, with specific affinities for dopamine, norepinephrine, and serotonin transporters (DAT, NET, and SERT, respectively), inducing euphoria and increased energy, but also tachycardia, elevated blood pressure, hyperthermia, agitation, delirium, psychosis, and death. SC use accounts for many intoxications and deaths, mainly through cardiac arrest or multiorgan failure [1,2]. SC effects are closely related to their specific selectivity for DAT, NET, and SERT.…”

“…All the cases involved the co-ingestion of other SCs, mainly α-pyrrolidinovalerophenone (α-PVP) and 3 ,4 -methylenedioxy-αpyrrolidinohexiophenone (MDPHP), or often opiates and/or benzodiazepines. A total of 13 α-PHP-related deaths were reported to the early warning system of the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) between 2017 and 2020 [2], with additional cases reported to the United Nations Office on Drugs and Crime (UNODC) early warning advisory system [11]. No intoxication cases or deaths involving 4F-α-PVP have been reported to date.…”

“…Halogenated SCs inhibit SERT with a higher potency than that of their non-halogenated analogues, inducing potentially fatal serotonin syndrome effects-tachycardia; nausea; hyperthermia; rhabdomyolysis; psychomotor tremors; and liver, kidney, and lung failure [12][13][14][15]. Therefore, 4F-α-PVP is expected to demonstrate higher toxicity than α-PVP, which has been involved in many intoxications and fatalities [1,2]. Halogenated SC use recently became popular, likely due to its higher potency [2], and 4F-α-PVP use is also expected to increase.…”

“…Therefore, 4F-α-PVP is expected to demonstrate higher toxicity than α-PVP, which has been involved in many intoxications and fatalities [1,2]. Halogenated SC use recently became popular, likely due to its higher potency [2], and 4F-α-PVP use is also expected to increase. In December 2019, the World Health Organization (WHO) recommended the control of α-PHP under Schedule II of the UNODC convention on psychotropic substances of 1971 [16].…”