Novel Synthetic Opioids: The Pathologist’s Point of View

Abstract

Background: New Psychoactive Substances (NPS) constitute a broad range of hundreds of natural and synthetic drugs, including synthetic opioids, synthetic cannabinoids, synthetic cathinones, and other NPS classes, which were not controlled from 1961 to 1971 by the United Nations drug control conventions. Among these, synthetic opioids represent a major threat to public health. Methods: A literature search was carried out using public databases (such as PubMed, Google Scholar, and Scopus) to survey fentanyl-, fentanyl analogs-, and other synthetic opioid-related deaths. Keywords including “fentanyl”, “fentanyl analogs”, “death”, “overdose”, “intoxication”, “synthetic opioids”, “Novel Psychoactive Substances”, “MT-45”, “AH-7921”, and “U-47700” were used for the inquiry. Results: From our literature examination, we inferred the frequent implication of fentanyls and synthetic opioids in side effects, which primarily affected the central nervous system and the cardiovascular and pulmonary systems. The data showed a great variety of substances and lethal concentrations. Multidrug-related deaths appeared very common, in most reported cases. Conclusions: The investigation of the contribution of novel synthetic opioid intoxication to death should be based on a multidisciplinary approach aimed at framing each case and directing the investigation towards targeted toxicological analyses.

Designer drugs: mechanism of action and adverse effects

“…Full names of the substances are provided in the supplementary information either designer opioids alone or designer opioids combined with other psychoactive substances (Coopman et al 2016a, b;Cunningham et al 2016;Dussy et al 2016;Dwyer et al 2018;Elliott et al 2016;Fels et al 2017Fels et al , 2019Fort et al 2016;Garneau et al 2019;Gillespie et al 1982;Guerrieri et al 2017;Helander et al 2017a;Karinen et al 2014;Koch et al 2018;Kriikku et al 2019;Kronstrand et al 2014;Krotulski et al 2018;Martucci et al 2018;McIntyre et al 2015bMcIntyre et al , 2016McIntyre et al , 2017Mohr et al 2016;Nash et al 2019;Ojanperä et al 2006;Papsun et al 2016;Partridge et al 2018;Poklis et al 2016;Richeval et al 2019;Ruan et al 2016;Sofalvi et al 2017;Staeheli et al 2016;Swanson et al 2017;Takase et al 2016;Vorce et al 2014;Yonemitsu et al 2016). Frisoni and colleagues recently published an overview of opioid-related fatalities that were attributed to synthetic opioids (Frisoni et al 2018). In addition to central nervous system and respiratory depression, chest wall rigidity after intravenous use could be a cause of death in synthetic opioid overdose cases…”

Novel Opioids: Systematic Web Crawling Within the e-Psychonauts’ Scenario

“…To the best of our knowledge, an unprecedented list of opioid drugs with a possible recreational/misuse potential was generated by these open web-only crawling software activities, which were focusing on a range of psychonaut forum entries. For all these fentanyl/non-fentanyl/miscellaneous drugs, only limited levels of preclinical/clinical data are typically available Armenian et al, 2018;Frisoni et al, 2018;Gerace et al, 2018a;Ventura et al, 2018; European Database on New Drugs [EDND], 2019; Tabarra et al, 2019; United Nations Office on Drugs and Crime [UNODC], 2019b). Apart from the vast range of previously undescribed fentanyl analogs, NPS.Finder R identified a further number of "novel" and potent/very potent, chemically diverse miscellaneous substances.…”

Quantification of U-47700 and its metabolites: N-desmethyl-U-47700 and N,N-didesmethyl-U-47700 in 12 autopsy blood samples employing SPE/LC–ESI-MS-MS

“…In 2016, Elliot et al [8] were the first to describe a U-47700-associated death and to attempt probing into the problem of analytic differentiation between synthetic opioids U-47700 and AH-7921 that were mutual isobaric compounds. Since that time, the number of cases of intoxication being reported in the scientific literature concerning morbidity and mortality associated with U-47700 use has been consistently increasing [9].…”

“…According to the published sources, the toxic effects of U-47700 in humans were demonstrated as overdosing [15][16][17] and fatalities [12,[18][19][20]. In the cases of U-47700-related deaths, the concentration of the drug in autopsy blood samples was in the range of 59-525 ng/mL [12,18,19], and in the cases of fatal poisonings in multiple drug use, U-47700 concentration values in autopsy blood samples were in the range of 13.8-1460 ng/mL [8,9].…”