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Suicide by vaping the synthetic cannabinoid 4F-MDMB-BINACA: cannabinoid receptors and fluoride at the crossroads of toxicity?

Abstract

A 22-year-old man was hospitalized after stating he would ‘commit suicide in a non-detectable way’. He was admitted with a severe necrotizing pancreatitis and acute kidney injury, evolving to multiple organ failure. His condition rapidly deteriorated, and he died 11 days after hospital admission. Postmortem histopathology confirmed fulminant necrotizing pancreatitis, acute tubular necrosis, cerebral edema, pericentral/midzonal hepatocellular necrosis and acute respiratory distress syndrome. Metabolites of 4F-MDMB-BINACA, a synthetic cannabinoid, were detected in urine and serum collected at hospital admission. The same drug was found in a vapor fluid found in the man’s apartment. As cannabis use has been etiologically linked to acute pancreatitis, we hypothesize that the more afferent and potent 4F-MDMB-BINACA could induce acute pancreatitis via stimulation of cannabinoid (CB)1-receptors. Alternatively, terminal fluorination could have induced a dose-dependent toxic effect on a wide range of cellular processes, leading to cell dysfunction and death. This is the first clinicopathological description of a lethal intoxication with 4F-MDMB-BINACA, following extensive vaping. Toxic effects could either relate to CB-receptor binding or to direct fluoride toxicity.

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References

  1. Centers for Disease Control and Prevention. Acute kidney injury associated with synthetic cannabinoid use—multiple states, 2012. MMWR Morb Mortal Wkly Rep. 2013;62(6):96–8.

    Google Scholar 

  2. Krotulski AJ, Mohr ALA, Kacinko SL, et al. 4F-MDMB-BINACA: A new synthetic cannabinoid widely implicated in forensic casework. J Forensic Sci. 2019;64:1451–61.

    CAS  Article  Google Scholar 

  3. Banister SD, Stuart J, Kevin RC, et al. Effects of bioisosteric fluorine in synthetic cannabinoid designer drugs JWH-018, AM-2201, UR-144, XLR-11, PB-22, 5F-PB-22, APICA, and STS-135. ACS Chem Neurosci. 2015;6:1445–58.

    CAS  Article  Google Scholar 

  4. World Health Organization. Critical Review Report: 4F-MDMB-BINACA. WHO expert committe drug depend. 2019.

  5. Haschimi B, Mogler L, Halter S, et al. Detection of the recently emerged synthetic cannabinoid 4F-MDMB-BINACA in “legal high” products and human urine specimens. Drug Test Anal. 2019;11:1377–86.

    CAS  Article  Google Scholar 

  6. Belze O, Legras A, Ehrmann S, et al. Cannabis-induced acute pancreatitis. Am J Emerg Med. 2011;29(131):e3-4.

    Google Scholar 

  7. Juan-Picó P, Fuentes E, Javier Bermúdez-Silva F, et al. Cannabinoid receptors regulate Ca2+ signals and insulin secretion in pancreatic β-cell. Cell Calcium. 2006;39:155–62.

    Article  Google Scholar 

  8. Linari G, Agostini S, Amadoro G, et al. Involvement of cannabinoid CB1- and CB2-receptors in the modulation of exocrine pancreatic secretion. Pharmacol Res. 2009;59:207–14.

    CAS  Article  Google Scholar 

  9. Wargo KA, Geveden BN, McConnell VJ. Cannabinoid-induced pancreatitis: A case series. J Pancreas. 2007;8:579–83.

    Google Scholar 

  10. Hermanns-Clausen M, Kneisel S, Szabo B, Auwärter V. Acute toxicity due to the confirmed consumption of synthetic cannabinoids: Clinical and laboratory findings. Addiction. 2013;108:534–44.

    Article  Google Scholar 

  11. Centers for Disease Control and Prevention. Notes from the field: Hospital outbreak of carbapenem-resistant Klebsiella pneumoniae producing New Delhi metallo-beta-lactamase—Denver, Colorado, 2012. JAMA. 2013;6:108.

    Google Scholar 

  12. Silva JP, Carmo H, Carvalho F. The synthetic cannabinoid XLR-11 induces in vitro nephrotoxicity by impairment of endocannabinoid-mediated regulation of mitochondrial function homeostasis and triggering of apoptosis. Toxicol Lett. 2018;287:59–69.

    CAS  Article  Google Scholar 

  13. Buser GL, Gerona RR, Horowitz BZ, et al. Acute kidney injury associated with smoking synthetic cannabinoid. Clin Toxicol. 2014;52:664–73.

    CAS  Article  Google Scholar 

  14. Araujo TT, Barbosa Silva Pereira HA, Dionizio A, et al. Changes in energy metabolism induced by fluoride: Insights from inside the mitochondria. Chemosphere. 2019;236:124357.

    CAS  Article  Google Scholar 

  15. Usuda K, Kono K, Dote T, et al. Usefulness of the assessment of urinary enzyme leakage in monitoring acute fluoride nephrotoxicity. Arch Toxicol. 1999;73:346–51.

    CAS  Article  Google Scholar 

  16. Barbier O, Arreola-Mendoza L, Del Razo LM. Molecular mechanisms of fluoride toxicity. Chem Biol Interact. 2010;188:319–33.

    CAS  Article  Google Scholar 

  17. Song C, Fu B, Zhang J, et al. Sodium fluoride induces nephrotoxicity via oxidative stress-regulated mitochondrial SIRT3 signaling pathway. Sci Rep. 2017;7:672.

    Article  Google Scholar 

  18. Larsson A, Ristoff E, Anderson ME. Glutathione synthetase deficiency and other disorders of the γ-glutamyl cycle. In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors. Metabolic and molecular bases of inherited disease. New York: McGraw-Hill; 1995.

    Google Scholar 

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Acknowledgements

The authors would like to thank Christophe Stove (Ghent University), Philippe Vervliet (University of Antwerp) and Volker Auwarter (University of Freiburg) for their valuable input.

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BVR—drafted the manuscript, performed forensic autopsy. AC—revised the manuscript extensively, performed toxicological analyses. KA—drafted the manuscript, provided clinical data. AVN, HN, BM—revised the manuscript, performed toxicological analyses. WJ—revised the manuscript, performed forensic autopsy.

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Correspondence to Babette Van Rafelghem.

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The current report was written in accordance with the ethical standard guidelines of the University of Antwerp.

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Van Rafelghem, B., Covaci, A., Anseeuw, K. et al. Suicide by vaping the synthetic cannabinoid 4F-MDMB-BINACA: cannabinoid receptors and fluoride at the crossroads of toxicity?. Forensic Sci Med Pathol 17, 684–688 (2021). https://doi.org/10.1007/s12024-021-00424-7

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  • DOI: https://doi.org/10.1007/s12024-021-00424-7

Keywords

  • 4F-MDMB-BINACA
  • Vaping
  • Acute pancreatitis
  • Acute kidney injury
  • Fluoride