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Acute Toxicity Associated with Use of 5F-Derivations of Synthetic Cannabinoid Receptor Agonists with Analytical Confirmation

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Abstract

Introduction

Synthetic Cannabinoid Receptor Agonists (SCRAs) are the largest group of new psychoactive substances reported to the European Warning System and the United Nations Office on Drugs and Crime to date. The heterogeneous nature and speed of diversification of these compounds make it challenging to accurately characterise and predict harms of these compounds in pre-clinical studies, ahead of their appearance.

Case Report

We report the case of a 19-year-old female who purchased three products from a headshop: two new psychoactive substances (sachets of “cannabis tea” and “mushroom tea”) as well as two LSD blotters. After the “cannabis tea” was smoked and the two LSD blotters and “mushroom tea” were ingested, the patient became tachycardic (HR 128), developed seizures, agitation, visual hallucinations as well as suspected serotonergic toxicity (sustained ankle clonus 20–30 beats) 1–2 hours after use. She was treated with 1 mg of intravenous midazolam. Symptoms/signs resolved within 13 hours. No further supportive care was required. Plasma, blood, and urine samples confirmed the presence of two SCRAs: 5FAKB-48 and 5F-PB-22. The patient also reported therapeutic use of both fluoxetine and citalopram for depression.

Discussion

To the best of our knowledge, this is the first case report of non-fatal intoxication with 5F-AKB-48 with analytical confirmation and exposure times. It also highlights the difficulties in understanding the pattern of toxicity of certain SCRAs in the context of psychotropic medications/co-morbid mental illness.

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References

  1. EMCDDA. European Drug Report (Trends and Developments). 2015. http://www.emcdda.europa.eu/edr2015. Accessed: 15 Nov 2015.

  2. Mechoulam R, Gaoni Y. A total synthesis of D1-delta-1-tetrahydrocannabinol, the active constituent of hashish. J Am Chem Soc. 1965;87:3273–5.

    Article  CAS  PubMed  Google Scholar 

  3. Wagner JA, Jarai Z, Batkai S, Kunos G. Hemodynamic effects of cannabinoids: coronary and cerebral vasodilation mediated by cannabinoid CB1 receptors. Eur J Pharmacol. 2001;423:203–10.

    Article  CAS  PubMed  Google Scholar 

  4. Calignano A, Katona I, Desarnaud F, Giuffrida A, La Rana G, Mackie K, Freund TF, Piomelli D. Bidirectional control of airway responsiveness by endogenous cannabinoids. Nature. 2000;408:96–101.

    Article  CAS  PubMed  Google Scholar 

  5. De Petrocellis L, Melck D, Bisogno T, Di Marzo V. Endocannabinoids and fatty acid amides in cancer, inflammation and related disorders. Chem Phys Lipids. 2000;108:191–209.

    Article  CAS  PubMed  Google Scholar 

  6. Wilson RI, Nicoll RA. Endocannabinoid signaling in the brain. Science. 2002;296:678–82.

    Article  CAS  PubMed  Google Scholar 

  7. Tomida I, Pertwee RG, Azuara-Blanco A. Cannabinoids and glaucoma. Br J Ophthalmol. 2004;88:708–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Maccarrone M. CB2 receptors in reproduction. Br J Pharmacol. 2008;153:189–98.

    Article  CAS  PubMed  Google Scholar 

  9. Le Foll B, Goldberg SR. Cannabinoid CB1 receptor antagonists as promising new medications for drug dependence. JPET. 2005;312:875–83.

    Article  CAS  Google Scholar 

  10. Cota D, Marsicano G, Lutz B, Vicennati V, Stalla GK, Pasquali R, Pagotto U. Endogenous cannabinoid system as a modulator of food intake. Int J Obes. 2003;27:289–301.

    Article  CAS  Google Scholar 

  11. Janero DR, Makriyannis A. Cannabinoid receptor antagonists: pharmacological opportunities, clinical experience, and translational prognosis. Expert Opin Emerg Drugs. 2009;14:43–65.

    Article  CAS  PubMed  Google Scholar 

  12. Devane WA, Dysarz 3rd FA, Johnson MR, Melvin LS, Howlett AC. Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol. 1988;34:605–13.

    CAS  PubMed  Google Scholar 

  13. Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature. 1990;346:561–4.

    Article  CAS  PubMed  Google Scholar 

  14. Everett RM, Descotes G, Rollin M, Greener Y, Bradford JC, Benziger DP, Ward SJ. Nephrotoxicity of pravadoline maleate (WIN 48098-6) in dogs: evidence of maleic acid-induced acute tubular necrosis. Fundam Appl Toxicol. 1993;21:59–65.

    Article  CAS  PubMed  Google Scholar 

  15. Wiley JL, Marusich JA, Huffman JW, Balster RL, Thomas BF. Hijacking of basic research: the case of synthetic cannabinoids. Methods Rep RTI Press. 2011;2011:17971.

    PubMed  PubMed Central  Google Scholar 

  16. EMCDDA. Perspectives on drugs. Synthetic cannabinoids in Europe. 2015. http://www.emcdda.europa.eu/attachements.cfm/att_212361_EN_Synthetic%20cannabinoids_updated2015.pdf. Accessed 22 Dec 2015.

  17. Karila L, Roux P, Rolland B, Benyamina A, Reynaud M, Aubin HJ, Lançon C. Acute and long-term effects of cannabis use: a review. Curr Pharm Des. 2014;20:4112–8.

    Article  CAS  PubMed  Google Scholar 

  18. Schneir AB, Cullen J, Ly BT. “Spice” girls: synthetic cannabinoid intoxication. J Emerg Med. 2011;40:296–9.

    Article  PubMed  Google Scholar 

  19. Tait RJ, Caldicott D, Mountain D, Hill SL, Lenton S. A systematic review of adverse events arising from the use of synthetic cannabinoids and their associated treatment. Clin Toxicol (Phila). 2015;15:1–13.

    Google Scholar 

  20. Lovett C, Wood DM, Dargan PI. Pharmacology and toxicology of the synthetic cannabinoid receptor agonists. Réanimation. 2015;24:527–41.

    Article  Google Scholar 

  21. EMCDDA–Europol joint publication. EMCDDA–Europol 2014 Annual Report on the implementation of Council Decision 2005/387/JHA. 2014. http://www.emcdda.europa.eu/attachements.cfm/att_240380_EN_TDAN15001ENN.pdf. Accessed 22 Nov 2015.

  22. United Nations Office on Drugs and Crime. Global synthetic drugs assessment amphetamine-type stimulants and new psychoactive substances. 2014. https://www.unodc.org/documents/scientific/2014_Global_Synthetic_Drugs_Assessment_web.pdf. Accessed 22 Dec 2015.

  23. De Luca MA, Castelli MP, Loi B, Porcu A, Martorelli M, Miliano C, Kellett K, Davidson C, Stair LJ, Schifano F, Di Chiara G. Native CB1 receptor affinity, intrinsic activity and accumbens shell dopamine stimulant properties of third generation SPICE/K2 cannabinoids: BB-22, 5F-PB-22, 5F-AKB-48 and STS-135. Neuropharmacology. 2015;11.

  24. BlueLight. AKB-48-F Experience report. http://www.bluelight.org/vb/threads/647964-AKB-48-F-Experience-report. Accessed 15 Nov 2015.

  25. BlueLight. 627774-Cannabinoid-AKB-48. http://www.bluelight.org/vb/threads/627774-Cannabinoid-AKB-48. Accessed 15 Nov 2015.

  26. Drugs-Forum. Experiences - 5F-AKB48, BB-22, 5F-PB22, STS-135 Last Gen Noids comparison from experience. https://drugs-forum.com/forum/showthread.php?t=226101. Accessed 15 Nov 2015.

  27. Gurney SMR, Scott KS, Kacinko SL, Presley BC, Logan BK. Pharmacology, toxicology, and adverse effects of synthetic cannabinoid drugs. Forensic Sci Rev. 2014;26:53–78.

    CAS  PubMed  Google Scholar 

  28. Banister SD, Stuart J, Kevin RC, Edington A, Longworth M, Wilkinson SM, Beinat C, Buchanan AS, Hibbs DE, Glass M, Connor M, McGregor IS, Kassiou M. 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.

    Article  CAS  PubMed  Google Scholar 

  29. Gatch MB, Forster MJ. Δ9-tetrahydrocannabinol-like effects of novel synthetic cannabinoids found on the gray market. Behav Pharmacol. 2015;26:460–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Trecki J, Gerona RR, Schwartz MD. Synthetic cannabinoid–related illnesses and deaths. (perspective). N Engl J Med. 2015;373:2.

    Article  Google Scholar 

  31. Schep LJ, Slaughter RJ, Hudson S, Place R, Watts M. Delayed seizure-like activity following analytically confirmed use of previously unreported synthetic cannabinoid analogues. Hum Exp Toxicol. 2015;34:557–60.

    Article  CAS  PubMed  Google Scholar 

  32. Gugelmann H, Gerona R, Li C, Tsutaoka B, Olson KR, Lung D. ‘Crazy monkey’ poisons man and dog: human and canine seizures due to PB-22, a novel synthetic cannabinoid. Clin Toxicol (Phila). 2014;52:635–8.

    Article  CAS  Google Scholar 

  33. Hussain F, Al-musawi H, Al-khateeb E, Abu sayf A. Ischemic cerebrovasular accident, uncontrolled seizuresand acute myocardial infarction associated with syn thetic marijuana abuse. Am J Intern Med. 2014;2:138–14.

    Google Scholar 

  34. 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  PubMed  Google Scholar 

  35. Behonick G, Shanks KG, Firchau DJ, Mathur G, Lynch CF, Nashelsky M, Jaskierny DJ, Meroueh C. Four postmortem case reports with quantitative detection of the synthetic cannabinoid, 5F-PB-22. J Anal Toxicol. 2014;38:559–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Rachelle Abouchedid.

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Conflict of Interest

Authors Rachelle Abouchedid, James H. Ho, Simon Hudson, Alison Dines, John RH. Archer, David M. Wood and Paul I. Dargan declare that they have no conflict of interest.

Professor Dargan reports that he is a member of the UK Advisory Council on the Misuse of Drugs and the Scientific Committee of the European Monitoring Centre for Drugs and Drug Addiction.

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Abouchedid, R., Ho, J.H., Hudson, S. et al. Acute Toxicity Associated with Use of 5F-Derivations of Synthetic Cannabinoid Receptor Agonists with Analytical Confirmation. J. Med. Toxicol. 12, 396–401 (2016). https://doi.org/10.1007/s13181-016-0571-7

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