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Clinical Effects of Synthetic Cannabinoid Receptor Agonists Compared with Marijuana in Emergency Department Patients with Acute Drug Overdose

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Abstract

Introduction

Synthetic cannabinoid receptor agonists (SCRAs) are heterogeneous compounds originally intended as probes of the endogenous cannabinoid system or as potential therapeutic agents. We assessed the clinical toxicity associated with recent SCRA use in a large cohort of drug overdose patients.

Methods

This subgroup analysis of a large (n = 3739) drug overdose cohort study involved consecutive ED patients at two urban teaching hospitals collected between 2009 and 2013. Clinical characteristics of patients with the exposure to SCRAs (SRCA subgroup) were compared with those from patients who smoked traditional cannabinoids (marijuana subgroup). Data included demographics, exposure details, vital signs, mental status, and basic chemistries gathered as part of routine clinical care. Study outcomes included altered mental status and cardiotoxicity.

Results

Eighty-seven patients reported exposure to any cannabinoid, of whom 17 reported SCRAs (17 cases, 70 controls, mean age 38.9 years, 77 % males, 31 % Hispanic). There were no significant differences between SRCA and marijuana with respect to demographics (age, gender, and race/ethnicity), exposure history (suicidality, misuse, and intent), vital signs, or serum chemistries. Mental status varied between SRCA and marijuana, with agitation significantly more likely in SCRA subgroup (OR = 3.8, CI = 1.2–11.9). Cardiotoxicity was more pronounced in the SCRA subgroup with dysrhythmia significantly more likely (OR = 9.2, CI = 1.0–108).

Conclusions

In the first clinical study comparing the adverse effects of SCRA overdose vs. marijuana controls in an ED population, we found that SCRA overdoses had significantly pronounced neurotoxicity and cardiotoxicity compared with marijuana.

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References

  1. Castaneto MS, Gorelick DA, Desrosiers NA, Hartman RL, Pirard S, Huestis MA. Synthetic cannabinoids: epidemiology, pharmacodynamics, and clinical implications. Drug Alcohol Depend. 2014;1(144):12–41.

    Article  Google Scholar 

  2. Guindon J, Hohmann AG. The endocannabinoid system and pain. CNS Neurol Disord Drug Targets. 2009;8(6):403–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Vardakou I, Pistos C, Spiliopoulou C. Spice drugs as a new trend: mode of action, identification and legislation. Toxicol Lett. 2010;197(3):157–62.

    Article  CAS  PubMed  Google Scholar 

  4. Rosenbaum CD, Carreiro SP, Babu KM. Here today, gone tomorrow … back again? A review of herbal marijuana alternatives (K2, Spice), synthetic cathinones (bath salts), kratom, Salvia divinorum, methoxetamine, and piperazines. J Med Toxicol. 2012;8:15–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Hermanns-Clausen M, Kithinji J, Spehl M, Angerer V, Franz F, Eyer F, et al. Adverse effects after the use of JWH-210 - a case series from the EU Spice II plus project. Drug Test Anal. 2016; Jan 15.

  6. 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(3):534–44.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  8. Young AC, Schwarz E, Medina G, Obafemi A, Feng SY, Kane C, et al. Cardiotoxicity associated with the synthetic cannabinoid, K9, with laboratory confirmation. Am J Emerg Med. 2012;1320:e5–7.

    Google Scholar 

  9. Every-Palmer S. Warning: legal synthetic cannabinoid-receptor agonists such as JWH 018 may precipitate psychosis in vulnerable individuals. Addiction. 2010;105:1859–60.

    Article  PubMed  Google Scholar 

  10. Müller H, Sperling W, Köhrmann M, Huttner HB, Kornhuber J, Maler JM. The synthetic cannabinoid Spice as a trigger for an acute exacerbation of cannabis induced recurrent psychotic episodes. Schizophr Res. 2010;118:309–10.

    Article  PubMed  Google Scholar 

  11. Zimmermann US, Winkelmann PR, Pilhatsch M, Nees JA, Spanagel R, Schulz K. Withdrawal phenomena and dependence syndrome after the consumption of “Spice Gold”. Dtsch Artzebl Int. 2009;106:464–7.

    Google Scholar 

  12. Forrester MB, Kleinschmidt K, Schwarz E, Young A. Synthetic cannabinoid and marijuana exposures reported to poison centers. Hum Exp Toxicol. 2012;31(10):1006–11.

    Article  CAS  PubMed  Google Scholar 

  13. 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). 2016;54(1):1–13.

    Article  CAS  Google Scholar 

  14. Gunderson EW, Haughey HM, Ait-Daoud N, Joshi AS, Hart CL. “Spice” and “K2” herbal highs: a case series and systematic review of the clinical effects and biopsychosocial implications of synthetic cannabinoid use in humans. Am J Addict. 2012;21(4):320–6.

    Article  PubMed  Google Scholar 

  15. Manini AF, Nelson LS, Stimmel B, Vlahov D, Hoffman RS. Incidence of adverse cardiovascular events in adults following drug overdose. Acad Emerg Med. 2012;19(7):843–9.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Manini AF, Hoffman RS, Stimmel B, Vlahov D. Clinical risk factors for in hospital adverse cardiovascular events after acute drug overdose. Acad Emerg Med. 2015;22(5):499–507.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Winstock A, Mitcheson L, Ramsey J, Marsden J. Mephedrone: use, subjective effects and health risks. Addiction. 2011;106(11):1991–6.

    Article  PubMed  Google Scholar 

  18. Oluwabusi O, Lobach L, Akhtar U, Youngman B, Ambrosini PJ. Synthetic cannabinoid induced psychosis: two adolescent cases. J Child Adolesc Psychopharmacol. 2012;22:393–5.

    Article  PubMed  Google Scholar 

  19. Peglow S, Buchner III J, Briscoe G. Synthetic cannabinoid induced psychosis in a previously nonpsychotic patient. Am J Addict. 2012;21:287–8.

    Article  PubMed  Google Scholar 

  20. Dines AM, Wood DM, Galicia M, Yates CM, Heyerdahl F, Hovda KE, et al. Euro-DEN research group, dargan PI. Presentations to the emergency department following cannabis use—a multi-centre case series from ten european countries. J Med Toxicol. 2015;11(4):415–21.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Al Kury LT, Voitychuk OI, Ali RM, et al. Effects of endogenous cannabinoid anandamide on excitation-contraction coupling in rat ventricular myocytes. Cell Calcium. 2014;55:104–18.

    Article  CAS  PubMed  Google Scholar 

  22. Al Kury LT, Voitychuk OI, Yang KH, et al. Effects of the endogenous cannabinoid anandamide on voltage-dependent sodium and calcium channels in rat ventricular myocytes. Br J Pharmacol. 2014;171:3485–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Al Kury LT, Yang KH, Thayyullathil FT, et al. Effects of endogenous cannabinoid anandamide on cardiac Na(+)/Ca(2)(+) exchanger. Cell Calcium. 2014;55:231–7.

    Article  CAS  PubMed  Google Scholar 

  24. Lapoint J, James LP, Moran CL, Nelson LS, Hoffman RS, Moran JH. Severe toxicity following synthetic cannabinoid ingestion. Clin Toxicol (Phila). 2011;49(8):760–4.

    Article  CAS  Google Scholar 

  25. Mir A, Obafemi A, Young A, Kane C. Myocardial infarction associated with use of the synthetic cannabinoid K2. Pediatrics. 2011;128:e1622–7.

    Article  PubMed  Google Scholar 

  26. Von Der Haar J, Talebi S, Ghobadi F, Singh S, Chirurgi R, Rajeswari P, et al. Synthetic cannabinoids and their effects on the cardiovascular system. J Emerg Med. 2016;50(2):258–62.

    Article  Google Scholar 

  27. Ibrahim S, Al-Saffar F, Wannenburg T. A unique case of cardiac arrest following K2 abuse. Case Rep Cardiology. 2014;2014.

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Acknowledgments

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Sources of funding

This study was supported in part by grant K23DA026476 from the National Institute on Drug Abuse (PI: AFM). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Drug Abuse or the National Institutes of Health.

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Correspondence to Alex F. Manini.

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Previous presentations

Presented in abstract form at the XXXV International Congress, European Association of Poisons Centres and Clinical Toxicologists, St. Julian’s, Malta, 2015.

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Zaurova, M., Hoffman, R.S., Vlahov, D. et al. Clinical Effects of Synthetic Cannabinoid Receptor Agonists Compared with Marijuana in Emergency Department Patients with Acute Drug Overdose. J. Med. Toxicol. 12, 335–340 (2016). https://doi.org/10.1007/s13181-016-0558-4

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  • DOI: https://doi.org/10.1007/s13181-016-0558-4

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