Synthetic Drug Intoxication in Children: Recognition and Management in the Emergency Department

Table of Contents

 

Due to the constantly changing chemical formulations of synthetic drugs and the prevalence of polysubstance abuse, diagnosing patients with intoxication from these substances is often challenging. In this issue, you will learn:

Basic terminology and background information on synthetic cannabinoids, synthetic cathinones, and phenethylamines

Common presentations of synthetic drug intoxication

To ask broad questions while taking the history to elicit productive answers

When diagnostic studies are warranted, and which studies can help identify more-serious complications

Best practices for managing patients with synthetic drug intoxication

1. Abstract
2. Case Presentations
3. Introduction
4. Critical Appraisal of the Literature
5. Etiology and Pathophysiology
   1. Synthetic Cannabinoids
      1. Development and Consumption of Synthetic Cannabinoids
      2. Adverse Effects of Synthetic Cannabinoids
   2. Synthetic Cathinones
   3. Phenethylamines
6. Differential Diagnosis
7. Prehospital Care
8. Emergency Department Evaluation
   1. History
   2. Physical Examination
      1. Synthetic Cannabinoids
      2. Synthetic Cathinones
      3. Phenethylamines
9. Diagnostic Studies
   1. Screening Tests
   2. Imaging Studies
      1. Brain Imaging
      2. Radiographic Imaging
   3. Testing for Patients With Altered Mental Status and Myalgias
   4. Testing for Patients With Chest Pain
10. Symptomatic Treatment
    1. Synthetic Cannabinoids
    2. Synthetic Cathinones and Phenethylamines
11. Special Circumstances
    1. Body Packing of Drugs
    2. Planning for Large-Scale Dance Festivals
12. Controversies and Cutting Edge
13. Disposition
14. Summary
15. Risk Management Pitfalls in the Management of Pediatric Patients With Synthetic Drug Intoxication
16. Time- and Cost-Effective Strategies
17. Case Conclusions
18. Key Points
19. Clinical Pathway for Management of Intoxication After Consumption of Synthetic Drugs
20. Tables and Images
    1. Table 1. Exposures to Synthetic Bath Salts and THC, by Age Range, for 2009-2012
    2. Table 2. Differential Diagnosis of Altered Level of Consciousness
    3. Table 3. Toxidromes, Complications, and Treatment Options for Poisoning from Drugs of Abuse
    4. Figure 1. Number of Calls Received by Poison Control Centers About Exposure to Synthetic Cannabinoids, 2009-2015
    5. Figure 2. Packages Of Synthetic Cannabinoids
21. References

Abstract

When children and adolescents present to the emergency department with agitation or mental status changes, intoxication from synthetic drug use should be in the differential diagnosis. Identifying the responsible compound(s) may be difficult, so asking the patient broad questions and utilizing appropriate diagnostic studies, when indicated, will aid in making the diagnosis and help identify more-serious complications. This issue discusses the challenges presented by the changing chemical formulations of synthetic cannabinoids, cathinones, and phenethylamines; outlines common presentations of intoxication from these substances; and summarizes best practices for evaluating and managing patients who present with intoxication after consumption of these synthetic drugs of abuse.

Case Presentations

A 15-year-old girl presents to your ED at 3 am. She is brought in by her mother, who woke up and found the girl staggering around their living room. The patient’s electronic medical record is unremarkable; the girl has no significant past medical history. On examination, she is mildly tachycardic; injected conjunctiva and diaphoresis are noted. The girl laughs intermittently and inappropriately during your encounter. Upon further discussion, she admits smoking marijuana that was purchased on the Internet by an older sibling. Several hours later, her mentation improves, but she now reports 6 out of 10 chest pain. What other substances could have been combined with the “marijuana?” Will blood or urine testing lead to a diagnosis? Is any management beyond supportive care indicated for this patient?

A 17-year-old boy presents to the ED via EMS after his friends called for help while at an electronic dance music festival. The patient’s vital signs are notable for tachycardia (110 beats/min) and hyperthermia (40°C [104°C]). On examination, the boy is agitated, and he admits drinking several alcoholic beverages but denies any co-ingestions. Are this patient’s vital sign abnormalities and altered mental status likely explained solely by his reported alcohol use? What other ingestions may have occurred? How can you anticipate such exposures?

Introduction

Synthetic cannabinoids, cathinones, and phenethylamines have gained popularity due to a public perception that they were relatively safe to consume and that they were legal. In 2011, a temporary ban was placed by the United States Drug Enforcement Administration on some synthetic cannabinoids, and in 2012, federal legislation was passed that covered all synthetic cannabimimetic agents. Other nations have also worked to close legal loopholes and target synthetic cannabinoids. One study from New Zealand demonstrated that legislation that reduced the availability of synthetic cannabinoids was correlated with a decrease in psychiatric ED visits associated with synthetic cannabinoid use.¹ Another study conducted in New Zealand found a 52% reduction in patient utilization of emergency psychiatric services after the enactment of legislation that sought to curb the supply of synthetic cannabinoids.² Today, however, new formulations have been developed to skirt restrictions, and synthetic cannabinoids remain the second most commonly used drugs of abuse, after conventional marijuana. Moreover, synthetic cannabinoids continue to be available for sale online and in many stores.^3-5 Additionally, as Mathai et al found in the city of Houston, Texas, use may continue to increase despite legislative attention given to synthetic cannabinoids.⁶

Many emergency clinicians remain unfamiliar with terminology regarding synthetic drugs. In a 2013 study that surveyed 83 physicians (88% response rate), most providers reported that they gathered a significant amount of their knowledge on this subject from nonmedical sources. The study found that 80% of respondents admitted to feeling uneasy about managing a patient with synthetic cannabinoid intoxication. Additionally, clinicians appeared less likely to ask about synthetic drug use compared to conventional drug use.⁷ Vazirian et al surveyed 124 emergency clinicians connected to the Cleveland Clinic health system. While analysis of this study’s results may be scrutinized for low participation (34% completion rate), approximately two-thirds of respondents reported having managed, in the prior 2 years, a patient with suspected synthetic cathinone intoxication. Despite this exposure, 77% of surveyed emergency clinicians did not ask about synthetic cathinone use.⁸ It is imperative that emergency clinicians include acute intoxication and synthetic drug abuse in their differential diagnosis for a wide variety of presentations. Most commonly, these patients will present with agitation or with changes in mental status; however, maintaining a high index of suspicion for complaints of chest or abdominal pain is necessary to detect some of the more serious sequelae.

In recent years, synthetic drugs have made their mark in the United States. While ascertaining the true prevalence of these synthetic drugs has been challenging because of underreporting, experts believe that their use has been on the rise.⁹ Emergency clinicians must be prepared to identify and manage exposures to synthetic drugs in a diverse range of ages within the pediatric population. This issue of Pediatric Emergency Medicine Practice will guide emergency clinicians through the diagnosis, management, and disposition of children who present with synthetic drug intoxication.

Critical Appraisal of the Literature

A literature search was performed in PubMed using the search terms synthetic cannabinoids and pediatric, synthetic cannabinoids and emergency medicine, synthetic cathinone and pediatrics, synthetic cathinone and emergency medicine, phenethylamines and pediatrics, and phenethylamines and emergency medicine. A search of the Library of Congress found 2 relevant reports. Background information on this topic was obtained from PubMed using the general search terms synthetic cannabinoids, synthetic cathinones, bath salts, phenethylamine intoxication, and MDMA intoxication.

The vast majority of publications were case reports, case series, or review articles. Higher-grade evidence was sparse for several possible reasons. The most significant reason is that designing randomized controlled trials of a toxic exposure would be clearly unethical. Diagnosis of synthetic cannabinoid and synthetic stimulant intoxication, in particular, is often presumed based on history only, as definitive laboratory testing is difficult to obtain and cost-prohibitive for many EDs. Moreover, many synthetic cannabinoids have a variety of active agents, complicating analysis of the clinical effects of a single substance. Finally, presentation of a patient with an acute intoxication to the ED is often due to polysubstance use. This creates a confounding effect, for which establishing an appropriate control is difficult.¹⁰ Because of these factors, significant gaps in knowledge remain. As technology is developed to better assess synthetic compound use, this may change. However, significant ethical considerations and confounding variables from polysubstance ingestion are still likely to limit quality evidence on this subject.

Risk Management Pitfalls in the Management of Pediatric Patients With Synthetic Drug Intoxication

4. “This patient already admitted taking MDMA earlier in the day. She was a bit anxious, but looked fine. It was a hot day, and I wanted to keep her hydrated, so I told her to drink plenty of water and sent her home.”

While this patient may appear to be doing well, MDMA is known to increase antidiuretic hormone release and can lead to hyponatremia. Multiple reports have found significant morbidity and mortality secondary to cerebral edema in patients who consumed MDMA, and this is thought to be secondary to low serum sodium levels. A basic metabolic panel should be ordered for any patient suspected of presenting with acute MDMA intoxication. Having the patient drink fluids containing electrolytes or administering a normal saline bolus would be more appropriate courses of management and can help prevent worsening electrolyte disturbances.

5. “My patient stated she had taken a small pill of ecstasy a few weeks ago; there is no way her current psychosis is related to that small quantity.”

This pitfall highlights 2 points. First, it is effectively impossible for patients to accurately know how much MDMA (or other substance, for that matter) they are ingesting when they take ecstasy. Studies have shown that the amount of psychoactive substances in such pills has increased dramatically compared to the drug’s introduction. The “small” size of the pill is meaningless. Second, cases of delayed psychosis secondary to MDMA use have been reported.^107,108

6. “While her parents admitted to the use of marijuana at their home, there is no way that this 18-month-old child could have been exposed to a toxic level.”

Children are adventurous explorers when they become mobile, and continuously place items in their mouths. Synthetic drugs are often packaged in shiny, colorful packaging, and may be especially enticing to young children. Oral ingestion of K2 by a 10-month-old child has been documented,³⁰ and such cases are likely to recur.

Tables and Figures

References

Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of patients. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study is included in bold type following the reference, where available. In addition, the most informative references cited in this paper, as determined by the author, are highlighted.

1. Glue P, Courts J, Gray A, et al. Influence of law changes affecting synthetic cannabinoid availability and frequency of hospital presentations: 4-year national survey. N Z Med J. 2016;129(1433):37-40. (Cross-sectional study)
2. Glue P, Courts J, MacDonald M, et al. Implementation of the 2013 Psychoactive Substances Act and mental health harms from synthetic cannabinoids. N Z Med J. 2015;128(1414):15-18. (Retrospective study)
3. Seely KA, Prather PL, James LP, et al. Marijuana-based drugs: innovative therapeutics or designer drugs of abuse? Mol Interv. 2011;11(1):36-51. (Review article)
4. Bhatty S, Wu W. Organic and synthetic cannabinoid use in adolescents. Pediatr Ann. 2013;42(1):31-35. (Review article)
5. Aoun EG, Christopher PP, Ingraham JW. Emerging drugs of abuse: clinical and legal considerations. R I Med J (2013). 2014;97(6):41-45. (Review article)
6. Mathai D, Gordon M, Muchmore P, et al. Paradoxical increase in synthetic cannabinoid emergency-related presentations after a citywide ban: lessons from Houston, Texas. Bull Menninger Clin. 2016;80(4):357-370. (Retrospective study)
7. Lank PM, Pines E, Mycyk MB. Emergency physicians’ knowledge of cannabinoid designer drugs. West J Emerg Med. 2013;14(5):467-470. (Physician survey; 83 emergency medicine physicians)
8. Vazirian M, Jerry JM, James J, et al. Bath salts in the emergency department: a survey of emergency clinicians’ experience with bath salts-intoxicated patients. J Addict Med. 2015;9(2):94-98. (Retrospective study; 124 patients)
9. Palamar JJ, Martins SS, Su MK, et al. Self-reported use of novel psychoactive substances in a US nationally representative survey: prevalence, correlates, and a call for new survey methods to prevent underreporting. Drug Alcohol Depend. 2015;156:112-119. (Cross-sectional study)
10. Cohen J, Morrison S, Greenberg J, et al. Clinical presentation of intoxication due to synthetic cannabinoids. Pediatrics. 2012;129(4):e1064-e1067. (Case series; 3 patients)
11. Heath TS, Burroughs Z, Thompson AJ, et al. Acute intoxication caused by a synthetic cannabinoid in two adolescents. J Pediatr Pharmacol Ther. 2012;17(2):177-181. (Case series; 2 patients)
12. Vandrey R, Dunn KE, Fry JA, et al. A survey study to characterize use of Spice products (synthetic cannabinoids). Drug Alcohol Depend. 2012;120(1-3):238-241. (Retrospective survey)
13. Palamar JJ, Su MK, Hoffman RS. Characteristics of novel psychoactive substance exposures reported to New York City Poison Center, 2011-2014. Am J Drug Alcohol Abuse. 2016;42(1):39-47. (Cross-sectional study)
14. Palamar JJ. There’s something about molly: the underresearched yet popular powder form of ecstasy in the United States. Subst Abus. 2017;38(1):15-17. (Review article)
15. American Association of Poison Control Centers. Synthetic cannabinoids. Accessed April 13, 2018. (Website)
16. Castellanos D, Gralnik LM. Synthetic cannabinoids 2015: an update for pediatricians in clinical practice. World J Clin Pediatr. 2016;5(1):16-24. (Review article)
17. Orsini J, Blaak C, Tam E, et al. The wide and unpredictable scope of synthetic cannabinoids toxicity. Case Rep Crit Care. 2015;2015:542490. (Case report; 1 patient)
18. Johnson LA, Johnson RL, Portier RB. Current “legal highs”. J Emerg Med. 2013;44(6):1108-1115. (Review article)
19. Mills B, Yepes A, Nugent K. Synthetic cannabinoids. Am J Med Sci. 2015;350(1):59-62. (Review article)
20. Sacco LN, Finklea K. Synthetic drugs: overview and issues for congress. Congressional Research Service Report. 2016. (Government report)
21. Ford BM, Tai S, Fantegrossi WE, et al. Synthetic pot: not your grandfather’s marijuana. Trends Pharmacol Sci. 2017;38(3):257-276. (Review article)
22. Nelson ME, Bryant SM, Aks SE. Emerging drugs of abuse. Emerg Med Clin North Am. 2014;32(1):1-28. (Review article)
23. Cooper ZD. Adverse effects of synthetic cannabinoids: management of acute toxicity and withdrawal. Curr Psychiatry Rep. 2016;18(5):52. (Review article)
24. Wells DL, Ott CA. The “new” marijuana. Ann Pharmacother. 2011;45(3):414-417. (Review article)
25. Andreeva-Gateva PA, Nankova VH, Angelova VT, et al. Synthetic cannabimimetics in Bulgaria 2010-2013. Drug Alcohol Depend. 2015;157:200-204. (Retrospective study; 210 patients)
26. Wood KE. Exposure to bath salts and synthetic tetrahydrocannabinol from 2009 to 2012 in the United States. J Pediatr. 2013;163(1):213-216. (Retrospective study; 19,028 patients)
27. Patrick ME, O’Malley PM, Kloska DD, et al. Novel psychoactive substance use by US adolescents: characteristics associated with use of synthetic cannabinoids and synthetic cathinones. Drug Alcohol Rev. 2016;35(5):586-590. (Survey)
28. Clayton HB, Lowry R, Ashley C, et al. Health risk behaviors with synthetic cannabinoids versus marijuana. Pediatrics. 2017. (Cross-sectional survey)
29. Dobaja M, Grenc D, Kozelj G, et al. Occupational transdermal poisoning with synthetic cannabinoid cumyl-PINACA. Clin Toxicol (Phila). 2017;55(3):193-195. (Case report)
30. Thornton SL, Akpunonu P, Glauner K, et al. Unintentional pediatric exposure to a synthetic cannabinoid (AB-PINACA) resulting in coma and intubation. Ann Emerg Med. 2015;66(3):343-344. (Case report; 1 patient)
31. Peterson BL, Couper FJ. Concentrations of AB-CHMINACA and AB-PINACA and driving behavior in suspected impaired driving cases. J Anal Toxicol. 2015;39(8):642-647. (Review of case reports)
32. Tai S, Fantegrossi WE. Pharmacological and toxicological effects of synthetic cannabinoids and their metabolites. Curr Top Behav Neurosci. 2017;32:249-262. (Review chapter)
33. Castaneto MS, Gorelick DA, Desrosiers NA, et al. Synthetic cannabinoids: epidemiology, pharmacodynamics, and clinical implications. Drug Alcohol Depend. 2014;144:12-41. (Review article)
34. Brents LK, Prather PL. The K2/Spice phenomenon: emergence, identification, legislation and metabolic characterization of synthetic cannabinoids in herbal incense products. Drug Metab Rev. 2014;46(1):72-85. (Review article)
35. Louh IK, Freeman WD. A ‘spicy’ encephalopathy: synthetic cannabinoids as cause of encephalopathy and seizure. Crit Care. 2014;18(5). (Case report)
36. Rosenbaum CD, Carreiro SP, Babu KM. Here today, gone tomorrow...and 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(1):15-32. (Review article)
37. Zaurova M, Hoffman RS, 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. 2016. (Subgroup analysis of cohort study; 3739 patients, 87 patients who reported exposure to any cannabinoid)
38. Hermanns-Clausen M, Kithinji J, Spehl M, et al. Adverse effects after the use of JWH-210 - a case series from the EU Spice II plus project. Drug Test Anal. 2016;8(10):1030-1038. (Retrospective study; 22 patients)
39. Backberg M, Tworek L, Beck O, et al. Analytically confirmed intoxications involving MDMB-CHMICA from the STRIDA Project. J Med Toxicol. 2016. (Observational case series)
40. Tyndall JA, Gerona R, De Portu G, et al. An outbreak of acute delirium from exposure to the synthetic cannabinoid AB-CHMINACA. Clin Toxicol (Phila). 2015;53(10):950-956. (Case series)
41. Adams AJ, Banister SD, Irizarry L, et al. “Zombie” outbreak caused by the synthetic cannabinoid AMB-FUBINACA in New York. N Engl J Med. 2017;376(3):234-241. (Case series; 8 patients who had used synthetic cannabinoids)
42. Thornton MD, Baum CR. Bath salts and other emerging toxins. Pediatr Emerg Care. 2014;30(1):47-52. (Review article)
43. Rasimas JJ. “Bath salts” and the return of serotonin syndrome. J Clin Psychiatry. 2012;73(8):1126-1127. (Commentary on case report)
44. Miotto K, Striebel J, Cho AK, et al. Clinical and pharmacological aspects of bath salt use: a review of the literature and case reports. Drug Alcohol Depend. 2013;132(1-2):1-12. (Review article)
45. Banks ML, Worst TJ, Rusyniak DE, et al. Synthetic cathinones (“bath salts”). J Emerg Med. 2014;46(5):632-642. (Review article)
46. Froberg BA, Levine M, Beuhler MC, et al. Acute methylenedioxypyrovalerone toxicity. J Med Toxicol. 2015;11(2):185-194. (Retrospective study; 23 patients)
47. Fischbach P. The role of illicit drug use in sudden death in the young. Cardiol Young. 2017;27(S1):S75-S79. (Review article)
48. Dean BV, Stellpflug SJ, Burnett AM, et al. 2C or not 2C: phenethylamine designer drug review. J Med Toxicol. 2013;9(2):172-178. (Review article)
49. Gahlinger PM. Club drugs: MDMA, gamma-hydroxybutyrate (GHB), rohypnol, and ketamine. Am Fam Physician. 2004;69(11):2619-2626. (Review article)
50. Hall AP, Henry JA. Acute toxic effects of ‘ecstasy’ (MDMA) and related compounds: overview of pathophysiology and clinical management. Br J Anaesth. 2006;96(6):678-685. (Review article)
51. Banken JA. Drug abuse trends among youth in the United States. Ann N Y Acad Sci. 2004;1025:465-471. (Review article, collection of surveys)
52. U.S. Department of Health and Human Services Substance Abuse and Mental Health Services Administration Center for Behavioral Health Statistics and Quality. Drug Abuse Warning Network, 2011: national estimates of drug-related emergency department visits. Accessed April 15, 2018. (Government report)
53. Halpern P, Moskovich J, Avrahami B, et al. Morbidity associated with MDMA (ecstasy) abuse: a survey of emergency department admissions. Hum Exp Toxicol. 2011;30(4):259-266.
54. Katz KD, Leonetti AL, Bailey BC, et al. Case series of synthetic cannabinoid intoxication from one toxicology center. West J Emerg Med. 2016;17(3):290-294. (Case series; 11 patients)
55. Westover AN, Nakonezny PA, Haley RW. Acute myocardial infarction in young adults who abuse amphetamines. Drug Alcohol Depend. 2008;96(1-2):49-56. (Epidemiology study relating use of amphetamines and acute myocardial infarction.)
56. Kiyatkin EA, Ren SE. MDMA, methylone, and MDPV: drug-induced brain hyperthermia and its modulation by activity state and environment. Curr Top Behav Neurosci. 2017;32:183-207. (Review article)
57. Palamar JJ, Acosta P. Synthetic cannabinoid use in a nationally representative sample of US high school seniors. Drug Alcohol Depend. 2015;149:194-202. (Cross-sectional study)
58. Kasper AM, Ridpath AD, Arnold JK, et al. Severe illness associated with reported use of synthetic cannabinoids - Mississippi, April 2015. MMWR Morb Mortal Wkly Rep. 2015;64(39):1121-1122. (Case series)
59. Prosser JM, Nelson LS. The toxicology of bath salts: a review of synthetic cathinones. J Med Toxicol. 2012;8(1):33-42. (Review article)
60. Qasim A, Townend J, Davies MK. Ecstasy induced acute myocardial infarction. Heart. 2001;85(6):E10. (Case report; 1 patient)
61. Maharaj R, Pingitore A, Menon K, et al. Images of the month: MDMA-induced acute liver failure and transient abdominal pneumatosis. Am J Gastroenterol. 2015;110(7):963. (Case report)
62. Chase PB, Hawkins J, Mosier J, et al. Differential physiological and behavioral cues observed in individuals smoking botanical marijuana versus synthetic cannabinoid drugs. Clin Toxicol (Phila). 2016;54(1):14-19. (Retrospective convenience sample)
63. Dargan PI, Sedefov R, Gallegos A, et al. The pharmacology and toxicology of the synthetic cathinone mephedrone (4-methylmethcathinone). Drug Test Anal. 2011;3(7-8):454-463. (Review article)
64. Imam SF, Patel H, Mahmoud M, et al. Bath salts intoxication: a case series. J Emerg Med. 2013;45(3):361-365. (Case series)
65. Levine M, Levitan R, Skolnik A. Compartment syndrome after “bath salts” use: a case series. Ann Emerg Med. 2013;61(4):480-483. (Case report)
66. Dinis-Oliveira RJ, Caldas I, Carvalho F, et al. Bruxism after 3,4-methylenedioxymethamphetamine (ecstasy) abuse. Clin Toxicol (Phila). 2010;48(8):863-864. (Case series)
67. Liechti ME, Kunz I, Kupferschmidt H. Acute medical problems due to Ecstasy use. Case-series of emergency department visits. Swiss Med Wkly. 2005;135(43-44):652-657. (Case series)
68. Greene SL, Kerr F, Braitberg G. Review article: amphetamines and related drugs of abuse. Emerg Med Australas. 2008;20(5):391-402. (Review article)
69. Adedinsewo DA, Odewole O, Todd T. Acute rhabdomyolysis following synthetic cannabinoid ingestion. N Am J Med Sci. 2016;8(6):256-258. (Case report)
70. Gee P, Jerram T, Bowie D. Multiorgan failure from 1-benzylpiperazine ingestion--legal high or lethal high? Clin Toxicol (Phila). 2010;48(3):230-233. (Case series)
71. Rogers SC, Pruitt CW, Crouch DJ, et al. Rapid urine drug screens: diphenhydramine and methadone cross-reactivity. Pediatr Emerg Care. 2010;26(9):665-666. (Case report)
72. Eskridge KD, Guthrie SK. Clinical issues associated with urine testing of substances of abuse. Pharmacotherapy. 1997;17(3):497-510. (Review article)
73. Kak M, Mikhail F, Yano ST, et al. Buzz juice: neurological sequelae of synthetic cannabinoids. J Clin Neurosci. 2016. (Case report)
74. Buyukbese Sarsu S. Unusual side effect of cannabis use: acute abdomen due to duodenal perforation. Int J Emerg Med. 2016;9(1):18. (Case report)
75. Kanahara S, El-Refai M, Lakkis N, et al. Acute ascending aortic dissection after MDMA/ecstasy use: a case report. Hellenic J Cardiol. 2016;57(5):351-354. (Case report, 1 patient)
76. Hamilton RJ, Keyfes V, Banka SS. Synthetic cannabinoid abuse resulting in ST-segment elevation myocardial infarction requiring percutaneous coronary intervention. J Emerg Med. 2017;52(4):496-498. (Case report)
77. Mir A, Obafemi A, Young A, et al. Myocardial infarction associated with use of the synthetic cannabinoid K2. Pediatrics. 2011;128(6):e1622-e1627. (Case series)
78. Naidoo M, Govind M. On your toes: detecting mediastinal air on the chest radiograph in ecstasy abusers. S Afr Med J. 2016;106(5):46-47. (Case report)
79. Ezoubi S, Kahal H, Waring WS. Pneumomediastinum as a complication of MDMA (3,4-methylenedioxymetamfetamine, ecstasy) ingestion. Acute Med. 2016;15(3):152-156. (Case report)
80. Ryan J, Banerjee A, Bong A. Pneumomediastinum in association with MDMA ingestion. J Emerg Med. 2001;20(3):305-306. (Letter to the editor)
81. Argamany JR, Reveles KR, Duhon B. Synthetic cannabinoid hyperemesis resulting in rhabdomyolysis and acute renal failure. Am J Emerg Med. 2016;34(4):765. (Case report; 1 patient)
82. Laskowski LK, Landry A, Vassallo SU, et al. Ice water submersion for rapid cooling in severe drug-induced hyperthermia. Clin Toxicol (Phila). 2015;53(3):181-184. (Case series)
83. Su M, Laskowski L, Hoffman RS. Hyperthermia and severe rhabdomyolysis from synthetic cannabinoids. Am J Emerg Med. 2016;34(8):1690. (Letter to the editor)
84. Sweeney B, Talebi S, Toro D, et al. Hyperthermia and severe rhabdomyolysis from synthetic cannabinoids. Am J Emerg Med. 2016;34(1):121 e121-e122. (Case report; 1 patient)
85. Roberto AJ, Lorenzo A, Li KJ, et al. First-episode of synthetic cannabinoid-induced psychosis in a young adult, successfully managed with hospitalization and risperidone. Case Rep Psychiatry. 2016;2016:7257489. (Case report; 1 patient)
86. Hysek CM, Vollenweider FX, Liechti ME. Effects of a beta-blocker on the cardiovascular response to MDMA (ecstasy). Emerg Med J. 2010;27(8):586-589. (Double-blind placebo-controlled cross-over trial; 16 subjects)
87. Hoffman RS. Cocaine and beta-blockers: should the controversy continue? Ann Emerg Med. 2008;51(2):127-129. (Editorial)
88. Dezieck L, Hafez Z, Conicella A, et al. Resolution of cannabis hyperemesis syndrome with topical capsaicin in the emergency department: a case series. Clin Toxicol (Phila). 2017;55(8):908-913. (Case series)
89. Giannini AJ. An approach to drug abuse, intoxication and withdrawal. Am Fam Physician. 2000;61(9):2763-2774. (Review article)
90. Ables AZ, Nagubilli R. Prevention, recognition, and management of serotonin syndrome. Am Fam Physician. 2010;81(9):1139-1142. (Review article)
91. Kant S, Liebelt E. Recognizing serotonin toxicity in the pediatric emergency department. Pediatr Emerg Care. 2012;28(8):817-821. (Review article)
92. Sterns RH, Hix JK, Silver S. Treating profound hyponatremia: a strategy for controlled correction. Am J Kidney Dis. 2010;56(4):774-779. (Case report)
93. Sterns RH, Nigwekar SU, Hix JK. The treatment of hyponatremia. Semin Nephrol. 2009;29(3):282-299. (Review article)
94. Adrogue HJ, Madias NE. Hyponatremia. N Engl J Med. 2000;342(21):1581-1589. (Review article)
95. Albanese J. Spontaneous pneumomediastinum: a rare complication of methamphetamine use. Respir Med Case Rep. 2017;21:25-26. (Case report)
96. Russo R, Marks N, Morris K, et al. Life-threatening necrotizing fasciitis due to ‘bath salts’ injection. Orthopedics. 2012;35(1):e124-e127. (Case report)
97. Ngatchou W, Lemogoum D, Essola B, et al. Cannabis body packing: a case report. Pan Afr Med J. 2016;24:327. (Case report)
98. Beno S, Calello D, Baluffi A, et al. Pediatric body packing: drug smuggling reaches a new low. Pediatr Emerg Care. 2005;21(11):744-746. (Case report; 1 patient)
99. Reginelli A, Russo A, Urraro F, et al. Imaging of body packing: errors and medico-legal issues. Abdom Imaging. 2015;40(7):2127-2142. (Review article)
100. Suy K, Gijsenbergh F, Baute L. Emergency medical assistance during a mass gathering. Eur J Emerg Med. 1999;6(3):249-254. (Event report)
101. Nadesan K, Kumari C, Afiq M. Dancing to death: a case of heat stroke. J Forensic Leg Med. 2017;50:1-5. (Case series, 12 patients)
102. Wood DM, Greene SL, Alldus G, et al. Improvement in the pre-hospital care of recreational drug users through the development of club specific ambulance referral guidelines. Subst Abuse Treat Prev Policy. 2008;3:14. (Prospective study)
103. Lyvers M. Recreational ecstasy use and the neurotoxic potential of MDMA: current status of the controversy and methodological issues. 200;25(3):269-276. (Review article)
104. Richards JR, Laurin EG, Albertson TE. Beta-blocker use for toxicity from “bath salts”. J Emerg Med. 2015;48(2):E45-E46. (Letter to the editor)
105. Samra K, Boon IS, Packer G, et al. Lethal high: acute disseminated encephalomyelitis (ADEM) triggered by toxic effect of synthetic cannabinoid black mamba. BMJ Case Rep. 2017;2017. (Case report; 1 patient)
106. Bush DM, Woodwell DA. Update: Drug-related emergency department visits involving synthetic cannabinoids. The CBHSQ Report. Rockville (MD)2013-2014. (Review article)
107. Soar K, Parrott AC, Fox HC. Persistent neuropsychological problems after 7 years of abstinence from recreational ecstasy (MDMA): a case study. Psychol Rep. 2004;95(1):192-196. (Case study)
108. McGuire P. Long term psychiatric and cognitive effects of MDMA use. Toxicol Lett. 2000;112-113:153-156. (Review article)