You Might Also Like

• Drug Overdoses from Acetyl Fentanyl Mixed Into Street Drugs On Rise
• Overdose Antidote Naloxone Hydrochloride Available in California Pharmacies
• Naloxone to Reduce Opiate Overdose Deaths Raises Cost, Liability, and Safety Concerns

Explore This Issue

ACEP Now: Vol 33 – No 11 – November 2014

ACEP Now features one article each issue related to an ACEP eCME CME activity.

Log on to the ACEP eCME CME site to complete the activity for this article and earn free AMA PRA Category 1 Credit.

The Case

It is a weekend, almost 3 a.m. in the emergency department. Paramedics report they are bringing in three patients from the same home, all with altered mentation and some with very abnormal vital signs. The simultaneous presentation of a toxidrome in three teens makes overdose from a recreational drug highly possible. After repeated questioning, one of the patients utters, “25-B.”

Here, we document the presentation and management of three patients who inadvertently overdosed on a new designer drug with the street name 25-B. Designer drugs are manufactured with similar chemical structure and effect to illicit drugs and are advertised as “legal highs.”¹ These substances are commonly procured through the Internet or in head shops and are rising in popularity.^2,3

The novel, synthetic, psychoactive substance 25B-NBOMe is one such compound. It was first synthesized in 2004 in Germany by Ralf Heim.⁴ 25B-NBOMe is also known by the names 2C-B-NBOMe, Cimbi-36, and 25-B. It is one of the NBOMe class of N-methoxybenzyl-substituted phenethylamine derivatives, similar to the 2C class of illicit hallucinogenic phenethylamines. Other NBOMe compounds include 25I-NBOMe and 25C-NBOMe, commonly known as 25-I and 25-C.

Abuse of these substances and reports of adverse reactions have increased.³ Their toxicology is not well-studied, and the dearth of literature complicates the clinician’s task of identifying and treating their toxicity.

Patient Presentation

The three patients were at the home of one of the individuals (patient 1). EMS was called by his mother, who heard him screaming and heard commotion from the other two patients.

Patient 1 is a 19-year-old male who arrives at 2:53 a.m. on a backboard with all extremities restrained because of flailing and constant uncontrolled movement. His extremities are tense and very tremulous. He is not convulsing. Abrasions are noted on his left shoulder and right eyebrow. His mother later states that he had been hallucinating and she had seen him hit his shoulder as if he was trying to hurt himself. He is noncommunicative. He appears frightened and confused. The patient’s temperature is 37.1oC, heart rate 171, and respirations 24. Initial blood pressure cannot be obtained because of motion. He has large nonreactive pupils estimated at 6 mm in diameter, has no bowel sounds, and is incontinent of urine. Laboratory studies include serum Na of 140 mmol/L, K 3.8 mmol/L, CO2 12 mmol/L, creatinine 1.88 mg/dL, and creatine phosphokinase 450 U/L. The WBC is 33,700. A urine drug screen is negative.

The patient is agitated and tremulous. He is given diazepam 5 mg IV, after which his heart rate is 159 and blood pressure is 128/86. He is given a second dose of diazepam 5 mg IV and two liters of IV normal saline. After the second dose of diazepam, he is calm, and the restraints are removed. Hospitalization is arranged, but on reevaluation, he is improving rapidly. He is discharged four hours after arrival following resolution of symptoms. At the time of discharge, he is ambulatory and conversant. He has no recollection of coming to the emergency department.

Patient 2 is an 18-year-old female who is awake and looking around the room but unable to communicate. She does say a few words, but they are either unintelligible or out of context. There are no visible signs of trauma.

Her temperature is 37.3°C, heart rate 108, respirations 22, and blood pressure 120/65. She is confused and also has dilated pupils. This patient is the first to mention the drug. With repeated questioning, she utters, “B-25.” When she improves to the point that she can communicate, she reports dysphoria and visual hallucinations. Later, she denies dysphoria and reports euphoria instead. The urine drug screen is negative. The WBC is normal. She is given 2 liters of normal saline. She is discharged four hours after arrival following resolution of symptoms.

Patient 3 is a 19-year-old male. He was found supine on the floor of the residence, where he was noted to be occasionally screaming and thrashing. Upon arrival, his temperature is 37.2°C, heart rate 114, respirations 22, and blood pressure 126/67. He is confused and also has large 5 mm nonreactive pupils. Documentation from the examining physician includes: “He is lying on the gurney looking straight up in the ceiling. He has a smile on his face. He does not appear combative. He does not interact with me.” Significant laboratory studies include CO2 20 mmol/L and a WBC of 28,900. Urine drug screen is negative.

He is lying on the gurney looking straight up in the ceiling. He has a smile on his face. He does not appear combative. He does not interact with me. Significant laboratory studies included CO2 20 mmol/L and a WBC of 28,900.

He never looks uncomfortable. He does not communicate initially, but when he improves and is able to communicate, he reports euphoria and visual hallucinations. He is discharged three hours after admission following resolution of symptoms.

When the patients have recovered, they report that they took 25-B after purchasing it on the Internet from another country. The drug had arrived by mail as a cardboard strip, presumably blotter paper for oral or sublingual administration.

Discussion

The NBOMe class of compounds has recently emerged as novel synthetic drug of abuse. In November 2013, the Department of Justice temporarily placed 25B-NBOMe in Schedule I of the Controlled Substances Act, along with 25I-NBOMe and 25C-NBOMe.⁵

Pharmacologically, 25B-NBOMe is an agonist of the 5-HT2A serotonin receptor.⁵ Our patients exhibited symptoms consistent with serotonin syndrome. An elevated WBC was noted with more severe symptoms.

Review of the literature shows limited information describing the clinical course in the emergency department. Toxicology journals report the case of a 19-year-old male with confirmed 25-B overdose who exhibited grand mal seizure activity, fever, sinus tachycardia, dilated pupils, erythema, and purpuric rash.⁶ The most common reported symptoms of acute 25I-NBOMe intoxication are tachycardia, agitation, hallucinations, hypertension, and seizures.⁷ Other reported symptoms include violent behavior, hyperpyrexia, clonus, an elevated WBC count, elevated creatine kinase, metabolic acidosis, and renal failure.8-10 Additionally, Poklis et al. report persistent seizure activity and resultant rhabdomyolysis, requiring sedatives and skeletal muscle blocking agents.⁷ Three deaths resulting from 25I-NBOMe toxicity have been reported in the medical literature, and in each, the decedents exhibited delirious or erratic behavior.^7,11 Dangerous behavior directly contributed to one death as the decedent appeared to have fallen from an apartment balcony.⁷ Forensic pathologic study in two cases revealed nonfatal injuries, leaving open the possibility of death from pharmacologic effects.¹¹

The patients described in this report improved with symptomatic treatment. One was given benzodiazepines for agitation. There are no antidotes available for 25B-NBOMe or similar compounds. Pharmacologically based therapies may be considered, but efficacy of 5-HT2A antagonists such as cyproheptadine is inconclusive.^12,13 Accidental NBOMe consumption is possible with intended LSD intoxication.^2,14

Complete the CME activity.

Mr. Su is in the department of otolaryngology, head and neck surgery, at Mount Sinai Beth Israel and a research associate at the Thyroid, Head and Neck Cancer Foundation, both in New York. Dr. Baker is in the department of emergency medicine Pali Momi Medical Center in Aiea, Hawaii. Dr. Baraff is with the emergency medicine center at David Geffen School of Medicine at the Universitycof California, Los Angeles.

References

1. Dean BV, Stellpflug SJ, Burnett AM, Engebretsen KM. 2C or not 2C: phenethylamine designer drug review. J Med Toxicology. 2013;9:172-8.
2. Ninnemann A, Stuart GL. The NBOMe Series: a novel, dangerous group of hallucinogenic drugs. J Stud Alcohol Drugs. 2013;74:977.
3. Erowid E, Erowid F. Spotlight on NBOMes: potent psychedelic issues. Erowid Extracts. 2013;24:2-5.
4. Heim R. Synthese und Pharmakologie potenter 5-HT2A-Rezeptoragonisten mit N-2-Methoxybenzyl-Partialatruktur: Entwicklung eines neuen Struktur-Wirkungskonzepts. Berlin, Freie University, Dissertation, 2003.
5. Administration DE. Schedules of controlled substances: temporary placement of three synthetic phenethylamines into Schedule I. Final order. Federal Register. 2013;78:68716.
6. Poklis JL, Nanco CR, Troendle MM, Wolf CE, Poklis A. Determination of 4 bromo 2, 5 dimethoxy N [(2 methoxyphenyl) methyl] benzeneethanamine (25B NBOMe) in serum and urine by high performance liquid chromatography with tandem mass spectrometry in a case of severe intoxication. Drug Test Anal. 2014;6:764-9.
7. Poklis JL, Devers KG, Arbefeville EF, Pearson JM, Houston E, Poklis A. Postmortem detection of 25I-NBOMe [2-(4-iodo-2, 5-dimethoxyphenyl)-N-[(2-methoxyphenyl) methyl] ethanamine] in fluids and tissues determined by high performance liquid chromatography with tandem mass spectrometry from a traumatic death. Forensic Sci Int. 2014;234:e14-e20.
8. Hill SL, Doris T, Gurung S, et al. Severe clinical toxicity associated with analytically confirmed recreational use of 25I-NBOMe: case series. Clin Toxicol. 2013;51:487-92.
9. Stellpflug SJ, Kealey SE, Hegarty CB, Janis GC. 2-(4-Iodo-2, 5-dimethoxyphenyl)-N-[(2-methoxyphenyl) methyl] ethanamine (25I-NBOMe): clinical case with unique confirmatory testing. J Med Toxicol. 2013:1-6.
10. Rose SR, Poklis JL, Poklis A. A case of 25I-NBOMe (25-I) intoxication: a new potent 5-HT2A agonist designer drug. Clin Toxicol. 2013;51:174-7.
11. Walterscheid JP, Phillips GT, Lopez AE, Gonsoulin ML, Chen H-H, Sanchez LA. Pathological findings in 2 cases of fatal 25I-NBOMe toxicity. Am J Forensic Med Pathol. 2014;35:20-5.
12. Boyer EW, Shannon M. The serotonin syndrome. N Eng J Med. 2005;352:1112-20.
13. Gillman PK. The serotonin syndrome and its treatment. J Psychopharmacol. 1999;13:100-9.
14. Caldicott D, Bright SJ, Barratt MJ. NBOMe—a very different kettle of fish. Med J Aust. 2013;199:322-3.