April 6, 2015: What is the new synthetic drug 25I-NBOMe (N-Bomb)?

 

 

The recreational use of synthetic (designer) psychoactive substances with stimulant, euphoric, and/or hallucinogenic properties has risen dramatically in recent years. The illegal status of classic recreational substances (e.g. cocaine, ecstasy, cannabis, etc.) has encouraged users and suppliers to seek alternative options in order to evade current drug legislation. These substances are usually created by modification to the molecular structures of existing illicit compounds to produce similar subjective effects but offer the advantages of being technically legal, less expensive, readily available, likely undetectable by routine drug abuse screens, or having more desirable/potent pharmacological effects. The substances abused frequently change in response to legislative controls and market demands, and it is important for health care providers to remain up-to-date on the toxicological effects of these emerging agents.

 

 

Blotter Paper Containing 25C-NBOMe

 

 

25I-NBOMe is a representative of a new class of hallucinogens called 25X-NBOMe or simply NBOMe (pronounced N-Bomb). These compounds are research chemicals originally developed as high affinity ligands for use in mapping the distribution of serotonin receptors in the brain. NBOMe have virtually no history of human use prior to 2010 when they initially became available over the internet. The United Nations Office on Drugs and Crime’s (UNODC) Early Warning Advisory noted that by September 2014 25I-NBOMe was the most frequently reported (43%) novel psychoactive substance that year.

 

NBOMe are sold as blotter paper, powder (loose or within capsules), and liquids with sublingual/buccal and nasal insufflation being the most common routes of administration though inhalation, parenteral, rectal, and vaginal use has been reported. These compounds are marketed as legal or natural LSD and sold under a variety of synonyms, depending on which NBOMe analog the product contains, including: N-Bomb, Solaris, Smiles, Cimbi, C-Boom, INB-MeO, Pandora, Dime, and Holland Film.

 

While marketed as an alternative to LSD, these compounds are actually derived from the 2C-X series of psychedelics originally developed by Alexander Shulgin in the 1970s. They are synthesized from the 2-CX compounds through the addition of a 2-methoxybenzyl (MeOB) function group onto the nitrogen (N) just off the core structure (hence NBOMe). Each NBOMe variant is differentiated by the specific halogen or other functional group added to the benzene ring (i.e. iodine substitution is 25I-NBOMe).

 

 

Table 1-1 Base 2C Structure and Derivative Compounds

R1 Substituent

R4 Substituent

Compound Name

H

H

2C-H

H

I

2C-I

H

Br

2C-B

H

Cl

2C-C

H

-C2H5

2C-E

-CH2C6H4OCH3

H

25H-NBOMe

-CH2C6H4OCH3

I

25I-NBOMe

-CH2C6H4OCH3

Br

25B-NBOMe

-CH2C6H4OCH3

Cl

25C-NBOMe

 

 

The pharmacological properties of NBOMe resemble their 2C derivatives which are primarily 5-HT2A (serotonin-2A) receptor and alpha-adrenergic receptor stimulants. In vitro displacement studies show that 25I-NBOMe is approximately 16-fold more potent at the serotonin receptor than its 2C-I derivative.

 

Independent reports from human use suggest that the threshold dosage is 50-250μg (micrograms) with a light dose between 200-600μg, a common dose between 500-800μg, and a strong dose between 700-1500μg. At this level of potency, it is impossible to accurately measure a single dose of NBOMe powder without an analytical balance and misjudging the dose could lead to significant toxicity. Furthermore, manipulation of the powder without proper personal protective equipment could result in toxicity due to accidental inhalation or touching of the eyes and/or mouth after handling.

 

Acute toxicity produces clinical features of both serotonergic and sympathomimetic toxidromes, including: hypertension, tachycardia, dilated pupils, diaphoresis, hyperthermia, agitation, aggressive behavior, delirium, visual and auditory hallucinations, tremulousness, bruxism, myoclonus, muscle rigidity, rhabdomyolysis with subsequent renal failure, seizures, status epilepticus, and coma.

 

According to medical examiner and postmortem toxicology reports available to the Drug Enforcement Agency (DEA), NBOMe have been implicated in the deaths of at least 17 individuals in the United States just prior to 2014. These reports suggest that 14 of the individuals died of acute toxicity while 3 other fatalities were attributed to unpredictable or violent behavior.

 

The goal of treatment is to manage agitation and prevent end-organ damage. Agitation or physical aggression may develop and require large doses of benzodiazepines for sedation. Severe cases may require orotracheal intubation and neuromuscular paralysis. External cooling measures may be needed for hyperthermia. If left untreated, hyperthermia will result in disseminated intravascular coagulopathy. At this time, it is unknown if hemodialysis or hemoperfusion would help enhance NBOMe elimination.

 

References

 

  1. Bersani FS, Corazza O, Albano G, et al. 25C-NBOMe: preliminary data on pharmacology, psychoactive effects, and toxicity of a new potent and dangerous hallucinogenic drug. Biomed Res Int. 2014; 2014: 734749.
  2. Braden MR, Parrish JC, Naylor JC, et al. Molecular interaction of serotonin 5-HT2A receptor residues Phe339(6.51) and Phe340(6.52) with superpotent N-benzyl phenethylamine agonists. Mol Pharmacol. 2006 Dec; 70(6):1956-64.
  3. Erowid. 25I-NBOMe (2C-I-NBOMe) Fatalities and deaths. (2015). Retrieved 20 March 2015, from https://www.erowid.org/chemicals/2ci_nbome/2ci_nbome_death.shtml
  4. Hill SL, Doris T, Gurung S, et al. Severe clinical toxicity associated with analytically confirmed recreational use of 25I-NBOMe: case series. Clin Toxicol (Phila). 2013 Jul; 51(6):487-92.
  5. Laskowski LK, Elbakoush F, Calvo J, et al. Evolution of the NBOMes: 25C- and 25B- sold as 25I-NBOMe. J Med Toxicol. 2014 Nov 12. [Epub ahead of print]
  6. Rose SR, Poklis JL, Poklis A. A case of 25I-NBOMe (25-I) intoxication: a new potent 5-HT2A agonist designer drug. Clin Toxicol (Phila). 2013 Mar; 51(3):174-7.
  7. Stellpflug SJ, Kealey SE, Hegarty CB, et al. 2-(4-Iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25I-NBOMe): clinical case with unique confirmatory testing. J Med Toxicol. 2014 Mar; 10(1):45-50.
  8. Suzuki J, Poklis JL, Poklis A. “My friend said it was good LSD”: a suicide attempt following analytically confirmed 25I-NBOMe ingestion. J Psychoactive Drugs. 2014 Nov-Dec; 46(5):379-82.
  9. Tang MH, Ching CK, Tsui MS, et al. Two cases of severe intoxication associated with analytically confirmed use of the novel psychoactive substances 25B-NBOMe and 25C-NBOMe. Clin Toxicol (Phila). 2014 Jun; 52(5):561-5.
  10. Temporary placement of three synthetic phenethylamines into Schedule I. Fed Reg.  2013 Nov 18; 78(221): 68716-68719 (to be codified at 21 C.F.R pt. 1308). Retrieved from http://www.gpo.gov/fdsys/pkg/FR-2013-11-15/html/2013-27315.htm
  11. UNODC-EWA: 25I-NBOMe is the most reported substance in 2014. (Oct 2014). United Nations Office on Drugs and Crime’s (UNODC) Early Warning Advisory (EWA) on New Psychoactive Substances (NPS). Retrieved from https://www.unodc.org/LSS/Announcement/Details/f6acf081-dd51-4d23-9c66-…
  12. Walterscheid JP, Phillips GT, Lopez AE, et al. Pathological findings in 2 cases of fatal 25I-NBOMe toxicity. Am J Forensic Med Pathol. 2014 Mar; 35(1):20-5.
  13. Wood DM, Sedefov R, Cunningham A, et al. Prevalence of use and acute toxicity associated with the use of NBOMe drugs. Clin Toxicol (Phila). 2015 Feb; 53(2):85-92.

 

This question prepared by:  Justin Loden, Pharm D  (CSPI)  Certified Specialist in Poison Information

 

I am interested in any questions you would like answered in the Question of the Week.  Please email me with any suggestion at donna.seger@vanderbilt.edu

 

Donna Seger, MD

Medical Director

Tennessee Poison Center

www.tnpoisoncenter.org

Poison Help Hotline:  1-800-222-1222

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