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Forensic Toxicology

, Volume 33, Issue 1, pp 1–11 | Cite as

25B-NBOMe and its precursor 2C-B: modern trends and hidden dangers

  • Ioannis Papoutsis
  • Panagiota NikolaouEmail author
  • Maria Stefanidou
  • Chara Spiliopoulou
  • Sotiris Athanaselis
Review Article

Abstract

Substituted phenethylamines are a class of designer drugs that hold a significant position in the drug abuse market. The most important substances within this class appear to be 4-bromo-2,5-dimethoxyphenethylamine (2C-B) and its novel derivative 2-(4-bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25B-NBOMe). Intoxications related to 2C-B use are still recorded worldwide, despite the fact that its use and trafficking are banned in many countries. 25B-NBOMe is a highly potent 2C-B derivative that has invaded recently in the “drug arena” and is considered legal to possess and supply in many countries. This manuscript reviews all available information regarding chemistry, availability, pharmacology, and toxicology of 2C-B and 25B-NBOMe. The intoxication and fatal cases reported, as well as the current legislation of these drugs, are also presented.

Keywords

2C-B Nexus 25B-NBOMe New Nexus Substituted phenethylamines Toxicology and pharmacology 

Notes

Conflict of interest

There are no financial or other relations that could lead to a conflict of interest.

References

  1. 1.
    Nieddu M, Trignano C, Burrai L, Pirisi MA, Boatto G (2013) Cross-reactivities of 41 new amphetamine designer drugs to EMIT® immunoassays. Forensic Toxicol 31:133–137CrossRefGoogle Scholar
  2. 2.
    Advisory Council on the Misuse of Drugs (ACMD) (2013) “NBOMe” compounds: a review of the evidence of use and harm. https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/204808/J_TCDO_report_on_5-6APB_and_NBOMe_compounds.pdf. Accessed 5 May 2014
  3. 3.
    Dean BV, Stellpflug SJ, Burnett AM, Engebretsen KM (2013) 2C or not 2C: phenethylamine designer drug review. J Med Toxicol 9:172–178PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Stellpflug SJ, Kealey SE, Hegarty CB, Janis GC (2014) 2-(4-Iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25I-NBOMe): clinical case with unique confirmatory testing. J Med Toxicol 10:45–50PubMedCrossRefGoogle Scholar
  5. 5.
    Wikipedia (2014) 2C (psychedelics). http://en.wikipedia.org/wiki/2C_(psychedelics). Accessed 8 May 2014
  6. 6.
    Shulgin A, Shulgin A (1991) PiHKAL: a chemical love story. Transform Press, BerkeleyGoogle Scholar
  7. 7.
    Bronson ME, Jiang W, DeRuiter J, Clark CR (1995) A behavioral comparison of Nexus, cathinone, BDB, and MDA. Pharmacol Biochem Behav 51:473–475PubMedCrossRefGoogle Scholar
  8. 8.
    Shulgin AT, Carter MF (1975) Centrally active phenethylamines. Psychopharmacol Commun 1:93–98PubMedGoogle Scholar
  9. 9.
    Lobos M, Borges Y, Gonzalez E, Cassels BK (1992) The action of the psychoactive drug 2C-B on isolated rat thoratic aorta. Gen Pharmacol 23:1139–1142PubMedCrossRefGoogle Scholar
  10. 10.
    Huang HH, Bai YM (2011) Persistent psychosis after ingestion of a single tablet of “2C-B”. Prog Neuropsychopharmacol Biol Psychiatry 35:293–294PubMedCrossRefGoogle Scholar
  11. 11.
    Ragan FA, Hite SA, Samuels MS, Garey RE (1985) 4-Bromo-2,5-dimethoxyphenethylamine: identification of a new street drug. J Anal Toxicol 9:91–93PubMedCrossRefGoogle Scholar
  12. 12.
    Giroud C, Augsburger M, Rivier L, Mangin P, Sadephipour F, Varesio E, Veuthey JL, Kamalaprija P (1998) 2C-B: a new psychoactive phenethylamine recently discovered in ecstasy tablets sold on the Swiss black market. J Anal Toxicol 22:345–354PubMedCrossRefGoogle Scholar
  13. 13.
    deBoer D, Gijzels MJ, Bosman IJ, Maes RA (1999) More data about the new psychoactive drug 2C-B. J Anal Toxicol 23:227–228CrossRefGoogle Scholar
  14. 14.
    Kanamori T, Nagasawa K, Kuwayama K, Tsujikawa K, Iwata YT, Inoue H (2013) Analysis of 4-bromo-2,5-dimethoxyphenethylamine abuser’s urine: identification and quantitation of urinary metabolites. J Forensic Sci 58:279–287PubMedCrossRefGoogle Scholar
  15. 15.
    Heim R (2003) Synthese und Pharmakologie potenter 5-HT2A-Rezeptoragonisten mit N-2-Methoxybenzyl-Partialstruktur. Entwicklung eines neuen Struktur-Wirkungskonzepts (in German). http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000001221. Accessed 9 May 2014
  16. 16.
    Blaazer AR, Smid P, Kruse CG (2008) Structure–activity relationships of phenylalkylamines as agonist ligands for 5-HT(2A) receptors. ChemMedChem 3:1299–1309PubMedCrossRefGoogle Scholar
  17. 17.
    Nichols DE, Frescas SP, Chemel BR, Rehder KS, Zhong D, Lewin AH (2008) High specific activity tritium-labeled N-(2-methoxybenzyl)-2,5-dimethoxy-4-iodophenethylamine (INBMeO): a high-affinity 5-HT2A receptor-selective agonist radioligand. Bioorg Med Chem 16:6116–6123PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Halberstadt AL, Geyer MA (2014) Effects of the hallucinogen 2,5-dimethoxy-4-iodophenethylamine (2C-I) and superpotent N-benzyl derivatives on the head twitch response. Neuropharmacology 77:200–207PubMedCrossRefGoogle Scholar
  19. 19.
    Tang MHY, Ching CK, Tsui MSH, Chu FKC, Mak TWL (2014) Two cases of severe intoxication associated with analytically confirmed use of the novel psychoactive substances 25B-NBOMe and 25C-NBOMe. Clin Toxicol 52:561–565CrossRefGoogle Scholar
  20. 20.
    Silva ME (2008) Theoretical study of the interaction of agonists with the 5-HT2A receptor. http://epub.uni-regensburg.de/12119/1/Maria_Elena_Silva_Doctor_Tesis.pdf. Accessed 8 May 2014
  21. 21.
    Silva ME, Heim R, Strasser A, Elz S, Dove S (2011) Theoretical studies on the interaction of partial agonists with the 5-HT2A receptor. J Comput Aided Mol Des 25:51–66PubMedCrossRefGoogle Scholar
  22. 22.
    European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) (2012) New drugs in Europe. EMCDDA-Europol 2012 annual report on the implementation of council decision 2005/387/JHA. http://www.emcdda.europa.eu/publications/implementation-reports/2012. Accessed 10 May 2014
  23. 23.
    Erowid (2005) 2C-B synthesis without LAH. http://www.erowid.org/archive/rhodium/chemistry/2cb.beaker.html. Accessed 8 May 2014
  24. 24.
    National Drug Intelligence Center (NDIC) (2001) Information bulletin 2C-B (Nexus) reappears on the club drug scene. http://www.justice.gov/archive/ndic/pubs0/665/index.htm. Accessed 9 May 2014
  25. 25.
    Cole MD, Lea C, Oxley N (2002) 4-Bromo-2,5-dimethoxyphenethylamine (2C-B): a review of the public domain literature. Sci Just 42:223–224CrossRefGoogle Scholar
  26. 26.
    Rohanova M, Palenicek T, Balikova M (2008) Disposition of 4-bromo-2,5-dimethoxyphenethylamine (2C-B) and its metabolite 4-bromo-2-hydroxy-5-methoxyphenethylamine in rats after subcutaneous administration. Toxicol Lett 178:29–36PubMedCrossRefGoogle Scholar
  27. 27.
    Caudevilla-Galligo F, Riba J, Ventura M, Gonzalez D, Farre M, Barbanoj MJ, Bouso JC (2012) 4-Bromo-2,5-dimethoxyphenethylamine (2C-B): presence in the recreational drug market in Spain, pattern of use and subjective effects. J Psychopharmacol 26:1026–1035PubMedCrossRefGoogle Scholar
  28. 28.
    Erowid (2014) 2C-B. http://www.erowid.org/chemicals/2cb/2cb.shtml. Accessed 8 May 2014
  29. 29.
    Wikipedia (2014) 2C-B. http://en.wikipedia.org/wiki/2CB. Accessed 8 May 2014
  30. 30.
    Leicester City Council (2014) Drug data, contents of section 5, general information. http://www.leicester.gov.uk/EasySiteWeb/GatewayLink.aspx?alId=74760. Accessed 2 May 2014
  31. 31.
    deBoer D, Bosman I (2004) A new trend in drugs-of-abuse; the 2C-series of phenethylamine designer drugs. Pharm World Sci 26:110–113CrossRefGoogle Scholar
  32. 32.
    King LA (2014) New phenethylamines in Europe. Drug Test Anal 6:808–818PubMedCrossRefGoogle Scholar
  33. 33.
    MixMag (2012) Global drug survey. http://issuu.com/mixmagfashion/docs/drugs_survey_2012_2?e=1541988/2686928#search. Accessed 9 May 2014
  34. 34.
    Burns L, Roxburgh A, Matthews A, Bruno R, Lenton S, Van Buskirk J (2014) The rise of new psychoactive substance use in Australia. Drug Test Anal 6:846–849PubMedCrossRefGoogle Scholar
  35. 35.
    Gine CV, Espinosa IF, Vilamala MV (2014) New psychoactive substances as adulterants of controlled drugs. A worrying phenomenon? Drug Test Anal 6:819–824PubMedCrossRefGoogle Scholar
  36. 36.
    PsychonautWiki (2014) 2C-B. http://psychonautwiki.org/wiki/2C-B. Accessed 10 May 2014
  37. 37.
    Red Button Forum (2014) 2CB. http://red-button.org/a-z/2cb/. Accessed 2 May 2014
  38. 38.
    Cayman Chemical (2014) Item number 12047, 25B-NBOMe (hydrochloride). https://www.caymanchem.com/app/template/Product.vm/catalog/12047;jsessionid=24B0B4AEB5BAD0573691AEFFF54C2622. Accessed 6 May 2014
  39. 39.
    Moya PR, Berg KA, Gutierrez-Hernandez MA, Saez-Briones P, Reyes-Parada M, Cassels BK, Clarke WP (2007) Functional selectivity of hallucinogenic phenethylamine and phenylisopropylamine derivatives at human 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors. J Pharmacol Exp Ther 321:1054–1061PubMedCrossRefGoogle Scholar
  40. 40.
    Kanamori T, Inoue H, Iwata Y, Ohmae Y, Kishi T (2002) In vivo metabolism of 4-bromo-2,5-dimethoxyphenethylamine (2C-B) in the rat: identification of urinary metabolites. J Anal Toxicol 26:61–66PubMedCrossRefGoogle Scholar
  41. 41.
    Carmo H, deBoer D, Remiao F, Carvalho F, dos Reys LA, Bastos ML (2004) Metabolism of the designer drug 4-bromo-2,5-dimethoxyphenethylamine (2C-B) in mice, after acute administration. J Chromatogr B 811:143–152CrossRefGoogle Scholar
  42. 42.
    Carmo H, Hengstler JG, deBoer D, Ringel M, Remiao F, Carvalho F, Fernandes E, dos Reys LA, Oesch F, Bastos ML (2005) Metabolic pathways of 4-bromo-2,5-dimethoxyphenethylamine (2C-B): analysis of phase I metabolism with hepatocytes of six species including human. Toxicology 206:75–89PubMedCrossRefGoogle Scholar
  43. 43.
    Kanamori T, Tsujikawa K, Ohmae Y, Iwata YT, Inoue H, Kishi T, Nakahama T, Inouye Y (2005) A study of the metabolism of methamphetamine and 4-bromo-2,5-dimethoxyphenethylamine (2C-B) in isolated rat hepatocytes. Forensic Sci Int 148:131–137PubMedCrossRefGoogle Scholar
  44. 44.
    Theobald DS, Fritschi G, Maurer HH (2007) Studies on the toxicological detection of the designer drug 4-bromo-2,5-dimethoxy-β-phenethylamine (2C-B) in rat urine using gas chromatography-mass spectrometry. J Chromatogr B 846:374–377CrossRefGoogle Scholar
  45. 45.
    Palenicek T, Fujakova M, Brunovsky M, Horacek J, Gorman I, Balikova M, Rambousek L, Syslova K, Kacer P, Zach P, Bubenikova-Valesova V, Tyls F, Kubesova A, Puskarcikova J, Hoschl C (2013) Behavioral, neurochemical and pharmaco-EEG profiles of the psychedelic drug 4-bromo-2,5-dimethoxyphenethylamine (2C-B) in rats. Psychopharmacology 225:75–93PubMedCrossRefGoogle Scholar
  46. 46.
    Talk to Frank Forum (2013) 2CB: random letters and numbers or something more serious? http://www.talktofrank.com/news/2cb-random-letters-and-numbers-or-something-more-serious. Accessed 9 May 2014
  47. 47.
    Disregard Everything I Say (DEIS) (2013) 2C-B, broken down and described. http://www.disregardeverythingisay.com/post/60184360278/2c-b-broken-down-and-described. Accessed 14 May 2014
  48. 48.
    Youth Rise Forum (2014) Phenethylamines (2CX, DOX, 25IX, etc.). http://www.youthrise.org/our-issues/harm-reduction/nightlife-and-party-drug-harm-reduction/Phenethylamines. Accessed 5 May 2014
  49. 49.
    Ambrose JB, Bennet BA, Lee HS, Josephson SA (2010) Cerebral vasculopathy after 4-bromo-2,5-dimethoxyphenethylamine ingestion. Neurologist 16:199–202PubMedCrossRefGoogle Scholar
  50. 50.
    Namera A, Yashiki M, Kojima T, Ueki M (2002) Automated headspace solid-phase microextraction and in-matrix derivatization for the determination of amphetamine-related drugs in human urine by gas chromatography–mass spectrometry. J Chromatogr Sci 40:19–25PubMedCrossRefGoogle Scholar
  51. 51.
    Soares ME, Carvalho M, Carmo H, Remiao F, Carvalho F, Bastos ML (2004) Simultaneous determination of amphetamine derivatives in human urine after SPE extraction and HPLC-UV analysis. Biomed Chromatogr 18:125–131PubMedCrossRefGoogle Scholar
  52. 52.
    Kim JY, Jung KS, Kim MK, Lee JII, In MK (2007) Simultaneous determination of psychotropic phenylalkylamine derivatives in human hair by gas chromatography/mass spectrometry. Rapid Commun Mass Spectrom 21:1705–1720PubMedCrossRefGoogle Scholar
  53. 53.
    Kerrigan S, Mott A, Jatzlau B, Ortiz F, Perrella L, Martin S, Bryand K (2014) Designer psychostimulants in urine by liquid chromatography-tandem mass spectrometry. J Forensic Sci 59:175–183PubMedCrossRefGoogle Scholar
  54. 54.
    World Health Organization (WHO) (2001) WHO expert committee on drug dependence. Thirty second report. http://whqlibdoc.who.int/trs/WHO_TRS_903.pdf. Accessed 8 May 2014
  55. 55.
    Casale JF, Hays PA (2012) Characterization of eleven 2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (NBOMe) derivatives and differentiation from their 3- and 4-methoxybenzyl analogues–Part I. Microgram J 9:84–109Google Scholar
  56. 56.
    United Nations Office on Drugs and Crime (UNODC) (2013) Global smart update. http://www.unodc.org/documents/scientific/Global_SMART_Update_9_web.pdf. Accessed 9 May 2014
  57. 57.
    European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) (2014) European database on new drugs (EDND), phenethylamines, 25B-NBOMe. https://ednd.emcdda.europa.eu/html.cfm/index7246EN.html. Accessed 6 May 2014
  58. 58.
    Wikipedia (2014) 25B-NBOMe. http://en.wikipedia.org/wiki/25B-NBOMe. Accessed 9 May 2014
  59. 59.
    Drug Enforcement Administration (DEA) (2013) 25I-NBOMe, 25C-NBOMe, and 25B-NBOMe (street names: N-bomb, Smiles, 25I, 25C, 25B). http://www.deadiversion.usdoj.gov/drug_chem_info/nbome.pdf. Accessed on 6 May 2014
  60. 60.
    Erowid (2012) 2C-B-NBOMe reports (also 25B-NBOMe). http://www.erowid.org/experiences/subs/exp_2CBNBOMe.shtml. Accessed 3 May 2014
  61. 61.
    Uchiyama N, Shimokawa Y, Matsuda S, Kawamura M, Kikura-Hanajiri R, Goda Y (2014) Two new synthetic cannabinoids, AM-2201 benzimidazole analog (FUBIMINA) and (4-methylpiperazin-1-yl)(1-pentyl-1H-indol-3-yl)methanone (MEPIRAPIM), and three phenethylamine derivatives, 25H-NBOMe 3,4,5-trimethoxybenzyl analog, 25B-NBOMe, and 2C-N-NBOMe, identified in illegal products. Forensic Toxicol 32:105–115CrossRefGoogle Scholar
  62. 62.
    Lawn W, Barratt M, Williams M, Horne A, Winstock A (2014) The NBOMe hallucinogenic drug series: patterns of use, characteristics of users and self-reported effects in a large international sample. J Psychopharmacol 28:780–788PubMedCrossRefGoogle Scholar
  63. 63.
    Drugs Forum (2014) 25B-NBOMe. http://www.drugs-forum.com/forum/showwiki.php?title=25B-NBOMe. Accessed 9 May 2014
  64. 64.
    PsychonautWiki (2014) 25B-NBOMe. http://psychonautwiki.org/wiki/25B-NBOMe. Accessed 10 May 2014
  65. 65.
    Ettrup A, Holm S, Hansen M, Wasim M, Santini MA, Palner M, Madsen J, Svarer C, Kristensen JL, Knudsen GM (2013) Preclinical safety assessment of the 5-HT2A receptor agonist PET radioligand [11C]Cimbi-36. Mol Imag Biol 15:376–383CrossRefGoogle Scholar
  66. 66.
    Poklis JL, Charles J, Wolf CE, Poklis A (2013) High-performance liquid chromatography tandem mass spectrometry method for the determination of 2CC-NBOMe and 25I-NBOMe in human serum. Biomed Chromatogr 27:1794–1800PubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    Disregard Everything I Say (DEIS) (2014) 25B-NBOMe, broken down and described. http://www.disregardeverythingisay.com/post/83025698345/25b-nbome-broken-down-and-described. Accessed 14 May 2014
  68. 68.
    Shroomery Forum (2012) New hallucinogenic drug 25B-NBOMe and 25I-NBOMe led to South Australian man’s bizarre death. http://www.shroomery.org/forums/showflat.php/Number/16834552. Accessed 9 May 2014
  69. 69.
    Rice S (2012) New hallucinogenic drug 25B-NBOMe and 25I-NBOMe led to South Australian man’s bizarre death. http://www.news.com.au/national-news-2/south-australia/new-hallucinogenic-drug-25b-nbome-and-25i-nbome-led-to-south-australian-mans-bizarre-death/story-fndo4dzn-1226472672220. Accessed 8 May 2014
  70. 70.
    Poklis JL, Nanco CR, Troendle MM, Wolf CE, Poklis A (2014) Determination of 4-bromo-2,5-dimethoxy-N-[(2-methoxyphenyl)methyl]-benzeneethanamine (25B-NBOMe) serum and urine by high performance liquid chromatography with tandem mass spectrometry in a case of severe intoxication. Drug Test Anal 6:764–769PubMedCentralPubMedCrossRefGoogle Scholar
  71. 71.
    Sporkert F, Augsburger M, Vilarino R, Michaud K, Schlapfer M, Marcourt L (2013) Identification and implication of the phenethylamine derivative 25B-NBOMe in a case of an unresolved fatality. The 51st annual meeting of the International Association of Forensic Toxicologists, MadeiraGoogle Scholar
  72. 72.
    Neurosoup Forum (2013) 25B-NBOMe (2C-B-NBOMe) hospitalization. http://www.neurosoup.com/25b-nbome-2c-b-nbome-hospitalization/. Accessed 8 May 2014
  73. 73.
    Erowid (2012) 25I-NBOMe. http://www.erowid.org/chemicals/2ci_nbome/. Accessed 3 May 2014
  74. 74.
    Scientific Working Group for the Analysis of Seized Drugs (SWGDRUG) (2013) 25B-NBOMe. http://www.swgdrug.org/Monographs/25B-NBOMe.pdf. Accessed 9 May 2014
  75. 75.
    Forendex Forum (2014) Southern Association of Forensic Scientists. http://forendex.southernforensic.org/index.php/detail/index/1246. Accessed 5 May 2014
  76. 76.
    Home Office (2013) ‘NBOMe’ and ‘Benzofury’ banned. https://www.gov.uk/government/news/nbome-and-benzofury-to-be-banned. Accessed 14 May 2014
  77. 77.
    Drug Enforcement Administration (DEA), Department of Justice (2013) Schedules of controlled substances: temporary placement of three synthetic phenethylamines into Schedule I. Final Order. Fed Reg 78:68716–68719Google Scholar
  78. 78.
    Läkemedelsverkets författningssamling (2013) Föreskrifter om ändring i Läkemedelsverkets föreskrifter (LVFS 2011:10) om förteckningar över narkotika (in Swedish). http://www.lakemedelsverket.se/upload/lvfs/LVFS_2013-15.pdf. Accessed 8 May 2014
  79. 79.
    Sundhedsstyrelsen (2013) Health and treatment/narcotico (in Danish). file:///C:/Users/user/Downloads/DK_NBOMe%20substances%20risk%20assessment%20(3).pdf. Accessed 8 May 2014Google Scholar

Copyright information

© Japanese Association of Forensic Toxicology and Springer Japan 2014

Authors and Affiliations

  • Ioannis Papoutsis
    • 1
  • Panagiota Nikolaou
    • 1
    Email author
  • Maria Stefanidou
    • 1
  • Chara Spiliopoulou
    • 1
  • Sotiris Athanaselis
    • 1
  1. 1.Department of Forensic Medicine and Toxicology, Faculty of MedicineNational and Kapodistrian University of AthensAthensGreece

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