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NBOMe compounds are often associated with life-threatening toxicity and death.[1][2] Studies on NBOMe family of compounds demonstrated that the substance exhibit neurotoxic and cardiotoxic activity.[3] Reports of autonomic dysfunction remains prevalent with NBOMe compounds, with most individuals experiencing sympathomimetic toxicity such as vasoconstriction, hypertension and tachycardia in addition to hallucinations.[4][5][6][7][8] Other symptoms of toxidrome of include agitation or aggression, seizure, hyperthermia, diaphoresis, hypertonia, rhabdomyolysis, and death.[4][8][2] Researchers report that NBOMe intoxication frequently display signs of serotonin syndrome.[9] The likelihood of seizure is higher in NBOMes compared to other psychedelics.[3]

NBOMe and NBOHs are regularly sold as LSD in blotter papers,[2][10] which have a bitter taste and different safety profiles.[4][1] Despite high potency, recreational doses of LSD have only produced low incidents of acute toxicity.[1] Fatalities involved in NBOMe intoxication suggest that a significant number of individuals ingested the substance which they believed was LSD,[6] and researchers report that "users familiar with LSD may have a false sense of security when ingesting NBOMe inadvertently".[4] While most fatalities are due to the physical effects of the drug, there have also been reports of death due to self-harm and suicide under the influence of the substance.[11][12][4]

Given limited documentation of NBOMe consumption, the long-term effects of the substance remain unknown.[4] NBOMe compounds are not active orally,[a] and are usually taken sublingually.[14]: 3  When NBOMes are administered sublingually, numbness of the tongue and mouth followed by a metallic chemical taste was observed, and researchers describe this physical side effect as one of the main discriminants between NBOMe compounds and LSD.[15][16][17]

Neurotoxic and cardiotoxic actions

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Many of the NBOMe compounds have high potency agonist activity at additional 5-HT receptors and prolonged activation of 5-HT2B can cause cardiac valvulopathy in high doses and chronic use.[2][7] 5-HT2B receptors have been strongly implicated in causing drug-induced valvular heart disease.[18][19][20] The high affinity of NBOMe compounds for adrenergic α1 receptor has been reported to contribute to the stimulant-type cardiovascular effects.[7]

In vitro studies, 25C-NBOMe has been shown to exhibit cytotoxicity on neuronal cell lines SH-SY5Y, PC12, and SN471, and the compound was more potent than methamphetamine at reducing the visibility of the respective cells; the neurotoxicity of the compound involves activation of MAPK/ERK cascade and inhibition of Akt/PKB signaling pathway.[3] 25C-NBOMe, including the other derivative 25D-NBOMe, reduced the visibility of cardiomyocytes H9c2 cells, and both substances downregulated expression level of p21 (CDC24/RAC)-activated kinase 1 (PAK1), an enzyme with documented cardiac protective effects.[3]

Preliminary studies on 25C-NBOMe have shown that the substance is toxic to development, heart health, and brain health in zebrafish, rats, and Artemia salina, a common organism for studying potential drug effects on humans, but more research is needed on the topic, the dosages, and if the toxicology results apply to humans. Researchers of the study also recommended further investigation of the drug's potential in damaging pregnant women and their fetus due to the substance's damaging effects to development.[21][22]

Emergency treatment

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At present, there are no specific antidotes for NBOMes, and all acute intoxication is managed by symptomatic treatments, such as administration of benzodiazepines, antipsychotic drugs, and antiarrhythmic agents, such as beta blockers; some emergency interventions are intended to specifically treat rhabdomyolysis, which may lead to critical complications such as metabolic acidosis and acute kidney injury.[3]

Other sources

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Reference

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  1. ^ a b c Sean I, Joe R, Jennifer S, and Shaun G (28 March 2022). "A cluster of 25B-NBOH poisonings following exposure to powder sold as lysergic acid diethylamide (LSD)". Clinical Toxicology. 60 (8): 966–969. doi:10.1080/15563650.2022.2053150. PMID 35343858.
  2. ^ a b c d Amy E, Katherine W, John R, Sonyoung K, Robert J, Aaron J (December 2018). "Neurochemical pharmacology of psychoactive substituted N-benzylphenethylamines: High potency agonists at 5-HT2A receptors". Biochemical Pharmacology. 158: 27–34. doi:10.1016/j.bcp.2018.09.024. PMC 6298744. PMID 30261175.
  3. ^ a b c d e Jolanta Z, Monika K, and Piotr A (26 February 2020). "NBOMes–Highly Potent and Toxic Alternatives of LSD". Frontiers in Neuroscience. 14: 1-12. doi:10.3389/fnins.2020.00078. PMID 32174803.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  4. ^ a b c d e f Lipow M, Kaleem SZ, Espiridion E (30 March 2022). "NBOMe Toxicity and Fatalities: A Review of the Literature". Transformative Medicine. 1 (1): 12–18. doi:10.54299/tmed/msot8578. ISSN 2831-8978. S2CID 247888583.
  5. ^ Micaela T, Sabrine B, Raffaella A, Giorgia C, Beatrice M, Tatiana B, Federica B, Giovanni S, Francesco B, Fabio G, Krystyna G, Matteo M (21 April 2022). "Effect of -NBOMe Compounds on Sensorimotor, Motor, and Prepulse Inhibition Responses in Mice in Comparison With the 2C Analogs and Lysergic Acid Diethylamide: From Preclinical Evidence to Forensic Implication in Driving Under the Influence of Drugs". Front Psychiatry. doi:10.3389/fpsyt.2022.875722. PMC 9069068. PMID 35530025.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  6. ^ a b Cristina M, Matteo M, Nicholas P, Maria C, Micaela T, Raffaella A, Maria L (12 December 2019). "Neurochemical and Behavioral Profiling in Male and Female Rats of the Psychedelic Agent 25I-NBOMe". Frontiers in Pharmacology. 10. doi:10.3389/fphar.2019.01406. PMC 6921684. PMID 31915427.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  7. ^ a b c Anna R, Dino L, Julia R, Daniele B, Marius H, Matthias L (December 2015). "Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs)". Neuropharmacology. 99: 546–553. doi:10.1016/j.neuropharm.2015.08.034. ISSN 1873-7064. PMID 26318099.
  8. ^ a b David W, Roumen S, Andrew C, Paul D (6 February 2015). "Prevalence of use and acute toxicity associated with the use of NBOMe drugs". Clinical Toxicology. 53 (2): 85–92. doi:10.3109/15563650.2015.1004179. PMID 25658166.
  9. ^ Humston C, Miketic R, Moon K, Ma P, Tobias J (2017-06-05). "Toxic Leukoencephalopathy in a Teenager Caused by the Recreational Ingestion of 25I-NBOMe: A Case Report and Review of Literature". Journal of Medical Cases. 8 (6): 174–179. doi:10.14740/jmc2811w. ISSN 1923-4163.
  10. ^ Justin P, Stephen R, Kylin A, Alphonse P, Michelle P. "Analysis of 25I-NBOMe, 25B-NBOMe, 25C-NBOMe and Other Dimethoxyphenyl-N-[(2-Methoxyphenyl) Methyl]Ethanamine Derivatives on Blotter Paper". Journal of Analytical Toxicology: 617–623. doi:10.1093/jat/bkv073. PMC 4570937. PMID 26378135.
  11. ^ Morini L, Bernini M, Vezzoli S, Restori M, Moretti M, Crenna S, et al. (October 2017). "Death after 25C-NBOMe and 25H-NBOMe consumption". Forensic Science International. 279: e1–e6. doi:10.1016/j.forsciint.2017.08.028. PMID 28893436.
  12. ^ Byard RW, Cox M, Stockham P (November 2016). "Blunt Craniofacial Trauma as a Manifestation of Excited Delirium Caused by New Psychoactive Substances". Journal of Forensic Sciences. 61 (6): 1546–1548. doi:10.1111/1556-4029.13212. PMID 27723094. S2CID 4734566.
  13. ^ a b Sabastian LP, Christoffer B, Martin H, Martin AC, Jan K, Jesper LK (14 February 2014). "Correlating the Metabolic Stability of Psychedelic 5-HT2A Agonists with Anecdotal Reports of Human Oral Bioavailability". NeuroChemical Research: 2018–2023. doi:10.1007/s11064-014-1253-y. PMID 24519542.
  14. ^ Adam H (18 January 2017). "Pharmacology and Toxicology of N-Benzylphenethylamine ("NBOMe") Hallucinogens". Neuropharmacology of New Psychoactive Substances. Springer. pp. 283–311. doi:10.1007/7854_2016_64. ISBN 978-3-319-52444-3. PMID 28097528.
  15. ^ Boris D, Cristian C, Marcelo K, Edwar F, Bruce KC (August 2016). "Analysis of 25 C NBOMe in Seized Blotters by HPTLC and GC–MS". Journal of Chromatographic Science. 54 (7): 1153–1158. doi:10.1093/chromsci/bmw095. PMC 4941995. PMID 27406128.
  16. ^ Francesco SB, Ornella C, Gabriella A, Giuseppe V, Rita S, Flaminia BP, Eduardo C, Pierluigi S, Giovanni M, Guiseppe B, Fabrizio S (3 July 2014). "25C-NBOMe: preliminary data on pharmacology, psychoactive effects, and toxicity of a new potent and dangerous hallucinogenic drug". BioMed Research International. 2014. doi:10.1155/2014/734749. PMC 4106087. PMID 25105138.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  17. ^ Adam JP, Simon HT, Simon LH (September 2021). "Pharmacology and toxicology of N-Benzyl-phenylethylamines (25X-NBOMe) hallucinogens". Novel Psychoactive Substances: Classification, Pharmacology and Toxicology (2 ed.). Academic Press. pp. 279–300. doi:10.1016/B978-0-12-818788-3.00008-5. ISBN 978-0-12-818788-3.
  18. ^ Rothman RB, Baumann MH, Savage JE, Rauser L, McBride A, Hufeisen SJ, Roth BL (Dec 2000). "Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications". Circulation. 102 (23): 2836–41. doi:10.1161/01.CIR.102.23.2836. PMID 11104741.
  19. ^ Fitzgerald LW, Burn TC, Brown BS, Patterson JP, Corjay MH, Valentine PA, Sun JH, Link JR, Abbaszade I, Hollis JM, Largent BL, Hartig PR, Hollis GF, Meunier PC, Robichaud AJ, Robertson DW (Jan 2000). "Possible role of valvular serotonin 5-HT(2B) receptors in the cardiopathy associated with fenfluramine". Molecular Pharmacology. 57 (1): 75–81. PMID 10617681.
  20. ^ Roth BL (Jan 2007). "Drugs and valvular heart disease". The New England Journal of Medicine. 356 (1): 6–9. doi:10.1056/NEJMp068265. PMID 17202450.
  21. ^ Xu P, Qiu Q, Li H, Yan S, Yang M, Naman CB, et al. (26 February 2019). "25C-NBOMe, a Novel Designer Psychedelic, Induces Neurotoxicity 50 Times More Potent Than Methamphetamine In Vitro". Neurotoxicity Research. 35 (4): 993–998. doi:10.1007/s12640-019-0012-x. PMID 30806983. S2CID 255763701.
  22. ^ Álvarez-Alarcón N, Osorio-Méndez JJ, Ayala-Fajardo A, Garzón-Méndez WF, Garavito-Aguilar ZV (2021). "Zebrafish and Artemia salina in vivo evaluation of the recreational 25C-NBOMe drug demonstrates its high toxicity". Toxicology Reports. 8: 315–323. doi:10.1016/j.toxrep.2021.01.010. ISSN 2214-7500. PMC 7868744. PMID 33598409.
  1. ^ The potency of N-benzylphenethylamines via buccal, sublingual, or nasal absorption is 50-100 greater (by weight) than oral route compared to the parent 2C-x compounds.[13] Researchers hypothesize the low oral metabolic stability of N-benzylphenethylamines is likely causing the low bioavailability on the oral route, although the metabolic profile of this compounds remains unpredictable; therefore researchers state that the fatalities linked to these substances may partly be explained by differences in the metabolism between individuals.[13]
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