25-NB

The 25-NB drugs are inactive orally and instead are typically used sublingually, buccally, by insufflation, or sometimes via inhalation. They are typically employed at doses in the range of 50 to 1,500{{nbsp}}μg, variable depending on the specific drug, and have durations in the range of 3 to 12{{nbsp}}hours. The table below provides an overview of the major 25-NB drugs and their properties.

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NBOMe compounds are often associated with life-threatening toxicity and death.{{cite journal | journal = Clinical Toxicology | title = A cluster of 25B-NBOH poisonings following exposure to powder sold as lysergic acid diethylamide (LSD) | doi = 10.1080/15563650.2022.2053150 | vauthors = Sean I, Joe R, Jennifer S, and Shaun G |url=https://www.tandfonline.com/doi/abs/10.1080/15563650.2022.2053150 | pages = 966–969 | date = 28 March 2022 | volume = 60 | issue = 8 | pmid = 35343858| s2cid = 247764056 | url-access = subscription }}{{cite journal | journal = Biochemical Pharmacology | vauthors = Amy E, Katherine W, John R, Sonyoung K, Robert J, Aaron J | title = Neurochemical pharmacology of psychoactive substituted N-benzylphenethylamines: High potency agonists at 5-HT2A receptors | doi = 10.1016/j.bcp.2018.09.024 | pmid = 30261175 | pmc = 6298744 | volume = 158 | pages = 27–34 | date = December 2018}} Studies on NBOMe family of compounds demonstrated that the substance exhibit neurotoxic and cardiotoxic activity.{{cite journal | journal = Frontiers in Neuroscience | vauthors = Jolanta Z, Monika K, and Piotr A | doi = 10.3389/fnins.2020.00078 | date = 26 February 2020 | volume = 14 | pmid = 32174803 | title = NBOMes–Highly Potent and Toxic Alternatives of LSD | page = 78 | pmc = 7054380 | doi-access = free | quote = Recently, a new class of psychedelic compounds named NBOMe (or 25X-NBOMe) has appeared on the illegal drug market. NBOMes are analogs of the 2C family of phenethylamine drugs, originally synthesized by Alexander Shulgin, that contain a N-(2-methoxy)benzyl substituent. The most frequently reported drugs from this group are 25I-NBOMe, 25B-NBOMe, and 25C-NBOMe. NBOMe compounds are ultrapotent and highly efficacious agonists of serotonin 5-HT2A and 5-HT2C receptors (Ki values in low nanomolar range) with more than 1000-fold selectivity for 5-HT2A compared with 5-HT1A. They display higher affinity for 5-HT2A receptors than their 2C counterparts and have markedly lower affinity, potency, and efficacy at the 5-HT2B receptor compared to 5-HT2A or 5-HT2C. }} 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.{{cite journal | vauthors = Tirri M, Bilel S, Arfè R, Corli G, Marchetti B, Bernardi T, Boccuto F, Serpelloni G, Botrè F, De-Giorgio F, Golembiowska K, Marti M | title = 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 | journal = Front Psychiatry | volume = 13 | issue = | pages = 875722 | date = 2022 | pmid = 35530025 | pmc = 9069068 | doi = 10.3389/fpsyt.2022.875722 | doi-access = free | url = }}{{cite journal | title = Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs) | journal = Neuropharmacology | doi = 10.1016/j.neuropharm.2015.08.034 | pmid = 26318099 | vauthors = Anna R, Dino L, Julia R, Daniele B, Marius H, Matthias L | pages = 546–553 | date = December 2015 |url=https://www.sciencedirect.com/science/article/abs/pii/S0028390815300794 | volume = 99 | s2cid = 10382311 | issn = 1873-7064}}{{cite journal | journal = Clinical Toxicology | title = Prevalence of use and acute toxicity associated with the use of NBOMe drugs | vauthors = David W, Roumen S, Andrew C, Paul D |url=https://www.tandfonline.com/doi/abs/10.3109/15563650.2015.1004179 | doi = 10.3109/15563650.2015.1004179 | date = 6 February 2015 | pages = 85–92 | volume = 53 | issue = 2 | pmid = 25658166| s2cid = 25752763 | url-access = subscription }} Other symptoms of toxidrome include agitation or aggression, seizure, hyperthermia, diaphoresis, hypertonia, rhabdomyolysis, and death.{{Cite journal | vauthors = Lipow M, Kaleem SZ, Espiridion E | date = 30 March 2022 | title = NBOMe Toxicity and Fatalities: A Review of the Literature |url=https://scholarcommons.towerhealth.org/t-med/vol1/iss1/3/ |journal=Transformative Medicine | volume = 1 | issue = 1 | pages = 12–18 | doi = 10.54299/tmed/msot8578 | s2cid = 247888583 | issn = 2831-8978 | doi-access = free }} Researchers report that NBOMe intoxication frequently display signs of serotonin syndrome.{{Cite journal | vauthors = Humston C, Miketic R, Moon K, Ma P, Tobias J |date=2017-06-05 |title=Toxic Leukoencephalopathy in a Teenager Caused by the Recreational Ingestion of 25I-NBOMe: A Case Report and Review of Literature |url=https://www.journalmc.org/index.php/JMC/article/view/2811 |journal=Journal of Medical Cases |volume=8 |issue=6 |pages=174–179 |doi=10.14740/jmc2811w |issn=1923-4163|doi-access=free }} The likelihood of seizure is higher in NBOMes compared to other psychedelics.

NBOMe and NBOHs are regularly sold as LSD in blotter papers,{{cite journal | journal = Journal of Analytical Toxicology | doi = 10.1093/jat/bkv073 | pmc = 4570937 | pmid = 26378135 | title = Analysis of 25I-NBOMe, 25B-NBOMe, 25C-NBOMe and Other Dimethoxyphenyl-N-[(2-Methoxyphenyl) Methyl]Ethanamine Derivatives on Blotter Paper | vauthors = Justin P, Stephen R, Kylin A, Alphonse P, Michelle P | year = 2015 | volume = 39 | issue = 8 | pages = 617–623}} which have a bitter taste and different safety profiles. Despite high potency, recreational doses of LSD have only produced low incidents of acute toxicity. Fatalities involved in NBOMe intoxication suggest that a significant number of individuals ingested the substance which they believed was LSD,{{cite journal | journal = Frontiers in Pharmacology | date = 12 December 2019 | doi = 10.3389/fphar.2019.01406 | vauthors = Cristina M, Matteo M, Nicholas P, Maria C, Micaela T, Raffaella A, Maria L | title = Neurochemical and Behavioral Profiling in Male and Female Rats of the Psychedelic Agent 25I-NBOMe | volume = 10 | page = 1406 | pmid = 31915427 | pmc = 6921684 | doi-access = free }} and researchers report that "users familiar with LSD may have a false sense of security when ingesting NBOMe inadvertently". 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.{{cite journal | vauthors = Morini L, Bernini M, Vezzoli S, Restori M, Moretti M, Crenna S, Papa P, Locatelli C, Osculati AM, Vignali C, Groppi A | title = Death after 25C-NBOMe and 25H-NBOMe consumption | journal = Forensic Science International | volume = 279 | pages = e1–e6 | date = October 2017 | pmid = 28893436 | doi = 10.1016/j.forsciint.2017.08.028 |url=https://www.sciencedirect.com/science/article/abs/pii/S0379073817303377| url-access = subscription }}{{cite journal | vauthors = Byard RW, Cox M, Stockham P | title = Blunt Craniofacial Trauma as a Manifestation of Excited Delirium Caused by New Psychoactive Substances | journal = Journal of Forensic Sciences | volume = 61 | issue = 6 | pages = 1546–1548 | date = November 2016 | pmid = 27723094 | doi = 10.1111/1556-4029.13212 | s2cid = 4734566 |url=https://onlinelibrary.wiley.com/doi/abs/10.1111/1556-4029.13212| url-access = subscription }}

Given limited documentation of NBOMe consumption, the long-term effects of the substance remain unknown. NBOMe compounds are not active orally,{{efn|The potency of N-benzylphenethylamines via buccal, sublingual, or nasal absorption is 50- to 100-fold greater (by weight) than oral route compared to the parent 2C-x compounds.{{cite journal | journal = Neurochemical Research | date = 14 February 2014 | vauthors = Sabastian LP, Christoffer B, Martin H, Martin AC, Jan K, Jesper LK | title = Correlating the Metabolic Stability of Psychedelic 5-HT2A Agonists with Anecdotal Reports of Human Oral Bioavailability | volume = 39 | issue = 10 |url=https://link.springer.com/article/10.1007/s11064-014-1253-y | pages = 2018–2023 | doi = 10.1007/s11064-014-1253-y | pmid = 24519542| s2cid = 254857910 | url-access = subscription }} 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.}} and are usually taken sublingually.{{cite book | title = Neuropharmacology of New Psychoactive Substances | vauthors = Adam H | doi = 10.1007/7854_2016_64 | date = 18 January 2017 | isbn = 978-3-319-52444-3 | publisher = Springer |chapter-url=https://link.springer.com/chapter/10.1007/7854_2016_64 | chapter = Pharmacology and Toxicology of N-Benzylphenethylamine ("NBOMe") Hallucinogens | series = Current Topics in Behavioral Neurosciences | volume = 32 | pages = 283–311 | pmid = 28097528}}{{rp|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.{{cite journal | vauthors = Boris D, Cristian C, Marcelo K, Edwar F, Bruce KC | journal = Journal of Chromatographic Science | volume = 54 | issue = 7 | date = August 2016 | pages = 1153–1158 | title = Analysis of 25 C NBOMe in Seized Blotters by HPTLC and GC–MS | pmc = 4941995 | pmid = 27406128 | doi = 10.1093/chromsci/bmw095 |url=https://academic.oup.com/chromsci/article/54/7/1153/2754859}}{{cite journal | pmid = 25105138 | pmc = 4106087 | doi = 10.1155/2014/734749 | title = 25C-NBOMe: preliminary data on pharmacology, psychoactive effects, and toxicity of a new potent and dangerous hallucinogenic drug | journal = BioMed Research International | date = 3 July 2014 | vauthors = Francesco SB, Ornella C, Gabriella A, Giuseppe V, Rita S, Flaminia BP, Eduardo C, Pierluigi S, Giovanni M, Guiseppe B, Fabrizio S | volume = 2014 | page = 734749 | doi-access = free }}{{cite book | title = Novel Psychoactive Substances: Classification, Pharmacology and Toxicology | chapter = Pharmacology and toxicology of N-Benzyl-phenylethylamines (25X-NBOMe) hallucinogens | vauthors = Adam JP, Simon HT, Simon LH | doi = 10.1016/B978-0-12-818788-3.00008-5 | isbn = 978-0-12-818788-3 | pages = 279–300 | edition = 2 | publisher = Academic Press | date = September 2021 | s2cid = 240583877 |chapter-url=https://www.sciencedirect.com/science/article/abs/pii/B9780128187883000085}}

Many of the NBOMe compounds have high potency agonist activity at additional 5-HT receptors and prolonged activation of 5-HT_2B can cause cardiac valvulopathy in high doses and chronic use. 5-HT_2B receptors have been strongly implicated in causing drug-induced valvular heart disease.{{cite journal | vauthors = Rothman RB, Baumann MH, Savage JE, Rauser L, McBride A, Hufeisen SJ, Roth BL|author7-link=Bryan Roth | title = Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications | journal = Circulation | volume = 102 | issue = 23 | pages = 2836–41 | date = Dec 2000 | pmid = 11104741 | doi = 10.1161/01.CIR.102.23.2836 | doi-access = free }}{{cite journal | vauthors = 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 | title = Possible role of valvular serotonin 5-HT(2B) receptors in the cardiopathy associated with fenfluramine |url=https://pubmed.ncbi.nlm.nih.gov/10617681/ | journal = Molecular Pharmacology | volume = 57 | issue = 1 | pages = 75–81 | date = Jan 2000 | doi = 10.1016/S0026-895X(24)26444-0 | pmid = 10617681 }}{{cite journal | vauthors = Roth BL | title = Drugs and valvular heart disease | journal = The New England Journal of Medicine | volume = 356 | issue = 1 | pages = 6–9 | date = Jan 2007 | pmid = 17202450 | doi = 10.1056/NEJMp068265 |url=https://www.nejm.org/doi/full/10.1056/NEJMp068265| url-access = subscription }} The high affinity of NBOMe compounds for adrenergic α₁ receptor has been reported to contribute to the stimulant-type cardiovascular effects.

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. 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.

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.{{cite journal | vauthors = Xu P, Qiu Q, Li H, Yan S, Yang M, Naman CB, Wang Y, Zhou W, Shen H, Cui W | title = 25C-NBOMe, a Novel Designer Psychedelic, Induces Neurotoxicity 50 Times More Potent Than Methamphetamine In Vitro | journal = Neurotoxicity Research | volume = 35 | issue = 4 | pages = 993–998 | date = 26 February 2019 | pmid = 30806983 | doi = 10.1007/s12640-019-0012-x |url=https://link.springer.com/article/10.1007/s12640-019-0012-x | s2cid = 255763701| url-access = subscription }}{{cite journal | vauthors = Álvarez-Alarcón N, Osorio-Méndez JJ, Ayala-Fajardo A, Garzón-Méndez WF, Garavito-Aguilar ZV | title = Zebrafish and Artemia salina in vivo evaluation of the recreational 25C-NBOMe drug demonstrates its high toxicity | journal = Toxicology Reports | volume = 8 | pages = 315–323 | year = 2021 | issn = 2214-7500 | pmid = 33598409 | pmc = 7868744 | doi = 10.1016/j.toxrep.2021.01.010 | bibcode = 2021ToxR....8..315A }}

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.

{{See also|Psychedelic drug#Interactions|Trip killer#Serotonergic psychedelic antidotes}}

2C drugs like 2C-I are metabolized by the monoamine oxidase (MAO) enzymes, including both MAO-A and MAO-B.{{cite journal | vauthors = Dean BV, Stellpflug SJ, Burnett AM, Engebretsen KM | title = 2C or not 2C: phenethylamine designer drug review | journal = J Med Toxicol | volume = 9 | issue = 2 | pages = 172–178 | date = June 2013 | pmid = 23494844 | pmc = 3657019 | doi = 10.1007/s13181-013-0295-x | url = }}{{cite journal | vauthors = Theobald DS, Maurer HH | title = Identification of monoamine oxidase and cytochrome P450 isoenzymes involved in the deamination of phenethylamine-derived designer drugs (2C-series) | journal = Biochem Pharmacol | volume = 73 | issue = 2 | pages = 287–297 | date = January 2007 | pmid = 17067556 | doi = 10.1016/j.bcp.2006.09.022 | url = }} As a result, 2C drugs may be potentiated by monoamine oxidase inhibitors (MAOIs), such as phenelzine, tranylcypromine, moclobemide, and selegiline.{{Cite journal |vauthors=Halman A, Kong G, Sarris J, Perkins D |date=January 2024 |title=Drug-drug interactions involving classic psychedelics: A systematic review |journal=J Psychopharmacol |volume=38 |issue=1 |pages=3–18 |doi=10.1177/02698811231211219 |pmc=10851641 |pmid=37982394}} This has the potential to lead to overdose and serious toxicity. In contrast to 2C drugs, 25I-NBOMe has been found not to be metabolized by MAO-A or MAO-B and instead only by cytochrome P450 enzymes.{{cite journal | vauthors = Nielsen LM, Holm NB, Leth-Petersen S, Kristensen JL, Olsen L, Linnet K | title = Characterization of the hepatic cytochrome P450 enzymes involved in the metabolism of 25I-NBOMe and 25I-NBOH | journal = Drug Test Anal | volume = 9 | issue = 5 | pages = 671–679 | date = May 2017 | pmid = 27400739 | doi = 10.1002/dta.2031 | url = }} Other 25-NB drugs besides 25I-NBOMe were not assessed.

The NBOMe drugs are highly potent and selective agonists of the serotonin 5-HT₂ receptors, including of the 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors.{{cite journal | vauthors = Eshleman AJ, Wolfrum KM, Reed JF, Kim SO, Johnson RA, Janowsky A | title = Neurochemical pharmacology of psychoactive substituted N-benzylphenethylamines: High potency agonists at 5-HT2A receptors | journal = Biochem Pharmacol | volume = 158 | issue = | pages = 27–34 | date = December 2018 | pmid = 30261175 | pmc = 6298744 | doi = 10.1016/j.bcp.2018.09.024 | url = }}{{cite journal | vauthors = Rickli A, Luethi D, Reinisch J, Buchy D, Hoener MC, Liechti ME | title = Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs) | journal = Neuropharmacology | volume = 99 | issue = | pages = 546–553 | date = December 2015 | pmid = 26318099 | doi = 10.1016/j.neuropharm.2015.08.034 | url = http://edoc.unibas.ch/56163/1/20170921163006_59c3cceeb8e5d.pdf}}{{cite journal | vauthors = Wallach J, Cao AB, Calkins MM, Heim AJ, Lanham JK, Bonniwell EM, Hennessey JJ, Bock HA, Anderson EI, Sherwood AM, Morris H, de Klein R, Klein AK, Cuccurazzu B, Gamrat J, Fannana T, Zauhar R, Halberstadt AL, McCorvy JD | title = Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential | journal = Nat Commun | volume = 14 | issue = 1 | pages = 8221 | date = December 2023 | pmid = 38102107 | pmc = 10724237 | doi = 10.1038/s41467-023-44016-1 }} However, they are much less potent and efficacious at the serotonin 5-HT_2B receptor compared to the serotonin 5-HT_2A and 5-HT_2C receptors. The drugs are highly selective for the serotonin 5-HT₂ receptors over other serotonin receptors and over a variety of other biological targets. They are likewise inactive as monoamine reuptake inhibitors and releasing agents. Many of the NBOMe drugs are partial agonists of the rat and mouse trace amine-associated receptor 1 (TAAR1), but they are inactive as agonists of the human TAAR1.{{cite journal | vauthors = Simmler LD, Buchy D, Chaboz S, Hoener MC, Liechti ME | title = In Vitro Characterization of Psychoactive Substances at Rat, Mouse, and Human Trace Amine-Associated Receptor 1 | journal = J Pharmacol Exp Ther | volume = 357 | issue = 1 | pages = 134–144 | date = April 2016 | pmid = 26791601 | doi = 10.1124/jpet.115.229765 | url = https://d1wqtxts1xzle7.cloudfront.net/74120533/eae6c6e62565b82d46b4d111bbea0f77b9c2-libre.pdf?1635931703=&response-content-disposition=inline%3B+filename%3DIn_Vitro_Characterization_of_Psychoactiv.pdf&Expires=1746838268&Signature=Sy4fJ90yUhxs68314NxYsW5PAaNrBGePRu35WRR4PIF-3YC7Z~sLdnCn5wfqqbLg9bDEGdt~oW55ugMP3D3jgA0BoRI~~GOb0NQOwrtfUEQK1PQs1uuN9qg5Y1ct8z5NsABm44RgtukkwRMdU6fO7OlfIsQ68hOiFk129Ll7UYqldxD2f1xhE2fTTfsxSpb8cMCJzHn7-ItqLdwnAUPFK7WggDIjmY1kCnaHLwIxMwdJCAq8L6DYzSTg7pZkbR8qlou~GXbTPQt~gYpyZTJp5hgW-7V6K5wLlQ7Z2xE7B0f9wEfuc1W1QNafg125Tr-vvAe4LEGKXV58bnn1bpfWKw__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA| archive-url = https://web.archive.org/web/20250509235235/https://d1wqtxts1xzle7.cloudfront.net/74120533/eae6c6e62565b82d46b4d111bbea0f77b9c2-libre.pdf?1635931703=&response-content-disposition=inline%3B+filename%3DIn_Vitro_Characterization_of_Psychoactiv.pdf&Expires=1746838268&Signature=Sy4fJ90yUhxs68314NxYsW5PAaNrBGePRu35WRR4PIF-3YC7Z~sLdnCn5wfqqbLg9bDEGdt~oW55ugMP3D3jgA0BoRI~~GOb0NQOwrtfUEQK1PQs1uuN9qg5Y1ct8z5NsABm44RgtukkwRMdU6fO7OlfIsQ68hOiFk129Ll7UYqldxD2f1xhE2fTTfsxSpb8cMCJzHn7-ItqLdwnAUPFK7WggDIjmY1kCnaHLwIxMwdJCAq8L6DYzSTg7pZkbR8qlou~GXbTPQt~gYpyZTJp5hgW-7V6K5wLlQ7Z2xE7B0f9wEfuc1W1QNafg125Tr-vvAe4LEGKXV58bnn1bpfWKw__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA | archive-date = 9 May 2025 }}

In accordance with their psychedelic effects, NBOMe drugs induce the head-twitch response, a behavioral proxy of psychedelic effects, in rodents.{{cite journal | vauthors = Gil-Martins E, Barbosa DJ, Borges F, Remião F, Silva R | title = Toxicodynamic insights of 2C and NBOMe drugs - Is there abuse potential? | journal = Toxicol Rep | volume = 14 | issue = | pages = 101890 | date = June 2025 | pmid = 39867514 | doi = 10.1016/j.toxrep.2025.101890 | url = | pmc = 11762925 | bibcode = 2025ToxR...1401890G }} They have also been found to produce hyperlocomotion at low doses and hypolocomotion at high doses in rodents.

Unlike most other serotonergic psychedelics, the NBOMe drugs 25B-NBOMe and 25N-NBOMe have been found to produce reinforcing effects in rodents, and hence may have misuse potential.{{cite journal | vauthors = Custodio RJ, Sayson LV, Botanas CJ, Abiero A, You KY, Kim M, Lee HJ, Yoo SY, Lee KW, Lee YS, Seo JW, Ryu IS, Kim HJ, Cheong JH | title = 25B-NBOMe, a novel N-2-methoxybenzyl-phenethylamine (NBOMe) derivative, may induce rewarding and reinforcing effects via a dopaminergic mechanism: Evidence of abuse potential | journal = Addict Biol | volume = 25 | issue = 6 | pages = e12850 | date = November 2020 | pmid = 31749223 | doi = 10.1111/adb.12850 | url = }}{{cite journal | vauthors = Seo JY, Hur KH, Ko YH, Kim K, Lee BR, Kim YJ, Kim SK, Kim SE, Lee YS, Kim HC, Lee SY, Jang CG | title = A novel designer drug, 25N-NBOMe, exhibits abuse potential via the dopaminergic system in rodents | journal = Brain Res Bull | volume = 152 | issue = | pages = 19–26 | date = October 2019 | pmid = 31279579 | doi = 10.1016/j.brainresbull.2019.07.002 | url = }} Relatedly, 25B-NBOMe robustly increased dopamine levels in the nucleus accumbens similarly to methamphetamine. The reinforcing effects of 25B-NBOMe were not blocked by serotonin 5-HT_2A receptor antagonism, and it is unclear how they are produced. However, some NBOMe drugs, such as 25N-NBOMe, have been found to increase phosphorylation of the dopamine transporter (DAT) in the striatum similarly to methamphetamine in rodents.{{cite journal | vauthors = Kim YJ, Ma SX, Hur KH, Lee Y, Ko YH, Lee BR, Kim SK, Sung SJ, Kim KM, Kim HC, Lee SY, Jang CG | title = New designer phenethylamines 2C-C and 2C-P have abuse potential and induce neurotoxicity in rodents | journal = Arch Toxicol | volume = 95 | issue = 4 | pages = 1413–1429 | date = April 2021 | pmid = 33515270 | doi = 10.1007/s00204-021-02980-x | bibcode = 2021ArTox..95.1413K | url = | quote = 25N-NBOMe and other 2C drug derivatives similarly increased p-DAT levels in the NAc and striatum of mice (Seo et al. 2019). [...] increased p-DAT levels lead to an increase in dopamine release, which contribute to elevated dopamine levels. }} DAT phosphorylation is associated with dopamine reverse transport and efflux, which in turn increases extracellular dopamine levels.

Similarly to other psychedelics like DOI and 2C-T-7, tolerance has been found to gradually develop to the head-twitch response induced by 25I-NBOMe with chronic administration in rodents.{{cite journal | vauthors = Herian M, Skawski M, Wojtas A, Sobocińska MK, Noworyta K, Gołembiowska K | title = Tolerance to neurochemical and behavioral effects of the hallucinogen 25I-NBOMe | journal = Psychopharmacology (Berl) | volume = 238 | issue = 8 | pages = 2349–2364 | date = August 2021 | pmid = 34032876 | pmc = 8292280 | doi = 10.1007/s00213-021-05860-5 | url = }}

Image:25-NB-structure-general.png of 25-NB derivatives, where R is usually 2,5-dimethoxy-4-(alkyl or halogen), R₁ is usually H but rarely methyl, and Cyc is usually 2-substituted phenyl but can be other heterocycles.]]

The 25-NB compounds are mostly N-benzylphenethylamines, though in some cases the phenyl ring of the N-benzyl group is replaced by other heterocycles such as thiophene, pyridine, furan, tetrahydrofuran, benzodioxole or naphthalene, among others.{{cite journal | url=https://docs.lib.purdue.edu/dissertations/AAI3287241/ | title=Towards a biophysical understanding of hallucinogen action | pages=1–176 | journal=Dissertation | date=2007 | author=Michael Robert Braden}}{{Cite journal |doi = 10.1002/wmts.42|title = Structure-activity relationships of serotonin 5-HT2A agonists|year = 2012| vauthors = Nichols DE |journal = Wiley Interdisciplinary Reviews: Membrane Transport and Signaling|volume = 1|issue = 5|pages = 559–579|doi-access = free}}

Generally speaking, they have methoxy groups at the 2 and 5 positions of the phenyl ring, a substitution such as a halogen or alkyl group at the 4 position of the phenyl ring, and a methoxy or other substitution (e.g., hydroxyl, fluoro) at the 2 position of the N-benzyl ring. More rarely, other substitution patterns may be present {{cite journal | vauthors = Leth-Petersen S, Petersen IN, Jensen AA, Bundgaard C, Bæk M, Kehler J, Kristensen JL | title = 5-HT_2A/5-HT_2C Receptor Pharmacology and Intrinsic Clearance of N-Benzylphenethylamines Modified at the Primary Site of Metabolism | journal = ACS Chemical Neuroscience | volume = 7 | issue = 11 | pages = 1614–1619 | date = November 2016 | pmid = 27564969 | doi = 10.1021/acschemneuro.6b00265 }}{{cite journal | vauthors = Prabhakaran J, Solingapuram Sai KK, Zanderigo F, Rubin-Falcone H, Jorgensen MJ, Kaplan JR, Tooke KI, Mintz A, Mann JJ, Kumar JS | title = In vivo evaluation of [¹⁸F]FECIMBI-36, an agonist 5-HT_2A/2C receptor PET radioligand in nonhuman primate | journal = Bioorganic & Medicinal Chemistry Letters | volume = 27 | issue = 1 | pages = 21–23 | date = January 2017 | pmid = 27889455 | pmc = 5348621 | doi = 10.1016/j.bmcl.2016.11.043 }} (see e.g. NBOMe-mescaline, 25G-NBOMe, 2CBFly-NBOMe, 25C-NB3OMe). They differ from the 2C series by the presence of the N-benzyl moiety.

Rarely an alpha-methyl group is present making them N-benzyl amphetamines rather than N-benzyl phenethylamines, but this greatly reduces potency and activity. However in some cases where a side chain methyl group is cyclised back to the ring (e.g. in 2CBCB-NBOMe) or links the two alpha positions (e.g. in DMBMPP), this can improve selectivity for the 5-HT_2A receptor subtype.{{cite journal | vauthors = Juncosa JI, Hansen M, Bonner LA, Cueva JP, Maglathlin R, McCorvy JD, Marona-Lewicka D, Lill MA, Nichols DE | title = Extensive rigid analogue design maps the binding conformation of potent N-benzylphenethylamine 5-HT2A serotonin receptor agonist ligands | journal = ACS Chemical Neuroscience | volume = 4 | issue = 1 | pages = 96–109 | date = January 2013 | pmid = 23336049 | pmc = 3547484 | doi = 10.1021/cn3000668 }}

2C-B, the first major 2C drug and an analogue of mescaline, was first described by Alexander Shulgin in the 1970s. Richard Glennon and colleagues synthesized and described 25B-NB (N-benzyl-2C-B) along with a variety of other 25-NB derivatives in 1994.{{cite book | vauthors = Halberstadt AL | date = 2017 | chapter = Pharmacology and Toxicology of N-Benzylphenethylamine (“NBOMe”) Hallucinogens | veditors = Baumann M, Glennon R, Wiley J | title = Neuropharmacology of New Psychoactive Substances (NPS). | series = Current Topics in Behavioral Neurosciences | volume = 32 | pages = 283–311 | publisher = Springer | location = Cham | doi = 10.1007/7854_2016_64 | pmid = 28097528 | isbn = 978-3-319-52444-3 }}{{cite journal | vauthors = Glennon RA, Dukat M, el-Bermawy M, Law H, De los Angeles J, Teitler M, King A, Herrick-Davis K | title = Influence of amine substituents on 5-HT2A versus 5-HT2C binding of phenylalkyl- and indolylalkylamines | journal = Journal of Medicinal Chemistry | volume = 37 | issue = 13 | pages = 1929–1935 | date = June 1994 | pmid = 8027974 | doi = 10.1021/jm00039a004 }} It was observed at the time that 25B-NB had slightly higher affinity for the serotonin 5-HT_2A receptor than 2C-B and that other 25-NB derivatives with substituents on the benzyl ring showed very high affinity for the receptor, though functional data were not reported.

N-Benzyl derivatives of the ketanserin-related quinazolinedione EZS-8, such as RH-34, were first described by Heinz Pertz, Sigurd Elz, and Ralf Heim by 1996 or 1998.{{cite journal | vauthors = Heim R, Pertz H, Walther I, Elz S | date = January 1998 | title = P 8.10. Congeners of 3-(2-benzylaminoethyl)-2, 4-quinazolinedione: Partial agonists for rat vascular 5-HT2A receptors. | journal = Naunyn-Schmiedebergs Archives of Pharmacology | volume = 358 | issue = 1 | pages = R105 | url = https://bitnest.netfirms.com/external/N-S.Arch.Pharmacol/358.S1.R105 }}{{cite journal | title = Abstracts: 331: Characterization of the Partial Agonism of Ergoline Reverse Esters, Indolyltetrahydropyridines, and Quinazolinediones at 5-HT2A receptors in Rat Tail Artery | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 353 | issue = S4 | pages = R1–R166 (R90–R91) | date = 1996 | doi = 10.1007/BF00625102 | issn = 0028-1298 | url = http://link.springer.com/10.1007/BF00625102 | quote = The aim of the study was to characterize the partial agonism of congeners of well-established 5-HT2A receptor ligands, identified in a series of ergot alkaloids (so-called ergoline reverse esters with lysergol and dihydrolysergol-I as alcoholic component), indolyltetrahydropyridines (RU 24969 and two derivatives), and quinazolinediones (derivatives of ketanserin), at 5-HT2A receptors in rat tail artery. [...] Quinazolinediones (derivatives of ketanserin) showed weak agonist activity (pKp = 3.83 - 4.66, α = 0.17 - 0,46) and antagonized contractile responses to 5-HT with calculated pKp values of 3.52 - 5.12. }}{{cite journal | vauthors = Elz S, Klass T, Heim R, Warnke U, Pertz HH | title = Development of highly potent partial agonists and chiral antagonists as tools for the study of 5-HT2A-receptor mediated function | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 365 | issue = 1 Suppl | pages = R21–R40 | year = 2002 | doi = 10.1007/s00210-002-0604-4 | url = https://bitnest.netfirms.com/external/N-S.Arch.Pharmacol/365.S1.R29 }} NBOMe-mescaline and NBOMe-escaline were first described by Pertz and colleagues by 1999,Pertz, H. H., Rheineck, A., & Elz, S. (1999). N-Benzylated derivatives of the hallucinogenic drugs mescaline and escaline as partial agonists at rat vascular 5-HT2A receptors. Naunyn-Schmiedeberg’s Arch Pharmacol, 359(Suppl 3), R29. https://scholar.google.com/scholar?cluster=8208583485236470656Ratzeburg, K., Heim, R., Mahboobi, S., Henatsch, J., Pertz, H. H., & Elz, S. (2003, March). Potent partial 5-HT2A-receptor agonism of phenylethan-amines related to mescaline in the rat tail artery model. Naunyn-Schmiedebergs Archives of Pharmacology, 167, R31–R31. https://scholar.google.com/scholar?cluster=411158176506751110 while 25B-NBOMe was first described by Heim and colleagues in 1999.Heim, R., Pertz, H. H., & Elz, S. (1999). Preparation and in vitro pharmacology of novel secondary amine-type 5-HT2A receptor agonists: from submillimolar to subnanomolar activity. Arch. Pharm. Pharm. Med. Chem, 332, 34. https://bitnest.netfirms.com/external/Arch.Pharm.Pharm.Med.Chem/331.S1.34 25I-NBOMe and other 25-NB compounds such as 25TFM-NBOMe and 2CBFly-NBOMe were described by Heim and colleagues by 2000.{{cite journal | vauthors = Heim R, Elz S | title = 39. Novel Extremely Potent Partial 5-HT2A-Receptor Agonists: Successful Application of a New Structure-Activity Concept | date = March 2000 | journal = Arch. Pharm. Pharm. Med. Chem. | volume = 333 | issue = Suppl 1 | pages = 1–40 (18) | issn = 0365-6233 | url = https://scholar.google.com/scholar?cluster=5753981208249154444 | archive-url = https://web.archive.org/web/20250320195942/https://bitnest.netfirms.com/external/Arch.Pharm.Pharm.Med.Chem/333.S1.18 | archive-date = 20 March 2025 }}{{cite journal | vauthors = Pertz HH, Heim R, Elz S | title = B 1.11. N-Benzylated phenylethanamines are highly potent partial agonists at 5-HT2A receptors | date = 2000 | journal = Arch. Pharm. Pharm. Med. Chem | volume = 333 | issue = Suppl 2 | pages = 1–84 (30) | url = https://scholar.google.com/scholar?cluster=18169232060279208950 | archive-url = https://web.archive.org/web/20250320194355/https://bitnest.netfirms.com/external/Arch.Pharm.Pharm.Med.Chem/333.S2.30 | archive-date = 20 March 2025}}Heim, R., Pertz, H. H., & Elz, S. (2000). Partial 5-HT2A-receptor agonists of the phenylethanamine series: effect of a trifluoromethyl substituent. Arch. Pharm. Pharm. Med. Chem, 333, 45. https://bitnest.netfirms.com/external/Arch.Pharm.Pharm.Med.Chem/333.S2.45{{cite web |vauthors=Heim R |title=Synthese und Pharmakologie potenter 5-HT_2A-Rezeptoragonisten mit N-2-Methoxybenzyl-Partialstruktur. Entwicklung eines neuen Struktur-Wirkungskonzepts. | trans-title=Synthesis and pharmacology of potent 5-HT2A receptor agonists with an N-2-methoxybenzyl partial structure. Development of a new structure-activity concept. | url=http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000001221 |publisher=diss.fu-berlin.de |date=25 March 2003 |language=German |access-date=2013-05-10 |archive-date=2012-04-16 |archive-url=https://web.archive.org/web/20120416040543/http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000001221 |url-status=live }} 25I-NBOMe and other 25-NB drugs were subsequently further described by Heim in his dissertation in 2003. 25C-NBOMe was not described in the literature until 2010.Ettrup, A. (2010). Serotonin receptor studies in the pig brain: pharmacological intervention and positron emission tomography tracer development (Doctoral dissertation, Faculty of Health Sciences, University of Copenhagen). https://research.regionh.dk/en/publications/serotonin-receptor-studies-in-the-pig-brain-pharmacological-inter{{cite journal | vauthors = Ettrup A, Hansen M, Santini MA, Paine J, Gillings N, Palner M, Lehel S, Herth MM, Madsen J, Kristensen J, Begtrup M, Knudsen GM | display-authors = 6 | title = Radiosynthesis and in vivo evaluation of a series of substituted 11C-phenethylamines as 5-HT (2A) agonist PET tracers | journal = European Journal of Nuclear Medicine and Molecular Imaging | volume = 38 | issue = 4 | pages = 681–693 | date = April 2011 | pmid = 21174090 | doi = 10.1007/s00259-010-1686-8 | s2cid = 12467684 }} The discovery of the 25-NB compounds by Heim and colleagues has been described by David E. Nichols as structurally remarkable, since N-alkylation of psychedelic phenethylamines, for instance Beatrice (N-methyl-DOM), has otherwise invariably abolished the hallucinogenic effects of this class of compounds.{{cite book | vauthors = Nichols DE | title = Chemistry and Structure-Activity Relationships of Psychedelics | series = Current Topics in Behavioral Neurosciences | volume = 36 | pages = 1–43 | date = 2018 | pmid = 28401524 | doi = 10.1007/7854_2017_475 | isbn = 978-3-662-55878-2 | url = https://bitnest.netfirms.com/external/10.1007/7854_2017_475 | quote = Although the most active tryptamine hallucinogens are N,N-dialkylated, the phenethylamines generally cannot tolerate even a single N-substitution. Even small groups such as methyl or ethyl (see Table 2) abolish their hallucinogenic activity. It was quite remarkable, therefore, when Heim and coworkers reported that N-benzyl groups afforded compounds with remarkable affinity and potency (Heim et al. 1999; Elz et al. 2002; Heim 2003). An oxygen atom at the ortho position of the N-benzyl group enhanced activity further (Braden et al. 2006).}}

The NBOMe drugs, primarily 25I-NBOMe, were encountered as novel recreational drugs by 2010, and by 2012 had eclipsed other psychedelics like LSD and psilocybin-containing mushrooms in popularity, at least for a time.{{cite journal | vauthors = Wood DM, Sedefov R, Cunningham A, Dargan PI | title = Prevalence of use and acute toxicity associated with the use of NBOMe drugs | journal = Clin Toxicol (Phila) | volume = 53 | issue = 2 | pages = 85–92 | date = February 2015 | pmid = 25658166 | doi = 10.3109/15563650.2015.1004179 | url = }}{{cite web | last=Morgans | first=Julian | title=NBOMe in Australia: Everything We Know About the Drug and Why it's Killing People | website=VICE | date=8 February 2017 | url=https://www.vice.com/en/article/nbome-in-australia-everything-we-know-about-what-it-is-and-why-its-killing-people/ | access-date=4 April 2025}}{{cite journal | vauthors = Lawn W, Barratt M, Williams M, Horne A, Winstock A | title = The NBOMe hallucinogenic drug series: Patterns of use, characteristics of users and self-reported effects in a large international sample | journal = J Psychopharmacol | volume = 28 | issue = 8 | pages = 780–788 | date = August 2014 | pmid = 24569095 | doi = 10.1177/0269881114523866 | hdl = 1959.4/unsworks_73366 | hdl-access = free }} Various NBOMes, such as 25I-NBOMe, became Schedule I controlled substances in the United States in 2013.

A large number of substances in the 25-NB class are Class A drugs in the United Kingdom as a result of the N-benzylphenethylamine catch-all clause in the Misuse of Drugs Act 1971{{cite web|title=The Misuse of Drugs Act 1971 (Ketamine etc.) (Amendment) Order 2014|url=http://www.legislation.gov.uk/uksi/2014/1106/made|website=www.legislation.gov.uk|language=en}} or are otherwise covered by the Psychoactive Substances Act 2016.{{cite web|title=Psychoactive Substances Act 2016|url=http://www.legislation.gov.uk/ukpga/2016/2/contents/enacted|website=www.legislation.gov.uk|language=en}}

This list includes notable compounds representative of most of the structural variations that have been explored in this series, but is by no means exhaustive. Many derivatives invented for scientific study into the structure-activity relationships of 5-HT₂ receptor agonists have never appeared as designer drugs, while conversely some derivatives that have appeared as designer drugs are structurally novel and of unknown pharmacological activity (e.g. C30-NBOMe, 5-APB-NBOMe).

{{Sticky}}

Similar compounds with related structures are also known including:

{{Sticky}}

• Substituted methoxyphenethylamine
• 4-Substituted 2,5-dimethoxyphenethylamines (2Cs)
• 4-Substituted 2,5-dimethoxyamphetamines (DOx)
• 4-Substituted 2,5-dimethoxy-α-ethylphenethylamines (4Cs)
• List of miscellaneous 5-HT_2A receptor agonists

{{Notelist}}

{{Reflist}}

• [https://www.youtube.com/watch?v=NzpqJgwuQuA VICE In-house Chemist Hamilton Morris on the Dangers of the NBOMe Hallucinogen - VICE - YouTube]
• [https://tripsitter.com/nbome/ What Are N-Bombs? (25-I-NBOMe) — Avoid This Psychedelic - Tripsitter]
• [https://psychedelicspotlight.com/unmasking-fake-acid-the-dangers-of-25i-nbome-disguised-as-lsd/ Unmasking Fake Acid: The Dangers of 25I-NBOMe Disguised as LSD - Psychedelic Spotlight]

{{Psychedelics}}

{{Serotonin receptor modulators}}

{{TAAR modulators}}

{{Phenethylamines}}

{{Chemical classes of psychoactive drugs}}

Category:5-HT2A agonists

Category:5-HT2B agonists

Category:5-HT2C agonists

Category:Chemical classes of psychoactive drugs

Category:Secondary amines

Category:TAAR1 agonists