Chemistry:25B-NBOMe

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25B-NBOMe, also known as NBOMe-2C-B and Cimbi-36, is a psychedelic drug of the 25-NB (NBOMe) family derived from 2C-B. It acts as a potent full agonist for the 5HT2A receptor.[1][2][3] Duration of effects lasts about 3 to 10 hours,[4] although the parent compound is rapidly cleared from the blood when used in the radiolabeled form in tracer doses.[5] Recently, Custodio et al. (2019) evaluated the potential involvement of dysregulated dopaminergic system, neuroadaptation, and brain wave changes which may contribute to the rewarding and reinforcing properties of 25B-NBOMe in rodents.[6]

The carbon-11 labeled version of this compound ([11C]Cimbi-36) was synthesized and validated as a radioactive tracer for positron emission tomography (PET) in Copenhagen.[7][8][9] As a 5-HT2A receptor agonist PET radioligand, [11C]Cimbi-36 was hypothesized to provide a more functional marker of these receptors. Also, [11C]Cimbi-36 is investigated as a potential marker of serotonin release and thus could serve as an indicator of serotonin levels in vivo. [11C]Cimbi-36 is now undergoing clinical trials as a PET-ligand in humans.[10][11][12]

25B-NBOMe was first described in the scientific literature by Ralf Heim and colleagues at the Free University of Berlin by 1999.[13]

Use and effects

The dose range of 25B-NBOMe has been given as 0.05 to 0.7 mg sublingually, with a typical dose estimate of 0.4 mg.[14]

Toxicity and harm potential

This section is an excerpt from 25-NB § Toxicity and harm potential[ edit ]

Neurotoxic and cardiotoxic actions

This section is an excerpt from 25-NB § Neurotoxic and cardiotoxic actions[ edit ]

Emergency treatment

This section is an excerpt from 25-NB § Emergency treatment[ edit ]

Interactions

Pharmacology

Pharmacodynamics

25B-NBOMe activities
Target Affinity (Ki, nM)
5-HT1A 1,255–3,600
5-HT1B >10,000
5-HT1D 1,472
5-HT1E >10,000
5-HT1F ND
5-HT2A 0.19–0.8 (Ki)
0.12–40 (EC50)
28–167% (Emax)
5-HT2B 0.5 (Ki)
7.3–10 (EC50)
19–79% (Emax)
5-HT2C 1.7–6.2 (Ki)
0.90–12 (EC50)
93–110% (Emax)
5-HT3 >10,000
5-HT4 ND
5-HT5A 4,087
5-HT6 48
5-HT7 4,720
α1A 430–1,256
α1B 6,180
α1D 2,253
α2A 430–3,551
α2B 1,264
α2C 646
β1 6,719
β2 >10,000
β3 ND
D1 9,300–>10,000
D2 840–>10,000
D3 718–2,700
D4 2,253
D5 >10,000
H1 80
H2 ND
H3 >10,000
H4 ND
M1–M4 >10,000
M5 5,241
I1 ND
σ1 310
σ2 64
MOR >10,000 (Ki)
4,730–>22,000 (EC50)
8–94% (Emax)
DOR ND
KOR 642
TAAR1 4,500 (Ki) (mouse)
280 (Ki) (rat)
6,100 (EC50) (mouse)
1,200 (EC50) (rat)
>10,000 (EC50) (human)
47% (Emax) (mouse)
37% (Emax) (rat)
SERT 388–840 (Ki)
4,900–7,100 (IC50)
ND (EC50)
NET 1,100–1,718 (Ki)
6,700–11,000 (IC50)
ND (EC50)
DAT 7,200–>10,000 (Ki)
99,000–117,000 (IC50)
ND (EC50)
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [15][16][17][18][8][19][20][21]
[22][23][24][25][26][27][28][29]

25B-NBOMe is a selective serotonin 5-HT2 receptor agonist.[16] It showed roughly the same affinity for the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors in one study (Ki = 0.5–1.7 nM).[16] However, in another study, it showed 12- to 20-fold selectivity for the serotonin 5-HT2A receptor (Ki = 0.5 nM) over the serotonin 5-HT2B and 5-HT2C receptors (Ki = 10 and 6.2 nM, respectively).[30] The drug is highly selective for the serotonin 5-HT2 receptors over a variety of other serotonin receptors, as well as over various other monoamine receptors and over the monoamine transporters (>200-fold selectivity).[16][30] However, 25B-NBOMe is a low-potency partial agonist of the rat and mouse trace amine-associated receptor 1 (TAAR1) but is inactive at the human TAAR1.[28]

25B-NBOMe has been found to increase levels of glutamate, serotonin, dopamine, and acetylcholine in the frontal cortex, striatum, and nucleus accumbens in rats.[31] Other serotonergic psychedelics like LSD and DOI have also been found to increase glutamate levels in the frontal cortex in rodents, and this effect can be blocked by the serotonin 5-HT2A receptor antagonist volinanserin (MDL-100,907).[31] 25B-NBOMe shows an inverted U-shaped dose–response curve in terms of neurotransmitter elevations in multiple brain areas.[31] This may be due to an inhibitory effect of serotonin 5-HT2C receptors at higher doses.[31] 25B-NBOMe produces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents, and this effect shows an inverted U-shaped dose–response curve similarly to its influences on neurotransmitter levels.[31] The head twitches and hallucinogenic effects of 25B-NBOMe may be due to increased cortical glutamate release secondary to serotonin 5-HT2A receptor activation.[31] The effects of 25B-NBOMe on levels of other neurotransmitters, such as accumbal dopamine concentrations, may also be mediated by activation of serotonin 5-HT2A receptors and glutamate elevation.[31] It has been suggested that the serotonin elevations with 25B-NBOMe may be involved in its production of serotonin syndrome in humans.[30]

Unlike many other serotonergic psychedelics, 25B-NBOMe has been found to produce reinforcing effects in rodents, including conditioned place preference (CPP) and self-administration, and hence may have misuse potential.[32][33][30] Accordingly, 25B-NBOMe robustly increased dopamine levels in the nucleus accumbens in rodents similarly to but a lesser extent than methamphetamine, and its reinforcing effects could be blocked by the dopamine receptor antagonists SCH-23390 and haloperidol.[32][33][30] Serotonin 5-HT2A receptor activation is known to increase dopamine release in the mesolimbic pathway.[33] However, the reinforcing effects of 25B-NBOMe were not blocked by the selective serotonin 5-HT2A receptor antagonist ketanserin.[32][33] Similarly to 25B-NBOMe, 25N-NBOMe has also shown reinforcing effects in rodents.[34] More research is needed to elucidate how 25B-NBOMe and other NBOMe drugs produce reinforcing effects in animals.[33]

25B-NBOMe has been found to decrease locomotor activity in rodents.[35][31]

Chemistry

Analogues and derivatives

Analogues and derivatives of 2C-B:

25-NB:

Substituted benzofurans:

Other:

Another analogue of 25B-NBOMe is DOB-NBOMe.

History

25B-NBOMe was first described in the scientific literature, in the form of conference abstracts, by Ralf Heim and colleagues at the Free University of Berlin by 1999.[13]

Society and culture

Canada

As of October 31, 2016; 25B-NBOMe is a controlled substance (Schedule III) in Canada.[36]

China

As of October 2015 25B-NBOMe is a controlled substance in China.[37]

Czech Republic

25B-NBOMe is banned in the Czech Republic.[38]

Finland

Scheduled in the "government decree on substances, preparations and plants considered to be narcotic drugs".[39]

Russia

Banned as a narcotic drug since May 5, 2015.[40]

Sweden

In Sweden, the Riksdag added 25B-NBOMe to schedule I ("substances, plant materials and fungi which normally do not have medical use") as narcotics in Sweden as of August 1, 2013, published by the Medical Products Agency in their regulation LVFS 2013:15 listed as 25B-NBOMe 2-(4-bromo-2,5-dimetoxifenyl)-N-(2-metoxibensyl)etanamin.[41]

United Kingdom

This substance is a Class A drug in the United Kingdom as a result of the N-benzylphenethylamine catch-all clause in the Misuse of Drugs Act 1971.[42]


United States

In November 2013, the U.S. Drug Enforcement Administration placed 25B-NBOMe (along with 25I-NBOMe and 25C-NBOMe) in Schedule I of the Controlled Substances Act, making it illegal to manufacture, buy, possess, process, or distribute.[43]

Notes

References

  1. ↑ Silva M (2009). Theoretical study of the interaction of agonists with the 5-HT2A receptor (Ph.D. thesis). Universität Regensburg.
  2. ↑ "Theoretical studies on the interaction of partial agonists with the 5-HT2A receptor". Journal of Computer-Aided Molecular Design 25 (1): 51–66. January 2011. doi:10.1007/s10822-010-9400-2. PMID 21088982. Bibcode: 2011JCAMD..25...51S. 
  3. ↑ "Synthesis and structure-activity relationships of N-benzyl phenethylamines as 5-HT2A/2C agonists". ACS Chemical Neuroscience 5 (3): 243–249. March 2014. doi:10.1021/cn400216u. PMID 24397362. 
  4. ↑ "25C-NBOMe: preliminary data on pharmacology, psychoactive effects, and toxicity of a new potent and dangerous hallucinogenic drug". BioMed Research International 2014. 3 July 2014. doi:10.1155/2014/734749. PMID 25105138. 
  5. ↑ "Serotonin 2A receptor agonist binding in the human brain with [¹¹CCimbi-36"]. Journal of Cerebral Blood Flow and Metabolism 34 (7): 1188–96. July 2014. doi:10.1038/jcbfm.2014.68. PMID 24780897. 
  6. ↑ "25B-NBOMe, a novel N-2-methoxybenzyl-phenethylamine (NBOMe) derivative, may induce rewarding and reinforcing effects via a dopaminergic mechanism: Evidence of abuse potential". Addiction Biology 25 (6). November 2020. doi:10.1111/adb.12850. PMID 31749223. 
  7. ↑ Hansen M (2010-12-16). Design and Synthesis of Selective Serotonin Receptor Agonists for Positron Emission Tomography Imaging of the Brain (Ph.D. thesis). University of Copenhagen. doi:10.13140/RG.2.2.33671.14245.
  8. ↑ 8.0 8.1 "Radiosynthesis and in vivo evaluation of a series of substituted 11C-phenethylamines as 5-HT (2A) agonist PET tracers". Eur J Nucl Med Mol Imaging 38 (4): 681–693. April 2011. doi:10.1007/s00259-010-1686-8. PMID 21174090. 
  9. ↑ "Preclinical safety assessment of the 5-HT2A receptor agonist PET radioligand [ 11C]Cimbi-36". Molecular Imaging and Biology 15 (4): 376–383. August 2013. doi:10.1007/s11307-012-0609-4. PMID 23306971. 
  10. ↑ "From molecule to man: The full CIMBI-36 story". cimbi.dk. http://www.cimbi.dk/images/stories/files/The_full_Cimbi36_story.pdf. 
  11. ↑ "Imanova announces the launch of a new imaging biomarker to investigate the serotonin system in psychiatric illness". imanova.co.uk. http://www.imanova.co.uk/news-and-publications/imanova-news/entry/imanova-announces-the-launch-of-a-new-imaging-biomarker-to-investigate-the-serotonin-system-in-psychiatric-illness.html. 
  12. ↑ "Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels". Neuropsychopharmacology 44 (7): 1328–1334. June 2019. doi:10.1038/s41386-019-0324-9. PMID 30685771. 
  13. ↑ 13.0 13.1 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
  14. ↑ "Monoamine Transporter and Receptor Interaction Profiles in Vitro Predict Reported Human Doses of Novel Psychoactive Stimulants and Psychedelics". Int J Neuropsychopharmacol 21 (10): 926–931. October 2018. doi:10.1093/ijnp/pyy047. PMID 29850881. "Supplementary Table S2. Dose estimates and data sources for psychedelics.". 
  15. ↑ "Kᵢ Database". 15 May 2025. https://pdspdb.unc.edu/kidb2/kidb/web/kis-results/index?KisResultsSearch%5Binput_receptors%5D=&KisResultsSearch%5Binput_sources%5D=&KisResultsSearch%5Binput_species%5D=&KisResultsSearch%5Binput_hot_ligands%5D=&KisResultsSearch%5Binput_test_ligands%5D=&KisResultsSearch%5Binput_citations%5D=&KisResultsSearch%5Binput_citations%5D%5B%5D=2187&KisResultsSearch%5BsearchType%5D=&KisResultsSearch%5Bki_val_from%5D=&KisResultsSearch%5Bki_val_to%5D=&KisResultsSearch%5Bcustom_ki_val%5D=&KisResultsSearch%5Binput_receptors%5D=&KisResultsSearch%5Binput_sources%5D=&KisResultsSearch%5Binput_species%5D=&KisResultsSearch%5Binput_hot_ligands%5D=&KisResultsSearch%5Binput_test_ligands%5D=&KisResultsSearch%5Binput_test_ligands%5D%5B%5D=14684&KisResultsSearch%5Binput_test_ligands%5D%5B%5D=14695&KisResultsSearch%5Binput_citations%5D=&KisResultsSearch%5Binput_citations%5D%5B%5D=2187&KisResultsSearch%5BsearchType%5D=&KisResultsSearch%5Bki_val_from%5D=&KisResultsSearch%5Bki_val_to%5D=&KisResultsSearch%5Bcustom_ki_val%5D=&KisResultsSearch%5Binput_receptors%5D=&KisResultsSearch%5Binput_sources%5D=&KisResultsSearch%5Binput_species%5D=&KisResultsSearch%5Binput_hot_ligands%5D=&KisResultsSearch%5Binput_test_ligands%5D=&KisResultsSearch%5Binput_test_ligands%5D%5B%5D=14694&KisResultsSearch%5Binput_test_ligands%5D%5B%5D=14679&KisResultsSearch%5Binput_citations%5D=&KisResultsSearch%5Binput_citations%5D%5B%5D=2187&KisResultsSearch%5BsearchType%5D=&KisResultsSearch%5Bki_val_from%5D=&KisResultsSearch%5Bki_val_to%5D=&KisResultsSearch%5Bcustom_ki_val%5D=. 
  16. ↑ 16.0 16.1 16.2 16.3 "DARK Classics in Chemical Neuroscience: NBOMes". ACS Chem Neurosci 11 (23): 3860–3869. December 2020. doi:10.1021/acschemneuro.9b00528. PMID 31657895. 
  17. ↑ "Toxicodynamic insights of 2C and NBOMe drugs - Is there abuse potential?". Toxicol Rep 14. June 2025. doi:10.1016/j.toxrep.2025.101890. PMID 39867514. Bibcode: 2025ToxR...1401890G. 
  18. ↑ "Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs)". Neuropharmacology 99: 546–553. December 2015. doi:10.1016/j.neuropharm.2015.08.034. PMID 26318099. https://psilosybiini.info/paperit/Receptor%20interaction%20profiles%20of%20novel%20N-2-methoxybenzyl%20(NBOMe)%20derivatives%20of%202,5-dimethoxy-substituted%20phenethylamines%20(2C%20drugs)%20(Rickli%20et%20al.,%202015).pdf. 
  19. ↑ "Extensive rigid analogue design maps the binding conformation of potent N-benzylphenethylamine 5-HT2A serotonin receptor agonist ligands". ACS Chem Neurosci 4 (1): 96–109. January 2013. doi:10.1021/cn3000668. PMID 23336049. 
  20. ↑ Hansen, M. (2010). Design and Synthesis of Selective Serotonin Receptor Agonists for Positron Emission Tomography Imaging of the Brain: PhD Thesis. Faculty of Pharmaceutical Sciences, University of Copenhagen. https://bitnest.netfirms.com/external/Theses/Hansen2011
  21. ↑ "Synthesis and structure-activity relationships of N-benzyl phenethylamines as 5-HT2A/2C agonists". ACS Chem Neurosci 5 (3): 243–249. March 2014. doi:10.1021/cn400216u. PMID 24397362. 
  22. ↑ "Synthesis and evaluation of (18)F-labeled 5-HT2A receptor agonists as PET ligands". Nucl Med Biol 43 (8): 455–462. August 2016. doi:10.1016/j.nucmedbio.2016.02.011. PMID 27209485. 
  23. ↑ "5-HT2A/5-HT2C Receptor Pharmacology and Intrinsic Clearance of N-Benzylphenethylamines Modified at the Primary Site of Metabolism". ACS Chem Neurosci 7 (11): 1614–1619. November 2016. doi:10.1021/acschemneuro.6b00265. PMID 27564969. 
  24. ↑ "Detailed Characterization of the In Vitro Pharmacological and Pharmacokinetic Properties of N-(2-Hydroxybenzyl)-2,5-Dimethoxy-4-Cyanophenylethylamine (25CN-NBOH), a Highly Selective and Brain-Penetrant 5-HT2A Receptor Agonist". J Pharmacol Exp Ther 361 (3): 441–453. June 2017. doi:10.1124/jpet.117.239905. PMID 28360333. 
  25. ↑ "In vitro characterization of new psychoactive substances at the μ-opioid, CB1, 5HT1A, and 5-HT2A receptors-On-target receptor potency and efficacy, and off-target effects". Forensic Sci Int 317. December 2020. doi:10.1016/j.forsciint.2020.110553. PMID 33160102. 
  26. ↑ "In vitro structure-activity relationship determination of 30 psychedelic new psychoactive substances by means of β-arrestin 2 recruitment to the serotonin 2A receptor". Arch Toxicol 94 (10): 3449–3460. October 2020. doi:10.1007/s00204-020-02836-w. PMID 32627074. Bibcode: 2020ArTox..94.3449P. 
  27. ↑ "Measuring inhibition of monoamine reuptake transporters by new psychoactive substances (NPS) in real-time using a high-throughput, fluorescence-based assay". Toxicol in Vitro 45 (Pt 1): 60–71. December 2017. doi:10.1016/j.tiv.2017.05.010. PMID 28506818. Bibcode: 2017ToxVi..45...60Z. 
  28. ↑ 28.0 28.1 "In Vitro Characterization of Psychoactive Substances at Rat, Mouse, and Human Trace Amine-Associated Receptor 1". J Pharmacol Exp Ther 357 (1): 134–144. April 2016. doi:10.1124/jpet.115.229765. PMID 26791601. 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. 
  29. ↑ "Off-target activity of NBOMes and NBOMe analogs at the µ opioid receptor". Arch Toxicol 97 (5): 1367–1384. May 2023. doi:10.1007/s00204-023-03465-9. PMID 36853332. Bibcode: 2023ArTox..97.1367D. 
  30. ↑ 30.0 30.1 30.2 30.3 30.4 "Molecular and Medical Aspects of Psychedelics". Int J Mol Sci 25 (1): 241. December 2023. doi:10.3390/ijms25010241. PMID 38203411. "Like 25I-NBOMe [55], 25B-NBOMe significantly increased the extracellular 5-HT levels [37]. This phenomenon may be the reason for the serotonin syndrome reported in humans after ingestion of 25B-NBOMe [51]. Furthermore, it increased the volume of dopaminergic neurotransmission akin to 25I-NBOMe. Those changes observed in NAC and STR suggest that it might exhibit reinforcing properties [37].". 
  31. ↑ 31.0 31.1 31.2 31.3 31.4 31.5 31.6 31.7 "Neurochemical and Behavioral Effects of a New Hallucinogenic Compound 25B-NBOMe in Rats". Neurotox Res 39 (2): 305–326. April 2021. doi:10.1007/s12640-020-00297-8. PMID 33337517. 
  32. ↑ 32.0 32.1 32.2 "NBOMes-Highly Potent and Toxic Alternatives of LSD". Front Neurosci 14. 2020. doi:10.3389/fnins.2020.00078. PMID 32174803. 
  33. ↑ 33.0 33.1 33.2 33.3 33.4 "25B-NBOMe, a novel N-2-methoxybenzyl-phenethylamine (NBOMe) derivative, may induce rewarding and reinforcing effects via a dopaminergic mechanism: Evidence of abuse potential". Addict Biol 25 (6). November 2020. doi:10.1111/adb.12850. PMID 31749223. 
  34. ↑ "A novel designer drug, 25N-NBOMe, exhibits abuse potential via the dopaminergic system in rodents". Brain Res Bull 152: 19–26. October 2019. doi:10.1016/j.brainresbull.2019.07.002. PMID 31279579. 
  35. ↑ "Locomotor and discriminative stimulus effects of four novel hallucinogens in rodents". Behav Pharmacol 28 (5): 375–385. August 2017. doi:10.1097/FBP.0000000000000309. PMID 28537942. 
  36. ↑ "Regulations Amending the Food and Drug Regulations (Part J — 2C-phenethylamines)". Canada Gazette 150 (9). 4 May 2016. http://gazette.gc.ca/rp-pr/p2/2016/2016-05-04/html/sor-dors72-eng.php. 
  37. ↑ "关于印发《非药用类麻醉药品和精神药品列管办法》的通知" (in zh). China Food and Drug Administration. 27 September 2015. http://www.sfda.gov.cn/WS01/CL0056/130753.html. 
  38. ↑ "Látky, o které byl doplněn seznam č. 4 psychotropních látek (příloha č. 4 k nařízení vlády č. 463/2013 Sb.)" (in cs). Ministerstvo zdravotnictví. http://www.mzcr.cz/Admin/_upload/files/3/Nov%C3%A9%20PL.pdf. 
  39. ↑ "543/2008". https://finlex.fi/fi/lainsaadanto/2008/543. 
  40. ↑ "Постановление Правительства РФ от 30.06.1998 N 681 "Об утверждении перечня наркотических средств, психотропных веществ и их прекурсоров, подлежащих контролю в Российской Федерации" (с изменениями и дополнениями)". http://base.garant.ru/12112176/. 
  41. ↑ "Föreskrifter om ändring i Läkemedelsverkets föreskrifter (LVFS 2011:10) om förteckningar över narkotika;" (in sv). lakemedelsverket.se. http://www.lakemedelsverket.se/upload/lvfs/LVFS_2013-15.pdf. 
  42. ↑ "The Misuse of Drugs Act 1971 (Ketamine etc.) (Amendment) Order 2014" (in en). http://www.legislation.gov.uk/uksi/2014/1106/made. 
  43. ↑ "2016 - Final Rule: Placement of Three Synthetic Phenethylamines Into Schedule I" (in en-US). https://www.deadiversion.usdoj.gov/fed_regs/rules/2016/fr0927_2.htm. 

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