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2C-I
Chemical compound

2C-I, also known as 2,5-dimethoxy-4-iodophenethylamine, is a phenethylamine of the 2C family with psychedelic effects. It was first synthesized by Alexander Shulgin, and is described in Shulgin's book PiHKAL (1991).

The substance is consumed as a recreational drug, and is circulated in the drug market in a powder form. 2C-I is sometimes confused with other related chemical substances such as 25I-NBOMe (2C-I-NBOMe), nicknamed "Smiles" and "N-bomb" in the media.

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Use

In the early 2000s, 2C-I was sold in Dutch smart shops as a recreational drug after the drug 2C-B was banned.5

According to the US Drug Enforcement Administration, 2C-I is taken orally or snorted in a powder form.6

Interactions

See also: Psychedelic drug § Interactions, and Trip killer § Serotonergic psychedelic antidotes

2C-I is metabolized by the monoamine oxidase (MAO) enzymes MAO-A and MAO-B.78 Monoamine oxidase inhibitors (MAOIs) such as phenelzine, tranylcypromine, moclobemide, and selegiline may potentiate the effects of 2C-I.91011 This may result in overdose and serious toxicity.1213

Pharmacology

Pharmacodynamics

2C-I activities
TargetAffinity (Ki, nM)
5-HT1A180–970 (Ki)4,900 (EC50Tooltip half-maximal effective concentration)102% (EmaxTooltip maximal efficacy)
5-HT1BND
5-HT1DND
5-HT1END
5-HT1FND
5-HT2A3.5–9.3 (Ki)1.48–513 (EC50)17–93% (Emax)
5-HT2B19.1–150 (EC50)70–101% (Emax)
5-HT2C10–40 (Ki)0.46–537 (EC50)44–107% (Emax)
5-HT3ND
5-HT4ND
5-HT5AND
5-HT6ND
5-HT7ND
α1A5,100
α1B, α1DND
α2A70
α2B, α2CND
β1–β3ND
D113,000
D22,700
D35,000
D4, D5ND
H16,100
TAAR1Tooltip Trace amine-associated receptor 13,300 (Ki) (mouse)120 (Ki) (rat)2,400 (EC50) (mouse)190 (EC50) (rat)>10,000 (EC50) (human)51% (Emax) (mouse)50% (Emax) (rat)
SERTTooltip Serotonin transporter950–4,900 (Ki)5,600–13,000 (IC50Tooltip half-maximal inhibitory concentration)IA (EC50)
NETTooltip Norepinephrine transporter15,000 (Ki)22,000 (IC50)IA (EC50)
DATTooltip Dopamine transporter>30,000 (Ki)126,000 (IC50)IA (EC50)
MAO-ATooltip Monoamine oxidase A125,000 (IC50)
MAO-BTooltip Monoamine oxidase B55,000 (IC50)
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: 1415161718192021222324

2C-I acts as a serotonin receptor agonist. It produces psychedelic effects via serotonin 5-HT2A receptor activation.

It is inactive as a monoamine releasing agent and shows negligible activity as a monoamine reuptake inhibitor.2526

2C-I is a highly potent anti-inflammatory drug similarly to various other serotonergic psychedelics.27 However, 2C-I showed the highest anti-inflammatory potency of any other assessed drug in a large series in one study.28 It was more potent than (R)-DOI in terms of anti-inflammatory activity.29

Chemistry

Analogues and derivatives

DOI

Analogues and derivatives of 2C-I:

25I-NB*:

N-(2C)-fentanyl:

  • N-(2C-I) fentanyl30

Society and culture

Legal status

Australia

2C-I is a schedule 9 prohibited substance in Australia under the Poisons Standard (October 2015).31 A schedule 9 drug is outlined in the Poisons Act 1964 as "Substances which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of the CEO".32

Canada

As of October 31, 2016, 2C-I is a controlled substance (Schedule III) in Canada.33

European Union

In December 2003, the European Council issued a binding order compelling all European Union member states to ban 2C-I within three months.34

Sweden

Sveriges riksdag added 2C-I to schedule I ("substances, plant materials and fungi which normally do not have medical use") as a narcotic on March 16, 2004, published by the Medical Products Agency in their regulation LVFS 2004:3.35

United Kingdom

In the United Kingdom, 2C-I is controlled as a Class A substance.36

United States

As of July 9, 2012, in the United States 2C-I is a Schedule I substance under the Synthetic Drug Abuse Prevention Act of 2012, making possession, distribution and manufacture illegal.37 A previous bill, introduced in March 2011, that would have done the same passed the House of Representatives, but was not passed by the Senate.38

See also

References

  1. Bosak A, LoVecchio F, Levine M (June 2013). "Recurrent seizures and serotonin syndrome following "2C-I" ingestion". Journal of Medical Toxicology. 9 (2): 196–198. doi:10.1007/s13181-013-0287-x. PMC 3657032. PMID 23378129. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3657032 ↩

  2. "25I-NBOMe (2C-I-NBOMe): Fatalities / Deaths". http://www.erowid.org/chemicals/2ci_nbome/2ci_nbome_death.shtml ↩

  3. Weiss, Piper (September 20, 2012). 2C-I or 'Smiles': The New Killer Drug Every Parent Should Know About. Yahoo! News http://shine.yahoo.com/healthy-living/2c-smiles-killer-drug-every-parent-know-234200299.html ↩

  4. Mackin T (October 9, 2012). "Dangerous synthetic drug making its way across the country". Archived from the original on October 31, 2012. WISH-TV https://web.archive.org/web/20121031163611/http://www.wishtv.com/dpp/news/indiana/dangerous-synthetic-drug-smiles-making-its-way-across-the-country ↩

  5. de Boer D, Gijzels MJ, Bosman IJ, Maes RA (May–June 1999). "More data about the new psychoactive drug 2C-B". Journal of Analytical Toxicology. 23 (3): 227–228. doi:10.1093/jat/23.3.227. PMID 10369336. https://doi.org/10.1093%2Fjat%2F23.3.227 ↩

  6. Reuters (March 20, 2011). Synthetic drug, subject of proposed bans, kill teen. https://web.archive.org/web/20160306161926/http://in.reuters.com/article/us-drugs-overdose-idINTRE72I3QT20110319 ↩

  7. Dean BV, Stellpflug SJ, Burnett AM, Engebretsen KM (June 2013). "2C or not 2C: phenethylamine designer drug review". J Med Toxicol. 9 (2): 172–178. doi:10.1007/s13181-013-0295-x. PMC 3657019. PMID 23494844. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3657019 ↩

  8. Theobald DS, Maurer HH (January 2007). "Identification of monoamine oxidase and cytochrome P450 isoenzymes involved in the deamination of phenethylamine-derived designer drugs (2C-series)". Biochem Pharmacol. 73 (2): 287–297. doi:10.1016/j.bcp.2006.09.022. PMID 17067556. /wiki/Doi_(identifier) ↩

  9. Dean BV, Stellpflug SJ, Burnett AM, Engebretsen KM (June 2013). "2C or not 2C: phenethylamine designer drug review". J Med Toxicol. 9 (2): 172–178. doi:10.1007/s13181-013-0295-x. PMC 3657019. PMID 23494844. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3657019 ↩

  10. Theobald DS, Maurer HH (January 2007). "Identification of monoamine oxidase and cytochrome P450 isoenzymes involved in the deamination of phenethylamine-derived designer drugs (2C-series)". Biochem Pharmacol. 73 (2): 287–297. doi:10.1016/j.bcp.2006.09.022. PMID 17067556. /wiki/Doi_(identifier) ↩

  11. Halman A, Kong G, Sarris J, Perkins D (January 2024). "Drug-drug interactions involving classic psychedelics: A systematic review". J Psychopharmacol. 38 (1): 3–18. doi:10.1177/02698811231211219. PMC 10851641. PMID 37982394. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10851641 ↩

  12. Halman A, Kong G, Sarris J, Perkins D (January 2024). "Drug-drug interactions involving classic psychedelics: A systematic review". J Psychopharmacol. 38 (1): 3–18. doi:10.1177/02698811231211219. PMC 10851641. PMID 37982394. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10851641 ↩

  13. Dean BV, Stellpflug SJ, Burnett AM, Engebretsen KM (June 2013). "2C or not 2C: phenethylamine designer drug review". J Med Toxicol. 9 (2): 172–178. doi:10.1007/s13181-013-0295-x. PMC 3657019. PMID 23494844. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3657019 ↩

  14. "Kᵢ Database". PDSP. 16 March 2025. Retrieved 16 March 2025. https://pdsp.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_test_ligands%5D%5B%5D=12953&KisResultsSearch%5Binput_test_ligands%5D%5B%5D=14673&KisResultsSearch%5Binput_citations%5D=&KisResultsSearch%5BsearchType%5D=&KisResultsSearch%5Bki_val_from%5D=&KisResultsSearch%5Bki_val_to%5D=&KisResultsSearch%5Bcustom_ki_val%5D= ↩

  15. Rickli A, Luethi D, Reinisch J, Buchy D, Hoener MC, Liechti ME (December 2015). "Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs)" (PDF). Neuropharmacology. 99: 546–553. 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 ↩

  16. Eshleman AJ, Forster MJ, Wolfrum KM, Johnson RA, Janowsky A, Gatch MB (March 2014). "Behavioral and neurochemical pharmacology of six psychoactive substituted phenethylamines: mouse locomotion, rat drug discrimination and in vitro receptor and transporter binding and function" (PDF). Psychopharmacology (Berl). 231 (5): 875–888. doi:10.1007/s00213-013-3303-6. PMC 3945162. PMID 24142203. https://www.researchgate.net/profile/Michael-Forster-2/publication/258061356_Behavioral_and_neurochemical_pharmacology_of_six_psychoactive_substituted_phenethylamines_Mouse_locomotion_rat_drug_discrimination_and_in_vitro_receptor_and_transporter_binding_and_function/links/53d119a00cf2f7e53cfbcd68/Behavioral-and-neurochemical-pharmacology-of-six-psychoactive-substituted-phenethylamines-Mouse-locomotion-rat-drug-discrimination-and-in-vitro-receptor-and-transporter-binding-and-function.pdf ↩

  17. Rudin D, Luethi D, Hoener MC, Liechti ME (2022). "Structure-activity Relation of Halogenated 2,5-Dimethoxyamphetamines Compared to their α‑Desmethyl (2C) Analogues". The FASEB Journal. 36 (S1). doi:10.1096/fasebj.2022.36.S1.R2121. ISSN 0892-6638. https://www.researchgate.net/publication/360423277_Structure-activity_relation_of_halogenated_25-dimethoxyamphetamines_compared_to_their_a-desmethyl_2C_analogues ↩

  18. Pottie E, Cannaert A, Stove CP (October 2020). "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. Bibcode:2020ArTox..94.3449P. doi:10.1007/s00204-020-02836-w. hdl:1854/LU-8687071. PMID 32627074. /wiki/Bibcode_(identifier) ↩

  19. Wallach J, Cao AB, Calkins MM, Heim AJ, Lanham JK, Bonniwell EM, et al. (December 2023). "Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential". Nat Commun. 14 (1): 8221. doi:10.1038/s41467-023-44016-1. PMC 10724237. PMID 38102107. https://bitnest.netfirms.com/external/10.1038/s41467-023-44016-1 ↩

  20. Acuña-Castillo C, Villalobos C, Moya PR, Sáez P, Cassels BK, Huidobro-Toro JP (June 2002). "Differences in potency and efficacy of a series of phenylisopropylamine/phenylethylamine pairs at 5-HT(2A) and 5-HT(2C) receptors". Br J Pharmacol. 136 (4): 510–519. doi:10.1038/sj.bjp.0704747. PMC 1573376. PMID 12055129. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1573376 ↩

  21. Moya PR, Berg KA, Gutiérrez-Hernandez MA, Sáez-Briones P, Reyes-Parada M, Cassels BK, et al. (June 2007). "Functional selectivity of hallucinogenic phenethylamine and phenylisopropylamine derivatives at human 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors" (PDF). J Pharmacol Exp Ther. 321 (3): 1054–1061. doi:10.1124/jpet.106.117507. PMID 17337633. https://repositorio.uchile.cl/bitstream/handle/2250/119461/Moya_Pablo_R.pdf ↩

  22. Flanagan TW, Billac GB, Landry AN, Sebastian MN, Cormier SA, Nichols CD (April 2021). "Structure-Activity Relationship Analysis of Psychedelics in a Rat Model of Asthma Reveals the Anti-Inflammatory Pharmacophore". ACS Pharmacol Transl Sci. 4 (2): 488–502. doi:10.1021/acsptsci.0c00063. PMC 8033619. PMID 33860179. https://www.researchgate.net/publication/360537036 ↩

  23. Wagmann L, Brandt SD, Stratford A, Maurer HH, Meyer MR (February 2019). "Interactions of phenethylamine-derived psychoactive substances of the 2C-series with human monoamine oxidases". Drug Test Anal. 11 (2): 318–324. doi:10.1002/dta.2494. PMID 30188017. /wiki/Doi_(identifier) ↩

  24. Simmler LD, Buchy D, Chaboz S, Hoener MC, Liechti ME (April 2016). "In Vitro Characterization of Psychoactive Substances at Rat, Mouse, and Human Trace Amine-Associated Receptor 1". J Pharmacol Exp Ther. 357 (1): 134–144. doi:10.1124/jpet.115.229765. PMID 26791601. /wiki/Doi_(identifier) ↩

  25. Eshleman AJ, Forster MJ, Wolfrum KM, Johnson RA, Janowsky A, Gatch MB (March 2014). "Behavioral and neurochemical pharmacology of six psychoactive substituted phenethylamines: mouse locomotion, rat drug discrimination and in vitro receptor and transporter binding and function" (PDF). Psychopharmacology (Berl). 231 (5): 875–888. doi:10.1007/s00213-013-3303-6. PMC 3945162. PMID 24142203. https://www.researchgate.net/profile/Michael-Forster-2/publication/258061356_Behavioral_and_neurochemical_pharmacology_of_six_psychoactive_substituted_phenethylamines_Mouse_locomotion_rat_drug_discrimination_and_in_vitro_receptor_and_transporter_binding_and_function/links/53d119a00cf2f7e53cfbcd68/Behavioral-and-neurochemical-pharmacology-of-six-psychoactive-substituted-phenethylamines-Mouse-locomotion-rat-drug-discrimination-and-in-vitro-receptor-and-transporter-binding-and-function.pdf ↩

  26. Rickli A, Luethi D, Reinisch J, Buchy D, Hoener MC, Liechti ME (December 2015). "Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs)" (PDF). Neuropharmacology. 99: 546–553. 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 ↩

  27. Flanagan TW, Billac GB, Landry AN, Sebastian MN, Cormier SA, Nichols CD (April 2021). "Structure-Activity Relationship Analysis of Psychedelics in a Rat Model of Asthma Reveals the Anti-Inflammatory Pharmacophore". ACS Pharmacol Transl Sci. 4 (2): 488–502. doi:10.1021/acsptsci.0c00063. PMC 8033619. PMID 33860179. https://www.researchgate.net/publication/360537036 ↩

  28. Flanagan TW, Billac GB, Landry AN, Sebastian MN, Cormier SA, Nichols CD (April 2021). "Structure-Activity Relationship Analysis of Psychedelics in a Rat Model of Asthma Reveals the Anti-Inflammatory Pharmacophore". ACS Pharmacol Transl Sci. 4 (2): 488–502. doi:10.1021/acsptsci.0c00063. PMC 8033619. PMID 33860179. https://www.researchgate.net/publication/360537036 ↩

  29. Flanagan TW, Billac GB, Landry AN, Sebastian MN, Cormier SA, Nichols CD (April 2021). "Structure-Activity Relationship Analysis of Psychedelics in a Rat Model of Asthma Reveals the Anti-Inflammatory Pharmacophore". ACS Pharmacol Transl Sci. 4 (2): 488–502. doi:10.1021/acsptsci.0c00063. PMC 8033619. PMID 33860179. https://www.researchgate.net/publication/360537036 ↩

  30. "Explore N-(2C-I)-Fentanyl | PiHKAL · info". isomerdesign.com. https://isomerdesign.com/PiHKAL/explore.php?domain=pk&id=14009 ↩

  31. Poisons Standard October 2015 https://www.comlaw.gov.au/Details/F2015L01534 ↩

  32. "Poisons Act 1964" (PDF). Archived from the original (PDF) on 2015-12-22. Retrieved 2015-12-13. https://web.archive.org/web/20151222191725/http://www.slp.wa.gov.au/pco/prod/FileStore.nsf/Documents/MRDocument%3A26063P/%24FILE/Poisons%20Act%201964%20-%20%5B09-f0-04%5D.pdf?OpenElement ↩

  33. Regulations Amending the Food and Drug Regulations (Part J — 2C-phenethylamines) http://gazette.gc.ca/rp-pr/p2/2016/2016-05-04/html/sor-dors72-eng.php ↩

  34. "Erowid 2C-I Vault : Legal Status". http://www.erowid.org/chemicals/2ci/2ci_law.shtml ↩

  35. "Läkemedelsverkets författningssamling" (PDF) (in Swedish). http://www.lakemedelsverket.se/upload/lvfs/LVFS_2004-3.pdf ↩

  36. "Erowid 2C-I Vault : Legal Status". http://www.erowid.org/chemicals/2ci/2ci_law.shtml ↩

  37. "Erowid 2C-I Vault : Legal Status". http://www.erowid.org/chemicals/2ci/2ci_law.shtml ↩

  38. "H.R. 1254 (112th): Synthetic Drug Control Act of 2011". GovTrack. Retrieved 30 September 2015. https://www.govtrack.us/congress/bills/112/hr1254 ↩