Wikipedia

2C-I

2C-I
Clinical data
Other names4-Iodo-2,5-dimethoxyphenethylamine; 2,5-Dimethoxy-4-iodophenethylamine; 25I; Cimbi-88; 2C-DOI
Routes of
administration		Oral[1][2]
Drug classSerotonin 5-HT2 receptor agonist; Serotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
Onset of action≤40 minutes[1]
Duration of action6–10 hours[1][2]
Identifiers
  • 2-(4-iodo-2,5-dimethoxyphenyl)ethan-1-amine
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.217.507 Edit this at Wikidata
Chemical and physical data
FormulaC10H14INO2
Molar mass307.131 g·mol−1
3D model (JSmol)
Melting point246 °C (475 °F)
  • Ic1cc(OC)c(cc1OC)CCN
  • InChI=1S/C10H14INO2/c1-13-9-6-8(11)10(14-2)5-7(9)3-4-12/h5-6H,3-4,12H2,1-2H3 checkY
  • Key:PQHQBRJAAZQXHL-UHFFFAOYSA-N checkY
  (verify)

2C-I, also known as 4-iodo-2,5-dimethoxyphenethylamine, is a psychedelic drug of the phenethylamine and 2C families.[1][3][2][4] It is taken orally.[1][2]

2C-I was first synthesized and described by Alexander Shulgin in 1977[5][6] and was described in further detail in his 1991 book PiHKAL (Phenethylamines I Have Known and Loved).[1] The drug is used recreationally. 2C-I is sometimes confused with other related psychedelic drugs such as 25I-NBOMe (NBOMe-2C-I), nicknamed "Smiles" and "N-bomb" in the media.[7][8][9]

Use and effects

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According to Alexander Shulgin in his book PiHKAL (Phenethylamines I Have Known and Loved), 2C-I has a dose range of 14 to 22 mg orally and a duration of 6 to 10 hours.[1][2] Its onset is within 40 minutes and peak effects occur after about 2 hours.[1] In addition to oral administration, 2C-I may also be insufflated.[10] The effects of 2C-I have been reported to include color enhancement, psychedelic visuals, emotional enhancement, limited insights, increased energy, enhanced conversation and honesty, improved mood, and sensual immersion.[1] The sensual effects of 2C-I were described as different from and possibly less than those of 2C-B.[1]

Interactions

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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.[2][11] Monoamine oxidase inhibitors (MAOIs) such as phenelzine, tranylcypromine, moclobemide, and selegiline may potentiate the effects of 2C-I.[2][11][12] This may result in overdose and serious toxicity.[12][2]

Pharmacology

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Pharmacodynamics

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2C-I activities
Target Affinity (Ki, nM)
5-HT1A 107–970 (Ki)
4,900 (EC50Tooltip half-maximal effective concentration)
102% (EmaxTooltip maximal efficacy)
5-HT1B 56
5-HT1D 40
5-HT1E 131
5-HT1F ND
5-HT2A 3.5–9.3 (Ki)
1.48–513 (EC50)
17–93% (Emax)
5-HT2B 9.3 (Ki)
19.1–150 (EC50)
70–101% (Emax)
5-HT2C 9.3–40 (Ki)
0.46–537 (EC50)
44–107% (Emax)
5-HT3 >10,000
5-HT4 ND
5-HT5A >10,000
5-HT6 ND
5-HT7 1,316
α1A 5,100–>10,000
α1B >10,000
α1D >10,000
α2A 70–305
α2B 608
α2C 315
β1 4,512
β2 >10,000
β3 ND
D1 13,000
D2 1,013–2,700
D3 989–5,000
D4 2,788
D5 >10,000
H1 6,100
H2 >10,000
H3 >10,000
M1 >10,000
M2 1,429
M3 950
M4 1,129
M5 2,151
I1 ND
σ1 >10,000
σ2 5,470
MOR 2,522
DOR ND
KOR >10,000
TAAR1Tooltip Trace amine-associated receptor 1 3,300 (Ki) (mouse)
120 (Ki) (rat)
2,400 (EC50) (mouse)
190 (EC50) (rat)
>10,000 (EC50) (human)
51% (Emax) (mouse)
50% (Emax) (rat)
SERTTooltip Serotonin transporter 950–4,900 (Ki)
5,600–13,000 (IC50Tooltip half-maximal inhibitory concentration)
IA (EC50)
NETTooltip Norepinephrine transporter 15,000 (Ki)
22,000 (IC50)
IA (EC50)
DATTooltip Dopamine transporter >30,000 (Ki)
126,000 (IC50)
IA (EC50)
MAO-ATooltip Monoamine oxidase A 125,000 (IC50)
MAO-BTooltip Monoamine oxidase B 55,000 (IC50)
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [13][14][15][16][17][18]
[19][20][21][22][23][24]

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.[15][14]

2C-I is a highly potent anti-inflammatory drug similarly to various other serotonergic psychedelics.[22] However, 2C-I showed the highest anti-inflammatory potency of any other assessed drug in a large series in one study.[22] It was more potent than (R)-DOI in terms of anti-inflammatory activity.[22]

Chemistry

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Synthesis

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The chemical synthesis of 2C-I has been described.[1][25]

Analogues

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Analogues of 2C-I include 2C-H (2,5-DMPEA), 2C-B, 2C-C, DOI, and 25I-NBOMe, among others.[1][26][3]

History

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2C-I was first described in the scientific literature by Alexander Shulgin and colleagues in 1977.[5][6] Its properties and effects in humans were described by Shulgin in 1978.[5] The drug was subsequently described in greater detail by Shulgin in his 1991 book PiHKAL (Phenethylamines I Have Known and Loved).[1] In the early 2000s, 2C-I was sold in Dutch smart shops as a recreational drug after the related drug 2C-B was banned.[27]

Society and culture

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[edit]
2C-I in powder form.

Australia

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2C-I is a schedule 9 prohibited substance in Australia under the Poisons Standard (October 2015).[28] 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".[29]

Canada

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As of October 31, 2016, 2C-I is a controlled substance (Schedule III) in Canada.[30]

European Union

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In December 2003, the European Council issued a binding order compelling all European Union member states to ban 2C-I within three months.[31]

Finland

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Illegal: scheduled in the "government decree on substances, preparations and plants considered to be narcotic drugs".[32]

Sweden

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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.[33]

United Kingdom

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In the United Kingdom, 2C-I is controlled as a Class A substance.[31]

United States

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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.[31] 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.[34]

See also

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References

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  1. ^ a b c d e f g h i j k l m Shulgin A, Shulgin A (September 1991). PiHKAL: A Chemical Love Story. Berkeley, California: Transform Press. ISBN 0-9630096-0-5. OCLC 25627628. https://erowid.org/library/books_online/pihkal/pihkal033.shtml
  2. ^ a b c d e f g h Dean BV, Stellpflug SJ, Burnett AM, Engebretsen KM (June 2013). "2C or not 2C: phenethylamine designer drug review". Journal of Medical Toxicology. 9 (2): 172–178. doi:10.1007/s13181-013-0295-x. PMC 3657019. PMID 23494844.
  3. ^ a b Anilanmert B, Yonar FÇ, Özdemir AA (31 January 2018). "2C Derivatives of Phenylethylamines and Their Analysis". Chromatographic Techniques in the Forensic Analysis of Designer Drugs. Chromatographic science series. Boca Raton : Taylor & Francis/CRC Press, 2018.: CRC Press. pp. 277–304. doi:10.1201/9781315313177-15. ISBN 978-1-315-31317-7. Retrieved 14 November 2025.{{cite book}}: CS1 maint: location (link)
  4. ^ 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.
  5. ^ a b c Shulgin AT (1978). "Psychotomimetic Drugs: Structure-Activity Relationships". In Iversen LL, Iversen SD, Snyder SH (eds.). Stimulants. Boston, MA: Springer US. pp. 243–333. doi:10.1007/978-1-4757-0510-2_6. ISBN 978-1-4757-0512-6.
  6. ^ a b Braun U, Shulgin AT, Braun G, Sargent T (December 1977). "Synthesis and body distribution of several iodine-131 labeled centrally acting drugs". Journal of Medicinal Chemistry. 20 (12): 1543–1546. doi:10.1021/jm00222a001. PMID 592317.
  7. ^ "25I-NBOMe (2C-I-NBOMe): Fatalities / Deaths".
  8. ^ Weiss, Piper (September 20, 2012). 2C-I or 'Smiles': The New Killer Drug Every Parent Should Know About. Yahoo! News
  9. ^ Mackin T (October 9, 2012). "Dangerous synthetic drug making its way across the country". Archived from the original on October 31, 2012. WISH-TV
  10. ^ Reuters (March 20, 2011). Synthetic drug, subject of proposed bans, kill teen.
  11. ^ a b 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)". Biochemical Pharmacology. 73 (2): 287–297. doi:10.1016/j.bcp.2006.09.022. PMID 17067556.
  12. ^ a b Halman A, Kong G, Sarris J, Perkins D (January 2024). "Drug-drug interactions involving classic psychedelics: A systematic review". Journal of Psychopharmacology. 38 (1): 3–18. doi:10.1177/02698811231211219. PMC 10851641. PMID 37982394.
  13. ^ "Kᵢ Database". PDSP. 16 March 2025. Retrieved 16 March 2025.
  14. ^ a b 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)". Neuropharmacology. 99: 546–553. doi:10.1016/j.neuropharm.2015.08.034. PMID 26318099.
  15. ^ a b 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". Psychopharmacology. 231 (5): 875–888. doi:10.1007/s00213-013-3303-6. PMC 3945162. PMID 24142203.
  16. ^ Ettrup A, Hansen M, Santini MA, Paine J, Gillings N, Palner M, et al. (April 2011). "Radiosynthesis and in vivo evaluation of a series of substituted 11C-phenethylamines as 5-HT (2A) agonist PET tracers". European Journal of Nuclear Medicine and Molecular Imaging. 38 (4): 681–693. doi:10.1007/s00259-010-1686-8. PMID 21174090.
  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) fasebj.2022.36.S1.R2121. doi:10.1096/fasebj.2022.36.S1.R2121. ISSN 0892-6638.
  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". Archives of Toxicology. 94 (10): 3449–3460. Bibcode:2020ArTox..94.3449P. doi:10.1007/s00204-020-02836-w. hdl:1854/LU-8687071. PMID 32627074.
  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". Nature Communications. 14 (1) 8221. Bibcode:2023NatCo..14.8221W. doi:10.1038/s41467-023-44016-1. PMC 10724237. PMID 38102107.
  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". British Journal of Pharmacology. 136 (4): 510–519. doi:10.1038/sj.bjp.0704747. PMC 1573376. PMID 12055129.
  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". The Journal of Pharmacology and Experimental Therapeutics. 321 (3): 1054–1061. doi:10.1124/jpet.106.117507. PMID 17337633.
  22. ^ a b c d 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 Pharmacology & Translational Science. 4 (2): 488–502. doi:10.1021/acsptsci.0c00063. PMC 8033619. PMID 33860179.
  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 Testing and Analysis. 11 (2): 318–324. doi:10.1002/dta.2494. PMID 30188017.
  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" (PDF). The Journal of Pharmacology and Experimental Therapeutics. 357 (1): 134–144. doi:10.1124/jpet.115.229765. PMID 26791601. Archived from the original (PDF) on 9 May 2025.
  25. ^ Shulgin A, Manning T, Daley P (2011). The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds. Vol. 1. Berkeley: Transform Press. ISBN 978-0-9630096-3-0.
  26. ^ Trachsel D, Lehmann D, Enzensperger C (2013). Phenethylamine: von der Struktur zur Funktion [Phenethylamines: From Structure to Function]. Nachtschatten-Science (in German) (1 ed.). Solothurn: Nachtschatten-Verlag. ISBN 978-3-03788-700-4. OCLC 858805226. Archived from the original on 21 August 2025.
  27. ^ 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.
  28. ^ Poisons Standard October 2015
  29. ^ "Poisons Act 1964" (PDF). Archived from the original (PDF) on 2015-12-22. Retrieved 2015-12-13.
  30. ^ Regulations Amending the Food and Drug Regulations (Part J — 2C-phenethylamines)
  31. ^ a b c "Erowid 2C-I Vault : Legal Status".
  32. ^ "Valtioneuvoston asetus huumausaineina pidettävistä aineista, valmisteista ja kasveista | 543/2008 | Lainsäädäntö | Finlex".
  33. ^ "Läkemedelsverkets författningssamling" (PDF) (in Swedish).
  34. ^ "H.R. 1254 (112th): Synthetic Drug Control Act of 2011". GovTrack. Retrieved 30 September 2015.
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