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2C-I

2C-I

FieldValue
Verifiedfieldsverified
Watchedfieldsverified
verifiedrevid477216266
image2C-I2DACS.svg
image_classskin-invert-image
width200px
image22C-I-3d-sticks.png
image_class2bg-transparent
width2200px
routes_of_administrationOral
classSerotonin [5-HT2 receptor](5-ht2-receptor) agonist; Serotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen
ATC_prefixNone
legal_AUSchedule 9
legal_BRF2
legal_CASchedule III
legal_UKClass A
legal_USSchedule I
onset≤40 minutes
duration_of_action6–10 hours
CAS_number_Ref
CAS_number69587-11-7
PubChem10267191
ChemSpiderID_Ref
ChemSpiderID8442670
UNII_Ref
UNIIS35362848V
KEGG_Ref
KEGGC22776
ChEMBL_Ref
ChEMBL338297
synonyms4-Iodo-2,5-dimethoxyphenethylamine; 2,5-Dimethoxy-4-iodophenethylamine; 25I; Cimbi-88; 2C-DOI
IUPAC_name2-(4-iodo-2,5-dimethoxyphenyl)ethan-1-amine
C10H=14I=1N=1O=2
SMILESIc1cc(OC)c(cc1OC)CCN
StdInChI_Ref
StdInChI1S/C10H14INO2/c1-13-9-6-8(11)10(14-2)5-7(9)3-4-12/h5-6H,3-4,12H2,1-2H3
StdInChIKey_Ref
StdInChIKeyPQHQBRJAAZQXHL-UHFFFAOYSA-N
melting_point246

| Drugs.com =

| elimination_half-life =

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

2C-I was first synthesized and described by Alexander Shulgin in 1977 and was described in further detail in his 1991 book PiHKAL (Phenethylamines I Have Known and Loved). 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.

Use and effects

According to Alexander Shulgin in his book PiHKAL (Phenethylamines I Have Known and Loved), 2C-I has a dose range of 14 to 22mg orally and a duration of 6 to 10hours. Its onset is within 40minutes and peak effects occur after about 2hours. In addition to oral administration, 2C-I may also be insufflated. 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. The sensual effects of 2C-I were described as different from and possibly less than those of 2C-B.

Interactions

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

Pharmacology

Pharmacodynamics

TargetAffinity (Ki, nM)
[5-HT1A](5-ht1a-receptor)107–970 (Ki)
4,900 ()
102% ()
[5-HT1B](5-ht1b-receptor)56
[5-HT1D](5-ht1d-receptor)40
[5-HT1E](5-ht1e-receptor)131
[5-HT1F](5-ht1f-receptor)ND
[5-HT2A](5-ht2a-receptor)3.5–9.3 (Ki)
1.48–513 (EC50)
17–93% (Emax)
[5-HT2B](5-ht2b-receptor)9.3 (Ki)
19.1–150 (EC50)
70–101% (Emax)
[5-HT2C](5-ht2c-receptor)9.3–40 (Ki)
0.46–537 (EC50)
44–107% (Emax)
[5-HT3](5-ht3-receptor)10,000
[5-HT4](5-ht4-receptor)ND
[5-HT5A](5-ht5a-receptor)10,000
[5-HT6](5-ht6-receptor)ND
[5-HT7](5-ht7-receptor)1,316
α1A5,100–10,000
α1B10,000
α1D10,000
α2A70–305
α2B608
α2C315
β14,512
β210,000
β3ND
D113,000
D21,013–2,700
D3989–5,000
D42,788
D510,000
H16,100
H210,000
H310,000
M110,000
M21,429
M3950
M41,129
M52,151
I1ND
σ110,000
σ25,470
MOR2,522
DORND
KOR10,000
3,300 (Ki) (mouse)
120 (Ki) (rat)
2,400 (EC50) (mouse)
190 (EC50) (rat)
10,000 (EC50) (human)
51% (Emax) (mouse)
50% (Emax) (rat)
950–4,900 (Ki)
5,600–13,000 ()
IA (EC50)
15,000 (Ki)
22,000 (IC50)
IA (EC50)
30,000 (Ki)
126,000 (IC50)
IA (EC50)
125,000 (IC50)
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:**

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.

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

Chemistry

Synthesis

The chemical synthesis of 2C-I has been described.

Analogues

Analogues of 2C-I include 2C-H (2,5-DMPEA), 2C-B, 2C-C, DOI, 4C-I, and 25I-NBOMe, among others.

History

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

Society and culture

2C-I in powder form.

Australia

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

Canada

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

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.

Finland

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

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.

United Kingdom

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

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. 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.

References

References

  1. {{CitePiHKAL https://erowid.org/library/books_online/pihkal/pihkal033.shtml
  2. (June 2013). "2C or not 2C: phenethylamine designer drug review". Journal of Medical Toxicology.
  3. (June 2013). "Recurrent seizures and serotonin syndrome following "2C-I" ingestion". Journal of Medical Toxicology.
  4. "25I-NBOMe (2C-I-NBOMe): Fatalities / Deaths".
  5. Weiss, Piper (September 20, 2012). [http://shine.yahoo.com/healthy-living/2c-smiles-killer-drug-every-parent-know-234200299.html 2C-I or 'Smiles': The New Killer Drug Every Parent Should Know About.] ''[[Yahoo! News]]''
  6. (October 9, 2012). "Dangerous synthetic drug making its way across the country.".
  7. Reuters (March 20, 2011). [https://web.archive.org/web/20160306161926/http://in.reuters.com/article/us-drugs-overdose-idINTRE72I3QT20110319 Synthetic drug, subject of proposed bans, kill teen.]
  8. (January 2007). "Identification of monoamine oxidase and cytochrome P450 isoenzymes involved in the deamination of phenethylamine-derived designer drugs (2C-series)". Biochemical Pharmacology.
  9. (January 2024). "Drug-drug interactions involving classic psychedelics: A systematic review". Journal of Psychopharmacology.
  10. (16 March 2025). "Kᵢ Database".
  11. (December 2015). "Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs)". Neuropharmacology.
  12. (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.
  13. (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.
  14. (2022). "Structure-activity Relation of Halogenated 2,5-Dimethoxyamphetamines Compared to their α‑Desmethyl (2C) Analogues". The FASEB Journal.
  15. (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.
  16. (December 2023). "Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential". Nature Communications.
  17. (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.
  18. (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.
  19. (February 2019). "Interactions of phenethylamine-derived psychoactive substances of the 2C-series with human monoamine oxidases". Drug Testing and Analysis.
  20. (April 2016). "In Vitro Characterization of Psychoactive Substances at Rat, Mouse, and Human Trace Amine-Associated Receptor 1". The Journal of Pharmacology and Experimental Therapeutics.
  21. (April 2021). "Structure-Activity Relationship Analysis of Psychedelics in a Rat Model of Asthma Reveals the Anti-Inflammatory Pharmacophore". ACS Pharmacology & Translational Science.
  22. (2011). "[[The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds]]". [[Transform Press]].
  23. (2013). "Phenethylamine: von der Struktur zur Funktion". Nachtschatten-Verlag.
  24. (31 January 2018). "Chromatographic Techniques in the Forensic Analysis of Designer Drugs". CRC Press.
  25. (1978). "Stimulants". Springer US.
  26. (December 1977). "Synthesis and body distribution of several iodine-131 labeled centrally acting drugs". Journal of Medicinal Chemistry.
  27. (May–June 1999). "More data about the new psychoactive drug 2C-B". Journal of Analytical Toxicology.
  28. [https://www.comlaw.gov.au/Details/F2015L01534 Poisons Standard October 2015]
  29. "Poisons Act 1964".
  30. [http://gazette.gc.ca/rp-pr/p2/2016/2016-05-04/html/sor-dors72-eng.php Regulations Amending the Food and Drug Regulations (Part J — 2C-phenethylamines)]
  31. "Erowid 2C-I Vault : Legal Status".
  32. "Valtioneuvoston asetus huumausaineina pidettävistä aineista, valmisteista ja kasveista | 543/2008 | Lainsäädäntö | Finlex".
  33. "Läkemedelsverkets författningssamling".
  34. "H.R. 1254 (112th): Synthetic Drug Control Act of 2011".
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