2C-I

2C-I
Legal status
Legal status	AU: S9 (Prohibited substance); BR: Class F2 (Prohibited psychotropics); CA: Schedule III; UK: Class A; US: Schedule I;
Identifiers
	IUPAC name 2-(4-iodo-2,5-dimethoxyphenyl)ethan-1-amine;
CAS Number	69587-11-7 ;
PubChem CID	10267191;
ChemSpider	8442670 ;
UNII	S35362848V;
KEGG	C22776 ;
ChEMBL	ChEMBL338297 ;
CompTox Dashboard (EPA)	DTXSID80893674 ;
ECHA InfoCard	100.217.507
Chemical and physical data
Formula	C10H14INO2
Molar mass	307.131 g·mol−1
3D model (JSmol)	Interactive image;
Melting point	246 °C (475 °F)
	SMILES Ic1cc(OC)c(cc1OC)CCN;
	InChI 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 ; Key:PQHQBRJAAZQXHL-UHFFFAOYSA-N ;
	(verify)

2C-I, also known as 2,5-dimethoxy-4-iodophenethylamine, is a phenethylamine of the 2C family with psychedelic effects.^[1] 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.^[2]^[3]^[4]

Patterns of 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]

Pharmacology

Pharmacodynamics

2C-I activities
Target	Affinity (K_i, nM)
5-HT_1A	180
5-HT_1B–5-HT_1F	ND
5-HT_2A	3.5 (K_i) 3.83–60 (EC₅₀Tooltip half-maximal effective concentration) 45–74% (E_maxTooltip maximal efficacy)
5-HT_2B	150 (EC₅₀) 70% (E_max)
5-HT_2C	40
5-HT₃–5-HT₇	ND
α_1A	5,100
α_1B, α_1D	ND
α_2A	70
α_2B, α_2C	ND
β₁–β₃	ND
D₁	13,000
D₂	2,700
D₃	5,000
D₄, D₅	ND
H₁	6,100
TAAR1Tooltip Trace amine-associated receptor 1	3,300 (K_i) (mouse) 120 (K_i) (rat) 2,400 (EC₅₀) (mouse) 190 (EC₅₀) (rat) >10,000 (EC₅₀) (human) 51% (E_max) (mouse) 50% (E_max) (rat)
SERTTooltip Serotonin transporter	4,900 (K_i) 13,000 (IC₅₀Tooltip half-maximal inhibitory concentration)
NETTooltip Norepinephrine transporter	15,000 (K_i) 22,000 (IC₅₀)
DATTooltip Dopamine transporter	>30,000 (K_i) 126,000 (IC₅₀)
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: ^[7]^[8]^[9]^[10]

2C-I acts as a serotonin receptor agonist. It produces psychedelic effects via serotonin 5-HT_2A receptor activation.

2C-I is a highly potent anti-inflammatory drug similarly to various other serotonergic psychedelics.^[11] However, 2C-I showed the highest anti-inflammatory potency of any other assessed drug in a large series in one study.^[11] It was more potent than (R)-DOI in terms of anti-inflammatory activity.^[11]

Chemistry

Analogues and derivatives

DOI

Analogues and derivatives of 2C-I:

25I-NB*:

N-(2C)-fentanyl:

N-(2C-I) fentanyl^[12]

Legal status

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.^[13]

Canada

As of October 31, 2016, 2C-I is a controlled substance (Schedule III) in Canada.^[14]

Australia

2C-I is a schedule 9 prohibited substance in Australia under the Poisons Standard (October 2015).^[15] 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".^[16]

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.^[17]

United Kingdom

In the United Kingdom, 2C-I is controlled as a Class A substance.^[13]

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.^[13] 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.^[18]

References

^ 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.
^ "25I-NBOMe (2C-I-NBOMe): Fatalities / Deaths".
^ Weiss, Piper (September 20, 2012). 2C-I or 'Smiles': The New Killer Drug Every Parent Should Know About. Yahoo! News
^ Mackin T (October 9, 2012). "Dangerous synthetic drug making its way across the country". Archived from the original on October 31, 2012. WISH-TV
^ 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.
^ Reuters (March 20, 2011). Synthetic drug, subject of proposed bans, kill teen.
^ 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.
^ 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.
^ 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.
^ 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.
^ ^a ^b ^c 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" (PDF). ACS Pharmacol Transl Sci. 4 (2): 488–502. doi:10.1021/acsptsci.0c00063. PMC 8033619. PMID 33860179.
^ "Explore N-(2C-I)-Fentanyl | PiHKAL · info". isomerdesign.com.
^ ^a ^b ^c "Erowid 2C-I Vault : Legal Status".
^ Regulations Amending the Food and Drug Regulations (Part J — 2C-phenethylamines)
^ Poisons Standard October 2015
^ "Poisons Act 1964" (PDF). Archived from the original (PDF) on 2015-12-22. Retrieved 2015-12-13.
^ "Läkemedelsverkets författningssamling" (PDF) (in Swedish).
^ "H.R. 1254 (112th): Synthetic Drug Control Act of 2011". GovTrack. Retrieved 30 September 2015.

External links

Erowid 2C-I Vault
Una experiencia con 2C-I de los Shulgin Archived 2021-04-19 at the Wayback Machine (In Spanish)
2C-I Entry in PiHKAL
2C-I Entry in PiHKAL • info

[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.

[2] "25I-NBOMe (2C-I-NBOMe): Fatalities / Deaths".

[weiss-3] Weiss, Piper (September 20, 2012). 2C-I or 'Smiles': The New Killer Drug Every Parent Should Know About. Yahoo! News

[mackin2012-4] Mackin T (October 9, 2012). "Dangerous synthetic drug making its way across the country". Archived from the original on October 31, 2012. WISH-TV

[Netherlands_2c-b_emergence-5] 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.

[reuters2011-6] Reuters (March 20, 2011). Synthetic drug, subject of proposed bans, kill teen.

[RickliLuethiReinisch2015-7] 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.

[PottieCannaertStove2020-8] 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.

[WagmannBrandtStratford2019-9] 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.

[SimmlerBuchyChaboz2016-10] 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.

[FlanaganBillacLandry2021-11] 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" (PDF). ACS Pharmacol Transl Sci. 4 (2): 488–502. doi:10.1021/acsptsci.0c00063. PMC 8033619. PMID 33860179.

[12] "Explore N-(2C-I)-Fentanyl | PiHKAL · info". isomerdesign.com.

[erowid-law-13] "Erowid 2C-I Vault : Legal Status".

[14] Regulations Amending the Food and Drug Regulations (Part J — 2C-phenethylamines)

[Poisons_Standard-15] Poisons Standard October 2015

[16] "Poisons Act 1964" (PDF). Archived from the original (PDF) on 2015-12-22. Retrieved 2015-12-13.

[17] "Läkemedelsverkets författningssamling" (PDF) (in Swedish).

[18] "H.R. 1254 (112th): Synthetic Drug Control Act of 2011". GovTrack. Retrieved 30 September 2015.

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v t e Phenethylamines
Phenethylamines	Psychedelics: 25B-NBOMe 25C-NBOMe 25D-NBOMe 25I-NBOMe 25N-NBOMe 2C-B 2C-B-AN 2C-Bn 2C-Bu 2C-C 2C-CN 2C-CP 2C-D 2C-E 2C-EF 2C-F 2C-G 2C-G-1 2C-G-2 2C-G-3 2C-G-4 2C-G-5 2C-G-6 2C-G-N 2C-H 2C-I 2C-iP 2C-N 2C-NH2 2C-O 2C-O-4 2C-P 2C-Ph 2C-SE 2C-T 2C-T-2 2C-T-3 2C-T-4 2C-T-5 2C-T-6 2C-T-7 2C-T-8 2C-T-9 2C-T-10 2C-T-11 2C-T-12 2C-T-13 2C-T-14 2C-T-15 2C-T-16 2C-T-17 2C-T-18 2C-T-19 2C-T-20 2C-T-21 2C-T-22 2C-T-22.5 2C-T-23 2C-T-24 2C-T-25 2C-T-27 2C-T-28 2C-T-30 2C-T-31 2C-T-32 2C-T-33 2C-TFE 2C-TFM 2C-YN 2C-V Allylescaline DESOXY Escaline Isoproscaline Jimscaline Macromerine MEPEA Mescaline Metaescaline Methallylescaline Proscaline Psi-2C-T-4 TCB-2 Stimulants: Phenylethanolamine Hordenine Phenethylamine Phenpromethamine α-Methylphenethylamine (amphetamine) β-Methylphenethylamine m-Methylphenethylamine N-Methylphenethylamine o-Methylphenethylamine p-Methylphenethylamine Methylphenidate Entactogens: Lophophine MDPEA MDMPEA Others: BOH DMPEA
Amphetamines	Psychedelics: 3C-AL 3C-BZ 3C-E 3C-MAL 3C-P Aleph Beatrice Bromo-DragonFLY D-Deprenyl DMA DMCPA DMMDA DOB DOC DOEF DOET DOI DOM DON DOPR DOTFM Ganesha MMDA MMDA-2 Psi-DOM TMA TeMA ZDCM-04 Stimulants: 2-FA 2-FMA 3-FA 3-FMA Acridorex Alfetamine Amfecloral Amfepentorex Amphetamine (Dextroamphetamine, Levoamphetamine) Amphetaminil Benfluorex Benzphetamine Cathine Clobenzorex Dimethylamphetamine Ephedrine Etilamfetamine Fencamfamin Fencamine Fenethylline Fenfluramine (Dexfenfluramine, Levofenfluramine) Fenproporex Flucetorex Fludorex Formetorex Furfenorex Gepefrine 4-Hydroxyamphetamine Iofetamine Isopropylamphetamine Lefetamine Lisdexamfetamine Mefenorex Metaraminol Methamphetamine (Dextromethamphetamine, Levomethamphetamine) Methoxyphenamine MMA Morforex Norfenfluramine L-Norpseudoephedrine N,alpha-Diethylphenylethylamine Oxifentorex Oxilofrine Ortetamine PBA PCA PFA PFMA PIA PMA PMEA PMMA Phenylpropanolamine Pholedrine Prenylamine Propylamphetamine Pseudoephedrine Sibutramine Tiflorex Tranylcypromine Xylopropamine Zylofuramine Entactogens: 4-FA 4-FMA 4-MA 4-MMA 4-MTA 5-APB 5-APDB 5-EAPB 5-IT 5-MAPB 5-MAPDB 6-APB 6-APDB 6-Chloro-MDMA 6-EAPB 6-IT 6-MAPB 6-MAPDB EDA IAP 2,3-MDA 3,4-MDA (tenamfetamine) MDEA MDHMA MDMA (midomafetamine) MDOH Methamnetamine MMDMA Naphthylaminopropane TAP Others: 3,4-DCA Amiflamine DiFMDA Selegiline (also D-Deprenyl)
Phentermines	Stimulants: Chlorphentermine Cloforex Clortermine Etolorex Mephentermine Pentorex Phentermine Entactogens: MDPH MDMPH Others: Cericlamine
Cathinones	Stimulants: 3-FMC 4-MC 4-BMC 4-CMC 4-EMC 4-FMC 4-MEC 4-MeMABP 4-MPD Amfepramone Benzedrone Brephedrone Buphedrone Bupropion Cathinone Dimethylcathinone Ethcathinone Eutylone Hydroxybupropion Methcathinone Methedrone NEB N-Ethylhexedrone N-Ethylpentedrone Pentedrone Pentylone Radafaxine Entactogens: 3,4-DMMC 3-MMC Butylone Ethylone Methylone Methylenedioxycathinone Mephedrone
Phenylisobutylamines	Entactogens: 4-CAB 4-MAB Ariadne BDB Butylone EBDB Eutylone MBDB Stimulants: Phenylisobutylamine
Phenylalkylpyrrolidines	Stimulants: α-PBP α-PHP α-PPP α-PVP MDPBP MDPPP MDPV 4-MePBP 4-MePHP 4-MePPP MOPPP MOPVP MPBP MPHP MPPP Naphyrone PEP Prolintane Pyrovalerone
Catecholamines (and close relatives)	6-FNE 6-OHDA a-Me-DA a-Me-TRA Adrenochrome Ciladopa D-DOPA (Dextrodopa) Dimetofrine Dopamine Epinephrine Epinine Etilefrine Ethylnorepinephrine Fenclonine Ibopamine Isoprenaline Isoetarine L-DOPA (Levodopa) L-DOPS (Droxidopa) L-Phenylalanine L-Tyrosine m-Tyramine Metanephrine Metaraminol Metaterol Metirosine Methyldopa N,N-Dimethyldopamine Nordefrin (Levonordefrin) Norepinephrine Norfenefrine (m-Octopamine) Normetanephrine Orciprenaline p-Octopamine p-Tyramine Phenylephrine Synephrine
Miscellaneous	AL-LAD Amidephrine Arbutamine Cafedrine Denopamine Desvenlafaxine Diphenidine Dizocilpine Dobutamine Dopexamine Ephenidine Etafedrine ETH-LAD Famprofazone Fluorolintane Hexapradol IP-LAD Lysergic acid amide Lysergic acid 2-butyl amide Lysergic acid 2,4-dimethylazetidide Lysergic acid diethylamide Methoxamine Methoxphenidine MT-45 PARGY-LAD Phenibut PRO-LAD Pronethalol Salbutamol (Levosalbutamol) Solriamfetol Theodrenaline Thiamphenicol UWA-101 Venlafaxine