2C-I

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

Clinical data
Other names	4-Iodo-2,5-dimethoxyphenethylamine; 2,5-Dimethoxy-4-iodophenethylamine; 25I; Cimbi-88; 2C-DOI
Routes of administration	Oral[1][2]
Drug class	Serotonin 5-HT2 receptor agonist; Serotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen
ATC code	None
Legal status
Legal status	AU: S9 (Prohibited substance) BR: Class F2 (Prohibited psychotropics) CA: Schedule III UK: Class A US: Schedule I
Pharmacokinetic data
Onset of action	≤40 minutes[1]
Duration of action	6–10 hours[1][2]
Identifiers
IUPAC name 2-(4-iodo-2,5-dimethoxyphenyl)ethan-1-amine
CAS Number	69587-11-7 Y
PubChem CID	10267191
ChemSpider	8442670 Y
UNII	S35362848V
KEGG	C22776 Y
ChEMBL	ChEMBL338297 Y
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 Y Key:PQHQBRJAAZQXHL-UHFFFAOYSA-N Y
(verify)

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

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

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

Pharmacodynamics

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-HT_2A 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

Synthesis

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

Analogues

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

History

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

Legal status

2C-I in powder form.

Australia

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

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

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.^[31]

Finland

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

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.^[33]

United Kingdom

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

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.^[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

• 2C (psychedelics)