2C-E

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2C-E
Clinical data
Other names4-Ethyl-2,5-dimethoxyphenethylamine; 2,5-Dimethoxy-4-ethylphenethylamine; 2C-DOET; 2C-DOEt; Aquarust
Routes of
administration		Oral[1]
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<2 hours[2]
Duration of action8–12 hours[1][3][2]
Identifiers
  • 2-(4-ethyl-2,5-dimethoxyphenyl)ethan-1-amine
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.221.016
Chemical and physical data
FormulaC12H19NO2
Molar mass209.289 g·mol−1
3D model (JSmol)
Solubility in water>70 mg/mL (20 °C)
  • COc1cc(CC)c(cc1CCN)OC
  • InChI=1S/C12H19NO2/c1-4-9-7-12(15-3)10(5-6-13)8-11(9)14-2/h7-8H,4-6,13H2,1-3H3 checkY
  • Key:VDRGNAMREYBIHA-UHFFFAOYSA-N checkY
  (verify)
Sample of 2C-E

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

The drug acts as an agonist of the serotonin 5-HT2 receptors, including of the serotonin 5-HT2A receptor.[4][5]

2C-E was first synthesized by Alexander Shulgin in 1977[6][7] and was documented in his 1991 book PiHKAL (Phenethylamines I Have Known and Loved).[1]

Use and effects

In his book PiHKAL (Phenethylamines I Have Known and Loved), Alexander Shulgin lists 2C-E's dose range as 10 to 25 mg orally and its duration as 8 to 12 hours.[1][8][9][3] However, in a couple of subsequent publications, he lists its dose range as only 10 to 15 mg orally.[8][9] Shulgin describes 2C-E as having a steep dose–response curve, such that a small increase in dose can result in an unexpectedly large increase in effects.[1][10] While a dose of 10 mg is often experienced as rich and well-tolerated, similar in character to 2C-D and 2C-B, doses of 20 to 30 mg have been described as too much and as very frightening.[1][10] The onset of 2C-E was not described.[1]

The effects of 2C-E have been reported to include color enhancement, visual changes and distortions, aesthetic enhancement, fantasy, profound and immersive psychedelic experiences, introspection, insights, dramatic recall of forgotten events, and discomfort, among others.[1][11] Several short reports of the effects of 2C-E were published in the 2C-E section in PiHKAL, but were mostly described in abstract or experiential terms.[1] However, a couple of in-depth long-form reports were also included in the first half of the book.[1]

According to Shulgin, 2C-E is "without any question, a complete psychedelic".[1] He also wrote the following of the drug: "Someday, the full character of 2C-E will be understood, but for the moment, let it rest as being a difficult and worth-while material. A very much worth-while material."[1] In other publications, Shulgin described 2C-E as an "extraordinarily powerful and effective compound" and said that it is "a most extraordinary drug, evoking for many subjects a dramatic recall of forgotten events, with a remarkable ability to interpret and analyze them. The alteration of one's state of consciousness is dramatic, often quite frightening, and yet consistently allowing a complete recall."[8][9] Along with a few other 2Cs like 2C-B, 2C-T-2, and 2C-T-7, 2C-E is listed in PiHKAL as one of Shulgin's "magical half-dozen".[1]

Subsequent to Shulgin's descriptions, the effects of 2C-E have been formally clinically studied.[2] Its effects included altered perceptions, hallucinations, and euphoria, among others.[2] The onset was within 2 hours and its duration was more than 6 hours, though these parameters were not precisely measured.[2]

Side effects

Adverse effects of 2C-E include tachycardia, hypertension, agitation, delirium, and hallucinations.[12] At least two deaths have been attributed to a 2C-E overdose.[12][13][14]

Interactions

2C-E is metabolized by the monoamine oxidase (MAO) enzymes MAO-A and MAO-B.[3][15] Monoamine oxidase inhibitors (MAOIs) such as phenelzine, tranylcypromine, moclobemide, and selegiline may potentiate the effects of 2C-E.[3][15][16] This may result in overdose and serious toxicity.[16][3]

Pharmacology

2C-E activities
TargetAffinity (Ki, nM)
5-HT1A307–1,190 (Ki)
>10,000 (EC50Tooltip half-maximal effective concentration)
<20% (EmaxTooltip maximal efficacy)
5-HT1B253
5-HT1D73.2
5-HT1E626
5-HT1FND
5-HT2A4.5–43.9 (Ki)
2.5–84 (EC50)
40–87% (Emax)
5-HT2B25.1 (Ki)
190 (EC50)
66% (Emax)
5-HT2C5.4–104 (Ki)
0.23–18.0 (EC50)
98–106% (Emax)
5-HT3>10,000
5-HT4ND
5-HT5A>10,000
5-HT62,971
5-HT7426
α1A7,400–>10,000
α1B>10,000
α1DND
α2A100–490
α2B306
α2C90.2
β1>10,000
β2ND
β3ND
D1>10,000
D23,200–3,339
D31,345–19,000
D4>10,000
D5>10,000
H1–H4>10,000
M1>10,000
M2>10,000
M32,557
M4>10,000
M51,725
I1>10,000
σ1ND
σ2>10,000
TAAR1Tooltip Trace amine-associated receptor 11,200 (Ki) (mouse)
66–70 (Ki) (rat)
1,100 (EC50) (mouse)
180 (EC50) (rat)
6,410–>10,000 (EC50) (human)
64% (Emax) (mouse)
72% (Emax) (rat)
SERTTooltip Serotonin transporter>10,000 (Ki)
62,000–72,000 (IC50Tooltip half-maximal inhibitory concentration)
>100,000 (EC50)
NETTooltip Norepinephrine transporter>10,000 (Ki)
26,000–89,000 (IC50)
>100,000 (EC50)
DATTooltip Dopamine transporter>10,000 (Ki)
275,000 (IC50)
>100,000 (EC50)
MAO-ATooltip Monoamine oxidase AND (IC50)
MAO-BTooltip Monoamine oxidase B124,000 (IC50)
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [17][18][4][5][19][20][21][22][23]

Pharmacodynamics

2C-E acts as a serotonin 5-HT2 receptor agonist.[4][5] Activation of the serotonin 5-HT2A receptor is thought to be responsible for its psychedelic effects.

It is inactive as a monoamine releasing agent and has negligible activity as a monoamine reuptake inhibitor.[19][20][5][4]

Chemistry

Properties

2C-E is a colorless oil. Crystalline forms are obtained as the amine salt by reacting the free base with a mineral acid, typically hydrochloric acid (HCl).

Shulgin does not report an exact boiling point for the free base, stating only that during one synthesis the fraction boiling between 90 and 100 °C at 0.25 mmHg pressure was collected and converted to the hydrochloride salt. Shulgin reports the melting point of the hydrochloride salt as 208.5–210.5 °C.[24]

Synthesis

Mass spectrometer analysis: 2C-E.

The chemical synthesis of 2C-E has been described.[1][24]

Analogues

Analogues of 2C-E include 2C-H (2,5-DMPEA), 2C-D, 2C-P, DOM, DOET, 2C-E-FLY, and 25E-NBOMe, among others.[1][25]

History

2C-E was first synthesized by Alexander Shulgin in 1977.[6][7] It was first briefly mentioned in the scientific literature by Shulgin and colleagues in 1978.[26] Then, it was described in greater detail by Shulgin in 1979.[10] Later, the drug was described in much greater detail by Shulgin in his book PiHKAL (Phenethylamines I Have Known and Loved) in 1991.[1]

Society and culture

2C-E 20 mg capsules.
2C-E powder.

Australia

In Queensland, 2C-E was added to the 'Dangerous Drugs' list of the 'Drugs Misuse Act 1986'[27] by the 'Drugs Misuse Amendment Act 2008'.[28] Making it illegal to produce, supply or possess.

Canada

As of October 31, 2016, 2C-E is a controlled substance (Schedule III) in Canada.[29]

China

As of October 2015, 2C-E is a controlled substance in China.[30]

Denmark

2C-E is added to the list of Schedule B controlled substances.[31]

Finland

Scheduled in "government decree on psychoactive substances banned from the consumer market".[32]

Germany

2C-E is an Anlage I controlled drug.

New Zealand

New Zealand has a catch-all Analogues section in Schedule 3 / Class C of their drug laws that would make 2C-I, 2C-E, DOI, ephedrine, and pseudoephedrine Schedule 3 compounds in New Zealand.

Portugal

Portugal has decriminalized possession of all recreational drugs in quantities no more than a ten-day supply of that substance. However production and distribution (buying/selling) are a criminal offense.

Sweden

Sveriges riksdags health ministry Statens folkhälsoinstitut classified 2C-E as "health hazard" under the act Lagen om förbud mot vissa hälsofarliga varor (translated Act on the Prohibition of Certain Goods Dangerous to Health) as of Oct 1, 2004, in their regulation SFS 2004:696 listed as 2,5-dimetoxi-4-etylfenetylamin (2C-E), making it illegal to sell or possess.[33]

United Kingdom

In the United Kingdom, 2C-E is a Class A controlled substance. The UK has the strictest laws in the EU on designer drugs. The Misuse Of Drugs Act was amended in 2002 to include a "catch most" clause outlawing every drug, and possible future drug, from the LSD (ergoline) and MDMA (phenethylamine) chemical families (including 2C-E). The amendment is a near verbatim quote from the books of the American biochemist Alexander Shulgin, who obtained a PhD from the University of California, Berkeley. Dr. Shulgin, a former research chemist at the Dow Chemical Company, re-discovered the synthesis for MDMA in 1976 and published the syntheses for more than 200 phenethylamine compounds of his own invention, and 55 tryptamine compounds many of which were also his own invention. The Shulgins were motivated to release the synthesis information as a way to protect the public's access to information about psychedelic compounds, a goal Alexander Shulgin has noted many times.

United States

As of July 9, 2012, in the United States 2C-E is a Schedule I substance under the Food and Drug Administration Safety and Innovation Act of 2012, making possession, distribution and manufacture illegal.[34]

See also

References

  1. Shulgin A, Shulgin A (September 1991). PiHKAL: A Chemical Love Story. Berkeley, California: Transform Press. ISBN 0-9630096-0-5. OCLC 25627628. 2C-E in PiHKAL
  2. Papaseit E, Olesti E, Pérez-Mañá C, Torrens M, Grifell M, Ventura M, et al. (2020). "Acute Effects of 2C-E in Humans: An Observational Study". Frontiers in Pharmacology. 11 233. doi:10.3389/fphar.2020.00233. PMC 7093582. PMID 32256350.
  3. 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.
  4. Ray TS (February 2010). "Psychedelics and the human receptorome". PLOS ONE. 5 (2) e9019. Bibcode:2010PLoSO...5.9019R. doi:10.1371/journal.pone.0009019. PMC 2814854. PMID 20126400.
  5. 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.
  6. Darie IF, Praisler M, Negoita C (12 November 2021). "2C-x and DOx hallucinogens: A systematic review". Annals of the "Dunarea de Jos" University of Galati Fascicle II Mathematics Physics Theoretical Mechanics. 44 (1): 46–52. doi:10.35219/ann-ugal-math-phys-mec.2021.1.07. ISSN 2668-7151. Retrieved 26 January 2025.
  7. Shulgin A (1980). Pharmacology Notes II (The Shulgin Lab Books) (PDF). Lafayette, CA, USA: Erowid. p. 236.
  8. Jacob P, Shulgin AT (1994). "Structure-Activity Relationships of the Classic Hallucinogens and Their Analogs". In Lin GC, Glennon RA (eds.). Hallucinogens: An Update (PDF). National Institute on Drug Abuse Research Monograph Series. Vol. 146. National Institute on Drug Abuse. pp. 74–91. PMID 8742795. Archived from the original on 13 July 2025. The base without this para-alkyl group is 2,5-dimethoxyphenethylamine (2C-H), but if this group is homologated to an ethyl, the extraordinarily powerful and effective compound 2,5-dimethoxy-4-ethylphenethylamine (2C-E) is found.
  9. Shulgin AT (2003). "Basic Pharmacology and Effects". In Laing RR (ed.). Hallucinogens: A Forensic Drug Handbook. Forensic Drug Handbook Series. Elsevier Science. pp. 67–137. ISBN 978-0-12-433951-4. Archived from the original on 13 July 2025. [2C-E] is a most extraordinary drug, evoking for many subjects a dramatic recall of forgotten events, with a remarkable ability to interpret and analyze them. The alteration of one's state of consciousness is dramatic, often quite frightening, and yet consistently allowing a complete recall.
  10. Shulgin AT (1979). "Chemistry of phenethylamines related to mescaline". J Psychedelic Drugs. 11 (1–2): 41–52. doi:10.1080/02791072.1979.10472091. PMID 522167. Archived from the original on 2025-07-12. The third of these compounds, 2-CE, is also active at about 10 mg and qualitatively at this level it is very similar to the first two. At twice this dosage, however, there is superimposed on this placid state a rather intense and somewhat frightening hallucinatory syndrome which is relatively long lasting.
  11. Shulgin AT (1 August 2005). "Abused Substances". MIT Technology Review. pp. 80–81. Archived from the original on 7 July 2025. When I moved one of the methoxy groups of mescaline to an adjacent position, and replaced another one with an ethyl group, I got a beautiful white solid that I named 2C-E. It was fully active in me at 20 milligrams taken orally. The visual activity and color enhancement it effected were very much like those of LSD, but 2C-E had a strange and (for me) novel property. On occasion, during a psychedelic experience, I would ask myself an important, private question to see what answer might bubble up. If the question turned out to be too complex, or touched on unpleasant subjects, I would drop it and ask another. But 2C-E wouldn't let me do that. I had to stay with each question until I worked through to an answer.
  12. JM T, H E, LA W, SA B, EM E, JB C (2011). "A case series of symptomatic patients, including one fatality, following 2C-E exposure". Clin. Toxicol. 49: 526.
  13. Pham S (18 March 2011). "Man Arrested in Mass Drug Overdose That Killed 1 Teen and Left 10 People Hospitalized". ABC World News. Retrieved 29 June 2014.
  14. J S, MJ R, S W, MJ O (2012). "Fatal toxic leukoencephalopathy secondary to overdose of a new psychoactive designer drug 2C-E ("Europa")". Baylor University Medical Center Proceedings. 25 (4): 374–376. doi:10.1080/08998280.2012.11928883. PMC 3448584. PMID 23077393.
  15. 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.
  16. 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.
  17. "Kᵢ Database". PDSP. 16 March 2025. Retrieved 16 March 2025.
  18. Liu T. "BindingDB BDBM50240788 2-(2,5-dimethoxy-4-ethylphenyl)ethylamine::2-(4-Ethyl-2,5-dimethoxy-phenyl)-ethylamine::CHEMBL124063::US20240166618, Compound 2C-E". BindingDB. Retrieved 3 March 2025.
  19. 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 (Berl). 231 (5): 875–888. doi:10.1007/s00213-013-3303-6. PMC 3945162. PMID 24142203.
  20. Nagai F, Nonaka R, Satoh Hisashi Kamimura K (March 2007). "The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain". Eur J Pharmacol. 559 (2–3): 132–137. doi:10.1016/j.ejphar.2006.11.075. PMID 17223101.
  21. 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.
  22. 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" (PDF). Drug Test Anal. 11 (2): 318–324. doi:10.1002/dta.2494. PMID 30188017.
  23. 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). J Pharmacol Exp Ther. 357 (1): 134–144. doi:10.1124/jpet.115.229765. PMID 26791601. Archived from the original (PDF) on 2025-05-09.
  24. 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.
  25. 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.
  26. Braun U, Braun G, Jacob P, Nichols DE, Shulgin AT (1978). "Mescaline Analogs: Substitutions at the 4-Position" (PDF). In Barnett G, Trsic M, Willette RE (eds.). QuaSAR: Quantitative Structure Activity Relationships Of Analgesics, Narcotic Antagonists, And Hallucinogens (PDF). National Institute on Drug Abuse Research Monograph Series. Vol. 22. National Institute on Drug Abuse. pp. 27–37. PMID 101882. TABLE I HUMAN ACTIVITY OF 2-CARBON AND ANALOGOUS 3-CARBON-CHAIN PSYCHOTOMIMETICS (a) [...] 2,5-OCH3-4-Et [...]
  27. "In force legislation - Queensland Legislation - Queensland Government" (PDF). legislation.qld.gov.au. Archived (PDF) from the original on 2014-09-11.
  28. "Acts as passed - Queensland Legislation - Queensland Government" (PDF). legislation.qld.gov.au. Archived (PDF) from the original on 2015-04-07.
  29. "Regulations Amending the Food and Drug Regulations (Part J — 2C-phenethylamines)". Canada Gazette. Vol. 150, no. 9. 4 May 2016. Archived from the original on 2016-08-31.
  30. "关于印发《非药用类麻醉药品和精神药品列管办法》的通知" (in Chinese). China Food and Drug Administration. 27 September 2015. Archived from the original on 1 October 2015. Retrieved 1 October 2015.
  31. Indenrigs- og Sundhedsministeriet. "Bekendtgørelse om euforiserende stoffer - retsinformation.dk". retsinformation.dk. Archived from the original on 2013-10-04.
  32. "1130/2014".
  33. "20040696" (PDF). Archived (PDF) from the original on 2013-09-29. Retrieved 2013-09-06.
  34. "Erowid 2C-E Vault: Legal Status". erowid.org. Archived from the original on 2015-12-08.