2C-E

Last updated

2C-E
2C-E.svg
2C-E-3d-sticks.png
Clinical data
Other names4-Ethyl-2,5-dimethoxyphenethylamine; 2,5-Dimethoxy-4-ethylphenethylamine; 2C-DOET; 2C-DOEt; Aquarust
Routes of
administration 		Oral [1]
Drug class Serotonin 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 action 8–12 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 InfoCard 100.221.016 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C12H19NO2
Molar mass 209.289 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 Yes check.svgY
  • Key:VDRGNAMREYBIHA-UHFFFAOYSA-N Yes check.svgY
   (verify)

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]

Contents

2C-E was first synthesized by Alexander Shulgin in 1977 [4] [5] 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] [3] He 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] While a dose of 10 mg is often experienced as rich and well-tolerated, doses of 25 to 30 mg have been described as too much and as very frightening. [1] The onset of 2C-E was not described. [1]

2C-E's effects are often described as "neutral", in comparison with other psychedelic chemicals and even other 2C drugs. In PiHKAL, Shulgin states: [1]

"Here is another of the magical half-dozen. The range is purposefully broad. At 10 milligrams there have been some pretty rich +++ [nb 1] experiences, and yet I have had the report from one young lady of a 30 milligram trial that was very frightening. My first experience with 2C-E was really profound, and it is the substance of a chapter within the story. Several people have said, about 2C-E, "I don't think I like it, since it isn't that much fun. But I intend to explore it again." There is something here that will reward the experimenter. 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."

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, although these parameters were not precisely measured. [2]

Side effects

Adverse effects of 2C-E include tachycardia, hypertension, agitation, delirium, and hallucinations. [6] At least two deaths have been attributed to a 2C-E overdose. [6] [7] [8]

Interactions

2C-E is metabolized by the monoamine oxidase (MAO) enzymes MAO-A and MAO-B. [3] [9] Monoamine oxidase inhibitors (MAOIs) such as phenelzine, tranylcypromine, moclobemide, and selegiline may potentiate the effects of 2C-E. [3] [9] [10] This may result in overdose and serious toxicity. [10] [3]

Pharmacology

Pharmacodynamics

2C-E activities
Target Affinity (Ki, nM)
5-HT1A 307–1,190 (Ki)
>10,000 (EC50 Tooltip half-maximal effective concentration)
<20% (Emax Tooltip maximal efficacy)
5-HT1B 253
5-HT1D 73.2
5-HT1E 626
5-HT1F ND
5-HT2A 4.5–43.9 (Ki)
2.5–84 (EC50)
40–87% (Emax)
5-HT2B 25.1 (Ki)
190 (EC50)
66% (Emax)
5-HT2C 5.4–104 (Ki)
0.23–18.0 (EC50)
98–106% (Emax)
5-HT3 >10,000
5-HT4 ND
5-HT5A >10,000
5-HT6 2,971
5-HT7 426
α1A 7,400–>10,000
α1B >10,000
α1D ND
α2A 100–490
α2B 306
α2C 90.2
β1 >10,000
β2 ND
β3 ND
D1 >10,000
D2 3,200–3,339
D3 1,345–19,000
D4 >10,000
D5 >10,000
H1–H4 >10,000
M1 >10,000
M2 >10,000
M3 2,557
M4 >10,000
M5 1,725
I1 >10,000
σ1 ND
σ2 >10,000
TAAR1 Tooltip 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)
SERT Tooltip Serotonin transporter>10,000 (Ki)
62,000–72,000 (IC50 Tooltip half-maximal inhibitory concentration)
>100,000 (EC50)
NET Tooltip Norepinephrine transporter>10,000 (Ki)
26,000–89,000 (IC50)
>100,000 (EC50)
DAT Tooltip Dopamine transporter>10,000 (Ki)
275,000 (IC50)
>100,000 (EC50)
MAO-A Tooltip Monoamine oxidase AND (IC50)
MAO-B Tooltip 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: [11] [12] [13] [14] [15] [16] [17] [18] [19]

2C-E acts as a serotonin 5-HT2 receptor agonist. [13] [14] Activation of the serotonin 5-HT2A receptor is thought to be responsible for its psychedelic effects.[ citation needed ]

It is inactive as a monoamine releasing agent and has negligible activity as a monoamine reuptake inhibitor. [15] [16] [14] [13]

Chemistry

Properties

Mass spectrometer analysis: 2C-E. MSpectro2C-E.gif
Mass spectrometer analysis: 2C-E.

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. [20]

Synthesis

The chemical synthesis of 2C-E has been described. [1] [20]

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] [21]

History

2C-E was first synthesized by Alexander Shulgin in 1977. [4] [5] It was described in greater detail by Shulgin in his 1991 book PiHKAL (Phenethylamines I Have Known and Loved). [1]

Society and culture

20 mg capsules of 2C-E. Ethylphenethylamine.jpg
20 mg capsules of 2C-E.
2C-E pile. 2,5-dimethoxy-4-ethyl.jpg
2C-E pile.

Australia

In Queensland, 2C-E was added to the 'Dangerous Drugs' list of the 'Drugs Misuse Act 1986' [22] by the 'Drugs Misuse Amendment Act 2008'. [23] Making it illegal to produce, supply or possess.

Canada

As of October 31, 2016, 2C-E is a controlled substance (Schedule III) in Canada. [24]

China

As of October 2015, 2C-E is a controlled substance in China. [25]

Denmark

2C-E is added to the list of Schedule B controlled substances. [26]

Finland

Scheduled in "government decree on psychoactive substances banned from the consumer market". [27]

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.[ citation needed ] 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. [28]

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. [29]

See also

Notes

  1. ↑ Shulgin's +/- rating scale, per PiHKAL. See References below. Quoting: "Plus Three (+++) = Not only are the chronology and the nature of a drug's action quite clear, but ignoring its action is no longer an option. The subject is totally engaged in the experience, for better or worse."

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 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. 1 2 3 4 5 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. 1 2 3 4 5 6 7 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. 1 2 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.
  5. 1 2 Shulgin A (1980). Pharmacology Notes II (The Shulgin Lab Books) (PDF). Lafayette, CA, USA: Erowid. p. 236.
  6. 1 2 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.
  7. ↑ 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.
  8. ↑ 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.
  9. 1 2 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.
  10. 1 2 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.
  11. ↑ "Kᵢ Database". PDSP. 16 March 2025. Retrieved 16 March 2025.
  12. ↑ 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.
  13. 1 2 3 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.
  14. 1 2 3 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.
  15. 1 2 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.
  16. 1 2 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.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ 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.
  20. 1 2 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.
  21. ↑ 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.
  22. ↑ "In force legislation - Queensland Legislation - Queensland Government" (PDF). legislation.qld.gov.au. Archived (PDF) from the original on 2014-09-11.
  23. ↑ "Acts as passed - Queensland Legislation - Queensland Government" (PDF). legislation.qld.gov.au. Archived (PDF) from the original on 2015-04-07.
  24. ↑ "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.
  25. ↑ "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.
  26. ↑ Indenrigs- og Sundhedsministeriet. "Bekendtgørelse om euforiserende stoffer - retsinformation.dk". retsinformation.dk. Archived from the original on 2013-10-04.
  27. ↑ "1130/2014".
  28. ↑ "20040696" (PDF). Archived (PDF) from the original on 2013-09-29. Retrieved 2013-09-06.
  29. ↑ "Erowid 2C-E Vault: Legal Status". erowid.org. Archived from the original on 2015-12-08.
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