Chemistry:2C-E

From HandWiki

2C-E is a psychedelic phenethylamine of the 2C family. It was first synthesized by Alexander Shulgin[1] and documented in his book PiHKAL. Like the other substances in its family, it produces sensory and cognitive effects in its physical reactions with living organisms.[2]

Use and dosage

Shulgin gives the dose range of 2C-E as 10 to 25 mg.[1] 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]

Effects

According to Shulgin, the duration of 2C-E's effects is 8 to 12 hours.[1]

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

"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."

Side effects

Adverse effects include tachycardia, hypertension, agitation, delirium, and hallucinations.[3] At least two deaths have been attributed to a 2C-E overdose.[3][4][5]

Interactions

2C-E is metabolized by the monoamine oxidase (MAO) enzymes MAO-A and MAO-B.[6][7] Monoamine oxidase inhibitors (MAOIs) such as phenelzine, tranylcypromine, moclobemide, and selegiline may potentiate the effects of 2C-E.[6][7][8] This may result in overdose and serious toxicity.[8][6]

Pharmacology

Pharmacodynamics

2C-E activities
Target Affinity (Ki, nM)
5-HT1A 307–1,190 (Ki)
>10,000 (EC50)
<20% (Emax)
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 1,200 (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 >10,000 (Ki)
62,000–72,000 (IC50)
>100,000 (EC50)
NET >10,000 (Ki)
26,000–89,000 (IC50)
>100,000 (EC50)
DAT >10,000 (Ki)
275,000 (IC50)
>100,000 (EC50)
MAO-A ND (IC50)
MAO-B 124,000 (IC50)
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [9][10][11][12][13][14][15][16][17]


It is inactive as a monoamine releasing agent and has negligible activity as a monoamine reuptake inhibitor.[13][14][12][11]

Chemistry

Properties

Mass spectrometer analysis: 2C-E.

2,5-Dimethoxy-4-ethylphenethylamine 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.[18]

Society and culture

20 mg capsules of 2C-E.
2C-E pile.

Australia

In Queensland, 2C-E was added to the 'Dangerous Drugs' list of the 'Drugs Misuse Act 1986'[19] by the 'Drugs Misuse Amendment Act 2008'.[20] Making it illegal to produce, supply or possess.

Canada

As of October 31, 2016, 2C-E is a controlled substance (Schedule III) in Canada.[21]

China

As of October 2015, 2C-E is a controlled substance in China.[22]

Denmark

2C-E is added to the list of Schedule B controlled substances.[23]

Finland

Scheduled in "government decree on psychoactive substances banned from the consumer market".[24]

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.[25]

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.[26]

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. ↑ 1.0 1.1 1.2 1.3 Shulgin, Alexander; Shulgin, Ann (September 1991). PiHKAL: A Chemical Love Story. Berkeley, California: Transform Press. ISBN 0-9630096-0-5. OCLC 25627628. http://www.erowid.org/library/books_online/pihkal/pihkal.shtml.  2C-E in PiHKAL
  2. ↑ "Acute Effects of 2C-E in Humans: An Observational Study". Frontiers in Pharmacology 11. 2020. doi:10.3389/fphar.2020.00233. PMID 32256350. 
  3. ↑ 3.0 3.1 Topeff JM; Ellsworth H; Willhite LA; Bangh SA; Edwards EM; Cole JB (2011). "A case series of symptomatic patients, including one fatality, following 2C-E exposure". Clin. Toxicol. 49: 526. 
  4. ↑ "Man Arrested in Mass Drug Overdose That Killed 1 Teen and Left 10 People Hospitalized". ABC World News. 18 March 2011. https://abcnews.go.com/US/man-arrested-minnesota-deadly-mass-drug-overdose/story?id=13166375. 
  5. ↑ Sacks J; Ray MJ; Williams S; Opatowsky MJ (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. PMID 23077393. 
  6. ↑ 6.0 6.1 6.2 "2C or not 2C: phenethylamine designer drug review". J Med Toxicol 9 (2): 172–178. June 2013. doi:10.1007/s13181-013-0295-x. PMID 23494844. 
  7. ↑ 7.0 7.1 "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. January 2007. doi:10.1016/j.bcp.2006.09.022. PMID 17067556. 
  8. ↑ 8.0 8.1 "Drug-drug interactions involving classic psychedelics: A systematic review". J Psychopharmacol 38 (1): 3–18. January 2024. doi:10.1177/02698811231211219. PMID 37982394. 
  9. ↑ "Kᵢ Database". 16 March 2025. https://pdsp.unc.edu/kidb2/kidb/web/kis-results/index?KisResultsSearch%5Binput_receptors%5D=&KisResultsSearch%5Binput_sources%5D=&KisResultsSearch%5Binput_species%5D=&KisResultsSearch%5Binput_hot_ligands%5D=&KisResultsSearch%5Binput_test_ligands%5D=&KisResultsSearch%5Binput_test_ligands%5D%5B%5D=14671&KisResultsSearch%5Binput_test_ligands%5D%5B%5D=12943&KisResultsSearch%5Binput_citations%5D=&KisResultsSearch%5BsearchType%5D=&KisResultsSearch%5Bki_val_from%5D=&KisResultsSearch%5Bki_val_to%5D=&KisResultsSearch%5Bcustom_ki_val%5D=. 
  10. ↑ "BindingDB BDBM50240788 2-(2,5-dimethoxy-4-ethylphenyl)ethylamine::2-(4-Ethyl-2,5-dimethoxy-phenyl)-ethylamine::CHEMBL124063::US20240166618, Compound 2C-E". https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50240788. 
  11. ↑ 11.0 11.1 "Psychedelics and the human receptorome". PLOS ONE 5 (2). February 2010. doi:10.1371/journal.pone.0009019. PMID 20126400. Bibcode: 2010PLoSO...5.9019R. 
  12. ↑ 12.0 12.1 "Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs)". Neuropharmacology 99: 546–553. December 2015. doi:10.1016/j.neuropharm.2015.08.034. PMID 26318099. https://psilosybiini.info/paperit/Receptor%20interaction%20profiles%20of%20novel%20N-2-methoxybenzyl%20(NBOMe)%20derivatives%20of%202,5-dimethoxy-substituted%20phenethylamines%20(2C%20drugs)%20(Rickli%20et%20al.,%202015).pdf. 
  13. ↑ 13.0 13.1 "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. March 2014. doi:10.1007/s00213-013-3303-6. PMID 24142203. PMC 3945162. https://www.researchgate.net/publication/258061356. 
  14. ↑ 14.0 14.1 "The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain". Eur J Pharmacol 559 (2–3): 132–137. March 2007. doi:10.1016/j.ejphar.2006.11.075. PMID 17223101. 
  15. ↑ "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. October 2020. doi:10.1007/s00204-020-02836-w. PMID 32627074. Bibcode: 2020ArTox..94.3449P. 
  16. ↑ "Interactions of phenethylamine-derived psychoactive substances of the 2C-series with human monoamine oxidases". Drug Test Anal 11 (2): 318–324. February 2019. doi:10.1002/dta.2494. PMID 30188017. https://publikationen.sulb.uni-saarland.de/bitstream/20.500.11880/29219/1/Interactions%20of%20phenethylamine-derived%20psychoactive%20substances%20of%20the%202C-series%20with%20human%20monoamine%20oxidases_mit_Vorblatt.pdf. 
  17. ↑ "In Vitro Characterization of Psychoactive Substances at Rat, Mouse, and Human Trace Amine-Associated Receptor 1". J Pharmacol Exp Ther 357 (1): 134–144. April 2016. doi:10.1124/jpet.115.229765. PMID 26791601. https://d1wqtxts1xzle7.cloudfront.net/74120533/eae6c6e62565b82d46b4d111bbea0f77b9c2-libre.pdf?1635931703=&response-content-disposition=inline%3B+filename%3DIn_Vitro_Characterization_of_Psychoactiv.pdf&Expires=1746838268&Signature=Sy4fJ90yUhxs68314NxYsW5PAaNrBGePRu35WRR4PIF-3YC7Z~sLdnCn5wfqqbLg9bDEGdt~oW55ugMP3D3jgA0BoRI~~GOb0NQOwrtfUEQK1PQs1uuN9qg5Y1ct8z5NsABm44RgtukkwRMdU6fO7OlfIsQ68hOiFk129Ll7UYqldxD2f1xhE2fTTfsxSpb8cMCJzHn7-ItqLdwnAUPFK7WggDIjmY1kCnaHLwIxMwdJCAq8L6DYzSTg7pZkbR8qlou~GXbTPQt~gYpyZTJp5hgW-7V6K5wLlQ7Z2xE7B0f9wEfuc1W1QNafg125Tr-vvAe4LEGKXV58bnn1bpfWKw__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA. 
  18. ↑ The Shulgin Index: Volume 1 (First ed.). Berkeley, CA: Transform Press. 2011. ISBN 978-0-9630096-3-0. 
  19. ↑ "In force legislation - Queensland Legislation - Queensland Government". https://www.legislation.qld.gov.au/LEGISLTN/CURRENT/D/DrugsMisuseA86.pdf. 
  20. ↑ "Acts as passed - Queensland Legislation - Queensland Government". https://www.legislation.qld.gov.au/LEGISLTN/ACTS/2008/08AC004.pdf. 
  21. ↑ "Regulations Amending the Food and Drug Regulations (Part J — 2C-phenethylamines)". Canada Gazette 150 (9). 4 May 2016. http://gazette.gc.ca/rp-pr/p2/2016/2016-05-04/html/sor-dors72-eng.php. 
  22. ↑ "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 zh). China Food and Drug Administration. 27 September 2015. http://www.sfda.gov.cn/WS01/CL0056/130753.html. 
  23. ↑ Sundheds- og Ældreministeriet. "Bekendtgørelse om euforiserende stoffer - retsinformation.dk". https://www.retsinformation.dk/Forms/R0710.aspx?id=137169. 
  24. ↑ "1130/2014". https://finlex.fi/fi/lainsaadanto/2014/1130. 
  25. ↑ "20040696". http://www.notisum.se/rnp/sls/sfs/20040696.pdf. 
  26. ↑ "Erowid 2C-E Vault: Legal Status". https://www.erowid.org/chemicals/2ce/2ce_law.shtml. 

Template:Psychedelics

Template:TAAR modulators



Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:2C-E&oldid=4031562"