2C (psychedelics)

{{Short description|Family of phenethylamine psychedelics}} [[File:2C-general.svg|thumb|175px|right|class=skin-invert-image|General structure of a 2C compound.]]

'''2C''' ('''2C-''x''''') is a general name for the family of psychedelic phenethylamines containing methoxy groups on the 2 and 5 positions of a benzene ring.<ref name="DeanStellpflugBurnett2013" /><ref name="ShulginManningDaley2011" /><ref name="WillsErickson2012" /> Most of these compounds also carry lipophilic substituents at the 4 position, usually resulting in more potent and more metabolically stable and longer acting compounds.<ref name="TrachselLehmannEnzensperger2013" />

Most of the early 2C drugs were developed by Alexander Shulgin in the 1970s and 1980s and were reviewed in his 1991 book ''PiHKAL'' (''Phenethylamines I Have Known And Loved'').<ref name="WillsErickson2012" /><ref name="AnilanmertYonarÖzdemir2018" /><ref name="PiHKAL" /> 2C-B is the most popular of the 2C drugs.<ref name="WillsErickson2012" /> The prefix "2C" comes from the fact that they are phenethylamines rather than amphetamines and have two carbon atoms in their side chain, whereas the suffix (''e.g.'',{{nbs}}the "–B" or "bromo" in the case of 2C–B) refers to the substituent at the 4-position.<ref name="PiHKAL" /><ref name="DeanStellpflugBurnett2013" /><ref name="WillsErickson2012" />

==Use and effects== The 2C drugs are orally active at doses of 6{{nbs}}to 150{{nbs}}mg, depending on the drug, and have durations of 3{{nbs}}to 48{{nbs}}hours, also depending on the drug.<ref name="DeanStellpflugBurnett2013" /><ref name="JacobShulgin1994" /><ref name="PiHKAL" /><ref name="BallentineFriedmanBzdok2022">{{cite journal |last1=Ballentine |first1=Galen |last2=Friedman |first2=Samuel Freesun |last3=Bzdok |first3=Danilo |date=March 2022 |title=Trips and neurotransmitters: Discovering principled patterns across 6850 hallucinogenic experiences |journal=Sci Adv |volume=8 |issue=11 |bibcode=2022SciA....8L6989B |doi=10.1126/sciadv.abl6989 |pmc=8926331 |pmid=35294242 |article-number=eabl6989}}</ref> Several have doses in the range of 10{{nbs}}to 60{{nbs}}mg and durations in the range of 4{{nbs}}to 12{{nbs}}hours.<ref name="DeanStellpflugBurnett2013" /> The 2C drugs produce psychedelic effects, such as perceptual enhancement, psychedelic visuals, and euphoria.<ref name="DeanStellpflugBurnett2013" /><ref name="PiHKAL" /><ref name="LuethiLiechti2020" /><ref name="WillsErickson2012" /> Some, such as 2C-B, have also been reported to produce some entactogen-like effects, but findings in this area appear to be mixed.<ref name="LuethiLiechti2020">{{cite journal | vauthors = Luethi D, Liechti ME | title = Designer drugs: mechanism of action and adverse effects | journal = Arch Toxicol | volume = 94 | issue = 4 | pages = 1085–1133 | date = April 2020 | pmid = 32249347 | pmc = 7225206 | doi = 10.1007/s00204-020-02693-7 | bibcode = 2020ArTox..94.1085L | url = | quote = In one of the few clinical studies of a designer drug, 4-bromo-2,5-dimethoxyphenylethylamine (2C-B) was shown to induce euphoria, well-being, and changes in perception, and to have mild stimulant properties (Gonzalez et al. 2015). 2C-B may thus be classified as a psychedelic with entactogenic properties, an effect profile that is similar to various other phenethylamine psychedelics (Shulgin and Shulgin 1995).}}</ref><ref name="WillsErickson2012" /><ref name="GonzálezTorrensFarré2015">{{cite journal |last1=González |first1=Débora |last2=Torrens |first2=Marta |last3=Farré |first3=Magí |date=2015 |title=Acute Effects of the Novel Psychoactive Drug 2C-B on Emotions |journal=Biomed Res Int |volume=2015 |doi=10.1155/2015/643878 |pmc=4620274 |pmid=26543863 |doi-access=free |article-number=643878}}</ref><ref name="MallaroniMasonReckweg2023">{{cite journal | vauthors = Mallaroni P, Mason NL, Reckweg JT, Paci R, Ritscher S, Toennes SW, Theunissen EL, Kuypers KP, Ramaekers JG | title = Assessment of the Acute Effects of 2C-B vs. Psilocybin on Subjective Experience, Mood, and Cognition | journal = Clin Pharmacol Ther | volume = 114 | issue = 2 | pages = 423–433 | date = August 2023 | pmid = 37253161 | doi = 10.1002/cpt.2958 | url = | doi-access = free }}</ref>

{{Sticky}} {| class="wikitable sortable sticky-header" |+ {{Nowrap|Oral doses and durations of 2C drugs}} |- ! Compound !! Chemical name !! Dose !! Duration |- | 2C-AL || 4-Allyl-2,5-dimethoxyphenethylamine || Unknown || Unknown |- | 2C-B || 4-Bromo-2,5-dimethoxyphenethylamine || 10–35{{nbsp}}mg || 4–8 hours |- | 2C-Bu || 4-Butyl-2,5-dimethoxyphenethylamine || Unknown || Unknown |- | 2C-C || 4-Chloro-2,5-dimethoxyphenethylamine || 20–40{{nbsp}}mg || 4–8 hours |- | 2C-CN || 4-Cyano-2,5-dimethoxyphenethylamine || >22{{nbsp}}mg || Unknown |- | 2C-CP || 4-Cyclopropyl-2,5-dimethoxyphenethylamine || 15–35{{nbsp}}mg || 3–6 hours |- | 2C-D (2C-M) || 4-Methyl-2,5-dimethoxyphenethylamine || 20–60{{nbsp}}mg || 4–6 hours |- | 2C-E || 4-Ethyl-2,5-dimethoxyphenethylamine || 10–25{{nbsp}}mg || 6–12 hours |- | 2C-EF || 4-Fluoroethyl-2,5-dimethoxyphenethylamine || 10–25{{nbsp}}mg || Unknown |- | 2C-F || 4-Fluoro-2,5-dimethoxyphenethylamine || ≥250{{nbsp}}mg || Unknown |- | 2C-G (2C-G-0) || 3,4-Dimethyl-2,5-dimethoxyphenethylamine || 20–35{{nbsp}}mg || 18–30 hours |- | 2C-G-3 || 3,4-Trimethylene-2,5-dimethoxyphenethylamine || 16–25{{nbsp}}mg || 12–24 hours |- | 2C-G-5|| 3,4-Norbornyl-2,5-dimethoxyphenethylamine || 10–16{{nbsp}}mg || 32–48 hours |- | 2C-G-N || 1,4-Dimethoxynaphthyl-2-ethylamine || 20–40 mg || 20–30 hours |- | 2C-H (2,5-DMPEA) || 2,5-Dimethoxyphenethylamine || Unknown || Unknown |- | 2C-I || 4-Iodo-2,5-dimethoxyphenethylamine || 14–22{{nbsp}}mg || 6–10 hours |- | 2C-iBu || 4-Isobutyl-2,5-dimethoxyphenethylamine || ≥5{{nbsp}}mg || ~20 hours |- | 2C-iP || 4-Isopropyl-2,5-dimethoxyphenethylamine || 8–25{{nbsp}}mg || 8–12 hours |- | 2C-N || 4-Nitro-2,5-dimethoxyphenethylamine || 100–150{{nbsp}}mg || 4–6 hours |- | 2C-O (2,4,5-TMPEA) || 4-Methoxy-2,5-dimethoxyphenethylamine || >300{{nbsp}}mg || Unknown |- | 2C-O-4 || 4-Isopropoxy-2,5-dimethoxyphenethylamine || >60{{nbsp}}mg || Unknown |- | 2C-O-22 || 4-(2,2,2-Trifluoroethoxy)-2,5-dimethoxyphenethylamine || ≥57{{nbsp}}mg || Unknown |- | 2C-P || 4-Propyl-2,5-dimethoxyphenethylamine || 6–10{{nbsp}}mg || 5–16 hours |- | 2C-Ph (2C-BI-1) || 4-Phenyl-2,5-dimethoxyphenethylamine || Unknown || Unknown |- | 2C-Se || 4-Methylseleno-2,5-dimethoxyphenethylamine || ~100{{nbsp}}mg || 6–8 hours |- | 2C-T (2C-T-1) || 4-Methylthio-2,5-dimethoxyphenethylamine || 60–100{{nbsp}}mg || 3–5 hours |- | 2C-T-2 || 4-Ethylthio-2,5-dimethoxyphenethylamine || 12–25{{nbsp}}mg || 6–8 hours |- | 2C-T-3 (2C-T-20) || 4-Methallylthio-2,5-dimethoxyphenethylamine || 15–40{{nbsp}}mg || 8–14 hours |- | 2C-T-4 || 4-Isopropylthio-2,5-dimethoxyphenethylamine || 8–20{{nbsp}}mg || 12–18 hours |- | 2C-T-7 || 4-Propylthio-2,5-dimethoxyphenethylamine || 10–30{{nbsp}}mg || 8–15 hours |- | 2C-T-8 || 4-Cyclopropylmethylthio-2,5-dimethoxyphenethylamine || 30–50{{nbsp}}mg || 10–15 hours |- | 2C-T-9 || 4-''tert''-Butylthio-2,5-dimethoxyphenethylamine || 60–100{{nbsp}}mg || 12–18 hours |- | 2C-T-13 || 4-(2-Methoxyethylthio)-2,5-dimethoxyphenethylamine || 25–40{{nbsp}}mg || 6–8 hours |- | 2C-T-15 || 4-Cyclopropylthio-2,5-dimethoxyphenethylamine || >30{{nbsp}}mg || Several hours |- | 2C-T-16 || 4-Allylthio-2,5-dimethoxyphenethylamine || 10–25{{nbsp}}mg || 4–6 hours |- | 2C-T-17 || 4-''sec''-Butylthio-2,5-dimethoxyphenethylamine || 60–100{{nbsp}}mg || 10–15 hours |- | 2C-T-19 || 4-Butylthio-2,5-dimethoxyphenethylamine || Unknown || Unknown |- | 2C-T-21 || 4-(2-Fluoroethylthio)-2,5-dimethoxyphenethylamine || 8–20{{nbsp}}mg || 7–10 hours |- | 2C-T-21.5 || 4-(2,2-Difluoroethylthio)-2,5-dimethoxyphenethylamine || 12–30{{nbsp}}mg || 8–14 hours |- | 2C-T-22 || 4-(2,2,2-Trifluoroethylthio)-2,5-dimethoxyphenethylamine || >10{{nbsp}}mg || ~6 hours |- | 2C-T-25 || 4-Isobutylthio-2,5-dimethoxyphenethylamine || >30{{nbsp}}mg || Unknown |- | 2C-T-27 || 4-Benzylthio-2,5-dimethoxyphenethylamine || ≥80{{nbsp}}mg || Unknown |- | 2C-T-28 || 4-(3-Fluoropropylthio)-2,5-dimethoxyphenethylamine || 8–20{{nbsp}}mg || 8–10 hours |- | 2C-T-30 || 4-(4-Fluorobutylthio)-2,5-dimethoxyphenethylamine || >8{{nbsp}}mg || Unknown |- | 2C-T-33 || 4-(3-Methoxybenzylthio)-2,5-dimethoxyphenethylamine || Unknown || Unknown |- | 2C-T-36 (2C-T-TFM) || 4-Trifluoromethylthio-2,5-dimethoxyphenethylamine || Unknown || Unknown |- | 2C-tBu || 4-''tert''-Butyl-2,5-dimethoxyphenethylamine || >5–10{{nbsp}}mg || Unknown |- | 2C-Te || 4-Methyltelluro-2,5-dimethoxyphenethylamine || Unknown || Unknown |- | 2C-TFE || 4-(2,2,2-Trifluoroethyl)-2,5-dimethoxyphenethylamine || 5–15{{nbsp}}mg || 12–24 hours |- | 2C-TFM || 4-Trifluoromethyl-2,5-dimethoxyphenethylamine || 3–6{{nbsp}}mg || ≥5–10 hours |- | 2C-V || 4-Ethenyl-2,5-dimethoxyphenethylamine || ~25{{nbsp}}mg || ~5 hours |- | 2C-YN || 4-Ethynyl-2,5-dimethoxyphenethylamine || ~50{{nbsp}}mg || ~2 hours |- class="sortbottom" | colspan="5" style="width: 1px; background-color:var(--background-color-notice-subtle,#eaecf0); color:inherit; text-align: center;" | '''Refs:''' <ref name="DeanStellpflugBurnett2013" /><ref name="JacobShulgin1994" /><ref name="WillsErickson2012" /><ref name="BallentineFriedmanBzdok2022" /><ref name="PiHKAL" /><ref name="ShulginManningDaley2011" /><ref name="LuethiLiechti2018">{{cite journal | vauthors = Luethi D, Liechti ME | title = Monoamine Transporter and Receptor Interaction Profiles in Vitro Predict Reported Human Doses of Novel Psychoactive Stimulants and Psychedelics | journal = Int J Neuropsychopharmacol | volume = 21 | issue = 10 | pages = 926–931 | date = October 2018 | pmid = 29850881 | pmc = 6165951 | doi = 10.1093/ijnp/pyy047 }}</ref><ref name="HalberstadtChathaKlein2020">{{cite journal |last1=Halberstadt |first1=Adam L. |last2=Chatha |first2=Muhammad |last3=Klein |first3=Adam K. |last4=Wallach |first4=Jason |last5=Brandt |first5=Simon D. |date=May 2020 |title=Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species |url=http://usdbiology.com/cliff/Courses/Advanced%20Seminars%20in%20Neuroendocrinology/Serotonergic%20Psychedelics%2020/Halberstadt%2020%20Neuropharm%20potency%20of%20hallucinogens%20%20head-twitch.pdf |journal=Neuropharmacology |volume=167 |doi=10.1016/j.neuropharm.2019.107933 |pmc=9191653 |pmid=31917152 |quote=Table 4 Human potency data for selected hallucinogens. [...] |article-number=107933}}</ref><ref name="Trachsel2012">{{cite journal | vauthors = Trachsel D | title = Fluorine in psychedelic phenethylamines | journal = Drug Test Anal | volume = 4 | issue = 7–8 | pages = 577–590 | date = 2012 | pmid = 22374819 | doi = 10.1002/dta.413 | url = https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=c7b41be36b1f580a264a752521d151e6e2d9409d| url-access = subscription }}</ref><ref name="TrachselLehmannEnzensperger2013">{{cite book | last1=Trachsel | first1=D. | last2=Lehmann | first2=D. | last3=Enzensperger | first3=C. | chapter=8.5.3. 4-Alkyl-2,5-dimethoxyphenethylamine (2C-R- oder 2C-Alkylderivate) | pages=763–771 | title=Phenethylamine: von der Struktur zur Funktion | trans-title = Phenethylamines: From Structure to Function | edition = 1 | publisher=Nachtschatten-Verlag | location = Solothurn | series=Nachtschatten-Science | year=2013 | isbn=978-3-03788-700-4 | oclc = 858805226 | url=https://books.google.com/books?id=-Us1kgEACAAJ | language=de }}</ref> |}

==Interactions== {{See also|Psychedelic drug#Interactions|Trip killer#Serotonergic psychedelic antidotes}}

The 2C drugs are metabolized by the monoamine oxidase (MAO) enzymes, including both MAO-A and MAO-B.<ref name="DeanStellpflugBurnett2013" /><ref name="TheobaldMaurer2007" /> As a result, they may be potentiated by monoamine oxidase inhibitors (MAOIs), such as phenelzine, tranylcypromine, moclobemide, and selegiline.<ref name="DeanStellpflugBurnett2013" /><ref name="TheobaldMaurer2007" /><ref name="HalmanKongSarris2024">{{Cite journal |vauthors=Halman A, Kong G, Sarris J, Perkins D |date=January 2024 |title=Drug-drug interactions involving classic psychedelics: A systematic review |journal=J Psychopharmacol |volume=38 |issue=1 |pages=3–18 |doi=10.1177/02698811231211219 |pmc=10851641 |pmid=37982394}}</ref> This may lead to overdose and serious toxicity.<ref name="DeanStellpflugBurnett2013" /><ref name="TheobaldMaurer2007" /><ref name="HalmanKongSarris2024" /><ref name="RachedCampanaFiani2026" /> There are anecdotal reports of strong potentiation of 2C-B by MAOIs, including hospitalization.<ref name="RachedCampanaFiani2026">{{cite journal | vauthors = Rached G, Campana A, Fiani D, Nguyen C, Van den Eynde V, Gillman PK, Barnett BS | title = Safety and Efficacy of Monoamine Oxidase Inhibitors in Patients Who Use Psychoactive Substances: Potential Drug Interactions and Substance Use Disorder Treatment Data | journal = CNS Drugs | volume = | issue = | pages = | date = January 2026 | pmid = 41546846 | doi = 10.1007/s40263-025-01256-7 | url = }}</ref> There is no known reversal agent for 2C drugs, and medical management for overdose involves treatment of symptoms until toxicity within the body subsides.<ref name="DeanStellpflugBurnett2013" />

==Pharmacology== ===Pharmacodynamics=== ====Actions==== The 2C drugs act as agonists of the serotonin 5-HT₂ receptors, including of the serotonin 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors.<ref name="Gil-MartinsBarbosaBorges2025">{{cite journal |last1=Gil-Martins |first1=Eva |last2=Barbosa |first2=Daniel José |last3=Borges |first3=Fernanda |last4=Remião |first4=Fernando |last5=Silva |first5=Renata |date=June 2025 |title=Toxicodynamic insights of 2C and NBOMe drugs - Is there abuse potential? |journal=Toxicol Rep |volume=14 |bibcode=2025ToxR...1401890G |doi=10.1016/j.toxrep.2025.101890 |pmc=11762925 |pmid=39867514 |article-number=101890}}</ref><ref name="RicliLuethiReinisch2015">{{cite journal | vauthors = Rickli A, Luethi D, Reinisch J, Buchy D, Hoener MC, Liechti ME | title = Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs) | journal = Neuropharmacology | volume = 99 | issue = | pages = 546–553 | date = December 2015 | pmid = 26318099 | doi = 10.1016/j.neuropharm.2015.08.034 | url = 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}}</ref><ref name="EshlemanForsterWolfrum2014" /><ref name="Ray2010">{{cite journal |last=Ray |first=Thomas S. |date=February 2010 |title=Psychedelics and the human receptorome |journal=PLOS ONE |volume=5 |issue=2 |bibcode=2010PLoSO...5.9019R |doi=10.1371/journal.pone.0009019 |pmc=2814854 |pmid=20126400 |doi-access=free |article-number=e9019}}</ref><ref name="VarìPichiniGiorgetti2019">{{cite journal | last1=Varì | first1=M. Rosaria | last2=Pichini | first2=Simona | last3=Giorgetti | first3=Raffaele | last4=Busardò | first4=Francesco P. | title=New psychoactive substances—Synthetic stimulants | journal=WIREs Forensic Science | volume=1 | issue=2 | date=2019 | issn=2573-9468 | doi=10.1002/wfs2.1197 | doi-access=free | article-number=e1197 }}</ref> They are partial agonists of the serotonin 5-HT_2A receptor.<ref name="Gil-MartinsBarbosaBorges2025" /><ref name="RicliLuethiReinisch2015" /> Most of the 2C drugs have much lower affinity for the serotonin 5-HT_1A receptor than for the serotonin 5-HT_2A receptor.<ref name="Gil-MartinsBarbosaBorges2025" /><ref name="RicliLuethiReinisch2015" /><ref name="EshlemanForsterWolfrum2014" /><ref name="Ray2010" /> Most of the 2C drugs have also shown about 5- to 15-fold higher affinity for the serotonin 5-HT_2A receptor over the serotonin 5-HT_2C receptor and about 15- to 100-fold higher affinity for the serotonin 5-HT_2A receptor over the serotonin 5-HT_1A receptor.<ref name="RicliLuethiReinisch2015" /> The psychedelic effects of the 2C drugs are thought to be mediated specifically by activation of the serotonin 5-HT_2A receptor.<ref name="Gil-MartinsBarbosaBorges2025" /><ref name="EshlemanForsterWolfrum2014" /><ref name="VarìPichiniGiorgetti2019" />

Unlike many other phenethylamines, 2C drugs, including 2C-C, 2C-D, 2C-E, 2C-I, and 2C-T-2 among others, are inactive as monoamine releasing agents and reuptake inhibitors.<ref name="Gil-MartinsBarbosaBorges2025" /><ref name="NagaiNonakaKamimura2007">{{cite journal | vauthors = Nagai F, Nonaka R, Satoh Hisashi Kamimura K | title = The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain | journal = European Journal of Pharmacology | volume = 559 | issue = 2–3 | pages = 132–137 | date = March 2007 | pmid = 17223101 | doi = 10.1016/j.ejphar.2006.11.075 }}</ref><ref name="EshlemanForsterWolfrum2014">{{cite journal | vauthors = Eshleman AJ, Forster MJ, Wolfrum KM, Johnson RA, Janowsky A, Gatch MB | title = Behavioral and neurochemical pharmacology of six psychoactive substituted phenethylamines: mouse locomotion, rat drug discrimination and in vitro receptor and transporter binding and function | journal = Psychopharmacology (Berl) | volume = 231 | issue = 5 | pages = 875–888 | date = March 2014 | pmid = 24142203 | pmc = 3945162 | doi = 10.1007/s00213-013-3303-6 | url = }}</ref><ref name="RicliLuethiReinisch2015" /><ref name="VarìPichiniGiorgetti2019" /> Most of the 2C drugs are agonists of the rat and mouse trace amine-associated receptor 1 (TAAR1).<ref name="Gil-MartinsBarbosaBorges2025" /><ref name="GainetdinovHoenerBerry2018">{{cite journal | vauthors = Gainetdinov RR, Hoener MC, Berry MD | title = Trace Amines and Their Receptors | journal = Pharmacol Rev | volume = 70 | issue = 3 | pages = 549–620 | date = July 2018 | pmid = 29941461 | doi = 10.1124/pr.117.015305 | url = | doi-access = free }}</ref><ref name="SimmlerBuchyChaboz2016">{{cite journal | vauthors = Simmler LD, Buchy D, Chaboz S, Hoener MC, Liechti ME | title = In Vitro Characterization of Psychoactive Substances at Rat, Mouse, and Human Trace Amine-Associated Receptor 1 | journal = J Pharmacol Exp Ther | volume = 357 | issue = 1 | pages = 134–144 | date = April 2016 | pmid = 26791601 | doi = 10.1124/jpet.115.229765 | url = 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 | archive-url = https://web.archive.org/web/20250509235235/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 | url-status = dead | archive-date = 2025-05-09 }}</ref><ref name="RicliLuethiReinisch2015" /> However, most are inactive as agonists of the human TAAR1.<ref name="Gil-MartinsBarbosaBorges2025" /><ref name="GainetdinovHoenerBerry2018" /><ref name="SimmlerBuchyChaboz2016" /><ref name="RicliLuethiReinisch2015" /> The 2C drugs show very weak monoamine oxidase inhibition, including of monoamine oxidase A (MAO-A) and/or monoamine oxidase B (MAO-B).<ref name="Gil-MartinsBarbosaBorges2025" />

{| class="wikitable" style="font-size: 90%;" |+ {{Nowrap|2C drugs at serotonin 5-HT₁ and 5-HT₂ receptors}} |- ! rowspan="2" | Drug !! colspan="3" | 5-HT_1A !! 5-HT_1B !! colspan="3" | 5-HT_2A !! colspan="3" | 5-HT_2B !! colspan="3" | 5-HT_2C |- ! K_i (nM) || EC₅₀ (nM) || E_max (%) || K_i (nM) || K_i (nM) || EC₅₀ (nM) || E_max (%) || K_i (nM) || EC₅₀ (nM) || E_max (%) || K_i (nM) || EC₅₀ (nM) || E_max (%) |- | 2C-B || 130–311 || {{Abbr|ND|No data}} || {{Abbr|ND|No data}} || 104.4 || 6.9–27.6 || 1.89–80 || 5–99% || 13.5 || 75–130 || 52–89% || 43–89.5 || 0.031–0.264 || 104–116% |- | 2C-C || 190–740 || >10,000 || <25% || 252.9 || 5.47–13 || 9.27–200 || 49–102% || {{Abbr|ND|No data}} || 280 || 81% || 5.4–90 || 24.2 || 94% |- | 2C-D || 440–1,630 || >10,000 || <25% || {{Abbr|ND|No data}} || 23.9–32.4 || 43.5–350 || 41–125% || {{Abbr|ND|No data}} || 230 || 77% || 12.7–150 || 71.1 || 100% |- | 2C-E || 307.3–1,190 || >10,000 || <25% || {{Abbr|ND|No data}} || 4.50–43.9 || 2.5–110 || 40–125% || 25.1 || 190 || 66% || 5.4–104.1 || 0.233–18.0 || 98–106% |- | 2C-H || 70 || {{Abbr|ND|No data}} || {{Abbr|ND|No data}} || {{Abbr|ND|No data}} || 1,600 || 2,408–9,400 || 28–67% || {{Abbr|ND|No data}} || 6,200 || 46% || 4,100 || {{Abbr|ND|No data}} || {{Abbr|ND|No data}} |- | 2C-I || 180–970 || 4,900 || 102% || {{Abbr|ND|No data}} || 3.5–9.3 || 3.83–60 || 15–82% || {{Abbr|ND|No data}} || 150 || 70% || 10.2–40 || 2.8 || 79–100% |- | 2C-N || 2,200 || {{Abbr|ND|No data}} || {{Abbr|ND|No data}} || {{Abbr|ND|No data}} || 23.5 || 170 || 20–48% || {{Abbr|ND|No data}} || 730 || 74% || 370 || {{Abbr|ND|No data}} || 40–50% |- | 2C-P || 110 || {{Abbr|ND|No data}} || {{Abbr|ND|No data}} || {{Abbr|ND|No data}} || 8.1 || 90 || 63% || {{Abbr|ND|No data}} || 130 || 72% || 40 || {{Abbr|ND|No data}} || {{Abbr|ND|No data}} |- | 2C-T-1 || 1,035 || {{Abbr|ND|No data}} || {{Abbr|ND|No data}} || {{Abbr|ND|No data}} || 49 || 2.0 || 75% || {{Abbr|ND|No data}} || 57 || 58% || 347 || {{Abbr|ND|No data}} || {{Abbr|ND|No data}} |- | 2C-T-2 || 370–1,740 || 3,000 || 76% || 857.5 || 9–39.9 || 0.354–80 || 67–128% || 6 || 130 || 75% || 14.2–69 || 0.0233–3.8 || 87–107% |- | 2C-T-4 || 470–916 || {{Abbr|ND|No data}} || {{Abbr|ND|No data}} || {{Abbr|ND|No data}} || 27.9–54 || 5.5–220 || 56–87% || {{Abbr|ND|No data}} || 63–160 || 68–75% || 180–295 || {{Abbr|ND|No data}} || {{Abbr|ND|No data}} |- | 2C-T-7 || 520–878 || {{Abbr|ND|No data}} || {{Abbr|ND|No data}} || {{Abbr|ND|No data}} || 5.3–6.5 || 1.2–130 || 49–101% || {{Abbr|ND|No data}} || 52–350 || 45–75% || 39–54 || {{Abbr|ND|No data}} || {{Abbr|ND|No data}} |- class="sortbottom" | colspan="14" style="width: 1px; background-color:var(--background-color-notice-subtle,#eaecf0); color:inherit; text-align: center;" | '''Notes:''' The smaller the value, the more avidly the drug binds to or activates the site. '''Refs:''' <ref name="RicliLuethiReinisch2015" /><ref name="EshlemanForsterWolfrum2014" /><ref name="Ray2010" /><ref name="Gil-MartinsBarbosaBorges2025" /><ref name="RudinLuethiHoener2022">{{cite journal | vauthors = Rudin D, Luethi D, Hoener MC, Liechti ME | title=Structure-activity Relation of Halogenated 2,5-Dimethoxyamphetamines Compared to their α‑Desmethyl (2C) Analogues | journal=The FASEB Journal | volume=36 | issue=S1 | date=2022 | article-number=fasebj.2022.36.S1.R2121 | issn=0892-6638 | doi=10.1096/fasebj.2022.36.S1.R2121 | doi-access=free | url=https://www.researchgate.net/publication/360423277}}</ref><ref name="PottieCannaertStove2020">{{cite journal | vauthors = Pottie E, Cannaert A, Stove CP | title = In vitro structure-activity relationship determination of 30 psychedelic new psychoactive substances by means of β-arrestin 2 recruitment to the serotonin 2A receptor | journal = Arch Toxicol | volume = 94 | issue = 10 | pages = 3449–3460 | date = October 2020 | pmid = 32627074 | doi = 10.1007/s00204-020-02836-w | bibcode = 2020ArTox..94.3449P | hdl = 1854/LU-8687071 | url = | hdl-access = free }}</ref><ref name="LuethiTrachselHoener2018">{{cite journal | vauthors = Luethi D, Trachsel D, Hoener MC, Liechti ME | title = Monoamine receptor interaction profiles of 4-thio-substituted phenethylamines (2C-T drugs) | journal = Neuropharmacology | volume = 134 | issue = Pt A | pages = 141–148 | date = May 2018 | pmid = 28720478 | doi = 10.1016/j.neuropharm.2017.07.012 | url = https://edoc.unibas.ch/57358/1/20170920150712_59c2680084ec5.pdf}}</ref><ref name="HalberstadtLuethiHoener2023">{{cite journal | vauthors = Halberstadt AL, Luethi D, Hoener MC, Trachsel D, Brandt SD, Liechti ME | title = Use of the head-twitch response to investigate the structure-activity relationships of 4-thio-substituted 2,5-dimethoxyphenylalkylamines | journal = Psychopharmacology (Berl) | volume = 240 | issue = 1 | pages = 115–126 | date = January 2023 | pmid = 36477925 | pmc = 9816194 | doi = 10.1007/s00213-022-06279-2 | url = https://core.ac.uk/download/pdf/543784099.pdf}}</ref> |}

====Effects==== In accordance with their psychedelic effects in humans, the 2C drugs produce the head-twitch response and wet dog shakes, behavioral proxies of psychedelic effects, in rodents.<ref name="Gil-MartinsBarbosaBorges2025" /> At least some 2C drugs, such as 2C-D and 2C-E, produce hyperlocomotion at lower doses in rodents.<ref name="Gil-MartinsBarbosaBorges2025" /> All 2C drugs produce hypolocomotion at higher doses in rodents.<ref name="Gil-MartinsBarbosaBorges2025" /> 2C drugs, including 2C-C, 2C-D, 2C-E, and 2C-I, substitute partially to fully for psychedelics like DOM, DMT, and LSD and/or for the entactogen MDMA in rodent drug discrimination tests.<ref name="Gil-MartinsBarbosaBorges2025" /><ref name="EshlemanForsterWolfrum2014" /> However, none of the assessed 2C drugs substituted for dextromethamphetamine, suggesting that they lack amphetamine-type or stimulant-like effects.<ref name="Gil-MartinsBarbosaBorges2025" /><ref name="EshlemanForsterWolfrum2014" />

In contrast to most psychedelics, at least two assessed 2C drugs, 2C-C and 2C-P, have shown reinforcing effects in rodents, including conditioned place preference (CPP) and self-administration.<ref name="Gil-MartinsBarbosaBorges2025" /><ref name="KimMaHur2021" /> The mechanism by which these effects are mediated is unknown.<ref name="Gil-MartinsBarbosaBorges2025" /> However, it may be related to reduced expression of the dopamine transporter (DAT) and increased DAT phosphorylation, in turn resulting in increased extracellular dopamine levels in certain brain areas.<ref name="Gil-MartinsBarbosaBorges2025" /><ref name="KimMaHur2021">{{cite journal | vauthors = Kim YJ, Ma SX, Hur KH, Lee Y, Ko YH, Lee BR, Kim SK, Sung SJ, Kim KM, Kim HC, Lee SY, Jang CG | title = New designer phenethylamines 2C-C and 2C-P have abuse potential and induce neurotoxicity in rodents | journal = Arch Toxicol | volume = 95 | issue = 4 | pages = 1413–1429 | date = April 2021 | pmid = 33515270 | doi = 10.1007/s00204-021-02980-x | bibcode = 2021ArTox..95.1413K | url = }}</ref> These 2C drugs might have misuse potential in humans.<ref name="Gil-MartinsBarbosaBorges2025" /><ref name="KimMaHur2021" /> Similar reinforcing effects in animals have been observed for NBOMe analogues of 2C drugs, including 25B-NBOMe, 25D-NBOMe, 25E-NBOMe, 25H-NBOMe, and 25N-NBOMe.<ref name="Gil-MartinsBarbosaBorges2025" /><ref name="ZawilskaKacelaAdamowicz2020">{{cite journal | vauthors = Zawilska JB, Kacela M, Adamowicz P | title = NBOMes-Highly Potent and Toxic Alternatives of LSD | journal = Front Neurosci | volume = 14 | issue = | article-number = 78 | date = 2020 | pmid = 32174803 | pmc = 7054380 | doi = 10.3389/fnins.2020.00078 | doi-access = free | url = }}</ref><ref name="CustodioSaysonBotanas2020">{{Cite journal |last1=Custodio |first1=Raly James Perez |last2=Sayson |first2=Leandro Val |last3=Botanas |first3=Chrislean Jun |last4=Abiero |first4=Arvie |last5=You |first5=Kyung Yi |last6=Kim |first6=Mikyung |last7=Lee |first7=Hyun Jun |last8=Yoo |first8=Sung Yeun |last9=Lee |first9=Kun Won |last10=Lee |first10=Yong Sup |last11=Seo |first11=Joung-Wook |last12=Ryu |first12=In Soo |last13=Kim |first13=Hee Jin |last14=Cheong |first14=Jae Hoon |date=November 2020 |title=25B-NBOMe, a novel ''N''-2-methoxybenzyl-phenethylamine (NBOMe) derivative, may induce rewarding and reinforcing effects via a dopaminergic mechanism: Evidence of abuse potential |url=https://onlinelibrary.wiley.com/doi/10.1111/adb.12850 |journal=Addiction Biology |language=en |volume=25 |issue=6 |doi=10.1111/adb.12850 |issn=1355-6215 |pmid=31749223 |article-number=e12850|url-access=subscription }}</ref><ref name="SeoHurKo2019">{{cite journal | vauthors = Seo JY, Hur KH, Ko YH, Kim K, Lee BR, Kim YJ, Kim SK, Kim SE, Lee YS, Kim HC, Lee SY, Jang CG | title = A novel designer drug, 25N-NBOMe, exhibits abuse potential via the dopaminergic system in rodents | journal = Brain Res Bull | volume = 152 | issue = | pages = 19–26 | date = October 2019 | pmid = 31279579 | doi = 10.1016/j.brainresbull.2019.07.002 | url = }}</ref><ref name="JoJooYoun2022">{{cite journal | vauthors = Jo C, Joo H, Youn DH, Kim JM, Hong YK, Lim NY, Kim KS, Park SJ, Choi SO | title = Rewarding and Reinforcing Effects of 25H-NBOMe in Rodents | journal = Brain Sci | volume = 12 | issue = 11 | date = November 2022 | page = 1490 | pmid = 36358416 | pmc = 9688077 | doi = 10.3390/brainsci12111490 | doi-access = free | url = }}</ref><ref name="LeeHurHwang2023">{{cite journal | vauthors = Lee JG, Hur KH, Hwang SB, Lee S, Lee SY, Jang CG | title = Designer Drug, 25D-NBOMe, Has Reinforcing and Rewarding Effects through Change of a Dopaminergic Neurochemical System | journal = ACS Chem Neurosci | volume = 14 | issue = 15 | pages = 2658–2666 | date = August 2023 | pmid = 37463338 | doi = 10.1021/acschemneuro.3c00196 | url = }}</ref><ref name="KimKookMa2024">{{cite journal | vauthors = Kim YJ, Kook WA, Ma SX, Lee BR, Ko YH, Kim SK, Lee Y, Lee JG, Lee S, Kim KM, Lee SY, Jang CG | title = The novel psychoactive substance 25E-NBOMe induces reward-related behaviors via dopamine D1 receptor signaling in male rodents | journal = Arch Pharm Res | volume = 47 | issue = 4 | pages = 360–376 | date = April 2024 | pmid = 38551761 | doi = 10.1007/s12272-024-01491-4 | url = }}</ref>

Similarly to DOI, tolerance has been found to gradually develop to the head-twitch response induced by 2C-T-7 with chronic administration in rodents.<ref name="Gil-MartinsBarbosaBorges2025" />

Various 2C drugs show potent anti-inflammatory effects mediated by serotonin 5-HT_2A receptor activation.<ref name="FlanaganBillacLandry2021">{{cite journal | vauthors = Flanagan TW, Billac GB, Landry AN, Sebastian MN, Cormier SA, Nichols CD | title = Structure-Activity Relationship Analysis of Psychedelics in a Rat Model of Asthma Reveals the Anti-Inflammatory Pharmacophore | journal = ACS Pharmacol Transl Sci | volume = 4 | issue = 2 | pages = 488–502 | date = April 2021 | pmid = 33860179 | pmc = 8033619 | doi = 10.1021/acsptsci.0c00063 | url = https://www.researchgate.net/publication/360537036}}</ref> Among these include 2C-I, 2C-B, 2C-H, and 2C-iBu.<ref name="FlanaganBillacLandry2021" /><ref name="WO2020210823A1">{{cite patent | country = WO | number = 2020210823 | inventor = Nichols CD, Billac G, Nichols DE | status = published | title = Compounds and methods for treating inflammatory disorders | pubdate = 15 October 2020 | gdate = | fdate = 13 April 2020 | pridate = 13 April 2020 | assign1 = | assign2 = | url = https://patents.google.com/patent/WO2020210823A1/en }}</ref> Others, such as 2C-B-Fly and 2C-T-33, were less effective.<ref name="FlanaganBillacLandry2021" /> 2C-iBu has shown a greater separation between anti-inflammatory effects and psychedelic-like effects in animals than other 2C drugs and is being investigated for possible use as a pharmaceutical drug.<ref name="WO2020210823A1" /><ref name="Newvine2020">{{cite web | vauthors = Newvine C | title=Eleusis Draws on Research Into Psychedelics To Develop New Medicines for Inflammation | website=Lucid News - Psychedelics, Consciousness Technology, and the Future of Wellness | date=8 July 2020 | url=https://www.lucid.news/eleusis-research-on-psychedelics-develop-inflammation-medicines/ | access-date=16 February 2025}}</ref>

===Pharmacokinetics=== The 2C drugs are orally active.<ref name="DeanStellpflugBurnett2013" /> They are metabolized by ''O''-demethylation and deamination.<ref name="DeanStellpflugBurnett2013" /><ref name="TheobaldMaurer2007">{{cite journal | vauthors = Theobald DS, Maurer HH | title = Identification of monoamine oxidase and cytochrome P450 isoenzymes involved in the deamination of phenethylamine-derived designer drugs (2C-series) | journal = Biochem Pharmacol | volume = 73 | issue = 2 | pages = 287–297 | date = January 2007 | pmid = 17067556 | doi = 10.1016/j.bcp.2006.09.022 | url = }}</ref> This is mediated specifically by monoamine oxidase (MAO) enzymes MAO-A and MAO-B, whereas cytochrome P450 enzymes appear to metabolize only some 2C drugs and to have only a very small role.<ref name="TheobaldMaurer2007" />

==Chemistry== The 2C drugs, also known as 4-substituted 2,5-dimethoxyphenethylamines, are substituted phenethylamines and can be thought of as synthetic analogues of the naturally occurring phenethylamine psychedelic mescaline (3,4,5-trimethoxyphenethylamine).<ref name="AnilanmertYonarÖzdemir2018">{{cite book | last1=Anilanmert | first1=Beril | last2=Yonar | first2=Fatma Çavuş | last3=Özdemir | first3=Ali Acar | title=Chromatographic Techniques in the Forensic Analysis of Designer Drugs | chapter=2C Derivatives of Phenylethylamines and Their Analysis | publisher=CRC Press | publication-place=Boca Raton : Taylor & Francis/CRC Press, 2018. | series= Chromatographic science series | date=31 January 2018 | isbn=978-1-315-31317-7 | doi=10.1201/9781315313177-15 | url=https://www.taylorfrancis.com/books/9781315313160/chapters/10.1201/9781315313177-15 | access-date=14 November 2025 | pages=277–304}}</ref><ref name="PiHKAL" /><ref name="JacobShulgin1994" /><ref name="Shulgin2003" /><ref name="TrachselLehmannEnzensperger2013" /> They are the phenethylamine (2C) analogues of the amphetamine (α-methylphenethylamine) DOx drugs like DOM, DOB, and DOI as well as of the phenylisobutylamine (α-ethylphenethylamine) 4C drugs like Ariadne (4C-D) and 4C-B.<ref name="PiHKAL" /><ref name="JacobShulgin1994" /><ref name="Shulgin2003" /><ref name="TrachselLehmannEnzensperger2013" /> The ''N''-benzylphenethylamines such as 25I-NBOMe, 25B-NBOMe, and 25C-NBOMe are derivatives of the 2C drugs.<ref name="PoulieJensenHalberstadt2020" /><ref name="AnilanmertYonarÖzdemir2018" /><ref name="TrachselLehmannEnzensperger2013" /> Certain FLY drugs such as 2C-B-FLY are also 2C derivatives.<ref name="AnilanmertYonarÖzdemir2018" /><ref name="TrachselLehmannEnzensperger2013" /><ref name="ShulginManningDaley2011" />

===Syntheses=== The chemical syntheses of 2C drugs have been described.<ref name="PiHKAL" /><ref name="ShulginManningDaley2011" />

===Analysis=== The chemical analysis of 2C drugs has been described.<ref name="AnilanmertYonarÖzdemir2018" />

==History== {{See also|DOx#History}}

2,4,5-Trimethoxyphenethylamine (2,4,5-TMPEA; 2C-O), the 2C positional isomer of mescaline (3,4,5-trimethoxyphenethylamine), was first synthesized by Max Jansen and was reported to produce psychedelic effects similar to those of mescaline in 1931.<ref name="Shulgin1978">{{cite book | veditors = Iversen LL, Iversen SD, Snyder SH | last=Shulgin | first=Alexander T. | title=Stimulants | chapter=Psychotomimetic Drugs: Structure-Activity Relationships | publisher=Springer US | publication-place=Boston, MA | date=1978 | isbn=978-1-4757-0512-6 | doi=10.1007/978-1-4757-0510-2_6 | pages=243–333 | chapter-url=https://bitnest.netfirms.com/external/10.1007/978-1-4757-0510-2_6 | url=https://books.google.com/books?id=h0_uBwAAQBAJ&pg=PA261 }}</ref><ref name="Jansen1931">{{cite journal | last=Jansen | first=Max. P. J. M. | title=β-2: 4: 5-Trimethoxyphenylethylamine, an isomer of mescaline | journal=Recueil des Travaux Chimiques des Pays-Bas | volume=50 | issue=4 | date=1931 | issn=0165-0513 | doi=10.1002/recl.19310500403 | pages=291–312}}</ref> However, subsequent studies in the 1960s and 1970s suggested that 2,4,5-TMPEA may actually be inactive as a psychedelic in animals and humans.<ref name="Shulgin1978" />

2C-D was the first of the 2C drugs after 2C-O to be discovered.<ref name="ShulginManningDaley2011">{{cite book | last1=Shulgin | first1=A. | last2=Manning | first2=T. | last3=Daley | first3=P.F. | title=The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds | publisher=Transform Press | location=Berkeley | volume=1 | year=2011 | isbn=978-0-9630096-3-0 | url=https://books.google.com/books?id=68-huAAACAAJ | access-date=2 November 2024 }}</ref><ref name="StanridgeHowellGylys1976">{{cite journal | vauthors = Standridge RT, Howell HG, Gylys JA, Partyka RA, Shulgin AT | title = Phenylakylamines with potential psychotherapeutic utility. 1. 2-Amino-1-(2,5-dimethoxy-4-methylphenyl)butane | journal = J Med Chem | volume = 19 | issue = 12 | pages = 1400–1404 | date = December 1976 | pmid = 1003425 | doi = 10.1021/jm00234a010 | url = https://www.erowid.org/archive/rhodium/pdf/shulgin/shulgin.4c-dom.pdf | quote = The α-H homologue [2C-D (2a)] has been reported in animal avoidance tests16 to be less active than [DOM (2b)] and substantially stimulant in nature. In human evaluation17 the decrease in potency is confirmed, but the psychopharmacological profile is largely one of sensory enhancement. [...] 2,5-Dimethoxy-4-methylphenethylamine Hydrochloride (2a).23 [...] (23) B. T. Ho, L. W. Tansey, R. L. Bolster, R. An, W. M. McIsaac, and R T. Harris, J. Med. Chem., 13, 134 (1970). }}</ref><ref name="HoTanseyBalster1970">{{cite journal | vauthors = Ho BT, Tansey LW, Balster RL, An R, McIsaac WM, Harris RT | title = Amphetamine analogs. II. Methylated phenethylamines | journal = J Med Chem | volume = 13 | issue = 1 | pages = 134–135 | date = January 1970 | pmid = 5412084 | doi = 10.1021/jm00295a034 | url = }}</ref><ref name="HoHuang1970">{{cite journal | vauthors = Ho BT, Huang JT | title = Effects of mescaline and 2,5-dimethoxy-4-methylphenethylamine on sleeping time in mice | journal = J Pharm Pharmacol | volume = 22 | issue = 12 | pages = 949–951 | date = December 1970 | pmid = 4395524 | doi = 10.1111/j.2042-7158.1970.tb08483.x | url = }}</ref> It was synthesized and studied in animals by Beng T. Ho and colleagues at the Texas Research Institute of Mental Sciences and they published their findings in 1970.<ref name="ShulginManningDaley2011" /><ref name="StanridgeHowellGylys1976" /><ref name="HoTanseyBalster1970" /><ref name="HoHuang1970" /> Alexander Shulgin synthesized 2C-B and 2C-D in 1974 and discovered their psychedelic effects in self-experiments conducted in 1974 and 1975.<ref name="DeanStellpflugBurnett2013">{{cite journal | vauthors = Dean BV, Stellpflug SJ, Burnett AM, Engebretsen KM | title = 2C or not 2C: phenethylamine designer drug review | journal = J Med Toxicol | volume = 9 | issue = 2 | pages = 172–178 | date = June 2013 | pmid = 23494844 | pmc = 3657019 | doi = 10.1007/s13181-013-0295-x | url = | quote = In 1974, 4-bromo-2,5-dimethoxyphenethylamine (2C-B), the first of the 2Cs, was synthesized by Alexander Shulgin as he was exploring homologs from 2,5-dimethoxy-4-bromoamphetamine [3]. 2C-B was manufactured in the 1980s and early 1990s under the names Nexus, Erox, Performax, Toonies, Bromo, Spectrum, and Venus and marketed as MDMA’s replacement after MDMA became scheduled in the USA [6, 7]. 2C-B was initially intended for psychotherapy use due to its short 1-h duration of action [3]. Due to 2C-B’s significant gastrointestinal effects and lack of empathogenic effects as compared to MDMA, it rapidly fell out of favor for psychotherapy. In 1995, 2C-B was placed on Schedule I of the Controlled Substances Act by the Drug Enforcement Agency (DEA) [6, 7]. However, following the scheduling of 2C-B, other 2C analogues were made available by suppliers as legal alternatives [8]. }}</ref><ref name="PoulieJensenHalberstadt2020">{{cite journal | vauthors = Poulie CB, Jensen AA, Halberstadt AL, Kristensen JL | title = DARK Classics in Chemical Neuroscience: NBOMes | journal = ACS Chem Neurosci | volume = 11 | issue = 23 | pages = 3860–3869 | date = December 2020 | pmid = 31657895 | pmc = 9191638 | doi = 10.1021/acschemneuro.9b00528 | url = | quote = In 1974, Shulgin translated this strategy back to the phenethylamine family with the synthesis of 2,5-dimethoxy-4-bromophenethylamine (2C-B),19 which he found to be a strong hallucinogen in a series of self-experiments conducted during 1974 and 1975 (the drug was described as “beautifully effective”).20 During the late 1970s and early 1980s, 2,5-dimethoxy-4-methylphenethylamine (2C-D), another compound from this class, received considerable attention from psychiatrists as a psychotherapeutic adjunct, most notably Hanscarl Leuner, who worked with 2C-D extensively under the code name LE-25 and pioneered the concept of psychedelic therapy.21 However, 2C-B was emergency scheduled by the Drug Enforcement Administration (DEA) in 1994, due to its appearance on the recreational drug market as a replacement for 3,4-methyl enedioxy methamphetamine (MDMA) (which had been scheduled in 1985). }}</ref><ref name="ShulginManningDaley2011" /><ref name="StanridgeHowellGylys1976" /><ref name="ShulginCarter1975">{{cite journal | vauthors = Shulgin AT, Carter MF | title = Centrally active phenethylamines | journal = Psychopharmacol Commun | volume = 1 | issue = 1 | pages = 93–98 | date = 1975 | pmid = 1223994 | doi = | url = https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=74dec91996ceb113d47eb4e819d2a3e2283d4019 }}</ref><ref name="Shulgin1974–1978">{{Cite news |title=Acute Trials |url=https://isomerdesign.com/pihkal/notebooks/transcripts/p1/p1.175.pdf}}</ref> He published his findings in the scientific literature in 1975.<ref name="DeanStellpflugBurnett2013" /><ref name="PoulieJensenHalberstadt2020" /><ref name="ShulginManningDaley2011" /><ref name="StanridgeHowellGylys1976" /><ref name="ShulginCarter1975" /> However, Shulgin had previously tested sub-threshold doses of 2C-D in 1964 and 1965.<ref name="Shulgin1964–1965">{{Cite news |title=Subacute evaluation |url=https://isomerdesign.com/pihkal/notebooks/transcripts/p1/p1.94.pdf}}</ref> 2C-T was first described by Shulgin and David E. Nichols in 1976.<ref name="NicholsShulgin1976">{{cite journal | vauthors = Nichols DE, Shulgin AT | title = Sulfur Analogs of Psychotomimetic Amines | journal = J Pharm Sci | volume = 65 | issue = 10 | pages = 1554–1556 | date = October 1976 | pmid = 978423 | doi = 10.1002/jps.2600651040 | bibcode = 1976JPhmS..65.1554S | url = https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=ccfa49101fe0e3039bd68c03263d22ae033cd3a7| url-access = subscription }}</ref> 2C-I was first described by Shulgin and colleagues in 1977 and initial psychoactivity was reported by Shulgin in 1978.<ref name="Shulgin1978" /><ref name="BraunShulginBraun1977">{{cite journal | vauthors = Braun U, Shulgin AT, Braun G, Sargent T | title = Synthesis and body distribution of several iodine-131 labeled centrally acting drugs | journal = J Med Chem | volume = 20 | issue = 12 | pages = 1543–1546 | date = December 1977 | pmid = 592317 | doi = 10.1021/jm00222a001 | url = https://www.erowid.org/archive/rhodium/pdf/shulgin.iodinated.peas.pdf }}</ref> Shulgin also first synthesized 2C-E in 1977.<ref name="DariePraisler2021">{{cite journal | last1=Darie | first1=Iulia-Florentina | last2=Praisler | first2=Mirela | last3=Negoita | first3=Catalin | title= 2C-x and DOx hallucinogens: A systematic review| journal= Annals of the "Dunarea de Jos" University of Galati Fascicle II Mathematics Physics Theoretical Mechanics| volume=44 | issue=1 | date=12 November 2021 | issn=2668-7151 | doi=10.35219/ann-ugal-math-phys-mec.2021.1.07 | doi-access=free | pages=46–52 | url=https://www.gup.ugal.ro/ugaljournals/index.php/math/article/download/4925/4350 | access-date=26 January 2025}}</ref><ref name="Shulgin1980">{{cite book|author=Alexander Shulgin|author-link=Alexander Shulgin|title=Pharmacology Notes II (The Shulgin Lab Books)|publisher=Erowid|url=https://erowid.org/library/books_online/shulgin_labbooks/shulgin_pharmacology_notebook9_searchable.pdf|page=236|place=Lafayette, CA, USA|year=1980}}</ref> He reviewed several of these 2C drugs in a literature review in 1979.<ref name="Shulgin1979">{{cite journal | vauthors = Shulgin AT | title = Chemistry of phenethylamines related to mescaline | journal = J Psychedelic Drugs | volume = 11 | issue = 1–2 | pages = 41–52 | date = 1979 | pmid = 522167 | doi = 10.1080/02791072.1979.10472091 | url = https://bitnest.netfirms.com/external/10.1080/02791072.1979.10472091}}</ref> Subsequently, numerous other 2C drugs have been synthesized and characterized.<ref name="PiHKAL" /><ref name="JacobShulgin1994">{{cite journal | vauthors = Jacob P, Shulgin AT | title = Structure-activity relationships of the classic hallucinogens and their analogs | journal = NIDA Res Monogr | volume = 146 | issue = | pages = 74–91 | date = 1994 | pmid = 8742795 | doi = | url = https://archives.nida.nih.gov/sites/default/files/monograph146.pdf#page=79 | archive-url = https://web.archive.org/web/20230805004551/https://archives.nida.nih.gov/sites/default/files/monograph146.pdf#page=79 | url-status = dead | archive-date = August 5, 2023 }}</ref><ref name="ShulginManningDaley2011" /><ref name="DeanStellpflugBurnett2013" /><ref name="PoulieJensenHalberstadt2020" /> Shulgin comprehensively reviewed and described the 2C drugs in his 1991 book ''PiHKAL'' (''Phenethylamines I Have Known and Loved'').<ref name="PiHKAL" /><ref name="WillsErickson2012" /> He coined the term "2C", this term being an acronym for the two carbon atoms between the benzene ring and the amino group of the 2C drugs and a means to distinguish them from the three-carbon DOx drugs.<ref name="PiHKAL">{{CitePiHKAL}}</ref><ref name="DeanStellpflugBurnett2013" /><ref name="WillsErickson2012" />

2C-D was extensively studied by Hanscarl Leuner under the names DMM-PEA and LE-25 in psychedelic-assisted psychotherapy in Germany in the 1970s and 1980s.<ref name="PoulieJensenHalberstadt2020" /><ref name="Passie2024">{{cite journal | last=Passie | first=Torsten | title=A history of the European Medical Society for Psycholytic Therapy (EPT) 1964–1974 | journal=Drug Science, Policy and Law | volume=10 | date=2024 | article-number=20503245231221154 | issn=2050-3245 | doi=10.1177/20503245231221154 | doi-access=free | quote=Like Jan Bastiaans, the Dutch chair of psychiatry at Leiden University, Leuner retained his license to use hallucinogens until his retirement in 1985. Leuner continued to conduct research on psycholytic therapy. There were studies on ketamine (Bolle, 1985, 1988), on the short-acting phenethylamine DMM-PEA (2C-D) (Schlichting, 1989, 1991), on the anal experience theme in psycholysis (Adler, 1981), and on results of other patients undergoing psycholysis (Schulz-Wittner, 1989). In Czechoslovakia and in England, psycholytic treatments were still carried out at some centers until the mid-1970s.}}</ref><ref name="Passie2022">{{cite book | last=Passie | first=Torsten | chapter=History of the Use of Hallucinogens in Psychiatric Treatment | pages = 95–118 | editor1-last=Grob | editor1-first=Charles S. | editor2-last=Grigsby | editor2-first=Jim | title=Handbook of Medical Hallucinogens | publisher=Guilford Publications | date=7 November 2022 | isbn=978-1-4625-5189-7 | chapter-url=https://books.google.com/books?id=r46ZEAAAQBAJ&pg=PA95 | quote = Also in the early 1950s, German psychiatrist Hanscarl Leuner (1984) developed guided affective imagery, a daydream technique used in psychotherapy. Concluding that small doses of hallucinogens may intensify imagery and induce regression and catharsis, Leuner (1959) began to use lowdose LSD with his psychotherapy patients. [...] During the 1960s, due to a continuous process of refinement, psycholytic therapists arrived at what might be considered today as a fully developed method (cf. Abramson, 1967; Grof, 1980b; Leuner, 1981). [...] Psycholytic therapy underwent a number of modifications during its active years. Some European therapists experimented with [...] the mescaline derivative 2-CD (2,5-dimethoxy-4-methylphenethylamine; Schlichting, 1989). [...] Leuner, H. (1981). Halluzinogene. Bern, Germany: Huber. [...] Schlichting, M. (1989). Psychotrope Eigenschaften des Phenäthylamins DMM-PEA (2,5-dimethoxy-4-methyl-phenathylamin). Unpublished doctoral thesis, Göttingen University, Göttingen, Germany.}}</ref><ref name="Leuner1981">{{cite book | last=Leuner | first=Hanscarl | title=Halluzinogene: psychische Grenzzustände in Forschung und Psychotherapie | trans-title=Hallucinogens: Altered Psychological States in Research and Psychotherapy | publisher=Huber | date=1981 | isbn=978-3-456-80933-5 | url=https://books.google.com/books?id=KwnEswEACAAJ | language=de}}</ref><ref name="Schlichting1989">{{cite thesis | author = Michael Schlichting | title = Psychotrope Eigenschaften des Phenäthylamins DMM-PEA (2,5-dimethoxy-4-methyl-phenathylamin) | trans-title = Psychotropic Properties of the Phenethylamine DMM-PEA (2,5-dimethoxy-4-methyl-phenethylamine) | publisher = Göttingen University | location = Göttingen, Germany | url = }}</ref> It was also informally studied by Darrell Lemaire as a potential "smart drug" in the 1970s and 1980s.<ref name="Erowid-Lemaire">{{cite web | title=Erowid Darrell Lemaire Vault | website=erowid.org | url=https://erowid.org/culture/characters/lemaire_darrell/lemaire_darrell.shtml | access-date=14 November 2025}}</ref><ref name="Morris2016-S01E06">{{cite episode | credits = Morris H | date = 7 December 2016 | title = The Lazy Lizard School of Hedonism | series = Hamilton's Pharmacopeia | season = 1 | number = 6 | url = https://vimeo.com/546752807| publisher = Vice Media | network = Viceland}}</ref><ref name="Nez2010">{{cite book | author = Hosteen Nez (Darrell Lemaire) | chapter = Notes About Psychoactive Compounds | pages = 201–207 | editor1-last = Targ | editor1-first = Russell | editor2-last = Radin | editor2-first = Dean | title = Radiant Minds: Scientists Explore the Dimensions of Consciousness | publisher = Millay | date = 2010 | isbn = 978-0-615-29633-3 | url = https://books.google.com/books?id=bF-jcQAACAAJ | chapter-url = https://erowid.org/culture/characters/lemaire_darrell/lemaire_darrell_article1.pdf}}</ref><ref name="LazarNez1990">{{citation | author1 = Lazar (Darrell Lemaire) | author2 = Hosteen Nez | title = Certain Exotic Transmitters as Smart Pills or Compounds that Increase the Capacity for Mental Work in Humans: A Story About LAZAR as Told by Hosteen Nez | edition = 2 | date = 1990 | url = https://erowid.org/chemicals/2cd/2cd_smartpills1.pdf | archive-url = https://web.archive.org/web/20010709231503/http://www.erowid.org/chemicals/2cd/2cd_smartpills1.shtml | archive-date = 9 July 2001}}</ref> He additionally developed the TWEETIO drugs such as 2CD-5-ETO via structural modification of the 2Cs.<ref name="Erowid-Lemaire" /><ref name="Morris2016-S01E06" /><ref name="Nez2010" /><ref name="LazarNez1990" /><ref name="Shulgin2003">{{cite book | vauthors = Shulgin AT | chapter=Basic Pharmacology and Effects | pages=67–137 | veditors = Laing RR | title=Hallucinogens: A Forensic Drug Handbook | publisher=Elsevier Science | series=Forensic Drug Handbook Series | year=2003 | isbn=978-0-12-433951-4 | url=https://books.google.com/books?id=l1DrqgobbcwC | chapter-url=https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=6bb3a7499da8e9852b39cd4db16891147c83f5c6}}</ref><ref name="JacobShulgin1994" /> 2C-B was legitimately marketed and sold as an over-the-counter sexual enhancer under brand names like Erox in several European countries such as Germany in the 1980s and early 1990s.<ref name="DOJ2006" /><ref name="AnilanmertYonarÖzdemir2018" /><ref name="Caudevilla-GálligoRibaVentura2012">{{cite journal | vauthors = Caudevilla-Gálligo F, Riba J, Ventura M, González D, Farré M, Barbanoj MJ, Bouso JC | title = 4-Bromo-2,5-dimethoxyphenethylamine (2C-B): presence in the recreational drug market in Spain, pattern of use and subjective effects | journal = J Psychopharmacol | volume = 26 | issue = 7 | pages = 1026–1035 | date = July 2012 | pmid = 22234927 | doi = 10.1177/0269881111431752 | url = | quote = 4-Bromo-2,5-dimethoxyphenethylamine (2C-B, Nexus, Afro) is one of these synthetic drugs. At the chemical level, 2C-B is structurally related to mescaline and was first synthesized in the mid-1970s (Shulgin and Carter, 1975). It gained certain popularity as a legal substitute for MDMA after its prohibition in 1985 (Bouso et al., 2008). In some European countries 2C-B was legally sold as an aphrodisiac under the brand names Nexus, Erox and Performax in stores specialized in psychoactive products, the so-called smart shops (US Department of Justice, 2001).}}</ref><ref name="Johnson2018">{{cite book | last=Johnson | first=Cody | title=Magic Medicine: A Trip Through the Intoxicating History and Modern-Day Use of Psychedelic Plants and Substances | publisher=Fair Winds Press | date=5 June 2018 | isbn=978-1-63159-428-1 | url=https://books.google.com/books?id=N-NfDwAAQBAJ&pg=PA25 | quote=During its legal heyday, a German company even marketed it as an aphrodisiac called Erox. Dutch “smart shops” also sold 2C-B as an Ecstasy-like legal high under the name “Nexus.”}}</ref> It was sold in adult stores, smart shops, and some nightclubs.<ref name="DOJ2006" /><ref name="Caudevilla-GálligoRibaVentura2012" />

2C-B was first encountered as a novel designer drug in the United States in 1979.<ref name="DOJ2006">{{cite web | title=Information Bulletin 2C-B (Nexus) Reappears on the Club Drug Scene | website=Department of Justice | date=1 January 2006 | url=https://www.justice.gov/archive/ndic/pubs0/665/index.htm | access-date=14 November 2025}}</ref> It gained popularity as a recreational drug and MDMA (ecstasy) alternative in the mid-1980s.<ref name="DeanStellpflugBurnett2013" /><ref name="WillsErickson2012" /><ref name="AnilanmertYonarÖzdemir2018" /> The drug became a controlled substance in the United States in 1994 or 1995.<ref name="DeanStellpflugBurnett2013" /><ref name="WillsErickson2012">{{cite book | vauthors = Wills B, Erickson T | chapter = Psychoactive Phenethylamine, Piperazine, and Pyrrolidinophenone Derivatives | editor-last=Barceloux | editor-first=Donald G. | title=Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants | publisher=Wiley | date=9 March 2012 | isbn=978-0-471-72760-6 | doi=10.1002/9781118105955.ch10 | pages=156–192 | quote=DOSE EFFECT: Anecdotal data suggests that recreational doses of 2C-B range from 4—30 mg with lower doses (4—10 mg) producing entactogenic effects, whereas high doses (10— 20 mg) cause psychedelic and sympathomimetic effects.}}</ref><ref name="AnilanmertYonarÖzdemir2018" /> It has been said to be the most popular of the 2C drugs in terms of recreational use.<ref name="WillsErickson2012" /><ref name="AnilanmertYonarÖzdemir2018" /> Numerous other 2C drugs besides 2C-B have also since been made controlled substances.<ref name="AnilanmertYonarÖzdemir2018" />

==Society and culture== ===Legal status=== ====Canada==== As of October 12, 2016, the 2C-''x'' family of substituted phenethylamines are controlled substances (Schedule III) in Canada.<ref>{{Cite web |title=Regulations Amending the Food and Drug Regulations (Part J — 2C-phenethylamines) |url=http://gazette.gc.ca/rp-pr/p2/2016/2016-05-04/html/sor-dors72-eng.php |work=Canada Gazette |volume=150 |issue=9 |date=April 15, 2016 |access-date=August 28, 2016}}</ref><ref name="CDSA">{{cite web | title=Controlled Drugs and Substances Act | website=Department of Justice Canada | url=https://laws-lois.justice.gc.ca/eng/acts/c-38.8/FullText.html | access-date=19 January 2026}}</ref>

==List of 2C drugs== {{Sticky}} {| class="wikitable sticky-header" |- ! Name ! style="width:10em"| R3 ! style="width:10em"| R4 ! Structure ! CAS # |- | 2C-B | H | Br | 115px|class=skin-invert-image | 66142–81–2 |- | 2C-Bn | H | CH₂C₆H₅ | 115px|class=skin-invert-image | ? |- | 2C-Bu | H | CH₂CH₂CH₂CH₃ | 115px|class=skin-invert-image | 2888537-44-6 |- | 2C-C | H | Cl | 115px|class=skin-invert-image | 88441–14–9 |- | 2C-C-3 <ref>{{cite journal | vauthors = Takahashi M, Nagashima M, Suzuki J, Seto T, Yasuda I, Yoshida T | year = 2009 | title = Creation and application of psychoactive designer drugs data library using liquid chromatography with photodiode array spectrophotometry detector and gas chromatography–mass spectrometry | url = | journal = Talanta | volume = 77 | issue = 4| pages = 1245–1272 | doi = 10.1016/j.talanta.2008.07.062 | pmid = 19084633 }}</ref> | Cl | Cl | 115px|class=skin-invert-image | ? |- | 2C-CN | H | C≡N | 115px|class=skin-invert-image | 88441–07–0 |- | 2C-D | H | CH₃ | 115px|class=skin-invert-image | 24333–19–5 |- | 2C-E | H | CH₂CH₃ | 115px|class=skin-invert-image | 71539–34–9 |- | 2C-EF | H | CH₂CH₂F | 115px|class=skin-invert-image | 1222814–77–8 |- | 2C-F | H | F | 115px|class=skin-invert-image | 207740–15–6 |- | 2C-G (2C-G-0) | CH₃ | CH₃ | 115px|class=skin-invert-image | 207740–18–9 |- | 2C-G-1 | colspan=2 | CH₂ | 80px|class=skin-invert-image | 2888537-47-9 |- | 2C-G-2 | colspan=2 | (CH₂)₂ | 80px|class=skin-invert-image | 2888537-48-0 |- | 2C-G-3 | colspan=2 | (CH₂)₃ | 115px|class=skin-invert-image | 207740–19–0 |- | 2C-G-4 | colspan=2 | (CH₂)₄ | 115px|class=skin-invert-image | 952006–59–6 |- | 2C-G-5 | colspan=2 | (CH₂)₅ | 80px|class=skin-invert-image | 207740–20–3 |- | 2C-G-6 | colspan=2 | (CH₂)₆ | 80px|class=skin-invert-image | 2888537-49-1 |- | 2C-G-N | colspan=2 | (CH)₄ | 115px|class=skin-invert-image | 207740–21–4 |- | 2C-H | H | H | 115px|class=skin-invert-image | 3600–86–0 |- | 2C-I | H | I | 115px|class=skin-invert-image | 69587–11–7 |- | 2C-iBu (2C-iB) | H | iBu | 115px|class=skin-invert-image | ? |- | 2C-iP | H | CH(CH₃)₂ | 115px|class=skin-invert-image | 1498978–47–4 |- | 2C-tBu | H | C(CH₃)₃ | 115px|class=skin-invert-image | ? |- | 2C-CP | H | C₃H₅ | 115px|class=skin-invert-image | 2888537–46–8 |- | 2C-CB | H | C₄H₇ | 115px|class=skin-invert-image | ? |- | 2C-CPe<ref>{{cite journal | vauthors = Varty GB, Canal CE, Mueller TA, Hartsel JA, Tyagi R, Avery K, Morgan ME, Reichelt AC, Pathare P, Stang E, Palfreyman MG, Nivorozhkin A | title = Synthesis and Structure-Activity Relationships of 2,5-Dimethoxy-4-Substituted Phenethylamines and the Discovery of CYB210010: A Potent, Orally Bioavailable and Long-Acting Serotonin 5-HT₂ Receptor Agonist | journal = Journal of Medicinal Chemistry | volume = 67 | issue = 8 | pages = 6144–6188 | date = April 2024 | pmid = 38593423 | doi = 10.1021/acs.jmedchem.3c01961 }}</ref> | H | C₅H₉ | 115px|class=skin-invert-image | ? |- | 2C-CPM | H | C₄H₇ | 115px|class=skin-invert-image | ? |- | 2C-N | H | NO₂ | 115px|class=skin-invert-image | 261789–00–8 |- | 2C-NH2 | H | NH₂ | 115px|class=skin-invert-image | 168699–66–9 |- | 2C-PYR | H | Pyrrolidine | 115px|class=skin-invert-image | ? |- | 2C-PIP <ref>{{cite patent | title = Phenethylamine compounds, compositions, and methods of use. | url = https://patents.google.com/patent/WO2024089226A1/ | inventor = Nivorozhkin A, Hartsel JA, Canal CE, Salituro FG, Mueller TA, Greene BJ, Belser A, Palfreyman M | country = WO | number = 2024/089226 | pubdate = 2 May 2024 | assign = Cybin IRL Ltd. }}</ref> | H | Piperidine | 115px|class=skin-invert-image | ? |- | 2C-O (2C-O-1) | H | OCH₃ | 115px|class=skin-invert-image | 15394–83–9 |- | 2C-O-4 | H | OCH(CH₃)₂ | 115px|class=skin-invert-image | 952006–65–4 |- | 2C-O-22 | H | OCH₂CF₃ | 115px|class=skin-invert-image | ? |- | 2C-MOM <ref>{{cite journal | vauthors = Leth-Petersen S, Petersen IN, Jensen AA, Bundgaard C, Bæk M, Kehler J, Kristensen JL | year = 2016| title = 5-HT2A/5-HT2C receptor pharmacology and intrinsic clearance of N-benzylphenethylamines modified at the primary site of metabolism | url = | journal = ACS Chem. Neurosci. | volume = 7 | issue = 11| pages = 1614–1619 | doi = 10.1021/acschemneuro.6b00265 | pmid = 27564969}}</ref> | H | CH₂OCH₃ | 115px|class=skin-invert-image | ? |- | 2C-P | H | CH₂CH₂CH₃ | 115px|class=skin-invert-image | 207740–22–5 |- | 2C-Ph (2C-BI-1) | H | C₆H₅ | 115px|class=skin-invert-image | ? |- | 2C-Se | H | SeCH₃ | 115px|class=skin-invert-image | 1189246–68–1 |- | 2C-Se-TFM | H | SeCF₃ | 115px|class=skin-invert-image | ? |- | 2C-Te | H | TeCH₃ | 115px|class=skin-invert-image | ? |- | 2C-Te-TFM | H | TeCF₃ | 115px|class=skin-invert-image | ? |- | 2C-T | H | SCH₃ | 115px|class=skin-invert-image | 61638–09–3 |- | 2C-T-2 | H | SCH₂CH₃ | 115px|class=skin-invert-image | 207740–24–7 |- | 2C-T-3<ref name="Shulgin's Sulfur Symphony - Part II">{{cite web|title=Shulgin's Sulfur Symphony – Part I|url=http://countyourculture.com/2011/01/15/shulgins-sulfur-symphony-part-i/|website=countyourculture|date=15 January 2011|access-date=22 October 2017|archive-url=https://web.archive.org/web/20190919063901/http://countyourculture.com/2011/01/15/shulgins-sulfur-symphony-part-i/|archive-date=19 September 2019|url-status=dead}}</ref> | H | SCH₂C(=CH₂)CH₃ | 115px|class=skin-invert-image | 648957–40–8 |- | 2C-T-4 | H | SCH(CH₃)₂ | 115px|class=skin-invert-image | 207740–25–8 |- | 2C-T-5<ref name="Shulgin's Sulfur Symphony - Part II"/> | H | | 115px|class=skin-invert-image | 1187859-38-6 |- | 2C-T-6<ref name="Shulgin's Sulfur Symphony - Part II"/> | H | SC₆H₅ | 115px|class=skin-invert-image | ? |- | 2C-T-7 | H | S(CH₂)₂CH₃ | 115px|class=skin-invert-image | 207740–26–9 |- | 2C-T-8 | H | SCH₂CH(CH₂)₂ | 115px|class=skin-invert-image | 207740–27–0 |- | 2C-T-9<ref name="Shulgin's Sulfur Symphony - Part II"/> | H | SC(CH₃)₃ | 115px|class=skin-invert-image | 207740–28–1 |- | 2C-T-10<ref name="Shulgin's Sulfur Symphony - Part II"/> | H | | 115px|class=skin-invert-image | ? |- | 2C-T-11<ref name="Shulgin's Sulfur Symphony - Part II"/> | H | SC₆H₄-''p''-Br | 115px|class=skin-invert-image | ? |- | 2C-T-12<ref name="Shulgin's Sulfur Symphony - Part II"/> | H | | 115px|class=skin-invert-image | ? |- | 2C-T-13 | H | S(CH₂)₂OCH₃ | 115px|class=skin-invert-image | 207740–30–5 |- | 2C-T-14<ref name="Shulgin's Sulfur Symphony - Part II"/> | H | S(CH₂)₂SCH₃ | 115px|class=skin-invert-image | ? |- | 2C-T-15 | H | SCH(CH₂)₂ | 115px|class=skin-invert-image | 952006-95-0 |- | 2C-T-16<ref>{{cite journal |author=Daniel Trachsel |year=2003 |title=Synthesis of novel (phenylalkyl)amines for the investigation of structure-activity relationships. Part 2. 4-Thio-substituted [2-(2,5-dimethoxyphenyl)ethyl]amines (=2,5-dimethoxybenzeneethanamines) |journal=Helvetica Chimica Acta |volume=86 |issue=7 |pages=2610–2619 |doi=10.1002/hlca.200390210}}</ref> | H | SCH₂CH=CH₂ | 120px|class=skin-invert-image | 648957–42–0 |- | 2C-T-17 | H | SCH(CH₃)CH₂CH₃ | 115px|class=skin-invert-image | 207740–32–7 |- | 2C-T-18<ref name="Shulgin's Sulfur Symphony - Part II" /> | H | | 115px|class=skin-invert-image | ? |- | 2C-T-19 | H | SCH₂CH₂CH₂CH₃ | 115px|class=skin-invert-image | 732244-33-6 |- | 2C-T-21 | H | S(CH₂)₂F | 115px|class=skin-invert-image | 207740–33–8 |- | 2C-T-21.5<ref name="Shulgin's Sulfur Symphony - Part II" /> | H | S(CH₂)CHF₂ | 115px|class=skin-invert-image | 648957–46–4 |- | 2C-T-22<ref name="Shulgin's Sulfur Symphony - Part II" /> | H | S(CH₂)CF₃ | 115px|class=skin-invert-image | 648957–48–6 |- | 2C-T-23<ref name="Shulgin's Sulfur Symphony - Part II" /> | H | | 115px|class=skin-invert-image | ? |- | 2C-T-24<ref name="Shulgin's Sulfur Symphony - Part II" /> | H | | 115px|class=skin-invert-image | ? |- | 2C-T-25<ref name="Shulgin's Sulfur Symphony - Part II" /> | H | SCH₂CH(CH₃)₂ | 115px|class=skin-invert-image | 648957-50-0 |- | 2C-T-27<ref name="Shulgin's Sulfur Symphony - Part II" /> | H | SCH₂C₆H₅ | 115px|class=skin-invert-image | 648957–52–2 |- | 2C-T-28<ref name="Shulgin's Sulfur Symphony - Part II" /> | H | S(CH₂)₃F | 115px|class=skin-invert-image | 648957–54–4 |- | 2C-T-29 (2C-T-PARGY) | H | S(CH₂)C≡CH | 115px|class=skin-invert-image | ? |- | 2C-T-30<ref name="Shulgin's Sulfur Symphony - Part II" /> | H | S(CH₂)₄F | 115px|class=skin-invert-image | 648957-56-6 |- | 2C-T-31<ref name="Shulgin's Sulfur Symphony - Part II" /> | H | SCH₂C₆H₄-''p''-CF₃ | 115px|class=skin-invert-image | ? |- | 2C-T-32<ref name="Shulgin's Sulfur Symphony - Part II" /> | H | SCH₂C₆F₅ | 115px|class=skin-invert-image | ? |- | 2C-T-33<ref name="Shulgin's Sulfur Symphony - Part II" /> | H | SCH₂C₆H₄-''m''-OCH₃ | 115px|class=skin-invert-image | ? |- | 2C-T-34 (2C-T-FM) | H | SCFH₂ | 115px|class=skin-invert-image | ? |- | 2C-T-35 (2C-T-DFM) | H | SCF₂H | 115px|class=skin-invert-image | ? |- | 2C-T-36 (2C-T-TFM; CYB210010;<br />CYB2108)<ref>{{cite journal | vauthors = Varty GB, Canal CE, Mueller TA, Hartsel JA, Tyagi R, Avery K, Morgan ME, Reichelt AC, Pathare P, Stang E, Palfreyman MG, Nivorozhkin A | date = Apr 2024 | title = Synthesis and Structure-Activity Relationships of 2,5-Dimethoxy-4-Substituted Phenethylamines and the Discovery of CYB210010: A Potent, Orally Bioavailable and Long-Acting Serotonin 5-HT2 Receptor Agonist | url = | journal = J Med Chem | volume = 67 | issue = 8| pages = 6144–6188 | doi = 10.1021/acs.jmedchem.3c01961 | pmid = 38593423 }}</ref> | H | SCF₃ | 115px|class=skin-invert-image | 2762567-99-5 |- | CYB2108D (deuterated 2C-T-36;<br />see HLP005 (CYB005))<ref name="PubChem">{{cite web | title=2-[2,5-Bis(trideuteriomethoxy)-4-(trifluoromethylsulfanyl)phenyl]ethanamine | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/168072138 | access-date=2 April 2026}}</ref><ref name="US12122741B2">{{cite web | title=Therapeutic phenethylamine compositions and methods of use | website=Google Patents | date=18 August 2021 | url=https://patents.google.com/patent/US12122741B2/ | access-date=10 November 2024}}</ref> | H | SCF₃ | 115px|class=skin-invert-image | ? |- | 2C-T-CH2CN | H | S(CH₂)C≡N | 115px|class=skin-invert-image | ? |- | 2C-T-pent-4-ynyl | H | S(CH₂)₃C≡CH | 115px|class=skin-invert-image | ? |- | 2C-T-TFM-sulfone | H | SO₂CF₃ | 115px|class=skin-invert-image | ? |- | 2C-T-DFP | H | SCH₂CH₂CF₂H | 115px|class=skin-invert-image | ? |- | 2C-T-TFP | H | SCH₂CH₂CF₃ | 115px|class=skin-invert-image | ? |- | 2C-DFM <ref name="TrachselLehmannEnzensperger2013" />{{rp|770}} | H | CHF₂ | 115px|class=skin-invert-image | ? |- | 2C-TFM | H | CF₃ | 115px|class=skin-invert-image | 159277–08–4 |- | 2C-TFE | H | CH₂CF₃ | 115px|class=skin-invert-image | ? |- | 2C-PFE | H | CF₂CF₃ | 115px|class=skin-invert-image | ? |- | 2C-PFS | H | SF₅ | 115px|class=skin-invert-image | ? |- | 2C-YN | H | C≡CH | 115px|class=skin-invert-image | 752982–24–4 |- | 2C-V | H | CH=CH₂ | 115px|class=skin-invert-image | 2888537-57-1 |- | 2C-AL<ref>Patentscope. [https://patentscope.wipo.int/search/docs2/pct/WO2022006186/pdf/Z6QRYQjRUoLeRiOeDWcMFqiVKf3MMTkWXfeRv-Yhpxk Kruegel AC. Phenalkylamines and Methods of Treating Mood Disorders. Patent WO 2022/006186]. Retrieved 2025-05-12</ref> | H | CH₂CH=CH₂ | 115px|class=skin-invert-image | 2756686-02-7 |- | 2C-1MV<ref>{{cite web | title=PiHKAL·info | website=Isomer Design | date=12 June 2025 | url=https://isomerdesign.com/pihkal/explore/10312 | access-date=26 May 2026}}</ref> | H | 1-Methylvinyl | 115px|class=skin-invert-image | ? |- | 2C-MAL<ref>{{cite web | title=PiHKAL·info | website=Isomer Design | date=12 June 2025 | url=https://isomerdesign.com/pihkal/explore/7206 | access-date=26 May 2026}}</ref> | H | Methallyl | 115px|class=skin-invert-image | ? |}

==Related compounds== {{See also|DOx (psychedelics)|25-NB|FLY (psychedelics)|TWEETIO (psychedelics)|BOx (psychedelics)|HOT-x (psychedelics)}}

{{Sticky}} {| class="wikitable sticky-header" |- ! Name ! Chemical name ! Structure ! CAS # ! Ref |- | 2C-DB (6-bromo-2C-B) | 2,5-Dimethoxy-4,6-dibromophenethylamine | 115px|class=skin-invert-image | ? | |- | 25H-NMe (''N''-methyl-2C-H) | 2,5-Dimethoxy-''N''-methylphenethylamine | 105px|class=skin-invert-image | 3489-95-0 | |- | ''N''-Methyl-2C-B (2C-B-M, 2C-BM) | ''N''-Methyl-4-bromo-2,5-dimethoxyphenethylamine | 115px|class=skin-invert-image | 155639-22-8 | |- | ''N''-Ethyl-2C-B (2C-B-E, 2C-BE) | ''N''-Ethyl-4-bromo-2,5-dimethoxyphenethylamine | 115px|class=skin-invert-image | 155639-24-0 | |- | 2C-B-OH (''N''-hydroxy-2C-B) | 4-Bromo-2,5-dimethoxy-''N''-hydroxyphenethylamine | 115px|class=skin-invert-image | ? | <ref name="Leth-PetersenGabel-JensenGillings2016">{{cite journal | vauthors = Leth-Petersen S, Gabel-Jensen C, Gillings N, Lehel S, Hansen HD, Knudsen GM, Kristensen JL | title = Metabolic Fate of Hallucinogenic NBOMes | journal = Chem Res Toxicol | volume = 29 | issue = 1 | pages = 96–100 | date = January 2016 | pmid = 26669514 | doi = 10.1021/acs.chemrestox.5b00450 | url = | quote = [Supporting Information] [...] Entry 35: N-(4-bromo-2,5-dimethoxyphenethyl)hydroxylamine [...]| doi-access = free }}</ref> |- | 25B-NB (''N''-benzyl-2C-B) | ''N''-Benzyl-4-bromo-2,5-dimethoxyphenethylamine | 115px|class=skin-invert-image | 155639-26-2 | |- | ''N''-Methyl-2C-I | ''N''-Methyl-4-iodo-2,5-dimethoxyphenethylamine | 115px|class=skin-invert-image | ? | |- | β-Methyl-2C-B (BMB) | 4-Bromo-2,5-dimethoxy-β-methylphenylethylamine | 115px|class=skin-invert-image | 52432-70-9 | |- | β-Keto-2C-B (βk-2C-B) | 4-Bromo-2,5-dimethoxy-β-ketophenylethylamine | 115px|class=skin-invert-image | 807631-09-0 | |- | β-Keto-2C-I (βk-2C-I) | 4-Iodo-2,5-dimethoxy-β-ketophenylethylamine | 115px|class=skin-invert-image | ? | |- | 2C-B-AN (2C-B-aminonitrile) | 4-Bromo-''N''-(α′-cyanobenzyl)-2,5-dimethoxyphenethylamine | 115px|class=skin-invert-image | ? | |- | 25D-NM-NDEAOP (25D-NM-NDEPA) | ''N''-Methyl-''N''-(3-diethylamino-3-oxopropyl)-2,5-dimethoxy-4-methylphenethylamine | 115px|class=skin-invert-image | ? | |- | 25B-NAcPip | ''N''-(Piperidin-1-ylcarbonylmethyl)-4-bromo-2,5-dimethoxyphenethylamine | 115px|class=skin-invert-image | ? | |- | XOB (ASR-6001) | ''N''-[(4-Phenylbutoxy)hexyl]-4-bromo-2,5-dimethoxyphenethylamine | 115px|class=skin-invert-image | ? | <ref name="DenommeHernandezBock2024">{{cite journal | vauthors = Denomme N, Hernandez CC, Bock HA, Ohana RF, Bakshi S, Sherwood AM, McCorvy JD, Daley PF, Callaway WB, Hull JM, Alt A, Isom LL, Cozzi NV | title = N-(4-Bromo-2,5-Dimethoxyphenethyl)-6-(4-Phenylbutoxy)Hexan-1-Amine (XOB): A Novel Phenylalkylamine Antagonist of Serotonin 2A Receptors and Voltage-Gated Sodium Channels | journal = Mol Pharmacol | volume = 106 | issue = 2 | pages = 92–106 | date = July 2024 | pmid = 38821630 | doi = 10.1124/molpharm.123.000837 | pmc = 11254453 | url = https://shulginresearch.net/wp-content/uploads/2024/07/XOB-a-novel-phenylalkylamine-antagonist-of-5-HT2A-receptors-and-VGSCs.-Denomme.-Mol.-Pharmacol.-106-92-106-2024.pdf}}</ref> |- | TCB-2 (2CBCB, 2C-BCB) | [3-Bromo-2,5-dimethoxy-bicyclo[4.2.0]octa-1,3,5-trien-7-yl]methanamine | 115px|class=skin-invert-image | ? | |- | 2CB-Ind | (5-Bromo-4,7-dimethoxy-2,3-dihydro-1''H''-inden-1-yl)methanamine | 115px|class=skin-invert-image | 912342-23-5 | |- | ZC-B (2C-B-AZET) | 3-(4-Bromo-2,5-dimethoxyphenyl)azetidine | 115px|class=skin-invert-image | 2641630-65-9 | |- | 2C-B-PYR | 3-(4-Bromo-2,5-dimethoxyphenyl)pyrrolidine | 115px|class=skin-invert-image | ? | |- | 2C-B-3PIP | 3-(4-Bromo-2,5-dimethoxyphenyl)piperidine | 115px|class=skin-invert-image | ? | |- | LPH-5 ((''S'')-2C-TFM-3PIP) | (''S'')-3-(2,5-Dimethoxy-4-(trifluoromethyl)phenyl)piperidine | 115px|class=skin-invert-image | 2641630-97-7 | |- | DEMPDHPCA-2C-D ("compound 45") | 1-Methyl-3-(1-oxo-1-diethylaminomethyl)-5-(2,5-dimethoxy-4-methylphenyl)-3,6-dihydro-2''H''-pyridine | 115px|class=skin-invert-image | ? | <ref name="Nichols1973">{{cite thesis | vauthors = Nichols DE | title = Potential Psychotomimetics: Bromomethoxyamphetamines and Structural Congeners of Lysergic Acid | date = May 1973 | publisher = University of Iowa | pages = 23 | oclc = 1194694085 | url = https://bitnest.netfirms.com/external/Theses/Nichols1973#page=32}}</ref> |- | DOM-CR (DOM-THIQ, 2C-D-CR) | 5,8-Dimethoxy-7-methyl-1,2,3,4-tetrahydroisoquinoline | 115px|class=skin-invert-image | ? | |- | DOB-CR (DOB-THIQ, 2C-B-CR) | 5,8-Dimethoxy-7-bromo-1,2,3,4-tetrahydroisoquinoline | 115px|class=skin-invert-image | 183429-24-5 | |- | ''N''-Methyl-DOM-CR (Beatrice-CR, ''N''-methyl-2C-D-CR) | 2,7-Dimethyl-5,8-dimethoxy-1,2,3,4-tetrahydroisoquinoline | 115px|class=skin-invert-image | 228997-46-4 | |- | 2C-B-morpholine (2C-B-MOR) | 2-(4-Bromo-2,5-dimethoxyphenyl)morpholine | 115px|class=skin-invert-image | 807631-07-8 | <ref>{{cite web | title=2C-B-morpholine | website=Isomer Design | date=1 April 2025 | url=https://isomerdesign.com/pihkal/explore/1075 | access-date=1 June 2025}}</ref><ref name="GlennonBondarevKhorana2004">{{cite journal | vauthors = Glennon RA, Bondarev ML, Khorana N, Young R, May JA, Hellberg MR, McLaughlin MA, Sharif NA | title = Beta-oxygenated analogues of the 5-HT2A serotonin receptor agonist 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane | journal = J Med Chem | volume = 47 | issue = 24 | pages = 6034–6041 | date = November 2004 | pmid = 15537358 | doi = 10.1021/jm040082s | url = https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=db12f5229bdabb798f5f0682120f9c7c5d20f479 | archive-url = https://web.archive.org/web/20240523143815/https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=db12f5229bdabb798f5f0682120f9c7c5d20f479 | url-status = dead | archive-date = 2024-05-23 }}</ref> |- | 2C-B-aminorex (2C-B-AR) | 5-(4-Bromo-2,5-dimethoxyphenyl)-4,5-dihydro-1,3-oxazol-2-amine | 115px|class=skin-invert-image | ? | |- | 2C-B-PP | 1-(2,5-Dimethoxy-4-bromophenyl)piperazine | 115px|class=skin-invert-image | 100939-87-5 | |- | 2C-B-BZP | 1-[(4-Bromo-2,5-dimethoxyphenyl)methyl]piperazine | 115px|class=skin-invert-image | 1094424-37 | |- | 2C-B-5-hemiFLY-α6 (BNAP) | 8-Bromo-6-methoxy-2a,3,4,5-tetrahydro-2H-naphtho[1,8-bc]furan-4-amine | 115px|class=skin-invert-image | ? | |- | 2CB7 (2C-B-5-hemiFLY-β7) | (5-Bromo-7-methoxy-3-oxatricyclo[6.4.1.0^4,13]trideca-4,6,8(13)-trien-9-yl)methanamine | 115px|class=skin-invert-image | ? | |- | 2-OH-2C-B (2-DM-2C-B; B-2-HMPEA) | 4-Bromo-2-hydroxy-5-methoxyphenethylamine | 115px|class=skin-invert-image | ? | |- | 2C-2-TOM (2-thio-2C-D) | 5-Methoxy-4-methyl-2-methylthiophenethylamine | 115px|class=skin-invert-image | ? | <ref name="PiHKAL" /><ref name="JacobShulgin1983">{{cite journal | vauthors = Jacob P, Shulgin AT | title = Sulfur analogues of psychotomimetic agents. 2. Analogues of (2,5-dimethoxy-4-methylphenyl)-and (2,5-dimethoxy-4-ethylphenyl)isopropylamine | journal = J Med Chem | volume = 26 | issue = 5 | pages = 746–752 | date = May 1983 | pmid = 6842515 | doi = 10.1021/jm00359a021 | url = }}</ref> |- | 2C-5-TOM (5-thio-2C-D) | 2-Methoxy-4-methyl-5-methylthiophenethylamine | 115px|class=skin-invert-image | ? | <ref name="PiHKAL" /><ref name="JacobShulgin1983" /> |- | 2C-2-TOET (2-thio-2C-E) | 4-Ethyl-5-methoxy-2-methylthiophenethylamine | 115px|class=skin-invert-image | ? | <ref name="PiHKAL" /><ref name="JacobShulgin1983" /> |- | 2C-5-TOET (5-thio-2C-E) | 4-Ethyl-2-methoxy-5-methylthiophenethylamine | 115px|class=skin-invert-image | ? | <ref name="PiHKAL" /><ref name="JacobShulgin1983" /> |- | 2T-2CTFM-3PIP (2-thio-LPH-5) | 3-(5-Methoxy-2-methylthio-4-(trifluoromethyl)phenyl)piperidine | 115px|class=skin-invert-image | ? | <ref name="US20210137908">{{cite patent | title = 5-HT2A Agonists for Use in Treatment of Depression. | number = 2021/0137908 | url = https://patentimages.storage.googleapis.com/a2/12/19/8424e3822cbe82/US20210137908A1.pdf | inventor = Kristensen JL, Jensen AA, Märcher-Rørsted E | country = US | assign1 = Lophora ApS | pubdate = 13 May 2021 | postscript = . }}</ref> |- |}

==See also== * 25-NB, BOx, HOT-x, scaline, 3C, DOx, 4C, Ψ-PEA, FLY, TWEETIO * List of miscellaneous serotonin 5-HT_2A receptor agonists * ''The Shulgin Index'' * Substituted amphetamines * Substituted methoxyphenethylamine * Substituted methylenedioxyphenethylamines * Substituted phenethylamines * Substituted tryptamines

== References == {{Reflist}}

==External links== * [https://tripsitter.com/psychedelics/2cx/ 2C Psychedelics - Tripsitter] * [https://pageviews.wmcloud.org/massviews/?platform=all-access&agent=user&source=category&range=latest-365&subjectpage=0&subcategories=0&sort=views&direction=1&view=list&target=https://en.wikipedia.org/wiki/Category:2C_(psychedelics) 2C (psychedelics) - Wikipedia Massviews Analysis (Wikipedia Page Views of Individual 2Cs)]

{{Psychedelics}} {{Serotonin receptor modulators}} {{TAAR modulators}} {{Phenethylamines}} {{Chemical classes of psychoactive drugs}}

{{DEFAULTSORT:2c (Psychedelics)}}

Category:2C (psychedelics) Category:Alexander Shulgin Category:Chemical classes of psychoactive drugs