2C (2C-x) is a general name for the family ofpsychedelicphenethylamines containingmethoxy groups on the 2 and 5positions of abenzene ring.[1][2][3] Most of these compounds also carrylipophilic substituents at the 4 position, usually resulting in more potent and moremetabolically stable and longer acting compounds.[4]
Most of the early 2C drugs were developed byAlexander Shulgin in the 1970s and 1980s and were reviewed in his 1991 bookPiHKAL (Phenethylamines I Have Known And Loved).[3][5][6]2C-B is the most popular of the 2C drugs.[3]
The 2C drugs areorally active, are used at oral doses of 6 to 150 mg depending on the drug, and havedurations of 3 to 48 hours depending on the drug.[1][7][6][8] However, many have doses in the range of 10 to 60 mg and durations in the range of 4 to 12 hours.[1] The 2C drugs producepsychedelic effects, such asperceptual enhancement,psychedelic visuals, andeuphoria.[1][6][9][3] Some, such as2C-B, have also been reported to produce someentactogen-like effects, but findings in this area appear to be mixed.[9][3][10][11]
| Compound | Chemical name | Dose | Duration | |
|---|---|---|---|---|
| 2C-AL | 4-Allyl-2,5-dimethoxyphenethylamine | Unknown | Unknown | |
| 2C-B | 4-Bromo-2,5-dimethoxyphenethylamine | 10–35 mg | 4–8 hours | |
| 2C-Bu | 4-Butyl-2,5-dimethoxyphenethylamine | Unknown | Unknown | |
| 2C-C | 4-Chloro-2,5-dimethoxyphenethylamine | 20–40 mg | 4–8 hours | |
| 2C-CN | 4-Cyano-2,5-dimethoxyphenethylamine | >22 mg | Unknown | |
| 2C-CP | 4-Cyclopropyl-2,5-dimethoxyphenethylamine | 15–35 mg | 3–6 hours | |
| 2C-D (2C-M) | 4-Methyl-2,5-dimethoxyphenethylamine | 20–60 mg | 4–6 hours | |
| 2C-E | 4-Ethyl-2,5-dimethoxyphenethylamine | 10–25 mg | 6–12 hours | |
| 2C-EF | 4-Fluoroethyl-2,5-dimethoxyphenethylamine | 10–25 mg | Unknown | |
| 2C-F | 4-Fluoro-2,5-dimethoxyphenethylamine | ≥250 mg | Unknown | |
| 2C-G (2C-G-0) | 3,4-Dimethyl-2,5-dimethoxyphenethylamine | 20–35 mg | 18–30 hours | |
| 2C-G-3 | 3,4-Trimethylene-2,5-dimethoxyphenethylamine | 16–25 mg | 12–24 hours | |
| 2C-G-5 | 3,4-Norbornyl-2,5-dimethoxyphenethylamine | 10–16 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 mg | 6–10 hours | |
| 2C-iBu | 4-Isobutyl-2,5-dimethoxyphenethylamine | ≥5 mg | ~20 hours | |
| 2C-iP | 4-Isopropyl-2,5-dimethoxyphenethylamine | 8–25 mg | 8–12 hours | |
| 2C-N | 4-Nitro-2,5-dimethoxyphenethylamine | 100–150 mg | 4–6 hours | |
| 2C-O (2,4,5-TMPEA) | 4-Methoxy-2,5-dimethoxyphenethylamine | Unknown | Unknown | |
| 2C-O-4 | 4-Isopropoxy-2,5-dimethoxyphenethylamine | >60 mg | Unknown | |
| 2C-O-22 | 4-(2,2,2-Trifluoroethoxy)-2,5-dimethoxyphenethylamine | ≥57 mg | Unknown | |
| 2C-P | 4-Propyl-2,5-dimethoxyphenethylamine | 6–10 mg | 5–16 hours | |
| 2C-Ph (2C-BI-1) | 4-Phenyl-2,5-dimethoxyphenethylamine | Unknown | Unknown | |
| 2C-Se | 4-Methylseleno-2,5-dimethoxyphenethylamine | ~100 mg | 6–8 hours | |
| 2C-T (2C-T-1) | 4-Methylthio-2,5-dimethoxyphenethylamine | 60–100 mg | 3–5 hours | |
| 2C-T-2 | 4-Ethylthio-2,5-dimethoxyphenethylamine | 12–25 mg | 6–8 hours | |
| 2C-T-3 (2C-T-20) | 4-Methallylthio-2,5-dimethoxyphenethylamine | 15–40 mg | 8–14 hours | |
| 2C-T-4 | 4-Isopropylthio-2,5-dimethoxyphenethylamine | 8–20 mg | 12–18 hours | |
| 2C-T-7 | 4-Propylthio-2,5-dimethoxyphenethylamine | 10–30 mg | 8–15 hours | |
| 2C-T-8 | 4-Cyclopropylmethylthio-2,5-dimethoxyphenethylamine | 30–50 mg | 10–15 hours | |
| 2C-T-9 | 4-tert-Butylthio-2,5-dimethoxyphenethylamine | 60–100 mg | 12–18 hours | |
| 2C-T-13 | 4-(2-Methoxyethylthio)-2,5-dimethoxyphenethylamine | 25–40 mg | 6–8 hours | |
| 2C-T-15 | 4-Cyclopropylthio-2,5-dimethoxyphenethylamine | >30 mg | Several hours | |
| 2C-T-16 | 4-Allylthio-2,5-dimethoxyphenethylamine | 10–25 mg | 4–6 hours | |
| 2C-T-17 | 4-sec-Butylthio-2,5-dimethoxyphenethylamine | 60–100 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 mg | 7–10 hours | |
| 2C-T-21.5 | 4-(2,2-Difluoroethylthio)-2,5-dimethoxyphenethylamine | 12–30 mg | 8–14 hours | |
| 2C-T-22 | 4-(2,2,2-Trifluoroethylthio)-2,5-dimethoxyphenethylamine | >10 mg | ~6 hours | |
| 2C-T-25 | 4-Isobutylthio-2,5-dimethoxyphenethylamine | >30 mg | Unknown | |
| 2C-T-27 | 4-Benzylthio-2,5-dimethoxyphenethylamine | ≥80 mg | Unknown | |
| 2C-T-28 | 4-(3-Fluoropropylthio)-2,5-dimethoxyphenethylamine | 8–20 mg | 8–10 hours | |
| 2C-T-30 | 4-(4-Fluorobutylthio)-2,5-dimethoxyphenethylamine | >8 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 mg | Unknown | |
| 2C-Te | 4-Methyltelluro-2,5-dimethoxyphenethylamine | Unknown | Unknown | |
| 2C-TFE | 4-(2,2,2-Trifluoroethyl)-2,5-dimethoxyphenethylamine | 5–15 mg | 12–24 hours | |
| 2C-TFM | 4-Trifluoromethyl-2,5-dimethoxyphenethylamine | 3–6 mg | ≥5–10 hours | |
| 2C-V | 4-Ethenyl-2,5-dimethoxyphenethylamine | ~25 mg | ~5 hours | |
| 2C-YN | 4-Ethynyl-2,5-dimethoxyphenethylamine | ~50 mg | ~2 hours | |
| Refs:[1][7][3][8][6][2][12][13][14][4] | ||||
The 2C drugs aremetabolized by themonoamine oxidase (MAO)enzymes, including bothMAO-A andMAO-B.[1][15] As a result, they may be potentiated bymonoamine oxidase inhibitors (MAOIs), such asphenelzine,tranylcypromine,moclobemide, andselegiline.[1][15][16] This may lead tooverdose and serioustoxicity.[1][15][16] There is no known reversal agent for 2C drugs, and medical management for overdose involves treatment of symptoms until toxicity within the body subsides.[17]
The 2C drugs act asagonists of theserotonin5-HT2 receptors, including of the serotonin5-HT2A,5-HT2B, and5-HT2C receptors.[18][19][20][21][22] They arepartial agonists of the serotonin 5-HT2A receptor.[18][19] Most of the 2C drugs have much loweraffinity for the serotonin5-HT1A receptor than for the serotonin 5-HT2A receptor.[18][19][20][21] Most of the 2C drugs have also shown about 5- to 15-fold higher affinity for the serotonin 5-HT2A receptor over the serotonin 5-HT2C receptor and about 15- to 100-fold higher affinity for the serotonin 5-HT2A receptor over the serotonin 5-HT1A receptor.[19] Thepsychedelic effects of the 2C drugs are thought to be mediated specifically by activation of the serotonin 5-HT2A receptor.[18][20][22]
Unlike many other phenethylamines, 2C drugs, including2C-C,2C-D,2C-E,2C-I, and2C-T-2 among others, are inactive asmonoamine releasing agents andreuptake inhibitors.[18][23][20][19][22] Most of the 2C drugs are agonists of the rat and mousetrace amine-associated receptor 1 (TAAR1).[18][24][25][19] However, most are inactive as agonists of the human TAAR1.[18][24][25][19] The 2C drugs show very weakmonoamine oxidase inhibition, including ofmonoamine oxidase A (MAO-A) and/ormonoamine oxidase B (MAO-B).[18]
| Drug | 5-HT1A | 5-HT1B | 5-HT2A | 5-HT2B | 5-HT2C | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Ki (nM) | EC50 (nM) | Emax (%) | Ki (nM) | Ki (nM) | EC50 (nM) | Emax (%) | Ki (nM) | EC50 (nM) | Emax (%) | Ki (nM) | EC50 (nM) | Emax (%) | |
| 2C-B | 130–311 | ND | ND | 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% | ND | 280 | 81% | 5.4–90 | 24.2 | 94% |
| 2C-D | 440–1,630 | >10,000 | <25% | ND | 23.9–32.4 | 43.5–350 | 41–125% | ND | 230 | 77% | 12.7–150 | 71.1 | 100% |
| 2C-E | 307.3–1,190 | >10,000 | <25% | ND | 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 | ND | ND | ND | 1,600 | 2,408–9,400 | 28–67% | ND | 6,200 | 46% | 4,100 | ND | ND |
| 2C-I | 180–970 | 4,900 | 102% | ND | 3.5–9.3 | 3.83–60 | 15–82% | ND | 150 | 70% | 10.2–40 | 2.8 | 79–100% |
| 2C-N | 2,200 | ND | ND | ND | 23.5 | 170 | 20–48% | ND | 730 | 74% | 370 | ND | 40–50% |
| 2C-P | 110 | ND | ND | ND | 8.1 | 90 | 63% | ND | 130 | 72% | 40 | ND | ND |
| 2C-T-1 | 1,035 | ND | ND | ND | 49 | 2.0 | 75% | ND | 57 | 58% | 347 | ND | ND |
| 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 | ND | ND | ND | 27.9–54 | 5.5–220 | 56–87% | ND | 63–160 | 68–75% | 180–295 | ND | ND |
| 2C-T-7 | 520–878 | ND | ND | ND | 5.3–6.5 | 1.2–130 | 49–101% | ND | 52–350 | 45–75% | 39–54 | ND | ND |
| Notes: The smaller the value, the more avidly the drug binds to or activates the site.Refs:[19][20][21][18][26][27][28][29] | |||||||||||||
In accordance with their psychedelic effects in humans, the 2C drugs produce thehead-twitch response andwet dog shakes, behavioral proxies of psychedelic effects, in rodents.[18] At least some 2C drugs, such as2C-D and2C-E, producehyperlocomotion at lower doses in rodents.[18] All 2C drugs producehypolocomotion at higher doses in rodents.[18] 2C drugs, including 2C-C, 2C-D, 2C-E, and 2C-I, substitute partially to fully for psychedelics likeDOM,DMT, andLSD and/or for theentactogenMDMA in rodentdrug discrimination tests.[18][20] However, none of the assessed 2C drugs substituted fordextromethamphetamine, suggesting that they lackamphetamine-type orstimulant-like effects.[18][20]
In contrast to most psychedelics, at least two assessed 2C drugs, 2C-C and2C-P, have shownreinforcing effects in rodents, includingconditioned place preference (CPP) andself-administration.[18][30] Themechanism by which these effects are mediated is unknown.[18] However, it may be related to reducedexpression of thedopamine transporter (DAT) and increased DATphosphorylation, in turn resulting in increasedextracellulardopamine levels in certain brain areas.[18][30] These 2C drugs might havemisuse potential in humans.[18][30] Similar reinforcing effects in animals have been observed forNBOMeanalogues of 2C drugs, including25B-NBOMe,25D-NBOMe,25E-NBOMe,25H-NBOMe, and25N-NBOMe.[18][31][32][33][34][35][36]
Similarly toDOI,tolerance has been found to gradually develop to the head-twitch response induced by2C-T-7 with chronic administration in rodents.[18]
Various 2C drugs show potentanti-inflammatory effects mediated by serotonin 5-HT2A receptor activation.[37] Among these include2C-I,2C-B,2C-H, and2C-iBu.[37][38] Others, such as2C-B-Fly and2C-T-33, were less effective.[37] 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 apharmaceutical drug.[38][39]
The 2C drugs areorally active.[1] They aremetabolized byO-demethylation anddeamination.[1][15] This is mediated specifically bymonoamine oxidase (MAO)enzymesMAO-A andMAO-B, whereascytochrome P450 enzymes appear to metabolize only some 2C drugs and to have only a very small role.[15]
The 2C drugs, also known as 4-substituted 2,5-dimethoxyphenethylamines, aresubstituted phenethylamines and can be thought of assyntheticanalogues of thenaturally occurring phenethylaminepsychedelicmescaline (3,4,5-trimethoxyphenethylamine).[5][6][7][40][4] They are the phenethylamine (2C)analogues of theamphetamine (α-methylphenethylamine)DOx drugs likeDOM,DOB, andDOI as well as of thephenylisobutylamine (α-ethylphenethylamine)4C drugs likeAriadne (4C-D) and4C-B.[6][7][40][4] TheN-benzylphenethylamines such as25I-NBOMe,25B-NBOMe, and25C-NBOMe arederivatives of the 2C drugs.[41][5][4] CertainFLY drugs such as2C-B-FLY are also 2C derivatives.[5][4][2]
Thechemical syntheses of 2C drugs have been described.[6][2]
Thechemical analysis of 2C drugs has been described.[5]
2,4,5-Trimethoxyphenethylamine (2,4,5-TMPEA; 2C-O), the 2Cpositional isomer ofmescaline (3,4,5-trimethoxyphenethylamine), was firstsynthesized by Max Jansen and was reported to produce psychedelic effects similar to those of mescaline in 1931.[42][43] 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.[42]
2C-D was the first of the 2C drugs after 2C-O to be discovered.[2][44][45][46] 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.[2][44][45][46]Alexander Shulgin synthesized2C-B and 2C-D in 1974 and discovered their psychedelic effects inself-experiments conducted in 1974 and 1975.[1][41][2][44][47][48] He published his findings in thescientific literature in 1975.[1][41][2][44][47] However, Shulgin had previously tested sub-threshold doses of 2C-D in 1964 and 1965.[49]2C-T was first described by Shulgin andDavid E. Nichols in 1976.[50]2C-I was first described by Shulgin and colleagues in 1977 and initial psychoactivity was reported by Shulgin in 1978.[42][51] Shulgin also first synthesized2C-E in 1977.[52][53] He reviewed several of these 2C drugs in aliterature review in 1979.[54] Subsequently, numerous other 2C drugs have been synthesized and characterized.[6][7][2][1][41] Shulgin comprehensively reviewed and described the 2C drugs in his 1991 bookPiHKAL (Phenethylamines I Have Known and Loved).[6][3] He coined the term "2C", this term being anacronym for the two carbon atoms between thebenzenering and theamino group of the 2C drugs and a means to distinguish them from the three-carbonDOx drugs.[6][1][3]
2C-D was extensively studied byHanscarl Leuner under the names DMM-PEA and LE-25 inpsychedelic-assisted psychotherapy inGermany in the 1970s and 1980s.[41][55][56][57][58] It was also informally studied byDarrell Lemaire as a potential "smart drug" in the 1970s and 1980s.[59][60][61][62] He additionally developed theTWEETIO drugs such as2CD-5-ETO viastructural modification of the 2Cs.[59][60][61][62][40][7] 2C-B was legitimately marketed and sold as anover-the-countersexual enhancer under brand names like Erox in severalEuropean countries such asGermany in the 1980s and early 1990s.[63][5][64][65] It was sold inadult stores,smart shops, and somenightclubs.[63][64]
2C-B was first encountered as a noveldesigner drug in theUnited States in 1979.[63] It gained popularity as arecreational drug andMDMA (ecstasy) alternative in the mid-1980s.[1][3][5] The drug became acontrolled substance in the United States in 1994 or 1995.[1][3][5] It has been said to be the most popular of the 2C drugs in terms of recreational use.[3][5] Numerous other 2C drugs besides 2C-B have also since been made controlled substances.[5]
As of October 12, 2016, the 2C-x family of substituted phenethylamines is a controlled substance (Schedule III) in Canada.[66]
| Name | R3 | R4 | Structure | CAS # |
|---|---|---|---|---|
| 2C-B | H | Br |  | 66142–81–2 |
| 2C-Bn | H | CH2C6H5 |  | |
| 2C-Bu | H | CH2CH2CH2CH3 |  | |
| 2C-C | H | Cl |  | 88441–14–9 |
| 2C-C-3[67] | Cl | Cl |  | |
| 2C-CN | H | C≡N |  | 88441–07–0 |
| 2C-D | H | CH3 |  | 24333–19–5 |
| 2C-E | H | CH2CH3 |  | 71539–34–9 |
| 2C-EF | H | CH2CH2F |  | 1222814–77–8 |
| 2C-F | H | F |  | 207740–15–6 |
| 2C-G (2C-G-0) | CH3 | CH3 |  | 207740–18–9 |
| 2C-G-1 | CH2 |  | ||
| 2C-G-2 | (CH2)2 |  | ||
| 2C-G-3 | (CH2)3 |  | 207740–19–0 | |
| 2C-G-4 | (CH2)4 |  | 952006–59–6 | |
| 2C-G-5 | (CH2)5 |  | 207740–20–3 | |
| 2C-G-6 | (CH2)6 |  | ||
| 2C-G-N | (CH)4 |  | 207740–21–4 | |
| 2C-H | H | H |  | 3600–86–0 |
| 2C-I | H | I |  | 69587–11–7 |
| 2C-iBu | H | iBu |  | |
| 2C-iP | H | CH(CH3)2 |  | 1498978–47–4 |
| 2C-tBu | H | C(CH3)3 |  | |
| 2C-CP | H | C3H5 |  | 2888537–46–8 |
| 2C-CB | H | C4H7 |  | |
| 2C-CPE[68] | H | C5H9 |  | |
| 2C-CPM | H | C4H7 |  | |
| 2C-N | H | NO2 |  | 261789–00–8 |
| 2C-NH2 | H | NH2 |  | 168699–66–9 |
| 2C-PYR | H | Pyrrolidine |  | |
| 2C-PIP[69] | H | Piperidine |  | |
| 2C-O | H | OCH3 |  | 15394–83–9 |
| 2C-O-4 | H | OCH(CH3)2 |  | 952006–65–4 |
| 2C-MOM[70] | H | CH2OCH3 |  | |
| 2C-P | H | CH2CH2CH3 |  | 207740–22–5 |
| 2C-Ph (2C-BI-1) | H | C6H5 |  | |
| 2C-Se | H | SeCH3 |  | 1189246–68–1 |
| 2C-Se-TFM | H | SeCF3 |  | |
| 2C-Te | H | TeCH3 |  | ? |
| 2C-T | H | SCH3 |  | 61638–09–3 |
| 2C-T-2 | H | SCH2CH3 |  | 207740–24–7 |
| 2C-T-3[71] | H | SCH2C(=CH2)CH3 |  | 648957–40–8 |
| 2C-T-4 | H | SCH(CH3)2 |  | 207740–25–8 |
| 2C-T-5[71] | H |  | ||
| 2C-T-6[71] | H | SC6H5 |  | |
| 2C-T-7 | H | S(CH2)2CH3 |  | 207740–26–9 |
| 2C-T-8 | H | SCH2CH(CH2)2 |  | 207740–27–0 |
| 2C-T-9[71] | H | SC(CH3)3 |  | 207740–28–1 |
| 2C-T-10[71] | H |  | ||
| 2C-T-11[71] | H | SC6H4-p-Br |  | |
| 2C-T-12[71] | H |  | ||
| 2C-T-13 | H | S(CH2)2OCH3 |  | 207740–30–5 |
| 2C-T-14[71] | H | S(CH2)2SCH3 |  | |
| 2C-T-15 | H | SCH(CH2)2 |  | |
| 2C-T-16[72] | H | SCH2CH=CH2 |  | 648957–42–0 |
| 2C-T-17 | H | SCH(CH3)CH2CH3 |  | 207740–32–7 |
| 2C-T-18[71] | H |  | ||
| 2C-T-19 | H | SCH2CH2CH2CH3 |  | |
| 2C-T-21 | H | S(CH2)2F |  | 207740–33–8 |
| 2C-T-21.5[71] | H | S(CH2)CHF2 |  | 648957–46–4 |
| 2C-T-22[71] | H | S(CH2)CF3 |  | 648957–48–6 |
| 2C-T-23[71] | H |  | ||
| 2C-T-24[71] | H |  | ||
| 2C-T-25[71] | H | SCH2CH(CH3)2 |  | |
| 2C-T-27[71] | H | SCH2C6H5 |  | 648957–52–2 |
| 2C-T-28[71] | H | S(CH2)3F |  | 648957–54–4 |
| 2C-T-29 (2C-T-PARGY) | H | S(CH2)C≡CH |  | |
| 2C-T-30[71] | H | S(CH2)4F |  | |
| 2C-T-31[71] | H | SCH2C6H4-p-CF3 |  | |
| 2C-T-32[71] | H | SCH2C6F5 |  | |
| 2C-T-33[71] | H | SCH2C6H4-m-OCH3 |  | |
| 2C-T-34 (2C-T-FM) | H | SCFH2 | ||
| 2C-T-35 (2C-T-DFM) | H | SCF2H |  | |
| CYB210010 (2C-T-36 / 2C-T-TFM)[73] | H | SCF3 |  | |
| 2C-T-CH2CN | H | S(CH2)C≡N |  | |
| 2C-T-pent-4-ynyl | H | S(CH2)3C≡CH |  | |
| 2C-T-TFM-sulfone | H | SO2CF3 |  | |
| 2C-T-DFP | H | SCH2CH2CF2H |  | |
| 2C-T-TFP | H | SCH2CH2CF3 |  | |
| 2C-DFM[4]: 770 | H | CHF2 |  | |
| 2C-TFM | H | CF3 |  | 159277–08–4 |
| 2C-TFE | H | CH2CF3 |  | |
| 2C-PFE | H | CF2CF3 |  | |
| 2C-PFS | H | SF5 |  | |
| 2C-YN | H | C≡CH |  | 752982–24–4 |
| 2C-V | H | CH=CH2 |  | |
| 2C-AL[74] | H | CH2CH=CH2 |  | |
| 2C-1MV | H | 1-Methylvinyl | ||
| 2C-MAL | H | Methallyl | ||
| Name | Chemical name | Structure | Ref |
|---|---|---|---|
| 2C-DB | 2,5-Dimethoxy-4,6-dibromophenethylamine |  | |
| N-Methyl-2C-B | N-Methyl-4-bromo-2,5-dimethoxyphenethylamine |  | |
| N-Ethyl-2C-B | N-Ethyl-4-bromo-2,5-dimethoxyphenethylamine |  | |
| 2C-B-OH (N-hydroxy-2C-B) | 4-Bromo-2,5-dimethoxy-N-hydroxyphenethylamine |  | [75] |
| 25B-NB (N-benzyl-2C-B) | N-Benzyl-4-bromo-2,5-dimethoxyphenethylamine |  | |
| N-Methyl-2C-I | N-Methyl-4-iodo-2,5-dimethoxyphenethylamine |  | |
| β-Methyl-2C-B | 4-Bromo-2,5-dimethoxy-β-methylphenylethylamine |  | |
| β-Keto-2C-B (βk-2C-B) | 4-Bromo-2,5-dimethoxy-β-ketophenylethylamine |  | |
| 2C-B-AN (2C-B-aminonitrile) | 4-Bromo-N-(α′-cyanobenzyl)-2,5-dimethoxyphenethylamine |  | |
| 25D-NM-NDEAOP (25D-NM-NDEPA) | N-Methyl-N-(3-diethylamino-3-oxopropyl)-2,5-dimethoxy-4-methylphenethylamine |  | |
| 25B-NAcPip | N-(Piperidin-1-ylcarbonylmethyl)-4-bromo-2,5-dimethoxyphenethylamine |  | |
| XOB | N-[(4-Phenylbutoxy)hexyl]-4-bromo-2,5-dimethoxyphenethylamine |  | [76] |
| TCB-2 | [(7R)-3-Bromo-2,5-dimethoxy-bicyclo[4.2.0]octa-1,3,5-trien-7-yl]methanamine |  | |
| 2CB-Ind | (5-Bromo-4,7-dimethoxy-2,3-dihydro-1H-inden-1-yl)methanamine |  | |
| ZC-B | 3-(4-Bromo-2,5-dimethoxyphenyl)azetidine |  | |
| 2C-B-PYR | 3-(4-Bromo-2,5-dimethoxyphenyl)pyrrolidine |  | |
| LPH-5 | (S)-3-(2,5-Dimethoxy-4-(trifluoromethyl)phenyl)piperidine |  | |
| DEMPDHPCA-2C-D ("compound 45") | 1-Methyl-3-(1-oxo-1-diethylaminomethyl)-5-(2,5-dimethoxy-4-methylphenyl)-3,6-dihydro-2H-pyridine |  | [77] |
| DOM-CR (DOM-THIQ, 2C-D-CR) | 5,8-Dimethoxy-7-methyl-1,2,3,4-tetrahydroisoquinoline |  | |
| DOB-CR (DOB-THIQ, 2C-B-CR) | 5,8-Dimethoxy-7-bromo-1,2,3,4-tetrahydroisoquinoline |  | |
| N-Methyl-DOM-CR (Beatrice-CR,N-methyl-2C-D-CR) | 2,7-Dimethyl-5,8-dimethoxy-1,2,3,4-tetrahydroisoquinoline |  | |
| 2C-B-morpholine | 2-(4-Bromo-2,5-dimethoxyphenyl)morpholine |  | [78][79] |
| 2C-B-aminorex | 5-(4-Bromo-2,5-dimethoxyphenyl)-4,5-dihydro-1,3-oxazol-2-amine |  | |
| 2C-B-PP | 1-(2,5-Dimethoxy-4-bromophenyl)piperazine |  | |
| 2C-B-BZP | 1-[(4-Bromo-2,5-dimethoxyphenyl)methyl]piperazine |  | |
| 2C-B-5-hemiFLY-α6 | 8-Bromo-6-methoxy-2a,3,4,5-tetrahydro-2H-naphtho[1,8-bc]furan-4-amine |  |
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].
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.
{{cite book}}: CS1 maint: location (link)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).
Table 4 Human potency data for selected hallucinogens. [...]
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).
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).
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.
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.
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).
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."
[Supporting Information] [...] Entry 35: N-(4-bromo-2,5-dimethoxyphenethyl)hydroxylamine [...]