# 2C (psychedelics)

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. 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.
Most of the currently known 2C compounds were first synthesized by Alexander Shulgin in the 1970s and 1980s and published in his book PiHKAL (Phenethylamines i Have Known And Loved). Shulgin also coined the term 2C, being an acronym for the 2 carbon atoms between the benzene ring and the amino group. 2C-B is the most popular of the 2C drugs.

## Use

The 2C drugs are orally active, are used at oral doses of 6 to 150 mg depending on the drug, and have durations of 3 to 48 hours depending on the drug. However, many have doses in the range of 10 to 60 mg and durations in the range of 4 to 12 hours. The 2C drugs produce psychedelic effects. Some, such as 2C-B, have also been reported to have some entactogenic qualities, though findings appear to be mixed.
Doses and durations of 2C drugs :
| Compound | Chemical name | Dosage | Duration |
| 2C-B | 4-Bromo-2,5-dimethoxyphenethylamine | 10–35 mg | 4–8 hours |
| 2C-C | 4-Chloro-2,5-dimethoxyphenethylamine | 20–40 mg | 4–8 hours |
| 2C-D | 4-Methyl-2,5-dimethoxyphenethylamine | 20–60 mg | 4–6 hours |
| 2C-E | 4-Ethyl-2,5-dimethoxyphenethylamine | 10–25 mg | 6–10 hours |
| 2C-EF | 4-Fluoroethyl-2,5-dimethoxyphenethylamine | 10–25 mg | Unknown |
| 2C-F | 4-Fluoro-2,5-dimethoxyphenethylamine | ≥250 mg | Unknown |
| 2C-G | 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-H | 2,5-Dimethoxyphenethylamine | Unknown | Unknown |
| 2C-iBu | 4-Isobutyl-2,5-dimethoxyphenethylamine | ≥5 mg | ~20 hours |
| 2C-I | 4-Iodo-2,5-dimethoxyphenethylamine | 14–22 mg | 6–10 hours |
| 2C-N | 4-Nitro-2,5-dimethoxyphenethylamine | 100–150 mg | 4–6 hours |
| 2C-O | 4-Methoxy-2,5-dimethoxyphenethylamine | Unknown | Unknown |
| 2C-P | 4-Propyl-2,5-dimethoxyphenethylamine | 6–10 mg | 5–16 hours |
| 2C-SE | 4-Methylseleno-2,5-dimethoxyphenethylamine | ~100 mg | 6–8 hours |
| 2C-T | 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-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-(t)-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-17 | 4-(s)-Butylthio-2,5-dimethoxyphenethylamine | 60–100 mg | 10–15 hours |
| 2C-T-21 | 4-(2-Fluoroethylthio)-2,5-dimethoxyphenethylamine | 8–12 mg | 7–10 hours |

## Pharmacology
### Pharmacodynamics
#### Actions

The 2C drugs act as agonists of the serotonin 5-HT$_2$ receptors, including of the serotonin 5-HT$_{2A}$, 5-HT$_{2B}$, and 5-HT$_{2C}$ receptors. They are partial agonists of the serotonin 5-HT$_{2A}$ receptor. Most of the 2C drugs have much lower affinity for the serotonin 5-HT$_{1A}$ receptor than for the serotonin 5-HT$_{2A}$ receptor. 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. The psychedelic effects of the 2C drugs are thought to be mediated specifically by activation of the serotonin 5-HT$_{2A}$ receptor.
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. Most of the 2C drugs are agonists of the rat and mouse trace amine-associated receptor 1 (TAAR1). However, most are inactive as agonists of the human TAAR1. The 2C drugs show very weak monoamine oxidase inhibition, including of monoamine oxidase A (MAO-A) and/or monoamine oxidase B (MAO-B).
2C drugs at serotonin 5-HT$_1$ and 5-HT$_2$ receptors :
| Drug | 5-HT$_{1A}$ | 5-HT$_{1A}$ | 5-HT$_{1A}$ | 5-HT$_{1B}$ | 5-HT$_{2A}$ | 5-HT$_{2A}$ | 5-HT$_{2A}$ | 5-HT$_{2B}$ | 5-HT$_{2B}$ | 5-HT$_{2B}$ | 5-HT$_{2C}$ | 5-HT$_{2C}$ | 5-HT$_{2C}$ |
| Drug | K$_i$ (nM) | EC$_{50}$ (nM) | E$_{max}$ (%) | K$_i$ (nM) | K$_i$ (nM) | EC$_{50}$ (nM) | E$_{max}$ (%) | K$_i$ (nM) | EC$_{50}$ (nM) | E$_{max}$ (%) | K$_i$ (nM) | EC$_{50}$ (nM) | E$_{max}$ (%) |
| 2C-B | 240–311 | 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: ||||||||||||||

#### 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. At least some 2C drugs, such as 2C-D and 2C-E, produce hyperlocomotion at lower doses in rodents. All 2C drugs produce hypolocomotion at higher doses in rodents. 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. However, none of the assessed 2C drugs substituted for dextromethamphetamine, suggesting that they lack amphetamine-type or stimulant-like effects.
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. The mechanism by which these effects are mediated is unknown. 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. These 2C drugs might have misuse potential in humans. 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.
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.
Various 2C drugs show potent anti-inflammatory effects mediated by serotonin 5-HT$_{2A}$ receptor activation. Among these include 2C-I, 2C-B, 2C-H, and 2C-iBu. Others, such as 2C-B-Fly and 2C-T-33, were less effective. 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.

### Pharmacokinetics

The 2C drugs are orally active. They are metabolized by O-demethylation and deamination. 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.

## Interactions

The 2C drugs are metabolized by the monoamine oxidase (MAO) enzymes, including both MAO-A and MAO-B. As a result, they may be potentiated by monoamine oxidase inhibitors (MAOIs), such as phenelzine, tranylcypromine, moclobemide, and selegiline. This may lead to overdose and serious toxicity.

## History

2,4,5-Trimethoxyphenethylamine (2,4,5-TMPEA; 2C-O or "2C-MeO") was first synthesized by Jansen and was found to produce psychedelic effects similar to those of mescaline (3,4,5-trimethoxyphenethylamine). He published his findings in 1931. 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.
2C-D (2C-M) was the first of the 2C drugs besides 2C-O to be discovered. It was synthesized and studied in animals by Ho and colleagues and they published their findings in 1970. Alexander Shulgin synthesized 2C-B and 2C-D in 1974 and discovered their psychedelic effects in self-experiments conducted in 1974 and 1975. He published his findings in the scientific literature in 1975. 2C-I was first described by Shulgin and colleagues in 1977 and initial psychoactivity was reported by Shulgin in 1978. Shulgin also first synthesized 2C-E in 1977. Subsequently, numerous other 2C drugs have been synthesized and characterized.
2C-B gained popularity as a recreational drug and MDMA alternative in the mid-1980s and became a controlled substance in the United States in 1994. It is said to be the most popular of the 2C drugs.

## List of 2C drugs

| Nomenclature | R3 | R4 | CAS number |
| 2C-B | H | Br | 66142-81-2 |
| 2C-Bn | H | CH$_2$C$_6$H$_5$ | |
| 2C-Bu | H | CH$_2$CH$_2$CH$_2$CH$_3$ | |
| 2C-C | H | Cl | 88441-14-9 |
| 2C-C-3 | Cl | Cl | |
| 2C-CN | H | C≡N | 88441-07-0 |
| 2C-D | H | CH$_3$ | 24333-19-5 |
| 2C-E | H | CH$_2$CH$_3$ | 71539-34-9 |
| 2C-EF | H | CH$_2$CH$_2$F | 1222814-77-8 |
| 2C-F | H | F | 207740-15-6 |
| 2C-G | CH$_3$ | CH$_3$ | 207740-18-9 |
| 2C-G-1 | CH$_2$ | CH$_2$ | |
| 2C-G-2 | (CH$_2$)$_2$ | (CH$_2$)$_2$ | |
| 2C-G-3 | (CH$_2$)$_3$ | (CH$_2$)$_3$ | 207740-19-0 |
| 2C-G-4 | (CH$_2$)$_4$ | (CH$_2$)$_4$ | 952006-59-6 |
| 2C-G-5 | (CH$_2$)$_5$ | (CH$_2$)$_5$ | 207740-20-3 |
| 2C-G-6 | (CH$_2$)$_6$ | (CH$_2$)$_6$ | |
| 2C-G-N | (CH)$_4$ | (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(CH$_3$)$_2$ | 1498978-47-4 |
| 2C-tBu | H | C(CH$_3$)$_3$ | |
| 2C-CP | H | C$_3$H$_5$ | 2888537-46-8 |
| 2C-CPE | H | C$_5$H$_9$ | |
| 2C-N | H | NO$_2$ | 261789-00-8 |
| 2C-NH2 | H | NH$_2$ | 168699-66-9 |
| 2C-PYR | H | Pyrrolidine | |
| 2C-PIP | H | Piperidine | |
| 2C-O | H | OCH$_3$ | 15394-83-9 |
| 2C-O-4 | H | OCH(CH$_3$)$_2$ | 952006-65-4 |
| 2C-MOM | H | CH$_2$OCH$_3$ | |
| 2C-P | H | CH$_2$CH$_2$CH$_3$ | 207740-22-5 |
| 2C-Ph (2C-BI-1) | H | C$_6$H$_5$ | |
| 2C-Se | H | Se CH$_3$ | 1189246-68-1 |
| 2C-T | H | SCH$_3$ | 61638-09-3 |
| 2C-T-2 | H | SCH$_2$CH$_3$ | 207740-24-7 |
| 2C-T-3 | H | SCH$_2$C(=CH$_2$)CH$_3$ | 648957-40-8 |
| 2C-T-4 | H | SCH(CH$_3$)$_2$ | 207740-25-8 |
| 2C-T-5 | | | |
| 2C-T-6 | | | |
| 2C-T-7 | H | S(CH$_2$)$_2$CH$_3$ | 207740-26-9 |
| 2C-T-8 | H | SCH$_2$CH(CH$_2$)$_2$ | 207740-27-0 |
| 2C-T-9 | | | 207740-28-1 |
| 2C-T-10 | | | |
| 2C-T-11 | | | |
| 2C-T-12 | | | |
| 2C-T-13 | H | S(CH$_2$)$_2$OCH$_3$ | 207740-30-5 |
| 2C-T-14 | | | |
| 2C-T-15 | H | SCH(CH$_2$)$_2$ | |
| 2C-T-16 | H | SCH$_2$CH=CH$_2$ | 648957-42-0 |
| 2C-T-17 | H | SCH(CH$_3$)CH$_2$CH$_3$ | 207740-32-7 |
| 2C-T-18 | | | |
| 2C-T-19 | H | SCH$_2$CH$_2$CH$_2$CH$_3$ | |
| 2C-T-21 | H | S(CH$_2$)$_2$F | 207740-33-8 |
| 2C-T-21.5 | | | 648957-46-4 |
| 2C-T-22 | | | 648957-48-6 |
| 2C-T-23 | | | |
| 2C-T-24 | | | |
| 2C-T-25 | | | |
| 2C-T-27 | | | 648957-52-2 |
| 2C-T-28 | | | 648957-54-4 |
| 2C-T-30 | | | |
| 2C-T-31 | | | |
| 2C-T-32 | | | |
| 2C-T-33 | | | |
| 2C-T-DFM | H | SCF$_2$H | |
| CYB210010 (2C-T-TFM) | H | SCF$_3$ | |
| 2C-T-DFP | H | SCH$_2$CH$_2$CF$_2$H | |
| 2C-T-PARGY | H | SCH$_2$C≡CH | |
| 2C-DFM$^{:770}$ | H | CHF$_2$ | |
| 2C-TFM | H | CF$_3$ | 159277-08-4 |
| 2C-TFE | H | CH$_2$CF$_3$ | |
| 2C-PFE | H | CF$_2$CF$_3$ | |
| 2C-PFS | H | SF$_5$ | |
| 2C-YN | H | C≡CH | 752982-24-4 |
| 2C-V | H | CH=CH$_2$ | |
| 2C-AL | H | CH$_2$CH=CH$_2$ | |

## Related compounds

| Name | Chemical name | Structure | Ref |
| XOB | N-[(4-Phenylbutoxy)hexyl]-4-bromo-2,5-dimethoxyphenethylamine | | |

## Legality
### Canada

As of October 12, 2016, the 2C-x family of substituted phenethylamines is a controlled substance (Schedule III) in Canada.