Posts Tagged ‘ 2C

Shulgin’s Sulfur Symphony – Part II

Substitution of sulfur at the 4-position of 2,5-dimethoxyphenethylamine provides a building block for many successful psychedelic compounds, initially explored by Shulgin and named in the format 2C-T-x. Generally, smaller substitutions tend to produce compounds which act as agonists, while larger substitutions are partial agonists or antagonists. The smaller substitutions described in Part I tend to be potent psychedelics, while the larger substitutions discussed here trend toward stimulant effects or are inactive. Determining the precise boundaries of this relationship was a major motivation of Daniel Trachsel who continued Shulgin’s work with the larger substitutions of 2C-T-25 and above.

2C-T-13 (2,5-dimethoxy-4-(β-methoxyethylthio)phenethylamine) Active in doses from 25 to 40 mg, it produces a experience 6 to 8 hours in length. There is a focus on closed eye visual effects, with only slight visual distortions present if the eyes are open.

2C-T-14 (2,5-dimethoxy-4-(2-methylthioethylthio)phenethylamine) The sulfur counterpart to 2C-T-13. Synthesis has been taken to the nitrostyrene stage by Shulgin, producing “garish orange-red ‘Las Vegas’ colored crystals” which at the time of writing were “sitting on the shelf waiting to be reduced to the target compound”. It is unclear if the synthesis was completed, and no bioassays are publicly known.

2C-T-15 (SESQUI, 2,5-dimethoxy-4-cyclopropylthiophenethylamine) Similar to 2C-T-8, with the cyclopropyl group one carbon closer to the phenyl ring. This compound appears to have been unremarkable, with only threshold effects noted at 30mg. Like 2C-T-8, this “particular substitution pattern is not one to set the world on fire”.

2C-T-16 (2,5-dimethoxy-4-allylthiophenethylamine) Synthesis was taken to the nitrostyrene stage by Shulgin, but has not been completed to public knowledge.

2C-T-17 (NIMITZ, 2,5-dimethoxy-4-sec-butylthiophenethylamine) Dubbed “Nimitz” by Shulgin after State Highway 17 from Oakland to San Jose (the Nimitz freeway), now called Interstate 880. Active in doses of 60 to 100 mg, it produces a 10-15 hour experience with alteration of thought patterns but little visual distortion. This compound is also notable for possessing a secondary butyl group containing an asymmetric carbon atom. Only racemic 2C-T-17 has been bioassayed, but Shulgin was extremely curious if the activity of the compound could be isolated to one of the two stereoisomers. This would be similar to the isolation of psychedelic effects to the R isomers of the substituted amphetamines, with their asymmetric carbon next to the amine group on the other side of the phenyl ring. Both stereoisomers of 2C-T-17 were brought to the nitrostyrene stage, but the independent synthesis of the individual stereoisomers was never completed to public knowledge.

2C-T-18 (2,5-dimethoxy-4-cyclobutylphenethylamine) Synthesis was taken to the nitrostyrene stage by Shulgin, but has not been completed to public knowledge.

2C-T-19 (2,5-dimethoxy-4-n-butylthiophenethylamine) Synthesis was taken to the nitrostyrene stage by Shulgin, but not completed to public knowledge.

2C-T-20 (2C-T-3, 2,5-dimethoxy-4-(beta-methallyl)thiophenethylamine) Also known as 2C-T-3. Before working on the 2C-T series Shulgin investigated a similar series of promising compounds dubbed the Alephs, of which Aleph-3 was the beta-methallyl homologue. The synthesis of Aleph-3 was attempted, abandoned, and eventually forgotten. Years later the idea came to Shulgin again, and the beta-methallyl Aleph was begun anew along with the corresponding beta-methallyl 2C-T compound (2C-T-20). This led to the rediscovery of notes referencing the initial Aleph-3 synthesis attempt, and 2C-T-20 was renamed 2C-T-3 in order to maintain consistency with the Aleph project.

2C-T-21 (2,5-dimethoxy-4-(2-fluoroethylthio)phenethylamine
) The fluoroalkyl counterpart to 2C-T-7. Active in dosages between 8 and 12 mg it produces a 7 to 12 hour experience with a euphoric push. It was the first psychedelic compound synthesized which contained six separate elements, was widely regarded as a rich and unique material, and now languishes in obscurity due to an infamous incident that led to a large-scale DEA investigation.

On March 9, 2004, a 22-year-old quadriplegic man named James Edwards Downs in St. Francisville, Louisiana, consumed an unknown dose of 2C-T-21 by sticking his tongue into a vial of powder he had purchased online. He developed a high fever, had a tonic-clonic seizure, and slipped into a coma. Four days later, on March 13, Downs died at Lane Memorial Hospital in Zachary, LA.

This death became part of a two year DEA investigation called Operation Web Tryp which was launched in 2002. On July 22, 2004, the owners of American Chemical Supply were arrested on federal charges relating to distribution of controlled substance analogues and the death of James Edwards Downs.

2C-T-21.5 (2,5-dimethoxy-4-(2,2-difluouroethylthio)phenethylamine
) Shulgin refers to this compound at the end of the 2C-T-21 entry in PiHKAL.

And it has just occurred to me that there is yet another effort that is certainly worth making, inspired by the observation that 2,2-difluoroethyl iodide is commercially available and not prohibitively expensive. It, with 2,5-dimethoxythiophenol, and following the obvious steps to the aldehyde, the nitrostyrene, and the final amine, would produce 2,5-dimethoxy-4-(2,2-difluoroethylthio)phenethylamine hydrochloride. It lies exactly half way between the highly potent 2C-T-21 (the mono-fluoro), and the yet to be finished 2C-T-22 (the trifluoro). Let’s be weird, and call it 2C-T-21.5. I will wager mucho that it will be very potent.

Synthesis of 2C-T-21.5 has not been completed to public knowledge.

2C-T-22 (2,5-dimethoxy-4-(2,2,2-trifluouroethylthio)phenethylamine
) Synthesis was abandoned due to difficulties in purifying the aldehyde, and has not been completed to public knowledge.

2C-T-23 (2,5-dimethoxy-4-cyclopentylthiophenethylamine
) Synthesis was taken to the aldehyde stage by Shulgin, but has not been completed to public knowledge.

2C-T-24 (2,5-dimethoxy-4-diethylaminothiophenethylamine
) Shulgin’s synthesis of this compound was unsuccessful, and it was not given a name. Murple dubbed it 2C-T-24. Shulgin describes his attempt in PiHKAL:

One additional effort was made to prepare a 2C-T-X thing with a sulfur-nitrogen bond. The acid chloride intermediate in the preparation of 2,5-dimethoxythiophenol (as described in the recipe for 2C-T-2) is 2,5-dimethoxybenzenesulfonyl chloride. It reacted smoothly with an excess of diethylamine to produce 2,5-dimethoxy-N,N-diethylbenzenesulfonamide which distilled at 155 °C at 0.13 mm/Hg and which could be recrystallized from a 4:1 mixture of cyclohexane/benzene to give a product with a melting point of 41-42 °C and an excellent proton NMR. This amide proved totally refractory to all efforts at reduction, so the target compound, 2,5-dimethoxy-4-diethylaminothiophenethylamine, has not been made. It has not even been given a 2C-T-X number.

This was the second attempt at creating a sulfur-nitrogen bonded phenethylamine, the first being 2C-T-12 which was also unsuccessful.

2C-T-25 (2,5-dimethoxy-4-isobutylthiophenethylamine
) The isobutyl to 2C-T-4’s isopropyl, or an unfluorinated 2C-T-21.5. This compound was synthesized by Daniel Trachsel but has not been bioassayed to public knowledge.

2C-T-27 (2,5-dimethoxy-4-benzylthiophenethylamine
) Synthesized by Daniel Trachsel but has not been bioassayed to public knowledge.

2C-T-28 (2,5-dimethoxy-4-(3-fluoropropylthio)phenethylamine
) The fluoroalkyl counterpart to 2C-T-19. Synthesized by Daniel Trachsel but has not been bioassayed to public knowledge.

2C-T-30 (2,5-dimethoxy-4-(4-fluorobutylthio)phenethylamine
) 2C-T-28 with an additional carbon in the alkyl chain. Synthesized by Daniel Trachsel but has not been bioassayed to public knowledge.

2C-T-31 (2,5-dimethoxy-4-(4-trifluoromethylbenzylthio)phenethylamine
) A 4-trifluoromethyl substituted 2C-T-27. Synthesized by Daniel Trachsel but has not been bioassayed to public knowledge.

2C-T-32 (2,5-dimethoxy-4-(2,3,4,5,6-pentafluorobenzylthio)phenethylamine
) A ring-fluorinated 2C-T-27. Synthesized by Daniel Trachsel but has not been bioassayed to public knowledge.

2C-T-33 (2,5-dimethoxy-4-(3-methoxybenzylthio)phenethylamine
) A 3-methoxy substituted 2C-T-27. Synthesized by Daniel Trachsel but has not been bioassayed to public knowledge.

Trachsel, D. 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). Helv. Chim. Acta, 5 Aug 2003, 86 (7), 2610–2619.

2C-T-x Substitution Size and Potency

The 2C phenethylamines typically refer to the 2,5-dimethoxy 4-substituted phenethylamines. Generally, small lipophilic substitutions at the 4-position tend to produce compounds which act as agonists, while larger substitutions are partial agonists or antagonists.

This statement appears to be borne out by investigation of the 2C-T-x series of compounds developed and studied by Shulgin. If we sort compounds with entries in PiHKAL by molecular mass to obtain a rough measure of substitution size, we can graph the reported dosage ranges to help illustrate this relationship.

2C-T-15 is shown as a dashed line due to the fact that it was only tested at 30mg and found to be underwhelming with no upper range established, in contrast to the more rigorously established dosage ranges for other compounds. This lack of potency could be a consequence of the inclusion of the atypical cyclopropyl group, which is also found in the disappointing 2C-T-8.

2C-T, 2C-T-2, 2C-T-4, 2C-T-7 and 2C-T-21 have smaller substitutions at the 4-position and are considered rather potent psychedelics. Similar to the relationship of 2C-D (the smallest alkylated substitution) to the rest of the active alkylated 2Cs, 2C-T is less potent per milligram but has a very similar mental state to the previously cited compounds if dosage is adjusted upwards appropriately. As the substitution size grows, compounds like 2C-T-9, 2C-T-13 and 2C-T-17 are encountered which are less potent and not as classically psychedelic, most notably possessing decreased open-eye visual activity and an increased focus on stimulant effects relative to smaller substitutions even when dosage levels are adjusted for.

Shulgin’s Sulfur Symphony – Part I

The 2C class of psychedelic compounds first researched by Alexander Shulgin encompasses a wide range of mental experiences, but one substitution in particular seemed to resonate with the magic seen in legendary compounds like mescaline. Thioalkylation at the 4-position produced the famed 2C-T-2 and 2C-T-7, compounds noted for an almost overwhelming visual character with echos of the cosmic choir, and a dismantling of the ego more prominent relative to the perceptually focused halogenated and alkylated 2Cs. This unique experience caused Shulgin to focus his substantial talents on sulfur based substitutions at the 4-position for a period of time, producing a large number compounds named in the format 2C-T-x. The first twelve are outlined in this post.

One attribute of these compounds must be emphasized at the outset. Unlike the halogenated or alkylated 2Cs, sulfur substitutions appear to be correlated with varying degrees of MAO inhibition, which can cause significant health issues up to and including death in extreme doses or in combination with other recreational drugs, particularly stimulants. These compounds were used safely in reasonable oral doses for twenty years among a qualified group of explorers, but the research chemical surge of the early 2000s introduced these compounds to an untrained audience in pure bulk forms. With resellers actively encouraged not to disseminate information on safer consumption due to legal pressures to maintain an appearance of “not for human consumption”, reckless dosing and routes of administration led to tragedy.

2C-T-2 has been sold widely, and has not been involved in any fatalities to my knowledge presumably due to less significant MAOI effect as judged by euphoric “push” relative to the other sulfur substitutions. 2C-T-7 can be considered the most popular of the group, and has nonetheless been involved in at least three deaths involving either excessive insufflated doses over 30mg, use in combination with stimulants such as MDMA or ephedrine, or both. The less popular 2C-T-21 has produced one death after an extreme oral dose (sticking tongue in full vial of pure compound).

The desire to experience the mental state produced by these compounds should be weighed with the intentions, ability, and risk tolerance of the end user. A society which allows the purchase of firearms with the assumption of responsibility should allow the same for self-exploration, but this is often not the case. If you are unfamiliar with the mechanism of risk of these compounds (ie MAO inhibition), if you are unable to weigh these compounds accurately, and if you are unwilling to respect the impact of route of administration, then an alternative should be selected.

 

2C-T (2C-T-1, 2,5-dimethoxy-4-methylthiophenethylamine) Active in doses of 50-150mg, this compound produces a euphoric psychedelic experience for 5-6 hours that nonetheless was described as “generic” by Shulgin. Lack of potency relative to other closely related compounds and the somewhat shallow mental state make this a rare find on the research chemical market.

 

2C-T-2 (2,5-dimethoxy-4-ethylthiophenethylamine) Active in doses of 10-30mg, this compound produces a 6-8 hour experience most notable for its intellectual introspection, mescaline styled visuals, and unholy ability at higher doses to cause physical distress including nausea during the first hour of the experience. Like mescaline, after the purge a sense of contentment develops and the experience then progresses naturally. 2C-T-2 first rose to wide fame after the banning of 2C-B, and was first sold by Dutch smartshops as a substitute in 1997. As it produced a much richer and deeper psychedelic experience than 2C-B, it did not have as wide an appeal on the club circuit, but still sold widely enough that it was eventually banned by Dutch authorities.

 

2C-T-3 (2C-T-20, 2,5-dimethoxy-4-(beta-methallyl)thiophenethylamine) Also known as 2C-T-20. Before working on the 2C-T series Shulgin investigated a similar series of promising compounds dubbed the Alephs, of which Aleph-3 was the beta-methallyl homologue. The synthesis of Aleph-3 was attempted, abandoned, and eventually forgotten. Years later the idea came to Shulgin again, and the beta-methallyl Aleph was begun anew along with the corresponding beta-methallyl 2C-T compound (2C-T-20). This led to the rediscovery of notes referencing the initial Aleph-3 synthesis attempt, and 2C-T-20 was renamed 2C-T-3 in order to maintain consistency with the Aleph project.

It is unclear if there was ever an “original” 2C-T-3 whose place was overwritten or shifted by insertion of the beta-methallyl. It is certainly an odd man out in the progression, as it would seem reasonable to place the n-propyl 2C-T-7 here after the ethyl 2C-T-2 and before the isopropyl 2C-T-4. A numbering system based on the previous Alephs appears to explain the gap, as perhaps the initial synthesis of the 2C-T-3 was simply left for later due to the increased difficulty relative to the alkyls surrounding it. The synthesis of 2C-T-3/2C-T-20 has never been completed according to public knowledge.

 

2C-T-4 (2,5-dimethoxy-4-isopropylthiophenethylamine) The isopropyl companion to the propyl substituted 2C-T-7. Active in doses between 8-20mg, it produces a long lasting change in mental state for 12 to 18 hours with a slight dissociative character. Human testing showed huge variance in responses, particularly in the subcategories of visual distortion and euphoric response. The inability to predict whether a 12+ hour long psychedelic experience would be euphoric and illuminating or dysphoric and anxiety ridden has contributed to a lack of recreational usage of this drug.

 

2C-T-5 (2,5-dimethoxy-4-cyclohexylthiophenethylamine) Has never been synthesized according to public knowledge, and was presumably based the similarly structured Aleph-5.

 

2C-T-6 (2,5-dimethoxy-4-phenylthiophenethylamine) Has never been synthesized according to public knowledge, and was presumably based the similarly structured and successfully synthesized Aleph-6.

 

2C-T-7 (2,5-dimethoxy-4-(n)-propylthiophenethylamine) Active in doses of 10-40mg with a duration of 8-16 hours, 2C-T-7 is perhaps the most popular of Shulgin’s sulfur substitutions likely due to a more consistent euphoric effect. A powerful psychedelic character lies underneath however, and initial hype about a easy to handle “candyflip” experience may have resulted in some overwhelming experiences. With nausea reported less frequently as a side effect in comparison to 2C-T-2, many cast 2C-T-2 aside as a shorter less euphoric 2C-T-7. This is not necessarily a valid critique, as the more euphoric mental state of 2C-T-7 often results in “sloppier” emotional analysis relative to the slightly more difficult and intellectual 2C-T-2. 2C-T-7 began its rise to fame in the summer of 1999 as Dutch smartshops began selling it in 7.5mg tablets dubbed “Blue Mystic” due to the success (and resulting ban) of 2C-T-2. Unsurprisingly, 2C-T-7 was quickly banned as well.

 

2C-T-8 (2,5-dimethoxy-4-cyclopropylmethylthiophenethylamine) Active in doses of 30-50mg and producing a 10-15 hour experience, this compound produces a mental state that many did not wish to repeat. Shulgin said in PiHKAL, “there are as many negatives as there are positives, and the particular substitution pattern is not one to set the world on fire.”

 

2C-T-9 (2,5-dimethoxy-4-(t)-butylthiophenethylamine) Active in doses of 60-100mg, it produces a 12-18 hour experience with significant peripheral body load and little psychedelic reward for the effort. Note that Wikipedia currently incorrectly refers to this as the n-butylthio substitution rather than the tert-butylthio referenced in PiHKAL, as the n-butylthio substitution should be referred to as 2C-T-19.

 

2C-T-10 (2,5-dimethoxy-4-(2-pyridylthio)phenethylamine) Synthesis was abandoned before completion, and has not been completed by others according to public knowledge.

 

2C-T-11 (2,5-dimethoxy-4-(4-bromophenylthio)phenethylamine) Synthesis was abandoned before completion, and has not been completed by others according to public knowledge.

 

2C-T-12 (2,5-dimethoxy-4-(1-morpholinothio)phenethylamine) Synthesis was abandoned before completion, and has not been completed by others according to public knowledge.

 

Sulfurous Samadhi, An Investigation of 2C-T-2 & 2C-T-7 by Murple, Feb 6, 2001.

Nichols, D. E. and Shulgin, A. T. (1976), Sulfur analogs of psychotomimetic amines. Journal of Pharmaceutical Sciences, 65: 1554–1556. doi: 10.1002/jps.2600651040

The Alkylated 2Cs

Alexander Shulgin investigated a large number of substituted phenethylamines, and dubbed one class with methoxy groups substituted on the 2 and 5 positions of the benzene ring the “2C”s, for the two carbon atoms between this ring and the amino group. A suprisingly large number of substitutions on the 3 and 4 positions demonstrated intruiging psychedelic activity, including halogenation at the 4 position. There are other possible substitutions as well, including the alkylated 2Cs, which are generally considered “deeper” psychedelics than their halogenated cousins, with complex visuals and a more analytical and challenging psychedelic state.

3 position: hydrogen

4 position: alkyl groups, consisting of only single bonded carbon and hydrogen atoms (methyl, ethyl, propyl, isopropyl)

2C-D (2,5-dimethoxy-4-methylphenethylamine) has the simplest alkyl substitution, a methyl group. Personally, I’m a bit confused why this isn’t called 2C-M, but I don’t get to name these things. Best known as as a “smart drug” at doses under 10mg, it has been reported to aid in learning but has produced inconsistent results in trials. Shulgin referred to it as “pharmacological tofu”, a substance that could be used to potentiate and extend the action of other materials without changing the experience significantly – similar to the manner in which tofu in a stirfry absorbs the surrounding flavors without contributing a significant taste of its own. At higher doses of 30-100mg it is a proper psychedelic in its own right, but this lower potency has contributed to a lack of relative popularity due to a higher cost per dose.

2C-E (2,5-dimethoxy-4-ethylphenethylamine) is currently the most well known of the alkylated 2Cs, a material Shulgin dubbed “difficult but worthwhile”. Typically taken orally in doses of 10-25mg, it produces a psychedelic state lasting 8-12 hours described as emotionally neutral by many. The dose-response curve is also significantly steeper than 2C-D, with 20mg subjectively producing an experience twice as powerful as 15mg, and quickly spiraling to undesirably intense states above 25mg. As one of the most visual and powerfully introspective phenethylamines, it has gained favor with those preferring the deeper psychedelic states produced by compounds such as LSD.

2C-P (2,5-dimethoxy-4-propylphenethylamine). As the length of the alkyl chain increases, potency and duration increase along with it. Oral doses of 5-15mg begin to show effect after 3 hours, and can last 10-16 hours. While the visual style is similar to 2C-E, the mental state is slightly deeper with a more stimulated feel. Doses of 2C-P were regarded with great caution due to a concise note by Shulgin indicating that 16mg was “clearly an overdose”. This cast fear in some and doubt in others, as no apparent toxic effects had been noted with dosage levels approaching this, although the dose-response curve for mental effects appeared even steeper than 2C-E. Shulgin responded to the statement in 2004 with the following clarification:

I contacted the person who tried the 16 milligram dose of 2C-P and who gave me the phrase, “16 mg was clearly an overdose, with the entire experiment labeled a physical disaster, not to be repeated.”

He checked his notes and shared more details that establishes context for this comment. When he was about eleven years old, he was sitting in his living room of his parent’s house, and a medium sized earthquake happened and knocked over some furniture including a full bookcase. This landed on his legs and hurt him very badly. Nothing was broken, but the pulled muscles made it painful to walk. This discomfort lasted for upwards of a year.

At the peak of the 2C-P trial (he about 45 years old at the time) he recalled and re-lived this frightening experience and there was extreme pain in his legs. No cardiovascular effects, or signs of toxicity. It was a childhood physical disaster that was re-lived and he had no wish to repeat that particular dose, as he didn’t want to repeat the pain. He did another experiment two weeks later, with 9 milligrams, and had a long-lived +++ but had no childhood memories!

This all took place in late 1985.

2C-iP (2,5-dimethoxy-4-isopropylphenethylamine) has had little testing in humans, was not investigated in PiHKAL, and existing reports are inconsistent. Some suggest it is effectively inactive, with a large (1-2 orders of magnitude) decrease in potency relative to 2C-P (similar to the relationship of DOIP to DOPR), while others describe an experience similar to 2C-E requiring 1.5x the material for a comparable (although longer lasting) experience. It seems likely that more reports will appear soon, and perhaps the effects of this rare material will become more clear with time.

What about the longer alkyl chains (butyl, pentyl, etc.)? To my knowledge, they have not been sufficiently tested in humans to draw any real conclusions about their activity at this point in time. Shulgin found that activity declined significantly with the butyl group in the substituted amphetamines (DOM ~ DOET ~ DOPR > DOBU), but the action in the 2C compounds may not be quite as clear. Combined with the increase in difficulty of synthesis and the infamous maxim “There’s ethyl and propyl, but butyl is futile”, 2C-BU and other related compounds are unlikely to gain popularity absent some surprises. In general, the alkylated 2Cs share a complex style of visual distortion and a similar psychedelic character – but potency per unit weight, duration, and steepness of the dose-response curve increase as the size of the first three normal alkyl groups grows.

The Halogenated 2Cs

Many phenethylamines can cause changes in consciousness or are involved in the natural neurochemistry of the brain itself, such as dopamine and norepinephrine. Alexander Shulgin described a wide variety of these compounds in his book “Phenethylamines I Have Known and Loved“, and one variant in particular seemed to stand out as a psychedelic superstar. If methoxy groups were substituted on the 2 and 5 positions of the benzene ring, a suprisingly large number of substitutions on the 3 and 4 positions demonstrated profound psychedelic activity. The particular group was dubbed the “2C”s, for the two carbon atoms between the benzene ring and the amino group.

A huge number of these compounds can be synthesized, and several groups stand out with a unique psychedelic character. One of these is the halogenated 2Cs, known for colorful “persian carpet” style visual patterning, peripheral effects including stimulation/sedation, a medium duration of 4-8 hours, and a generally more “shallow” psychedelic feel.

3 position: hydrogen

4 position: the highly reactive halogens (fluorine, chlorine, bromine, iodine)

2C-F (2,5-dimethoxy-4-fluorophenethylamine) is a rare compound, tested by only a few subjects and possibly inactive. Only doses of greater than 100mg produced reports of a possible shift in consciousness, but these reports were inconsistent and the shift, if any, was so mild as to be irrelevant for the purposes of further research.

2C-C (2,5-dimethoxy-4-chlorophenethylamine) has been tested more widely, but does not currently have mass appeal presumably due to its mild effect. Oral doses can range from 20-80mg, which produces a psychedelic state with a unique physical character described as “intensely relaxing”, a change from other halogenated 2Cs which tend to produce a stimulated state.

2C-B (2,5-dimethoxy-4-bromophenethylamine) produced the most consistently positive reviews of the halogenated 2Cs in initial tests, and was the first to gain popularity with the wider public. It was used in psychiatric therapy in the 1980s after being first synthesized by Shulgin in 1974 and found favor as a compound that produced a more predictable and empathetic state than other psychedelics like LSD or psilocybin. Word also quickly spread about other side effects, including a distinct erotic enhancement which led to the worldwide sale of 5mg tablets under the brand names Eros and Nexus. Doses from 15-35mg produced a unique psychedelic state characterized by mild stimulation and euphoria, and 2C-B quickly became a drug of choice in the underground. The transition from psychiatric aid to club drug doomed 2C-B to eventual illegality, as it is now internationally controlled under the UN Convention on Psychotropic Substances.

2C-I (2,5-dimethoxy-4-iodophenethylamine) was first sold widely by Dutch smart shops who introduced it as a replacement to the recently banned 2C-B in 2000. Slightly more potent with a dosage range of 10-25mg, it was a good substitute but not “quite there”. With a jitterier stimulant character and less consistent erotic effects it once again gained popularity on the club circuit, but was quickly banned in the Netherlands in 2003. While still legal in many areas of the world, it is unlikely to ever regain the critical mass of popularity 2C-B possessed.

2C-A (2,5-dimethoxy-4-astatophenethylamine) would be the next logical extension after iodine as we march down the periodic table – but the only problem is that astatine is the rarest naturally occurring element due to its radioactive nature and short half-life. Quite a stir was created among some in the research chemical market when it was finally announced that 2C-A would be available for sale, until it became clear that the date of the announcement was April 1st. Shulgin had this to say about 2C-A:

What might be speculated as to [2C-A’s] activity? Probably similar in potency to 2C-I, requiring maybe 10 or 20 milligrams. The duration would be dicey to measure, since the isotope with the longest known half-life is half decayed in about 8 hours, and the longest lived natural isotope (for those who insist on natural rather than man-made things) is half decayed in less than a minute. Two predictions would be pretty solid. You might have quite a job accumulating your 10 milligrams of Astatine, as the most that has so far been made at one time is only about 0.05 micrograms, approximately a millionth of the amount needed. And the second prediction? You would not survive the screaming radiation that would bombard you if you could get the needed 5 or 10 milligrams of radio-astatine onto that magic 4-position, and the resulting 2C-A into your tummy!

In general, the halogenated 2Cs share a unique style of visual distortion, have similar durations, and the character and depth of the psychedelic experience remains fairly consistent – but potency per unit weight and stimulant effects increase as we move up through the halogens by molecular weight.