Clinical data | |
---|---|
Routes of administration | By mouth, insufflation, rectal |
Drug class | Serotonergic psychedelic |
Legal status | |
Legal status |
|
Pharmacokinetic data | |
Metabolism | Liver |
Onset of action | 20–40 min (oral) |
Elimination half-life | 2.48 ± 3.20 h [1] |
Duration of action | 4–12 hours depending on route of administration |
Identifiers | |
| |
CAS Number | |
PubChem CID | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
ChEMBL | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.164.088 |
Chemical and physical data | |
Formula | C10H14BrNO2 |
Molar mass | 260.131 g·mol−1 |
3D model (JSmol) | |
| |
|
2C-B (4-bromo-2,5-dimethoxyphenethylamine), also known as Nexus, is a synthetic psychedelic drug of the 2C family, mainly used as a recreational drug. [2] The substance was first synthesized by Alexander Shulgin in 1974, and gained an initial reputation for potential psychotherapeutic use, but its use has been limited to mainly recreational use. To date, there is limited scientific information regarding the drug's pharmacokinetics and pharmacological effects in humans. The existing studies primarily classify 2C-B as a stimulant and hallucinogen, and less commonly an entactogen and empathogen. [3]
2C-B, also referred to by a number of slang names, is known to circulate in the illicit market in multiple forms: [4] [5] as a powder, in capsules or pills. For recreational use, the substance is generally consumed orally or nasally. In Shulgin's book PiHKAL , the oral dosage range is listed as 12–24 mg. [6]
2C-B was synthesized from 2,5-dimethoxybenzaldehyde by American chemist Alexander Shulgin in 1974. It first saw use among the psychiatric community as an aid during therapy.[ citation needed ] 2C-B was first sold commercially as a purported aphrodisiac [7] under the trade name "Erox", which was manufactured by the German pharmaceutical company Drittewelle. [8] For several years, it was available as tablets in Dutch smart shops under the name "Nexus" and "B-Dub".[ citation needed ]
2C-B first became popularized in the United States as a short-lived substitute for the street drug ecstasy (MDMA) when the latter became illegal in 1985. [9] Many 2C-B users are young adults who attend raves. [4] Though 2C-B is still used in the rave subculture, commonly mistaken for and/or sold as ecstasy, its intentional use has become more common in the 2000s. [10]
In 2011, street prices in the United States ranged between $10 and $30 per tablet when purchased in small quantities. [4] Larger retail purchases cost between $200 and $500 per gram. Wholesale purchases of 2C-B would lower the price ($100 to $300 per gram in 2001, $30 to $100 on the darknet in 2020). [7]
2C-B was used as entheogen by the Sangoma, Nyanga, and Amagqirha people in place of their traditional plants; they refer to the chemical as Ubulawu Nomathotholo, which roughly translates to "Medicine of the Singing Ancestors". [11] [12] [13]
Little academic research has been conducted on the effects of 2C-B in humans. The information available is largely anecdotal and limited. Effects are often described as being more easily managed than other psychedelics; [14] [15] it is often compared to a mixture of a serotonergic psychedelic and MDMA. [16] At 5–10 mg, experiments with young chickens have shown it to produce effects similar to a low dosage of amphetamines. [17]
The anecdotal effects of 2C-B that have been reported by users on online discussion forums include: [18] [19] [20]
When orally consumed, 2C-B has a much longer delay before the onset of effects than when it is insufflated. Oral ingestion generally takes roughly 45–75 minutes for the effects to be felt, plateau lasts 2–4 hours, and coming down lasts 1–2 hours. Rectal administration onset varies from 5–20 minutes. Insufflated onset takes 1–10 minutes for effects to be felt. The duration can last from 4 to 12 hours depending on route of administration, dose, and other factors. [18]
With insufflation, the effects are more abrupt and intense but have a significantly shorter duration, while oral usage results in a milder, longer experience. When insufflated, the onset happens very rapidly, usually reaching the peak at about 20–40 minutes and plateauing for 2–3 hours. 2C-B is also considered one of the most painful drugs to insufflate, with users reporting intense nasal burning. [14] The sudden intensity of the experience combined with the pain can often start the experience with a negative imprint and nausea is also increased with insufflation, compounding the issue.
The September 1998 issue of Journal of Analytical Toxicology reported that very little data exists about the pharmacological properties, metabolism, and toxicity of 2C-B. The relationship between its use and death is unknown. [7] The common oral recreational dose is around 15–25 mg, [24] at which visual and auditory effects are experienced. Severe adverse reactions are extremely rare, but use of 2C-B was linked to significant brain injury in one case report; the alleged "2C-B" was never actually discovered by testing so the only evidence suggesting 2C-B was the cause was the victim's own words, without taking into consideration that adulteration and impurities are very common in illicit drugs. [25]
Oral | Insufflated | |
---|---|---|
ED50 | 10 mg | 4–6 mg |
Moderate | 15–25 mg | 5–9 mg |
Strong | 26–35 mg | 10–20 mg |
Extremely Intense | >35 mg | >20 mg |
Duration | 4–8 hours | 2–4 hours |
The lethal dosage is unknown. It was reported in PiHKAL , by Alexander Shulgin, that a psychologist had accidentally taken a 100 mg dose orally without apparent harm. [6]
When sold as "Ecstasy", tablets containing 2C-B often contain about 5 mg of the drug, an amount which produces stimulatory effects that mimic the effects of MDMA; in contrast, tablets marketed as 2C-B have larger quantities of the drug (10–20 mg) which cause hallucinogenic effects. [26] Street purity of 2C-B, when tested, has been found to be relatively high. [27] Researchers in Spain found that 2C-B samples in the country doubled between 2006 and 2009, switched from primarily powder form to tablets, and exhibited "low falsification rates". [16] An analysis of street samples in the Netherlands found impurities "in small percentages"; only one of the impurities, the N-acetyl derivative of 2C-B, could be identified, and comprised 1.3% of the sample. The authors suggested that this compound was a by-product of 2C-B synthesis. [26]
Unlike most psychedelics, 2C-B has been shown to be a low efficacy human serotonin 5-HT2A and 5-HT2C receptor partial agonist. [28] This suggests that activation of the 5-HT2A-coupled phospholipase D pathway [28] or functional antagonism of 5-HT2A may also play a role. The rank order of 5-HT2A receptor antagonist potency for this family of drugs in Xenopus is 2C-I > 2C-B > 2C-D > 2C-H. [29]
Research suggests that 2C-B increases dopamine levels in the brains of rats, which may contribute to its psychoactivity. [30]
2C-B has been shown to be metabolized by liver hepatocytes, resulting in deamination and demethylation that produces several products. Oxidative deamination results in the 2-(4-bromo-2,5-dimethoxyphenyl)-ethanol (BDMPE) and 4-bromo-2,5-dimethoxyphenylacetic acid (BDMPAA) metabolites. Additionally, 4-bromo-2,5-dimethoxybenzoic acid (BDMBA) can also be produced by oxidative deamination. Further metabolism of BDMPE and BDMPAA may occur by demethylation. Alternatively, the later metabolites can be generated by demethylation of 2C-B followed by oxidative deamination. [22]
There is species differentiation in the metabolism of 2C-B. Mice hepatocytes produce 4-bromo-2,5-dimethoxy-phenol (BDMP), a previously unknown metabolite. Meanwhile, human, monkey and rabbit hepatocytes produce 2-(4-bromo-2-hydroxy-5-methoxyphenyl)-ethanol (B-2-HMPE), but dog, rat and mouse hepatocytes do not. [22] 2C-B also reduces aggressive responses in drugged rats. [31]
Analogues and derivatives of 2C-B:
25-N:
Other:
A variety of N-substituted derivatives of 2C-B have been tested, including N-methyl-2CB, N,N-dimethyl-2CB, N-ethyl-2CB and N-benzyl-2CB. Most simple alkyl derivatives were considerably less potent than 2C-B, with N-ethyl-2CB for instance having a 40 times lower affinity for the 5-HT2A receptor. The N-benzyl derivative however was found to have higher binding affinity than 2C-B itself, with N-(4-bromobenzyl)-2CB binding even more tightly. [36] This initial research did not include functional assays of activity, but later led to the development of potent substituted N-benzyl derivatives such as 25B-NBOMe, [37] and 25B-NBOH.
Exposing compounds to the reagents gives a colour change which is indicative of the compound under test.
Marquis | Mecke | Mandelin | Liebermann | Froehde | Robadope |
---|---|---|---|---|---|
Yellow to green | Yellow to olive brownish | green | Yellow to black | Yellow to green | Slow pink |
Ehrlich | Hofmann | Simon's | Scott | Folin | |
No reaction | No reaction | No reaction | No reaction | (Light) purple |
The UN Commission on Narcotic Drugs added 2C-B to Schedule II of the Convention on Psychotropic Substances in March 2001. [38]
2C-B is a scheduled drug in most jurisdictions. [39] The following is a partial list of territories where the substance has been scheduled.
2C-B is controlled under the List 1, as well as similar substances like 2C-I or 2C-T-2. [40]
2C-B is controlled in Australia and on the list of substances subject to import and export controls (Appendix B). It was placed on Schedule One of the Drugs Misuse and Trafficking Act when it first came to notice in 1994, when in a showcase legal battle chemist R. Simpson was charged with manufacturing the substance in Sydney. Alexander Shulgin came to Australia to testify on behalf of the defense, to no avail.
2C-B is not specifically listed in the Australia Poisons Standard (October 2015), however similar drugs such as 2C-T-2 and 2C-I are making 2C-B fall under the Australian analogue act. [41]
In Belgium, 2C-B is a controlled substance making production, distribution, and possession illegal.
In Brazil, 2C-B is a controlled substance making production, distribution, and possession illegal.
In Canada, 2C-B is classified under Controlled Drugs and Substances Act as Schedule III as "4-bromo-2,5-dimethoxybenzeneethanamine and any salt, isomer or salt of isomer thereof". [42]
2C-B has been rescheduled (Schedule III), in a new amendment, taking effect on October 31, 2016. This is to include the other 2C-x analogues. [43]
In August 2007, 2C-B, along with many other psychologically active substances, [44] was added to Ley 20.000, known as the Ley de Drogas .
Possession of more than 200 mg of 2C-B is punishable with a two years jail sentence. [45] Smaller amount is punishable by a fine. The 200 mg threshold is merely a guideline which the court can reconsider depending on circumstances.
In Estonia, 2C-B is classified as Schedule I.
In Germany, 2C-B is controlled in the Betäubungsmittelgesetz (BtMG) Anlage I as "Bromdimethoxyphenethylamin" (BDMPEA).
2C-B is schedule I (tabella I). [47]
In Japan, 2C-B was scheduled in 1998. It was previously marketed as "Performax".
In Luxembourg, 2C-B is a prohibited substance since 2001. [48]
In the Netherlands, 2C-B was scheduled on July 9, 1997.
In the Netherlands, 2C-B became a list I substance of the Opium Law despite no health incidents occurring. Following the ban, other phenethylamines were sold in place of 2C-B until the Netherlands became the first country in the world to ban 2C-I, 2C-T-2 and 2C-T-7 alongside 2C-B.
In Norway, 2C-B was classified as Schedule II on March 22, 2004, listed as 4-bromo-2,5-dimethoxyphenethylamine. [49]
2C-B is schedule I (I-P group) in Poland.
Banned as a narcotic drug with a criminal penalty for possession of at least 10 mg. [50]
In Spain, 2C-B was added to Category 2 prohibited substances in 2002.
2C-B is currently classified as Schedule I in Sweden.
2C-B was first classified as "health hazard" under the act Lagen om förbud mot vissa hälsofarliga varor (Act on the Prohibition of Certain Goods Dangerous to Health) as of April 1, 1999, under SFS 1999:58 [51] that made it illegal to sell or possess. Then it became schedule I as of June 1, 2002, published in LVFS 2002:4 [52] but mislabeled "2-CB" in the document. However, this was corrected in a new document, LVFS 2009:22 [53] effective December 9, 2009.
In Switzerland, 2C-B is listed in Anhang D of the DetMV and is illegal to possess. [54]
All drugs in the 2C family are Class A under the Misuse of Drugs Act which means they are illegal to produce, supply or possess. Possession carries a maximum sentence of seven years imprisonment while supply is punishable by life imprisonment and an unlimited fine. [55]
In the United States, 2C-B is classified as CSA Schedule I Section (d) Subsection (3) 4-Bromo-2,5-dimethoxyphenethylamine.
In the United States, a notice of proposed rulemaking published on December 20, 1994, in the Federal Register and after a review of relevant data, the Deputy Administrator of the Drug Enforcement Administration (DEA) proposed to place 4-bromo-2,5-DMPEA into Schedule I, making 2C-B illegal in the United States. [56] This became permanent law on July 2, 1995. [57]
2C-I (2,5-Dimethoxy-4-iodophenethylamine) is a phenethylamine of the 2C family with psychedelic properties, primarily used as a recreational drug. 2C-I substance has been first synthesized by Alexander Shulgin, and is described in Shulgin's book PiHKAL (1991).
2C-T-7 is a psychedelic phenethylamine of the 2C family. In his book PiHKAL: A Chemical Love Story, Alexander Shulgin lists the dosage range as 10–30 mg. 2C-T-7 is generally taken orally, and produces psychedelic and entactogenic effects that last 8 to 15 hours. Up until Operation Web Tryp and three deaths, two of which involved the use of other drugs in addition to 2C-T-7, and one which involved an excessive insufflated dose, 2C-T-7 was sold commercially in Dutch and Japanese smartshops and online. It is known on the streets as Blue Mystic or 7th Heaven. There has been little real research done on this chemical other than Shulgin's comments in PiHKAL and a few small animal studies mostly aimed at detecting metabolites.
2C-C is a psychedelic drug of the 2C family. It was first synthesized by Alexander Shulgin, sometimes used as an entheogen. In his book PiHKAL , Shulgin lists the dosage range as 20–40 mg. 2C-C is usually taken orally, but may also be insufflated. 2C-C is schedule I of section 202(c) of the Controlled Substances Act in the United States, signed into law as of July, 2012 under the Food and Drug Administration Safety and Innovation Act.
2C-D is a psychedelic drug of the 2C family that is sometimes used as an entheogen. It was first synthesized in 1970 by a team from the Texas Research Institute of Mental Sciences, and its activity was subsequently investigated in humans by Alexander Shulgin. In his book PiHKAL, Shulgin lists the dosage range as being from 20 to 60 mg. Lower doses of 10 mg or less have been explored for microdosing.
2C-T-21 is a psychedelic phenethylamine of the 2C family sometimes used as an entheogen. It was first synthesized by Alexander Shulgin.
2,5-Dimethoxy-4-methylamphetamine is a psychedelic and a substituted amphetamine. It was first synthesized by Alexander Shulgin, and later reported in his book PiHKAL: A Chemical Love Story. DOM is classified as a Schedule I substance in the United States, and is similarly controlled in other parts of the world. Internationally, it is a Schedule I drug under the Convention on Psychotropic Substances. It is generally taken orally.
Dimethoxybromoamphetamine (DOB), also known as brolamfetamine and bromo-DMA, is a psychedelic drug and substituted amphetamine of the phenethylamine class of compounds. DOB was first synthesized by Alexander Shulgin in 1967. Its synthesis and effects are documented in Shulgin's book PiHKAL: A Chemical Love Story.
2C-T-8 is a psychedelic phenethylamine of the 2C family. It was first synthesized by Alexander Shulgin, sometimes used as an entheogen.
2,5-Dimethoxy-4-iodoamphetamine (DOI) is a psychedelic drug and a substituted amphetamine. Unlike many other substituted amphetamines, however, it is not primarily a stimulant. DOI has a stereocenter and R-(−)-DOI is the more active stereoisomer. In neuroscience research, [125I]-R-(−)-DOI is used as a radioligand and indicator of the presence of 5-HT2A serotonin receptors. DOI's effects have been compared to LSD, although there are differences that experienced users can distinguish. Besides the longer duration, the trip tends to be more energetic than an LSD trip, with more body load and a different subjective visual experience. The after effects include residual stimulation and difficulty sleeping, which, depending on the dose, may persist for days. While rare, it is sometimes sold as a substitute for LSD, or even sold falsely as LSD, which may be dangerous because DOI does not have the same established safety profile as LSD.
2C-B-FLY is a psychedelic phenethylamine and designer drug of the 2C family. It was first synthesized in 1996 by Aaron Monte, Professor of Chemistry at UW-La Crosse.
25I-NBOMe, also known as Smiles, or N-Bomb, is a novel synthetic psychoactive substance with strong hallucinogenic properties, synthesized in 2003 for research purposes. Since 2010, it has circulated in the recreational drug scene, often misrepresented as LSD.
2CBCB-NBOMe (NBOMe-TCB-2) is a compound indirectly derived from the phenethylamine series of hallucinogens, which was discovered in 2007 at Purdue University as part of the ongoing research program of the team led by David Nichols focusing on the mapping of the specific amino acid residues responsible for ligand binding to the 5HT2A receptor. 2CBCB-NBOMe acts as a potent and selective agonist for the 5-HT2A and 5-HT2C receptors, with a Ki of 0.27 nM at the human 5-HT2A receptor, a similar potency to other agonists such as TCB-2, NBOMe-2C-I and Bromo-DragonFLY.
2CBFly-NBOMe is a compound indirectly derived from the phenethylamine hallucinogen 2C-B, and related to benzodifurans like 2C-B-FLY and N-benzylphenethylamines like 25I-NBOMe. It was discovered in 2002, and further researched by Ralf Heim at the Free University of Berlin, and subsequently investigated in more detail by a team at Purdue University led by David E. Nichols. It acts as a potent partial agonist for the 5-HT2A serotonin receptor subtype.
25B-NBOMe is a derivative of the phenethylamine psychedelic 2C-B, discovered in 2004 by Ralf Heim at the Free University of Berlin. It acts as a potent full agonist for the 5HT2A receptor. Duration of effects lasts about 3–10 hours, although the parent compound is rapidly cleared from the blood when used in the radiolabeled form in tracer doses. Recently, Custodio et al. (2019) evaluated the potential involvement of dysregulated dopaminergic system, neuroadaptation, and brain wave changes which may contribute to the rewarding and reinforcing properties of 25B-NBOMe in rodents.
2CB-Ind is a conformationally-restricted derivative of the phenethylamine hallucinogen 2C-B, discovered in 1974 by Alexander Shulgin. It acts as a moderately potent and selective agonist for the 5-HT2A and 5-HT2C receptors, but unlike the corresponding benzocyclobutene derivative TCB-2 which is considerably more potent than the parent compound 2C-B, 2CB-Ind is several times weaker, with racemic 2CB-Ind having a Ki of 47nM at the human 5-HT2A receptor, only slightly more potent than the mescaline analogue (R)-jimscaline.
25C-NBOMe is a psychedelic drug and derivative of the psychedelic phenethylamine 2C-C. 25C-NBOMe appeared on online vendor sites in 2010 but was not reported in the literature until 2011. It acts as a potent agonist of the 5-HT2A receptor, and has been studied in its 11C radiolabelled form as a potential ligand for mapping the distribution of 5-HT2A receptors in the brain, using positron emission tomography (PET). Multiple deaths have occurred from usage of 25C-NBOMe due to the ease of accidental overdose. The long-term toxic effects of the drug have not been researched.
25B-NBOH is a derivative of the phenethylamine derived hallucinogen 2C-B which has been sold as a designer drug. It acts as a potent serotonin receptor agonist with similar affinity to the better-known compound 25B-NBOMe at 5-HT2A and 5-HT2C receptors with pKis values of 8.3 and 9.4, respectively.
2C-B-BUTTERFLY is a conformationally-restricted derivative of the phenethylamine hallucinogen 2C-B, which was discovered in 1999 by Michael S. Whiteside and Aaron Monte. It is a ring-expanded homologue of the better known compound 2C-B-FLY, and has similar properties as an agonist for serotonin receptors, but with more selectivity for 5-HT2C over 5-HT2A.
25B-NBF is a derivative of the phenethylamine hallucinogen 2C-B, which acts as a highly potent partial agonist for the human 5-HT2A receptor.
25G-NBOMe (NBOMe-2C-G) is a derivative of the phenethylamine hallucinogen 2C-G, which acts as a highly potent agonist for the human 5-HT2A receptor.