2C (psychedelics)

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General structure of a 2C compound. 2C-general.png
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. [1] [2] [3] 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. [4]

Contents

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). [3] [5] [6] 2C-B is the most popular of the 2C drugs. [3]

Use and effects

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. [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 produce psychedelic effects, such as perceptual enhancement, psychedelic visuals, and euphoria. [1] [6] [9] [3] Some, such as 2C-B, have also been reported to produce some entactogen-like effects, but findings in this area appear to be mixed. [9] [3] [10] [11]

Interactions

The 2C drugs are metabolized by the monoamine oxidase (MAO) enzymes, including both MAO-A and MAO-B. [1] [15] As a result, they may be potentiated by monoamine oxidase inhibitors (MAOIs), such as phenelzine, tranylcypromine, moclobemide, and selegiline. [1] [15] [16] This may lead to overdose and serious toxicity. [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]

Pharmacology

Pharmacodynamics

Actions

The 2C drugs act as agonists of the serotonin 5-HT2 receptors, including of the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors. [18] [19] [20] [21] [22] They are partial agonists of the serotonin 5-HT2A receptor. [18] [19] Most of the 2C drugs have much lower affinity for the serotonin 5-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] The psychedelic 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, including 2C-C, 2C-D, 2C-E, 2C-I, and 2C-T-2 among others, are inactive as monoamine releasing agents and reuptake inhibitors. [18] [23] [20] [19] [22] Most of the 2C drugs are agonists of the rat and mouse trace 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 weak monoamine oxidase inhibition, including of monoamine oxidase A (MAO-A) and/or monoamine oxidase B (MAO-B). [18]

2C drugs at serotonin 5-HT1 and 5-HT2 receptors
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 130–311NDND104.46.9–27.61.89–805–99%13.575–13052–89%43–89.50.031–0.264104–116%
2C-C 190–740>10,000<25%252.95.47–139.27–20049–102%ND28081%5.4–9024.294%
2C-D 440–1,630>10,000<25%ND23.9–32.443.5–35041–125%ND23077%12.7–15071.1100%
2C-E 307.3–1,190>10,000<25%ND4.50–43.92.5–11040–125%25.119066%5.4–104.10.233–18.098–106%
2C-H 70NDNDND1,6002,408–9,40028–67%ND6,20046%4,100NDND
2C-I 180–9704,900102%ND3.5–9.33.83–6015–82%ND15070%10.2–402.879–100%
2C-N 2,200NDNDND23.517020–48%ND73074%370ND40–50%
2C-P 110NDNDND8.19063%ND13072%40NDND
2C-T-1 1,035NDNDND492.075%ND5758%347NDND
2C-T-2 370–1,7403,00076%857.59–39.90.354–8067–128%613075%14.2–690.0233–3.887–107%
2C-T-4 470–916NDNDND27.9–545.5–22056–87%ND63–16068–75%180–295NDND
2C-T-7 520–878NDNDND5.3–6.51.2–13049–101%ND52–35045–75%39–54NDND
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]

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. [18] At least some 2C drugs, such as 2C-D and 2C-E, produce hyperlocomotion at lower doses in rodents. [18] All 2C drugs produce hypolocomotion at higher doses in rodents. [18] 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. [18] [20] However, none of the assessed 2C drugs substituted for dextromethamphetamine, suggesting that they lack amphetamine-type or stimulant-like effects. [18] [20]

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. [18] [30] The mechanism by which these effects are mediated is unknown. [18] 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. [18] [30] These 2C drugs might have misuse potential in humans. [18] [30] 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. [18] [31] [32] [33] [34] [35] [36]

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. [18]

Various 2C drugs show potent anti-inflammatory effects mediated by serotonin 5-HT2A receptor activation. [37] Among these include 2C-I, 2C-B, 2C-H, and 2C-iBu. [37] [38] Others, such as 2C-B-Fly and 2C-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 a pharmaceutical drug. [38] [39]

Pharmacokinetics

The 2C drugs are orally active. [1] They are metabolized by O-demethylation and deamination. [1] [15] 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. [15]

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). [5] [6] [7] [40] [4] 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. [6] [7] [40] [4] The N-benzylphenethylamines such as 25I-NBOMe, 25B-NBOMe, and 25C-NBOMe are derivatives of the 2C drugs. [41] [5] [4] Certain FLY drugs such as 2C-B-FLY are also 2C derivatives. [5] [4] [2]

Syntheses

The chemical syntheses of 2C drugs have been described. [6] [2]

Analysis

The chemical analysis of 2C drugs has been described. [5]

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. [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 synthesized 2C-B and 2C-D in 1974 and discovered their psychedelic effects in self-experiments conducted in 1974 and 1975. [1] [41] [2] [44] [47] [48] He published his findings in the scientific 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 and David 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 synthesized 2C-E in 1977. [52] [53] He reviewed several of these 2C drugs in a literature 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 book PiHKAL (Phenethylamines I Have Known and Loved). [6] [3] 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. [6] [1] [3]

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. [41] [55] [56] [57] [58] It was also informally studied by Darrell Lemaire as a potential "smart drug" in the 1970s and 1980s. [59] [60] [61] [62] He additionally developed the TWEETIO drugs such as 2CD-5-ETO via structural modification of the 2Cs. [59] [60] [61] [62] [40] [7] 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. [63] [5] [64] [65] It was sold in adult stores, smart shops, and some nightclubs. [63] [64]

2C-B was first encountered as a novel designer drug in the United States in 1979. [63] It gained popularity as a recreational drug and MDMA (ecstasy) alternative in the mid-1980s. [1] [3] [5] The drug became a controlled 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]

Society and culture

Canada

As of October 12, 2016, the 2C-x family of substituted phenethylamines is a controlled substance (Schedule III) in Canada. [66]

List of 2C drugs

See also

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Dean BV, Stellpflug SJ, Burnett AM, Engebretsen KM (June 2013). "2C or not 2C: phenethylamine designer drug review". J Med Toxicol. 9 (2): 172–178. doi:10.1007/s13181-013-0295-x. PMC   3657019 . PMID   23494844. 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].
  2. 1 2 3 4 5 6 7 8 9 Shulgin, A.; Manning, T.; Daley, P.F. (2011). The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds. Vol. 1. Berkeley: Transform Press. ISBN   978-0-9630096-3-0 . Retrieved 2 November 2024.
  3. 1 2 3 4 5 6 7 8 9 10 11 Wills B, Erickson T (9 March 2012). "Psychoactive Phenethylamine, Piperazine, and Pyrrolidinophenone Derivatives". In Barceloux DG (ed.). Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants. Wiley. pp. 156–192. doi:10.1002/9781118105955.ch10. ISBN   978-0-471-72760-6. 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.
  4. 1 2 3 4 5 6 7 Trachsel, D.; Lehmann, D.; Enzensperger, C. (2013). "8.5.3. 4-Alkyl-2,5-dimethoxyphenethylamine (2C-R- oder 2C-Alkylderivate)". Phenethylamine: von der Struktur zur Funktion [Phenethylamines: From Structure to Function]. Nachtschatten-Science (in German) (1 ed.). Solothurn: Nachtschatten-Verlag. pp. 763–771. ISBN   978-3-03788-700-4. OCLC   858805226.
  5. 1 2 3 4 5 6 7 8 9 10 Anilanmert, Beril; Yonar, Fatma Çavuş; Özdemir, Ali Acar (31 January 2018). "2C Derivatives of Phenylethylamines and Their Analysis". Chromatographic Techniques in the Forensic Analysis of Designer Drugs. Chromatographic science series. Boca Raton : Taylor & Francis/CRC Press, 2018.: CRC Press. pp. 277–304. doi:10.1201/9781315313177-15. ISBN   978-1-315-31317-7 . Retrieved 14 November 2025.{{cite book}}: CS1 maint: location (link)
  6. 1 2 3 4 5 6 7 8 9 10 Shulgin, Alexander; Shulgin, Ann (September 1991). PiHKAL: A Chemical Love Story. Berkeley, California: Transform Press. ISBN   0-9630096-0-5. OCLC   25627628.
  7. 1 2 3 4 5 6 Jacob P, Shulgin AT (1994). "Structure-activity relationships of the classic hallucinogens and their analogs" (PDF). NIDA Res Monogr. 146: 74–91. PMID   8742795. Archived from the original (PDF) on August 5, 2023.
  8. 1 2 Ballentine, Galen; Friedman, Samuel Freesun; Bzdok, Danilo (March 2022). "Trips and neurotransmitters: Discovering principled patterns across 6850 hallucinogenic experiences". Sci Adv. 8 (11) eabl6989. Bibcode:2022SciA....8L6989B. doi:10.1126/sciadv.abl6989. PMC   8926331 . PMID   35294242.
  9. 1 2 Luethi D, Liechti ME (April 2020). "Designer drugs: mechanism of action and adverse effects". Arch Toxicol. 94 (4): 1085–1133. Bibcode:2020ArTox..94.1085L. doi:10.1007/s00204-020-02693-7. PMC   7225206 . PMID   32249347. 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).
  10. ↑ González, Débora; Torrens, Marta; Farré, Magí (2015). "Acute Effects of the Novel Psychoactive Drug 2C-B on Emotions". Biomed Res Int. 2015 643878. doi: 10.1155/2015/643878 . PMC   4620274 . PMID   26543863.
  11. ↑ Mallaroni P, Mason NL, Reckweg JT, Paci R, Ritscher S, Toennes SW, Theunissen EL, Kuypers KP, Ramaekers JG (August 2023). "Assessment of the Acute Effects of 2C-B vs. Psilocybin on Subjective Experience, Mood, and Cognition". Clin Pharmacol Ther. 114 (2): 423–433. doi: 10.1002/cpt.2958 . PMID   37253161.
  12. ↑ Luethi D, Liechti ME (October 2018). "Monoamine Transporter and Receptor Interaction Profiles in Vitro Predict Reported Human Doses of Novel Psychoactive Stimulants and Psychedelics". Int J Neuropsychopharmacol. 21 (10): 926–931. doi:10.1093/ijnp/pyy047. PMC   6165951 . PMID   29850881.
  13. ↑ Halberstadt, Adam L.; Chatha, Muhammad; Klein, Adam K.; Wallach, Jason; Brandt, Simon D. (May 2020). "Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species" (PDF). Neuropharmacology. 167 107933. doi:10.1016/j.neuropharm.2019.107933. PMC   9191653 . PMID   31917152. Table 4 Human potency data for selected hallucinogens. [...]
  14. ↑ Trachsel D (2012). "Fluorine in psychedelic phenethylamines" . Drug Test Anal. 4 (7–8): 577–590. doi:10.1002/dta.413. PMID   22374819.
  15. 1 2 3 4 5 Theobald DS, Maurer HH (January 2007). "Identification of monoamine oxidase and cytochrome P450 isoenzymes involved in the deamination of phenethylamine-derived designer drugs (2C-series)". Biochem Pharmacol. 73 (2): 287–297. doi:10.1016/j.bcp.2006.09.022. PMID   17067556.
  16. 1 2 Halman A, Kong G, Sarris J, Perkins D (January 2024). "Drug-drug interactions involving classic psychedelics: A systematic review". J Psychopharmacol. 38 (1): 3–18. doi:10.1177/02698811231211219. PMC   10851641 . PMID   37982394.
  17. ↑ Dean, Be Vang; Stellpflug, Samuel J.; Burnett, Aaron M.; Engebretsen, Kristin M. (June 2013). "2C or not 2C: phenethylamine designer drug review". Journal of Medical Toxicology. 9 (2): 172–178. doi:10.1007/s13181-013-0295-x. ISSN   1937-6995. PMC   3657019 . PMID   23494844.
  18. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Gil-Martins, Eva; Barbosa, Daniel José; Borges, Fernanda; Remião, Fernando; Silva, Renata (June 2025). "Toxicodynamic insights of 2C and NBOMe drugs - Is there abuse potential?". Toxicol Rep. 14 101890. Bibcode:2025ToxR...1401890G. doi:10.1016/j.toxrep.2025.101890. PMC   11762925 . PMID   39867514.
  19. 1 2 3 4 5 6 7 8 Rickli A, Luethi D, Reinisch J, Buchy D, Hoener MC, Liechti ME (December 2015). "Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs)" (PDF). Neuropharmacology. 99: 546–553. doi:10.1016/j.neuropharm.2015.08.034. PMID   26318099.
  20. 1 2 3 4 5 6 7 Eshleman AJ, Forster MJ, Wolfrum KM, Johnson RA, Janowsky A, Gatch MB (March 2014). "Behavioral and neurochemical pharmacology of six psychoactive substituted phenethylamines: mouse locomotion, rat drug discrimination and in vitro receptor and transporter binding and function". Psychopharmacology (Berl). 231 (5): 875–888. doi:10.1007/s00213-013-3303-6. PMC   3945162 . PMID   24142203.
  21. 1 2 3 Ray, Thomas S. (February 2010). "Psychedelics and the human receptorome". PLOS ONE. 5 (2) e9019. Bibcode:2010PLoSO...5.9019R. doi: 10.1371/journal.pone.0009019 . PMC   2814854 . PMID   20126400.
  22. 1 2 3 Varì, M. Rosaria; Pichini, Simona; Giorgetti, Raffaele; Busardò, Francesco P. (2019). "New psychoactive substances—Synthetic stimulants". WIREs Forensic Science. 1 (2) e1197. doi: 10.1002/wfs2.1197 . ISSN   2573-9468.
  23. ↑ Nagai F, Nonaka R, Satoh Hisashi Kamimura K (March 2007). "The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain". European Journal of Pharmacology. 559 (2–3): 132–137. doi:10.1016/j.ejphar.2006.11.075. PMID   17223101.
  24. 1 2 Gainetdinov RR, Hoener MC, Berry MD (July 2018). "Trace Amines and Their Receptors". Pharmacol Rev. 70 (3): 549–620. doi: 10.1124/pr.117.015305 . PMID   29941461.
  25. 1 2 Simmler LD, Buchy D, Chaboz S, Hoener MC, Liechti ME (April 2016). "In Vitro Characterization of Psychoactive Substances at Rat, Mouse, and Human Trace Amine-Associated Receptor 1" (PDF). J Pharmacol Exp Ther. 357 (1): 134–144. doi:10.1124/jpet.115.229765. PMID   26791601. Archived from the original (PDF) on 2025-05-09.
  26. ↑ Rudin D, Luethi D, Hoener MC, Liechti ME (2022). "Structure-activity Relation of Halogenated 2,5-Dimethoxyamphetamines Compared to their α‑Desmethyl (2C) Analogues". The FASEB Journal. 36 (S1) fasebj.2022.36.S1.R2121. doi: 10.1096/fasebj.2022.36.S1.R2121 . ISSN   0892-6638.
  27. ↑ Pottie E, Cannaert A, Stove CP (October 2020). "In vitro structure-activity relationship determination of 30 psychedelic new psychoactive substances by means of β-arrestin 2 recruitment to the serotonin 2A receptor". Arch Toxicol. 94 (10): 3449–3460. Bibcode:2020ArTox..94.3449P. doi:10.1007/s00204-020-02836-w. hdl: 1854/LU-8687071 . PMID   32627074.
  28. ↑ Luethi D, Trachsel D, Hoener MC, Liechti ME (May 2018). "Monoamine receptor interaction profiles of 4-thio-substituted phenethylamines (2C-T drugs)" (PDF). Neuropharmacology. 134 (Pt A): 141–148. doi:10.1016/j.neuropharm.2017.07.012. PMID   28720478.
  29. ↑ Halberstadt AL, Luethi D, Hoener MC, Trachsel D, Brandt SD, Liechti ME (January 2023). "Use of the head-twitch response to investigate the structure-activity relationships of 4-thio-substituted 2,5-dimethoxyphenylalkylamines" (PDF). Psychopharmacology (Berl). 240 (1): 115–126. doi:10.1007/s00213-022-06279-2. PMC   9816194 . PMID   36477925.
  30. 1 2 3 Kim YJ, Ma SX, Hur KH, Lee Y, Ko YH, Lee BR, Kim SK, Sung SJ, Kim KM, Kim HC, Lee SY, Jang CG (April 2021). "New designer phenethylamines 2C-C and 2C-P have abuse potential and induce neurotoxicity in rodents". Arch Toxicol. 95 (4): 1413–1429. Bibcode:2021ArTox..95.1413K. doi:10.1007/s00204-021-02980-x. PMID   33515270.
  31. ↑ Zawilska JB, Kacela M, Adamowicz P (2020). "NBOMes-Highly Potent and Toxic Alternatives of LSD". Front Neurosci. 14 78. doi: 10.3389/fnins.2020.00078 . PMC   7054380 . PMID   32174803.
  32. ↑ Custodio, Raly James Perez; Sayson, Leandro Val; Botanas, Chrislean Jun; Abiero, Arvie; You, Kyung Yi; Kim, Mikyung; Lee, Hyun Jun; Yoo, Sung Yeun; Lee, Kun Won; Lee, Yong Sup; Seo, Joung-Wook; Ryu, In Soo; Kim, Hee Jin; Cheong, Jae Hoon (November 2020). "25B-NBOMe, a novel N-2-methoxybenzyl-phenethylamine (NBOMe) derivative, may induce rewarding and reinforcing effects via a dopaminergic mechanism: Evidence of abuse potential" . Addiction Biology. 25 (6) e12850. doi:10.1111/adb.12850. ISSN   1355-6215. PMID   31749223.
  33. ↑ Seo JY, Hur KH, Ko YH, Kim K, Lee BR, Kim YJ, Kim SK, Kim SE, Lee YS, Kim HC, Lee SY, Jang CG (October 2019). "A novel designer drug, 25N-NBOMe, exhibits abuse potential via the dopaminergic system in rodents". Brain Res Bull. 152: 19–26. doi:10.1016/j.brainresbull.2019.07.002. PMID   31279579.
  34. ↑ Jo C, Joo H, Youn DH, Kim JM, Hong YK, Lim NY, Kim KS, Park SJ, Choi SO (November 2022). "Rewarding and Reinforcing Effects of 25H-NBOMe in Rodents". Brain Sci. 12 (11): 1490. doi: 10.3390/brainsci12111490 . PMC   9688077 . PMID   36358416.
  35. ↑ Lee JG, Hur KH, Hwang SB, Lee S, Lee SY, Jang CG (August 2023). "Designer Drug, 25D-NBOMe, Has Reinforcing and Rewarding Effects through Change of a Dopaminergic Neurochemical System". ACS Chem Neurosci. 14 (15): 2658–2666. doi:10.1021/acschemneuro.3c00196. PMID   37463338.
  36. ↑ Kim YJ, Kook WA, Ma SX, Lee BR, Ko YH, Kim SK, Lee Y, Lee JG, Lee S, Kim KM, Lee SY, Jang CG (April 2024). "The novel psychoactive substance 25E-NBOMe induces reward-related behaviors via dopamine D1 receptor signaling in male rodents". Arch Pharm Res. 47 (4): 360–376. doi:10.1007/s12272-024-01491-4. PMID   38551761.
  37. 1 2 3 Flanagan TW, Billac GB, Landry AN, Sebastian MN, Cormier SA, Nichols CD (April 2021). "Structure-Activity Relationship Analysis of Psychedelics in a Rat Model of Asthma Reveals the Anti-Inflammatory Pharmacophore". ACS Pharmacol Transl Sci. 4 (2): 488–502. doi:10.1021/acsptsci.0c00063. PMC   8033619 . PMID   33860179.
  38. 1 2 WOpublished 2020210823, Nichols CD, Billac G, Nichols DE,"Compounds and methods for treating inflammatory disorders",published 15 October 2020
  39. ↑ Newvine C (8 July 2020). "Eleusis Draws on Research Into Psychedelics To Develop New Medicines for Inflammation". Lucid News - Psychedelics, Consciousness Technology, and the Future of Wellness. Retrieved 16 February 2025.
  40. 1 2 3 Shulgin AT (2003). "Basic Pharmacology and Effects". In Laing RR (ed.). Hallucinogens: A Forensic Drug Handbook. Forensic Drug Handbook Series. Elsevier Science. pp. 67–137. ISBN   978-0-12-433951-4.
  41. 1 2 3 4 5 Poulie CB, Jensen AA, Halberstadt AL, Kristensen JL (December 2020). "DARK Classics in Chemical Neuroscience: NBOMes". ACS Chem Neurosci. 11 (23): 3860–3869. doi:10.1021/acschemneuro.9b00528. PMC   9191638 . PMID   31657895. 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).
  42. 1 2 3 Shulgin AT (1978). "Psychotomimetic Drugs: Structure-Activity Relationships". In Iversen LL, Iversen SD, Snyder SH (eds.). Stimulants. Boston, MA: Springer US. pp. 243–333. doi:10.1007/978-1-4757-0510-2_6. ISBN   978-1-4757-0512-6.
  43. ↑ Jansen, Max. P. J. M. (1931). "β-2: 4: 5-Trimethoxyphenylethylamine, an isomer of mescaline". Recueil des Travaux Chimiques des Pays-Bas. 50 (4): 291–312. doi:10.1002/recl.19310500403. ISSN   0165-0513.
  44. 1 2 3 4 Standridge RT, Howell HG, Gylys JA, Partyka RA, Shulgin AT (December 1976). "Phenylakylamines with potential psychotherapeutic utility. 1. 2-Amino-1-(2,5-dimethoxy-4-methylphenyl)butane" (PDF). J Med Chem. 19 (12): 1400–1404. doi:10.1021/jm00234a010. PMID   1003425. 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).
  45. 1 2 Ho BT, Tansey LW, Balster RL, An R, McIsaac WM, Harris RT (January 1970). "Amphetamine analogs. II. Methylated phenethylamines". J Med Chem. 13 (1): 134–135. doi:10.1021/jm00295a034. PMID   5412084.
  46. 1 2 Ho BT, Huang JT (December 1970). "Effects of mescaline and 2,5-dimethoxy-4-methylphenethylamine on sleeping time in mice". J Pharm Pharmacol. 22 (12): 949–951. doi:10.1111/j.2042-7158.1970.tb08483.x. PMID   4395524.
  47. 1 2 Shulgin AT, Carter MF (1975). "Centrally active phenethylamines". Psychopharmacol Commun. 1 (1): 93–98. PMID   1223994.
  48. ↑ https://isomerdesign.com/pihkal/notebooks/transcripts/p1/p1.175.pdf
  49. ↑ https://isomerdesign.com/pihkal/notebooks/transcripts/p1/p1.94.pdf
  50. ↑ Nichols DE, Shulgin AT (October 1976). "Sulfur Analogs of Psychotomimetic Amines" . J Pharm Sci. 65 (10): 1554–1556. Bibcode:1976JPhmS..65.1554S. doi:10.1002/jps.2600651040. PMID   978423.
  51. ↑ Braun U, Shulgin AT, Braun G, Sargent T (December 1977). "Synthesis and body distribution of several iodine-131 labeled centrally acting drugs" (PDF). J Med Chem. 20 (12): 1543–1546. doi:10.1021/jm00222a001. PMID   592317.
  52. ↑ Darie, Iulia-Florentina; Praisler, Mirela; Negoita, Catalin (12 November 2021). "2C-x and DOx hallucinogens: A systematic review". Annals of the "Dunarea de Jos" University of Galati Fascicle II Mathematics Physics Theoretical Mechanics. 44 (1): 46–52. doi: 10.35219/ann-ugal-math-phys-mec.2021.1.07 . ISSN   2668-7151 . Retrieved 26 January 2025.
  53. ↑ Alexander Shulgin (1980). Pharmacology Notes II (The Shulgin Lab Books) (PDF). Lafayette, CA, USA: Erowid. p. 236.
  54. ↑ Shulgin AT (1979). "Chemistry of phenethylamines related to mescaline". J Psychedelic Drugs. 11 (1–2): 41–52. doi:10.1080/02791072.1979.10472091. PMID   522167.
  55. ↑ Passie, Torsten (2024). "A history of the European Medical Society for Psycholytic Therapy (EPT) 1964–1974". Drug Science, Policy and Law. 10. doi: 10.1177/20503245231221154 . ISSN   2050-3245 . Retrieved 14 November 2025. 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.
  56. ↑ Passie, Torsten (7 November 2022). "History of the Use of Hallucinogens in Psychiatric Treatment". In Grob, Charles S.; Grigsby, Jim (eds.). Handbook of Medical Hallucinogens. Guilford Publications. pp. 95–118. ISBN   978-1-4625-5189-7. 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.
  57. ↑ Leuner, Hanscarl (1981). Halluzinogene: psychische Grenzzustände in Forschung und Psychotherapie [Hallucinogens: Altered Psychological States in Research and Psychotherapy] (in German). Huber. ISBN   978-3-456-80933-5.
  58. ↑ Michael Schlichting. Psychotrope Eigenschaften des Phenäthylamins DMM-PEA (2,5-dimethoxy-4-methyl-phenathylamin)[Psychotropic Properties of the Phenethylamine DMM-PEA (2,5-dimethoxy-4-methyl-phenethylamine)] (Thesis). Göttingen, Germany: Göttingen University.
  59. 1 2 "Erowid Darrell Lemaire Vault". erowid.org. Retrieved 14 November 2025.
  60. 1 2 Morris H (7 December 2016). "The Lazy Lizard School of Hedonism". Hamilton's Pharmacopeia . Season 1. Episode 6. Vice Media. Viceland.
  61. 1 2 Hosteen Nez (Darrell Lemaire) (2010). "Notes About Psychoactive Compounds" (PDF). In Targ, Russell; Radin, Dean (eds.). Radiant Minds: Scientists Explore the Dimensions of Consciousness. Millay. pp. 201–207. ISBN   978-0-615-29633-3.
  62. 1 2 Lazar (Darrell Lemaire); Hosteen Nez (1990), 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 (2 ed.), archived from the original (PDF) on 9 July 2001
  63. 1 2 3 "Information Bulletin 2C-B (Nexus) Reappears on the Club Drug Scene". Department of Justice. 1 January 2006. Retrieved 14 November 2025.
  64. 1 2 Caudevilla-Gálligo F, Riba J, Ventura M, González D, Farré M, Barbanoj MJ, Bouso JC (July 2012). "4-Bromo-2,5-dimethoxyphenethylamine (2C-B): presence in the recreational drug market in Spain, pattern of use and subjective effects". J Psychopharmacol. 26 (7): 1026–1035. doi:10.1177/0269881111431752. PMID   22234927. 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).
  65. ↑ Johnson, Cody (5 June 2018). Magic Medicine: A Trip Through the Intoxicating History and Modern-Day Use of Psychedelic Plants and Substances. Fair Winds Press. ISBN   978-1-63159-428-1. 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."
  66. ↑ "Regulations Amending the Food and Drug Regulations (Part J — 2C-phenethylamines)". Canada Gazette . April 15, 2016. Retrieved August 28, 2016.
  67. ↑ Takahashi M, Nagashima M, Suzuki J, Seto T, Yasuda I, Yoshida T (2009). "Creation and application of psychoactive designer drugs data library using liquid chromatography with photodiode array spectrophotometry detector and gas chromatography–mass spectrometry". Talanta. 77 (4): 1245–1272. doi:10.1016/j.talanta.2008.07.062.
  68. ↑ Varty GB, Canal CE, Mueller TA, Hartsel JA, Tyagi R, Avery K, Morgan ME, Reichelt AC, Pathare P, Stang E, Palfreyman MG, Nivorozhkin A (April 2024). "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 of Medicinal Chemistry. 67 (8): 6144–6188. doi:10.1021/acs.jmedchem.3c01961. PMID   38593423.
  69. ↑ WO 2024/089226,Nivorozhkin A, Hartsel JA, Canal CE, Salituro FG, Mueller TA, Greene BJ, Belser A, Palfreyman M,"Phenethylamine compounds, compositions, and methods of use.",published 2 May 2024, assigned to Cybin IRL Ltd.
  70. ↑ Leth-Petersen S, Petersen IN, Jensen AA, Bundgaard C, Bæk M, Kehler J, Kristensen JL (2016). "5-HT2A/5-HT2C receptor pharmacology and intrinsic clearance of N-benzylphenethylamines modified at the primary site of metabolism". ACS Chem. Neurosci. 7 (11): 1614–1619. doi:10.1021/acschemneuro.6b00265.
  71. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 "Shulgin's Sulfur Symphony – Part I". countyourculture. 15 January 2011. Archived from the original on 19 September 2019. Retrieved 22 October 2017.
  72. ↑ Daniel Trachsel (2003). "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)". Helvetica Chimica Acta . 86 (7): 2610–2619. doi:10.1002/hlca.200390210.
  73. ↑ Varty GB, Canal CE, Mueller TA, Hartsel JA, Tyagi R, Avery K, Morgan ME, Reichelt AC, Pathare P, Stang E, Palfreyman MG, Nivorozhkin A (Apr 2024). "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". J Med Chem. 67 (8): 6144–6188. doi:10.1021/acs.jmedchem.3c01961. PMID   38593423.
  74. ↑ Patentscope. Kruegel AC. Phenalkylamines and Methods of Treating Mood Disorders. Patent WO 2022/006186. Retrieved 2025-05-12
  75. ↑ Leth-Petersen S, Gabel-Jensen C, Gillings N, Lehel S, Hansen HD, Knudsen GM, Kristensen JL (January 2016). "Metabolic Fate of Hallucinogenic NBOMes". Chem Res Toxicol. 29 (1): 96–100. doi:10.1021/acs.chemrestox.5b00450. PMID   26669514. [Supporting Information] [...] Entry 35: N-(4-bromo-2,5-dimethoxyphenethyl)hydroxylamine [...]
  76. ↑ 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 (July 2024). "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" (PDF). Mol Pharmacol. 106 (2): 92–106. doi:10.1124/molpharm.123.000837. PMC   11254453 . PMID   38821630.
  77. ↑ Nichols DE (May 1973). Potential Psychotomimetics: Bromomethoxyamphetamines and Structural Congeners of Lysergic Acid (Thesis). University of Iowa. p. 23. OCLC   1194694085.
  78. ↑ "2C-B-morpholine". Isomer Design. 1 April 2025. Retrieved 1 June 2025.
  79. ↑ Glennon RA, Bondarev ML, Khorana N, Young R, May JA, Hellberg MR, McLaughlin MA, Sharif NA (November 2004). "Beta-oxygenated analogues of the 5-HT2A serotonin receptor agonist 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane". J Med Chem. 47 (24): 6034–6041. doi:10.1021/jm040082s. PMID   15537358. Archived from the original on 2024-05-23.
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