2C-B-FLY

Last updated

2C-B-FLY
2C-B-FLY structure.svg
2C-B-FLY 3D BS.png
Clinical data
Routes of
administration 		Oral [1] [2] [3] [4]
Drug class Serotonin 5-HT2 receptor agonist; Serotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen
Legal status
Legal status
Pharmacokinetic data
Duration of action 6–10 hours (but up to 20 hours) [4]
Identifiers
  • 2-(4-bromo-2,3,6,7-tetrahydrofuro[2,3-f][1]benzofuran-8-yl)ethanamine
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C12H14BrNO2
Molar mass 284.153 g·mol−1
3D model (JSmol)
Melting point 310 °C (590 °F)
  • NCCc1c2CCOc2c(Br)c3CCOc13
  • InChI=1S/C12H14BrNO2/c13-10-9-3-6-15-11(9)7(1-4-14)8-2-5-16-12(8)10/h1-6,14H2 Yes check.svgY
  • Key:YZDFADGMVOSVIX-UHFFFAOYSA-N Yes check.svgY

2C-B-FLY is a psychedelic and designer drug of the phenethylamine, 2C, and FLY families. [4] It was first described in 1995 by Aaron Monte, Professor of Chemistry at UW-La Crosse. [4] [5] [6]

Contents

Use and effects

2C-B-FLY was not included nor mentioned in Alexander Shulgin's 1991 book PiHKAL (Phenethylamines I Have Known and Loved). [7] In his subsequent 2011 book The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds however, he listed 2C-B-FLY's dose as 2.5 to 10 mg orally. [1] [2] On the other hand, other sources give 2C-B-FLY's typical dose range as 10 to 20 mg orally. [3] [4] The duration of 2C-B-FLY is said to be 6 to 10 hours but up to 20 hours. [4] The effects of 2C-B-FLY have been reported to include euphoria, enhanced interpersonal communication, improved mood, closed- and open-eye visuals such as brightening of colors and visual hallucinations, feelings of insight, stimulation, tactile enhancement, sexual enhancement, and altered time perception. [4] [8] [9] Other reported effects include pupil dilation, muscle twitching, restlessness, tachycardia, and body temperature changes. [4]

Toxicity

The toxicity of 2C-B-FLY in humans is unknown. Two deaths occurred in October 2009, in Denmark and the United States, after ingestion of a substance that was sold as 2C-B-FLY in a small-time RC shop, but in fact consisted of Bromo-DragonFLY contaminated with a small amount of unidentified impurities. [10]

Interactions

Pharmacology

Pharmacodynamics

2C-B-FLY activities
Target Affinity (Ki, nM)
5-HT1A 147–350
5-HT1B 185
5-HT1D 1.4
5-HT1E 110
5-HT1F ND
5-HT2A 11–11.6 (Ki)
0.029–53.7 (EC50 Tooltip half-maximal effective concentration)
80–104% (Emax Tooltip maximal efficacy)
5-HT2B 0.9 (Ki)
0.123–40 (EC50)
56–108% (Emax)
5-HT2C 10.6–12 (Ki)
0.0615–0.149 (EC50)
100–108% (Emax)
5-HT3 >10,000
5-HT4 ND
5-HT5A >10,000
5-HT6 150
5-HT7 606
α1A 11,000
α1B >10,000
α1D ND
α2A 145–780
α2B 624
α2C 233
β1 >10,000
β2 >10,000
β3 ND
D1 1,400–4,963
D2 1,900–6,835
D3 6,800
D4 >10,000
D5 >10,000
H1 3,400–5,753
H2–H4 >10,000
M1 643
M2 2,029
M3 339
M4 520
M5 873
I1 >10,000
σ1 >10,000
σ2 >10,000
TAAR1 Tooltip Trace amine-associated receptor 1710 (Ki) (mouse)
30 (Ki) (rat)
1,800 (EC50) (mouse)
270 (EC50) (rat)
>30,000 (EC50) (human)
49% (Emax) (mouse)
48% (Emax) (rat)
SERT Tooltip Serotonin transporter10,000 (Ki)
73,000 (IC50 Tooltip half-maximal inhibitory concentration)
(EC50)
NET Tooltip Norepinephrine transporter17,000 (Ki)
97,000 (IC50)
(EC50)
DAT Tooltip Dopamine transporter>26,000 (Ki)
187,000 (IC50)
(EC50)
MAO-A Tooltip Monoamine oxidase A19,000 (IC50)
MAO-B Tooltip Monoamine oxidase BND (IC50)
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [11] [12] [13] [14] [15] [16] [17] [18]

2C-B-FLY is a potent agonist of the serotonin 5-HT2 receptors, including the serotonin 5-HT2A, serotonin 5-HT2B, and serotonin 5-HT2C receptors. [13] [14] Unusually among 2C drugs, 2C-B-FLY also shows high affinity for the serotonin 5-HT1D receptor. [13] It also has relatively weak affinity for the serotonin 5-HT1A, 5-HT1B, and 5-HT1E receptors. [13] [14]

Chemistry

2C-B-Fly in powder form 2C-B-FLY.jpg
2C-B-Fly in powder form

2C-B-FLY is 8-bromo-2,3,6,7-benzo-dihydro-difuran-ethylamine. The full name of the chemical is 2-(8-bromo-2,3,6,7-tetrahydrofuro[2,3-f] [1]benzofuran-4-yl)ethanamine. It has been subject of little formal study, but its appearance as a designer drug has led the DEA to release analytical results for 2C-B-FLY and several related compounds.

Analogues and derivatives

Analogues of 2C-B-FLY include 2C-B, DOB-FLY, and Bromo-DragonFLY (DOB-DFLY), among others. [4] [19] [20]

In theory, dihydro-difuran analogs of any of the 2Cx / DOx family of drugs could be made, and would be expected to show similar activity to the parent compounds, 2-CB, DOB, DOM, etc. In the same way that 2C-B-FLY is the dihydro-difuran analog of 2C-B, the 8-iodo equivalent, "2C-I-FLY," would be the dihydro-difuran analogue of 2C-I, and the 8-methyl equivalent, "2C-D-FLY," would be the dihydro-difuran analogue of 2C-D.

Other related compounds can also be imagined and produced in which the alpha carbon of the ethylamine sidechain is methylated, giving the amphetamine derivative DOB-FLY, with this compound being the dihydro-difuran analogue of DOB, which can be viewed as the fully unsaturated derivative of Bromo-DragonFLY.

When only one methoxy group of a 2Cx drug is cyclized into a dihydro-furan ring, the resulting compound is known as a "hemifly", (and these could be termed 2- or 5- "hemis," depending on where the single dihydro-furan ring is placed). And when an unsaturated furan ring is inserted, the compound is known as a "hemi-dragonfly". The larger, fully saturated, hexahydro-benzo-dipyran ring derivative has been referred to as "2C-B-MOTH." The 8-bromo group can also be replaced by other groups to produce compounds such as TFMFly.

2C-B-FLY and some selected analogues (SAR). Bfly structures for wiki2.png
2C-B-FLY and some selected analogues (SAR).

A large number of symmetrical and asymmetrical derivatives can be produced by using different combinations of ring systems. Because the 2- and 5- positions (using the common phenylethylamine numbering scheme), the 2- and 5-positions of the benzene ring, if named as benzo-difurans are not equivalent.[ clarification needed ] Asymmetrical combinations have two possible positional isomers, with different pharmacological activities, at the various 5-HT2 subtypes. These compounds were casually referred to as the "2C-B-GNAT," and "2C-B-FLEA" compounds, which contain 5 or 6 membered rings at the 2- vs. 5-positions, respectively. Isomeric "Ψ"-derivatives with the oxygens positioned at the 2,6- positions, and mescaline analogues with the oxygens at 3,5- have also been made, but both are less potent than the corresponding 2,5- isomers. [21] [22] The symmetrical aromatic benzodifuran derivatives tend to have the highest binding affinity at 5-HT2A, but the saturated benzodifuran derivatives have higher efficacy, while the saturated benzodipyran derivatives are more selective for 5-HT2C. A large number of possible combinations have been synthesised and tested for activity, but these represent only a fraction of the many variations that could be produced. [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33]

History

2C-B-FLY was first described in the scientific literature by Aaron Phillip Monte and David E. Nichols and colleagues at Purdue University in 1995. [4] [5] [34] Following its discovery, Alexander Shulgin evaluated 2C-B-FLY. [35] [9] It was Ann Shulgin's favorite psychedelic drug and she found it particularly enjoyable in terms of enhanced eroticism. [36] [35] [9] [8] [37]

Society and culture

Canada

As of October 31, 2016; 2C-B-FLY is a controlled substance (Schedule III) in Canada. [38]

Finland

Scheduled in the "government decree on psychoactive substances banned from the consumer market". [39]

United States

2C-B-FLY is unscheduled and uncontrolled in the United States. However, it may fall under the scope of the Federal Analog Act if it is intended for human consumption given its similarity to 2C-B.

See also

References

  1. 1 2 Shulgin A, Manning T, Daley P (2011). The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds. Vol. 1. Berkeley: Transform Press. ISBN   978-0-9630096-3-0. 2C-B-FLY [733720-95-1] (2-5) [...] (2) Assayed in a drug discrimination paradigm with LSD-trained rats, and for interactions with various serotonin receptors (Monte et al., 1996). (3) Orally active in humans at 2.5-10 mg (Shulgin, 2003). (4) Synthesis (Monte et al., 1996). (5) Mass spectra of 2C-B-FLY, B-FLY and B-DFLY (Reed and Kiddon, 2007).
  2. 1 2 Luethi D, Liechti ME (October 2018). "Monoamine Transporter and Receptor Interaction Profiles in Vitro Predict Reported Human Doses of Novel Psychoactive Stimulants and Psychedelics". The International Journal of Neuropsychopharmacology. 21 (10): 926–931. doi:10.1093/ijnp/pyy047. PMC   6165951 . PMID   29850881.
  3. 1 2 Halberstadt AL, Chatha M, Klein AK, Wallach J, Brandt SD (May 2020). "Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species". Neuropharmacology. 167 107933. doi:10.1016/j.neuropharm.2019.107933. PMC   9191653 . PMID   31917152. Table 4 Human potency data for selected hallucinogens. [...]
  4. 1 2 3 4 5 6 7 8 9 10 Greene SL (2013). "Benzofurans and Benzodifurans". Novel Psychoactive Substances. Elsevier. pp. 383–392. doi:10.1016/b978-0-12-415816-0.00016-x. ISBN   978-0-12-415816-0. A typical reported dose of 2C-BFLY is 10–20mg orally [13,18].
  5. 1 2 Monte AP (August 1995). Structure-activity relationships of hallucinogens: Design, synthesis, and pharmacological evaluation of a series of conformationally restricted phenethylamines (Ph.D. thesis). Purdue University. Retrieved 15 April 2025.
  6. ↑ "Profile for Aaron Monte". UW-La Crosse. 2013-04-10. Dr. Monte has designed and synthesized several potent and selective drug molecules used to map the structural features of serotonin 5-HT2 receptor proteins, which mediate states of consciousness in the human central nervous system (CNS)
  7. ↑ Shulgin A, Shulgin A (September 1991). PiHKAL: A Chemical Love Story. Berkeley, California: Transform Press. ISBN   0-9630096-0-5. OCLC   25627628.
  8. 1 2 Hufford S (2007). "An Interview with Ann Shulgin on Psychedelics and Self-Discovery" (PDF). MAPS Newsletter. 17 (2). Multidisciplinary Association for Psychedelic Studies: 23–24. In one recent case, I said often, too often, that something called 2CB Fly was absolutely great for me. To me, it's the loveliest thing, especially for eroticism. But I found out that it's not interesting to anybody else. I realized that having said that, I was putting things in motion. The Internet was full of 2CB Fly, and people were asking about it and I thought "uh-oh." It turned out that it's a disappointment to most other people. So if I say what my favorite psychedelics are, it's almost meaningless for other people, because they have to find their allies very carefully.
  9. 1 2 3 Cooke J (1 July 2021). "2C-B-FLY: Is It The Best Psychedelic For Arousal & Sexual Intimacy?". Tripsitter. Retrieved 26 March 2025. The overall sentiment for [2C-B-FLY] is that it's one of the most enjoyable of the research psychedelics. Ann Shulgin — wife of Alexander Shulgin and co-author of the books TiHKAL and PiHKAL — once stated that 2C-B-FLY was one of her favorite psychedelics.
  10. ↑ "Erowid 2C-B-Fly Vault: Death Reports 2009". www.erowid.org. Retrieved 18 December 2022.
  11. ↑ "Kᵢ Database". PDSP. 16 March 2025. Retrieved 16 March 2025.
  12. ↑ Liu T. "BDBM50052339 2-(8-Bromo-2,3,6,7-tetrahydro-benzo[1,2-b;4,5-b']difuran-4-yl)-ethylamine::CHEMBL101189". BindingDB. Retrieved 3 March 2025.
  13. 1 2 3 4 Ray TS (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.
  14. 1 2 3 Rickli A, Kopf S, Hoener MC, Liechti ME (July 2015). "Pharmacological profile of novel psychoactive benzofurans". British Journal of Pharmacology. 172 (13): 3412–3425. doi:10.1111/bph.13128. PMC   4500375 . PMID   25765500.
  15. ↑ 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". Archives of Toxicology. 94 (10): 3449–3460. Bibcode:2020ArTox..94.3449P. doi:10.1007/s00204-020-02836-w. hdl: 1854/LU-8687071 . PMID   32627074.
  16. ↑ Wallach J, Cao AB, Calkins MM, Heim AJ, Lanham JK, Bonniwell EM, et al. (December 2023). "Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential". Nature Communications. 14 (1) 8221. Bibcode:2023NatCo..14.8221W. doi:10.1038/s41467-023-44016-1. PMC   10724237 . PMID   38102107.
  17. ↑ Wagmann L, Brandt SD, Stratford A, Maurer HH, Meyer MR (February 2019). "Interactions of phenethylamine-derived psychoactive substances of the 2C-series with human monoamine oxidases". Drug Testing and Analysis. 11 (2): 318–324. doi:10.1002/dta.2494. PMID   30188017.
  18. ↑ 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). The Journal of Pharmacology and Experimental Therapeutics. 357 (1): 134–144. doi:10.1124/jpet.115.229765. PMID   26791601. Archived from the original (PDF) on 9 May 2025.
  19. ↑ Luethi D, Liechti ME (April 2020). "Designer drugs: mechanism of action and adverse effects". Archives of Toxicology. 94 (4): 1085–1133. Bibcode:2020ArTox..94.1085L. doi:10.1007/s00204-020-02693-7. PMC   7225206 . PMID   32249347. The incorporation of 2'- and 5'-methoxy groups into rigid rings resulted in tetrahydrobenzodifuran and benzodifuran analogs that have been sold as designer drugs. These tetrahydrobenzodifuran and benzodifuran designer drugs are referred to as FLY and dragonFLY analogs, respectively, because of the shape of their chemical structure (Halberstadt et al. 2019; Trachsel et al. 2013)
  20. ↑ Trachsel D, Lehmann D, Enzensperger C (2013). Phenethylamine: von der Struktur zur Funktion [Phenethylamines: From Structure to Function]. Nachtschatten-Science (in German) (1 ed.). Solothurn: Nachtschatten-Verlag. ISBN   978-3-03788-700-4. OCLC   858805226.
  21. ↑ Monte AP, Waldman SR, Marona-Lewicka D, Wainscott DB, Nelson DL, Sanders-Bush E, et al. (September 1997). "Dihydrobenzofuran analogues of hallucinogens. 4. Mescaline derivatives". Journal of Medicinal Chemistry. 40 (19): 2997–3008. CiteSeerX   10.1.1.690.9370 . doi:10.1021/jm970219x. PMID   9301661.
  22. ↑ Chambers JJ, Kurrasch-Orbaugh DM, Nichols DE (August 2002). "Translocation of the 5-alkoxy substituent of 2,5-dialkoxyarylalkylamines to the 6-position: effects on 5-HT(2A/2C) receptor affinity". Bioorganic & Medicinal Chemistry Letters. 12 (15): 1997–1999. CiteSeerX   10.1.1.688.9483 . doi:10.1016/S0960-894X(02)00306-2. PMID   12113827.
  23. ↑ Nichols DE, Snyder SE, Oberlender R, Johnson MP, Huang XM (January 1991). "2,3-Dihydrobenzofuran analogues of hallucinogenic phenethylamines". Journal of Medicinal Chemistry. 34 (1): 276–281. doi:10.1021/jm00105a043. PMID   1992127.
  24. ↑ Monte AP, Marona-Lewicka D, Parker MA, Wainscott DB, Nelson DL, Nichols DE (July 1996). "Dihydrobenzofuran analogues of hallucinogens. 3. Models of 4-substituted (2,5-dimethoxyphenyl)alkylamine derivatives with rigidified methoxy groups". Journal of Medicinal Chemistry. 39 (15): 2953–2961. doi:10.1021/jm960199j. PMID   8709129.
  25. ↑ Parker M (1998). Studies of perceptiotropic phenethylamines: Determinants of affinity for the 5-HT2A receptor (PhD. Thesis). Purdue University. Archived from the original on 2012-04-25. Retrieved 2011-12-16.
  26. ↑ Chambers JJ, Kurrasch-Orbaugh DM, Parker MA, Nichols DE (March 2001). "Enantiospecific synthesis and pharmacological evaluation of a series of super-potent, conformationally restricted 5-HT(2A/2C) receptor agonists". Journal of Medicinal Chemistry. 44 (6): 1003–1010. CiteSeerX   10.1.1.691.362 . doi:10.1021/jm000491y. PMID   11300881.
  27. ↑ Whiteside MS, Kurrasch-Orbaugh D, Marona-Lewicka D, Nichols DE, Monte A (October 2002). "Substituted hexahydrobenzodipyrans as 5-HT2A/2C receptor probes". Bioorganic & Medicinal Chemistry. 10 (10): 3301–3306. CiteSeerX   10.1.1.1010.6813 . doi:10.1016/S0968-0896(02)00209-2. PMID   12150876.
  28. ↑ Chambers JJ, Parrish JC, Jensen NH, Kurrasch-Orbaugh DM, Marona-Lewicka D, Nichols DE (July 2003). "Synthesis and pharmacological characterization of a series of geometrically constrained 5-HT(2A/2C) receptor ligands". Journal of Medicinal Chemistry. 46 (16): 3526–3535. CiteSeerX   10.1.1.688.3544 . doi:10.1021/jm030064v. PMID   12877591.
  29. ↑ Schultz DM, Prescher JA, Kidd S, Marona-Lewicka D, Nichols DE, Monte A (June 2008). "'Hybrid' benzofuran-benzopyran congeners as rigid analogs of hallucinogenic phenethylamines". Bioorganic & Medicinal Chemistry. 16 (11): 6242–6251. doi:10.1016/j.bmc.2008.04.030. PMC   2601679 . PMID   18467103.
  30. ↑ Evans P (2000). Design and Synthesis of Novel 5-HT2A/2C Receptor Agonists (PDF) (PhD.). University of Wisconsin-La Cross. Archived from the original (PDF) on 2011-07-16. Retrieved 2010-05-27.
  31. ↑ Heim R (2004). Synthese und Pharmakologie potenter 5-HT2A-Rezeptoragonisten mit N-2-Methoxybenzyl-Partialstruktur. Entwicklung eines neuen Struktur-Wirkungskonzepts (PhD.). Der Freien Universität Berlin.
  32. ↑ Braden MR (2007). Towards a biophysical understanding of hallucinogen action (PhD.). Purdue University. ProQuest   304838368.
  33. ↑ Silva M (2009). Theoretical study of the interaction of agonists with the 5-HT2A receptor (PhD.). Universität Regensburg.
  34. ↑ Monte AP, Marona-Lewicka D, Parker MA, Wainscott DB, Nelson DL, Nichols DE (July 1996). "Dihydrobenzofuran analogues of hallucinogens. 3. Models of 4-substituted (2,5-dimethoxyphenyl)alkylamine derivatives with rigidified methoxy groups". Journal of Medicinal Chemistry. 39 (15): 2953–2961. doi:10.1021/jm960199j. PMID   8709129.
  35. 1 2 Kent J (17 June 2022). "Remembering Psychedelic Chemist Alexander Shulgin". Psychedelic Spotlight. Retrieved 26 March 2025. Ann and Sasha often experimented with psychedelics together, and shared their findings with their confidential research group. "Different people have different body types, so Sasha thought it was important to see how a drug reacts in all kinds of people." When I ask Ann what Sasha's favorite of his own chemicals is she knows immediately. "It would have to be 2C-B. He was always very proud of that one. He called it the Great Teacher. Although I preferred 2C-B-Fly a bit more." But there are so many to choose from. DiPT, 5-MeO-AMT, 5-MeO-DALT, Methylone, 2C-T-7, and this list goes on. Ann can't say for sure how many trips they shared together, she just smiles and says, "We stopped counting at around two-thousand." This is a mind-boggling number considering the total may actually be closer to four-thousand.
  36. ↑ "Godfather of Ecstasy: Alexander Shulgin's Last Trip". High Times. 10 September 2014. Retrieved 15 November 2025.
  37. ↑ Connie Littlefield (director, writer), Siobhan Flanagan, Alexander Shulgin (subject), Ann Shulgin (subject), Paul F. Daley (subject), Myron Stolaroff (subject), Jean Stolaroff (subject), Wendy Perry Tucker (subject), Tania Manning (subject), Greg Manning (subject), Keeper Trout (subject), Earth and Fire Erowid, others (2021). Better Living Through Chemistry (Motion picture). Better Living Through Film, Incorporated. Event occurs at ~49:50. Archived from the original on 21 September 2021.
  38. ↑ Government of Canada PW (May 4, 2016). "Regulations Amending the Food and Drug Regulations (Part J — 2C-phenethylamines)". Canada Gazette. Retrieved 2025-09-11.
  39. ↑ "Valtioneuvoston asetus kuluttajamarkkinoilta kielletyistä psykoaktiivisista aineista | 1130/2014" [Government Decree on psychoactive substances banned from the consumer market]. Lainsäädäntö [Legislation]. www.finlex.fi (in Finnish). Finlex . Retrieved 2025-09-11.
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