2C-B-FLY
| 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 |
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| Pharmacokinetic data | |
| Duration of action | 6–10 hours (but up to 20 hours)[4] |
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| Chemical and physical data | |
| Formula | C12H14BrNO2 |
| Molar mass | 284.153 g·mol−1 |
| 3D model (JSmol) | |
| Melting point | 310 °C (590 °F) |
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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]
Use and effects
[edit ]2C-B-FLY was not included or 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
[edit ]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
[edit ]Pharmacology
[edit ]Pharmacodynamics
[edit ]| 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 1 | 710 (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 transporter | 10,000 (Ki) 73,000 (IC50 Tooltip half-maximal inhibitory concentration) (EC50) |
| NET Tooltip Norepinephrine transporter | 17,000 (Ki) 97,000 (IC50) (EC50) |
| DAT Tooltip Dopamine transporter | >26,000 (Ki) 187,000 (IC50) (EC50) |
| MAO-A Tooltip Monoamine oxidase A | 19,000 (IC50) |
| MAO-B Tooltip Monoamine oxidase B | ND (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
[edit ]
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
[edit ]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.
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
[edit ]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]
Society and culture
[edit ]Legal status
[edit ]Canada
[edit ]As of October 31, 2016; 2C-B-FLY is a controlled substance (Schedule III) in Canada.[37]
Finland
[edit ]Scheduled in the "government decree on psychoactive substances banned from the consumer market".[38]
United States
[edit ]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
[edit ]References
[edit ]- ^ a b 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.
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).
- ^ a b 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.
- ^ a b 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" (PDF). Neuropharmacology. 167 107933. doi:10.1016/j.neuropharm.2019.107933. PMC 9191653 . PMID 31917152.
Table 4 Human potency data for selected hallucinogens. [...]
- ^ a b c d e f g h i j Greene, Shaun L (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].
- ^ a b 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.
- ^ "Profile for Aaron Monte". UW-La Crosse. 2013年04月10日.
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) – see, for example, https://en.wikipedia.org/wiki/2C-B-FLY.
{{cite web}}: External link in|quote= - ^ Shulgin, Alexander; Shulgin, Ann (September 1991). PiHKAL: A Chemical Love Story. Berkeley, California: Transform Press. ISBN 0-9630096-0-5. OCLC 25627628.
- ^ a b Sarah Hufford (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.
- ^ a b c Cooke, Justin (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.
- ^ "Erowid 2C-B-Fly Vault: Death Reports 2009". www.erowid.org. Retrieved 18 December 2022.
- ^ "Ki Database". PDSP. 16 March 2025. Retrieved 16 March 2025.
- ^ 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.
- ^ a b c d 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.
- ^ a b c Rickli A, Kopf S, Hoener MC, Liechti ME (July 2015). "Pharmacological profile of novel psychoactive benzofurans". Br J Pharmacol. 172 (13): 3412–3425. doi:10.1111/bph.13128. PMC 4500375 . PMID 25765500.
- ^ 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.
- ^ Wallach J, Cao AB, Calkins MM, Heim AJ, Lanham JK, Bonniwell EM, Hennessey JJ, Bock HA, Anderson EI, Sherwood AM, Morris H, de Klein R, Klein AK, Cuccurazzu B, Gamrat J, Fannana T, Zauhar R, Halberstadt AL, McCorvy JD (December 2023). "Identification of 5-HT2A receptor signaling pathways associated with psychedelic potential". Nat Commun. 14 (1) 8221. Bibcode:2023NatCo..14.8221W. doi:10.1038/s41467-023-44016-1. PMC 10724237 . PMID 38102107.
- ^ 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 Test Anal. 11 (2): 318–324. doi:10.1002/dta.2494. PMID 30188017.
- ^ 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 9 May 2025.
- ^ Luethi D, Liechti ME (April 2020). "Designer drugs: mechanism of action and adverse effects" (PDF). Arch Toxicol. 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)
- ^ 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.
- ^ Monte AP; 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.
- ^ 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): 1997–9. CiteSeerX 10.1.1.688.9483 . doi:10.1016/S0960-894X(02)00306-2. PMID 12113827.
- ^ Nichols DE; et al. (January 1991). "2,3-Dihydrobenzofuran analogues of hallucinogenic phenethylamines". Journal of Medicinal Chemistry. 34 (1): 276–81. doi:10.1021/jm00105a043. PMID 1992127.
- ^ Monte AP; et al. (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): 2953–61. doi:10.1021/jm960199j. PMID 8709129.
- ^ Parker, MA (1998). Studies of perceptiotropic phenethylamines: Determinants of affinity for the 5-HT2A receptor (PhD. Thesis). Purdue University. Archived from the original on 2012年04月25日. Retrieved 2011年12月16日.
- ^ 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): 1003–10. CiteSeerX 10.1.1.691.362 . doi:10.1021/jm000491y. PMID 11300881.
- ^ Whiteside MS; et al. (October 2002). "Substituted hexahydrobenzodipyrans as 5-HT2A/2C receptor probes". Bioorganic & Medicinal Chemistry. 10 (10): 3301–6. CiteSeerX 10.1.1.1010.6813 . doi:10.1016/S0968-0896(02)00209-2. PMID 12150876.
- ^ Chambers JJ; et al. (July 2003). "Synthesis and pharmacological characterization of a series of geometrically constrained 5-HT(2A/2C) receptor ligands". Journal of Medicinal Chemistry. 46 (16): 3526–35. CiteSeerX 10.1.1.688.3544 . doi:10.1021/jm030064v. PMID 12877591.
- ^ Schultz DM; et al. (June 2008). ""Hybrid" Benzofuran–Benzopyran Congeners as Rigid Analogues of Hallucinogenic Phenethylamines". Bioorganic & Medicinal Chemistry. 16 (11): 6242–51. doi:10.1016/j.bmc.2008年04月03日0. PMC 2601679 . PMID 18467103.
- ^ Evans, Paul (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年07月16日. Retrieved 2010年05月27日.
- ^ Heim, Ralf (2004). Synthese und Pharmakologie potenter 5-HT2A-Rezeptoragonisten mit N-2-Methoxybenzyl-Partialstruktur. Entwicklung eines neuen Struktur-Wirkungskonzepts (PhD.). Der Freien Universität Berlin.
- ^ Braden, Michael Robert (2007). Towards a biophysical understanding of hallucinogen action (PhD.). Purdue University. ProQuest 304838368.
- ^ Silva, Maria (2009). Theoretical study of the interaction of agonists with the 5-HT2A receptor (PhD.). Universität Regensburg.
- ^ 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". J Med Chem. 39 (15): 2953–2961. doi:10.1021/jm960199j. PMID 8709129.
- ^ a b Kent, James (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.
- ^ "Godfather of Ecstasy: Alexander Shulgin's Last Trip". High Times. 10 September 2014. Retrieved 15 November 2025.
- ^ Government of Canada, Public Works and Government Services Canada (May 4, 2016). "Regulations Amending the Food and Drug Regulations (Part J — 2C-phenethylamines)". Canada Gazette. Retrieved 2025年09月11日.
- ^ "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年09月11日.