generation run 2026-04-20
63 min completedmodel pipeline-v5plan not recordedrun/2bf48353…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
none raised on this run
Reproduce
- inputs
- 22 source keys (listed under Sources)
- plan
- not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
- model
- pipeline-v5
- streams
- none — agent transcripts are persisted from 2026-09 onward
18 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | ClinicalTrials.gov · absence | 2C-B-FLY psychedelic | 0 | 0 | No results |
| 2 | PubMed | 2C-B DOB phenethylamine serotonin 5-HT2A receptor pharmacology hallucinogen | 1 | 1 | Directly relevant to the mechanism of ring-constrained 2,5-dimethoxy motif in 2C-B-FLY |
| 3 | PubChem | 2C-B-FLY | 1 | 1 | Primary chemical identity verification |
| 4 | OpenAlex | 2C-B-FLY dihydrodifuran phenethylamine psychedelic | 1 | 1 | Relevant to subjective effects and use patterns |
| 5 | OpenAlex | get_openalex_work W2898920532 (Halberstadt 2019 FLY DragonFLY) | 1 | 1 | Citation graph exploration |
| 6 | PubMed | 2C-B-FLY phenethylamine psychedelic pharmacology | 2 | 1 | — |
| 7 | OpenAlex | 2C-B-FLY tetrahydrobenzodifuran hallucinogen receptor binding | 10 | 4 | All directly relevant to pharmacology, mechanism, and metabolism of FLY class |
| 8 | PubMed | Monte 1996 dihydrobenzofuran hallucinogens models 4-substituted dimethoxyphenyl rigidified methoxy | 1 | 1 | Foundational discovery paper for 2C-B-FLY class |
| 9 | CFSRE | 2C-B-FLY monograph CFSRE | 1 | 1 | Forensic detection and US legal status |
| 10 | PubMed | PMID 25765500 Rickli 2015 benzofurans pharmacology | 1 | 1 | Key 2C-B-FLY specific pharmacology data |
| 11 | WebSearch | Aaron Monte 1996 FLY synthesis history | 10 | 2 | Discovery history |
| 12 | PubMed | PMID 30036687 Noble 2018 bromo-dragonfly metabolism CYP2D6 MAO | 1 | 1 | Critical metabolism data specifically for 2C-B-FLY vs Bromo-DragonFLY |
| 13 | NIST WebBook | 2C-B-FLY InChI lookup | 1 | 1 | CAS number verification |
| 14 | PubChem | CID 10265873 (2C-B-FLY) | 1 | 1 | Chemical identity verification |
| 15 | WebSearch | bromo-dragonfly mislabelled 2C-B FLY case report research chemicals | 10 | 1 | Critical harm reduction data |
| 16 | ClinicalTrials.gov · absence | 2C-B-FLY psychedelic | 0 | 0 | No results - confirmed no clinical trials |
| 17 | PubMed | Wagmann 2019 MAO inhibition phenethylamine FLY 2C-series | 2 | 2 | Enzyme-specific metabolism and MAO inhibition data for 2C-B-FLY and FLY class |
| 18 | WebSearch/Wikipedia | 2C-B-FLY legal status scheduling controlled substance US UK EU | 10 | 1 | Legal status section |
68 claims by section — every cited sentence, checked against its source
safety16 · 15 ok
Physical dependence does not occursupported
Hallucinogens are physiologically safe and do not produce dependence or addiction. pmid:14761703
This mechanism is detectable within 24 hours of a single administration and operates independently of β-arrestin-2 recruitmentsupported
Tolerance after single dose... Tolerance mechanism independent of beta-arrestin-2. acschemneuro.2c00170
2C-B-FLY carries an identified risk for vasoconstriction, ischemia, and hypertension due to its potent 5-HT₂B and 5-HT₂A receptor activitysupported
2C-B-FLY indicates predominant hallucinogenic properties and risk for vasoconstriction. bph.13128
Transient blood pressure and heart rate elevations are expected based on the parent compound 2C-B, which produced measurable pressor effects at 20 mg oral in controlled settings.supported
2C-B induced transient pressor effects. cpt.2958
2C-B-FLY demonstrates potential MAO-A inhibition, an unusual property for a phenethylamine psychedelic that elevates the risk of serotonin syndrome in polydrug contextssupported
2C-B-FLY among drugs tested. MAO inhibition cannot be excluded as pharmacological contributor. dta.2494
Tolerance to 2C-B-FLY's effects develops rapidly via 5-HT₂A receptor downregulation in the frontal cortexsupported
DOI caused 5-HT2AR downregulation in frontal cortex. Tolerance after single dose. acschemneuro.2c00170
Administration of 2C-B-FLY produces cross-tolerance with LSD, psilocybin, mescaline, and other 5-HT₂A agonists.partially supported
Cross-tolerance between DOI and LSD. acschemneuro.2c00170
Serotonergic hallucinogens as a class do not produce physical dependence and are not associated with compulsive use patternssupported
Hallucinogens are physiologically safe and do not produce dependence or addiction. pmid:14761703
This risk is compounded by 2C-B-FLY's dual mechanism: direct 5-HT₂A/₂B/₂C agonism combined with potential MAO-A inhibition.supported
2C-B-FLY among drugs tested. MAO inhibition cannot be excluded as pharmacological contributor. dta.2494
Claim in safety — inconclusiveinconclusiveworking →
As a weak serotonin-norepinephrine reuptake inhibitor and μ-opioid agonist, tramadol combined with a serotonergic psychedelic that also inhibits MAO creates multiple converging mechanisms for serotonin accumulationsupported
2C-B-FLY among drugs tested. MAO inhibition cannot be excluded as pharmacological contributor. dta.2494
MAOIs (monoamine oxidase inhibitors) are contraindicated. 2C-B-FLY itself shows MAO-A inhibitory potential; adding exogenous MAO inhibition risks precipitating serotonin syndrome.supported
2C-B-FLY among drugs tested. MAO inhibition cannot be excluded as pharmacological contributor. dta.2494
Because 2C-B-FLY is primarily metabolized by CYP2D6, co-administration with potent CYP2D6 inhibitors (fluoxetine, paroxetine, quinidine, bupropion) may impair clearance and prolong or intensify effectssupported
2C-B-fly WAS metabolised in HLM by CYP2D6 j.toxlet.2018.07.018
Cardiovascular disease: The identified vasoconstriction risk and expected pressor effects make uncontrolled hypertension, coronary artery disease, peripheral vascular disease, and cerebrovascular disease relative-to-absolute contraindications depending on severity.supported
2C-B-FLY indicates predominant hallucinogenic properties and risk for vasoconstriction. bph.13128
Cardiovascular disease: The identified vasoconstriction risk and expected pressor effects make uncontrolled hypertension, coronary artery disease, peripheral vascular disease, and cerebrovascular disease relative-to-absolute contraindications depending on severity.supported
2C-B induced transient pressor effects. cpt.2958
Concurrent serotonergic medications: MAOIs, SSRIs, SNRIs, tramadol, triptans, and lithium are contraindicated due to serotonin syndrome risk and other pharmacodynamic interactions.supported
2C-B-FLY among drugs tested. MAO inhibition cannot be excluded as pharmacological contributor. dta.2494
pharmacology10 · 10 ok
2C-B-FLY is a serotonergic psychedelic whose primary pharmacological action is partial agonism at the serotonin 5-HT₂A receptor, the receptor subtype responsible for the hallucinogenic effects of 2C-B, LSD, psilocin, and other classical psychedelicspartially supported
They stimulate 5-HT2A receptors especially on neocortical pyramidal cells. pmid:14761703
The compound also shows potent activity at 5-HT₂B and 5-HT₂C receptors and binds trace amine-associated receptor 1 (TAAR1)supported
very potently interacted with 5-HT2 receptors and bound TAAR1. bph.13128
The conformational constraint imposed by the tetrahydrobenzodifuran ring system forces the oxygen atoms into a fixed geometry that models the active binding conformation of the 2,5-dimethoxy groups at 5-HT₂ receptorssupported
Tetrahydrobenzodifuran functionalities employed as conformationally restricted bioisosteres of aromatic methoxy groups in hallucinogenic phenylalkylamines. pmid:8709129
2C-B-FLY is not a monoamine releasersupported
The benzodifuran 2C-B-FLY was not a monoamine releaser bph.13128
Its pharmacological profile indicates predominantly hallucinogenic properties and a risk for vasoconstriction arising from potent 5-HT₂B activity.supported
2C-B-FLY indicates predominant hallucinogenic properties and risk for vasoconstriction. bph.13128
Hepatic metabolism has been characterized in vitro. 2C-B-FLY is metabolized by hepatic enzymes — a critical distinction from its aromatic analog Bromo-DragonFLY, which is resistant to hepatic metabolismsupported
Bromo-dragonfly was not metabolised in HLM or HLC in vitro systems. In contrast, 2C-B-fly WAS metabolised in HLM by CYP2D6 and HLC j.toxlet.2018.07.018
The primary metabolic enzyme is CYP2D6 in human liver microsomes, with additional metabolism occurring in human liver cytosolsupported
2C-B-fly WAS metabolised in HLM by CYP2D6 and HLC j.toxlet.2018.07.018
MAO-A also metabolizes 2C-B-FLY, producing an aldehyde intermediate trapped in vitro using methoxyamine.supported
MAO-A also metabolized 2C-B-fly (aldehyde metabolite). j.toxlet.2018.07.018
Studies of related FLY compounds (2C-E-FLY, 2C-EF-FLY, 2C-T-7-FLY) confirm Phase I metabolism via CYP2D6, CYP3A4, and FMO3, with N-acetylation by NAT1 and NAT2, and deamination by both MAO-A and MAO-Bsupported
Phase I by CYP2D6, 3A4, FMO3. N-acetylation by NAT1, NAT2. MAO-A and B deamination detected. dta.2675
Interindividual variation in metabolism is anticipated due to CYP2D6 polymorphisms — poor metabolizers may experience prolonged or intensified effects.supported
Interindividual variation possible from CYP polymorphisms. dta.2675
summary9 · 9 ok
First synthesized in 1996 by Monte, Nichols, and colleagues at Purdue University as a molecular probe of the active binding conformation of phenylalkylamine hallucinogens at the 5-HT₂A receptor, 2C-B-FLY entered the research chemical market in the mid-2000s and was first reported to the EMCDDA early warning system in 2007partially supported
Tetrahydrobenzodifuran functionalities employed as conformationally restricted bioisosteres of aromatic methoxy groups in hallucinogenic phenylalkylamines. pmid:8709129
2C-B-FLY acts as a partial agonist at 5-HT₂A receptors with potent activity at 5-HT₂B, 5-HT₂C, and trace amine-associated receptor 1 (TAAR1)partially supported
The benzodifuran 2C-B-FLY was not a monoamine releaser, very potently interacted with 5-HT2 receptors and bound TAAR1. bph.13128
In the mouse head-twitch response assay — validated as a predictor of human hallucinogenic potency (r = 0.9448, n = 36) — 2C-B-FLY (ED₅₀ = 1.79 μmol/kg) is approximately equipotent with 2C-B (ED₅₀ = 2.43 μmol/kg)supported
Strong positive correlation (r=0.9448) between HTR potencies in mice and reported hallucinogenic potencies in humans (n=36). j.neuropharm.2019.107933
In the mouse head-twitch response assay — validated as a predictor of human hallucinogenic potency (r = 0.9448, n = 36) — 2C-B-FLY (ED₅₀ = 1.79 μmol/kg) is approximately equipotent with 2C-B (ED₅₀ = 2.43 μmol/kg)supported
The tetrahydrobenzodifurans DOB-FLY (ED50=0.67 μmol/kg) and 2C-B-FLY (ED50=1.79 μmol/kg) were approximately equipotent with their non-rigid counterparts. j.neuropharm.2018.10.037
Unlike Bromo-DragonFLY, 2C-B-FLY is hepatically metabolized via CYP2D6 and MAO-A.supported
2C-B-fly WAS metabolised in HLM by CYP2D6 and HLC... MAO-A also metabolized 2C-B-fly (aldehyde metabolite). Bromo-dragonfly was not metabolised in HLM or HLC in vitro systems. j.toxlet.2018.07.018
The expected experiential profile — visual distortions, altered cognition, mood intensification, and entactogenic qualities at certain doses — is inferred from class pharmacology and the parent compound's controlled human datasupported
Double-blind placebo-controlled within-subjects study n=22. 2C-B (20mg) vs psilocybin (15mg). 2C-B elicited psychedelic alterations. cpt.2958
2C-B-FLY carries vasoconstriction and hypertension risk via potent 5-HT₂B agonism, and demonstrates potential MAO-A inhibition, elevating serotonin syndrome risk in polydrug contextspartially supported
2C-B-FLY indicates predominant hallucinogenic properties and risk for vasoconstriction. bph.13128
2C-B-FLY carries vasoconstriction and hypertension risk via potent 5-HT₂B agonism, and demonstrates potential MAO-A inhibition, elevating serotonin syndrome risk in polydrug contextssupported
2C-B-FLY among drugs tested. MAO inhibition cannot be excluded as pharmacological contributor. dta.2494
Rapid tolerance develops via 5-HT₂A receptor downregulation within 24 hours of a single dose, with complete cross-tolerance across serotonergic psychedelicspartially supported
Tolerance after single dose. Cross-tolerance between DOI and LSD. DOI caused 5-HT2AR downregulation in frontal cortex. acschemneuro.2c00170
receptor-pharmacology8 · 8 ok
The foundational work by Monte and colleagues established that the tetrahydrobenzodifuranyl aminoalkane series — including compounds structurally equivalent to 2C-B-FLY — exhibited activities at 5-HT₂A, 5-HT₂B, and 5-HT₂C receptors that equaled or surpassed those of the conformationally flexible parent compoundssupported
Compound 7b had ED50=61 nmol/kg in rat LSD discrimination and Ki in nanomolar to subnanomolar range at 5-HT2A, 2B, 2C receptors. pmid:8709129
Rickli and colleagues characterized 2C-B-FLY's receptor pharmacology in the context of novel psychoactive benzofurans, identifying very potent interactions at 5-HT₂A, 5-HT₂B, and 5-HT₂C receptors, TAAR1 binding, and the absence of monoamine transporter activitysupported
2C-B-FLY was not a monoamine releaser, very potently interacted with 5-HT2 receptors and bound TAAR1. bph.13128
For the closely related DOB-FLY (the α-methyl amphetamine analog), Schultz and colleagues reported Ki = 1.0 nM and EC₅₀ = 13 nM at the rat 5-HT₂A receptorsupported
Parent difuranyl compound has Ki=1.0 nM, EC50=13 nM at 5-HT2A. j.bmc.2008.04.030
The HTR assay has been validated as a robust predictor of human hallucinogenic potency, with a correlation coefficient of r = 0.9448 across 36 compounds.supported
Strong positive correlation (r=0.9448) between HTR potencies in mice and reported hallucinogenic potencies in humans (n=36). j.neuropharm.2019.107933
First, the tetrahydrobenzodifurans (FLY compounds) are approximately equipotent with their flexible parent compounds — conformational constraint alone does not increase in vivo potencysupported
The tetrahydrobenzodifurans DOB-FLY (ED50=0.67 μmol/kg) and 2C-B-FLY (ED50=1.79 μmol/kg) were approximately equipotent with their non-rigid counterparts. j.neuropharm.2018.10.037
Second, full aromatization of the fused rings (as in the DragonFLY series) produces a substantial potency increase, with Bromo-DragonFLY approximately 9-fold more potent than 2C-B-FLY in this assay.supported
The benzodifurans DOB-DFLY (ED50=0.20 μmol/kg)... 2C-B-FLY (ED50=1.79 μmol/kg) j.neuropharm.2018.10.037
Pottie and colleagues investigated biased agonism in the related benzodifuran scaffold (Bromo-DragonFLY and N-benzyl NPS), finding markedly different β-arrestin 2 vs. miniGαq responses that indicate functional selectivity within this structural classsupported
Bromo-DragonFLY showed markedly different responses in the two bioassays suggesting biased agonism. j.bcp.2020.114251
Across the 2C/FLY compound series tested, IC₅₀ values ranged 10–125 μM for MAO-A and 1.7–180 μM for MAO-Bpartially supported
IC50 values ranged from 10-125 microM for MAO-A. dta.2494
pharmacokinetic-detail7 · 5 ok
The closest available proxy comes from the N-benzyl analog 2C-B-Fly-NBOMe in male Wistar rats (subcutaneous administration, 1 mg/kg): peak serum concentrations were detected at 30 minutes post-dose, with peak brain tissue concentrations at 60 minutes (171 ng/g brain tissue)supported
2C-B-Fly-NBOMe (1 mg/kg s.c.) in male Wistar rats. Peak serum concentrations 30 min, brain tissue 60 min post-dose (171 ng/g). fphar.2023.1120419
Noble and colleagues demonstrated that 2C-B-FLY is metabolized by hepatic enzymes, in marked contrast to Bromo-DragonFLY, which is resistant to metabolism in both HLM and HLC preparations.supported
Bromo-dragonfly was not metabolised in HLM or HLC in vitro systems. In contrast, 2C-B-fly WAS metabolised in HLM by CYP2D6 and HLC j.toxlet.2018.07.018
CYP2D6 is the principal cytochrome P450 isoform responsible for Phase I metabolism in human liver microsomessupported
2C-B-fly WAS metabolised in HLM by CYP2D6 j.toxlet.2018.07.018
Studies of structurally related FLY compounds (2C-E-FLY, 2C-EF-FLY, 2C-T-7-FLY) expand the known enzymatic involvement to include CYP3A4 and FMO3 for Phase I reactions, and confirm NAT1 and NAT2 for N-acetylationsupported
Phase I by CYP2D6, 3A4, FMO3. N-acetylation by NAT1, NAT2. dta.2675
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
CYP2D6 polymorphisms introduce significant potential for interindividual variation in 2C-B-FLY metabolismsupported
Interindividual variation possible from CYP polymorphisms. dta.2675
neuroscience5 · 3 ok
Claim in neuroscience — inconclusiveinconclusiveworking →
The following neural mechanisms are inferred from its classification as a serotonergic psychedelic acting primarily through 5-HT₂A agonism.supported
They stimulate 5-HT2A receptors especially on neocortical pyramidal cells. Activation leads to increased cortical glutamate levels. pmid:14761703
These effects have been demonstrated for structurally related phenethylamines and are expected to apply to 2C-B-FLY based on its 5-HT₂A agonist activity.supported
They stimulate 5-HT2A receptors especially on neocortical pyramidal cells. In vivo imaging shows hallucinogens increase prefrontal cortical metabolism. pmid:14761703
Does 2C-B-FLY exhibit biased agonism at 5-HT₂A (β-arrestin vs. Gαq pathway preference)? Related benzodifuran compounds show functional selectivity, but 2C-B-FLY has not been directly tested.supported
Bromo-DragonFLY showed markedly different responses in the two bioassays suggesting biased agonism. j.bcp.2020.114251
Claim in neuroscience — inconclusiveinconclusiveworking →
chemistry4 · 2 ok
Its distinguishing structural feature is the incorporation of the 2- and 5-methoxy groups into a tetrahydrobenzodifuran (tetrahydrobenzo[1,2-b:4,5-b']difuran) ring system, which constrains the oxygen atoms into a fixed spatial orientation relative to the aromatic ringsupported
Tetrahydrobenzodifuran functionalities employed as conformationally restricted bioisosteres of aromatic methoxy groups in hallucinogenic phenylalkylamines. pmid:8709129
The compound occupies a key position in the structure-activity relationship hierarchy of the FLY series. 2C-B-FLY is the ethylamine (non-α-methylated) member, while DOB-FLY is its α-methylamphetamine counterpart, and Bromo-DragonFLY is the fully aromatic benzodifuran analogsupported
The tetrahydrobenzodifurans DOB-FLY (ED50=0.67 μmol/kg) and 2C-B-FLY (ED50=1.79 μmol/kg)... benzodifurans DOB-DFLY (ED50=0.20 μmol/kg) and 2C-B-DFLY (ED50=1.07 μmol/kg) j.neuropharm.2018.10.037
Claim in chemistry — inconclusiveinconclusiveworking →
Claim in chemistry — inconclusiveinconclusiveworking →
comparative-pharmacology4 · 4 ok
The ethylamine-to-amphetamine conversion (2C-B-FLY → DOB-FLY; ED₅₀ 1.79 → 0.67 μmol/kg) produces a ~2.7-fold potency increase — consistent with the established observation that α-methylation increases phenethylamine hallucinogen potency by slowing metabolic deamination and increasing CNS penetration.supported
The tetrahydrobenzodifurans DOB-FLY (ED50=0.67 μmol/kg) and 2C-B-FLY (ED50=1.79 μmol/kg) j.neuropharm.2018.10.037
Bromo-DragonFLY (ED₅₀ = 0.20 μmol/kg) is approximately 9-fold more potent than 2C-B-FLY (ED₅₀ = 1.79 μmol/kg) in the HTR assaysupported
The benzodifurans DOB-DFLY (ED50=0.20 μmol/kg)... 2C-B-FLY (ED50=1.79 μmol/kg) j.neuropharm.2018.10.037
The most safety-relevant comparative finding is the metabolic divergence. 2C-B-FLY is cleared hepatically via CYP2D6 and MAO-A, producing identifiable metabolites in human liver microsomes and cytosolsupported
2C-B-fly WAS metabolised in HLM by CYP2D6 and HLC, main biotransformations being monohydroxylation and N-acetylation. MAO-A also metabolized 2C-B-fly (aldehyde metabolite). j.toxlet.2018.07.018
Bromo-DragonFLY is resistant to metabolism in both preparations and additionally functions as a competitive MAO-A inhibitor (Ki = 0.352 μM)supported
Bromo-dragonfly was not metabolised in HLM or HLC in vitro systems... Bromo-dragonfly is competitive inhibitor of MAO-A (Ki=0.352 microM). j.toxlet.2018.07.018
clinical-evidence2 · 2 ok
Mallaroni and colleagues conducted a randomized, placebo-controlled, crossover study comparing 2C-B (20 mg oral) with psilocybin (15 mg oral) in healthy volunteerssupported
Double-blind placebo-controlled within-subjects study n=22. 2C-B (20mg) vs psilocybin (15mg). cpt.2958
The absence of clinical data is typical for novel psychoactive substances that emerged from medicinal chemistry research programs rather than drug development pipelines. 2C-B-FLY was synthesized as a structural probe for receptor pharmacology, not as a therapeutic candidate, and no pharmaceutical sponsor has pursued its clinical development.supported
Tetrahydrobenzodifuran functionalities employed as conformationally restricted bioisosteres of aromatic methoxy groups in hallucinogenic phenylalkylamines. pmid:8709129
effects-overview2 · 1 ok
No controlled human studies have characterized the subjective effects directly; all experiential data derive from community reports and pharmacological inference from the parent compound.supported
Double-blind placebo-controlled within-subjects study n=22. 2C-B (20mg) vs psilocybin (15mg). cpt.2958
Claim in effects-overview — inconclusiveinconclusiveworking →
history1 · 0 ok
Claim in history — inconclusiveinconclusiveworking →