Bromo-DragonFLY

# Research Output: Bromo-DragonFLY

## Chemical Identity

**PubChem CID:** 10544447 [verified via API]

**Systematic/IUPAC Name:** (2R)-1-(4-bromofuro[2,3-f][1]benzofuran-8-yl)propan-2-amine
- Confirmed via PubChem CID lookup; matches brief seed data exactly.
- Alternative systematic name used in literature: 1-(8-bromobenzo[1,2-b;4,5-b']difuran-4-yl)-2-aminopropane (Corazza et al. 2011 [Ref 6]; Halberstadt et al. 2019 [Ref 5])

**Molecular Formula:** C₁₃H₁₂BrNO₂ — verified via PubChem [CID 10544447]

**Molecular Weight:** 294.14 g/mol — verified via PubChem

**Isomeric SMILES:** `C[C@H](CC1=C2C=COC2=C(C3=C1OC=C3)Br)N` — retrieved from PubChem REST API (CID 10544447)

**Canonical SMILES:** `CC(CC1=C2C=COC2=C(C3=C1OC=C3)Br)N`

**InChI:** `InChI=1S/C13H12BrNO2/c1-7(15)6-10-8-2-4-17-13(8)11(14)9-3-5-16-12(9)10/h2-5,7H,6,15H2,1H3/t7-/m1/s1`

**InChIKey:** GIKPTWKWYXCBEC-SSDOTTSWSA-N — verified via PubChem

**CAS Number:** Not confirmed via API; literature references do not consistently cite a CAS number. This is a **gap to flag** — editorial review needed.

**Stereochemistry:** The commercially and recreationally encountered form is the (R)-(−) enantiomer. The enantiospecific synthesis was reported by Nichols' group in 2001, which enabled study of individual enantiomers; the (R)-(−)-enantiomer possesses greater binding affinity at 5-HT2A and 5-HT2C receptors than the (S)-(+)-enantiomer (web-retrieved from synthesis history; see Gaps). The PubChem entry (CID 10544447) represents the R-enantiomer explicitly.

**Brief discrepancies:**
- SMILES was blank in the brief; now confirmed from PubChem REST API.
- PubChem CID was blank in the brief; now confirmed as 10544447.
- Molecular formula and weight were blank; now confirmed as C₁₃H₁₂BrNO₂ / 294.14 g/mol.
- InChIKey was blank; now confirmed.

---

## Pharmacology

### Primary Receptor: 5-HT2A Agonist

Bromo-DragonFLY is among the most potent known agonists at the serotonin 5-HT2A receptor. Åstrand et al. (2020 [Ref 3]) screened 60 new psychoactive substances at four receptors using the AequoZen cell system and found that bromo-dragonfly had the **highest 5-HT2A potency of all compounds tested: EC₅₀ = 0.05 nM, making it approximately 400 times more potent than LSD** at this receptor. Binding affinity (Ki) values reported across studies range from 0.04–1.86 nM at 5-HT2A (HandWiki, citing multiple published studies; primary source verification of the range endpoints needed — see Gaps).

The benzodifuran ring system is responsible for this exceptional potency. Chambers, Kurrasch-Orbaugh, & Nichols (2002 [Ref 7]) established the structure-activity relationship: incorporating the methoxy groups of 2,5-dimethoxyphenethylamines into aromatic furan rings of the benzo[1,2-b;4,5-b']difuran nucleus confers an approximately **27-fold increase in 5-HT2A affinity** compared to the non-rigid positional isomer. Halberstadt et al. (2019 [Ref 5]) confirmed enhanced in vivo potency in mouse head twitch response (HTR) assay: DOB-DFLY (Bromo-DragonFLY) ED₅₀ = **0.20 µmol/kg** versus DOB (its non-rigid analog) at 0.75 µmol/kg — a **3.75-fold potency increase** in vivo. The α-methyl group additionally contributes to potency enhancement.

### 5-HT2B and 5-HT2C Agonism

The compound is also a potent 5-HT2B agonist (Ki = 0.126–0.19 nM; EC₅₀ = 0.0851–0.457 nM per HandWiki, citing multiple sources). 5-HT2B activation is associated with vasoconstriction and, in chronic use contexts, heart valve pathology. 5-HT2C binding affinity: Ki = 0.02–1.48 nM (HandWiki). Rickli et al. (2015 [Ref 9]) characterized the benzodifuran 2C-B-FLY (a close analogue lacking the α-methyl group) as very potently interacting with 5-HT2 receptors and concluded its pharmacology indicates "predominant hallucinogenic properties and a risk for vasoconstriction" — this characterization applies a fortiori to Bromo-DragonFLY given its greater potency.

> **⚠️ FLAG for human review:** The Ki ranges (0.04–1.86 nM for 5-HT2A) represent values aggregated across studies and cited via secondary sources (HandWiki). The primary published sources for these specific values need direct verification. The Noble et al. 2018 [Ref 2] and Parker et al. 1998 [Ref 1] papers are likely primary sources; abstracts were not fully available for binding tabulation. Generation agent should treat these ranges as indicative, not definitively verified.

### Off-Target Receptor Activity

Åstrand et al. (2020 [Ref 3]) found Bromo-DragonFLY to be **the only compound among 60 NPS tested that activated all four receptors**: μ-opioid, CB1, 5-HT1A, and 5-HT2A. This multi-receptor profile is clinically significant: it may explain complex toxicity presentations that differ from pure 5-HT2A agonism. The μ-opioid and CB1 activities are relatively minor compared to 5-HT2A but represent off-target effects not described for LSD or most other serotonergic psychedelics.

Pottie, Dedecker, & Stove (2020 [Ref 4]) found markedly different responses for Bromo-DragonFLY in β-arrestin 2 versus miniGαq bioassays, suggesting **functional bias** at 5-HT2AR, though the calculated bias factor approximated 0. This highlights complexity in accurately assessing biased agonism for this compound.

### MAO-A Inhibition

Noble et al. (2018 [Ref 2]) identified a **critical secondary pharmacological activity**: Bromo-DragonFLY is a **competitive inhibitor of MAO-A with Ki = 0.352 µM** (IC₅₀ approximately 540 nM). This is clinically relevant — MAO-A normally degrades serotonin and tyramine. MAO-A inhibition by Bromo-DragonFLY may potentiate serotonin accumulation in vivo, contributing to both its prolonged effects and its dangerous interaction with serotonergic drugs such as tramadol. The IC₅₀ value indicates the inhibition may be clinically significant, though more in vivo data are needed (Noble et al. 2018 [Ref 2]).

### Mechanism of Vasoconstriction

The extreme peripheral vasoconstriction that distinguishes Bromo-DragonFLY from most psychedelics operates through α-1 adrenergic receptor agonism combined with 5-HT2B receptor activation. The α-1 adrenergic mechanism is consistent with the compound's amphetamine-like structural scaffold (Corazza et al. 2011 [Ref 6]; Tennessee Poison Center 2016 [Ref 15]). The combination of sustained high-level 5-HT2B and α-1 activation during a multi-day exposure window explains why peripheral ischemia and gangrene have been observed in overdose cases.

### Pharmacokinetics

**Metabolic stability (in vitro):** Noble et al. (2018 [Ref 2]) tested Bromo-DragonFLY in pooled human liver microsomes (HLM) and pooled human liver cytosol (HLC) and found **no metabolism in either system**. By comparison, the close structural analogue 2C-B-FLY was metabolized by CYP2D6 in HLM (main biotransformations: monohydroxylation and N-acetylation) and by MAO-A (aldehyde metabolite). Additionally, MAO-A does not metabolize Bromo-DragonFLY — instead, the compound inhibits MAO-A. This metabolic resistance is the primary explanation for the extraordinary duration of effects (2–3 days, sometimes longer), which is unique among phenethylamine psychedelics.

> **⚠️ DISCREPANCY — FLAG for human review:** Noga & Jurowski (2025 [Ref 22], in silico) predict that Bromo-DragonFLY DOES undergo CYP450-mediated metabolism (epoxidation, quinone formation, UGT conjugation, N-dealkylation) and renal excretion. This contradicts Noble et al. 2018's direct in vitro experimental finding of no hepatic metabolism. The discrepancy likely reflects limitations of computational prediction versus actual metabolic behavior. The **experimental finding (Noble 2018) should be treated as more reliable**, but the in silico predictions may reflect metabolic pathways that are simply not active in HLM/HLC assay conditions (e.g., extrahepatic metabolism). Generation agent should present both findings with appropriate confidence weighting.

Noga & Jurowski (2025 [Ref 22]) also predict: high gastrointestinal absorption, blood-brain barrier penetration, significant plasma protein binding, and primarily renal excretion.

**Plasma protein binding:** Noble et al. (2018 [Ref 2]) state in their abstract that plasma protein binding was determined as part of the study, but the specific value is not stated in the available abstract. This is a **gap** — the full paper would contain this value.

**Half-life:** No published human pharmacokinetic half-life data are available. The clinical duration of 2–3+ days is consistent with metabolic resistance rather than a known elimination half-life.

**Plasma concentrations in cases:** Andreasen et al. (2009 [Ref 16]) measured femoral blood 0.0047 mg/kg (4.7 ng/g), urine 0.033 mg/kg, vitreous humour 0.0005 mg/kg in a fatal overdose. Wood et al. (2009 [Ref 10]) measured 0.95 ng/mL serum in a surviving case (polydrug exposure with ketamine and cannabis).

---

## History

### Discovery and Synthesis

Bromo-DragonFLY was first synthesized in **1998 by Matthew A. Parker** in the laboratory of **David E. Nichols** at Purdue University. The compound was reported in Parker, Marona-Lewicka, Lucaites, Nelson & Nichols (1998 [Ref 1]), "A novel (benzodifuranyl)aminoalkane with extremely potent activity at the 5-HT2A receptor," Journal of Medicinal Chemistry — representing the first report of the DragonFLY-class compounds and documenting their exceptional 5-HT2A receptor potency. The name "DragonFLY" derives from the compound's overall shape resembling a dragonfly, with the extended fused ring system forming "wings."

The design concept emerged from systematic SAR work in the Nichols laboratory on rigid analogs of phenethylamine psychedelics. Earlier work by Chambers, Kurrasch-Orbaugh & Nichols (2002 [Ref 7]) characterized the benzodifuran ring system's potency-enhancing properties. In **2001**, Nichols' group reported an **enantiospecific synthesis** of Bromo-DragonFLY, enabling study of individual R and S enantiomers; the (R)-(−) enantiomer was found to have greater affinity at 5-HT2A and 5-HT2C receptors. This enantiospecific synthesis confirmed the compound's pharmacophore model and the significance of stereochemistry for receptor binding (web-retrieved synthesis history — no direct PMID found for the 2001 paper; see Gaps).

The historical context of the DOx class is reviewed in Glennon & Dukat (2024 [Ref 26]): DOI, DOC, and DOB (the structural parent of the DragonFLY series) were first synthesized by Shulgin in 1973, and Bromo-DragonFLY represents a rigid cyclized analog of DOB incorporating the benzodifuran scaffold.

### Market Emergence and Key Incidents

- **~2006–2007:** Bromo-DragonFLY first appeared on the research chemical/designer drug market, primarily sold through internet vendors.
- **August 2007:** First documented DEA seizure — a dropper bottle containing Bromo-DragonFLY in aqueous solution from an Ashland, Oregon resident suspected of drug distribution (DEA Microgram Bulletin, Reed & Kiddon 2007 [Ref 19]).
- **September 2007:** The first well-documented serious overdose cluster in **Sweden** — two men consumed an unknown quantity; one died within hours, the other (Pers Ståhl, age 35) developed severe vasoconstrictive complications requiring amputation of fingers and toes after seven weeks of hospitalization (Erowid documentation [Ref 14]). This incident prompted Denmark to ban the substance in December 2007.
- **2009:** Andreasen et al. (2009 [Ref 16]) published the first forensic case report — an 18-year-old Danish woman found dead, with Bromo-DragonFLY confirmed as cause of death at femoral blood 0.0047 mg/kg with no other drugs detected. This was the first analytical quantification in a death case.
- **October 2009 (CRITICAL INCIDENT):** A batch of **Bromo-DragonFLY was mislabeled and distributed as 2C-B-FLY** — a structurally similar compound approximately 20 times less potent by weight. Users who calibrated doses for 2C-B-FLY unknowingly ingested approximately 20-fold overdoses of Bromo-DragonFLY, causing mass poisonings in the UK and elsewhere (web-retrieved; see Refs 15, 18). This incident is widely cited as the primary harm reduction impetus for volumetric dosing practices and contributed to Wood et al. (2009 [Ref 10]).
- **2012:** O'Connor & Keating (2014 [Ref 20]) characterized synthetic precursor ketone routes, indicating clandestine laboratory production was anticipated and that forensic authorities developed detection capabilities for precursors.

---

## Subjective Effects

No controlled human pharmacology studies exist for Bromo-DragonFLY. All human effect descriptions derive from case reports, emergency toxicology records, and user reports from online communities.

**Documented in clinical case reports (peer-reviewed):**
- Agitation, hallucinations, tachycardia, mydriasis, and tonic-clonic seizures (Wood et al. 2009 [Ref 10])
- Deeply disoriented mental state; inability to stand; convulsions; respiratory difficulty (Erowid case 2007 [Ref 14])
- Delayed toxicity onset — symptoms appeared hours to more than a day post-ingestion (Wood et al. 2009 [Ref 10])
- Prolonged effects lasting 2–3 days in clinical context (Noble et al. 2018 [Ref 2])

**From clinical toxicology summaries:**
- LSD-like hallucinogenic effects (Corazza et al. 2011 [Ref 6]; Tennessee Poison Center 2016 [Ref 15])
- Onset: delayed up to 6 hours post-ingestion (Tennessee Poison Center 2016 [Ref 15])
- Duration: typically 12–24 hours for most users; up to 2–3 days at higher doses (web-retrieved clinical data [Ref 15])
- Total duration including aftereffects: 1–4 days, consistent with brief's seed data
- Sympathomimetic component: stimulation, wakefulness, cardiovascular activation
- Peripheral vasoconstriction is a distinguishing feature not seen with LSD or psilocybin

**Effects taxonomy (from brief — label as user-report-based, no controlled study data):**
The extensive effects taxonomy in the seed data (cognitive, perceptual, physical, emotional) is consistent with the compound's 5-HT2A agonist pharmacology and is supported by class-level evidence, but is based on user reports rather than controlled studies. No published controlled observational study documents the subjective effect profile in structured form.

**Dose sensitivity:**
- Typical oral dose: 100–1,000 µg (web-retrieved clinical summary [Ref 15]; HandWiki)
- The Tennessee Poison Center reports 0.2–1 mg as typical dose [Ref 15]
- Approximately 300x more potent than mescaline; slightly less potent than LSD (by weight per dose, not by receptor potency)
- A death has been reported at approximately 700 µg (HandWiki — not primary source verified; see Gaps)
- **Extreme dose sensitivity** — the 2009 mislabeling incident demonstrates catastrophic risk from ~20x overdosing
- Seed data doses (threshold: 75 µg; heavy: 750+ µg) are within the range of published clinical estimates but are not directly sourced from a controlled study

---

## Safety & Toxicity

### Documented Fatalities and Serious Harm

**Published case reports confirm multiple fatalities:**

1. **Andreasen et al. 2009 [Ref 16]** — First forensic quantification of a fatal case. 18-year-old woman, Denmark. Femoral blood 0.0047 mg/kg, urine 0.033 mg/kg, vitreous humour 0.0005 mg/kg. No other drugs detected. Cause of death: fatal overdose of Bromo-DragonFLY. This case prompted Denmark's ban (December 2007).

2. **Wood et al. 2009 [Ref 10]** — Non-fatal case with delayed onset severe agitation, hallucinations, tonic-clonic seizures. White powder confirmed as Bromo-DragonFLY by GC/MS. Serum concentration 0.95 ng/mL (polydrug: also ketamine 20 ng/mL and cannabis). Treated with IV benzodiazepines and supportive care; discharged with no long-term sequelae.

3. **Iwersen-Bergmann et al. 2019 [Ref 17]** — Mass poisoning event with 2C-E combined with Bromo-DragonFLY. Multiple middle-aged victims.

4. **Documented fatalities in Norway, Sweden, Denmark, Finland, and the United States** (Corazza et al. 2011 [Ref 6]; Tennessee Poison Center 2016 [Ref 15]). At least five deaths have been attributed to Bromo-DragonFLY. Exact case counts vary by source.

### Vasoconstrictive Toxicology (Mechanism and Severity)

The most distinctive toxicity of Bromo-DragonFLY is its extreme, sustained peripheral vasoconstriction, mechanistically explained by:
- Potent α-1 adrenergic receptor agonism (sympathomimetic)
- Prolonged 5-HT2B receptor activation (direct vasoconstriction)
- Multi-day duration due to metabolic resistance (Noble et al. 2018 [Ref 2])
- MAO-A inhibition maintaining elevated serotonin tone (Noble et al. 2018 [Ref 2])

The 2007 Swedish case ([Ref 14]) involved progressive extremity discoloration beginning day 2, acute liver and renal failure, gangrene detected at day 9, and eventual amputation of fingers and toes at 7 weeks. Treatment involved nitroglycerin infusions, calcium channel blockers, ACE inhibitors, and prostacyclin analogues.

### Acute Toxicity (In Silico Estimates)

Noga & Jurowski (2024 [Ref 25]) applied in silico methods to predict toxicological parameters:
- **Acute toxicity (LD₅₀):** Predicted significant acute toxicity with notable species variation; human equivalent LD₅₀ not stated — computational values only
- **Genotoxicity:** Low likelihood of genotoxic potential, but suggestions of possible DNA damage
- **Cardiotoxicity:** **Notable risk via hERG channel inhibition** — this is clinically significant and should be flagged
- **Endocrine disruption:** Low probability of estrogenic (ERα) activity

> **⚠️ FLAG:** No human LD₅₀ data or therapeutic index is published. All acute toxicity estimates are computational. The "toxic dose is unknown" notation in the brief is accurate and confirmed.

### Analytical Detection

Standard emergency toxicology screening (immunoassay) does NOT detect Bromo-DragonFLY. Confirmation requires GC/MS, LC-MS/MS, or UPLC-TOFMS (Andreasen et al. 2009 [Ref 16]; Tennessee Poison Center 2016 [Ref 15]; Wood et al. 2009 [Ref 10]).

---

## Harm Reduction

### Key Risk Factors

1. **Extreme potency and narrow therapeutic window:** Active in sub-milligram doses. The 2009 mass poisoning from mislabeled Bromo-DragonFLY (sold as 2C-B-FLY, ~20× less potent) demonstrates catastrophic risk from dose estimation errors (web-retrieved [Ref 18]).

2. **Delayed onset (up to 6 hours):** Users who redose before onset appears have died. This is likely the most important harm reduction message for this substance.

3. **Multi-day duration:** The metabolic resistance (Noble et al. 2018 [Ref 2]) means effects cannot be terminated by clearance; supportive care is the only treatment.

4. **Standard drug tests do not detect it** (Wood et al. 2009 [Ref 10]; Tennessee Poison Center [Ref 15]).

5. **Adulteration risk:** Bromo-DragonFLY may be misrepresented as 2C-B-FLY, LSD, or other substances.

### Published Treatment Approach

Tennessee Poison Center (2016 [Ref 15]) and Wood et al. (2009 [Ref 10]) indicate:
- High-dose benzodiazepines for agitation and seizure control (primary symptom management)
- Supportive care is the mainstay of treatment
- Vascular complications: nitroglycerin, calcium channel blockers, prostaglandin analogues for vasoconstriction
- Standard opioid antagonists (naloxone) not likely to reverse effects given multi-receptor mechanism
- Intensive care for severe cases (respiratory support, renal support)

### Volumetric Dosing

Given sub-milligram dosing requirements and the 2009 mislabeling incident, clinical and harm reduction consensus emphasizes:
- Verified identity testing (reagent tests; laboratory confirmation)
- Volumetric dosing in solution to achieve accurate microgram quantities
- Never redosing before onset is confirmed

---

## Tolerance & Dependence

### Tolerance Development

The brief states "buildup: almost immediately after ingestion" — this is consistent with the established mechanism for serotonergic psychedelics. De la Fuente Revenga et al. (2022 [Ref 23]) demonstrated in mouse HTR assay that:
- Tolerance to 5-HT2AR-mediated behavior (HTR) develops **within a single administration**
- **Mechanism:** 5-HT2A receptor downregulation in frontal cortex
- This mechanism is independent of β-arrestin-2

**Cross-tolerance:** De la Fuente Revenga et al. (2022 [Ref 23]) confirmed mutual cross-tolerance between psychedelic 5-HT2A agonists (DOI and LSD demonstrated bidirectional cross-tolerance). Given Bromo-DragonFLY's potent 5-HT2A agonism, cross-tolerance with other psychedelic 5-HT2A agonists (LSD, psilocin, mescaline, DOB, DMT) is pharmacologically predicted and listed in the brief as "psychedelic" cross-tolerance. No Bromo-DragonFLY-specific cross-tolerance experiments were found in published literature.

The brief's tolerance data (half-life 6 days, full reset 14 days) is consistent with general psychedelic class data but not verified by a Bromo-DragonFLY-specific study. These values are based on structural analogy and class inference.

### Dependence

The brief notes "not habit-forming." This is consistent with the pharmacological profile of serotonergic psychedelics, which do not produce classical physical dependence or reinforcing dopaminergic reward, and is supported by class-level evidence. No published dependence study specific to Bromo-DragonFLY was found.

---

## Interactions

### Tramadol: DANGEROUS (Brief classification confirmed)

**Mechanism established via published evidence:**
- Bromo-DragonFLY is a competitive MAO-A inhibitor (Ki = 0.352 µM, IC₅₀ ≈ 540 nM; Noble et al. 2018 [Ref 2])
- Tramadol is a serotonin and norepinephrine reuptake inhibitor with weak μ-opioid activity
- **MAO-A inhibitor + serotonin reuptake inhibitor = serotonin syndrome risk** — a well-established pharmacological principle (Schenk & Wirz 2015 [Ref 25, not cited separately]; Fox et al. 2009 [Ref 24])
- Fox et al. (2009 [Ref 24]) specifically demonstrated in SERT-deficient mice that tramadol induces exaggerated serotonin syndrome behaviors, and explicitly warned that "caution seems warranted in prescribing or not warning patients receiving... MAOIs that dangerous side-effects may occur during concurrent use of tramadol"
- The combination of Bromo-DragonFLY's prolonged duration (2–3+ days) with its MAO-A inhibitory activity creates an extended window of dangerous interaction potential even after the subjective effects have resolved

This interaction is **mechanistically verified** from primary literature. The "dangerous" severity classification in the brief is supported.

### Cannabis: Unknown (Brief classification confirmed)

No published interaction data between cannabis and Bromo-DragonFLY found. The combination is predicted to intensify psychedelic effects via additive CNS effects, but no specific mechanism data exists. The "unknown" classification is appropriate.

### General Serotonergic Interactions

Given Bromo-DragonFLY's:
1. Potent 5-HT2A agonism
2. MAO-A inhibitory activity (Ki = 0.352 µM)
3. Multi-day duration

The following classes of interactions represent theoretical risk based on pharmacological class evidence (not Bromo-DragonFLY-specific published studies):
- **SSRIs/SNRIs:** Risk of serotonin syndrome (MAO-A inhibition + serotonin reuptake blockade)
- **MAOIs:** Risk of severe serotonin syndrome (additive MAO-A inhibition + 5-HT agonism)
- **Other serotonergic psychedelics:** Cross-tolerance (de la Fuente Revenga et al. 2022 [Ref 23])
- **Vasoconstrictors (triptans, ergotamines):** Additive vasoconstriction risk — potentially life-threatening

> **⚠️ FLAG:** Only the tramadol interaction has a mechanistic basis in published primary literature. All other interactions listed above are based on pharmacological class inference. The generation agent should clearly label these as class-inferred rather than substance-specific.

---

## Legal Status

All data below is from the Erowid legal vault ([Ref 27]) and web-retrieved synthesis history ([Ref 18]) unless noted otherwise.

| Jurisdiction | Status | Schedule/Classification | Date |
|---|---|---|---|
| United States | **Federally unscheduled** | Possible prosecution under Federal Analogue Act as DOB/2C-B analog; Schedule I in Oklahoma | No federal scheduling date confirmed |
| Australia | **Prohibited** | Schedule 9 (Poisons Standard) | February 2009 (national); September 9, 2011 (Queensland Drugs Misuse Regulation Schedule 2) |
| Canada | **Controlled** | Schedule III (CDSA — "2C-phenethylamines" catch-all clause) | October 12, 2016 |
| Denmark | **Illegal** | Non-research use banned | December 5, 2007 (first country to ban) |
| Sweden | **Illegal** | "Health hazard" classification | July 15, 2007 |
| Norway | **Controlled** | Narcotics list (via "Derivatbestemmelsen" analog law) | Before April 29, 2009 |
| Finland | **Illegal** | Controlled substances list | Before October 3, 2012 |
| Romania | **Illegal** | Controlled | February 10, 2010 |
| United Kingdom | **Covered** | Not explicitly named in Misuse of Drugs Act; debated whether phenylethylamine catch-all applies (the benzodifuran structure differs from phenylethylamines); **covered by Psychoactive Substances Act 2016** | 2016 |

> **⚠️ FLAG — US Federal Status:** Multiple secondary sources conflict on US status. The Tennessee Poison Center (2016 [Ref 15]) describes it as "Schedule I controlled substance in the United States." The Erowid legal vault and web research indicate it is **not explicitly federally scheduled**, with only Oklahoma having explicit Schedule I placement. This contradiction requires editorial resolution. The DEA Microgram Bulletin documentation (2007 [Ref 19]) from Oregon predates any known formal scheduling. Generation agent should present the federal unscheduled status with the analog act caveat and note the discrepancy.

---

## Clinical Trials

**No clinical trials found.** ClinicalTrials.gov search returned zero results for Bromo-DragonFLY. This is consistent with the substance's Schedule I-equivalent status in most jurisdictions and its exclusively forensic/toxicological research profile.

---

## Community Feedback Analysis

No community feedback was submitted in Part A2 of the brief. No feedback items to evaluate.

---

## Gaps & Flags

### Data Gaps

1. **CAS number:** Not confirmed via API or primary literature. Multiple sources do not cite it.

2. **Nichols 2001 enantiospecific synthesis paper:** Referenced in web sources but no PMID found. This paper is cited as establishing the R > S potency difference at 5-HT2A/2C. The 1998 Parker et al. paper (PMID 9857084 [Ref 1]) is confirmed; the 2001 enantiospecific paper remains unverified in primary databases.

3. **Specific Ki binding data primary sources:** The ranges reported (5-HT2A Ki = 0.04–1.86 nM; 5-HT2B Ki = 0.126–0.19 nM; 5-HT2C Ki = 0.02–1.48 nM) are from HandWiki citing multiple studies. The original binding assay papers (likely NIMH PDSP database, Parker 1998, and subsequent publications from Nichols lab) were not directly retrieved for abstract verification. These values are well within what the literature supports qualitatively but need primary source tracing.

4. **Plasma protein binding value:** Noble et al. (2018 [Ref 2]) state plasma protein binding was measured but the specific percentage is not in the available abstract. The full paper contains this value.

5. **Confirmed human lethal dose:** The "approximately 700 µg" reported death dose comes from non-primary web sources. The Andreasen 2009 case [Ref 16] measured postmortem blood concentrations but the administered dose was unknown. This remains unverified.

6. **Tolerance half-life (6 days), full reset (14 days):** These values from the brief are not verified against a published Bromo-DragonFLY-specific study. They are based on general psychedelic class inference. See Gaps.

7. **Physical properties** (melting point, solubility, log P): Not found in any retrieved source.

### Safety-Critical Flags

**⚠️ FLAG 1 — US Federal Scheduling Conflict:** Tennessee Poison Center calls it "Schedule I in the United States"; Erowid legal data indicates it is federally unscheduled with only Oklahoma state scheduling. This directly affects harm reduction messaging and legal warnings. Needs editorial resolution before publication.

**⚠️ FLAG 2 — Metabolism Contradiction:** Noble et al. (2018 [Ref 2], experimental in vitro) found NO hepatic metabolism. Noga & Jurowski (2025 [Ref 22], in silico) predict multiple CYP-mediated metabolic pathways. These contradict each other. The experimental data is more reliable, but the computational predictions may represent metabolic routes not active in the specific in vitro conditions used. Generation agent should present Noble 2018 as the primary reliable data point with appropriate uncertainty.

**⚠️ FLAG 3 — Vasoconstriction lethal risk:** The brief notes "extreme vasoconstrictive effects" and that the "toxic dose is unknown." Published case evidence (Andreasen 2009 [Ref 16]) confirms fatality at blood concentrations of ~4.7 ng/g — the only confirmed lethal blood concentration in a single-drug case. This value should be flagged as unconfirmed for dose conversion purposes.

**⚠️ FLAG 4 — Cardiotoxicity (hERG):** Noga & Jurowski (2024 [Ref 25]) predict notable hERG channel inhibition (cardiac arrhythmia risk). This is an in silico prediction not confirmed by published clinical or experimental electrophysiology data, but it is a serious safety concern that should be prominently noted and flagged for expert cardiological review.

**⚠️ FLAG 5 — Tramadol interaction basis:** The dangerous tramadol interaction is mechanistically supported by published evidence (Noble 2018 MAO-A Ki; Fox 2009 tramadol serotonin syndrome) but no published case report specifically documents a Bromo-DragonFLY + tramadol co-ingestion adverse event. The danger classification is pharmacologically well-founded but empirically unconfirmed as a specific case.

**⚠️ FLAG 6 — 2009 UK mislabeling incident:** The critical incident of Bromo-DragonFLY mislabeled as 2C-B-FLY causing mass overdoses is referenced in multiple web sources but the primary case series publication was not directly identified via PubMed search. Wood et al. (2009 [Ref 10]) may document this incident but the abstract does not confirm it. Generation agent should present this with appropriate sourcing uncertainty.

### Structural Analogy Reliance

The following content points rely primarily on class-level evidence rather than Bromo-DragonFLY-specific published data:
- Cross-tolerance with psychedelic 5-HT2A agonists (extrapolated from de la Fuente Revenga et al. 2022 [Ref 23] using DOI/LSD)
- SSRIs, other MAOI, triptan interactions (class inference only)
- Dependence liability characterization (class-level: non-habit-forming for serotonergic psychedelics)
- Tolerance half-life and full-reset duration values

All of the above should be clearly labeled in article prose as class-inferred rather than Bromo-DragonFLY-specific findings.