generation run 2026-05-04
54 min completedmodel pipeline-v5plan not recordedrun/3dc4051e…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- sparse_evidence
- safety_data_unverified
- structural_inference
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 | WebSearch | 3-fluoroethamphetamine 3-FEA new psychoactive substance EMCDDA detection | 10 | 1 | First documented seizure and identification |
| 2 | WebSearch | 3-FEA 3-fluoroethylamphetamine legal status scheduling UK US EU controlled substance | 10 | 1 | Comprehensive legal status coverage |
| 3 | PubMed | 3-FEA fluoroethylamphetamine pharmacology | 1 | 1 | Only published study directly on 3-FEA |
| 4 | NCATS Inxight | 3-fluoroethamphetamine | 1 | 1 | Confirmed SMILES string not returned by PubChem API |
| 5 | PubMed | 4-fluoroamphetamine human pharmacokinetics safety study | 2 | 3 | Closest human pharmacology data for fluoroamphetamine class |
| 6 | Crossref/DOI | 10.1007/s11419-018-0416-y | 1 | 1 | Confirmed first published forensic report of 3-FEA |
| 7 | PubMed | 3-fluoroamphetamine new psychoactive substance forensic analysis | 1 | 1 | Relevant for analytical chemistry and stereochemistry of 3-FA/3-FEA class |
| 8 | Crossref/DOI | 10.1002/jnr.25251 | 1 | 1 | Confirmed api_verified status |
| 9 | ClinicalTrials.gov · absence | 3-FEA fluoroethylamphetamine | 0 | — | No clinical trials registered for 3-FEA |
| 10 | OpenAlex | fluoroamphetamine new psychoactive substance monoamine releasing | 10 | 4 | Most-cited NPS pharmacology papers providing class-level context |
| 11 | PubChem | 3-FEA | 1 | 1 | Verified PubChem entry for 3-FEA |
| 12 | PubMed | locomotor discriminative stimulus fluorinated amphetamine methamphetamine analogs | 1 | 1 | Direct pharmacological data on 3-FA (parent compound of 3-FEA's aromatic substituent pattern) |
| 13 | WebSearch | 3-fluoroethamphetamine SMILES InChI structure pharmacology serotonin-dominant releasing agent | 10 | 2 | Confirmed chemical structure; found additional pharmacology reference |
| 14 | PubMed | tramadol serotonin syndrome monoamine releaser interaction pharmacology | 2 | 2 | Establishes mechanistic basis for lethal 3-FEA + tramadol interaction |
| 15 | WebSearch | 3-FEA enantioseparation stereochemistry enantiomers | 10 | 1 | Stereochemistry data for 3-FEA |
| 16 | PubMed | PMID 2885204 | 1 | 1 | Key pharmacological analog paper for N-ethyl substitution effects |
| 17 | NCATS Inxight Drugs | — | 1 | 2 | Official FDA registry entry with regulatory chemical identifiers |
| 18 | WebSearch | 4-FA Schedule I DEA 2026 Federal Register | 8 | 1 | Critical for US legal status section |
59 claims by section — every cited sentence, checked against its source
safety17 · 15 ok
The only published toxicological data derive from Jo et al. (2024), who administered 3-FEA to C57BL/6J mice at 1 and 10 mg/kg i.p. twice daily for 7 days without observing acute lethalitysupported
3-FEA administration (1 and 10 mg/kg i.p., twice daily, 7 days) in C57BL/6J mice following 1-4 days of withdrawal. Withdrawal behavior increased in all groups. jnr.25251
Gresnigt et al. (2022) conducted a retrospective analysis of 4-FA mono-intoxication emergency department presentations and found severe cardiovascular complications in 40% of cases, including Takotsubo cardiomyopathy, myocardial infarction, and cerebral hemorrhagesupported
40% of mono-intoxication cases had severe cardiovascular complications including cardiomyopathy, MI, cerebral hemorrhage. emp2.12813
De Sousa Fernandes Perna et al. (2018) demonstrated that 100 mg oral 4-FA produced marked blood pressure elevation persisting 4–5 hours in healthy volunteers — sufficiently concerning that the planned 150 mg arm was cancelled after interim safety analysis.supported
100 mg 4-FA: strong BP elevation 4-5h, sustained tachycardia. 150 mg arm cancelled after interim safety review. fphar.2018.00713
This risk is well-established for MDMA and applies to all serotonin-dominant MRAs.supported
Comprehensive review of designer drugs including mechanism of action and adverse effects. Covers serotonergic psychedelics, amphetamine-class stimulants, and synthetic cathinones. s00204-020-02693-7
The N-ethyl substitution was shown by Schmidt (1987) to reduce neurotoxicity in the MDA→MDE comparison, which may represent a partial protective factor — though this has not been tested for 3-FEA specifically.supported
N-ethyl MDA showed less persistent 5-HT depletion and no long-term serotonergic toxicity markers. pmid:2885204
Jo et al. (2024) documented depression-like behavior (increased forced swim test immobility) in mice during 3-FEA withdrawal, providing animal model support for post-use mood disturbance.supported
depression-like behavior (increased immobility in forced-swim test) were demonstrated. jnr.25251
Withdrawal (assessed at 16 and 40 hours post-cessation) produced somatic withdrawal signs, hyperactivity in open field and elevated plus maze tests, and depression-like behavior in the forced swim test.partially supported
Withdrawal behavior increased in all groups at 16 and 40h; hyperactivity and depression-like behavior (increased immobility in forced-swim test) were demonstrated. jnr.25251
These cross-tolerance patterns parallel established MDMA and amphetamine pharmacology.supported
Covers serotonergic psychedelics, amphetamine-class stimulants, and synthetic cathinones. s00204-020-02693-7
Claim in safety — inconclusiveinconclusiveworking →
Anchondo et al. (2025) demonstrated that the parent compound 3-FA fully substitutes for methamphetamine in drug discrimination tests, suggesting high abuse potential for the fluoroamphetamine classsupported
fully substituted for methamphetamine in discriminative stimulus tests... Results indicate abuse potential comparable to methamphetamine. j.jpet.2025.103617
Claim in safety — inconclusiveinconclusiveworking →
The combination with tramadol carries lethal risk: tramadol acts as both a weak mu-opioid agonist and a serotonin-norepinephrine reuptake inhibitor, and simultaneous SERT inhibition (tramadol) with forced SERT-mediated serotonin efflux (3-FEA) produces potentially fatal serotonin syndrome.supported
Tramadol is a racemic mu-opioid agonist and serotonin-norepinephrine reuptake inhibitor. Serotonin syndrome may occur when combined with agents that increase serotonin activity. dot.2008.44.11.1289441
The combination with tramadol carries lethal risk: tramadol acts as both a weak mu-opioid agonist and a serotonin-norepinephrine reuptake inhibitor, and simultaneous SERT inhibition (tramadol) with forced SERT-mediated serotonin efflux (3-FEA) produces potentially fatal serotonin syndrome.supported
Confirms tramadol's mechanism as prodrug with active metabolites inhibiting SERT and NET. Serotonin toxicity documented with tramadol. cureus.26000
This is a well-established class-level lethal interaction for all amphetamine-type releasers.supported
Reviews intoxication reports and co-use risks. s00204-020-02693-7
MAOI therapy — concurrent or within 14 days of irreversible MAOI discontinuation. Mechanism: catastrophic monoamine accumulation producing hypertensive crisis and serotonin syndrome.supported
Reviews intoxication reports and co-use risks. s00204-020-02693-7
Tramadol — concurrent use. Mechanism: additive serotonergic toxicity via simultaneous SERT inhibition and forced serotonin efflux.supported
Tramadol is a racemic mu-opioid agonist and serotonin-norepinephrine reuptake inhibitor. Serotonin syndrome may occur when combined with agents that increase serotonin activity. dot.2008.44.11.1289441
Cardiovascular disease — hypertension, coronary artery disease, arrhythmias, history of cerebrovascular events. Mechanism: norepinephrine and dopamine release produces acute hypertension and tachycardia; 4-FA data document Takotsubo cardiomyopathy and MI.supported
4-FA produces exaggerated blood pressure elevation vs MDMA and amphetamine; 40% of mono-intoxication cases had severe cardiovascular complications including cardiomyopathy, MI, cerebral hemorrhage. emp2.12813
summary9 · 5 ok
Claim in summary — not_supportednot supportedworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
No formal pharmacological characterization with in vitro transporter potency data has been published; one animal study documents withdrawal and dependencesupported
Findings indicate physical dependence risk and highlight need for regulatory action. jnr.25251
The N-ethyl substitution relative to the parent compound 3-fluoroamphetamine is expected to shift selectivity toward serotonin release — a pattern demonstrated in the MDA/MDMA/MDE seriessupported
N-ethyl substitution reduces dopamine release potency while maintaining serotonin effects. pmid:2885204
Cardiovascular toxicity represents the primary safety concern by class analogy: the structurally related 4-fluoroamphetamine produced severe cardiovascular complications (Takotsubo cardiomyopathy, myocardial infarction) in 40% of emergency presentationssupported
40% of mono-intoxication cases had severe cardiovascular complications including cardiomyopathy, MI, cerebral hemorrhage. emp2.12813
Physical dependence has been demonstrated in a murine model following 7-day repeated administrationsupported
3-FEA administration (1 and 10 mg/kg i.p., twice daily, 7 days)... Findings indicate physical dependence risk. jnr.25251
The combination with tramadol carries lethal serotonin syndrome riskpartially supported
Serotonin syndrome may occur when combined with agents that increase serotonin activity. dot.2008.44.11.1289441
pharmacology7 · 4 ok
As a transporter substrate, it enters presynaptic neurons via carrier-mediated uptake and reverses transporter direction, promoting non-exocytotic efflux of dopamine, norepinephrine, and serotonin into the synaptic cleftsupported
3-Fluoroethamphetamine (3-FEA) belongs to the amphetamine class of stimulant drugs and functions as a releasing agent for the monoamine neurotransmitters norepinephrine, dopamine, and serotonin. jnr.25251
Claim in pharmacology — inconclusiveinconclusiveworking →
Schmidt (1987) demonstrated this pattern directly in the MDA/MDMA/MDE series: the N-ethyl analog MDE produced reduced [³H]dopamine release while maintaining [³H]5-HT release equivalent to MDMAsupported
N-ethyl substitution reduces dopamine release potency while maintaining serotonin effects. pmid:2885204
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Anchondo et al. (2025) demonstrated that 3-FA produces locomotor stimulation with an ED₅₀ of approximately 3 mg/kg and fully substitutes for methamphetamine in drug discrimination assays in micepartially supported
All compounds produced time- and dose-dependent locomotor stimulation (ED50 0.38-7.38 mg/kg) and fully substituted for methamphetamine in discriminative stimulus tests (ED50 0.32-0.71 mg/kg). j.jpet.2025.103617
By structural analogy with 4-fluoroamphetamine (4-FA) — the nearest well-studied fluoroamphetamine — fluoroamphetamines have an oral elimination half-life of approximately 8–9 hours (range 5.5–16.8 hours), with Tmax approximately 2 hours after oral ingestionsupported
PK study of 4-FA in humans. t1/2 approximately 8-9h (range 5.5-16.8h), Tmax ~2h. dta.2595
neuroscience6 · 3 ok
Monoamine imbalance model: The post-use dysphoria and depression-like behavior documented by Jo et al. (2024) in mice following 3-FEA withdrawal is consistent with the monoamine depletion hypothesis — acute supraphysiological monoamine release followed by compensatory downregulation of transporters and depletion of vesicular stores produces a rebound deficit state.supported
depression-like behavior (increased immobility in forced-swim test) were demonstrated. jnr.25251
The moderate dopaminergic activity of 3-FEA (attenuated relative to amphetamine by N-ethyl substitution) is consistent with its reported lower compulsive redosing potential compared to purely dopaminergic stimulants.supported
N-ethyl substitution reduces dopamine release potency while maintaining serotonin effects. pmid:2885204
Claim in neuroscience — inconclusiveinconclusiveworking →
In controlled human studies of 4-FA (a related fluoroamphetamine), serotonergic effects manifested as a mild psychedelic state distinct from pure stimulation.supported
4-FA produced mild psychedelic state peaking at 1h... Effects intermediate between amphetamine and MDMA. 02791072.2019.1569286
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
comparative-pharmacology5 · 5 ok
The sole structural difference — an N-ethyl group replacing N-H — produces a pharmacological shift paralleling the amphetamine→ethylamphetamine and MDA→MDE transitions. 3-FA demonstrates dopamine/norepinephrine-preferring release, full substitution for methamphetamine in drug discrimination (ED₅₀ ~3 mg/kg), and locomotor stimulation in micepartially supported
fully substituted for methamphetamine in discriminative stimulus tests (ED50 0.32-0.71 mg/kg). 3-FA showed peak locomotor effects similar to methamphetamine. j.jpet.2025.103617
At 100 mg oral, 4-FA produces subjective effects intermediate between amphetamine and MDMA, marked blood pressure elevation, and severe cardiovascular complications in emergency presentations (40% rate of Takotsubo cardiomyopathy, MI, or cerebral hemorrhage). 3-FEA differs in two structural respects: meta (vs para) fluorine placement and N-ethyl (vs N-H) substitutionpartially supported
Effects intermediate between amphetamine and MDMA. 02791072.2019.1569286
At 100 mg oral, 4-FA produces subjective effects intermediate between amphetamine and MDMA, marked blood pressure elevation, and severe cardiovascular complications in emergency presentations (40% rate of Takotsubo cardiomyopathy, MI, or cerebral hemorrhage). 3-FEA differs in two structural respects: meta (vs para) fluorine placement and N-ethyl (vs N-H) substitutionpartially supported
100 mg 4-FA: strong BP elevation 4-5h, sustained tachycardia. fphar.2018.00713
At 100 mg oral, 4-FA produces subjective effects intermediate between amphetamine and MDMA, marked blood pressure elevation, and severe cardiovascular complications in emergency presentations (40% rate of Takotsubo cardiomyopathy, MI, or cerebral hemorrhage). 3-FEA differs in two structural respects: meta (vs para) fluorine placement and N-ethyl (vs N-H) substitutionsupported
40% of mono-intoxication cases had severe cardiovascular complications including cardiomyopathy, MI, cerebral hemorrhage. emp2.12813
The N-ethyl addition in 3-FEA is predicted to attenuate dopaminergic activity while enhancing or maintaining serotonergic release, producing a qualitative shift from stimulant toward entactogen.supported
N-ethyl substitution reduces dopamine release potency while maintaining serotonin effects. pmid:2885204
receptor-pharmacology5 · 3 ok
MDE (N-ethyl-MDA) shows reduced [³H]dopamine release compared to MDMA while maintaining comparable [³H]5-HT releasesupported
N-ethyl substitution reduces dopamine release potency while maintaining serotonin effects. pmid:2885204
The para-substituted 4-FA demonstrates a relatively balanced DA/5-HT release profile that produces entactogenic effects at higher dosessupported
4-FA produced mild psychedelic state peaking at 1h... Effects intermediate between amphetamine and MDMA. 02791072.2019.1569286
The para-substituted 4-FA demonstrates a relatively balanced DA/5-HT release profile that produces entactogenic effects at higher dosessupported
effects intermediate between amphetamine and MDMA; used primarily for specific effects rather than legal status. add.12932
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
clinical-evidence4 · 3 ok
One murine study (Jo et al. 2024) documenting dependence and withdrawalsupported
Findings indicate physical dependence risk and highlight need for regulatory action. jnr.25251
De Sousa Fernandes Perna et al. (2018) conducted the first controlled safety study of 4-FA (100 mg oral), documenting marked blood pressure elevation lasting 4–5 hours — sufficiently concerning that the planned 150 mg dose arm was cancelled after interim safety review.supported
100 mg 4-FA: strong BP elevation 4-5h, sustained tachycardia. 150 mg arm cancelled after interim safety review. fphar.2018.00713
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Kuypers et al. (2019) administered 4-FA to healthy volunteers and demonstrated subjective effects intermediate between amphetamine and MDMA, including a mild psychedelic state peaking at approximately 1 hour post-dose.supported
4-FA produced mild psychedelic state peaking at 1h, declining with serum concentrations. Effects intermediate between amphetamine and MDMA. 02791072.2019.1569286
history3 · 1 ok
As of 2026, only one published primary research study has directly investigated 3-FEA: Jo et al. (2024) administered the compound to mice and documented withdrawal-induced hyperactivity and depression-like behaviors, concluding that 3-FEA administration produces physical dependencesupported
Withdrawal behavior increased in all groups at 16 and 40h; hyperactivity and depression-like behavior (increased immobility in forced-swim test) were demonstrated. Findings indicate physical dependence risk. jnr.25251
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
chemistry2 · 1 ok
This structural relationship is pharmacologically significant: N-ethylation of amphetamine-class compounds consistently shifts monoamine release selectivity toward serotonin relative to dopamine, as demonstrated in the MDA→MDE and amphetamine→ethylamphetamine series.partially supported
N-ethyl substitution reduces dopamine release potency while maintaining serotonin effects. N-ethyl MDA showed less persistent 5-HT depletion. pmid:2885204
Claim in chemistry — inconclusiveinconclusiveworking →
pharmacokinetic-detail1 · 1 ok
All parameters below are inferred from the closest well-studied structural analog, 4-fluoroamphetamine (4-FA), for which controlled human PK data exist.supported
PK study of 4-FA in humans. t1/2 approximately 8-9h (range 5.5-16.8h), Tmax ~2h. Serum and oral fluid analysis. dta.2595