generation run 2026-05-07
61 min completedmodel pipeline-v5plan not recordedrun/5d254f41…Selection
Verification
- record
- seen / partial
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The model's own caveats
- sparse_evidence
- structural_inference
- safety_data_unverified
Reproduce
- inputs
- 29 source keys (listed under Sources)
- plan
- not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
- model
- pipeline-v5
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- none — agent transcripts are persisted from 2026-09 onward
21 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | WebSearch | 2-FEA legal status UK EU Germany Sweden | 10 | 3 | — |
| 2 | WebSearch | 2-FEA N-ethyl-1-(2-fluorophenyl)propan-2-amine pharmacology drug stimulant | 10 | 2 | Community-sourced data on dose, duration, and subjective effects |
| 3 | PubMed | phenethylamine N-ethyl substituted amphetamine structure activity relationship | 3 | 2 | N-ethyl SAR data directly applicable to 2-FEA structure |
| 4 | PubMed · absence | 2-FEA 2-fluoroethylamphetamine fluorinated amphetamine pharmacology | 0 | — | — |
| 5 | PubMed | 2-fluorophenethylamine amphetamine stimulant NPS forensic toxicology | 10 | — | — |
| 6 | PubChem | 2-FEA | 1 | 1 | Confirmed chemical identity data |
| 7 | Bluelight | — | — | 1 | — |
| 8 | PubMed | fluorinated amphetamine methamphetamine locomotor discriminative stimulus | 1 | 1 | Critical paper: directly tests 2-FA (closest 2-FEA structural analog) for locomotor stimulation and methamphetamine-like discriminative stimulus effects |
| 9 | PubMed | amphetamine dopamine norepinephrine releasing agent mechanism | 4 | 3 | Class-level mechanism of action reviews applicable to 2-FEA |
| 10 | PubMed · absence | fluoroamphetamine pharmacokinetics half-life human plasma | 0 | — | — |
| 11 | OpenAlex | 2-FEA fluorophenyl amphetamine designer stimulant | 3 | 2 | Analytical chemistry papers showing 2-FEA class compounds resolved by chiral separation methods |
| 12 | PubMed · absence | fluorinated amphetamine monoamine releasing agent dopamine norepinephrine | 0 | — | — |
| 13 | PubMed | 4-fluoroamphetamine human study clinical safety cardiovascular | 2 | 2 | Only controlled human study of a fluoroamphetamine class compound; provides analog reference data |
| 14 | PsychonautWiki | — | — | 2 | — |
| 15 | Cayman Chemical | — | — | — | — |
| 16 | WebSearch | 2-FEA legal status UK Psychoactive Substances Act Germany Sweden scheduling | 10 | — | — |
| 17 | PubMed | UK Psychoactive Substances Act 2016 NPS toxicity | 2 | 1 | — |
| 18 | PubMed · absence | 3-fluoroethamphetamine identification characterization seized material NPS | 0 | — | — |
| 19 | WebSearch | 3-fluoroethamphetamine identification characterization seized journal article doi 2018 | 10 | 1 | — |
| 20 | PubMed | 2-fluoromethamphetamine metabolites human urine identification | 2 | 1 | 2-FMA metabolic pathway data (N-hydroxylation, beta-hydroxylation) directly applicable to predicted 2-FEA metabolism |
| 21 | Crossref via verify_doi | 10.1007/s11419-018-0416-y | 1 | — | — |
63 claims by section — every cited sentence, checked against its source
safety22 · 21 ok
Cardiovascular toxicity represents the primary acute safety concern for fluorinated amphetamines. 4-Fluoroamphetamine produces exaggerated blood pressure effects compared to both MDMA and amphetamine in emergency department presentations, with documented cases of cardiomyopathy, myocardial infarction, and cerebral hemorrhagesupported
4-FA produces exaggerated BP effects vs MDMA and amphetamine. Documents cardiomyopathy, myocardial infarction, and cerebral hemorrhage in ED presentations. emp2.12813
In the only controlled human trial of a fluoroamphetamine, the 150 mg oral arm of a 4-FA study was cancelled after interim safety review due to severe blood pressure elevation at the 100 mg dosesupported
100 mg arm completed; 150 mg cancelled after interim review due to severe BP elevation. fphar.2018.00713
Amphetamine-type stimulants broadly cause hypertension, accelerated atherosclerosis, vasospasm-induced acute coronary syndromes, sudden cardiac death, and dilated cardiomyopathy via excessive catecholamine release leading to vasoconstriction, tachycardia, and endothelial dysfunction.supported
METH causes hypertension, accelerated atherosclerosis, vasospasm-induced acute coronary syndromes, sudden cardiac death, dilated cardiomyopathy via excessive catecholamine release causing vasoconstriction, tachycardia, endothelial dysfunction. s00059-024-05279-6
Stimulant-induced hyperthermia can progress to blood-brain barrier leakage, vasogenic edema, and death, a cascade potentiated by warm ambient temperatures and physical exertionsupported
METH increases body/brain temperature; hyperthermia → BBB leakage → vasogenic edema → death. Potentiated in warm environments. bs.irn.2019.06.010
Amphetamine-like NPS share this cardiovascular and thermodysregulatory toxicity profile with MDMA-type stimulants.supported
Stimulants act on monoamine transporters NET, DAT, and SERT; can cause serious and potentially fatal adverse events via thermodysregulatory and cardiovascular mechanisms. jcph.1918
Para-halogenation of amphetamine increases mitochondrial toxicity and apoptosis in neuronal cells (SH-SY5Y model) compared to non-halogenated analogssupported
Halogenation increases neurotoxic properties via mitochondrial impairment and apoptosis induction. Cytotoxic concentrations were higher than pharmacological activity concentrations. ijms21082841
Based on class-level data for amphetamine-type stimulant overdose, the expected clinical features include mydriasis, tremor, agitation, hyperreflexia, combative behavior, confusion, hallucinations, delirium, anxiety, paranoia, movement disorders, and seizuressupported
Amphetamine overdose: mydriasis, tremor, agitation, hyperreflexia, hallucinations, delirium, anxiety, paranoia, seizures. s40263-013-0084-8
Analog data support this assessment: fluorinated amphetamines produce drug liking and wanting comparable to classical stimulants, 2-FA shows full methamphetamine-like abuse potential in rodent discriminative stimulus studies, and primarily catecholaminergic releasing agents carry higher abuse liability than serotonin-selective releasers.supported
4-FA 100mg increased self-ratings of drug liking and wanting at 1h. s00213-018-4931-7
Analog data support this assessment: fluorinated amphetamines produce drug liking and wanting comparable to classical stimulants, 2-FA shows full methamphetamine-like abuse potential in rodent discriminative stimulus studies, and primarily catecholaminergic releasing agents carry higher abuse liability than serotonin-selective releasers.supported
All produced dose-dependent stimulation; full substitution for methamphetamine in discriminative tests. 2-FA showed peak locomotor effects comparable to methamphetamine. j.jpet.2025.103617
Claim in safety — inconclusiveinconclusiveworking →
Analog data support this assessment: fluorinated amphetamines produce drug liking and wanting comparable to classical stimulants, 2-FA shows full methamphetamine-like abuse potential in rodent discriminative stimulus studies, and primarily catecholaminergic releasing agents carry higher abuse liability than serotonin-selective releasers.supported
Amphetamine-like NPS induce psychostimulation and euphoria mediated predominantly by norepinephrine and dopamine transporter inhibition... showing a more catecholamine-selective profile. 164_2018_113
Concurrent serotonergic medication (SSRIs, SNRIs, tramadol, other serotonin-active drugs) represents a relative-to-absolute contraindication depending on the specific agent and dosage, due to additive serotonin toxicity risk.supported
Drug-drug interaction potential anticipated via MAO for both compounds; monoamine transporters more specific to 4-FA. ftd.0000000000000725
Tramadol inhibits SERT and NET, and its combination with a monoamine releaser creates conditions for serotonin toxicity syndrome — hyperthermia, rigidity, myoclonus, seizures, and deathsupported
Tramadol, meperidine, methadone, tapentadol, and dextromethorphan inhibit SERT in human HEK293 cells... Heightened risk with serotonergic antidepressants and stimulants. s00204-018-2244-6
This risk is compounded by potential pharmacokinetic interaction: tramadol is metabolized by CYP2D6 and CYP3A4, and co-administered monoamine releasers may inhibit these pathwayssupported
MDMA inhibits CYP2D6 and CYP3A4; tramadol is metabolized by CYP2D6 and CYP3A4 to active metabolites. Co-administration risk via enzyme inhibition. apb.2021.061
MDMA co-administration produces additive monoamine excess through competing reverse-transport mechanisms at shared transporters, creating synergistic risk for serotonin syndrome, extreme hyperthermia, and cardiovascular collapsesupported
Overview of MDMA drug interactions; polydrug use leads to higher risk of acute and life-threatening toxicity. 17425255.2020.1749262
MDMA additionally inhibits CYP2D6 via mechanism-based inhibition, potentially reducing metabolism of co-administered 2-FEAsupported
CYP2D6 mediates O-demethylenation; mechanism-based inhibition makes all users phenotypic poor metabolizers after 2 doses. pmid:15228154
Fatal serotonin toxicity from MDMA combined with MAO-modulating drugs is documented in forensic case series.supported
Four fatal serotonin toxicity cases from MDMA+moclobemide combination. Symptoms: hyperthermia, hyperkalemia, sweating, twitching/shaking. j.forsciint.2011.04.008
Amphetamine derivatives themselves exhibit MAO inhibitory activity at higher concentrations, meaning 2-FEA may potentiate its own serotonergic toxicity risk in MAOI combinations.supported
Review of how structural modifications of amphetamine scaffold modulate MAO inhibitory properties. MAO inhibition by ring-substituted amphetamines may influence pharmacology and toxicity. fphar.2019.01590
Stimulant-stimulant combinations — specifically cocaine co-administration — create massive unsustainable increases in extracellular dopamine and norepinephrine: cocaine blocks DAT/NET while 2-FEA reverses transport through the same carrierssupported
Stimulants act on monoamine transporters NET, DAT, and SERT; can cause serious and potentially fatal adverse events via thermodysregulatory and cardiovascular mechanisms. jcph.1918
SSRIs and SNRIs present pharmacodynamic interaction potential via additive serotonin load, increasing serotonin syndrome risk.supported
Systematic review of 4-FA and 2C-B interactions with antidepressants, ADHD medications, antiretrovirals. Drug-drug interaction potential anticipated via MAO for both compounds; monoamine transporters more specific to 4-FA. ftd.0000000000000725
Pre-existing hypertension, coronary artery disease, cardiomyopathy, arrhythmias, or cerebrovascular disease significantly elevate the risk of acute cardiovascular events — myocardial infarction, stroke, cardiac arrest — when combined with a catecholamine-releasing stimulant.supported
METH causes hypertension, accelerated atherosclerosis, vasospasm-induced acute coronary syndromes, sudden cardiac death, dilated cardiomyopathy via excessive catecholamine release. s00059-024-05279-6
Concurrent MAOI therapy is an absolute contraindication due to the risk of hypertensive crisis and serotonin syndrome.supported
MAO inhibition by ring-substituted amphetamines may influence pharmacology and toxicity. fphar.2019.01590
neuroscience9 · 6 ok
Does 2-FEA produce neurotoxicity at recreational doses? Para-halogenation of amphetamine increases mitochondrial toxicity in neuronal cells, but whether this extends to ortho-fluorination is unknown.supported
Halogenation increases neurotoxic properties via mitochondrial impairment and apoptosis induction. ijms21082841
Amphetamine-type stimulants potentiate the mesolimbic dopamine pathway — specifically, dopamine release from ventral tegmental area (VTA) neurons projecting to the nucleus accumbens (NAc) — producing the reinforcing subjective effects of euphoria, motivation enhancement, and rewardsupported
Amphetamine-like NPS induce psychostimulation and euphoria mediated predominantly by norepinephrine and dopamine transporter inhibition and transporter-mediated release of NE and DA. 164_2018_113
If 2-FEA produces meaningful serotonin release (as predicted by N-ethyl SAR data), additional modulation of amygdala reactivity and prefrontal-amygdala connectivity would be expected, consistent with the mild entactogenic qualities reported by userssupported
SAR for locomotor stimulant and monoamine transporter effects of 12 phenethylamines with N-ethyl substitutions characterized at DAT, NET, and SERT in rat brain synaptosomes. j.neuropharm.2023.109827
Stimulant-induced hyperthermia involves disruption of hypothalamic thermoregulatory circuits, with severe cases progressing to blood-brain barrier breakdown and vasogenic edema.supported
METH increases body/brain temperature; hyperthermia → BBB leakage → vasogenic edema → death. bs.irn.2019.06.010
Fluorinated amphetamines including 4-FA elevate both drug liking and wanting in humans, consistent with high abuse liabilitysupported
4-FA 100mg increased self-ratings of drug liking and wanting at 1h. s00213-018-4931-7
Claim in neuroscience — inconclusiveinconclusiveworking →
Does ortho-fluorination produce the same serotonergic augmentation as para-fluorination? Published data on fluorine position effects on SERT activity are limited to para-substituted compounds; the ortho position's influence remains uncharacterized.supported
Para-(4)-substituted amphetamines including 4-fluoroamphetamine were relatively more serotonergic compared with non-substituted analogs. j.euroneuro.2014.12.012
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
comparative-pharmacology7 · 3 ok
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
4-FA (4-fluoroamphetamine) is the most pharmacologically characterized fluoroamphetamine, with published human trial data. 4-FA at 100 mg oral dose produces severe blood pressure elevation and mood effects peaking at 1 hour, with elevated drug liking indicative of abuse liability. 4-FA exhibits exaggerated cardiovascular toxicity relative to both MDMA and amphetamine in emergency department presentations. 2-FEA differs in fluorine position (ortho versus para), N-substitution (N-ethyl versus primary amine), and reported duration profile.supported
100 mg arm completed; 150 mg cancelled after interim review due to severe BP elevation. Strong BP elevation up to 4-5h, sustained tachycardia. Peak mood effects at 1h: vigor, elation, arousal, positive mood. fphar.2018.00713
4-FA (4-fluoroamphetamine) is the most pharmacologically characterized fluoroamphetamine, with published human trial data. 4-FA at 100 mg oral dose produces severe blood pressure elevation and mood effects peaking at 1 hour, with elevated drug liking indicative of abuse liability. 4-FA exhibits exaggerated cardiovascular toxicity relative to both MDMA and amphetamine in emergency department presentations. 2-FEA differs in fluorine position (ortho versus para), N-substitution (N-ethyl versus primary amine), and reported duration profile.supported
4-FA 100mg increased self-ratings of drug liking and wanting at 1h; did not affect impulsive behavior. s00213-018-4931-7
4-FA (4-fluoroamphetamine) is the most pharmacologically characterized fluoroamphetamine, with published human trial data. 4-FA at 100 mg oral dose produces severe blood pressure elevation and mood effects peaking at 1 hour, with elevated drug liking indicative of abuse liability. 4-FA exhibits exaggerated cardiovascular toxicity relative to both MDMA and amphetamine in emergency department presentations. 2-FEA differs in fluorine position (ortho versus para), N-substitution (N-ethyl versus primary amine), and reported duration profile.supported
4-FA produces exaggerated BP effects vs MDMA and amphetamine. Documents cardiomyopathy, myocardial infarction, and cerebral hemorrhage in ED presentations. emp2.12813
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
summary6 · 4 ok
Claim in summary — inconclusiveinconclusiveworking →
As a substituted amphetamine, 2-FEA is presumed to act primarily through carrier-mediated reverse transport of dopamine and norepinephrine via DAT and NETsupported
Amphetamine-like NPS induce psychostimulation and euphoria mediated predominantly by norepinephrine and dopamine transporter inhibition and transporter-mediated release of NE and DA. 164_2018_113
Structure-activity relationship data suggest that the N-ethyl substitution augments relative potency at the serotonin transporter (SERT) compared to N-methyl analogs such as 2-FMA, and community sources classify 2-FEA as both a stimulant and entactogen, implying a serotonergic contribution that has not been quantifiedsupported
SAR for locomotor stimulant and monoamine transporter effects of 12 phenethylamines with N-ethyl substitutions characterized at DAT, NET, and SERT in rat brain synaptosomes. j.neuropharm.2023.109827
Cardiovascular toxicity is the primary acute concern by analog inference: the structurally related 4-fluoroamphetamine produces exaggerated blood pressure elevation relative to both MDMA and amphetamine, and amphetamine-type stimulants broadly cause hypertension, tachycardia, and endothelial dysfunction via excessive catecholamine releasesupported
4-FA produces exaggerated BP effects vs MDMA and amphetamine. Documents cardiomyopathy, myocardial infarction, and cerebral hemorrhage in ED presentations. emp2.12813
Cardiovascular toxicity is the primary acute concern by analog inference: the structurally related 4-fluoroamphetamine produces exaggerated blood pressure elevation relative to both MDMA and amphetamine, and amphetamine-type stimulants broadly cause hypertension, tachycardia, and endothelial dysfunction via excessive catecholamine releasesupported
METH causes hypertension, accelerated atherosclerosis, vasospasm-induced acute coronary syndromes, sudden cardiac death, dilated cardiomyopathy via excessive catecholamine release causing vasoconstriction, tachycardia, endothelial dysfunction. s00059-024-05279-6
Claim in summary — inconclusiveinconclusiveworking →
receptor-pharmacology5 · 3 ok
For comparative context, 4-fluoroamphetamine (4-FA) at 100 mg oral dose produced strong blood pressure elevation persisting to 4–5 hours, sustained tachycardia, and peak mood effects at 1 hour post-dose in a controlled human trial; the planned 150 mg arm was cancelled after interim safety reviewsupported
100 mg arm completed; 150 mg cancelled after interim review due to severe BP elevation. Strong BP elevation up to 4-5h, sustained tachycardia. Peak mood effects at 1h: vigor, elation, arousal, positive mood. fphar.2018.00713
Rank-order locomotor potency places 2-FA above 4-FMA but below 2-FMA and methamphetamine.partially supported
Investigates 2-FA, 3-FA, 2-FMA, 3-FMA, and 4-FMA in locomotor and discriminative stimulus assays. 2-FA showed peak locomotor effects comparable to methamphetamine. j.jpet.2025.103617
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Monoamine transporter interaction profiles for para-halogenated amphetamines demonstrate that fluorination increases serotonergic activity relative to unsubstituted analogs, though these data derive from para-substitution and may not directly translate to ortho-fluorinated compounds.supported
Para-(4)-substituted amphetamines including 4-fluoroamphetamine were relatively more serotonergic compared with non-substituted analogs. j.euroneuro.2014.12.012
pharmacology4 · 3 ok
As a substituted amphetamine, 2-FEA is presumed to act as a monoamine releasing agent — inducing reverse transport of dopamine (DA) and norepinephrine (NE) through the dopamine transporter (DAT) and norepinephrine transporter (NET), the primary mechanism by which amphetamine-type NPS produce psychostimulation and euphoriasupported
Amphetamine-like NPS induce psychostimulation and euphoria mediated predominantly by norepinephrine and dopamine transporter inhibition and transporter-mediated release of NE and DA. 164_2018_113
Claim in pharmacology — inconclusiveinconclusiveworking →
Second, para-fluorination of amphetamines (e.g., 4-FA, 4-FMA) increases serotonergic relative to catecholaminergic activitysupported
Para-(4)-substituted amphetamines including 4-fluoroamphetamine were relatively more serotonergic compared with non-substituted analogs. j.euroneuro.2014.12.012
Metabolic pathways are predicted by analogy to 2-fluoromethamphetamine (2-FMA): (1) N-deethylation to produce 2-fluoroamphetamine (2-FA) as the primary metabolite, analogous to 2-FMA's N-demethylation to 2-FA; (2) N-hydroxylation to form N-OH-2-FEA; and (3) beta-hydroxylation to produce a 2-fluoroephedrine-like productsupported
N-hydroxylation and aliphatic hydroxylation are characteristic metabolic pathways of 2-FMA. N-OH-2-FMA and 2-fluoroephedrine identified as analytical targets. 2-FA is a metabolite of 2-FMA via N-demethylation. bkac026
history3 · 0 ok
pharmacokinetic-detail3 · 3 ok
Based on the metabolic characterization of 2-FMA in human urine, the following metabolic transformations are predicted for 2-FEA:supported
N-hydroxylation and aliphatic hydroxylation are characteristic metabolic pathways of 2-FMA. N-OH-2-FMA and 2-fluoroephedrine identified as analytical targets. 2-FA is a metabolite of 2-FMA via N-demethylation. bkac026
Ring hydroxylation: By analogy to 4-FA metabolism, aromatic hydroxylation may occur, though the ortho-fluorine position may sterically or electronically disfavor this pathway.supported
Three metabolites identified: diastereomers of fluorophenylpropanolamine and ring-hydroxylated 4-FA. j.jpba.2019.113008
MDMA inhibits CYP2D6 via mechanism-based inhibition, meaning co-administration of MDMA with 2-FEA could reduce 2-FEA metabolism and elevate plasma levels unpredictably.supported
CYP2D6 mediates O-demethylenation; mechanism-based inhibition makes all users phenotypic poor metabolizers after 2 doses. pmid:15228154
chemistry2 · 0 ok
clinical-evidence2 · 2 ok
The only controlled human study of any fluoroamphetamine is a Phase I safety and neurocognitive assessment of 4-fluoroamphetamine (4-FA) at 100 mg oral dosesupported
Phase 1, placebo-controlled within-subject trial N=12. 100 mg arm completed; 150 mg cancelled after interim review due to severe BP elevation. fphar.2018.00713
That trial demonstrated significant blood pressure elevation, sustained tachycardia, elevated drug liking and wanting, and peak mood effects (vigor, friendliness, elation, positive mood) within the first 1–2 hours post-dosepartially supported
4-FA 100mg increased self-ratings of drug liking and wanting at 1h; did not affect impulsive behavior. s00213-018-4931-7