generation run 2026-05-07
57 min completedmodel pipeline-v5plan not recordedrun/328e42cf…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- sparse_evidence
- structural_inference
- safety_data_unverified
Reproduce
- inputs
- 17 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
17 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | OpenAlex | 2-fluoromethamphetamine 2-FMA stimulant pharmacology | 15 | 0 | No directly relevant 2-FMA papers; structural analog literature already captured via PubMed |
| 2 | PubMed | Rickli Liechti para-halogenated amphetamine methamphetamine monoamine transporter release | 1 | 1 | Key pharmacological reference for fluoromethamphetamine class; 4-FMA is the para-position isomer of 2-FMA and provides the best available analog pharmacology data |
| 3 | ClinicalTrials.gov · absence | 2-fluoromethamphetamine | 0 | 0 | No clinical trial data exists |
| 4 | PubMed · absence | 2-fluoromethamphetamine 2-FMA pharmacology | 0 | 0 | Query returned 0 results; substance lacks dedicated PubMed literature |
| 5 | PubMed | fluoroamphetamine new psychoactive substance stimulant | 15 | 4 | Only papers directly naming 2-FMA or providing structural analog pharmacology data (4-FMA para isomer) selected; 4-FA/4-FMA-specific papers kept for analog comparison |
| 6 | PubChem | 2-fluoromethamphetamine | 1 | 1 | Direct chemical identity verification; confirms IUPAC name and molecular formula in seed data |
| 7 | PubMed | PMID 35562170 - Ishii 2023 | 1 | 1 | — |
| 8 | PubMed | fluoromethamphetamine metabolism metabolites human urine forensic | 1 | 1 | — |
| 9 | PubMed | PMID 15639609 - Rösner 2005 | 1 | 1 | — |
| 10 | WebSearch | 2-FMA early 2000s illicit market history first appearance research chemical | 10 | 0 | Market history context; sourced from aggregated web content cross-referencing primary sources |
| 11 | PubMed | PMID 40553972 - Anchondo 2025 | 1 | 1 | — |
| 12 | WebFetch | — | 1 | 3 | — |
| 13 | WebSearch | 2-FMA 2-fluoromethamphetamine legal status scheduling UK US EU Germany | 10 | 2 | Legal status confirmed from multiple sources |
| 14 | Multiple · absence | 2-FMA dose data cross-reference seed vs community | 0 | 0 | Cross-reference confirms no contradictions between seed data and community sources; both derived from PsychonautWiki community consensus |
| 15 | WebSearch | 2-FMA dose duration subjective effects lisdexamfetamine productivity | 10 | 2 | Community evidence for subjective effects profile; no published controlled studies available |
| 16 | WebSearch | 2-FMA UK Australia scheduling Psychoactive Substances Act analog | 10 | 0 | Legal status confirmed for UK; Australia remains unresolved |
| 17 | OpenAlex | NPS designer drugs mechanism of action adverse effects review | 5 | 1 | Key review applicable to amphetamine-class NPS pharmacology context |
55 claims by section — every cited sentence, checked against its source
safety13 · 12 ok
The fluorinated amphetamine/methamphetamine class is associated with significant adverse effects including heart failure, cerebral hemorrhage, and death, as noted by Anchondo et al. (2025) in the context of rising emergency department visits involving these compoundspartially supported
Adverse effects noted include heart failure, cerebral hemorrhage, death. j.jpet.2025.103617
By structural analogy to methamphetamine, 2-FMA carries risk of dose-dependent cardiovascular toxicity: hypertension, tachycardia, vasoconstriction, and — at high doses or with chronic exposure — arrhythmia, vasospasm-induced acute coronary syndrome, and cerebral hemorrhagesupported
Chronic methamphetamine use causes... cardiovascular effects including hypertension, atherosclerosis, vasospasm, sudden cardiac death, dilated cardiomyopathy. Mechanism: excessive catecholamine release causing vasoconstriction, tachycardia, endothelial dysfunction. s00059-024-05279-6
By structural analogy to methamphetamine, 2-FMA carries risk of dose-dependent cardiovascular toxicity: hypertension, tachycardia, vasoconstriction, and — at high doses or with chronic exposure — arrhythmia, vasospasm-induced acute coronary syndrome, and cerebral hemorrhagesupported
Review of methamphetamine clinical toxicology: CNS stimulant effects, sympathomimetic toxidrome, cardiovascular/neurological/psychiatric effects, treatment approaches. 15563650.2010.516752
The sympathomimetic overdose toxidrome includes mydriasis, tremor, agitation, hyperreflexia, seizures, and hyperthermia.supported
sympathomimetic toxidrome; mydriasis, tremor, agitation, hyperreflexia, combative behavior, hallucinations, delirium, anxiety, paranoia, seizures s40263-013-0084-8
Standard immunoassay amphetamine screens are unlikely to detect 2-FMAsupported
4-FA was the only novel stimulant with cross-reactivity to amphetamine ELISA (3354%), implying other novel stimulants (including those like 2-FMA) would produce false negatives on standard immunoassay screens. bkae017
Recommended forensic targets are N-OH-2-FMA and 2-fluoroephedrinesupported
Metabolites: N-OH-2-FMA (N-hydroxylation) and 2-fluoroephedrine diastereomers (aliphatic hydroxylation). N-demethylation product 2-FA also detected but insufficient alone as forensic marker. bkac026
Standard GC-MS cannot reliably discriminate 2-FMA from its positional isomers (3-FMA, 4-FMA) without derivatization or NMR.supported
Mass spectra insufficient to discriminate 2- from 3-FA; acetylation/trifluoroacetylation required. pmid:15639609
Psychosis: Amphetamine-induced psychosis is a well-documented phenomenon characterized by paranoid delusions, auditory hallucinations, and agitation, typically precipitated by high doses or chronic usesupported
Paranoia and hallucinations common with chronic high-dose use. pmid:11687172
The risk of 2-FMA-induced psychosis has not been studied, but is assumed to exist given full discriminative stimulus substitution for methamphetamine.supported
All compounds produced full substitution for methamphetamine in discriminative stimulus tests (ED50 0.32-0.71 mg/kg). j.jpet.2025.103617
2-FMA is classified in community sources as "moderately addictive with a high potential for abuse." Anchondo et al. (2025) demonstrated abuse potential comparable to methamphetamine based on discriminative stimulus data, though the weaker locomotor stimulant effect may attenuate acute reinforcing propertiessupported
Indicates abuse potential comparable to methamphetamine. 2-FMA was a weak locomotor stimulant with lower peak effects. j.jpet.2025.103617
Claim in safety — inconclusiveinconclusiveworking →
Pharmacological management options for amphetamine-class withdrawal remain limited; mirtazapine, naltrexone, and bupropion have shown preliminary efficacy for methamphetamine withdrawal in clinical settings.supported
Mirtazapine, naltrexone, bupropion show potential for MA withdrawal. add.16093
History of psychosis or schizophrenia: Amphetamine-type stimulants can precipitate or exacerbate psychotic episodes.supported
Cochrane review: dopamine antagonists effective for amphetamine psychosis. Paranoia and hallucinations common with chronic high-dose use. pmid:11687172
history8 · 8 ok
Aromatic fluoro analogs of methamphetamine and amphetamine have been present on illicit drug markets since the early 2000ssupported
Aromatic fluoro analogs on illicit market since early 2000s. bkac026
The earliest published analytical characterization relevant to 2-FMA is the 2005 study by Rösner et al., which systematically described the positional isomers of fluoroamphetamine (2-, 3-, and 4-fluoroamphetamine) and their N-alkylated derivatives — including fluoromethamphetamines — encountered in forensic samplespartially supported
Analytical characterization of fluoroamphetamine positional isomers (2-, 3-, 4-fluoroamphetamines) and fluoro-methoxyamphetamines via GC-MS, NMR, and GC-IR. pmid:15639609
Italian forensic laboratories documented 2-fluoromethamphetamine among NPS detected in seized materials purchased via the Internet between 2013 and 2015supported
162 NPS seizures in Italy 2013-2015; among compounds detected was 2-fluoromethamphetamine (first European detection noted). j.forsciint.2016.01.037
A Japanese forensic case involving 2-FMA abuse was published in 2023, providing the only human metabolic data for the compound.supported
Forensic case study of 2-FMA abuse in Japan. Urine analyzed by LC-MS/MS. bkac026
Published research is limited to forensic analytical characterization, a single human metabolite identification study, and one in vivo rodent pharmacology study examining locomotor and discriminative stimulus effects. 2-FMA remains an unscheduled or variably controlled compound in most jurisdictions, with its significance residing primarily in forensic toxicology, harm reduction, and the study of structure-activity relationships within the fluorinated amphetamine class.supported
Analytical characterization of fluoroamphetamine positional isomers (2-, 3-, 4-fluoroamphetamines)... One of the earliest published characterizations of these compounds. pmid:15639609
Published research is limited to forensic analytical characterization, a single human metabolite identification study, and one in vivo rodent pharmacology study examining locomotor and discriminative stimulus effects. 2-FMA remains an unscheduled or variably controlled compound in most jurisdictions, with its significance residing primarily in forensic toxicology, harm reduction, and the study of structure-activity relationships within the fluorinated amphetamine class.supported
162 NPS seizures in Italy 2013-2015; among compounds detected was 2-fluoromethamphetamine. j.forsciint.2016.01.037
Published research is limited to forensic analytical characterization, a single human metabolite identification study, and one in vivo rodent pharmacology study examining locomotor and discriminative stimulus effects. 2-FMA remains an unscheduled or variably controlled compound in most jurisdictions, with its significance residing primarily in forensic toxicology, harm reduction, and the study of structure-activity relationships within the fluorinated amphetamine class.supported
Forensic case study of 2-FMA abuse in Japan. Urine analyzed by LC-MS/MS. bkac026
Published research is limited to forensic analytical characterization, a single human metabolite identification study, and one in vivo rodent pharmacology study examining locomotor and discriminative stimulus effects. 2-FMA remains an unscheduled or variably controlled compound in most jurisdictions, with its significance residing primarily in forensic toxicology, harm reduction, and the study of structure-activity relationships within the fluorinated amphetamine class.supported
Investigates 2-FA, 3-FA, 2-FMA, 3-FMA, 4-FMA in mice and rats. Locomotor ED50 0.38-7.38 mg/kg. j.jpet.2025.103617
pharmacology8 · 7 ok
They enter presynaptic neurons via the dopamine transporter (DAT), norepinephrine transporter (NET), and serotonin transporter (SERT), where they reverse transporter direction and cause active efflux of cytoplasmic monoamines into the synaptic cleftsupported
Covers mechanism of action via NET/DAT/SERT inhibition and transporter-mediated release. 164_2018_113
They enter presynaptic neurons via the dopamine transporter (DAT), norepinephrine transporter (NET), and serotonin transporter (SERT), where they reverse transporter direction and cause active efflux of cytoplasmic monoamines into the synaptic cleftsupported
Comprehensive review of designer drug pharmacology including stimulants (cathinones, amphetamine-like NPS): monoamine transporter interactions, sympathomimetic adverse effects. s00204-020-02693-7
Rickli et al. demonstrated that para-halogenated amphetamines — including 4-fluoromethamphetamine (4-FMA) — exhibit significantly enhanced serotonergic release potency relative to unsubstituted methamphetamine, producing an MDMA-like mixed DA/NE/5-HT profilesupported
Para-substituted amphetamines are more serotonergic and act as releasing agents at NE, DA, 5-HT transporters. j.euroneuro.2014.12.012
Claim in pharmacology — not_supportednot supportedworking →
Anchondo, Shetty, and Gatch (2025) published the only in vivo pharmacology study directly testing 2-FMA, examining fluorinated analogs of amphetamine and methamphetamine (2-FA, 3-FA, 2-FMA, 3-FMA, and 4-FMA) in rodent models.supported
Investigates 2-FA, 3-FA, 2-FMA, 3-FMA, 4-FMA in mice and rats. j.jpet.2025.103617
Metabolism: The only published metabolic data derive from a Japanese forensic case study in which urine from a 2-FMA user was analyzed by LC-MS/MSsupported
Forensic case study of 2-FMA abuse in Japan. Urine analyzed by LC-MS/MS. bkac026
N-hydroxylation and aliphatic hydroxylation are described as "characteristic features of 2-FMA metabolism".supported
N-hydroxylation and aliphatic hydroxylation are characteristic metabolic pathways distinct from methamphetamine. bkac026
Duration context: Community-derived oral duration data (onset 30–60 min, peak 2.5–4 h, total 7–9 h) are broadly consistent with the pharmacokinetic properties of the amphetamine class — the parent compound methamphetamine has a plasma elimination half-life of approximately 11 hourssupported
geometric mean plasma half-life 11.1 hr (smoked), 12.2 hr (IV) pmid:8104133
summary8 · 8 ok
Standard amphetamine immunoassay screens are unlikely to detect 2-FMA, complicating clinical identification in emergency settingssupported
4-FA was the only novel stimulant with cross-reactivity to amphetamine ELISA (3354%), implying other novel stimulants (including those like 2-FMA) would produce false negatives on standard immunoassay screens. bkae017
Aromatic fluoro analogs of methamphetamine and amphetamine have circulated on illicit and gray markets since the early 2000ssupported
Aromatic fluoro analogs on illicit market since early 2000s. bkac026
The earliest systematic analytical characterization of fluoroamphetamine positional isomers appeared in 2005, and 2-FMA itself was available as a research chemical by approximately 2007–2010partially supported
One of the earliest published characterizations of these compounds. pmid:15639609
2-FMA is presumed to act as a substrate-type releaser at monoamine transporters, entering presynaptic terminals and reversing transporter direction to cause efflux of dopamine and norepinephrinesupported
Covers mechanism of action via NET/DAT/SERT inhibition and transporter-mediated release. Amphetamine-like NPS show catecholamine-selective profile. 164_2018_113
2-FMA is presumed to act as a substrate-type releaser at monoamine transporters, entering presynaptic terminals and reversing transporter direction to cause efflux of dopamine and norepinephrinesupported
Comprehensive review of designer drug pharmacology including stimulants (cathinones, amphetamine-like NPS): monoamine transporter interactions, sympathomimetic adverse effects. s00204-020-02693-7
In rodent models, 2-FMA produces dose-dependent locomotor stimulation — weaker than methamphetamine — yet fully substitutes for methamphetamine in discriminative stimulus assays, consistent with the user-reported profile of a "functional" stimulant with reduced acute euphoriasupported
2-FMA was a weak locomotor stimulant with lower peak effects (2200-3980 counts)... All compounds produced full substitution for methamphetamine in discriminative stimulus tests. j.jpet.2025.103617
Cardiovascular risk is the primary safety concern: hypertension, tachycardia, vasoconstriction, and — by class inference from methamphetamine — potential for arrhythmia, vasospasm, and cerebral hemorrhage at high doses or with chronic usesupported
Chronic methamphetamine use causes... cardiovascular effects including hypertension, atherosclerosis, vasospasm, sudden cardiac death, dilated cardiomyopathy. Mechanism: excessive catecholamine release causing vasoconstriction, tachycardia, endothelial dysfunction. s00059-024-05279-6
Cardiovascular risk is the primary safety concern: hypertension, tachycardia, vasoconstriction, and — by class inference from methamphetamine — potential for arrhythmia, vasospasm, and cerebral hemorrhage at high doses or with chronic usesupported
Review of methamphetamine clinical toxicology: CNS stimulant effects, sympathomimetic toxidrome, cardiovascular/neurological/psychiatric effects, treatment approaches. 15563650.2010.516752
pharmacokinetic-detail6 · 5 ok
Standard GC-MS cannot reliably discriminate 2-FMA from 3-FMA or 4-FMA without derivatization (trifluoroacetylation) or complementary NMR analysis.supported
Mass spectra insufficient to discriminate 2- from 3-FA; acetylation/trifluoroacetylation required. pmid:15639609
Ishii et al. (2023) identified three metabolic routes from a single forensic case:supported
Metabolites: N-OH-2-FMA (N-hydroxylation) and 2-fluoroephedrine diastereomers (aliphatic hydroxylation). N-demethylation product 2-FA also detected. bkac026
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
For reference, the structural parent methamphetamine has an oral bioavailability of approximately 67%, Tmax of 3.13 ± 1.25 hours (smoked), and a plasma t½ of approximately 11 hourspartially supported
Methamphetamine PK: oral bioavailability 67.2%, smoked 90.3%; geometric mean plasma half-life 11.1 hr (smoked), 12.2 hr (IV) pmid:8104133
Standard immunoassay amphetamine screens (ELISA-based) are unlikely to detect 2-FMA: Cieri et al. (2024) demonstrated that among NPS stimulants tested, only 4-fluoroamphetamine showed cross-reactivity with amphetamine immunoassayssupported
4-FA was the only novel stimulant with cross-reactivity to amphetamine ELISA (3354%). bkae017
Confirmatory analysis requires LC-MS/MS targeting N-OH-2-FMA and 2-fluoroephedrine as characteristic metabolitessupported
Urine analyzed by LC-MS/MS. Metabolites: N-OH-2-FMA (N-hydroxylation) and 2-fluoroephedrine diastereomers (aliphatic hydroxylation). N-demethylation product 2-FA also detected but insufficient alone as forensic marker. bkac026
comparative-pharmacology4 · 4 ok
Anchondo et al. (2025) provide the only head-to-head in vivo comparison of 2-FMA against its positional isomers (3-FMA, 4-FMA) and the non-methylated fluoroamphetamines (2-FA, 3-FA):supported
Investigates 2-FA, 3-FA, 2-FMA, 3-FMA, 4-FMA in mice and rats. j.jpet.2025.103617
4-FMA is the best-characterized positional isomer, with published in vitro transporter datasupported
In vitro transporter inhibition and release potency at NET, DAT, SERT for para-halogenated amphetamines including 4-fluoromethamphetamine (4-FMA). j.euroneuro.2014.12.012
Methamphetamine is a potent releaser at all three monoamine transporters with a plasma half-life of approximately 11 hours. 2-FMA shares the methamphetamine backbone but produces weaker locomotor stimulation, a shorter reported subjective duration (7–9 hours oral vs. methamphetamine's 8–12+ hours), and a qualitatively different experience described as more cognitive and less euphoricpartially supported
geometric mean plasma half-life 11.1 hr (smoked), 12.2 hr (IV); volume of distribution 3.24-3.73 L/kg pmid:8104133
The metabolic profile diverges substantially: methamphetamine undergoes aromatic 4-hydroxylation and N-demethylation, while 2-FMA is metabolized via N-hydroxylation and aliphatic hydroxylation.supported
N-hydroxylation and aliphatic hydroxylation are characteristic metabolic pathways distinct from methamphetamine. bkac026
chemistry2 · 1 ok
The ortho position distinguishes 2-FMA pharmacologically from its para isomer: Rickli et al. demonstrated that para-halogen substitution on amphetamine significantly increases serotonergic release potency relative to the unsubstituted parent, an effect not characterized for ortho substitution.supported
Para-substituted amphetamines are more serotonergic and act as releasing agents at NE, DA, 5-HT transporters. j.euroneuro.2014.12.012
Claim in chemistry — inconclusiveinconclusiveworking →
neuroscience2 · 1 ok
Claim in neuroscience — inconclusiveinconclusiveworking →
The relatively weak locomotor stimulant effect of 2-FMA observed in mice may reflect a preferential engagement of cortical over subcortical dopaminergic circuits — higher DA release in PFC relative to NAc — though this hypothesis has not been tested with microdialysis or positron emission tomographysupported
2-FMA was a weak locomotor stimulant with lower peak effects (2200-3980 counts) vs 3-FA/2-FA/3-FMA (5905-7758 counts). j.jpet.2025.103617
receptor-pharmacology2 · 2 ok
Rickli et al. (2015) characterized the in vitro transporter pharmacology of para-halogenated amphetamines, including 4-fluoromethamphetamine (4-FMA)supported
In vitro transporter inhibition and release potency at NET, DAT, SERT for para-halogenated amphetamines including 4-fluoromethamphetamine (4-FMA). j.euroneuro.2014.12.012
Based on the community-reported effect profile — predominant cognitive stimulation and wakefulness with attenuated euphoria relative to methamphetamine — and the weak locomotor stimulant effect observed in mice, 2-FMA is provisionally characterized as:supported
2-FMA was a weak locomotor stimulant with lower peak effects (2200-3980 counts) vs 3-FA/2-FA/3-FMA (5905-7758 counts). j.jpet.2025.103617
clinical-evidence1 · 1 ok
The only published human data derive from a single forensic case report in which urine from an individual who had used 2-FMA was analyzed for metabolite identification purposessupported
Forensic case study of 2-FMA abuse in Japan. Urine analyzed by LC-MS/MS. Metabolites: N-OH-2-FMA (N-hydroxylation) and 2-fluoroephedrine diastereomers. bkac026
legal-status1 · 1 ok
The full discriminative stimulus substitution for methamphetamine demonstrated by Anchondo et al. (2025) could constitute pharmacological evidence of substantial similarity in a prosecution context.supported
All compounds produced full substitution for methamphetamine in discriminative stimulus tests (ED50 0.32-0.71 mg/kg). j.jpet.2025.103617