N-Ethylhexedrone

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what any key link opens

psx:substance/n-ethylhexedrone/section/effects-overview.full@1

sectionreferenced by edges — no row of its own

derived from · upstream

informed_byClaim in effects-overview — supportedpsx:substance/n-ethylhexedrone/claim/544cfc5f-6d5c-4ca6-bcef-69861c08317c

feeds · downstream

none recorded

psx:substance/n-ethylhexedrone/section/effects-overview.full@1
├─ informed_by  claim/544cfc5f-6d5c-4ca6-bcef-69861c08317c  Claim in effects-overview — supported
  ├─ used  src/doi:10.1111/adb.12987  Behavioral effects of four novel synthetic cathinone analogs in rodents
      ├─ used  src/doi:10.1002/dta.3547  Characterization of neurotransmitter inhibition for seven cathinones by a proprietary fluorescent dye method.
      ├─ used  src/doi:10.1093/jat/bkae040  N-Ethylhexedrone: A very long and bad trip! A case series
      ├─ used  src/url:3f8f8d2f08c404f5  N-Ethylhexedrone
      ├─ used  src/doi:10.1097/FTD.0000000000000808
      ├─ used  src/doi:10.3390/ph18050721  Acute Pharmacological Effects of Two Synthetic Cathinones in Humans: N-Ethylhexedrone and N-Ethyl-nor-pentedrone
      ├─ used  src/doi:10.1021/acschemneuro.2c00772  Structure-Activity Relationship of N-Ethyl-Hexedrone Analogues: Role of the alpha-Carbon Side-Chain Length
      ├─ used  src/doi:10.1007/s12640-020-00229-6  Designer Cathinones N-Ethylhexedrone and Buphedrone Show Different In Vitro Neurotoxicity and Mice Behaviour Impairment
      ├─ used  src/doi:10.1093/jat/bkaa159  Fatal N-Ethylhexedrone Intoxication
      ├─ used  src/doi:10.1111/bcpt.13786  Retrospective identification of new psychoactive substances in patient samples submitted for clinical drug analysis
      ├─ used  src/url:3c0a926a9003c891  Schedules of Controlled Substances: Placement of N-Ethylhexedrone, alpha-Pyrrolidinohexanophenone [et al.] in Schedule I
      ├─ used  src/url:58baf0d56c650a8b  Critical Review Report: N-Ethylhexedrone — WHO Expert Committee on Drug Dependence (47th ECDD)
      ├─ used  src/url:65a60d1d25557bad  N-Ethylhexedrone — PubChem CID 134822125
      ├─ used  src/doi:10.3390/molecules27072057  Synthetic Cathinones: Recent Developments, Enantioselectivity Studies and Enantioseparation Methods
      ├─ used  src/doi:10.1021/acschemneuro.3c00156  Structure-Activity Relationships for a Recently Controlled Synthetic Cathinone Dopamine Transporter Reuptake Inhibitor: α-Pyrrolidinohexiophenone (α-PHP)
      ├─ used  src/doi:10.1016/j.jpba.2024.115994  Metabolic profile of N-ethylhexedrone, N-ethylpentedrone, and 4-chloromethcathinone in urine samples by UHPLC-QTOF-HRMS.
      ├─ used  src/doi:10.1016/j.jchromb.2020.122340  Metabolism of N-ethylhexedrone and buphedrone: An in vivo study in mice using HPLC-MS/MS
      ├─ used  src/doi:10.1007/s11419-020-00568-1  Fatal intoxication with U-47700 in combination with other NPS (N-ethylhexedrone, adinazolam, 4-CIC, 4-CMC) confirmed by identification and quantification in autopsy specimens and evidences.
      ├─ used  src/doi:10.1007/s00204-020-02693-7  Designer drugs: mechanism of action and adverse effects
      ├─ used  src/doi:10.3390/ijms24076230  Synthetic Cathinones and Neurotoxicity Risks: A Systematic Review
      ├─ used  src/doi:10.1016/j.pnpbp.2022.110562  Repeated administration of N-ethyl-pentedrone induces increased aggression and impairs social exploration after withdrawal in mice
      ├─ used  src/doi:10.1016/j.jflm.2019.04.012  Fatal intoxication of a regular drug user following N-ethyl-hexedrone and ADB-FUBINACA consumption
      ├─ used  src/doi:10.1007/s13181-019-00734-x  Severe Toxicity to the New Psychoactive Substances 3-Hydroxyphencyclidine and N-Ethylhexedrone: an Analytically Confirmed Case Report
      ├─ used  src/doi:10.1097/FTD.0000000000000682
      ├─ derived_from  gen/bafe12a1-7376-4483-98fa-c17d9b8db1aa  Generation — pipeline-v5
      └─ generated_by  pub/09ec6b0f-5a5c-4dba-877c-85158dd991b0  Publication — backfill
    ├─ used  version/1  Revision 1
    ├─ used  claim/a27955ea-75e1-467a-8bbe-59e7a220e83c  Claim in summary — inconclusive  working
    ├─ used  claim/eb194d09-036e-4b9d-be57-0a53ebed737b  Claim in summary — partially_supported
    ├─ used  claim/1cf8eecf-33ed-4db7-bc4c-12afde33666e  Claim in pharmacology — inconclusive  working
    ├─ used  claim/c8634dc2-cf50-4634-a45a-ef6d370bfc03  Claim in safety — partially_supported
    ├─ used  claim/a9da119f-b5bd-4a13-b699-9631031dd52c  Claim in safety — inconclusive  working
    ├─ used  claim/5441e076-7299-4b5c-b484-d283474c754c  Claim in safety — supported
    ├─ used  claim/d770ee27-bae6-481f-8bed-ecec7b93cf95  Claim in receptor-pharmacology — inconclusive  working
    ├─ used  claim/e136ebf7-202c-4e00-a0be-f5cd3a902af8  Claim in neuroscience — supported
      ├─ derived_from  issue/notice@710e21e348e3  Issued notice
      ├─ derived_from  issue/info_card@b47cd38da77d  Issued info_card
      ├─ derived_from  issue/emergency@58d3299a8754  Issued emergency
      ├─ derived_from  issue/info_card@5c98b45dd2ce  Issued info_card
      ├─ informed_by  section/summary.full@1
      ├─ informed_by  section/pharmacology.full@1
      ├─ informed_by  section/safety.full@1
      ├─ informed_by  section/receptor-pharmacology.full@1
      └─ informed_by  section/neuroscience.full@1
… closure truncated at 200 nodes

indented by distance from this node, not by parentage

1Provenance card

the boundary, as counts

Sources

2420 with DOI

3 strong · 12 moderate · 9 weak

Compilations

12026-05-12T01:49:33.610Z

pipeline-v5 · prompt hash not recorded — run predates 2026-09

Decisions

45last ruled 2026-06-04

0 awaiting a ruling

Issued documents

42026-10-19T20:33:16.222Z

notice · info card · emergency

Searches

181 with no results

queries and counts on the build

Claims checked

10378 supported

78 supported · 25 not

Correspondence

0received

consent field ships in Phase 4

Edges

306

derivations recorded for this entity

Complete over 24 sources, 1 compilation, and 45 decisions.Not here: the private journal (never).Working material — drafts, discards, unsupported claims — is listed below and readable on the working page.Cite: psychedex.org/substances/n-ethylhexedrone/archive

2Build

one panel per compilation run

generation run 2026-05-12

94 min completedmodel pipeline-v5plan not recordedrun/a655cb26…

Selection

results seen98

selected by the model31

consumed as sources24

Verification

claims checked103

supported65

partially supported13

not supported0

inconclusive25

record
seen / partial
working

The model's own caveats

sparse_evidence
sparse_evidence
safety_data_unverified

Reproduce

inputs: 24 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

18 searches for this run
#	source	query	seen	kept	rationale
1	OpenAlex	N-ethylhexedrone synthetic cathinone pharmacology	10	6	High-citation review articles providing broader pharmacological and toxicological context
2	PubMed	N-ethylhexedrone DAT NET SERT transporter inhibition cathinone	1	1	Key pharmacological binding data
3	PubMed	N-ethylhexedrone metabolism metabolite identification forensic	1	1	Already captured
4	PubChem	N-Ethylhexedrone	1	1	Primary chemical identity verification
5	PubMed	N-Ethylhexedrone pharmacology	12	10	All selected as directly relevant to NEH pharmacology, toxicity, or metabolism
6	ClinicalTrials.gov · absence	N-Ethylhexedrone	0	0	No trials registered
7	PubMed	N-Ethylhexedrone toxicity case report	1	1	Already captured in prior search
8	WebSearch	N-Ethylhexedrone legal status scheduling DEA UK Germany 2024	10	2	Official regulatory sources confirming scheduling dates
9	WebSearch	N-ethylhexedrone structure-activity SAR analogue hexedrone ACS chemical neuroscience 2023	10	1	Key pharmacological SAR paper specific to NEH
10	PsychonautWiki	—	1	0	Dose cross-reference (community source)
11	WebSearch	N-Ethylhexedrone Australia ACMS scheduling analog act Canada controlled	9	1	Australia scheduling confirmation
12	WebSearch	N-Ethylhexedrone HEXEN first appearance market 2015 2016 research chemical	10	1	Historical market emergence data
13	WebSearch	N-Ethylhexedrone half-life pharmacokinetics 19 hours 28 hours elimination	9	1	Clarifying seed data tolerance half-life vs elimination half-life
14	WebSearch	N-Ethylhexedrone CAS number SMILES InChI PubChem 134822125	10	2	Chemical identity data extraction
15	WebSearch	N-Ethylhexedrone tramadol interaction serotonin syndrome fatality	10	0	Flagging unverified interaction
16	PubMed	N-ethyl-hexedrone analogues alpha-carbon side-chain mechanism cytotoxicity mice 2023	1	1	Key SAR paper specifically on NEH
17	Crossref/DOI	10.1007/s11419-020-00568-1	1	1	Fatal polydrug case involving NEH
18	Crossref/DOI	10.1021/acschemneuro.2c00772	1	1	DOI verification of key SAR paper

103 claims by section — every cited sentence, checked against its source

safety39 · 34 ok

A fatal polydrug case involving NEH (58 ng/mL) with U-47700 (1470 ng/mL) and adinazolam documents the lethal potential of cathinone-opioid-benzodiazepine combinations.supported
NEH blood concentration 58 ng/mL alongside U-47700 (1470 ng/mL), adinazolam (18 ng/mL). s11419-020-00568-1
A fatal combination of NEH with ADB-FUBINACA (synthetic cannabinoid) has been reported.supported
Hungary case: 23-year-old male fatally intoxicated by NEH and synthetic cannabinoid ADB-FUBINACA. j.jflm.2019.04.012
Severe acute toxicity from combined 3-HO-PCP and NEH has been analytically confirmed.supported
Analytically confirmed case of acute toxicity from combined 3-HO-PCP and NEH use. s13181-019-00734-x
Post-withdrawal depression-like behavior is supported by both human clinical observations (asthenia, abulia, psychomotor slowing) and animal models.supported
Clinical effects: anxiety, persecution, asthenia, anhedonia, abulia, psychomotor slowing, loss of consciousness. bkae040
Claim in safety — inconclusiveinconclusiveworking →
Case 2: A 23-year-old male in Hungary following combined NEH and ADB-FUBINACA (synthetic cannabinoid) consumption.supported
Hungary case: 23-year-old male fatally intoxicated by NEH and synthetic cannabinoid ADB-FUBINACA. j.jflm.2019.04.012
Case 3: A polydrug fatality in Poland with NEH at 58 ng/mL in postmortem blood alongside U-47700 (1470 ng/mL), adinazolam (18 ng/mL), 4-CIC (8.0 ng/mL), and 4-CMC (1.7 ng/mL). Death was attributed primarily to U-47700 with synergistic benzodiazepine contribution.supported
Poland: polydrug fatality. NEH blood concentration 58 ng/mL alongside U-47700 (1470 ng/mL), adinazolam (18 ng/mL), 4-CIC (8.0 ng/mL), 4-CMC (1.7 ng/mL). Primary cause: lethal U-47700 opioid intoxication, synergistic with benzodiazepine adinazolam. s11419-020-00568-1
A review of synthetic cathinone-related fatalities from 2017–2020 identified NEH as one of the three most frequently occurring substances among 75 reported deaths.supported
31 different SCs in 75 fatalities 2017-2020. NEH among most abused SCs (alongside N-ethylpentylone and 4-CMC). ftd.0000000000000808
Lefeuvre et al. (2024) reported three analytically confirmed monosubstance NEH intoxications:supported
3 documented NEH intoxication cases. Plasma NEH: 97.2→0.7 µg/L Day 1-7 (Case 1). bkae040
An additional case of severe acute toxicity from combined 3-HO-PCP and NEH has been analytically confirmed.supported
Analytically confirmed case of acute toxicity from combined 3-HO-PCP and NEH use. s13181-019-00734-x
The sympathomimetic toxidrome observed in clinical cases includes severe tachycardia (>160 bpm), hypertension, and hyperthermiapartially supported
Hyperthermia >41°C, tachycardia >160bpm, acute kidney failure. bkaa159
Neuronal and microglial viability loss at 100 µM in human nerve cell linessupported
Neuronal viability loss at 100 µM; microglial activation unique to NEH; late apoptosis/necrosis in microglia. s12640-020-00229-6
Claim in safety — inconclusiveinconclusiveworking →
Higher cytotoxicity than methamphetamine in PC12 cellssupported
All cathinones more cytotoxic than methamphetamine. acschemneuro.2c00772
Post-withdrawal depression-like behavior in mice, suggesting neuroadaptive changes specific to NEHsupported
Withdrawal: depression-like behaviour. s12640-020-00229-6
Clinical case data document paranoia, feelings of persecution, anxiety, and anhedonia during and following NEH intoxicationsupported
Clinical effects: anxiety, persecution, asthenia, anhedonia, abulia, psychomotor slowing, loss of consciousness. bkae040
Post-withdrawal depression-like behavior is supported by both human clinical observations (asthenia, abulia, psychomotor slowing) and animal models.supported
Withdrawal: depression-like behaviour. s12640-020-00229-6
Conditioned place preference at 4–16 mg/kg in mice and full substitution for cocaine and methamphetamine discriminative cues indicate that the compound engages addiction-relevant reward circuits with efficacy comparable to established drugs of abuse.partially supported
Place preference at 4 and 16 mg/kg (abuse potential). s12640-020-00229-6
Conditioned place preference at 4–16 mg/kg in mice and full substitution for cocaine and methamphetamine discriminative cues indicate that the compound engages addiction-relevant reward circuits with efficacy comparable to established drugs of abuse.partially supported
Fully substitutes for discriminative stimulus effects of methamphetamine and cocaine. adb.12987
Agitation and aggression have been documented in severe intoxication, consistent with the sympathomimetic-psychostimulant toxidrome class.supported
Admitted for disorientation, aggression, loss of consciousness. bkaa159
These values are unverified against any controlled pharmacological study and must be distinguished from the pharmacokinetic elimination half-life (19–28 hours).supported
Half-life: 19-28h. bkae040
Conditioned place preference in mice at 4–16 mg/kgsupported
Place preference at 4 and 16 mg/kg (abuse potential). s12640-020-00229-6
Claim in safety — inconclusiveinconclusiveworking →
ΔFosB upregulation in striatum following repeated dosing of the structural analogue NEP — a biomarker of neuroplastic changes associated with addictionsupported
Increased ΔFosB in striatum suggesting high dependence risk. j.pnpbp.2022.110562
Post-withdrawal depression-like behavior in mice, specific to NEH (not observed with buphedrone)supported
Withdrawal: depression-like behaviour. s12640-020-00229-6
This is consistent with NEH's full substitution for cocaine and methamphetamine discriminative stimuli.supported
Fully substitutes for discriminative stimulus effects of methamphetamine and cocaine. adb.12987
The animal data showing post-withdrawal depressive behavior suggest a withdrawal syndrome is plausible, but its severity, timeline, and specific symptom profile in humans are unknown.supported
Withdrawal: depression-like behaviour. s12640-020-00229-6
The interaction data below are based on mechanistic pharmacological reasoning and class-level evidence from synthetic cathinone reviews.supported
Review of pharmacokinetic and pharmacodynamic interactions between synthetic cathinones and prescription drugs. ftd.0000000000000682
NEH's inhibition of norepinephrine reuptake, combined with MAOI-mediated blockade of monoamine catabolism, produces dangerously elevated synaptic catecholamine concentrations.supported
Serotonin syndrome risk with MAOIs and serotonergic medications; cardiovascular interactions with antihypertensives. ftd.0000000000000682
SSRIs, SNRIs, triptans, and tramadol combined with NEH create theoretical risk of serotonin syndrome, particularly if NEH engages SERT at higher dosessupported
Serotonin syndrome risk with MAOIs and serotonergic medications. ftd.0000000000000682
NEH's sympathomimetic effects may overwhelm antihypertensive medications, creating complex and unpredictable pharmacodynamic interactions.supported
cardiovascular interactions with antihypertensives. ftd.0000000000000682
Claim in safety — inconclusiveinconclusiveworking →
NEH produces tachycardia exceeding 160 bpm and hypertension in severe intoxication casespartially supported
Hyperthermia >41°C, tachycardia >160bpm, acute kidney failure. bkaa159
Acute kidney failure has been documented in a fatal NEH casesupported
acute kidney failure. Death after a few hours. bkaa159
Claim in safety — inconclusiveinconclusiveworking →
Synthetic cathinones as a class reduce seizure thresholdsupported
Brain-related adverse effects: encephalopathy, coma, convulsions, sympathomimetic/hallucinogenic toxidromes. ijms24076230
NEH-induced paranoia, persecution ideation, and agitation make the compound particularly hazardous for individuals with pre-existing psychotic disorders, severe anxiety disorders, or bipolar disordersupported
Clinical effects: anxiety, persecution, asthenia, anhedonia. bkae040
The post-withdrawal depressive syndrome represents additional risk for individuals with major depressive disorder.supported
Withdrawal: depression-like behaviour. s12640-020-00229-6
The report of SIADH following NEH intoxication indicates particular risk for individuals with pre-existing hyponatremia or conditions predisposing to electrolyte imbalance.supported
SIADH. bkae040

summary14 · 11 ok

N-Ethylhexedrone (NEH, also marketed as hexen or hex-en; systematic name 2-(ethylamino)-1-phenylhexan-1-one) is a synthetic cathinone stimulant acting as a norepinephrine-dopamine reuptake inhibitor (NDRI) with a DAT IC₅₀ of 44.5 nM, placing it in the high-potency range among second-generation cathinonessupported
DAT IC50 for NEH = 44.5 nM. All more potent than cocaine (111 nM). High DAT/SERT selectivity. NET inhibition also demonstrated. dta.3547
Insufflated, the compound produces stimulant effects lasting 2–5 hours, though its plasma elimination half-life of 19–28 hours prolongs systemic exposure well beyond subjective offset.partially supported
Half-life: 19-28h. Plasma NEH: 97.2→0.7 µg/L Day 1-7 (Case 1). bkae040
Claim in summary — inconclusiveinconclusiveworking →
The first prospective human observational study was not published until 2025, leaving the evidence base dependent on in vitro pharmacology, animal behavioral models, forensic case reports, and clinical toxicology series.supported
First naturalistic prospective observational study of NEH in humans. ph18050721
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Its DAT IC₅₀ of 44.5 nM exceeds the potency of both cocaine (~111 nM) and amphetamine (~257 nM) in the same assay system, with a DAT/SERT selectivity ratio greater than that of cocaine.partially supported
DAT IC50 for NEH = 44.5 nM. All more potent than cocaine (111 nM). High DAT/SERT selectivity. dta.3547
Compulsive redosing is a prominent behavioral feature, consistent with high DAT selectivity and confirmed rewarding properties in conditioned place preference paradigms.supported
Place preference at 4 and 16 mg/kg (abuse potential). s12640-020-00229-6
Cardiovascular toxicity is the primary acute safety concern — fatal cases document hyperthermia exceeding 41°C, tachycardia above 160 bpm, and acute renal failuresupported
Hyperthermia >41°C, tachycardia >160bpm, acute kidney failure. Death after a few hours. bkaa159
NEH demonstrates greater in vitro neurotoxicity than methamphetamine in PC12 cells, with unique microglial activation not observed with structurally simpler cathinonespartially supported
Neuronal viability loss at 100 µM; microglial activation unique to NEH; late apoptosis/necrosis in microglia. s12640-020-00229-6
NEH demonstrates greater in vitro neurotoxicity than methamphetamine in PC12 cells, with unique microglial activation not observed with structurally simpler cathinonespartially supported
Increasing chain length increases cytotoxicity in PC12 cells. All cathinones more cytotoxic than methamphetamine. acschemneuro.2c00772
The prolonged elimination half-life creates accumulation risk with repeated dosing — NEH remained detectable in plasma up to ten days after intoxicationpartially supported
Plasma NEH: 97.2→0.7 µg/L Day 1-7 (Case 1). Half-life: 19-28h. bkae040
Dependence liability is moderate, supported by full substitution for cocaine and methamphetamine discriminative cues in rats and post-withdrawal depressive behavior in mice.partially supported
Fully substitutes for discriminative stimulus effects of methamphetamine and cocaine. adb.12987
Dependence liability is moderate, supported by full substitution for cocaine and methamphetamine discriminative cues in rats and post-withdrawal depressive behavior in mice.partially supported
Withdrawal: depression-like behaviour. s12640-020-00229-6

pharmacology12 · 4 ok

Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Lefeuvre et al. (2024) estimated the plasma elimination half-life of NEH at 19 hours (Case 1) and 28 hours (Case 3) by non-compartmental trapezoidal analysis from serial plasma samples taken over seven days following acute intoxicationsupported
Half-life: 19-28h. Plasma NEH: 97.2→0.7 µg/L Day 1-7 (Case 1); 49→1.8 µg/L Day 1-7 (Case 3). bkae040
Claim in pharmacology — inconclusiveinconclusiveworking →
In humans, NEH undergoes Phase I metabolism via ketone reduction, N-dealkylation, and hydroxylation (both ring and aliphatic), followed by Phase II glucuronide conjugationsupported
Phase-I and glucuronide phase-II metabolites identified. Keto reduction, hydroxylation, dealkylation. NEH-glucuronide relevant. j.jpba.2024.115994
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
In mice, N-dealkylation is the primary metabolic pathway (most abundant metabolite at ~80 µg/mL in urine), with secondary pathways including ketone reduction, combined ketone reduction with N-dealkylation, and 4-aryl hydroxylation — the latter being the first report of aromatic hydroxylation for a non-ring-substituted cathinonesupported
N-dealkylation primary pathway (~80 µg/mL urine). Also ketone reduction, aryl hydroxylation. j.jchromb.2020.122340
Phase II metabolites include N-acetylated, glucuronide, and dicarboxylic acid conjugates.supported
Phase II: N-acetylated, glucuronides, dicarboxylic acid conjugates. j.jchromb.2020.122340

pharmacokinetic-detail9 · 5 ok

Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
58 ng/mL — polydrug fatality attributed primarily to U-47700 (1470 ng/mL), with adinazolam (18 ng/mL), 4-CIC (8.0 ng/mL), and 4-CMC (1.7 ng/mL) also presentsupported
NEH blood concentration 58 ng/mL alongside U-47700 (1470 ng/mL), adinazolam (18 ng/mL), 4-CIC (8.0 ng/mL), 4-CMC (1.7 ng/mL). s11419-020-00568-1
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Elimination half-life estimated by non-compartmental trapezoidal analysis: 19 hours (Case 1) and 28 hours (Case 3).supported
Half-life: 19-28h. bkae040
Phase I transformations identified in human biological samples include:supported
Phase-I and glucuronide phase-II metabolites identified. Keto reduction, hydroxylation, dealkylation. j.jpba.2024.115994
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Carrola et al. (2020) characterized NEH metabolism in mice via HPLC-MS/MS:supported
Mouse urine study (64 mg/kg IP). NEH at 58.3±14.4 µg/mL. j.jchromb.2020.122340
The observation of 4-aryl hydroxylation was notable as the first published report of this metabolic pathway for a non-ring-substituted cathinone.supported
Also ketone reduction, aryl hydroxylation. j.jchromb.2020.122340

neuroscience7 · 7 ok

The cytotoxicity data of Nadal-Gratacós et al. (2023) extend this picture: NEH and all tested N-ethyl cathinone homologues exceeded methamphetamine cytotoxicity in PC12 cells, with toxicity increasing monotonically as the alpha-carbon chain lengthens.supported
Increasing chain length increases cytotoxicity in PC12 cells. All cathinones more cytotoxic than methamphetamine. acschemneuro.2c00772
Post-withdrawal depression-like behavior observed in mice dosed with NEH — but not with buphedrone — suggests neuroadaptive changes specific to higher-potency cathinonessupported
Withdrawal: depression-like behaviour. s12640-020-00229-6
The compound's high DAT selectivity (DAT IC₅₀ = 44.5 nM with minimal SERT contribution) predicts preferential engagement of dopaminergic reward circuitry over serotonergic mood and perceptual systems.supported
DAT IC50 for NEH = 44.5 nM. High DAT/SERT selectivity. dta.3547
Full substitution for both cocaine and methamphetamine discriminative stimuli in rats confirms that NEH engages the same interoceptive states as established dopaminergic stimulants — a behavioral finding consistent with shared mesolimbic activation patternssupported
Fully substitutes for discriminative stimulus effects of methamphetamine and cocaine. adb.12987
De Mello-Sampayo et al. (2021) provided the most detailed neurotoxicological characterization of NEH:supported
In vivo: excitation/stereotypies at 4-64 mg/kg. NEH: retropulsion, circling. Place preference at 4 and 16 mg/kg. Withdrawal: depression-like behaviour. In vitro: neuronal viability loss at 100 µM; microglial activation unique to NEH. s12640-020-00229-6
At the systems level, a systematic review of synthetic cathinone neurotoxicity confirmed that the cathinone class produces brain-related adverse effects including encephalopathy, coma, convulsions, and combined sympathomimetic and hallucinogenic toxidromes.supported
Brain-related adverse effects: encephalopathy, coma, convulsions, sympathomimetic/hallucinogenic toxidromes. ijms24076230
Although ΔFosB induction has not been measured for NEH directly, repeated administration of the structural analogue N-ethyl-nor-pentedrone (NEP) upregulates ΔFosB in the striatum — a transcription factor recognized as a biomarker of the neuroplastic changes underlying addictionsupported
Increased ΔFosB in striatum suggesting high dependence risk. j.pnpbp.2022.110562

receptor-pharmacology6 · 3 ok

The most comprehensive quantitative data on NEH transporter inhibition come from Persson et al. (2024), who characterized seven cathinones using a proprietary fluorescent dye uptake inhibition assay in CHO-K1 cells expressing human monoamine transporters.supported
Characterization of neurotransmitter inhibition for seven cathinones by a proprietary fluorescent dye method. dta.3547
NEH inhibits the dopamine transporter with an IC₅₀ of 44.5 nMsupported
DAT IC50 for NEH = 44.5 nM. dta.3547
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
NEH ranks sixth among the seven cathinones tested — approximately 10-fold less potent at DAT than the most potent compound (MPHP, 4.53 nM) but 2.5-fold more potent than cocaine and 5.8-fold more potent than amphetamine.partially supported
Rank: MPHP > 4Cl-α-PVP > 3F-α-PVP > α-PiHP > N-ethylpentylone > N-ethylhexedrone > 4-methylpentedrone. All more potent than cocaine (111 nM). dta.3547
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →

comparative-pharmacology5 · 5 ok

The structure-activity relationship study by Nadal-Gratacós et al. (2023) provides the most direct comparative data, evaluating five N-ethyl cathinones differing only in alpha-carbon chain length:supported
Five N-ethyl cathinones (NEC, NEB, NEPD, NEH, NEHP) synthesized and compared. acschemneuro.2c00772
Cytotoxicity, however, increases monotonically with chain length: all five compounds exceeded methamphetamine cytotoxicity in PC12 cells.supported
Increasing chain length increases cytotoxicity in PC12 cells. All cathinones more cytotoxic than methamphetamine. acschemneuro.2c00772
In vivo, NEH and its homologues produced conditioned place preference (indicative of rewarding properties) and anxiety-like behavior at high doses in Swiss CD-1 mice.supported
NEH demonstrated rewarding properties. Anxiety-like behavior at high doses. acschemneuro.2c00772
The DAT IC₅₀ comparison supports this positioning: NEH (44.5 nM) is approximately 2.5-fold more potent than cocaine (111 nM) at DAT but less potent than the pyrrolidine-type cathinones (α-PVP, α-PHP, MPHP) that occupy the 4–13 nM range.supported
DAT IC50 for NEH = 44.5 nM. Rank: MPHP > 4Cl-α-PVP > 3F-α-PVP > α-PiHP > N-ethylpentylone > N-ethylhexedrone > 4-methylpentedrone. All more potent than cocaine (111 nM). dta.3547
NEH's classification as a pure transport blocker rather than a substrate-type releaser places it mechanistically closer to α-PVP and α-PHP than to mephedrone or methylonesupported
alpha-PHP is one-carbon extended homolog of alpha-PVP; both are DAT reuptake inhibitors (blockers). acschemneuro.3c00156

clinical-evidence4 · 3 ok

Lefeuvre et al. (2024) reported a case series of three non-fatal NEH intoxications (monosubstance, analytically confirmed)supported
3 documented NEH intoxication cases. Plasma NEH: 97.2→0.7 µg/L Day 1-7 (Case 1). bkae040
The fatal case reported by Domagalska et al. (2021) documented disorientation, aggression, loss of consciousness, hyperthermia exceeding 41°C, tachycardia above 160 bpm, and acute kidney failure preceding death.supported
21-year-old male. Admitted for disorientation, aggression, loss of consciousness. Hyperthermia >41°C, tachycardia >160bpm, acute kidney failure. Death after a few hours. bkaa159
The only prospective human data come from Núñez-Montero et al. (2025), who conducted the first naturalistic observational study of NEHsupported
First naturalistic prospective observational study of NEH in humans. ph18050721
Claim in clinical-evidence — inconclusiveinconclusiveworking →

history4 · 3 ok

A review of synthetic cathinone-related fatalities from 2017–2020 identified NEH as one of the three most frequently encountered substances, alongside N-ethylpentylone and 4-CMC.supported
NEH among most abused SCs (alongside N-ethylpentylone and 4-CMC). 31 different SCs in 75 fatalities 2017-2020. ftd.0000000000000808
The first prospective human observational study — eight participants self-administering 20–40 mg intranasally — was published by Núñez-Montero et al. in 2025.partially supported
First naturalistic prospective observational study of NEH in humans. 16 participants, intranasal self-administration. NEH 20-40mg. ph18050721
Claim in history — inconclusiveinconclusiveworking →
NEH was retrospectively identified in a Swedish clinical oral fluid surveillance dataset covering 2019, confirming continued use in clinical populations beyond the initial market surgesupported
Retrospective analysis of 14,367 clinical oral fluid samples. NEH identified among 34 NPS found. bcpt.13786

chemistry2 · 2 ok

Nadal-Gratacós et al. (2023) systematically characterized five N-ethyl cathinones differing only in alpha-carbon chain length: N-ethyl-cathinone (NEC), N-ethyl-buphedrone (NEB), N-ethyl-pentedrone (NEPD), N-ethylhexedrone (NEH), and N-ethyl-heptedrone (NEHP)supported
Five N-ethyl cathinones (NEC, NEB, NEPD, NEH, NEHP) synthesized and compared. acschemneuro.2c00772
Longer alpha-carbon chains also correlate with increased cytotoxicity in PC12 cells — all five compounds exceeded methamphetamine cytotoxicity in this assay.supported
Increasing chain length increases cytotoxicity in PC12 cells. All cathinones more cytotoxic than methamphetamine. acschemneuro.2c00772

effects-overview1 · 1 ok

The subjective profile most closely resembles a longer-acting cocaine: comparable discriminative stimulus properties in animal models, approximately equipotent DAT blockade, but with a peak stimulant duration roughly twice that of cocaine.supported
Maximal stimulant effects similar to cocaine and methamphetamine. Peak dose effects lasted 4h. Fully substitutes for discriminative stimulus effects of methamphetamine and cocaine. adb.12987

3Sources

24 consumed · sorted by year · feeds = sections resting on it

Sources
year	source	tier	status	feeds
2025	Acute Pharmacological Effects of Two Synthetic Cathinones in Humans: N-Ethylhexedrone and N-Ethyl-nor-pentedroneNúñez-Montero M, Pérez-Mañá C, Hladun O, et al. · Pharmaceuticals (Basel)doi:10.3390/ph18050721	moderate	consumed	3 sections
2024	Characterization of neurotransmitter inhibition for seven cathinones by a proprietary fluorescent dye method.Persson M, Vikingsson S, Kronstrand R, Green H · Drug Testing and Analysisdoi:10.1002/dta.3547	moderate	consumed	5 sections
2024	Metabolic profile of N-ethylhexedrone, N-ethylpentedrone, and 4-chloromethcathinone in urine samples by UHPLC-QTOF-HRMS.Massano M, Nuñez-Montero M, Papaseit E, Hladun O, Pérez-Mañá C, Ventura M, Marchei E, Alladio E, Gerace E, Pichini S, Farré M, Salomone A · Journal of pharmaceutical and biomedical analysisdoi:10.1016/j.jpba.2024.115994	moderate	consumed	2 sections
2024	N-EthylhexedroneWikipedia contributorsurl:3f8f8d2f08c404f5	weak	consumed	cited only
2024	N-Ethylhexedrone — PubChem CID 134822125National Center for Biotechnology Informationurl:65a60d1d25557bad	weak	consumed	cited only
2024	N-Ethylhexedrone: A very long and bad trip! A case seriesLefeuvre S, Richeval C, Lelong J, Venisse N, Humbert L, Brunet B · Journal of Analytical Toxicologydoi:10.1093/jat/bkae040	weak	consumed	5 sections
2023	Critical Review Report: N-Ethylhexedrone — WHO Expert Committee on Drug Dependence (47th ECDD)World Health Organizationurl:58baf0d56c650a8b	weak	consumed	cited only
2023	Structure-Activity Relationship of N-Ethyl-Hexedrone Analogues: Role of the alpha-Carbon Side-Chain LengthNadal-Gratacós N, Ríos-Rodríguez E, Pubill D, et al. · ACS chemical neurosciencedoi:10.1021/acschemneuro.2c00772	moderate	consumed	7 sections
2023	Structure-Activity Relationships for a Recently Controlled Synthetic Cathinone Dopamine Transporter Reuptake Inhibitor: α-Pyrrolidinohexiophenone (α-PHP)Davies RA, Nguyen VT, Eltit JM, Glennon RA · ACS Chemical Neurosciencedoi:10.1021/acschemneuro.3c00156	strong	consumed	2 sections
2023	Synthetic Cathinones and Neurotoxicity Risks: A Systematic ReviewDaziani G, Lo Faro AF, Montana V, Goteri G, Pesaresi M, Bambagiotti G, Montanari E, Giorgetti R, Montana A · International Journal of Molecular Sciencesdoi:10.3390/ijms24076230	strong	consumed	2 sections
2022	Repeated administration of N-ethyl-pentedrone induces increased aggression and impairs social exploration after withdrawal in miceEspinosa-Velasco M, Reguilón MD, Bellot M, et al. · Progress in neuro-psychopharmacology & biological psychiatrydoi:10.1016/j.pnpbp.2022.110562	moderate	consumed	2 sections
2022	Retrospective identification of new psychoactive substances in patient samples submitted for clinical drug analysisAxelsson MAB, Lövgren H, Kronstrand R, Green H, Bergström MA · Basic & Clinical Pharmacology & Toxicologydoi:10.1111/bcpt.13786	moderate	consumed	1 section
2022	Schedules of Controlled Substances: Placement of N-Ethylhexedrone, alpha-Pyrrolidinohexanophenone [et al.] in Schedule IDrug Enforcement Administration, US DOJ · Federal Registerurl:3c0a926a9003c891	weak	consumed	cited only
2022	Synthetic Cathinones: Recent Developments, Enantioselectivity Studies and Enantioseparation MethodsAlmeida AS, Silva B, Guedes de Pinho P, Remião F, Fernandes C · Moleculesdoi:10.3390/molecules27072057	moderate	consumed	cited only
2021	A Review of Synthetic Cathinone-Related Fatalities From 2017 to 2020La Maida N, Di Trana A, Giorgetti R, Tagliabracci A, Busardò FP, Huestis MA · Therapeutic Drug Monitoringdoi:10.1097/ftd.0000000000000808	moderate	consumed	cited only
2021	Behavioral effects of four novel synthetic cathinone analogs in rodentsGatch MB, Shetty RA, Sumien N, Forster MJ · Addiction Biologydoi:10.1111/adb.12987	moderate	consumed	6 sections
2021	Designer Cathinones N-Ethylhexedrone and Buphedrone Show Different In Vitro Neurotoxicity and Mice Behaviour Impairmentde Mello-Sampayo C, Vaz AR, Henriques SC, Fernandes A, Paradinha F, Florindo P, Faria P, Moreira R, Brites D, Lopes A · Neurotoxicity Researchdoi:10.1007/s12640-020-00229-6	moderate	consumed	3 sections
2021	Fatal intoxication with U-47700 in combination with other NPS (N-ethylhexedrone, adinazolam, 4-CIC, 4-CMC) confirmed by identification and quantification in autopsy specimens and evidences.Nowak K, Szpot P, Zawadzki M · Forensic Toxicologydoi:10.1007/s11419-020-00568-1	weak	consumed	2 sections
2021	Fatal N-Ethylhexedrone IntoxicationDomagalska E, Banaszkiewicz L, Woźniak MK, Kata M, Szpiech B, Kaliszan M · Journal of Analytical Toxicologydoi:10.1093/jat/bkaa159	weak	consumed	4 sections
2020	Designer drugs: mechanism of action and adverse effectsLuethi D, Liechti ME · Archives of Toxicologydoi:10.1007/s00204-020-02693-7	strong	consumed	cited only
2020	Metabolism of N-ethylhexedrone and buphedrone: An in vivo study in mice using HPLC-MS/MSCarrola J, Duarte N, Florindo P, Henriques S, da Silva G, Bijlsma L, Moreira R, Correia C, Perry MJ, Lopes Á, de Mello-Sampayo C, Bronze MDR · Journal of Chromatography Bdoi:10.1016/j.jchromb.2020.122340	moderate	consumed	2 sections
2020	Severe Toxicity to the New Psychoactive Substances 3-Hydroxyphencyclidine and N-Ethylhexedrone: an Analytically Confirmed Case ReportDunlop LC, Wood D, Archer J, Hudson S, Dargan P · Journal of Medical Toxicologydoi:10.1007/s13181-019-00734-x	weak	consumed	1 section
2020	Synthetic Cathinones and Their Potential Interactions with Prescription Drugs.Contrucci RR, Brunt TM, Inan F, Franssen EJF, Hondebrink L · Therapeutic Drug Monitoringdoi:10.1097/ftd.0000000000000682	moderate	consumed	cited only
2019	Fatal intoxication of a regular drug user following N-ethyl-hexedrone and ADB-FUBINACA consumptionKovács K, Kereszty É, Berkecz R, Tiszlavicz L, et al. · Journal of Forensic and Legal Medicinedoi:10.1016/j.jflm.2019.04.012	weak	consumed	1 section
—	Searched ClinicalTrials.gov for "N-Ethylhexedrone" — no resultsabsence		no results	—

4Docket

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0012026-05-12revisionRevision 1
Initial LLM generation (v5 pipeline, wiki, prose phase)
psx:substance/n-ethylhexedrone/version/1
0022026-06-04proposal43 value proposals approved together
one review action inferred from a shared reviewer and instant — the graph records one activity per proposal
43 items in this filing
- contraindication · renal
- contraindication · hepatic
- contraindication · neurological
- contraindication · psychiatric
- contraindication · psychiatric
- contraindication · psychiatric
- contraindication · psychiatric
- contraindication · pregnancy_breastfeeding
- contraindication · metabolic
- contraindication · other
- contraindication · other
- contraindication · other
- dose_tier · threshold
- dose_tier · light
- dose_tier · common
- dose_tier · strong
- dose_tier · heavy
- toxicity
- dependence · full
- withdrawal
- tolerance
- dosage · insufflated
- dosage · smoked
- duration · insufflated · onset
- duration · insufflated · peak
- duration · insufflated · offset
- duration · insufflated · total
- duration · insufflated · aftereffects
- duration · smoked · onset
- duration · smoked · peak
- duration · smoked · offset
- duration · smoked · total
- duration · smoked · aftereffects
- timeline · insufflated · onset
- timeline · insufflated · come_up
- timeline · insufflated · peak
- timeline · insufflated · resolution
- timeline · insufflated · afterglow
- timeline · smoked · onset
- timeline · smoked · peak
- timeline · smoked · resolution
- timeline · smoked · afterglow
psx:substance/n-ethylhexedrone/proposal/contraindication/7fb59939-2556-43b2-b846-8b9b0895f82a
0032026-06-04publicationPublication — backfill
psx:substance/n-ethylhexedrone/pub/09ec6b0f-5a5c-4dba-877c-85158dd991b0

5Issued documents

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Issued documents
document	content hash	issued	from version	superseded
info_card	5c98b45dd2ce0929d9f54174…	2026-10-19 20:33	Revision 1	current
emergency	58d3299a8754d788e3d74c0e…	2026-09-04 04:31	Revision 1	current
info_card	b47cd38da77d497acff0ca80…	2026-09-04 04:31	Revision 1	superseded2026-10-19
notice	710e21e348e3e695dc8afb7c…	2026-09-04 04:31	Revision 1	current

N-Ethylhexedrone

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