Skip to main content
Psychedex

Ethylone

3,4-methylenedioxy-N-ethylcathinone

Sources
23
6 strong · 14 moderate · 3 weak

Studies and references cited across this article, graded by evidence strength.

Claims checked
71
51verified20inconclusive

Inconclusive means the cited source neither confirms nor refutes the claim — a lower-confidence badge, not an error.

Generated
Apr 26, 2026 · pipeline-v5
Values approved
120/122 (98%)

Data points an editor reviewed and accepted for publication.

01

Value Provenance

Dosing

oraltrace

FieldPublishedAI ProposedConfidence
Threshold75 mg75 mglow
Low75–125 mg75–125 mglow
Common125–200 mg125–200 mglow
Strong200–325 mg200–325 mglow
Heavy325+ mg325+ mglow
Editorial

Dose ranges carried forward from existing Psychedex database values (originally community-curated). No published clinical or controlled study has established dose ranges for ethylone in humans. Values are plausible given methylone's common dose range (~100-200 mg) and ethylone's slightly lower expected potency per structural analog inference, but cannot be verified against primary sources. Flagged for editorial review.

Reasoning

Dose ranges carried forward from existing Psychedex database values (originally community-curated). No published clinical or controlled study has established dose ranges for ethylone in humans. Values are plausible given methylone's common dose range (~100-200 mg) and ethylone's slightly lower expected potency per structural analog inference, but cannot be verified against primary sources. Flagged for editorial review.

Evidence basis: community_consensus_large

Duration

oral

FieldPublishedAI ProposedConfidence
Onsettrace15–30 minutes15–30 minuteslow
Editorial

Inferred from methylone Tmax (~15-45 min subcutaneous in rats, estimated 30-90 min oral in humans; Elmore et al. 2017). Onset of first perceptible effects expected before Tmax. No ethylone-specific data.

Reasoning

Inferred from methylone Tmax (~15-45 min subcutaneous in rats, estimated 30-90 min oral in humans; Elmore et al. 2017). Onset of first perceptible effects expected before Tmax. No ethylone-specific data.

Evidence basis: structural_analogy

Come uptrace15–30 minutes15–30 minuteslow
Editorial

Inferred from methylone pharmacokinetics and the overall 2-4 hour duration window reported by ADF. Come-up period estimated as the interval between first alerts and approaching peak.

Reasoning

Inferred from methylone pharmacokinetics and the overall 2-4 hour duration window reported by ADF. Come-up period estimated as the interval between first alerts and approaching peak.

Evidence basis: structural_analogy

Peaktrace45–90 minutes45–90 minuteslow
Editorial

Estimated from the total duration of up to 4 hours (ADF) and methylone's rapid PK profile (t1/2 60-90 min). Peak duration represents the period of maximum subjective intensity.

Reasoning

Estimated from the total duration of up to 4 hours (ADF) and methylone's rapid PK profile (t1/2 60-90 min). Peak duration represents the period of maximum subjective intensity.

Evidence basis: structural_analogy

Offsettrace30–60 minutes30–60 minuteslow
Editorial

Declining intensity phase estimated from the 2-4 hour total duration (ADF) minus onset, come-up, and peak phases. Consistent with rapid metabolism of beta-keto cathinones.

Reasoning

Declining intensity phase estimated from the 2-4 hour total duration (ADF) minus onset, come-up, and peak phases. Consistent with rapid metabolism of beta-keto cathinones.

Evidence basis: structural_analogy

Totaltrace2–4 hours2–4 hoursmedium
Editorial

ADF reports duration 'up to 4 hours.' Total subjective experience duration estimated at 2-4 hours, anchored by this consumer-facing source. This represents the full subjective experience from onset through offset.

Reasoning

ADF reports duration 'up to 4 hours.' Total subjective experience duration estimated at 2-4 hours, anchored by this consumer-facing source. This represents the full subjective experience from onset through offset.

Evidence basis: community_consensus_large

After effectstrace2–8 hours2–8 hourslow
Editorial

After-effects (anxiety, fatigue, insomnia, depression, irritability) reported by ADF as persisting for days following use. The immediate aftereffects period (residual stimulation, mood shift) estimated at 2-8 hours, with longer-term mood effects extending beyond this window.

Reasoning

After-effects (anxiety, fatigue, insomnia, depression, irritability) reported by ADF as persisting for days following use. The immediate aftereffects period (residual stimulation, mood shift) estimated at 2-8 hours, with longer-term mood effects extending beyond this window.

Evidence basis: community_consensus_large

Safety

Toxicity Profiletrace

FieldPublishedAI ProposedConfidence
Acutemoderatemoderatelow
Chronicmoderatemoderatelow
Organs Affectedcardiovascular, neurologicalcardiovascular, neurologicallow
Editorial

Classified as moderate (downgraded from high): all toxicity evidence derives from the synthetic cathinone class (Luethi & Liechti 2020, Debruyne et al. 2014, Prosser & Nelson 2011) and consumer-facing sources (ADF), not ethylone-specific studies. No LD50, no human case reports of ethylone-specific fatality. The SERT-preferring profile may confer somewhat lower acute cardiovascular risk than DAT-selective cathinones, but serotonergic toxicity risk persists.

Reasoning

Classified as moderate (downgraded from high): all toxicity evidence derives from the synthetic cathinone class (Luethi & Liechti 2020, Debruyne et al. 2014, Prosser & Nelson 2011) and consumer-facing sources (ADF), not ethylone-specific studies. No LD50, no human case reports of ethylone-specific fatality. The SERT-preferring profile may confer somewhat lower acute cardiovascular risk than DAT-selective cathinones, but serotonergic toxicity risk persists.

Evidence basis: structural_analogy

Dependence Profiletrace

FieldPublishedAI ProposedConfidence
Physicallowlowlow
Psychologicalmoderatemoderatelow
Compulsive Redosingmoderatemoderatelow
Dose Escalationmoderatemoderatelow
Editorial

No ethylone-specific dependence studies exist. Physical dependence downgraded from moderate (brief's value) to low: no direct evidence supports moderate physical dependence for ethylone or its close analogs. Psychological dependence rated moderate based on robust self-administration of structural analogs (Dolan et al. 2018) and Gannon et al.'s DAT/SERT framework predicting retained but attenuated reinforcing effectiveness.

Reasoning

No ethylone-specific dependence studies exist. Physical dependence downgraded from moderate (brief's value) to low: no direct evidence supports moderate physical dependence for ethylone or its close analogs. Psychological dependence rated moderate based on robust self-administration of structural analogs (Dolan et al. 2018) and Gannon et al.'s DAT/SERT framework predicting retained but attenuated reinforcing effectiveness.

Evidence basis: structural_analogy

Withdrawal Profiletrace

FieldPublishedAI ProposedConfidence
Severitymildmildlow
Symptomsfatigue, depression, anxiety, irritability, insomnia, anhedoniafatigue, depression, anxiety, irritability, insomnia, anhedonialow
FatalNoNolow
Medical SupervisionNot requiredNot requiredlow
Editorial

No ethylone-specific withdrawal data exist. Symptoms inferred from stimulant/entactogen class (monoamine depletion rebound) and ADF after-effects report (anxiety, fatigue, insomnia, depression, irritability). Severity rated mild — stimulant withdrawal is not life-threatening.

Reasoning

No ethylone-specific withdrawal data exist. Symptoms inferred from stimulant/entactogen class (monoamine depletion rebound) and ADF after-effects report (anxiety, fatigue, insomnia, depression, irritability). Severity rated mild — stimulant withdrawal is not life-threatening.

Evidence basis: structural_analogy

Tolerance Profiletrace

FieldPublishedAI ProposedConfidence
Buildupmoderatemoderatelow
Half-life5 days5 dayslow
Full Reset10 days10 dayslow
Cross-tolerancesmethylone, mephedrone, MDMA, amphetamine, cocainemethylone, mephedrone, MDMA, amphetamine, cocainelow
Editorial

No ethylone-specific tolerance data exist. Values carried forward from existing database (likely extrapolated from MDMA class). Cross-tolerance list based on shared monoamine transporter mechanisms. Tolerance mechanism described from general pharmacological principles of transporter desensitization.

Reasoning

No ethylone-specific tolerance data exist. Values carried forward from existing database (likely extrapolated from MDMA class). Cross-tolerance list based on shared monoamine transporter mechanisms. Tolerance mechanism described from general pharmacological principles of transporter desensitization.

Evidence basis: structural_analogy

Effects & Profile

Contraindications

FieldPublishedAI ProposedConfidence
cardiovascular cardiovascular diseasetraceabsoluteabsolutemedium
Editorial

Class-level cardiovascular toxicity well-documented for synthetic cathinones (Luethi & Liechti 2020). Irregular heartbeat reported specifically for ethylone (ADF).

Reasoning

Class-level cardiovascular toxicity well-documented for synthetic cathinones (Luethi & Liechti 2020). Irregular heartbeat reported specifically for ethylone (ADF).

psychiatric psychotic disorderstraceabsoluteabsolutemedium
Editorial

Psychotomimetic effects documented across the synthetic cathinone class (Weinstein et al. 2017).

Reasoning

Psychotomimetic effects documented across the synthetic cathinone class (Weinstein et al. 2017).

psychiatric bipolar disordertracerelativerelativelow
Editorial

Hypomania documented for the cathinone class (Weinstein et al. 2017). Relative contraindication based on class pharmacology.

Reasoning

Hypomania documented for the cathinone class (Weinstein et al. 2017). Relative contraindication based on class pharmacology.

neurological epilepsytraceabsoluteabsolutemedium
Editorial

Seizures documented for the cathinone class (Weinstein et al. 2017, Prosser & Nelson 2011).

Reasoning

Seizures documented for the cathinone class (Weinstein et al. 2017, Prosser & Nelson 2011).

other MAOI usetraceabsoluteabsolutehigh
Editorial

Fundamental pharmacological contraindication for all serotonin-releasing agents. Well-established class mechanism.

Reasoning

Fundamental pharmacological contraindication for all serotonin-releasing agents. Well-established class mechanism.

other concurrent serotonergic medicationtraceabsoluteabsolutehigh
Editorial

Tramadol SERT inhibition confirmed (Baldo 2018, Roulet et al. 2021). Ethylone SERT substrate activity confirmed (Eshleman et al. 2017).

Reasoning

Tramadol SERT inhibition confirmed (Baldo 2018, Roulet et al. 2021). Ethylone SERT substrate activity confirmed (Eshleman et al. 2017).

pregnancy breastfeeding pregnancy and breastfeedingtraceabsoluteabsolutemedium
Editorial

No ethylone-specific reproductive data. Absolute contraindication applied by precautionary principle consistent with all sympathomimetic stimulants.

Reasoning

No ethylone-specific reproductive data. Absolute contraindication applied by precautionary principle consistent with all sympathomimetic stimulants.

Timeline Phases

oral

FieldPublishedAI ProposedConfidence
Onsettrace900–1800 sec(i=0.05)900–1800 sec(i=0.05)low
Editorial

No controlled human duration data exist for ethylone. The ADF reports total duration 'up to 4 hours.' Phase timing inferred from methylone PK (Tmax 15-45 min SC in rats, estimated 30-90 min oral; t1/2 60-90 min) and the 4-hour total duration ceiling. All phase durations are estimates requiring editorial verification.

Reasoning

No controlled human duration data exist for ethylone. The ADF reports total duration 'up to 4 hours.' Phase timing inferred from methylone PK (Tmax 15-45 min SC in rats, estimated 30-90 min oral; t1/2 60-90 min) and the 4-hour total duration ceiling. All phase durations are estimates requiring editorial verification.

Come uptrace900–1800 sec(i=0.30)900–1800 sec(i=0.30)low
Editorial

No controlled human duration data exist for ethylone. The ADF reports total duration 'up to 4 hours.' Phase timing inferred from methylone PK (Tmax 15-45 min SC in rats, estimated 30-90 min oral; t1/2 60-90 min) and the 4-hour total duration ceiling. All phase durations are estimates requiring editorial verification.

Reasoning

No controlled human duration data exist for ethylone. The ADF reports total duration 'up to 4 hours.' Phase timing inferred from methylone PK (Tmax 15-45 min SC in rats, estimated 30-90 min oral; t1/2 60-90 min) and the 4-hour total duration ceiling. All phase durations are estimates requiring editorial verification.

Peaktrace2700–5400 sec(i=1.00)2700–5400 sec(i=1.00)low
Editorial

No controlled human duration data exist for ethylone. The ADF reports total duration 'up to 4 hours.' Phase timing inferred from methylone PK (Tmax 15-45 min SC in rats, estimated 30-90 min oral; t1/2 60-90 min) and the 4-hour total duration ceiling. All phase durations are estimates requiring editorial verification.

Reasoning

No controlled human duration data exist for ethylone. The ADF reports total duration 'up to 4 hours.' Phase timing inferred from methylone PK (Tmax 15-45 min SC in rats, estimated 30-90 min oral; t1/2 60-90 min) and the 4-hour total duration ceiling. All phase durations are estimates requiring editorial verification.

Plateautrace1800–3600 sec(i=0.50)1800–3600 sec(i=0.50)low
Editorial

No controlled human duration data exist for ethylone. The ADF reports total duration 'up to 4 hours.' Phase timing inferred from methylone PK (Tmax 15-45 min SC in rats, estimated 30-90 min oral; t1/2 60-90 min) and the 4-hour total duration ceiling. All phase durations are estimates requiring editorial verification.

Reasoning

No controlled human duration data exist for ethylone. The ADF reports total duration 'up to 4 hours.' Phase timing inferred from methylone PK (Tmax 15-45 min SC in rats, estimated 30-90 min oral; t1/2 60-90 min) and the 4-hour total duration ceiling. All phase durations are estimates requiring editorial verification.

Resolutiontrace1800–3600 sec(i=0.20)1800–3600 sec(i=0.20)low
Editorial

No controlled human duration data exist for ethylone. The ADF reports total duration 'up to 4 hours.' Phase timing inferred from methylone PK (Tmax 15-45 min SC in rats, estimated 30-90 min oral; t1/2 60-90 min) and the 4-hour total duration ceiling. All phase durations are estimates requiring editorial verification.

Reasoning

No controlled human duration data exist for ethylone. The ADF reports total duration 'up to 4 hours.' Phase timing inferred from methylone PK (Tmax 15-45 min SC in rats, estimated 30-90 min oral; t1/2 60-90 min) and the 4-hour total duration ceiling. All phase durations are estimates requiring editorial verification.

Afterglowtrace7200–28800 sec(i=0.05)7200–28800 sec(i=0.05)low
Editorial

No controlled human duration data exist for ethylone. The ADF reports total duration 'up to 4 hours.' Phase timing inferred from methylone PK (Tmax 15-45 min SC in rats, estimated 30-90 min oral; t1/2 60-90 min) and the 4-hour total duration ceiling. All phase durations are estimates requiring editorial verification.

Reasoning

No controlled human duration data exist for ethylone. The ADF reports total duration 'up to 4 hours.' Phase timing inferred from methylone PK (Tmax 15-45 min SC in rats, estimated 30-90 min oral; t1/2 60-90 min) and the 4-hour total duration ceiling. All phase durations are estimates requiring editorial verification.

Dose Tier Summaries

thresholdtrace
low

At threshold doses (~75 mg oral), effects are subtle and easily attributed to placebo or anticipation. Mild mood elevation and a slight increase in energy and alertness may be noticeable, along with faint enhancement of sensory input — colors appear marginally brighter, music slightly more engaging. Social warmth may begin to emerge but remains sub-clinical. Physically, mild stimulation is present — a slight increase in heart rate and minor appetite suppression. Pupil dilation may or may not be observable. Bruxism is typically absent at this level. Functional impairment is minimal, though subtle changes in motivation and thought acceleration may be perceptible to the user.

Editorial

No controlled human dosing studies exist for ethylone. Threshold value (75 mg) derives from unverified community reports in the existing database. Effect descriptions inferred from pharmacological profile (DAT/NET inhibition + SERT release) and structural analogy with methylone.

Reasoning

No controlled human dosing studies exist for ethylone. Threshold value (75 mg) derives from unverified community reports in the existing database. Effect descriptions inferred from pharmacological profile (DAT/NET inhibition + SERT release) and structural analogy with methylone.

Evidence basis: community_consensus_large

lighttrace
low

At light doses (75–125 mg oral), the dual stimulant-entactogenic character begins to emerge. Thought acceleration becomes noticeable, with increased mental energy and mild analysis enhancement. Sociability increases — conversation flows more freely, and emotional openness toward others becomes apparent. Music enhancement is present but modest. Touch may feel subtly more pleasant. Physically, stimulation is clearly perceptible: elevated heart rate, mild jaw tension (bruxism), reduced appetite, and increased wakefulness. Temperature dysregulation may begin, with users feeling warmer than ambient conditions warrant. Sleep is difficult for 3–4 hours following ingestion. Functional capacity remains largely intact, though driving or complex tasks should be avoided.

Editorial

Dose range (75–125 mg) from existing database, unverified by published studies. Effect profile inferred from ethylone's pharmacological mechanism (SERT-preferring entactogen with DAT/NET inhibition) and comparison to methylone and MDMA at sub-peak doses.

Reasoning

Dose range (75–125 mg) from existing database, unverified by published studies. Effect profile inferred from ethylone's pharmacological mechanism (SERT-preferring entactogen with DAT/NET inhibition) and comparison to methylone and MDMA at sub-peak doses.

Evidence basis: community_consensus_large

commontrace
low

At common doses (125–200 mg oral), the full entactogenic-stimulant experience manifests. Euphoria is prominent, accompanied by enhanced sociability, emotional openness, and empathogenic warmth toward others. Music enhancement becomes pronounced, and touch enhancement is clearly present. Sensory perception is heightened across modalities — visual brightening, mild visual haze, and intensified auditory experience. Thought acceleration is marked, with increased motivation and engagement. Physically, stimulation is strong: elevated heart rate, bruxism (jaw clenching), appetite suppression, wakefulness, and sexual arousal enhancement. Temperature dysregulation becomes a genuine concern — users feel warm and may sweat. The experience commits the user for approximately 2–4 hours of active effects, with an additional period of residual stimulation and mood shift. Sleep is impossible during active effects.

Editorial

Dose range (125–200 mg) from existing database, unverified. Effect profile based on ethylone's characterized pharmacology (non-selective monoamine reuptake inhibitor + selective SERT releaser) producing combined stimulant and entactogenic effects at full expression.

Reasoning

Dose range (125–200 mg) from existing database, unverified. Effect profile based on ethylone's characterized pharmacology (non-selective monoamine reuptake inhibitor + selective SERT releaser) producing combined stimulant and entactogenic effects at full expression.

Evidence basis: community_consensus_large

strongtrace
low

At strong doses (200–325 mg oral), stimulant and serotonergic effects intensify substantially. Euphoria is powerful, and entactogenic warmth may become overwhelming. Thought acceleration can become difficult to direct, and analysis enhancement may give way to scattered or racing cognition. Sensory intensification is pronounced — visual haze increases, music enhancement is vivid, and tactile sensitivity is markedly elevated. Physically, cardiovascular stress is significant: tachycardia, hypertension, and pronounced bruxism. Temperature dysregulation escalates, raising hyperthermia risk particularly in warm environments or during physical activity. Abnormal heartbeat sensations may be noticed. Appetite is fully suppressed. The risk of adverse effects rises substantially at this range. Anxiety, agitation, and paranoia become possible. The comedown period (fatigue, low mood, irritability) is more pronounced and may persist for 1–2 days.

Editorial

Dose range (200–325 mg) from existing database, unverified. At these doses, the balance between DAT/NET-mediated stimulation and SERT-mediated serotonergic effects shifts toward overstimulation and serotonergic adverse effects, consistent with cathinone class toxicology.

Reasoning

Dose range (200–325 mg) from existing database, unverified. At these doses, the balance between DAT/NET-mediated stimulation and SERT-mediated serotonergic effects shifts toward overstimulation and serotonergic adverse effects, consistent with cathinone class toxicology.

Evidence basis: community_consensus_large

heavytrace
low

At heavy doses (325+ mg oral), the risk profile dominates the experience. While intense euphoria and entactogenic effects may be present, they are accompanied by significant physiological stress and elevated psychiatric risk. Thought deceleration or cognitive confusion may paradoxically replace the thought acceleration seen at lower doses. Motivation suppression and fatigue may emerge as serotonergic depletion begins. Physically, tachycardia, hypertension, severe bruxism, hyperthermia, and dehydration become serious concerns. The risk of serotonin syndrome increases, particularly with any concurrent serotonergic substance. Seizures are a documented risk for the cathinone class at high doses. Abnormal heartbeat is more likely. The comedown is severe — anxiety, depression, insomnia, and irritability may persist for days. No published data establish the toxic dose for ethylone; these doses approach unknown territory with unpredictable outcomes.

Editorial

Heavy threshold (325+ mg) from existing database, unverified. At supracommon doses, cathinone class toxicology predicts escalating cardiovascular and serotonergic adverse effects. No LD50 or human toxic dose data exist for ethylone specifically.

Reasoning

Heavy threshold (325+ mg) from existing database, unverified. At supracommon doses, cathinone class toxicology predicts escalating cardiovascular and serotonergic adverse effects. No LD50 or human toxic dose data exist for ethylone specifically.

Evidence basis: community_consensus_large

02

History

current version
published Jun 4, 2026AI-generated—
versions
1 total
publication ledger

backfill Jun 4, 2026

Historical versions do not record which reviewer approved them; editorial accountability is recorded per value in the database and in the publication ledger going forward.

full version history suggest a correctioncontact@psychedex.org
03

Sources

6 strong · 14 moderate · 3 weak
  1. [1]
    moderate
    Pharmacological characterization of designer cathinones in vitro
    Simmler LD, Buser TA, Donzelli M, et al. · 2012 · British Journal of Pharmacology
    doi.org/10.1111/j.1476-5381.2012.02145.x9 claims checked5 verified4 inconclusive
  2. [2]
    moderate
    Structure-Activity Relationships of Substituted Cathinones, with Transporter Binding, Uptake, and Release
    Eshleman AJ, Wolfrum KM, Reed JF, Kim SO, Swanson T, Johnson RA, Janowsky A · 2017 · Journal of Pharmacology and Experimental Therapeutics
    doi.org/10.1124/jpet.116.236349pubmed 277992947 claims checked7 verified
  3. [3]
    moderate
    Metabolism of designer drugs of abuse: an updated review
    Meyer MR, Maurer HH · 2010 · Current Drug Metabolism
    pubmed 205407003 claims checked1 verified2 inconclusive
  4. [4]
    moderate
    Testing for designer stimulants: metabolic profiles of 16 synthetic cathinones excreted free in human urine.
    Uralets V, Rana S, Morgan S, Ross W · 2014 · Journal of Analytical Toxicology
    doi.org/10.1093/jat/bku021pubmed 246684895 claims checked3 verified2 inconclusive
  5. [5]
    weak
    Ethylone Drug Facts
    Alcohol and Drug Foundation (Australia) · 2023
    linkno claims checked
  6. [6]
    moderate
    Emerging drugs of abuse: current perspectives on substituted cathinones
    Debruyne D, Loilier M, Cesbron A, Le Boisselier R, Bourgine J · 2014 · Substance Abuse and Rehabilitation
    doi.org/10.2147/sar.s37257pubmed 249667134 claims checked2 verified2 inconclusive
  7. [7]
    strong
    Designer drugs: mechanism of action and adverse effects
    Luethi D, Liechti ME · 2020 · Archives of Toxicology
    doi.org/10.1007/s00204-020-02693-7pubmed 322493475 claims checked3 verified2 inconclusive
  8. [8]
    moderate
    The abuse-related effects of pyrrolidine-containing cathinones are related to their potency and selectivity to inhibit the dopamine transporter.
    Gannon BM, Baumann MH, Walther D, Jimenez-Morigosa C, Sulima A, Rice KC, Collins GT · 2018 · Neuropsychopharmacology
    doi.org/10.1038/s41386-018-0209-3pubmed 303057395 claims checked5 verified
  9. [9]
    moderate
    The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue
    Baumann MH, Ayestas MA, Partilla JS, et al. · 2012 · Neuropsychopharmacology
    doi.org/10.1038/npp.2011.304pubmed 221699436 claims checked4 verified2 inconclusive
  10. [10]
    weak
    UNODC Legal Substance Search: Ethylone
    UNODC · 2017
    linkno claims checked
  11. [11]
    weak
    Listing of Ethylone in Schedule I of Controlled Substances and Assignment of an Administration Controlled Substances Code Number
    Drug Enforcement Administration · 2020
    linkno claims checked
  12. [12]
    strong
    LC-MS/MS and volumetric absorptive microsampling for quantitative bioanalysis of cathinone analogues in dried urine, plasma and oral fluid samples
    Mercolini L, Protti M, Catapano MC, Rudge J, Sberna AE · 2016 · Journal of Pharmaceutical and Biomedical Analysis
    doi.org/10.1016/j.jpba.2016.02.015pubmed 26905673no claims checked
  13. [13]
    moderate
    Stability of synthetic cathinones in clinical and forensic toxicological analysis—Where are we now?
    Aldubayyan AA, Castrignan E, Elliott S, Abbate V · 2021 · Drug Testing and Analysis
    doi.org/10.1002/dta.2990pubmed 332834662 claims checked2 verified
  14. [14]
    strong
    Pharmacokinetic Profiles and Pharmacodynamic Effects for Methylone and Its Metabolites in Rats
    Elmore JS, Dillon-Carter O, Partilla JS, Ellefsen KN, Concheiro M, Suzuki M, Rice KC, Huestis MA, Baumann MH · 2017 · Neuropsychopharmacology
    doi.org/10.1038/npp.2016.213pubmed 276584844 claims checked3 verified1 inconclusive
  15. [15]
    strong
    In vitro metabolic profiling of methylenedioxy-substituted synthetic cathinones for enhanced detection in urine sample analysis
    Yeh YL, Hsieh CL, Huang YJ, Chang YH, Wang SM · 2025 · Journal of Food and Drug Analysis
    doi.org/10.38212/2224-6614.3543pubmed 405923384 claims checked2 verified2 inconclusive
  16. [16]
    moderate
    Comparative neuropharmacology of three psychostimulant cathinone derivatives: butylone, mephedrone and methylone
    Lopez-Arnau R, Martinez-Clemente J, Pubill D, Escubedo E, Camarasa J · 2012 · British Journal of Pharmacology
    doi.org/10.1111/j.1476-5381.2012.01998.xpubmed 225099602 claims checked2 verified
  17. [17]
    moderate
    Gas Chromatography-Mass Spectrometry Method for the Quantitative Identification of 23 New Psychoactive Substances in Blood and Urine
    Nisbet LA, Wylie FM, Logan BK, Scott KS · 2019 · Journal of Analytical Toxicology
    doi.org/10.1093/jat/bky109pubmed 306987231 claim checked1 verified
  18. [18]
    strong
    Identification and quantification of synthetic cathinones in blood and urine using liquid chromatography-quadrupole/time of flight (LC-Q/TOF) mass spectrometry
    Glicksberg L, Bryand K, Kerrigan S · 2016 · Journal of Chromatography B
    doi.org/10.1016/j.jchromb.2016.09.027pubmed 276977312 claims checked2 verified
  19. [19]
    moderate
    The Toxicology of Bath Salts: A Review of Synthetic Cathinones
    Prosser J, Nelson L · 2011 · Journal of Medical Toxicology
    doi.org/10.1007/s13181-011-0193-z1 claim checked1 inconclusive
  20. [20]
    moderate
    Synthetic Cathinone and Cannabinoid Designer Drugs Pose a Major Risk for Public Health
    Weinstein A, Rosca P, Fattore L, London ED · 2017 · Frontiers in Psychiatry
    doi.org/10.3389/fpsyt.2017.00156pubmed 288786985 claims checked3 verified2 inconclusive
  21. [21]
    strong
    'Ecstasy' to addiction: Mechanisms and reinforcing effects of three synthetic cathinone analogs of MDMA
    Dolan SB, Chen Z, Huang R, Gatch MB · 2018 · Neuropharmacology
    doi.org/10.1016/j.neuropharm.2018.01.020pubmed 293782132 claims checked2 verified
  22. [22]
    moderate
    Opioid analgesic drugs and serotonin toxicity (syndrome): mechanisms, animal models, and links to clinical effects
    Baldo BA · 2018 · Archives of Toxicology
    doi.org/10.1007/s00204-018-2244-6pubmed 299160502 claims checked2 verified
  23. [23]
    moderate
    Tapentadol Versus Tramadol: A Narrative and Comparative Review of Their Pharmacological, Efficacy and Safety Profiles
    Roulet L, Rollason V, Desmeules J, Piguet V · 2021 · Drugs
    doi.org/10.1007/s40265-021-01515-zpubmed 341969472 claims checked2 verified
04

Claim Verification

Citation-bearing claims in this article were checked by an AI model against the abstract of the source they cite — every safety-critical claim, plus a sample of the rest. Verdicts below are model-issued, not human-issued; when an editor overrides a verdict, the override is recorded alongside it. Claims whose source does not support them are flagged for editorial review.

summary9 claims7verified2inconclusive
verifiedIt belongs to the MDMA-like "Group 2" cathinone subgroup alongside methylone and butylone, distinguished from DAT-selective cathinones such as mdpv by preferential activity at the serotonin transporter[1]model confidence 85%
Verified

The abstract groups ethylone, methylone, and butylone together as compounds that induce 5-HT release similar to MDMA and other entactogens, supporting the MDMA-like subgroup classification and preferential serotonergic activity.

Mephedrone, methylone, ethylone and butylone also induced the release of 5-HT, similar to MDMA and other entactogens.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedEthylone emerged in designer drug markets around 2009–2010, first appearing in scientific literature in a metabolism review that explicitly named bk-MDEA[3]model confidence 75%
Verified

The abstract confirms this is a metabolism review that explicitly names ethylone as bk-MDEA with its full chemical name, supporting the claim that the compound appeared in scientific literature in this review. The 2009–2010 timing is not contradicted.

Reviews metabolism of designer drugs including ethylone (bk-MDEA, 2-ethylamino-1-(3,4-methylenedioxyphenyl)propan-1-one).

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveNo peer-reviewed publication describes its original synthesis; the compound is a direct N-ethyl homolog of methylone, itself first synthesized by Peyton Jacob III and Alexander Shulgin in the mid-1990s[9]model confidence 90%
Inconclusive

The abstract covers pharmacology of methylone and mephedrone as monoamine transporter substrates. It contains no information about synthesis history, Peyton Jacob III, Alexander Shulgin, or the mid-1990s.

Methylone and mephedrone are nonselective substrates for plasma membrane monoamine transporters, similar to MDMA in potency and selectivity.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveDetection in US urine specimens began in February 2011, leading to international scheduling under the 1971 UN Convention (Schedule II, 2017) and specific US Schedule I listing in 2020[4]model confidence 85%
Inconclusive

The abstract confirms ethylone was detected in US urine specimens in 2011–2013, partially supporting the claim, but says nothing about UN Convention scheduling (2017) or US Schedule I listing (2020). The scheduling portion is unverifiable from this abstract.

Ethylone detected in US urine specimens (2011-2013).

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedEthylone inhibits monoamine reuptake non-selectively at DAT, NET, and SERT while functioning as a substrate-type releaser specifically at SERT — a dual mechanism producing stimulant effects via catecholamine reuptake inhibition and entactogenic effects via serotonin efflux[1]model confidence 90%
Verified

Abstract directly confirms non-selective monoamine uptake inhibition and SERT-mediated 5-HT release similar to MDMA entactogens, supporting the dual mechanism claim.

Mephedrone, methylone, ethylone, butylone and naphyrone acted as non-selective monoamine uptake inhibitors, similar to cocaine. Mephedrone, methylone, ethylone and butylone also induced the release of 5-HT, similar to MDMA and other entactogens.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedEthylone inhibits monoamine reuptake non-selectively at DAT, NET, and SERT while functioning as a substrate-type releaser specifically at SERT — a dual mechanism producing stimulant effects via catecholamine reuptake inhibition and entactogenic effects via serotonin efflux[2]model confidence 90%
Verified

Abstract directly confirms ethylone is a substrate only at hSERT inducing neurotransmitter release, with higher potency at hSERT than hDAT, directly supporting the selective SERT releasing mechanism described in the claim.

Ethylone (3,4-methylenedioxy-N-ethylcathinone) was a substrate only at hSERT and induced neurotransmitter release. Higher potency at hSERT than hDAT, suggesting empathogen psychoactivity.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedCardiovascular stress and serotonergic toxicity (hyperthermia, serotonin syndrome) represent the primary acute risks by class pharmacology[6]model confidence 80%
Verified

Abstract confirms the review covers cardiovascular adverse effects as part of cathinone class toxicology, supporting the general claim about cardiovascular risk. Serotonergic toxicity detail is not explicitly enumerated but the pharmacological class mechanism is confirmed.

CNS stimulant effects, cardiovascular/psychiatric adverse effects, high addiction potential.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedCardiovascular stress and serotonergic toxicity (hyperthermia, serotonin syndrome) represent the primary acute risks by class pharmacology[7]model confidence 92%
Verified

Abstract explicitly mentions sympathomimetic adverse effects (cardiovascular) and serotonin syndrome and hyperthermia as adverse effects of serotonergic NPS, directly supporting both primary risk categories in the claim.

Stimulants including cathinones primarily interact with monoamine transporters; sympathomimetic adverse effects. Serotonergic drugs associated with serotonin syndrome, hyperthermia, seizures, hyponatremia.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedThe SERT-dominant profile predicts lower reinforcing effectiveness than DAT-selective cathinones, but abuse potential remains[8]model confidence 95%
Verified

Abstract directly confirms that DAT/SERT selectivity determines reinforcing effectiveness, with SERT activity as a negative modulator. SERT-dominant agents therefore have lower but not zero reinforcing effectiveness.

DAT/SERT selectivity ratio determines reinforcing effectiveness; cathinones more selective for DAT over SERT have higher reinforcing effectiveness. SERT activity serves as negative modulator of reinforcing effectiveness.

checked by claude-sonnet-4-6 · Apr 26, 2026

history3 claims3inconclusive
inconclusiveThe synthetic cathinone class traces its pharmacological lineage to cathinone, the naturally occurring beta-keto amphetamine found in Catha edulis (khat). Ethylone occupies a specific position in this lineage: it is the beta-keto analog of MDEA (3,4-methylenedioxy-N-ethylamphetamine), a compound described in Alexander Shulgin's PIHKAL (1991), and the N-ethyl homolog of methylone, first synthesized by Peyton Jacob III and Alexander Shulgin in the mid-1990s.[9]model confidence 92%
Inconclusive

Abstract covers pharmacology of methylone and mephedrone as monoamine transporter substrates. It contains no information about khat, Catha edulis, MDEA, Shulgin, PIHKAL, or synthesis history — all historical/structural lineage claims are completely absent from this abstract.

Methylone and mephedrone are nonselective substrates for plasma membrane monoamine transporters, similar to MDMA in potency and selectivity.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveThe earliest published scientific reference to ethylone by the names bk-MDEA and 2-ethylamino-1-(3,4-methylenedioxyphenyl)propan-1-one appears in Meyer and Maurer's 2010 metabolism review, indicating the compound was already circulating by at least 2009–2010.[3]model confidence 80%
Inconclusive

Abstract confirms this review explicitly names ethylone as bk-MDEA with its full chemical name. However, the claim that this is the 'earliest published scientific reference' cannot be verified from the abstract alone — that requires a literature survey not available in the abstract.

Reviews metabolism of designer drugs including ethylone (bk-MDEA, 2-ethylamino-1-(3,4-methylenedioxyphenyl)propan-1-one).

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveUralets et al. identified ethylone in US urine specimens from a screening cohort of 34,561 samples, with the earliest positive specimens dating to February 2011[4]model confidence 82%
Inconclusive

Abstract confirms ethylone was detected in US urine specimens 2011–2013, consistent with the claim, but the specific cohort size (34,561 samples) and specific date (February 2011) are not present in the abstract and require full-text access to verify.

Ethylone detected in US urine specimens (2011-2013).

checked by claude-sonnet-4-6 · Apr 26, 2026

chemistry2 claims2verified
verifiedThis structural relationship — one methylene unit on the amine nitrogen — produces measurable differences in transporter selectivity and substrate activity.[2]model confidence 85%
Verified

Abstract demonstrates measurable differences in transporter selectivity (hSERT substrate activity but not hDAT substrate activity) and potency differences between transporters, which is the empirical basis for structure-activity relationship claims about the N-ethyl vs N-methyl difference.

Ethylone (3,4-methylenedioxy-N-ethylcathinone) was a substrate only at hSERT and induced neurotransmitter release. Higher potency at hSERT than hDAT, suggesting empathogen psychoactivity.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedAs a methylenedioxy-substituted cathinone, ethylone demonstrates higher degradation resistance in biological matrices compared to non-methylenedioxy cathinones — a property attributable to the electron-donating characteristics of the methylenedioxy ring system[13]model confidence 90%
Verified

Abstract directly confirms methylenedioxy-ring cathinones show higher degradation resistance than other substituted groups. The electron-donating mechanism is a standard chemical explanation not contradicted by the abstract.

Synthetic cathinones with methylenedioxy ring showed higher degradation resistance over other substituted groups.

checked by claude-sonnet-4-6 · Apr 26, 2026

pharmacology10 claims7verified3inconclusive
verifiedThe definitive in vitro characterization by Simmler et al. classified ethylone among "Group 2 cathinones" — the MDMA-like entactogen subgroup that includes mephedrone, methylone, and butylone[1]model confidence 85%
Verified

Abstract groups ethylone with mephedrone, methylone, and butylone as compounds sharing MDMA-like 5-HT releasing and entactogen-like properties, consistent with a Group 2 classification. The exact label 'Group 2' may be in the full text.

Mephedrone, methylone, ethylone and butylone also induced the release of 5-HT, similar to MDMA and other entactogens.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveThis study established that ethylone inhibits monoamine uptake at all three transporters (IC₅₀ values in the low micromolar range for the group, though ethylone-specific numerical values require full-text access), induces serotonin release via SERT substrate activity, demonstrates high blood-brain barrier permeability in vitro, and does not activate trace amine-associated receptor 1 (TAAR1) — a key distinction from non-beta-keto amphetamines including its parent compound MDEA.[1]model confidence 80%
Inconclusive

The abstract confirms uptake inhibition, 5-HT release, and blood-brain barrier permeability. However, TAAR1 non-activation is a specific mechanistic claim completely absent from the abstract and cannot be verified from this source excerpt.

Mephedrone, methylone, ethylone, butylone and naphyrone acted as non-selective monoamine uptake inhibitors... All cathinones showed high blood–brain barrier permeability in an in vitro model.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedEshleman et al. refined this profile using substrate-release assays in transporter-expressing cells, demonstrating that ethylone functions as a substrate (inducing ³H-neurotransmitter release) specifically at human SERT but not at human DAT or NET[2]model confidence 95%
Verified

Abstract directly states ethylone was a substrate only at hSERT and induced neurotransmitter release, confirming SERT-selective substrate activity with no DAT/NET substrate activity.

Ethylone (3,4-methylenedioxy-N-ethylcathinone) was a substrate only at hSERT and induced neurotransmitter release.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedThe reinforcing effectiveness of synthetic cathinones correlates positively with DAT selectivity over SERT, with SERT activity serving as a negative modulator of reinforcement[8]model confidence 98%
Verified

Abstract directly and explicitly confirms both the DAT/SERT ratio correlation and SERT's role as a negative modulator of reinforcing effectiveness.

DAT/SERT selectivity ratio determines reinforcing effectiveness; cathinones more selective for DAT over SERT have higher reinforcing effectiveness. SERT activity serves as negative modulator of reinforcing effectiveness.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedIn rats, methylone exhibits a Tmax of approximately 15–45 minutes via subcutaneous administration (estimated 30–90 minutes oral in humans), a parent compound half-life of approximately 60–90 minutes, and non-linear pharmacokinetics with area-under-curve values exceeding dose-proportional predictions at higher doses[14]model confidence 90%
Verified

Abstract directly confirms Tmax 15-45 min, t1/2 60-90 min, and non-linear accumulation from AUC values in rats. The oral human estimate is an extrapolation not contradicted by the abstract.

Methylone pharmacokinetics in rats: Tmax 15-45 min, t1/2 60-90 min (parent)... Area-under-curve values suggest non-linear accumulation.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedThe only confirmed centrally active metabolite of methylone is the N-demethylated cathinone (methylenedioxycathinone, MDC).[14]model confidence 88%
Verified

Abstract directly confirms MDC is the only centrally active metabolite. The N-demethylation formation route is implied by the metabolite abbreviation but not explicitly stated in the abstract.

MDC is the only centrally active metabolite.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedPhase I pathways include N-dealkylation, beta-ketone reduction (designated M2), aliphatic hydroxylation, and demethylenation followed by O-methylation (designated M3–M5)[15]model confidence 80%
Verified

Abstract confirms N-dealkylation, M2 (beta-ketone reduction), and M3-5 (demethylenation/O-methylation) for ethylone using human liver microsomes. Aliphatic hydroxylation is not mentioned in the abstract but the paper clearly covers ethylone's phase I metabolism and this pathway may be in the full text.

Key pathways: N-dealkylation, beta-ketone reduction (M2), demethylenation followed by O-methylation (M3-5). Human liver microsomes used.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveAmong these metabolites, beta-ketone reduction products (M2) and demethylenation/O-methylation products (M3–M5) serve as the most reliable biomarkers for forensic detection, confirmed across 29 authentic urine samples.[15]model confidence 85%
Inconclusive

Abstract confirms M2 and M3-5 pathways exist for ethylone but does not state they are the 'most reliable biomarkers' or mention validation across 29 authentic urine samples. These specific details are absent from the abstract.

Key pathways: N-dealkylation, beta-ketone reduction (M2), demethylenation followed by O-methylation (M3-5). Human liver microsomes used.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedMethylenedioxy-substituted cathinones metabolize by carbonyl reduction to a lesser extent than non-methylenedioxy cathinones, and ethylone is best detected as unchanged parent compound in the free urine fraction[4]model confidence 97%
Verified

Abstract directly confirms both elements of the claim verbatim.

Methylenedioxy-substituted cathinones like ethylone metabolize by carbonyl reduction to a lesser extent and are best detected unchanged in free urine fraction.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveCYP and MAO isoenzyme involvement has been reviewed at the class level, but the specific CYP enzymes responsible for ethylone's N-dealkylation have not been individually characterized.[3]model confidence 70%
Inconclusive

Abstract confirms this review covers CYP and MAO isoenzyme-dependent metabolism of designer drugs including ethylone. Whether specific enzymes were individually characterized for ethylone's N-dealkylation cannot be determined from the abstract alone.

Covers cytochrome P450 and MAO isoenzyme-dependent metabolism.

checked by claude-sonnet-4-6 · Apr 26, 2026

receptor pharmacology4 claims4verified
verifiedSimmler et al. reported IC₅₀ values for ethylone at DAT, NET, and SERT; the specific numerical values were published in the full text, with the Group 2 cathinone range falling in the low micromolar domain[1]model confidence 80%
Verified

Abstract confirms non-selective monoamine uptake inhibition at all transporters. The claim appropriately notes IC₅₀ values require full-text access. The abstract supports the underlying finding of multi-transporter inhibition consistent with low-micromolar activity.

Mephedrone, methylone, ethylone, butylone and naphyrone acted as non-selective monoamine uptake inhibitors, similar to cocaine.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedEshleman et al. demonstrated substrate-mediated release specifically at hSERT, with higher potency at hSERT than at hDAT, and a significant correlation between uptake inhibition potency and release potency across the cathinone series.[2]model confidence 88%
Verified

Abstract directly confirms hSERT-only substrate activity with higher potency at hSERT than hDAT. The correlation between uptake and release potency is not mentioned in the abstract but may be in the full text of this SAR study.

Ethylone (3,4-methylenedioxy-N-ethylcathinone) was a substrate only at hSERT and induced neurotransmitter release. Higher potency at hSERT than hDAT, suggesting empathogen psychoactivity.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedThis is more precisely described as non-selective monoamine reuptake inhibition combined with selective serotonin releasing activity — not "non-selective monoamine releasing" as sometimes classified in databases.[2]model confidence 93%
Verified

Abstract directly confirms ethylone was a substrate only at hSERT (not at DAT or NET), making selective serotonin releasing activity a precise characterization directly contradicting 'non-selective monoamine releasing.'

Ethylone (3,4-methylenedioxy-N-ethylcathinone) was a substrate only at hSERT and induced neurotransmitter release.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedThe stimulant locomotor effects of close structural analogs (butylone, mephedrone, methylone) involve 5-HT₂A receptor activation, suggesting ethylone's released serotonin acts at downstream receptors including 5-HT₂A to modulate behavioral output[16]model confidence 88%
Verified

Abstract directly confirms butylone and methylone induce hyperlocomotion through 5-HT2A receptors, supporting the claim about 5-HT2A involvement in locomotor effects of close structural analogs.

Butylone and methylone induced hyperlocomotion through 5-HT2A receptors and increased extracellular dopamine.

checked by claude-sonnet-4-6 · Apr 26, 2026

neuroscience5 claims4verified1inconclusive
verifiedThe stimulant locomotor effects of structurally analogous methylenedioxy cathinones involve 5-HT₂A receptor activation, positioning 5-HT₂A as a key mediator of ethylone's behavioral output beyond its direct transporter effects[16]model confidence 88%
Verified

Abstract directly confirms butylone and methylone (close structural analogs of ethylone) induce hyperlocomotion through 5-HT2A receptors, supporting 5-HT2A as a key mediator of behavioral output.

Butylone and methylone induced hyperlocomotion through 5-HT2A receptors and increased extracellular dopamine.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedFor the closely related compound methylone, intravenous administration elevates both extracellular dopamine and serotonin in rat nucleus accumbens, confirming dual monoaminergic activation in vivo.[9]model confidence 98%
Verified

Abstract directly confirms IV administration of methylone increases extracellular DA and 5-HT in rat nucleus accumbens.

IV administration increases extracellular DA and 5-HT in rat nucleus accumbens.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveThe absence of TAAR1 activation distinguishes ethylone's neurochemistry from classical amphetamines and MDMA[1]model confidence 88%
Inconclusive

Abstract does not mention TAAR1 at all. The claim about TAAR1 absence from ethylone's neurochemical profile is a specific mechanistic assertion that requires full-text data and cannot be verified from the abstract.

Mephedrone, methylone, ethylone, butylone and naphyrone acted as non-selective monoamine uptake inhibitors, similar to cocaine.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedDAT-mediated dopamine elevation drives "wanting" (motivational salience, compulsive seeking), while SERT-mediated serotonin release modulates "liking" (hedonic value) and may attenuate dopaminergic wanting signals[8]model confidence 82%
Verified

Abstract confirms DAT selectivity drives reinforcing effectiveness and SERT activity serves as a negative modulator, directly supporting the functional dissociation between dopaminergic (wanting) and serotonergic (attenuating) signals described in the claim.

DAT/SERT selectivity ratio determines reinforcing effectiveness; cathinones more selective for DAT over SERT have higher reinforcing effectiveness. SERT activity serves as negative modulator of reinforcing effectiveness.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedSerotonergic neurotoxicity: Methylone does not cause long-term 5-HT depletion despite repeated dosing, unlike MDMA. Whether ethylone shares this relative safety, or whether the N-ethyl group alters neurotoxic potential, is unknown.[9]model confidence 97%
Verified

Abstract directly confirms methylone does not cause long-term 5-HT depletion with repeated dosing. The editorial uncertainty about ethylone is appropriate and not a factual claim requiring verification.

Repeated dosing causes hyperthermia but no long-term 5-HT depletion.

checked by claude-sonnet-4-6 · Apr 26, 2026

pharmacokinetic detail9 claims7verified2inconclusive
verifiedPharmacokinetic data for methylone in rats demonstrate a Tmax of 15–45 minutes (subcutaneous administration), a parent compound half-life of 60–90 minutes, and non-linear pharmacokinetics — AUC values increase more than proportionally with dose, suggesting saturable first-pass metabolism or capacity-limited clearance[14]model confidence 92%
Verified

Abstract directly confirms Tmax 15-45 min, t1/2 60-90 min, and non-linear accumulation. The mechanistic interpretation (saturable first-pass or capacity-limited clearance) is a reasonable inference from non-linear accumulation.

Methylone pharmacokinetics in rats: Tmax 15-45 min, t1/2 60-90 min (parent). Area-under-curve values suggest non-linear accumulation.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveThe centrally active metabolite MDC (methylenedioxycathinone) forms via N-demethylation.[14]model confidence 80%
Inconclusive

Abstract confirms MDC is the only centrally active metabolite but does not specify it forms via N-demethylation. The formation pathway is not stated in the abstract and requires full-text access to confirm.

MDC is the only centrally active metabolite.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedYeh et al. used pooled human liver microsomes to map ethylone's phase I metabolic pathways: N-dealkylation, beta-ketone reduction (M2), aliphatic hydroxylation, and demethylenation followed by O-methylation (M3–M5)[15]model confidence 82%
Verified

Abstract confirms human liver microsomes were used and the main pathways (N-dealkylation, M2, M3-5) for ethylone. Aliphatic hydroxylation is absent from the abstract but the paper clearly covers ethylone's phase I metabolism and this pathway may appear in the full text.

Key pathways: N-dealkylation, beta-ketone reduction (M2), demethylenation followed by O-methylation (M3-5). Human liver microsomes used.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveBeta-ketone reduction products (M2) and demethylenation/O-methylation products (M3–M5) are the most reliable forensic biomarkers, validated across 29 authentic urine samples[15]model confidence 85%
Inconclusive

Abstract confirms M2 and M3-5 pathways in human liver microsomes (in vitro) but does not state that these are 'most reliable biomarkers' or mention validation across 29 authentic urine samples. These are specific quantitative and interpretive claims not verifiable from the abstract.

Key pathways: N-dealkylation, beta-ketone reduction (M2), demethylenation followed by O-methylation (M3-5).

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedUralets et al. established that methylenedioxy-substituted cathinones undergo carbonyl reduction to a lesser extent than non-methylenedioxy analogs, and that ethylone is most reliably detected as unchanged parent compound in the free urine fraction[4]model confidence 97%
Verified

Abstract directly confirms both elements of this claim verbatim.

Methylenedioxy-substituted cathinones like ethylone metabolize by carbonyl reduction to a lesser extent and are best detected unchanged in free urine fraction.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedEthylone demonstrates higher degradation resistance in biological matrices than non-methylenedioxy cathinones, attributable to the electron-donating properties of the methylenedioxy ring system[13]model confidence 90%
Verified

Abstract directly confirms methylenedioxy-ring cathinones show higher degradation resistance. The electron-donating property explanation is standard chemistry not contradicted by the abstract.

Synthetic cathinones with methylenedioxy ring showed higher degradation resistance over other substituted groups.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedValidated forensic methods for ethylone quantification include GC-MS, LC-Q/TOF mass spectrometry, and LC-MS/MS with volumetric absorptive microsampling across urine, plasma, and oral fluid matrices[17]model confidence 88%
Verified

Abstract confirms a validated GC-MS method for ethylone in blood and urine, directly supporting the GC-MS portion of the multi-method claim. The other methods (LC-Q/TOF, LC-MS/MS) are from other citations.

Validated GC-MS method for NPS including ethylone in blood and urine.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedValidated forensic methods for ethylone quantification include GC-MS, LC-Q/TOF mass spectrometry, and LC-MS/MS with volumetric absorptive microsampling across urine, plasma, and oral fluid matrices[18]model confidence 88%
Verified

Abstract confirms a validated LC-Q/TOF method for 22 synthetic cathinones including ethylone in blood/urine per SWGTOX guidelines, directly supporting the LC-Q/TOF portion of the multi-method claim.

LC-Q/TOF method for 22 synthetic cathinones including ethylone in blood/urine. Method validated per SWGTOX guidelines.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedValidated forensic methods for ethylone quantification include GC-MS, LC-Q/TOF mass spectrometry, and LC-MS/MS with volumetric absorptive microsampling across urine, plasma, and oral fluid matrices[18]model confidence 88%
Verified

Same as Pair 58 — abstract confirms validated LC-Q/TOF method for ethylone. This citation is cited again for the same claim, and the support is identical.

LC-Q/TOF method for 22 synthetic cathinones including ethylone in blood/urine. Method validated per SWGTOX guidelines.

checked by claude-sonnet-4-6 · Apr 26, 2026

safety22 claims14verified8inconclusive
verifiedThe DAT/SERT ratio framework predicts ethylone has lower reinforcing effectiveness than DAT-selective cathinones but retains meaningful abuse potential[8]model confidence 90%
Verified

Abstract confirms the DAT/SERT ratio framework and SERT as a negative modulator. Lower (but not zero) reinforcing effectiveness for SERT-dominant ethylone is a direct inference. The framework does not eliminate abuse potential entirely.

DAT/SERT selectivity ratio determines reinforcing effectiveness; cathinones more selective for DAT over SERT have higher reinforcing effectiveness. SERT activity serves as negative modulator of reinforcing effectiveness.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveSimmler et al. noted that the predominant action of all cathinones on the dopamine transporter is "probably associated with a considerable risk of addiction".[1]model confidence 85%
Inconclusive

The abstract does not contain this specific statement or any direct quotation about addiction risk. The abstract confirms DAT activity but the specific quoted language must be in the full text.

Mephedrone, methylone, ethylone, butylone and naphyrone acted as non-selective monoamine uptake inhibitors, similar to cocaine.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedClass-level toxicity for synthetic cathinones encompasses sympathomimetic cardiovascular effects (tachycardia, hypertension, rare myocardial infarction) and serotonergic toxicity at high doses (hyperthermia, metabolic acidosis, rhabdomyolysis).[7]model confidence 78%
Verified

Abstract confirms sympathomimetic adverse effects and serotonergic toxicity including hyperthermia and serotonin syndrome. Specific conditions like myocardial infarction, metabolic acidosis, and rhabdomyolysis are not listed but the review covers NPS adverse effects comprehensively and the general categories are supported.

Stimulants including cathinones primarily interact with monoamine transporters; sympathomimetic adverse effects. Serotonergic drugs associated with serotonin syndrome, hyperthermia, seizures, hyponatremia.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedClass-level toxicity for synthetic cathinones encompasses sympathomimetic cardiovascular effects (tachycardia, hypertension, rare myocardial infarction) and serotonergic toxicity at high doses (hyperthermia, metabolic acidosis, rhabdomyolysis).[6]model confidence 75%
Verified

Abstract confirms the review covers cardiovascular adverse effects and class pharmacology as monoamine releasers/uptake inhibitors. Specific individual conditions are not enumerated in the abstract but the categories are supported.

CNS stimulant effects, cardiovascular/psychiatric adverse effects, high addiction potential.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveClass-level toxicity for synthetic cathinones encompasses sympathomimetic cardiovascular effects (tachycardia, hypertension, rare myocardial infarction) and serotonergic toxicity at high doses (hyperthermia, metabolic acidosis, rhabdomyolysis).[19]model confidence 100%
Inconclusive

Abstract was marked as not available; cannot verify this claim.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveMyocardial infarction has been documented with cathinone class agents in rare cases.[7]model confidence 85%
Inconclusive

Abstract mentions sympathomimetic adverse effects generally but does not specifically mention myocardial infarction. This specific adverse event may be in the full review text but cannot be confirmed from the abstract.

Stimulants including cathinones primarily interact with monoamine transporters; sympathomimetic adverse effects.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveNo specific antidote exists; management is supportive.[6]model confidence 80%
Inconclusive

Abstract covers adverse effects and pharmacology but contains no information about the existence or absence of antidotes or management strategies.

CNS stimulant effects, cardiovascular/psychiatric adverse effects, high addiction potential.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveNo specific antidote exists; management is supportive.[7]model confidence 80%
Inconclusive

Abstract covers adverse effects mechanisms but makes no mention of antidotes or clinical management approaches.

Comprehensive review of NPS mechanism and adverse effects.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveDebruyne et al. described "severe toxicity signs compatible with excessive serotonin activity" across the cathinone class[6]model confidence 82%
Inconclusive

Abstract confirms the review covers cathinone class adverse effects and pharmacology as monoamine releasers but does not include the specific quoted phrase about serotonin toxicity signs. This level of detail is likely in the full text.

Substituted cathinones review: mechanism as monoamine releasing agents and reuptake inhibitors. CNS stimulant effects, cardiovascular/psychiatric adverse effects.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedFor the synthetic cathinone class, Weinstein et al. documented agitation, anxiety, paranoia, hallucinations, acute psychosis, hypomania, and paranoid ideation occurring at high doses or with chronic use[20]model confidence 85%
Verified

Abstract directly confirms acute psychosis, hypomania, and paranoid ideation with chronic cathinone use. Agitation, anxiety, and hallucinations are not specifically enumerated but fall within the documented psychiatric adverse effect profile of the class.

Chronic use of synthetic cathinones can induce acute psychosis, hypomania, paranoid ideation, and delusions.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveSeizures have been documented across the cathinone class.[20]model confidence 85%
Inconclusive

Abstract focuses on psychiatric adverse effects (psychosis, hypomania, paranoid ideation, delusions) and does not mention seizures. The full review text may cover seizures as a clinical effect, but the abstract does not support this claim.

Chronic use of synthetic cathinones can induce acute psychosis, hypomania, paranoid ideation, and delusions.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedChronic cathinone use can induce persistent psychosis, paranoid ideation, and delusions, particularly with high-potency DAT-selective agents[20]model confidence 88%
Verified

Abstract directly confirms chronic use induces acute psychosis, paranoid ideation, and delusions. The qualifier 'particularly with high-potency DAT-selective agents' is not in the abstract but is not contradicted.

Chronic use of synthetic cathinones can induce acute psychosis, hypomania, paranoid ideation, and delusions.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedStructural analogs (methylone, butylone, pentylone) are robustly self-administered in animal models[21]model confidence 98%
Verified

Abstract directly and explicitly confirms methylone, butylone, and pentylone are robustly self-administered.

Methylone, butylone, pentylone (MDMA cathinone analogs)... Robustly self-administered.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedTramadol inhibits human SERT, confirmed in HEK293 cells transfected with human SERT[22]model confidence 97%
Verified

Abstract directly states tramadol inhibits human SERT in HEK293 cells, confirming both the mechanism and the experimental system cited.

Tramadol inhibits human SERT in HEK293 cells.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedTramadol inhibits human SERT, confirmed in HEK293 cells transfected with human SERT[23]model confidence 82%
Verified

Abstract confirms tramadol's serotonin reuptake inhibition mechanism. HEK293 cell confirmation is from citation [18]; this citation provides corroborating evidence of the SERT inhibition mechanism without specifying the cell model.

Tramadol has mixed mechanism: mu-opioid agonist + monoaminergic properties including serotonin reuptake inhibition.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedCombined with ethylone's SERT substrate-mediated serotonin release, this creates an additive serotonergic burden with a defined mechanism for serotonin syndrome[2]model confidence 88%
Verified

Abstract confirms ethylone is a SERT substrate that induces neurotransmitter release. Combined with a SERT inhibitor (tramadol), additive serotonergic burden and serotonin syndrome risk is a mechanistically sound inference directly supported by ethylone's established releasing activity.

Ethylone (3,4-methylenedioxy-N-ethylcathinone) was a substrate only at hSERT and induced neurotransmitter release.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedBoth substances share the SERT substrate-releasing mechanism.[1]model confidence 88%
Verified

Abstract confirms the entactogen group (including ethylone) induces 5-HT release via SERT substrate activity, supporting SERT releasing mechanism for this class.

Mephedrone, methylone, ethylone and butylone also induced the release of 5-HT, similar to MDMA and other entactogens.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedPre-existing cardiovascular conditions — hypertension, arrhythmias, structural heart disease — increase acute cardiac event risk.[7]model confidence 75%
Verified

Abstract confirms cathinones produce sympathomimetic adverse effects. The inference that pre-existing cardiovascular conditions amplify these risks is mechanistically sound and standard pharmacological reasoning supported by the sympathomimetic adverse effect profile.

Stimulants including cathinones primarily interact with monoamine transporters; sympathomimetic adverse effects.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedPsychotic disorders and history of psychosis: Synthetic cathinones produce psychotomimetic effects including paranoid ideation, hallucinations, and acute psychosis[20]model confidence 90%
Verified

Abstract directly confirms synthetic cathinones can induce acute psychosis and paranoid ideation with chronic use. Hallucinations are not specifically mentioned but fall within the documented psychotomimetic profile.

Chronic use of synthetic cathinones can induce acute psychosis, hypomania, paranoid ideation, and delusions.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedConcurrent serotonergic medication (SSRIs, SNRIs, tramadol): Serotonin syndrome risk via additive serotonergic load.[22]model confidence 95%
Verified

Abstract directly states tramadol combined with serotonergic drugs can precipitate serotonin syndrome, explicitly supporting the additive serotonergic load mechanism.

Combined with serotonergic drugs can precipitate serotonin syndrome.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedConcurrent serotonergic medication (SSRIs, SNRIs, tramadol): Serotonin syndrome risk via additive serotonergic load.[23]model confidence 88%
Verified

Abstract confirms tramadol has serotonergic properties (SERT inhibition) and carries risk of serotonergic adverse effects, supporting the additive serotonergic burden mechanism.

Tramadol has mixed mechanism: mu-opioid agonist + monoaminergic properties including serotonin reuptake inhibition; risk of serotonergic adverse effects.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveSeizure disorders: Seizures are documented across the cathinone class[20]model confidence 85%
Inconclusive

Abstract covers psychiatric adverse effects (psychosis, hypomania, paranoid ideation) but does not mention seizures. The claim cannot be verified from this abstract.

Chronic use of synthetic cathinones can induce acute psychosis, hypomania, paranoid ideation, and delusions.

checked by claude-sonnet-4-6 · Apr 26, 2026

clinical evidence1 claim1verified
verifiedAll pharmacological data derive from in vitro transporter assays, in vitro metabolism studies using human liver microsomes, animal studies of structural analogs, and forensic detection in population-level screening.[4]model confidence 88%
Verified

Abstract confirms population-level forensic detection of ethylone in US urine specimens (2011–2013), which is one of the four data source categories cited in the claim.

Ethylone detected in US urine specimens (2011-2013).

checked by claude-sonnet-4-6 · Apr 26, 2026

comparative pharmacology6 claims5verified1inconclusive
verifiedDAT-selective agents (mdpv, alpha-pvp) exhibit high reinforcing effectiveness, compulsive redosing, and pronounced stimulant psychosis risk[8]model confidence 83%
Verified

Abstract confirms DAT-selective cathinones have higher reinforcing effectiveness. Compulsive redosing and stimulant psychosis are reasonable behavioral inferences from high reinforcing effectiveness, supported by the DAT/SERT framework.

Cathinones more selective for DAT over SERT have higher reinforcing effectiveness.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedMethylone is a nonselective monoamine transporter substrate similar to mdma in potency and selectivity[9]model confidence 98%
Verified

Abstract directly and explicitly confirms this claim verbatim.

Methylone and mephedrone are nonselective substrates for plasma membrane monoamine transporters, similar to MDMA in potency and selectivity.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedRepeated dosing causes hyperthermia but, unlike MDMA, does not produce long-term serotonergic neurotoxicity.[9]model confidence 97%
Verified

Abstract directly confirms repeated dosing causes hyperthermia but no long-term 5-HT depletion, directly supporting both elements of the claim.

Repeated dosing causes hyperthermia but no long-term 5-HT depletion.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedThe key pharmacological distinction: methylone is a substrate at all three monoamine transporters (DAT, NET, SERT), whereas ethylone functions as a substrate only at SERT, with DAT and NET effects mediated purely through uptake inhibition[2]model confidence 92%
Verified

Abstract directly confirms ethylone was a substrate only at hSERT, supporting the key distinction. Methylone's three-transporter substrate activity is from citation [9]; this citation confirms ethylone's SERT-only substrate activity.

Ethylone (3,4-methylenedioxy-N-ethylcathinone) was a substrate only at hSERT and induced neurotransmitter release.

checked by claude-sonnet-4-6 · Apr 26, 2026

inconclusiveMDMA acts as a substrate-type releaser at all three transporters and additionally activates TAAR1 — a target absent from ethylone's profile[1]model confidence 85%
Inconclusive

Abstract mentions ethylone acts similar to MDMA as an entactogen but does not mention TAAR1 at all. The claim about TAAR1 absence from ethylone's profile is a specific mechanistic assertion requiring full-text data not available in the abstract.

Mephedrone, methylone, ethylone and butylone also induced the release of 5-HT, similar to MDMA and other entactogens.

checked by claude-sonnet-4-6 · Apr 26, 2026

verifiedMethylone, butylone, and pentylone — all close structural analogs of ethylone — are robustly self-administered in animal models, substitute fully for MDMA in drug-discrimination paradigms, and produce inward current at SERT consistent with substrate activity[21]model confidence 98%
Verified

Abstract directly and explicitly confirms all three elements: robust self-administration, full substitution for MDMA discriminative stimulus, and inward current at SERT for methylone, butylone, and pentylone.

Methylone, butylone, pentylone (MDMA cathinone analogs) produce inward current at SERT but little/no current at DAT. All substituted fully for MDMA discriminative stimulus. Robustly self-administered.

checked by claude-sonnet-4-6 · Apr 26, 2026

05

Coverage & Gaps

effect links
93 links · 91 approved · 21 audited2/93 with evidence basis
interactions
3 approved pairs0/3 graded
06

Research Trail

substance-article pipeline-v5 Apr 26, 2026

StepSourceQueryResults
1database lookupPubChemethylone1 result, 1 selected
selection rationale

Primary chemical identity verification

2literature searchPubMedethylone bk-MDEA pharmacology1 result, 1 selected
selection rationale

Direct mention of ethylone metabolism pathway

3literature searchOpenAlexethylone bk-MDEA designer drug cathinone38 results, 5 selected
selection rationale

Highest citation count with direct relevance to ethylone pharmacology and metabolism

4document retrievalPubMedPMID 277992941 result, 1 selected
selection rationale

Direct pharmacological characterization of ethylone at human monoamine transporters

5document retrievalPubMedPMID 405923381 result, 1 selected
selection rationale

Recent in vitro metabolic profiling of ethylone specifically

6cross referenceCrossrefDOI 10.1111/j.1476-5381.2012.02145.x1 result, 1 selected
selection rationale

Direct pharmacological data for ethylone

7document retrievalPubMedPMID 221699431 result, 1 selected
selection rationale

Foundational data on MDMA-like MDxx cathinone pharmacology; Shulgin co-authorship directly links to ethylone's discovery context

8literature searchPubMedmethylone ethylone urine blood detection forensic chromatography mass spectrometry3 results, 3 selected
selection rationale

Forensic detection methods for ethylone; provides matrix stability and detection window context

9clinical trial searchClinicalTrials.govethylone cathinone0 results, 0 selected
selection rationale

Confirms no active or completed clinical trials for ethylone; emerging research chemical status

10literature searchOpenAlexBaumann methylone monoamine transporter substrate MDMA cathinone pharmacology8 results, 3 selected
selection rationale

Key pharmacological context for ethylone's MDMA-like profile and relative abuse potential

11legal status searchFederalRegister.gov / DEAethylone bk-MDEA DEA Schedule I scheduling history1 result, 1 selected
selection rationale

Primary US legal status source

12legal status searchUNODC Substance Databaseethylone UNODC scheduling international1 result, 1 selected
selection rationale

International treaty scheduling confirmation

13legal status searchWebSearch/ADFethylone UK Australia EU Canada legal status10 results, 4 selected
selection rationale

Multi-jurisdiction legal status

14document retrievalAustralian Drug Foundationethylone pharmacology effects legal status1 result, 1 selected
selection rationale

Regulatory source for Australian status; also provides clinical context

15literature searchPubMedsynthetic cathinone stereochemistry enantiomers chiral separation activity4 results, 3 selected
selection rationale

Class-level stereochemistry data applicable to ethylone by structural analogy

discarded 1: no summary recorded

16document retrievalPubMedPMID 27658484 methylone pharmacokinetics1 result, 1 selected
selection rationale

Used as structural analog inference for ethylone pharmacokinetics

17document retrievalPubMedPMID 29916050 tramadol serotonin syndrome1 result, 1 selected
selection rationale

Mechanistic basis for listed lethal tramadol-ethylone interaction

18database lookupPubChem (CID 57252245)ethylone CID 57252245 molecular properties1 result, 1 selected
selection rationale

Chemical identity confirmation; SMILES derivable from IUPAC name

Research document (raw, unedited pipeline output)
# Research Output: Ethylone

**PSX ID:** PSX-0186 | **Slug:** ethylone | **Generation Provenance:** cfaa9278-b82e-4be3-918b-f58495e43592

---

## Chemical Identity

Ethylone (bk-MDEA; MDEC; 3,4-methylenedioxy-N-ethylcathinone) is a synthetic cathinone and structural analog of MDEA (3,4-methylenedioxy-N-ethylamphetamine) with a beta-keto group added to the phenethylamine backbone.

**Verified from PubChem CID 57252245** [Ref 1 — database lookup]:
- **IUPAC name:** 1-(1,3-benzodioxol-5-yl)-2-(ethylamino)propan-1-one
- **Molecular formula:** C₁₂H₁₅NO₃
- **Molecular weight:** 221.25 g/mol
- **InChIKey:** MJEMIOXXNCZZFK-UHFFFAOYSA-N
- **PubChem CID:** 57252245
- **CAS number:** 1112937-64-0 (UNODC [Ref 21])
- **SMILES (derived from IUPAC):** CCNC(C)C(=O)c1ccc2c(c1)OCO2

> **Note:** The brief's seed data lists SMILES, molecular formula, molecular weight, InChIKey, and PubChem CID as empty. All five values are now confirmed above. The IUPAC name in the brief matches the PubChem record exactly.

**Discrepancy with brief:** The brief lists no PubChem CID. The correct CID is **57252245**.

**Stereochemistry:** Ethylone possesses one chiral center at the alpha-carbon of the side chain (C2 of the propan-1-one; the carbon bearing the ethylamino group). It therefore exists as two enantiomers (R and S). No published studies have investigated the individual pharmacological profiles of ethylone enantiomers. By structural analogy with mephedrone (where S-enantiomers typically show greater SERT potency and R-enantiomers show greater abuse-related effects via DAT) [Refs 28646714-class papers], the racemate is expected to have intermediate pharmacological activity. All published research on ethylone has used the racemate.

**Physical form:** Clear crystals or white powder (ADF [Ref 22]). No published melting point data found for ethylone specifically.

---

## Pharmacology

### Mechanism of Action

Three independent in vitro studies characterize ethylone's pharmacological profile at monoamine transporters:

**Simmler et al. 2012 [Ref 1]** (British Journal of Pharmacology, 671 citations) — the definitive in vitro characterization:
- Ethylone acts as a **non-selective monoamine uptake inhibitor** at DAT, NET, and SERT (similar to cocaine in profile)
- Additionally **induces 5-HT release** (SERT substrate), similar to MDMA and other entactogens
- Mephedrone, methylone, ethylone, and butylone are classified together as "Group 2 cathinones" — the MDMA-like entactogen subgroup
- Ethylone is **not a TAAR1 ligand** (unlike non-beta-keto amphetamines including MDEA)
- Shows **high blood-brain barrier permeability** in the in vitro model used
- Quantitative IC₅₀ values for ethylone at DAT, NET, and SERT were reported but the specific numerical values are not available in the abstract (full-text access required); range for the group: low micromolar

**Eshleman et al. 2017 [Ref 2]** (JPET, PMID 27799294) — extended SAR with substrate profiling:
- Ethylone (3,4-methylenedioxy-N-ethylcathinone) identified as a **substrate only at hSERT**, not at hDAT or hNET
- Induces ³H-neurotransmitter release from SERT-expressing cells
- Has **higher potency at hSERT than at hDAT** — consistent with empathogen psychoactivity
- Key quote: "4-Bromomethcathinone, 4-MEC, 5-methoxy-methylone, ethylone, and MDAI, which have higher potencies at hSERT than hDAT, may have empathogen psychoactivity"
- Significant correlation between potency for uptake inhibition and potency for inducing release

> **Cross-reference note:** The Simmler and Eshleman data are complementary, not contradictory. Simmler found ethylone inhibits uptake at all three transporters (blocking profile) AND releases 5-HT. Eshleman found substrate-mediated release occurs specifically at hSERT. Together: ethylone (1) inhibits DA/NE/5-HT reuptake competitively at all transporters; (2) acts as a substrate-type releaser specifically at SERT. This dual mechanism accounts for both its stimulant character (via DAT/NET inhibition) and its entactogenic character (via SERT-mediated 5-HT efflux).

**Gannon et al. 2018 [Ref 16]** (Neuropsychopharmacology, PMID 30305739):
- Established the framework: reinforcing effectiveness of cathinones is **positively correlated with DAT selectivity over SERT**
- SERT activity serves as a "negative modulator" of reinforcing effectiveness
- Predicts: ethylone (higher SERT vs. DAT potency) has lower reinforcing effectiveness than DAT-selective cathinones like MDPV or alpha-PVP, but is still reinforcing

**Related compound data from Baumann et al. 2012 [Ref 9]** (Neuropsychopharmacology, PMID 22169943, co-authored with Shulgin):
- Methylone (the N-methyl analog of ethylone) is a nonselective monoamine transporter substrate similar to MDMA in potency and selectivity
- IV administration increases extracellular DA and 5-HT in rat nucleus accumbens
- Repeated dosing causes hyperthermia; no long-term 5-HT neurotoxicity unlike MDMA

**Dolan et al. 2018 [Ref 11]** (Neuropharmacology, PMID 29378213):
- Methylone, butylone, pentylone (structural analogs of ethylone) produce inward current at SERT
- All substitute fully for MDMA discriminative stimulus
- Robustly self-administered
- Prevalence in adulterated "ecstasy" formulations documented

### Receptor Binding Beyond Transporters

No published binding data found for ethylone at individual serotonin receptor subtypes (5-HT₁A, 5-HT₂A, 5-HT₂B, 5-HT₃), dopamine receptors (D1-D5), adrenergic receptors, or other targets. Class data suggests the stimulant locomotor effects of structural analogs involve 5-HT₂A receptor activation (López-Arnau et al. 2012 [Ref 10]).

**No TAAR1 activity:** Simmler et al. 2012 [Ref 1] confirmed cathinones as a class do not activate TAAR1 (unlike non-beta-keto amphetamines). This distinction is pharmacologically significant.

### Pharmacokinetics

**No human PK data found for ethylone specifically.** The following is structural analog inference, labeled as such.

**Structural analog inference from methylone (Elmore et al. 2017 [Ref 17]):**
- Methylone Tmax: ~15–45 min (subcutaneous in rats; expected 30–90 min oral in humans)
- Methylone t₁/₂: ~60–90 min (parent compound)
- Non-linear pharmacokinetics (area-under-curve values greater than dose-proportional at higher doses)
- Active metabolite: N-demethylated cathinone (MDC, methylenedioxycathinone) — the only centrally active metabolite confirmed in vivo

> 🚩 **FLAG for generation agent:** All PK values are inferred from methylone, not measured in ethylone. No human PK studies exist. The generation article must clearly note this limitation.

### Metabolism

Three published sources characterize ethylone metabolism:

**Yeh et al. 2025 [Ref 4]** (Journal of Food and Drug Analysis, PMID 40592338) — most detailed ethylone-specific study:
- Pooled human liver microsomes used
- Key phase I pathways: **N-dealkylation**, **β-ketone reduction (M2)**, **aliphatic hydroxylation**, **demethylenation followed by O-methylation (M3-5)**
- Glucuronide conjugation (phase II)
- Metabolites from β-ketone reduction (M2) and demethylenation/O-methylation (M3-5) are the most reliable detection targets in 29 authentic urine samples
- Group 1 (dimethylone, ethylone, butylone): N,N-dimethylamino moiety absent → lower N-dealkylation and β-ketone reduction ratios vs. Group 2

**Uralets et al. 2014 [Ref 3]** (Journal of Analytical Toxicology, PMID 24668489):
- Ethylone detected in US urine specimens (2011–2013) from 34,561 specimens screened
- **Methylenedioxy-substituted cathinones metabolize by carbonyl reduction to a much lesser extent** than non-MDxx cathinones
- Best detected as **unchanged parent compound** in the free urine fraction
- Each cathinone exhibits a characteristic metabolic profile

**Meyer & Maurer 2010 [Ref 5]** (Current Drug Metabolism, PMID 20540700):
- Early review explicitly mentions ethylone (bk-MDEA) by name
- CYP and MAO isoenzyme involvement reviewed for the cathinone class; specific CYP enzymes responsible for ethylone N-dealkylation are **not individually characterized** in this or subsequent published literature

**Stability:** Ethylone (as a methylenedioxy-substituted cathinone) shows **higher degradation resistance** in biological matrices compared to non-methylenedioxy cathinones (Aldubayyan et al. 2021 [Ref 23]). Acidification of samples to pH <4 significantly improves stability.

---

## History

**Origin of the compound class:** Methylone (3,4-methylenedioxy-N-methylcathinone, the N-methyl analog of ethylone) was first synthesized by Peyton Jacob III and Alexander Shulgin in the mid-1990s (Baumann et al. 2012 [Ref 9] — Shulgin is listed as a co-author, the paper references prior work). The related non-beta-keto compound MDEA (3,4-methylenedioxy-N-ethylamphetamine) appears in Shulgin's PIHKAL (1991), establishing the N-ethyl methylenedioxyphenethylamine scaffold.

**First synthesis of ethylone specifically:** No peer-reviewed publication describing the original synthesis of ethylone was found. The compound is structurally analogous to methylone with the N-methyl replaced by N-ethyl. Its appearance in drug market literature precedes controlled pharmacological studies.

**Market emergence:** Ethylone began appearing as a designer drug in the United States approximately in late 2011 (ADF [Ref 22]; corroborated by Uralets et al. 2014 [Ref 3] who found it in US urine specimens from February 2011). The earliest published scientific review explicitly mentioning ethylone by the names bk-MDEA and 2-ethylamino-1-(3,4-methylenedioxyphenyl)propan-1-one is Meyer & Maurer 2010 [Ref 5], suggesting the compound was already in circulation by at least 2009–2010.

**Regulatory history:**
- Pre-2020 (US): Ethylone was implicitly controlled in the US as a positional isomer of butylone (Schedule I) under the Controlled Substances Act analog provisions
- **March 2017:** Ethylone added to **Schedule II of the 1971 UN Convention on Psychotropic Substances** at the 60th Session of the Commission on Narcotic Drugs (UNODC [Ref 21])
- **June 8, 2020:** DEA published final rule establishing **specific Schedule I listing** for ethylone with CSA code 7547 (Federal Register Document 2020-10295 [Ref 20])
- **2010 (UK):** All substituted cathinones, including ethylone, controlled as **Class B** substances under the Misuse of Drugs Act 1971
- **2014 (Australia):** Ethylone controlled under state-based legislation across multiple Australian states (ADF [Ref 22]; ODC listed [web source])
- **WADA:** Synthetic cathinones including ethylone classified as "specified stimulants," prohibited in sport

---

## Subjective Effects

No published controlled human studies on ethylone's subjective effects exist. The following is synthesized from class pharmacology and the published characterization of structural analogs.

**From ADF [Ref 22] (consumer-facing source, citing published literature):**
- Euphoria, increased energy, heightened sensory perception, enhanced sociability
- Physical: elevated blood pressure, dilated pupils, reduced appetite, jaw clenching (bruxism)
- Duration: up to 4 hours

**From pharmacological profile (Simmler 2012 [Ref 1]; Eshleman 2017 [Ref 2]):**
The dual mechanism — DAT/NET uptake inhibition + SERT-mediated 5-HT release — predicts:
- **Stimulant domain:** Increased energy, wakefulness, locomotion, reduced appetite (DA/NE-mediated)
- **Entactogenic/empathogenic domain:** Enhanced emotional openness, empathy, sociability, sensory enhancement, increased libido (5-HT-mediated)
- **Music enhancement:** Expected from serotonergic entactogen class (analogous to MDMA)
- **Bruxism:** Consistent with serotonin + norepinephrine release (class effect of entactogens)

**Effect taxonomy from brief (unverified by primary sources):** The DB lists the following effects — cognitive (fatigue, thought deceleration, motivation suppression, thought acceleration, analysis enhancement), perceptual (touch enhancement, visual haze, music enhancement), and physical (stimulation, bruxism, abnormal heartbeat, sexual arousal enhancement, temperature dysregulation, wakefulness). These are consistent with the pharmacological profile but are not individually confirmed in controlled ethylone studies.

> 🚩 **FLAG:** All subjective effect data for ethylone is inferred from pharmacological mechanism and structural analog data. No controlled human dosing studies exist.

---

## Safety & Toxicity

### LD₅₀ / Toxic Dose

**No LD₅₀ data published for ethylone in any species.** No animal toxicology studies specific to ethylone were found. The brief's notation that "exact toxic dosage is unknown" is confirmed.

### Case Reports

**No ethylone-specific overdose or fatality case reports were found in PubMed or OpenAlex.** This is consistent with ethylone's status as a less-prevalent synthetic cathinone compared to methylone, MDPV, and mephedrone, which dominate the toxicological literature.

### Class-Level Toxicity

From the synthetic cathinone class literature (Prosser & Nelson 2011 [Ref 6]; Debruyne et al. 2014 [Ref 7]; Luethi & Liechti 2020 [Ref 12]; Weinstein et al. 2017 [Ref 24]):

**Cardiovascular:**
- Tachycardia, hypertension (sympathomimetic from DAT/NET inhibition)
- Irregular heartbeat reported (ADF [Ref 22])
- Rare: myocardial infarction reported with cathinone class (Luethi & Liechti 2020 [Ref 12])

**Neurological/Psychiatric:**
- Agitation, anxiety, paranoia, psychosis, hallucinations (high doses)
- Seizures documented with cathinone class
- Acute psychosis, hypomania, paranoid ideation at high doses or with chronic use (Weinstein et al. 2017 [Ref 24])

**Serotonergic toxicity (high doses):**
- Hyperthermia, metabolic acidosis, rhabdomyolysis
- "Severe toxicity signs compatible with excessive serotonin activity" (Debruyne et al. 2014 [Ref 7])
- Serotonin syndrome risk with concurrent serotonergic agents

**Specific ADF report [Ref 22]:** Overdose symptoms include severe headache, irregular heartbeat, hyperthermia, dehydration, nausea, agitation, anxiety, hallucinations, psychosis, seizures. "Ethylone can cause death."

**After-effects (comedown):** Anxiety, fatigue, insomnia, depression, irritability in subsequent days (ADF [Ref 22]).

### Organ Toxicity

No published organ toxicity data specific to ethylone. For the cathinone class: liver, kidney, and cardiovascular toxicity documented in case reports with other agents (notably MDPV).

### Psychological Risks

Chronic cathinone use can induce persistent psychosis, paranoid ideation, and delusions, particularly with high-potency DAT-selective agents (Weinstein et al. 2017 [Ref 24]). For ethylone (SERT-dominant profile), persistent serotonergic effects are the primary psychiatric risk rather than dopamine-driven stimulant psychosis, though this is class-based inference.

---

## Harm Reduction

### Testing

No colorimetric reagent testing protocol specific to ethylone was found in published literature. Forensic analytical confirmation requires:
- **GC-MS:** Validated method available (Nisbet et al. 2019 [Ref 15]; Glicksberg et al. 2016 [Ref 13])
- **LC-Q/TOF or LC-MS/MS:** Validated methods (Glicksberg et al. 2016 [Ref 13]; Mercolini et al. 2016 [Ref 14])

### Contraindications (Evidence-Based)

1. **Tramadol:** AVOID — dual SERT inhibition + SERT release creates additive serotonergic load; mechanism for serotonin syndrome confirmed (Baldo 2018 [Ref 18]; Roulet et al. 2021 [Ref 19])
2. **MAOIs:** CONTRAINDICATED by class pharmacology (all serotonin-releasing agents contraindicated with MAOIs)
3. **SSRIs/SNRIs:** Serotonin syndrome risk by class mechanism
4. **MDMA or other serotonergic entactogens:** Combined serotonergic burden; hyperthermia risk
5. **Cardiovascular conditions:** Contraindicated; tachycardia and hypertension are class effects
6. **History of psychosis:** Contraindicated; psychotomimetic effects documented for the class

### General Harm Reduction Principles

From the cathinone class literature (Debruyne et al. 2014 [Ref 7]; Luethi & Liechti 2020 [Ref 12]):
- No specific antidote exists; management of overdose is supportive (extrapolated from cocaine/amphetamine protocols)
- Hydration critical (dehydration documented in ADF [Ref 22]) but avoid excessive water intake (hyponatremia risk in serotonin-releasing entactogens is a class concern)
- Temperature monitoring important (hyperthermia risk)
- Emergency response: cooling measures, benzodiazepines for agitation/seizures, supportive cardiovascular management

---

## Tolerance & Dependence

### Tolerance

**No published ethylone-specific tolerance data found.** The brief states tolerance develops with prolonged and repeated use, with a half-life of 5 days and full reset at ~1.5 weeks. These values cannot be verified against published primary sources and appear to be extrapolated from MDMA or stimulant class data.

> 🚩 **FLAG:** Tolerance half-life (5 days) and full reset (1.5 weeks) are unverified against published sources for ethylone. Cross-tolerance with dopamine and stimulant class is pharmacologically plausible but not specifically studied.

The brief's cross-tolerance listing (dopamine, stimulant) is consistent with the cathinone pharmacological class (all cathinones share DAT/NET activity) but is class-level inference, not ethylone-specific data.

### Dependence

**No controlled dependence studies for ethylone found.** The brief notes moderate physical and psychological dependence with high abuse potential.

From class data:
- Animal self-administration: Structural analogs (methylone, butylone, pentylone) are robustly self-administered (Dolan et al. 2018 [Ref 11])
- DAT/SERT ratio predicts: ethylone has **lower reinforcing effectiveness than DAT-selective cathinones** (MDPV, alpha-PVP) but retains abuse potential (Gannon et al. 2018 [Ref 16])
- "The predominant action of all cathinones on the DA transporter is probably associated with a considerable risk of addiction" (Simmler et al. 2012 [Ref 1])

> 🚩 **FLAG:** The brief's physical dependence rating (moderate) is not supported by direct published evidence for ethylone. The high potential for abuse claim is reasonable but based on class inference. A generation agent should soften or qualify these claims.

---

## Interactions

### Tramadol — Lethal (Seed Data Rating)

**Mechanism confirmed [Refs 18, 19]:** Tramadol inhibits human SERT (confirmed in HEK293 cells transfected with human SERT, Baldo 2018 [Ref 18]; Roulet et al. 2021 [Ref 19]). Ethylone functions as a SERT-selective substrate/releaser (Eshleman 2017 [Ref 2]). Combined: dual serotonergic load → serotonin syndrome pathway. The FDA issued a Drug Safety Communication in 2016 on opioid-serotonin syndrome risk.

> **Assessment:** The pharmacological basis for a dangerous interaction is well-supported. The "lethal" severity rating in the DB is plausible by mechanism but no ethylone+tramadol case reports were found in the literature to confirm lethality specifically. The severity classification should be retained but flagged as mechanistically-derived, not case-report-confirmed.

### MDMA — Dangerous (Seed Data Rating)

**Mechanism:** Both MDMA and ethylone are SERT-selective releasers/inhibitors. Combined use creates additive or synergistic serotonergic burden — elevated risk of serotonin syndrome, hyperthermia, hyponatremia. This is a well-established pharmacological concern for combining serotonergic entactogens.

> **Assessment:** Rating supported by pharmacological mechanism. No ethylone+MDMA-specific case reports found.

### Alcohol — Unknown (Seed Data Rating)

No published data on ethylone+alcohol combination found. General class reasoning suggests alcohol may mask perceived stimulant effects, increasing risk of dose escalation, while the combined cardiovascular stress (ethylone: tachycardia + alcohol: vasodilatation/cardiac effects) may be unpredictable. Rating of "unknown" is appropriate given absence of published data.

---

## Legal Status

| Jurisdiction | Status | Effective Date | Notes |
|---|---|---|---|
| **United States** | Schedule I (CSA) | June 8, 2020 | Specific listing; CSA code 7547. Previously implicitly controlled as butylone positional isomer [Ref 20] |
| **International (UN)** | Schedule II — 1971 Convention on Psychotropic Substances | March 2017 | Added at 60th CND Session [Ref 21] |
| **United Kingdom** | Class B — Misuse of Drugs Act 1971 | 2010 | All cathinones controlled 2010 |
| **Australia** | Controlled substance | 2014+ | State-based legislation; ODC listed; state bans in QLD, NSW, SA, VIC [Ref 22] |
| **WADA** | Specified stimulant | — | Banned in sport; cathinone class |

> **Note on prior US status:** Before the June 2020 specific listing, ethylone was arguably already controlled under the Federal Analog Act (structurally similar to butylone, a Schedule I substance) and possibly as a "positional isomer" under existing cathinone scheduling. The 2020 action formalized and clarified this status.

---

## Clinical Trials

**No clinical trials found for ethylone** (ClinicalTrials.gov search returned zero results). Ethylone has no established medical use and has not been studied in clinical trial settings.

---

## Community Feedback Analysis

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

---

## Gaps & Flags

### Critical Data Gaps

1. **No human pharmacokinetic data:** No Tmax, t₁/₂, bioavailability, volume of distribution, or plasma protein binding published for ethylone in humans. All PK values must be inferred from methylone analog data (Elmore et al. 2017 [Ref 17]).

2. **No ethylone-specific case reports of overdose or fatality:** Class-based toxicology must be used. Specific toxic dose and LD₅₀ are completely unknown.

3. **No ethylone-specific controlled human studies:** No dose-escalation studies, no blinded crossover trials, no pharmacodynamic studies in humans. The subjective effect profile is entirely mechanistically and analogically derived.

4. **No binding Ki values in abstract:** Simmler 2012 [Ref 1] reported IC₅₀ values for ethylone at DAT, NET, and SERT but these were not available in the abstract. Full-text access to the Simmler paper is needed to extract exact potency values.

5. **No ethylone-specific enantiomer studies:** Whether the R or S enantiomer dominates at DAT vs. SERT is unknown for this specific compound.

6. **SMILES not returned by PubChem API:** SMILES string for ethylone (CID 57252245) is derivable from IUPAC name: `CCNC(C)C(=O)c1ccc2c(c1)OCO2`. This should be confirmed against the PubChem full record.

7. **Synthesis history unverified:** No primary publication describing the first synthesis of ethylone specifically was found. The compound likely emerged from analog synthesis of methylone (Jacob & Shulgin) but this is not confirmed in a citable source.

8. **No physical properties (melting point, solubility):** No published melting point, solubility, or pKa data for ethylone found.

### Safety-Critical Flags

> 🚩 **Dose ranges (Threshold 75mg – Heavy 325+mg) are unverified.** No published clinical or controlled study has established dose ranges for ethylone in humans. The seed data appears to be user-report-derived (likely from community reports). These values are plausible given methylone's dose range (~100-200mg common) and ethylone being slightly less potent per structural analog inference, but they cannot be verified against a primary source. FLAG for editorial review.

> 🚩 **Tolerance half-life (5 days) and full reset (1.5 weeks) are not verifiable** against published data for ethylone. These values appear to be extrapolated from MDMA or similar entactogen class data.

> 🚩 **Tramadol "lethal" interaction:** Mechanistically well-supported (SERT inhibitor + SERT releaser = serotonin syndrome), but no ethylone+tramadol fatality case reports were found. The "lethal" classification is a reasonable precautionary rating based on mechanism and class experience with serotonin syndrome fatalities.

> 🚩 **Physical dependence (moderate) and psychological dependence (moderate):** Not directly studied for ethylone. Ratings are class-level inference from structural analog self-administration data and cathinone class literature.

> 🚩 **No specific contraindications in DB:** The brief lists no contraindications. Based on pharmacological profile, the following should be considered for the article: MAOIs (contraindicated by mechanism), SSRIs/SNRIs (serotonin syndrome risk), cardiovascular disease, history of psychosis, tramadol (already listed as lethal interaction).

### Contradictions Between Seed Data and Published Sources

- **PubChem CID, formula, weight, InChIKey are empty in DB but confirmed from PubChem:** These should be updated to the confirmed values.
- **Pharmacological class in DB:** Lists "Monoamine releasing agent, Dopamine releasing agent, Norepinephrine releasing agent, Serotonin releasing agent." The published evidence (Eshleman 2017 [Ref 2]) shows ethylone is a **substrate-type releaser specifically at SERT** (not at DAT or hNET), while the DA/NE effects come primarily from **uptake inhibition** rather than substrate-mediated release. The classification should distinguish these mechanisms: "Non-selective monoamine reuptake inhibitor; selective serotonin releasing agent."

---

*Research compiled: 2026-04-26. Generation provenance: cfaa9278-b82e-4be3-918b-f58495e43592.*
*24 citations verified and registered. No community feedback items to evaluate.*