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psx:substance/4-cmc/value/dose_tier/heavy@1

valuereferenced by edges — no row of its own

derived from · upstream

  • derived_fromdose_tier · heavypsx:substance/4-cmc/proposal/dose_tier/39e88f22-0051-4916-b295-828234a50755

feeds · downstream

none recorded

Closure of psx:substance/4-cmc/value/dose_tier/heavy@1: 1 upstream, 0 downstream.

psx:substance/4-cmc/value/dose_tier/heavy@1
└─ derived_from  proposal/dose_tier/39e88f22-0051-4916-b295-828234a50755  dose_tier · heavy

indented by distance from this node, not by parentage

1Provenance card

the boundary, as counts

Sources

2725 with DOI

2 strong · 18 moderate · 7 weak

Compilations

12026-05-08T20:18:06.522Z

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

Decisions

30last ruled 2026-06-04

0 awaiting a ruling

Issued documents

42026-10-19T20:29:53.184Z

notice · info card · emergency

Searches

241 with no results

queries and counts on the build

Claims checked

9274 supported

74 supported · 18 not

Correspondence

0received

consent field ships in Phase 4

Edges

278

derivations recorded for this entity

Complete over 27 sources, 1 compilation, and 30 decisions.Not here: the private journal (never).Working material — drafts, discards, unsupported claims — is listed below and readable on the working page.Cite: psychedex.org/substances/4-cmc/archive

2Build

one panel per compilation run

generation run 2026-05-08

65 min completedmodel pipeline-v5plan not recordedrun/096abe08…

Selection

results seen116
selected by the model44
consumed as sources27

Verification

claims checked92
supported71
partially supported3
not supported4
inconclusive14
  • record
  • seen / partial
  • working

The model's own caveats

9 further caveats recorded as free text — readable on the working page

Reproduce

inputs
27 source keys (listed under Sources)
plan
not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
model
pipeline-v5
streams
none — agent transcripts are persisted from 2026-09 onward
24 searches — query, source, results, what was kept and why
24 searches for this run
#sourcequeryseenkeptrationale
1OpenAlexsynthetic cathinone monoamine transporter substrate releaser (citations sort)82Foundational pharmacology papers for cathinone class, provides context for 4-CMC mechanism
2ClinicalTrials.gov · absenceclephedrone 4-CMC synthetic cathinone00No results - absence of trials is itself a finding
3PubChemclephedrone11Primary chemical identity confirmation
4PubMedPMID 41515970 - Poyatos et al. IJMS 202511Only controlled human study of clephedrone effects and PK
5PubMed4-CMC cathinone synthetic stimulant114Additional relevant papers on behavioral pharmacology, stability, and detection
6PubMed/OpenAlexPMID 29963211 - Tomczak et al. Forensic Toxicology 201811Only forensic blood concentration dataset for 4-CMC with case data
7PubMedclephedrone 4-chloromethcathinone pharmacology1414All directly relevant to 4-CMC pharmacology, toxicology, metabolism, or detection
8PubMedPMID 36669877 - Chojnacki et al. JPET 202311Key pharmacology paper with transporter data
9OpenAlex4-chloromethcathinone clephedrone pharmacology (citations sort)103High-citation review and forensic case data directly relevant to 4-CMC
10PubMedPMID 28657185 - Grifell et al. Human Psychopharmacology 201711Early systematic review of 4-CMC patterns and toxicity
11WebSearch4-CMC clephedrone harm reduction drug checking testing101Harm reduction context for adulteration risk
12PubMedPMID 25280452 Taschwer 201411First literature description of clephedrone
13PubMedPMID 37033613 Lopes 2023 metabolic stability cathinones11Key pharmacokinetic classification of 4-CMC clearance
14WebSearch4-chloromethcathinone first appearance drug market 2014 EMCDDA Europe seizures101Establishes historical first appearance
15WebSearchclephedrone 4-CMC legal status scheduling UK US EU controlled substance 2026103Core legal status data for major jurisdictions
16PubMedPMID 37698450 postmortem chloromethcathinone isomers11Largest postmortem case series for CMC isomers
17WebFetch / PMCExtract specific EC50, Ki values for 4-CMC transporter assays11Critical quantitative pharmacology data
18WebSearchDEA Schedule I 4-chloromethcathinone 4-CMC effective date 2025 Federal Register101Definitive US scheduling date and justification
19WebSearchclephedrone 4-CMC Australia Canada controlled substance scheduling102Australia confirmed; Canada unclear
20PubMedPMID 31425490 Contrucci 2020 cathinone drug interactions11Drug interaction profile for synthetic cathinone class
21WebFetchSpecific EC50 and transporter data for 4-CMC11Critical quantitative pharmacology data for article
22MultipleCross-reference pharmacological mechanism, seizure data, and legal status10Consistency check across sources
23WebSearchDEA Schedule I 4-chloromethcathinone 4-CMC effective date 2025 Federal Register101Definitive US scheduling confirmation
24WebFetchDosage, duration, subjective effects, harm reduction for 4-CMC11Only user-report harm reduction data found for onset timing; labeled web_retrieved/low confidence
92 claims by section — every cited sentence, checked against its source
safety30 · 26 ok
  • Claim in safety — inconclusiveinconclusiveworking →

  • Jurowski published the first in silico toxicity assessment, which predicted significant acute toxicity with species-specific variability, moderate genotoxic potential (risk of DNA damage), and notable cardiotoxicity risk via hERG channel inhibitionsupported

    First in silico toxicity assessment of 4-CMC. Predicted significant acute toxicity, moderate genotoxic potential, notable cardiotoxicity risk via hERG channel inhibition. ijms25115867

  • Bassi et al. independently predicted drug-drug interaction potential and cardiotoxicity for CMC compounds including 4-CMC. All LD₅₀, genotoxicity, and hERG inhibition values are computational predictions only — no in vitro or in vivo confirmation has been published.supported

    ADMET prediction for 4-CMC compared to 3-CMC analogues. Drug-drug interaction potential and cardiotoxicity predicted for all CMC compounds. ijms262311600

  • Zhou et al. demonstrated cytotoxicity in SH-SY5Y human neuroblastoma cells: ATP depletion (IC₅₀ ~1.4 mM), decreased mitochondrial membrane potential, impaired electron transport chain function, increased reactive oxygen species (ROS), and induction of apoptosis via the endogenous (mitochondrial) pathwaysupported

    4-CMC is cytotoxic in SH-SY5Y cells (IC50 for ATP depletion ~1.4 mM). Decreases mitochondrial membrane potential, impairs electron transport chain, increases ROS, induces apoptosis via endogenous pathway. ijms21082841

  • The para-chloro substitution specifically increased toxicity compared to unsubstituted methcathinonesupported

    Para-chloro substitution increases neurotoxicity. ijms21082841

  • Critically, the cytotoxic concentration (~1.4 mM) substantially exceeds plasma concentrations observed in living users (1.3–75.3 ng/mL ≈ 0.007–0.38 µM) and even in fatalities (56.2–1870 ng/mL ≈ 0.28–9.5 µM)supported

    blood concentrations: nonfatal 1.3-75.3 ng/mL, fatalities 56.2-1870 ng/mL s11419-018-0427-8

  • Wojcieszak et al. found that 4-CMC cytotoxicity in SH-SY5Y cells emerged and intensified after prolonged incubation, suggesting an indirect mechanism unrelated to acute monoamine transporter interactions — potentially relevant to chronic or repeated-use toxicity.supported

    Cytotoxicity vs SH-SY5Y cells intensifies after prolonged incubation, suggesting indirect mechanism unrelated to monoamine transporters. s12640-020-00227-8

  • In telemetry-implanted rats, clephedrone produced blood pressure and heart rate elevation comparable to mephedrone at equivalent dosessupported

    Increased BP, HR, and locomotor activity to similar extent as mephedrone in rats. jpet.122.001478

  • In silico modeling predicts hERG channel inhibition, suggesting potential QT interval prolongation — though this prediction lacks experimental confirmationsupported

    notable cardiotoxicity risk via hERG channel inhibition. ijms25115867

  • Claim in safety — inconclusiveinconclusiveworking →

  • Trynda et al. demonstrated that clephedrone at forensically relevant concentrations (170 ng/mL and 2700 ng/mL) alters the surface charge density of erythrocyte and platelet membranessupported

    Clephedrone at 170 ng/mL and 2700 ng/mL alters surface charge density of erythrocyte and platelet membranes measured by microelectrophoresis. molecules31020234

  • Tomczak et al. reported forensic blood concentrations from 15 cases: non-fatal intoxications ranged from 1.3 to 75.3 ng/mL; fatalities ranged from 56.2 to 1870 ng/mLsupported

    15 forensic cases; blood concentrations: nonfatal 1.3-75.3 ng/mL, fatalities 56.2-1870 ng/mL s11419-018-0427-8

  • Romańczuk et al. examined 27 CMC-related deaths in Kraków, Poland (2016–2022), involving primarily 3-CMC and/or 4-CMC isomers. All published fatalities involved polydrug use; no clean 4-CMC monocause fatality has been confirmed in published literaturesupported

    27 CMC-related deaths in Kraków 2016-2022. Toxicological interpretation is challenging; unpredictable effects noted. bkad070

  • A fatal polydrug case reported by Nowak et al. involved 4-CMC alongside U-47700, N-ethylhexedrone, adinazolam, 4-CIC, and sertraline — U-47700 concentration (1470 ng/mL) was consistent with lethal opioid toxicity, and 4-CMC was not the proximate cause of death.supported

    Fatal polydrug intoxication (Poland 2017). Blood: 4-CMC 1.7 ng/mL, U-47700 1470 ng/mL. s11419-020-00568-1

  • Klavž et al. reported the first clinical identification of 4-CMC in Slovenia: a 38-year-old male presented after ingesting a mixture including AB-CHMINACA, AB-FUBINACA, alpha-PHP, alpha-PVP, and 4-CMC in a suicide attemptsupported

    Case report: 38-year-old male, non-fatal intoxication with 5 NPS including 4-CMC. First positive identification of these 5 drugs by a clinical laboratory in Slovenia. j.forsciint.2016.01.018

  • Claim in safety — inconclusiveinconclusiveworking →

  • Compulsive redosing is driven by the dopaminergic component (DAT release EC₅₀ = 91 nM). The compound's low clearance means each subsequent dose compounds existing plasma concentration, escalating both cardiovascular and psychological risksupported

    4-CMC is a LOW clearance compound (unlike most other cathinones which are intermediate clearance). fphar.2023.1145140

  • Sensitization rather than tolerance: Wojcieszak et al. found that 7-day intermittent 4-CMC treatment produced behavioral sensitization in DBA/2J mice — locomotor activity increased with repeated exposuresupported

    4-CMC increases locomotor activity and produces behavioral sensitization after 7-day intermittent treatment. s12640-021-00329-x

  • Conditioned place preference: 4-CMC produced no conditioned place preference in DBA/2J mice at tested doses, contrasting with the more dopamine-selective 4-MeO-PVPsupported

    4-CMC did NOT produce conditioned place preference (unlike 4-MeO-PVP). s12640-021-00329-x

  • Withdrawal: No significant withdrawal symptoms were detected in mice following 14-day intermittent treatment, as assessed by tail suspension test, forced swim test, and sucrose preference testsupported

    No significant withdrawal symptoms after 14-day treatment. s12640-021-00329-x

  • Abuse liability framework: The balanced DAT/SERT activity theoretically reduces abuse liability relative to purely dopamine-selective agents, though clephedrone's DAT release EC₅₀ of 91 nM is sufficient to produce robust reinforcement.supported

    DAT>SERT selectivity associated with high abuse potential. 7854_2016_18

  • Clephedrone releases large quantities of serotonin, dopamine, and norepinephrine; MAOIs prevent their metabolic degradation, producing potentially fatal monoamine accumulation.supported

    Serotonin syndrome risk with MAOIs and serotonergic medications. ftd.0000000000000682

  • Claim in safety — inconclusiveinconclusiveworking →

  • Opioids: While not a direct pharmacodynamic interaction with clephedrone's mechanism, the fatal case reported by Nowak et al. — involving U-47700 (a synthetic opioid) alongside 4-CMC — demonstrates the extreme fatality risk of stimulant-opioid polydrug combinations.supported

    Fatal polydrug intoxication (Poland 2017). Blood: 4-CMC 1.7 ng/mL, U-47700 1470 ng/mL. s11419-020-00568-1

  • Antihypertensives: Clephedrone's robust α₁-adrenergic-mediated hypertension may overcome antihypertensive medications, producing unpredictable blood pressure effects.supported

    Increased BP, HR, and locomotor activity to similar extent as mephedrone in rats. jpet.122.001478

  • Given its low-clearance classification, CYP inhibitors that further reduce clephedrone clearance could significantly increase plasma concentrations — a potentially dangerous interaction that cannot currently be predicted or quantified.supported

    4-CMC is a LOW clearance compound. Keto reduction and hydroxylation are main Phase I reactions; glucuronide conjugation as Phase II. fphar.2023.1145140

  • Concurrent MAOI therapy (including moclobemide, phenelzine, tranylcypromine, selegiline at antidepressant doses) — risk of fatal serotonin syndrome and hypertensive crisissupported

    Serotonin syndrome risk with MAOIs and serotonergic medications; cardiovascular interactions with antihypertensives. ftd.0000000000000682

  • Severe cardiovascular disease (uncontrolled hypertension, recent myocardial infarction, decompensated heart failure, known arrhythmias) — clephedrone produces significant blood pressure and heart rate elevation with predicted hERG channel inhibitionsupported

    Increased BP, HR, and locomotor activity to similar extent as mephedrone in rats. jpet.122.001478

  • Severe cardiovascular disease (uncontrolled hypertension, recent myocardial infarction, decompensated heart failure, known arrhythmias) — clephedrone produces significant blood pressure and heart rate elevation with predicted hERG channel inhibitionsupported

    notable cardiotoxicity risk via hERG channel inhibition. ijms25115867

  • Hepatic impairment — low-clearance compound; impaired hepatic metabolism could produce dangerous accumulationsupported

    4-CMC is a LOW clearance compound. Keto reduction and hydroxylation are main Phase I reactions; glucuronide conjugation as Phase II. fphar.2023.1145140

pharmacokinetic-detail13 · 13 ok
  • Oral fluid concentration peaked within the first 3 hours after 100 mg oral dosing — a substantially delayed profile compared to methylone under similar conditionssupported

    delayed onset and peak compared to methylone. ijms27010089

  • Human pharmacokinetic data are limited to observational studies using oral doses of 100–150 mg in small cohortssupported

    Human observational study: 8 volunteers self-administered 100 or 150 mg oral clephedrone. Oral fluid PK data collected over 5 h. ijms27010089

  • Human pharmacokinetic data are limited to observational studies using oral doses of 100–150 mg in small cohortssupported

    4-CMC (100 mg oral) in 6 consumers. ijms24119387

  • Human pharmacokinetic data are limited to observational studies using oral doses of 100–150 mg in small cohortssupported

    4-CMC administered orally (100-150 mg) to volunteers. j.jpba.2024.115994

  • Oral fluid concentration peaked within the first 3 hours after 100 mg oral dosing — a substantially delayed profile compared to methylone under similar conditionssupported

    peak oral fluid concentration in first 3 hours. ijms24119387

  • No intranasal pharmacokinetic data exist for 4-CMC; intranasal data reported in the same studies pertain to N-ethylpentedrone and N-ethylhexedrone, not clephedrone.supported

    4-CMC administered orally (100-150 mg) to volunteers. j.jpba.2024.115994

  • No intranasal pharmacokinetic data exist for 4-CMC; intranasal data reported in the same studies pertain to N-ethylpentedrone and N-ethylhexedrone, not clephedrone.supported

    4-CMC (100 mg oral) in 6 consumers. ijms24119387

  • Berardinelli et al. conducted the most comprehensive metabolic profiling of clephedrone using human hepatocyte incubation combined with LC-HRMS/MS, validated against clinical and forensic urine samplessupported

    Identified 10 metabolites for 4-CMC via human hepatocyte incubation. s12248-024-00940-8

  • Massano et al. confirmed Phase I metabolites (ketoreduction, hydroxylation, dealkylation) and identified 4-CMC-glucuronide as a relevant Phase II metabolite in urinesupported

    Phase-I and glucuronide metabolites identified. 4-CMC detected at high concentrations in original form up to 5h post-administration. j.jpba.2024.115994

  • Lopes et al. identified ketoreduction and hydroxylation as common metabolic pathways, with glucuronic acid conjugation to ketoreduced metabolites as the sole Phase II transformation.supported

    Keto reduction and hydroxylation are main Phase I reactions; glucuronide conjugation as Phase II. fphar.2023.1145140

  • Lopes et al. formally classified 4-CMC as a low-clearance compound based on human hepatocyte incubation — distinct from the intermediate-clearance classification of most other synthetic cathinones studiedsupported

    4-CMC is a LOW clearance compound (unlike most other cathinones which are intermediate clearance). fphar.2023.1145140

  • Romańczuk et al. detected dihydro-CMC in blood in all 27 CMC-related deaths examined, even when the parent compound was absent due to degradation.supported

    Stability problems in biological matrices; dihydro-CMC is better biomarker of intake. bkad070

  • Adamowicz documented degradation in blood and urine at room temperature and at +4°Cpartially supported

    Significant instability observed, particularly at room temperature. j.forsciint.2018.12.001

pharmacology13 · 12 ok
  • Chojnacki et al. characterized the transporter pharmacology in rat synaptosomes using both uptake inhibition and substrate release assayssupported

    4-CMC functions as substrate at DAT, NET, and SERT with potency similar to mephedrone. jpet.122.001478

  • The DAT/SERT release potency ratio of approximately 1.85:1 places clephedrone in an intermediate selectivity range: modestly dopamine-preferring relative to MDMA but substantially less DAT-selective than purely dopaminergic cathinones such as α-PVP.supported

    QSAR analysis of 4-substituted methcathinone series. DAT>SERT selectivity associated with high abuse potential. Volume of 4-position substituent is key determinant of DAT vs SERT selectivity. 7854_2016_18

  • As a β-keto amphetamine, clephedrone does not appear to be a TAAR1 (trace amine-associated receptor 1) ligand — a class distinction between cathinones and non-β-keto amphetaminessupported

    Cathinones not TAAR1 ligands. j.1476-5381.2012.02145.x

  • Claim in pharmacology — inconclusiveinconclusiveworking →

  • In telemetry-implanted rats, clephedrone (1, 3, and 10 mg/kg i.p.) produced dose-dependent cardiovascular and locomotor effects:supported

    Increased BP, HR, and locomotor activity to similar extent as mephedrone in rats. jpet.122.001478

  • Wojcieszak et al. confirmed dose-dependent horizontal locomotor stimulation in mice, with a locomotor profile consistent with monoamine releasing agents — enhanced horizontal but not vertical locomotion, contrasting with dopamine-selective cathinones.supported

    4-CMC stimulates horizontal locomotor activity in mice dose-dependently. s12640-020-00227-8

  • Human pharmacokinetic data for clephedrone derive from small observational studies using oral administration at 100–150 mgsupported

    Human observational study: 8 volunteers self-administered 100 or 150 mg oral clephedrone. ijms27010089

  • Human pharmacokinetic data for clephedrone derive from small observational studies using oral administration at 100–150 mgsupported

    4-CMC administered orally (100-150 mg) to volunteers; urine collected. j.jpba.2024.115994

  • Human pharmacokinetic data for clephedrone derive from small observational studies using oral administration at 100–150 mgsupported

    4-CMC (100 mg oral) in 6 consumers; peak oral fluid concentration in first 3 hours. ijms24119387

  • After 100 mg oral administration, 4-CMC reached maximum oral fluid concentration within the first 3 hours — substantially later than intranasally administered cathinones (NEP and NEH), which peaked within the first hoursupported

    4-CMC (100 mg oral) in 6 consumers; peak oral fluid concentration in first 3 hours. ijms24119387

  • High concentrations of unchanged parent compound persisted in urine 5 hours after oral administration, attributed to a long half-life and low intrinsic clearancesupported

    4-CMC detected at high concentrations in original form up to 5h post-administration, suggesting long half-life and low intrinsic clearance. j.jpba.2024.115994

  • Lopes et al. formally classified 4-CMC as a low-clearance compound using human hepatocyte incubation — in contrast to most other cathinones tested, which were classified as intermediate clearancesupported

    4-CMC is a LOW clearance compound (unlike most other cathinones which are intermediate clearance). fphar.2023.1145140

  • Approximately 0.3% of an orally administered dose was recovered in sweat over 4 hours.supported

    Excreted in sweat ~0.3% of administered dose. ijms24119387

summary12 · 6 ok
  • Claim in summary — not_supportednot supportedworking →

  • Claim in summary — not_supportednot supportedworking →

  • Clephedrone (4-chloromethcathinone, 4-CMC) is a synthetic substituted cathinone and non-selective monoamine releasing agent that acts as a full substrate at the dopamine, norepinephrine, and serotonin transporters with potency virtually identical to mephedronesupported

    4-CMC functions as substrate at DAT, NET, and SERT with potency similar to mephedrone. jpet.122.001478

  • Claim in summary — inconclusiveinconclusiveworking →

  • First characterized in 2014 from a commercially available online research chemical sample, clephedrone rapidly became one of the most frequently seized synthetic cathinones in Europe by the mid-2020spartially supported

    First characterization of clephedrone. Confirmed identity by GC-MS and NMR. Sold via Internet from deboralabs.com. j.forsciint.2014.09.007

  • Claim in summary — inconclusiveinconclusiveworking →

  • Claim in summary — inconclusiveinconclusiveworking →

  • Subjective effects have been broadly described as stimulant-like in the single controlled human observation, with pharmacological modeling predicting both psychostimulant and empathogenic qualities based on the balanced monoamine release profile.supported

    Stimulant-like subjective effects; delayed onset and peak compared to methylone. ijms27010089

  • Claim in summary — inconclusiveinconclusiveworking →

  • No in vivo LD₅₀ data exist; in silico modeling predicts significant acute toxicity and hERG channel inhibitionsupported

    First in silico toxicity assessment of 4-CMC. Predicted significant acute toxicity, moderate genotoxic potential, notable cardiotoxicity risk via hERG channel inhibition. ijms25115867

  • All published fatalities involving clephedrone are polydrug cases, and forensic blood concentrations in non-fatal and fatal cases overlap substantially (1.3–75.3 ng/mL vs 56.2–1870 ng/mL), precluding any concentration-based lethality thresholdsupported

    15 forensic cases; blood concentrations: nonfatal 1.3-75.3 ng/mL, fatalities 56.2-1870 ng/mL s11419-018-0427-8

  • The compound's low intrinsic clearance raises the risk of accumulation with repeated dosingsupported

    4-CMC is a LOW clearance compound (unlike most other cathinones which are intermediate clearance). fphar.2023.1145140

chemistry6 · 3 ok
  • Claim in chemistry — inconclusiveinconclusiveworking →

  • Within the quantitative structure-activity framework established for 4-substituted methcathinones, the chloro substituent — a large, moderately electronegative halogen — produces a balanced DAT/SERT selectivity profile intermediate between the fluorine analogue (flephedrone, SERT-preferring) and the methyl analogue (mephedrone, slightly DAT-preferring).supported

    Volume of 4-position substituent is key determinant of DAT vs SERT selectivity. 7854_2016_18

  • Claim in chemistry — inconclusiveinconclusiveworking →

  • Commercially available material is a racemic mixture, as confirmed by Taschwer et al. using enantioselective gas chromatography and capillary electrophoresissupported

    Racemic mixture confirmed; chiral separation by GC and CE developed. j.forsciint.2014.09.007

  • Claim in chemistry — inconclusiveinconclusiveworking →

  • The compound is notably unstable in biological matrices: degradation occurs at room temperature and even at +4°C over extended storage periodspartially supported

    Significant instability observed, particularly at room temperature. j.forsciint.2018.12.001

history6 · 4 ok
  • Clephedrone was first described in the scientific literature in 2014 by Taschwer et al. at Karl-Franzens-University Graz, who characterized a commercially available sample obtained from an online vendorsupported

    First characterization of clephedrone. Confirmed identity by GC-MS and NMR. Sold via Internet from deboralabs.com. j.forsciint.2014.09.007

  • The compound was first detected on the European drug market in June 2014, placing it among a wave of para-halogenated cathinones that emerged following the scheduling of earlier cathinones — particularly mephedrone and flephedrone — in several European jurisdictions.supported

    Systematic review of clephedrone (4-CMC), 4-CEC, and 4-BMC on recreational drug markets. Analysis of market samples and available information on these para-halogenated cathinones. hup.2621

  • Majchrzak et al. identified 4-CMC as part of a broader wave of ring-substituted methcathinone analogues designed to circumvent scheduling laws during 2014–2017supported

    Review of new synthetic cathinones 2014-2017. Para-substituted methcathinone derivatives including 4-CMC discussed. s11419-017-0385-6

  • Claim in history — not_supportednot supportedworking →

  • Spanish drug checking services (Energy Control) identified clephedrone in 29 samples between 2014 and 2016, often sold misrepresented as 3-MMC, MDMA, ketamine, or other cathinonessupported

    Systematic review of clephedrone (4-CMC), 4-CEC, and 4-BMC on recreational drug markets. Analysis of market samples. hup.2621

  • Claim in history — not_supportednot supportedworking →

neuroscience5 · 3 ok
  • What is the dose-response relationship for cardiovascular toxicity in humans? Animal data confirm dose-dependent hypertension and tachycardia, but no human dose-response data exist for any cardiovascular endpoint.supported

    Increased BP, HR, and locomotor activity to similar extent as mephedrone in rats. jpet.122.001478

  • Claim in neuroscience — inconclusiveinconclusiveworking →

  • Claim in neuroscience — inconclusiveinconclusiveworking →

  • The absence of conditioned place preference in DBA/2J mice is consistent with this framework, though species-specific factors limit extrapolation.supported

    4-CMC did NOT produce conditioned place preference (unlike 4-MeO-PVP). s12640-021-00329-x

  • The low-clearance profile of clephedrone may extend both the acute pharmacodynamic window and the subsequent recovery phase relative to faster-metabolized cathinones.supported

    4-CMC is a LOW clearance compound (unlike most other cathinones which are intermediate clearance). fphar.2023.1145140

comparative-pharmacology3 · 3 ok
  • Clephedrone and mephedrone differ by a single structural modification — chlorine versus methyl at the para-position of the phenyl ring — and display virtually identical transporter potency in the same assay system:supported

    4-CMC functions as substrate at DAT, NET, and SERT with potency similar to mephedrone. jpet.122.001478

  • Cardiovascular effects (blood pressure and heart rate elevation) in telemetry-implanted rats were comparable between the two compounds at equivalent dosessupported

    Increased BP, HR, and locomotor activity to similar extent as mephedrone in rats. jpet.122.001478

  • Negus and Banks established a quantitative structure-activity relationship (QSAR) framework demonstrating that the volume and electronic character of the para-substituent on 4-substituted methcathinones determines the DAT/SERT selectivity ratio and, consequently, abuse potentialsupported

    QSAR analysis of 4-substituted methcathinone series. DAT>SERT selectivity associated with high abuse potential. Volume of 4-position substituent is key determinant of DAT vs SERT selectivity. 7854_2016_18

effects-overview2 · 2 ok
  • Pharmacologically, clephedrone is the nearest analogue to mephedrone among widely circulated synthetic cathinones — near-identical transporter potency but slower metabolic clearancesupported

    4-CMC functions as substrate at DAT, NET, and SERT with potency similar to mephedrone. jpet.122.001478

  • Pharmacologically, clephedrone is the nearest analogue to mephedrone among widely circulated synthetic cathinones — near-identical transporter potency but slower metabolic clearancesupported

    4-CMC is a LOW clearance compound (unlike most other cathinones which are intermediate clearance). fphar.2023.1145140

clinical-evidence1 · 1 ok
  • The sole controlled human pharmacological study was an observational investigation in which 8 healthy volunteers (6 women) self-administered a single oral dose of 100 or 150 mg, with oral fluid sampling and vital sign monitoring over 5 hourssupported

    Human observational study: 8 volunteers self-administered 100 or 150 mg oral clephedrone. Oral fluid PK data collected over 5 h. ijms27010089

receptor-pharmacology1 · 1 ok
  • The definitive quantitative dataset for clephedrone's transporter interactions was established by Chojnacki et al. in rat synaptosomes:supported

    4-CMC functions as substrate at DAT, NET, and SERT with potency similar to mephedrone. jpet.122.001478

3Sources

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

Sources
yearsourcetierstatusfeeds
2026The Effect of Selected Cathinones on Natural Cell Membranes: Microelectrophoretic Methods.Trynda A, Karwowska K, Karpowicz W, Kazimierska-Drobny K, Petelska AD · Moleculesdoi:10.3390/molecules31020234moderateconsumed1 section
20253-CMC: Acute Effects in Male and Female Mice, Human Intoxication Case Series (Italy, 2014-2025), and Prediction of ADMET Properties.Bassi M, Roda E, Corli G, Bilel S, De Luca F, Bernardi T, Gregori A, Di Rosa F, Lonati D, Locatelli CA, Marti M · International Journal of Molecular Sciencesdoi:10.3390/ijms262311600weakconsumed1 section
2025Oral Fluid Concentrations and Pharmacological Effects of Clephedrone and Methylone in Humans.Poyatos L, Núñez-Montero M, Hladun O, Rosa G, Martín S, Videla S, Martínez-Couselo S, Ventura M, La Maida N, Trana AD, Busardò FP, Torrens M, Pichini S, Pérez-Maña C, Farré M, Papaseit E · International Journal of Molecular Sciencesdoi:10.3390/ijms27010089moderateconsumed5 sections
2025Schedules of Controlled Substances: Placement of 4-Chloromethcathinone in Schedule IDrug Enforcement Administration (DEA) · Federal Registerurl:67f2b33ce280dc06weakconsumedcited only
20243-CMC, 4-CMC, and 4-BMC Human Metabolic Profiling: New Major Pathways to Document Consumption of Methcathinone Analogues?Berardinelli D, Taoussi O, Daziani G, Tavoletta F, Ricci G, Tronconi LP, Adamowicz P, Busardò FP, Carlier J · The AAPS journaldoi:10.1208/s12248-024-00940-8moderateconsumed3 sections
2024Challenges encountered in the enantioselective analysis of new psychoactive substances exemplified by clephedrone (4-CMC).Jorbenadze S, Khatiashvili T, Giunashvili L, Tchelidze A, Lo Faro AF, Pichini S, Farré M, Papaseit E, Nuñez-Montero M, Carlier J, Farkas T, Busardo FP, Chankvetadze B · Journal of Pharmaceutical and Biomedical Analysisdoi:10.1016/j.jpba.2024.116275moderateconsumedcited only
2024Metabolic profile of N-ethylhexedrone, N-ethylpentedrone, and 4-chloromethcathinone in urine samples by UHPLC-QTOF-HRMS.Massano M, Nuñez-Montero M, Papaseit E, Hladun O, Pérez-Mañá C, Ventura M, Marchei E, Alladio E, Gerace E, Pichini S, Farré M, Salomone A · Journal of pharmaceutical and biomedical analysisdoi:10.1016/j.jpba.2024.115994moderateconsumed2 sections
2024Toxicity of the New Psychoactive Substance (NPS) Clephedrone (4-Chloromethcathinone, 4-CMC): Prediction of Toxicity Using In Silico Methods for Clinical and Forensic Purposes.Jurowski K, Niżnik Ł · International Journal of Molecular Sciencesdoi:10.3390/ijms25115867moderateconsumed2 sections
2023GC-MS/MS Determination of N-ethyl Pentedrone and N-ethyl Hexedrone in Oral Fluid and Sweat after Controlled AdministrationNuñez-Montero M, Lombroni C, Maida N, et al. · International journal of molecular sciencesdoi:10.3390/ijms24119387moderateconsumed2 sections
2023Interpretative problems due to the presence of chloromethcathinone isomers in the biological material from postmortem cases.Romańczuk A, Rojek S, Synowiec K, Maciów-Głąb M, Kula K · Journal of Analytical Toxicologydoi:10.1093/jat/bkad070weakconsumed2 sections
2023Metabolic stability and metabolite profiling of emerging synthetic cathinones.Lopes RP, Ferro RA, Milhazes M, Figueira M, Caldeira MJ, Antunes AMM, Gaspar H · Frontiers in Pharmacologydoi:10.3389/fphar.2023.1145140moderateconsumed6 sections
2023Neurochemical and Cardiovascular Effects of 4-Chloro Ring-Substituted Synthetic Cathinones in RatsChojnacki MR, Thorndike EB, Partilla JS, et al. · Journal of Pharmacology and Experimental Therapeuticsdoi:10.1124/jpet.122.001478moderateconsumed7 sections
2022Neuropsychopharmacology of Emerging Drugs of Abuse: meta- and para-Halogen-Ring-Substituted α-PVP ("flakka") Derivatives.Nadal-Gratacós N, Lleixà E, Gibert-Serramià M, Estrada-Tejedor R, Berzosa X, Batllori X, Pubill D, Camarasa J, Escubedo E, López-Arnau R · International Journal of Molecular Sciencesdoi:10.3390/ijms23042226moderateconsumedcited only
2021Behavioral Effects of 4-CMC and 4-MeO-PVP in DBA/2J Mice After Acute and Intermittent Administration and Following Withdrawal from Intermittent 14-Day Treatment.Wojcieszak J, Kuczyńska K, Zawilska JB · Neurotoxicity Researchdoi:10.1007/s12640-021-00329-xmoderateconsumed3 sections
2021Fatal intoxication with U-47700 in combination with other NPS (N-ethylhexedrone, adinazolam, 4-CIC, 4-CMC) confirmed by identification and quantification in autopsy specimens and evidences.Nowak K, Szpot P, Zawadzki M · Forensic Toxicologydoi:10.1007/s11419-020-00568-1weakconsumed1 section
2020Four Synthetic Cathinones: 3-Chloromethcathinone, 4-Chloromethcathinone, 4-Fluoro-α-Pyrrolidinopentiophenone, and 4-Methoxy-α-Pyrrolidinopentiophenone Produce Changes in the Spontaneous Locomotor Activity and Motor Performance in Mice with Varied Profiles.Wojcieszak J, Kuczyńska K, Zawilska JB · Neurotoxicity Researchdoi:10.1007/s12640-020-00227-8moderateconsumed2 sections
2020Para-Halogenation of Amphetamine and Methcathinone Increases the Mitochondrial Toxicity in Undifferentiated and Differentiated SH-SY5Y CellsZhou X, Bouitbir J, Liechti ME, Krähenbuhl S, Mancuso RV · International Journal of Molecular Sciencesdoi:10.3390/ijms21082841strongconsumed1 section
2020Substance Details 4-CMCUNODCurl:e4b08eeddfcad025weakconsumedcited only
2020Synthetic Cathinones and Their Potential Interactions with Prescription Drugs.Contrucci RR, Brunt TM, Inan F, Franssen EJF, Hondebrink L · Therapeutic Drug Monitoringdoi:10.1097/ftd.0000000000000682moderateconsumedcited only
2019Stability of synthetic cathinones in blood and urine.Adamowicz P, Malczyk A · Forensic Science Internationaldoi:10.1016/j.forsciint.2018.12.001moderateconsumed2 sections
2018Blood concentrations of a new psychoactive substance 4-chloromethcathinone (4-CMC) determined in 15 forensic cases.Tomczak E, Woźniak MK, Kata M, Wiergowski M, Szpiech B, Biziuk M · Forensic Toxicologydoi:10.1007/s11419-018-0427-8weakconsumed3 sections
2017Decoding the Structure of Abuse Potential for New Psychoactive Substances: Structure-Activity Relationships for Abuse-Related Effects of 4-Substituted Methcathinone Analogs.Negus SS, Banks ML · Current Topics in Behavioral Neurosciencesdoi:10.1007/7854_2016_18moderateconsumed5 sections
2017Patterns of use and toxicity of new para-halogenated substituted cathinones: 4-CMC (clephedrone), 4-CEC (4-chloroethcatinone) and 4-BMC (brephedrone).Grifell M, Ventura M, Carbón X, Quintana P, Galindo L, Palma Á, Fornis I, Gil C, Farre M, Torrens M · Human Psychopharmacologydoi:10.1002/hup.2621moderateconsumed1 section
2017The newest cathinone derivatives as designer drugs: an analytical and toxicological reviewMajchrzak M, Celinski R, Kus P, Kowalska T, Sajewicz M · Forensic Toxicologydoi:10.1007/s11419-017-0385-6strongconsumed1 section
2016Suicide attempt with a mix of synthetic cannabinoids and synthetic cathinones: Case report of non-fatal intoxication with AB-CHMINACA, AB-FUBINACA, alpha-PHP, alpha-PVP and 4-CMC.Klavž J, Gorenjak M, Marinšek M · Forensic Science Internationaldoi:10.1016/j.forsciint.2016.01.018weakconsumed1 section
2014Analysis and characterization of the novel psychoactive drug 4-chloromethcathinone (clephedrone).Taschwer M, Weiß JA, Kunert O, Schmid MG · Forensic Science Internationaldoi:10.1016/j.forsciint.2014.09.007moderateconsumed3 sections
2012Pharmacological characterization of designer cathinones in vitroSimmler LD, Buser TA, Donzelli M, et al. · British Journal of Pharmacologydoi:10.1111/j.1476-5381.2012.02145.xmoderateconsumed2 sections
—Searched ClinicalTrials.gov for "clephedrone 4-CMC synthetic cathinone" — no resultsabsenceno results—

4Docket

one filing per activity — decisions, correspondence, reports

  1. 0012026-05-08revisionRevision 1

    Initial LLM generation (v5 pipeline, wiki, prose phase)

    psx:substance/4-cmc/version/1
  2. 0022026-06-04proposal28 value proposals approved together

    one review action inferred from a shared reviewer and instant — the graph records one activity per proposal

    28 items in this filing

    • contraindication · cardiovascular
    • contraindication · other
    • contraindication · neurological
    • contraindication · hepatic
    • contraindication · pregnancy_breastfeeding
    • contraindication · psychiatric
    • dose_tier · threshold
    • dose_tier · light
    • dose_tier · common
    • dose_tier · strong
    • dose_tier · heavy
    • timeline · oral · onset
    • timeline · oral · come_up
    • timeline · oral · peak
    • timeline · oral · resolution
    • timeline · oral · afterglow
    • toxicity
    • dependence · full
    • withdrawal
    • tolerance
    • dosage · oral
    • duration · oral · onset
    • duration · oral · come_up
    • duration · oral · peak
    • duration · oral · offset
    • duration · oral · total
    • duration · oral · aftereffects
    psx:substance/4-cmc/proposal/contraindication/b011a6c8-6848-4376-82de-0b558e83c3bd
  3. 0032026-06-04publicationPublication — backfill

5Issued documents

what the notice, info card and emergency page said, by hash

Issued documents
documentcontent hashissuedfrom versionsuperseded
info_card7dd89065e7529a5836b0d1a4…2026-10-19 20:29Revision 1current
emergency58d3299a8754d788e3d74c0e…2026-09-04 04:27Revision 1current
info_card0a86e4803a6b2f4d5b0f4383…2026-09-04 04:27Revision 1superseded2026-10-19
noticee5c05948955df740b964a7dc…2026-09-04 04:27Revision 1current