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psx:substance/3-cmc/value/dose_tier/heavy@1

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derived from · upstream

  • derived_fromdose_tier · heavypsx:substance/3-cmc/proposal/dose_tier/442ba969-8465-4eed-aee3-1d4f5fffc36a

feeds · downstream

none recorded

Closure of psx:substance/3-cmc/value/dose_tier/heavy@1: 1 upstream, 0 downstream.

psx:substance/3-cmc/value/dose_tier/heavy@1
└─ derived_from  proposal/dose_tier/442ba969-8465-4eed-aee3-1d4f5fffc36a  dose_tier · heavy

indented by distance from this node, not by parentage

1Provenance card

the boundary, as counts

Sources

2921 with DOI

4 strong · 14 moderate · 11 weak

Compilations

12026-05-08T20:18:06.527Z

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

Decisions

44last ruled 2026-06-04

0 awaiting a ruling

Issued documents

42026-10-19T20:29:33.351Z

notice · info card · emergency

Searches

201 with no results

queries and counts on the build

Claims checked

8274 supported

74 supported · 8 not

Correspondence

0received

consent field ships in Phase 4

Edges

270

derivations recorded for this entity

Complete over 29 sources, 1 compilation, and 44 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/3-cmc/archive

2Build

one panel per compilation run

generation run 2026-05-08

63 min completedmodel pipeline-v5plan not recordedrun/366e18c7…

Selection

results seen87
selected by the model37
consumed as sources29

Verification

claims checked82
supported68
partially supported6
not supported0
inconclusive8
  • record
  • seen / partial
  • working

The model's own caveats

  • sparse_evidence
  • structural_inference
  • safety_data_unverified

Reproduce

inputs
29 source keys (listed under Sources)
plan
not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
model
pipeline-v5
streams
none — agent transcripts are persisted from 2026-09 onward
20 searches — query, source, results, what was kept and why
20 searches for this run
#sourcequeryseenkeptrationale
1PubMed3-chloromethcathinone metabolism metabolites urine blood11Duplicate of earlier find
2PubMedsynthetic cathinone chloromethcathinone pharmacology transporter11Directly relevant to chloro-substituted cathinone pharmacology; provides analogy context for 3-CMC
3PubMedmephedrone methcathinone cathinone monoamine releasing agent DAT SERT NET substrate11Provides SAR data for meta-substituted cathinones - structural analog context
4PubMed3-CMC 3-chloromethcathinone clophedrone pharmacology66All directly relevant to 3-CMC pharmacology, metabolism, toxicology
5ClinicalTrials.gov · absence3-CMC chloromethcathinone synthetic cathinone00No trials exist
6PubChem3-chloromethcathinone11Primary chemical identity data for 3-CMC
7OpenAlex3-CMC 3-chloromethcathinone cathinone stimulant104These provide class-level context, analytical methods, and cathinone market background relevant to 3-CMC article
8PubMed3-methylmethcathinone 3-MMC monoamine transporter pharmacology11Relevant - covers mephedrone-class cathinone pharmacology with potential 3-MMC data that can be used as structural analog context
9WebSearch3-CMC clophedrone EMCDDA European drug report seizures 2023 202482Seizure data context
10PubMedmephedrone synthetic cathinone human cardiovascular subjective effects clinical32Mephedrone human pharmacology as closest analog to 3-CMC
11EUDA—11Key seizure and market data
12PubMed—11Mephedrone CYP2D6 data relevant as 3-CMC analog model
13WebSearch3-CMC 3-chloromethcathinone legal status scheduling UK US EU countries 2024 2025105Primary legal status sources
14EUDA—11EU regulatory history and risk assessment data
15WebSearch3-CMC first detected Europe year history market 2014 2015103Market history data
16ECDD Repository—11Authoritative WHO scheduling and pharmacology summary
17OpenAlex3-CMC 3-chloromethcathinone human pharmacology effects seizures102Fatal chemsex case is critical new evidence; 3-MMC review provides closest analog market/dependence data
18WebSearch3-chloromethcathinone CAS number structure 3-CMC102Chemical identity data
19PubChemCID 5099928511Chemical identity verification
20WebSearch3-CMC UK Psychoactive Substances Act 2016 Australia Canada scheduling101Legal status
82 claims by section — every cited sentence, checked against its source
safety29 · 26 ok
  • Romańczuk et al. (2023) reported 27 deaths at one Polish forensic medicine department (2016–2022) involving CMC isomers, of which 13 involved 3-CMCsupported

    27 death cases from Department of Forensic Medicine in Kraków, 2016-2022. 52% 4-CMC, 48% 3-CMC. bkad070

  • Polydrug use was the norm: 82% of cases (22/27) involved co-detected substances including synthetic cannabinoids, synthetic opioids, cocaine, opiates, medications, and/or ethanol.supported

    82% polydrug cases. bkad070

  • Pélissier-Alicot et al. (2026) reported a fatal chemsex case: a 62-year-old man found dead with chemsex paraphernalia, with toxic GHB concentrations (330 µg/mL) in combination with 3-CMC (17 ng/mL in frozen blood).supported

    62-year-old man found dead with chemsex paraphernalia. GHB toxic (330 µg/mL) + 3-CMC 17 ng/mL in frozen blood. toxics14020131

  • Claim in safety — inconclusiveinconclusiveworking →

  • Claim in safety — inconclusiveinconclusiveworking →

  • Cardiac arrhythmias and thoracic pain are documented in human intoxication casessupported

    cardiac arrhythmias, thoracic pain, tachypnea. ijms262311600

  • Computational ADMET modelling predicts cardiotoxicity risk for 3-CMC and all CMC isomers, including drug–drug interaction potentialpartially supported

    Cardiotoxicity risk predicted for all CMC compounds. ijms262311600

  • The structural analog 4-CMC increases blood pressure and heart rate in rats. No hERG channel binding data or QTc prolongation measurements have been published for 3-CMC.supported

    4-CMC increased blood pressure, heart rate, and locomotor activity in rats. jpet.122.001478

  • Langa et al. (2026) administered 3-CMC (10 or 20 mg/kg i.p.) to Wistar rats with sacrifice at 24 hourssupported

    Rats given 10 or 20 mg/kg i.p., sacrificed 24h later. bkaf103

  • Wojcieszak et al. (2020) demonstrated cytotoxicity of 3-CMC on SH-SY5Y human neuroblastoma cells, with toxicity emerging and intensifying during prolonged incubationsupported

    First cytotoxicity data for 3-CMC and 4-CMC on SH-SY5Y neuroblastoma cells — emerges with prolonged incubation, suggesting indirect mechanism. s12640-020-00227-8

  • Bassi et al. (2025) reported that 3-CMC produces hypothermia in CD-1 mice (0.1–30 mg/kg i.p.), contrasting with the hyperthermia produced by many other synthetic cathinones and MDMAsupported

    3-CMC induced locomotor stimulation in CD-1 mice (0.1-30 mg/kg i.p.), tachypnoea and hypothermia. ijms262311600

  • Willeman et al. (2025) demonstrated that 3-CMC caused false-positive MDMA results at 100 µg/mL and contributed to 17.1% of false-positive MDMA tests in a clinical cohortsupported

    3-CMC at 100 µg/mL caused false-positive MDMA assay results. False-positive rate: 16.3% for amphetamine, 17.1% for MDMA assays in 2033 urine samples from 1812 patients. 00045632251331404

  • Psychosis is documented in human intoxication cases at the Italian Poison Control Centresupported

    Human intoxications (Italy, 2014-2025): all non-fatal, male patients, psychomotor agitation, psychosis, aggressiveness ijms262311600

  • Psychomotor agitation and aggressiveness are reported alongside psychotic symptomssupported

    psychomotor agitation, psychosis, aggressiveness, CNS depression ijms262311600

  • At the cathinone class level, Daziani et al. (2023) documented encephalopathy, coma, convulsions, sympathomimetic and hallucinogenic toxidromes, and excited/agitated delirium syndrome as neurological complications of synthetic cathinone usesupported

    Neurotoxic effects include encephalopathy, coma, convulsions, sympathomimetic and hallucinogenic toxidromes, excited delirium syndrome, serotonin syndrome. ijms24076230

  • Claim in safety — inconclusiveinconclusiveworking →

  • Van Amsterdam et al. (2025) documented that 3-MMC's shorter duration of action relative to mephedrone leads to increased craving and more frequent redosingsupported

    Shorter duration leads to increased craving and redosing. j.drugpo.2025.104971

  • Treatment-seeking for problematic 3-MMC use in the Netherlands increased from 33 cases in 2021 to 330 cases in 2023, with most cases involving polydrug userssupported

    Treatment-seeking increased from 33 to 330 cases 2021-2023. j.drugpo.2025.104971

  • Pélissier-Alicot et al. (2026) documented a fatal case involving 3-CMC combined with GHB in a chemsex context — a 62-year-old man found dead with a toxic GHB concentration of 330 µg/mL alongside 3-CMC at 17 ng/mLsupported

    62-year-old man found dead with chemsex paraphernalia. GHB toxic (330 µg/mL) + 3-CMC 17 ng/mL in frozen blood. toxics14020131

  • For the structural analog mephedrone, Papaseit et al. (2019) demonstrated in a randomised crossover trial that mephedrone combined with alcohol (0.8 g/kg) produced significantly increased cardiovascular effects and greater euphoria than either drug alone, with mephedrone reducing alcohol's perceived sedationsupported

    Mephedrone 200 mg + alcohol 0.8 g/kg. Combination increased cardiovascular effects and euphoria vs either drug alone. Mephedrone reduced alcohol sedation. fphar.2019.01588

  • If CYP2D6 is the primary metabolising enzyme for 3-CMC — as established for mephedrone — co-administration with CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion, quinidine) could reduce 3-CMC metabolism, elevating plasma exposure and toxicity risksupported

    Mephedrone metabolic disposition mediated by CYP2D6. Low CYP2D6 functionality increases toxicity risk. cpt.1417

  • Daziani et al. (2023) documented serotonin syndrome within the broader synthetic cathinone classsupported

    Neurotoxic effects include encephalopathy, coma, convulsions, sympathomimetic and hallucinogenic toxidromes, excited delirium syndrome, serotonin syndrome. ijms24076230

  • Romańczuk et al. (2023) found that 82% of fatal CMC-related cases (22/27) involved co-detected substances, including synthetic cannabinoids, synthetic opioids, cocaine, opiates, medications, and/or ethanolsupported

    27 death cases... 82% polydrug cases. bkad070

  • Cardiac arrhythmias and thoracic pain are documented in human intoxication cases, and ADMET modelling predicts cardiotoxicity across CMC isomerssupported

    cardiac arrhythmias, thoracic pain... Cardiotoxicity risk predicted for all CMC compounds. ijms262311600

  • Nephrotoxicity signals (histopathological kidney changes at high dose, elevated urea) were observed in acute rat exposuresupported

    increased glucose and urea... Histopathological changes in brain, liver, lungs (both doses), kidneys (high dose). bkaf103

  • Liver histopathological changes were observed at both doses in the rat studysupported

    Histopathological changes in brain, liver, lungs (both doses), kidneys (high dose). bkaf103

  • If CYP2D6 mediates 3-CMC metabolism as predicted, CYP2D6 poor-metaboliser phenotype represents an additional risk factor for elevated exposure.supported

    Low CYP2D6 functionality increases toxicity risk. cpt.1417

  • Class-level seizure threshold reduction is documented for synthetic cathinones.supported

    Neurotoxic effects include encephalopathy, coma, convulsions, sympathomimetic and hallucinogenic toxidromes ijms24076230

  • Psychosis is documented in intoxication casessupported

    psychomotor agitation, psychosis, aggressiveness ijms262311600

pharmacology11 · 11 ok
  • This classification places it in the same mechanistic category as mephedrone and other ring-substituted methcathinone analogs, which act as transporter substrates rather than reuptake inhibitors.supported

    Ring-substituted cathinones like mephedrone are transporter substrates (releasers) that evoke neurotransmitter release via reversed transporter flux 164_2018_178

  • Direct evidence for 3-CMC's releaser activity comes from Wojcieszak et al. (2020), who demonstrated that chloromethcathinones including 3-CMC and 4-CMC enhance non-selective dopamine and serotonin release, consistent with substrate-type activity at DAT and SERTsupported

    Chloromethcathinones enhance non-selective DA/5-HT release. s12640-020-00227-8

  • The positional isomer 4-CMC has been directly characterised at monoamine transporters in rats, where it functions as a substrate at DAT, NET, and SERT with comparable potency across all three transporters, similar to mephedronesupported

    4-CMC functions as substrate (releaser) at DAT, NET, SERT with similar potency at all three transporters, comparable to mephedrone. jpet.122.001478

  • Structure-activity relationship data from meta-substituted trifluoromethyl methcathinone analogs indicate that meta-ring substitution increases SERT potency relative to DAT compared to unsubstituted analogs, suggesting 3-CMC may exhibit relatively greater serotonergic activity than its para-substituted isomersupported

    Meta-substituted (3-position) ring substituents on methcathinone analogs increase SERT potency but decrease NET/DAT activity. j.ejphar.2012.11.008

  • The most direct human data come from Di Trana et al. (2026), who conducted an observational naturalistic study in 16 regular psychostimulant users who self-administered 3-CMC orally (100–150 mg) or intranasally (60–80 mg)supported

    16 regular psychostimulant users self-administered 3-CMC orally (100-150 mg) or intranasally (60-80 mg). s12248-025-01200-z

  • N-glucuronidation of 3-CMC was hypothesised for the first time in this study.supported

    3-CMC N-glucuronidation hypothesized for first time. s12248-025-01200-z

  • Berardinelli et al. (2024) conducted the most comprehensive metabolite profiling, identifying 12 metabolites via human hepatocyte incubation with LC-HRMS/MS confirmation in clinical and forensic specimens (blood, urine, oral fluid)supported

    12 metabolites identified for 3-CMC via human hepatocyte incubation + LC-HRMS/MS... 3-CMC-positive blood, urine, and oral fluid analyzed from clinical/forensic casework. s12248-024-00940-8

  • Major metabolic reactions included β-keto reduction (producing dihydro-3-CMC), N-demethylation, and a combined N-demethylation plus ω-carboxylation pathway that produced the predominant urinary metabolite — a pathway previously unreported for any methcathinone analog.supported

    Major reactions: ketoreduction, N-demethylation. Predominant urinary metabolite: N-demethylation + ω-carboxylation combination. s12248-024-00940-8

  • M3 (dihydro-3-CMC) was the predominant metabolite in postmortem samplessupported

    M3 (beta-keto reduction). M3 was predominant metabolite in postmortem samples. j.forsciint.2025.112364

  • Mestria et al. (2025) confirmed dihydro-CMC stereoisomers and N-demethyl-CMC as key metabolites in a murine dried blood spot model.supported

    DBS technique in murine model. Main metabolites: dihydro-CMC stereoisomers, N-demethyl-CMC, dihydro-N-demethyl-CMC. dta.3782

  • By structural analogy to mephedrone, CYP2D6 is the probable primary metabolising enzyme: Olesti et al. (2019) demonstrated in a Phase I clinical trial that mephedrone metabolism is CYP2D6-mediated, with individuals carrying low or absent CYP2D6 activity at elevated risk of toxicity. This CYP2D6 involvement has not been directly confirmed for 3-CMC.supported

    Mephedrone metabolic disposition mediated by CYP2D6. Low CYP2D6 functionality increases toxicity risk. cpt.1417

neuroscience10 · 8 ok
  • Claim in neuroscience — inconclusiveinconclusiveworking →

  • Langa et al. (2026) reported oxidative stress and energy biomarker alterations in brain, lung, and kidney tissue of Wistar rats following acute 3-CMC exposure (10 or 20 mg/kg i.p.), with histopathological changes observed in the brain at both doses.supported

    Oxidative stress in brain, lungs, kidneys. Histopathological changes in brain, liver, lungs (both doses), kidneys (high dose). bkaf103

  • What is the dose-response curve for cardiovascular toxicity? Cardiac arrhythmias are documented in clinical intoxication but the dose threshold, exposure duration, and individual risk factors (e.g., pre-existing cardiac conditions, CYP2D6 status) have not been characterised.supported

    Human intoxications (Italy, 2014-2025): all non-fatal, male patients... cardiac arrhythmias, thoracic pain, tachypnea. ijms262311600

  • Dopaminergic reward pathway. Substrate-type monoamine releasers increase extracellular dopamine concentrations in the mesolimbic pathway (ventral tegmental area → nucleus accumbens), producing the reinforcing and euphoric effects characteristic of psychostimulantssupported

    transporter substrates (releasers) that evoke neurotransmitter release via reversed transporter flux... All increase extracellular monoamines. 164_2018_178

  • The dose-dependent locomotor stimulation observed with 3-CMC in mice is a standard behavioural correlate of mesolimbic dopamine releasesupported

    3-CMC and 4-CMC stimulate horizontal locomotor activity dose-dependently in mice. Chloromethcathinones enhance non-selective DA/5-HT release. s12640-020-00227-8

  • Claim in neuroscience — inconclusiveinconclusiveworking →

  • Noradrenergic activation. NET substrate activity produces the sympathomimetic effects documented in human intoxication cases: tachycardia, hypertension, tachypnoea, and psychomotor agitationpartially supported

    Human intoxications (Italy, 2014-2025): all non-fatal, male patients, psychomotor agitation, psychosis, aggressiveness, CNS depression, cardiac arrhythmias, thoracic pain, tachypnea. ijms262311600

  • The parallel with 3-MMC's documented compulsive redosing pattern supports this framework.supported

    Shorter duration leads to increased craving and redosing. j.drugpo.2025.104971

  • What is the DAT/SERT selectivity ratio of 3-CMC? The meta-chloro substitution is predicted to shift selectivity toward SERT based on trifluoromethyl SAR data, but no direct measurement exists. This ratio determines whether 3-CMC's profile is more stimulant-like (DAT-preferring) or entactogen-like (balanced/SERT-preferring).supported

    Meta-substituted (3-position) ring substituents on methcathinone analogs increase SERT potency but decrease NET/DAT activity. j.ejphar.2012.11.008

  • Does 3-CMC produce enantioselective pharmacological effects? Enantioselective metabolism is confirmed, but whether the (R)- or (S)-enantiomer drives the primary pharmacological effects — as demonstrated for mephedrone — is unknown.supported

    Mephedrone has chiral centre, exists as R and S enantiomers. Enantiomer-specific effects at monoamine transporters demonstrated. bph.12951

pharmacokinetic-detail8 · 7 ok
  • Langa et al. (2026) administered racemic 3-CMC (10 or 20 mg/kg i.p.) to Wistar rats and demonstrated enantioselective metabolismsupported

    Sold as racemate, exhibits enantioselective metabolism. Rats given 10 or 20 mg/kg i.p. bkaf103

  • Di Trana et al. (2026) enrolled 16 regular psychostimulant users who self-administered 3-CMC at the following doses:supported

    16 regular psychostimulant users self-administered 3-CMC orally (100-150 mg) or intranasally (60-80 mg). s12248-025-01200-z

  • Berardinelli et al. (2024) identified 12 metabolites via human hepatocyte incubation confirmed by LC-HRMS/MS in clinical and forensic specimenssupported

    12 metabolites identified for 3-CMC via human hepatocyte incubation + LC-HRMS/MS. s12248-024-00940-8

  • Feliu et al. (2025) confirmed four primary HLM metabolites: M1 (aliphatic hydroxylation), M2 (N-demethylation), M3 (β-keto reduction), and M4 (M1 + β-keto reduction)supported

    Four primary metabolites: M1 (hydroxylation of aliphatic group), M4 (M1 + beta-keto reduction), M2 (N-demethylation), M3 (beta-keto reduction). j.forsciint.2025.112364

  • A notable finding from Di Trana et al. (2026) is route-dependent metabolic divergence: oral administration produced three exclusive metabolites absent after intranasal dosing, while the β-hydroxylated metabolite (β-OH-3-CMC) accumulated preferentially after intranasal administrationpartially supported

    N-acetylation occurs primarily via oral route; β-OH-3-CMC accumulates more after intranasal use. s12248-025-01200-z

  • Olesti et al. (2019) demonstrated in a double-blind, randomised, Phase I clinical trial that mephedrone metabolism is CYP2D6-mediatedsupported

    Randomized crossover Phase I clinical trial of mephedrone 50-200 mg... Mephedrone metabolic disposition mediated by CYP2D6. cpt.1417

  • Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →

  • Dihydro-3-CMC is therefore the recommended forensic biomarker for documenting 3-CMC intake, particularly in cases where specimen collection is delayed or storage conditions are suboptimalsupported

    Dihydrometabolites more stable. All detectable to 90 days. dta.3782

comparative-pharmacology6 · 6 ok
  • Mephedrone's pharmacokinetics have been characterised in a Phase I clinical trial: CYP2D6 mediates its primary metabolism, and poor metabolisers face elevated plasma concentrations and toxicity risksupported

    Randomized crossover Phase I clinical trial of mephedrone 50-200 mg... Mephedrone metabolic disposition mediated by CYP2D6. Low CYP2D6 functionality increases toxicity risk. cpt.1417

  • Structure-activity relationship data from trifluoromethyl methcathinone analogs demonstrate that meta-ring substitution increases SERT release potency relative to DAT compared to para- and unsubstituted analogssupported

    Meta-substituted (3-position) ring substituents on methcathinone analogs increase SERT potency but decrease NET/DAT activity. j.ejphar.2012.11.008

  • 4-CMC has been characterised in standardised in vitro assays: Chojnacki et al. (2023) demonstrated that it functions as a substrate at DAT, NET, and SERT with comparable potency, increasing blood pressure, heart rate, and locomotor activity in ratssupported

    4-CMC functions as substrate (releaser) at DAT, NET, SERT with similar potency at all three transporters... 4-CMC increased blood pressure, heart rate, and locomotor activity in rats. jpet.122.001478

  • Its acute pharmacological effects have been studied in controlled human settings, including route comparison (oral vs intranasal) and alcohol interactionpartially supported

    10 subjects self-administered mephedrone orally (100-200 mg) or intranasally (50-100 mg). Both routes enhanced euphoria and cardiovascular effects. ph14020100

  • Van Amsterdam et al. (2025) documented a systematic pattern with 3-MMC: its shorter duration of action relative to mephedrone leads to increased craving and more frequent redosingsupported

    Shorter duration leads to increased craving and redosing. j.drugpo.2025.104971

  • This distinction, established by Baumann et al. (2018), separates compounds like 3-CMC, 4-CMC, and mephedrone (releasers) from α-pyrrolidinophenone cathinones such as α-PVP and MDPV (DAT blockers)supported

    Ring-substituted cathinones like mephedrone are transporter substrates (releasers)... whereas pyrrolidine cathinones are blockers. 164_2018_178

receptor-pharmacology6 · 5 ok
  • Claim in receptor-pharmacology — inconclusiveinconclusiveworking →

  • The same study confirmed enhanced non-selective dopamine/serotonin release for chloromethcathinone analogs.supported

    Chloromethcathinones enhance non-selective DA/5-HT release. s12640-020-00227-8

  • Structure-activity relationships. Cozzi et al. (2013) demonstrated that meta-ring substitution on the methcathinone scaffold (using trifluoromethyl probes) increases SERT release potency relative to DAT compared to unsubstituted analogssupported

    Meta-substituted (3-position) ring substituents on methcathinone analogs increase SERT potency but decrease NET/DAT activity. j.ejphar.2012.11.008

  • Saha et al. (2015) demonstrated differential monoamine transporter effects among second-generation mephedrone analogs, confirming that minor structural modifications significantly alter the DAT/SERT selectivity ratio.supported

    4-MEC is SERT substrate + DAT blocker; 4-MePPP is DAT/NET blocker. Structural modifications govern DAT vs SERT selectivity in cathinone class. npp.2014.325

  • Baumann et al. (2018) established the canonical framework: ring-substituted cathinones are transporter substrates (releasers), not blockers, and all cathinones in this structural class increase extracellular monoamine concentrations in the brain.supported

    Ring-substituted cathinones like mephedrone are transporter substrates (releasers)... All increase extracellular monoamines. 164_2018_178

  • Enantioselective metabolism is confirmed: Langa et al. (2026) demonstrated that enantiomeric fractions of both parent compound and three metabolite pairs deviated significantly from 0.5 in Wistar ratssupported

    exhibits enantioselective metabolism... three enantiomeric metabolite pairs. Enantiomeric enrichment observed. bkaf103

summary6 · 6 ok
  • It emerged as a successive replacement following international control of mephedrone (2010) and 4-CMC (2020), and by 2024 accounted for over 63% of all new psychoactive substance seizures in Europepartially supported

    In 2024, 3-Chloromethcathinone (3-CMC) accounted for over 63% of all New Psychoactive Substances seized in Europe s12248-025-01200-z

  • 3-CMC functions as a substrate-type releaser, increasing extracellular concentrations of dopamine, serotonin, and norepinephrinepartially supported

    Chloromethcathinones enhance non-selective DA/5-HT release. s12640-020-00227-8

  • Structural analogy with 4-CMC and structure-activity relationship data for meta-substituted cathinones suggest relatively greater serotonergic activity compared to para-substituted analogs, though this has not been confirmed with direct binding assayssupported

    Meta-substituted (3-position) ring substituents on methcathinone analogs increase SERT potency but decrease NET/DAT activity. j.ejphar.2012.11.008

  • Cardiovascular toxicity is the primary safety concern: cardiac arrhythmias and thoracic pain are documented in human intoxication cases, and computational ADMET modelling predicts cardiotoxicity risk across all CMC isomerssupported

    cardiac arrhythmias, thoracic pain, tachypnea. Main predicted metabolism: N-dealkylation, N-hydroxylation, phenyl hydroxylation. Cardiotoxicity risk predicted for all CMC compounds. ijms262311600

  • Fatal cases involving 3-CMC have been reported, including cases where it was the sole identified substance, though the majority of fatalities involve polydrug usesupported

    27 death cases from Department of Forensic Medicine in Kraków, 2016-2022. 52% 4-CMC, 48% 3-CMC. 82% polydrug cases. bkad070

  • The compound's short duration of action is associated with compulsive redosing and elevated dependence liability, mirroring patterns documented for the structural analog 3-MMCsupported

    Shorter duration leads to increased craving and redosing. j.drugpo.2025.104971

chemistry4 · 3 ok
  • Enantioselective metabolism has been confirmed in Wistar rats: both the parent drug and its three pairs of enantiomeric metabolites exhibited enantiomeric fractions significantly different from 0.5 following acute intraperitoneal exposure at 10 and 20 mg/kgsupported

    exhibits enantioselective metabolism. Rats given 10 or 20 mg/kg i.p., sacrificed 24h later. 3-CMC detected exclusively in urine with three enantiomeric metabolite pairs. Enantiomeric enrichment observed. bkaf103

  • Meta-substitution on the cathinone scaffold has been associated with increased serotonin transporter potency relative to dopamine transporter potency compared to para-substituted analogs.supported

    Meta-substituted (3-position) ring substituents on methcathinone analogs increase SERT potency but decrease NET/DAT activity. j.ejphar.2012.11.008

  • For the structural analog mephedrone, enantioselective neurochemical and behavioural effects have been demonstrated in rats, suggesting that enantiomer-specific pharmacology may be clinically relevant for 3-CMC as well.supported

    Mephedrone has chiral centre, exists as R and S enantiomers. Enantiomer-specific effects at monoamine transporters demonstrated. bph.12951

  • Claim in chemistry — inconclusiveinconclusiveworking →

clinical-evidence1 · 1 ok
  • The most direct human pharmacological data come from Di Trana et al. (2026), an observational, uncontrolled, naturalistic study in 16 regular psychostimulant users who self-administered 3-CMCsupported

    16 regular psychostimulant users self-administered 3-CMC orally (100-150 mg) or intranasally (60-80 mg). s12248-025-01200-z

history1 · 1 ok
  • 2023: 3-CMC accounted for more than 46% of all NPS-related seizures in Europesupported

    3-CMC accounts for over 46% of NPS-related seizures in 2023. bkaf103

3Sources

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

Sources
yearsourcetierstatusfeeds
2026Enantiomeric biodistribution, metabolic profile, and toxicity of 3-chloromethcathinone in Wistar rats following acute exposure.Langa I, Rocha-Pereira C, Silva P, Milhazes N, Dias da Silva D, Domingues S, Resende AD, Barbosa J, Faria J, Tiritan ME, Ribeiro C · Journal of Analytical Toxicologydoi:10.1093/jat/bkaf103moderateconsumed6 sections
2026The Influence of Routes of Administration on 3-chloromethcathinone Urinary Biomarkers Disposition: Preliminary In Vivo Study of Unknown Metabolites Profiling on Healthy Volunteers.Di Trana A, La Maida N, Graziano S, Pichini S, Hladun O, Poyatos L, Ventura M, Papaseit E, Farré M, Perez-Maña C · The AAPS Journaldoi:10.1208/s12248-025-01200-zmoderateconsumed4 sections
2026Unusual Case of Fatal Virtual Chemsex Session Involving 3-Chloromethcathinone (3-CMC).Pélissier-Alicot AL, Fabresse N, Petitcollin A, Costagliola R, Dubertrand C, Baillif-Couniou V, Sastre C, Piercecchi MD, Leonetti G · Toxicsdoi:10.3390/toxics14020131weakconsumed1 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/ijms262311600weakconsumed3 sections
2025Appearance of 2-MMC and 3-MMC on the illicit drug market in the Netherlands: A systematic narrative review of the prevalence and risksvan Amsterdam J, Nabben T, van den Brink W · The International journal on drug policydoi:10.1016/j.drugpo.2025.104971moderateconsumed4 sections
2025Investigating 3-CMC metabolism: Insights from liver microsomes and postmortem biological matrix.Feliu C, Hattat E, Tholance Y, Hodin S, Pipet J, Panther T, Bidat C, Delavenne X · Forensic Science Internationaldoi:10.1016/j.forsciint.2025.112364moderateconsumed2 sections
2025Metabolism study of 3-chloromethcathinone (3-CMC) by dried blood spot (DBS) sampling after controlled administration using a murine model.Mestria S, Odoardi S, Valentini V, Corli G, Bassi M, Marti M, Strano-Rossi S · Drug Testing and Analysisdoi:10.1002/dta.3782moderateconsumed3 sections
2025Underreporting of synthetic cathinone poisoning with clinical immunoassays: An experimental and observational study.Willeman T, Laudet M, Revol B, Boudin C, Eysseric-Guerin H, Scolan V, Stanke-Labesque F · Annals of clinical biochemistrydoi:10.1177/00045632251331404moderateconsumed1 section
20243-CMC - PsychonautWikiPsychonautWiki contributorsurl:4313bfbc3a33754dweakconsumedcited 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/s12248-024-00940-8moderateconsumed2 sections
2024Chloromethcathinone - Center for Forensic Science Research & Education MonographCFSREurl:c47b83209c6de423weakconsumedcited only
2024Council Decision (EU) 2024/832 of 4 March 2024 on international scheduling of 3-CMCCouncil of the European Unionurl:3726a9b0d96ef244weakconsumedcited only
2024EU Drug Markets Report: Synthetic Cathinones Distribution and Supply in EuropeEuropean Union Drugs Agency (EUDA)url:4bb744e1ce8f6856weakconsumedcited only
20233-CMC - Expert Committee on Drug Dependence Information RepositoryWorld Health Organization ECDDurl:65a993351212f32bweakconsumedcited only
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
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.122.001478moderateconsumed3 sections
2023Synthetic Cathinones and Neurotoxicity Risks: A Systematic ReviewDaziani G, Lo Faro AF, Montana V, Goteri G, Pesaresi M, Bambagiotti G, Montanari E, Giorgetti R, Montana A · International Journal of Molecular Sciencesdoi:10.3390/ijms24076230strongconsumed1 section
2023WHO ECDD 46th Meeting: Scheduling Recommendation for 3-CMCWorld Health Organization Expert Committee on Drug Dependenceurl:44317fb471afb6d6weakconsumedcited only
2022European Commission adopts measures to control two harmful new drugs (3-CMC and 3-MMC)European Union Drugs Agency (EUDA)url:db6fb3d3b5f6574fweakconsumedcited only
2021Acute Pharmacological Effects of Oral and Intranasal Mephedrone: An Observational Study in HumansPapaseit E, Olesti E, Perez-Mana C, et al. · Pharmaceuticalsdoi:10.3390/ph14020100moderateconsumed1 section
2021EMCDDA Initial Report on 3-CMC (1-(3-chlorophenyl)-2-(methylamino)propan-1-one)EMCDDAurl:523c35cc672f0e6eweakconsumedcited only
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/s12640-020-00227-8moderateconsumed5 sections
2019Dose-Response Pharmacological Study of Mephedrone and Its Metabolites: Pharmacokinetics, Serotoninergic Effects, and Impact of CYP2D6 Genetic VariationOlesti E, Farre M, Carbo ML, et al. · Clinical Pharmacology and Therapeuticsdoi:10.1002/cpt.1417strongconsumed4 sections
2019Mephedrone and Alcohol Interactions in HumansPapaseit E, Perez-Mana C, de Sousa Fernandes Perna EB, et al. · Frontiers in Pharmacologydoi:10.3389/fphar.2019.01588strongconsumed1 section
2018Neuropharmacology of Synthetic CathinonesBaumann MH, Walters HM, Niello M, Sitte HH · Handbook of Experimental Pharmacologydoi:10.1007/164_2018_178moderateconsumed4 sections
2018Pharmacological profile of mephedrone analogs and related new psychoactive substancesLuethi D, Kolaczynska KE, Docci L, Krähenbühl S, Hoener MC, Liechti ME · Neuropharmacologydoi:10.1016/j.neuropharm.2017.07.026moderateconsumedcited only
2015'Second-generation' mephedrone analogs, 4-MEC and 4-MePPP, differentially affect monoamine transporter function.Saha K, Partilla JS, Lehner KR, Seddik A, Stockner T, Holy M, Sandtner W, Ecker GF, Sitte HH, Baumann MH · Neuropsychopharmacologydoi:10.1038/npp.2014.325moderateconsumed1 section
2015Stereochemistry of mephedrone neuropharmacology: enantiomer-specific behavioural and neurochemical effects in rats.Gregg RA, Baumann MH, Partilla JS, Bonano JS, Vouga A, Tallarida CS, Velvadapu V, Smith GR, Peet MM, Reitz AB, Negus SS, Rawls SM · British Journal of Pharmacologydoi:10.1111/bph.12951moderateconsumed2 sections
2013Pharmacological examination of trifluoromethyl ring-substituted methcathinone analogs.Cozzi NV, Brandt SD, Daley PF, Partilla JS, Rothman RB, Tulzer A, Sitte HH, Baumann MH · European Journal of Pharmacologydoi:10.1016/j.ejphar.2012.11.008strongconsumed6 sections
—Searched ClinicalTrials.gov for "3-CMC chloromethcathinone 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/3-cmc/version/1
  2. 0022026-06-04proposal42 value proposals approved together

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

    42 items in this filing

    • contraindication · other
    • contraindication · renal
    • contraindication · hepatic
    • contraindication · neurological
    • contraindication · pregnancy_breastfeeding
    • contraindication · psychiatric
    • contraindication · other
    • contraindication · metabolic
    • 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
    • timeline · insufflated · onset
    • timeline · insufflated · come_up
    • timeline · insufflated · peak
    • timeline · insufflated · resolution
    • timeline · insufflated · afterglow
    • toxicity
    • dependence · full
    • withdrawal
    • tolerance
    • dosage · oral
    • dosage · insufflated
    • duration · oral · onset
    • duration · oral · come_up
    • duration · oral · peak
    • duration · oral · offset
    • duration · oral · total
    • duration · oral · aftereffects
    • duration · insufflated · onset
    • duration · insufflated · come_up
    • duration · insufflated · peak
    • duration · insufflated · offset
    • duration · insufflated · total
    • duration · insufflated · aftereffects
    psx:substance/3-cmc/proposal/contraindication/94c3c460-d276-472b-9740-6f2cb9714d1a
  3. 0032026-06-04publicationPublication — backfill

5Issued documents

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

Issued documents
documentcontent hashissuedfrom versionsuperseded
info_card98c2677da1c149265cfb948b…2026-10-19 20:29Revision 1current
emergency58d3299a8754d788e3d74c0e…2026-09-04 04:27Revision 1current
info_cardfecd37129b2a089a131c2a65…2026-09-04 04:27Revision 1superseded2026-10-19
noticedacbc6aaa7b95bcfe1a57ea6…2026-09-04 04:27Revision 1current