generation run 2026-04-24
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18 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed | methylone cathinone monoamine transporter serotonin dopamine | 12 | 10 | All directly relevant to methylone mechanism of action and pharmacology |
| 2 | PubMed | methylone self-administration reinforcing abuse potential rats | 2 | 1 | Direct methylone self-administration data relevant to abuse liability |
| 3 | ClinicalTrials.gov · absence | methylone cathinone | 0 | 0 | No trials to select; confirms absence of human clinical trial data |
| 4 | PubChem | methylone | 1 | 1 | Primary chemical identity verification |
| 5 | PubMed | methylone bath salts forensic analysis detection | 6 | 5 | Forensic/toxicology data supporting safety section |
| 6 | PubMed | methylone toxicity overdose death case report | 1 | 1 | Key fatal case report with postmortem methylone concentrations |
| 7 | OpenAlex | methylone cathinone pharmacology neurotoxicity | 260 | 5 | Selected top-cited works directly relevant to methylone pharmacology and mechanism of action |
| 8 | PubMed | PMID 41706459, 40849539 | 2 | 2 | Primary clinical trial data and mechanistic data published in high-impact journals |
| 9 | PubChem | CID 45789647 | 1 | 1 | Chemical identity verification; SMILES not returned by API tool |
| 10 | ClinicalTrials.gov | methylone PTSD Transcend Therapeutics | 5 | 5 | All trials directly relevant; Phase 3 EMPOWER-1 currently recruiting is most critical finding |
| 11 | Web | Transcend Therapeutics methylone TSND-201 PTSD Phase 2 results breakthrough therapy FDA | 10 | 3 | Critical clinical development data; FDA designation and Phase 2 results directly document methylone's current therapeutic status |
| 12 | Web | methylone DEA Schedule I scheduling date UK Misuse of Drugs Act | 10 | 3 | Primary legal sources for scheduling history by jurisdiction |
| 13 | OpenAlex | methylone neuropharmacology locomotion hyperthermia body temperature rat | 8 | 2 | Pharmacokinetics paper is direct methylone-specific PK data; systematic review covers neurotoxicity comprehensively |
| 14 | OpenAlex | methylone Jacob Shulgin patent 1996 history first synthesis antidepressant | 6 | 2 | Reviews providing pharmacological context for methylone; history data confirmed through web sources |
| 15 | Web | methylone Australia TGA Schedule 9 controlled substance | 9 | 1 | Primary regulatory source for Australian scheduling status |
| 16 | Multiple · absence | methylone tramadol lethal interaction mechanism | 0 | 0 | No primary sources found; flagged as unverified claim from seed data requiring editorial review |
| 17 | Web | methylone SMILES CAS 186028-79-5 chemical properties | 10 | 2 | Chemical identity verification from multiple sources |
| 18 | PubMed | methylenedioxymethcathinone methylone stereoisomer enantiomer pharmacology | 2 | 2 | Directly relevant to stereochemistry section; first published data on methylone enantiomer-specific effects |
114 claims by section — every cited sentence, checked against its source
safety42 · 27 ok
Liver: Microvascular steatosis documented in fatal casessupported
Microvascular steatosis of liver and striated heart muscle damage observed. oh.2012.29310
Heart: Sudden cardiac death, arrhythmias, myocardial infarctionsupported
Fatal methylone case in a 16-year-old with cardiac malformation... striated heart muscle damage observed. oh.2012.29310
Multiple forensic analyses confirm that blood methylone concentration does not reliably predict lethality.supported
Blood concentration does not predict outcome for fatalities or impairment. bks136
Multiple forensic analyses confirm that blood methylone concentration does not reliably predict lethality.supported
Lethal concentrations cannot be established. 1556-4029.13316
A 16-year-old male with pre-existing cardiac malformation and asthma experienced sudden cardiac arrest after methylone ingestion at a party (blood methylone: 272 ng/mL; liver: 387 ng/g). Histopathology revealed microvascular steatosis of the liver and striated heart muscle damage; the authors concluded that pre-existing conditions were predisposing factors for fatal outcome at a relatively low concentration.supported
Fatal methylone case in a 16-year-old with cardiac malformation. Blood methylone 272 ng/mL, liver 387 ng/g. Microvascular steatosis of liver and striated heart muscle damage observed. oh.2012.29310
The first reported sudden cardiac death attributed to methylone in a previously healthy 19-year-old (postmortem blood: 0.7 mg/L), prompting the authors to state that methylone toxicity had been "greatly underestimated".supported
First reported case of sudden cardiac death associated with methylone in a previously healthy 19-year-old. Postmortem methylone 0.07 mg/dL. paf.0b013e31827ab5da
A 3-year retrospective of 30 cathinone cases at the New York City Medical Examiner's office identified two deaths attributed solely to cathinones (one with blood methylone 0.71 mg/L), while the highest incidental methylone concentration (4.8 mg/L) was found in a surviving individual — underscoring the absence of a reliable lethal threshold.supported
Two deaths attributed solely to cathinone: one with blood methylone 0.71 mg/L. Highest incidental methylone was 4.8 mg/L. Lethal concentrations cannot be established. 1556-4029.13316
Claim in safety — inconclusiveinconclusiveworking →
In rats, 40 mg/kg subcutaneous was surprisingly lethal to some animals, indicating a narrow margin between pharmacologically active and lethal doses at the high end.supported
40 mg/kg s.c. lethal to some animals. Short duration of action. fpsyt.2017.00232
Cardiac toxicity: Tachycardia, hypertension, arrhythmias, myocardial infarction, and sudden cardiac death result from direct sympathomimetic effects of catecholamine release. Pre-existing cardiac conditions substantially increase risk.supported
Sympathomimetic toxidrome from synthetic cathinones: tachycardia, hypertension, hyperthermia, myocardial infarction, death. Via direct and indirect activation of sympathetic nervous system. j.jemermed.2013.11.104
Hyperthermia: Dose-dependent and significantly worsened in crowded or socially active environments. Hyperthermia is a precursor to multi-organ failure.supported
Methylone dose-dependently increased locomotion and induced hyperthermia (more pronounced in group-housed conditions). fpsyt.2017.00232
Serotonin syndrome: Risk increases with high doses or co-administration with other serotonergic agents.supported
DA/SERT ratio determines psychotropic vs toxic effects; serotonergic drugs cause serotonin syndrome, hyperthermia, seizures, hyponatremia. smw.2015.14043
Serotonin syndrome: Risk increases with high doses or co-administration with other serotonergic agents.supported
Comprehensive review of designer drug mechanisms including methylone. Serotonergic drugs associated with serotonin syndrome, hyperthermia, seizures, hyponatremia. s00204-020-02693-7
Claim in safety — inconclusiveinconclusiveworking →
Excited delirium: Agitated delirium with psychosis, hyperthermia, and risk of death from trauma or cardiovascular collapse has been documented with synthetic cathinones.supported
Adverse effects include encephalopathy, coma, convulsions, sympathomimetic and hallucinogenic toxidromes, excited delirium syndrome, and serotonin syndrome. ijms24076230
Unlike MDMA, repeated methylone dosing (3.0 and 10.0 mg/kg s.c.) in rats does not produce long-term depletion of cortical or striatal serotonin, suggesting reduced serotonergic neurotoxicitysupported
Repeated dosing causes hyperthermia but no long-term 5-HT depletion unlike MDMA. npp.2011.304
Unlike MDMA, repeated methylone dosing (3.0 and 10.0 mg/kg s.c.) in rats does not produce long-term depletion of cortical or striatal serotonin, suggesting reduced serotonergic neurotoxicitysupported
Methylone does not cause long-term 5-HT depletion unlike MDMA despite hyperthermia. 7854_2016_21
However, prolonged high-concentration exposure partially inhibits neuronal activity in a non-reversible manner in vitro.supported
Irreversible neuronal activity inhibition at high concentrations. hDAT and hNET are primary targets. fnins.2020.00009
R-(+)-methylone is the more oxidative and cytotoxic enantiomer in dopaminergic SH-SY5Y cells, with oxidative stress identified as the primary mechanism of cytotoxicity.supported
R-(+)-methylone is the most oxidative and cytotoxic enantiomer in SH-SY5Y dopaminergic cells. Cytotoxicity mediated by oxidative stress. j.taap.2021.115442
Heart: Sudden cardiac death, arrhythmias, myocardial infarctionsupported
First reported case of sudden cardiac death associated with methylone in a previously healthy 19-year-old. paf.0b013e31827ab5da
Claim in safety — inconclusiveinconclusiveworking →
Brain: Encephalopathy, seizures, psychosis, agitated deliriumsupported
Adverse effects include encephalopathy, coma, convulsions, sympathomimetic and hallucinogenic toxidromes, excited delirium syndrome, and serotonin syndrome. ijms24076230
Claim in safety — inconclusiveinconclusiveworking →
Acute psychological adverse effects reported in clinical and review literature include anxiety, paranoia, agitation, psychosis, and excited deliriumsupported
Adverse effects include encephalopathy, coma, convulsions, sympathomimetic and hallucinogenic toxidromes, excited delirium syndrome, and serotonin syndrome. ijms24076230
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Methylone functions as a dose-dependent reinforcer in rat self-administration paradigms (0.05–0.5 mg/kg/infusion IV), with short-access sessions (2 hr/day) producing robust responding exceeding that seen in previous MDMA studiessupported
Methylone functions as dose-dependent IV reinforcer in rats. Short access sessions robust; long access did not lead to escalated intake unlike cocaine. Abuse potential similar to or greater than MDMA. pmid:24244886
However, long-access sessions (6 hr/day) do not produce escalated intake or increased reinforcer efficacy — a pattern that contrasts with cocaine and methamphetamine and suggests lower compulsive use potential.supported
Long access did not lead to escalated intake unlike cocaine. Abuse potential similar to or greater than MDMA but lower compulsive use potential than prototypical stimulants. pmid:24244886
Claim in safety — inconclusiveinconclusiveworking →
The primary pharmacological concern with methylone combinations is serotonin syndrome: as a non-selective serotonin releasing agent, methylone combined with any drug that increases serotonergic neurotransmission creates additive or synergistic risk of serotonin toxicity.supported
DA/SERT ratio determines psychotropic vs toxic effects; serotonergic drugs cause serotonin syndrome, hyperthermia, seizures, hyponatremia. smw.2015.14043
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Confirmatory identification requires LC-MS/MS methodology.supported
Validated LC-MS/MS method for 30 cathinones in postmortem blood. Methylone detected in cases from 2015. LOQ 1 ng/mL. bkaa071
Claim in safety — inconclusiveinconclusiveworking →
Published fatal case data demonstrate that congenital cardiac malformation, arrhythmia, and structural heart disease substantially increase the risk of sudden cardiac death, even at relatively low methylone concentrations.supported
Fatal methylone case in a 16-year-old with cardiac malformation. Blood methylone 272 ng/mL, liver 387 ng/g. oh.2012.29310
Published fatal case data demonstrate that congenital cardiac malformation, arrhythmia, and structural heart disease substantially increase the risk of sudden cardiac death, even at relatively low methylone concentrations.supported
First reported case of sudden cardiac death associated with methylone in a previously healthy 19-year-old. paf.0b013e31827ab5da
Claim in safety — inconclusiveinconclusiveworking →
MAOI co-administration is an absolute contraindication due to the risk of fatal serotonin syndrome.supported
DA/SERT ratio determines psychotropic vs toxic effects; serotonergic drugs cause serotonin syndrome, hyperthermia, seizures, hyponatremia. smw.2015.14043
pharmacology24 · 13 ok
Two primary metabolic pathways have been identified:supported
N-demethylation or opening of the 3,4-methylenedioxy ring via O-demethylenation gives rise to pharmacologically active metabolites of methylone. 0269881119844185
Methylone is a non-selective monoamine transporter substrate (releaser) that simultaneously functions as an uptake inhibitor — classified pharmacologically as a "cocaine-MDMA mixed cathinone"supported
Methylone, mephedrone, ethylone, butylone act as non-selective monoamine uptake inhibitors similar to cocaine. Mephedrone, methylone, ethylone and butylone also induced 5-HT release similar to MDMA. j.1476-5381.2012.02145.x
Methylone is a non-selective monoamine transporter substrate (releaser) that simultaneously functions as an uptake inhibitor — classified pharmacologically as a "cocaine-MDMA mixed cathinone"supported
Methylone and mephedrone are nonselective substrates for plasma membrane monoamine transporters, similar to MDMA in potency and selectivity. npp.2011.304
Methylone is a non-selective monoamine transporter substrate (releaser) that simultaneously functions as an uptake inhibitor — classified pharmacologically as a "cocaine-MDMA mixed cathinone"supported
MDPV is a potent uptake blocker at DAT and NET while methylone is a non-selective releaser at transporters for dopamine, norepinephrine, and serotonin (5-HT). s00213-015-4057-0
Claim in pharmacology — inconclusiveinconclusiveworking →
In vitro, methylone inhibits monoamine uptake at human DAT and NET at low micromolar concentrations, with higher concentrations required to inhibit SERTsupported
Methylone at low micromolar concentrations inhibits monoamine uptake via hDAT and hNET; higher concentrations needed for hSERT inhibition. fnins.2020.00009
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Methylone increases locomotor activity dose-dependently, though less potently than methamphetamine, with locomotion enhanced via 5-HT₂A receptor activation and increased extracellular dopamine.supported
Methylone was the most potent 5-HT and dopamine uptake inhibitor; induced hyperlocomotion through 5-HT2A receptors and increased extracellular dopamine. j.1476-5381.2012.01998.x
Claim in pharmacology — inconclusiveinconclusiveworking →
Recent preclinical and clinical research has recharacterized methylone as a "highly selective, rapid-acting neuroplastogen"supported
Described as highly selective rapid-acting neuroplastogen releasing 5-HT, NE, DA without 5-HT2A activity. jamapsychiatry.2025.4625
In cultured cortical neurons, methylone stimulates neurite outgrowth — specifically increasing the number of neuritic branches (an effect blocked by monoamine transporter inhibitors) and the length of the longest neurite (mediated by trkB receptor and mTOR signaling pathways)supported
Methylone stimulates neurite outgrowth via monoamine transporter activity and trkB/mTOR signaling. s41386-025-02206-z
Claim in pharmacology — inconclusiveinconclusiveworking →
Behaviorally, methylone produces rapid and long-lasting improvements in fear extinction recall in rodent models — an effect requiring NET activity, as demonstrated by blockade with the selective NET inhibitor reboxetinesupported
Long-lasting effects on fear extinction learning and memory observed. NET activity required for behavioral effect (blocked by reboxetine). s41386-025-02206-z
Methylone does not directly activate 5-HT₂A receptors, distinguishing its mechanism from classical psychedelics used in psychedelic-assisted therapy.supported
Described as highly selective rapid-acting neuroplastogen releasing 5-HT, NE, DA without 5-HT2A activity. jamapsychiatry.2025.4625
Claim in pharmacology — inconclusiveinconclusiveworking →
In rats (subcutaneous administration), peak serum and brain concentrations occur at 30 minutes, with maximum behavioral effects corresponding to peak brain levelssupported
Serum and brain levels of methylone and nor-methylone peaked at 30 min after s.c. administration. fpsyt.2017.00232
Brain penetration is highly preferential, with a serum:brain ratio of 1:7.97supported
Both drugs readily penetrated brain with serum:brain ratio 1:7.97. fpsyt.2017.00232
Claim in pharmacology — not_supportednot supportedworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
The ring-opened metabolites interact differentially with human monoaminergic systemssupported
N-demethylation or opening of the 3,4-methylenedioxy ring via O-demethylenation gives rise to pharmacologically active metabolites of methylone. 0269881119844185
summary15 · 12 ok
Unlike MDMA, repeated dosing in rats does not produce long-term serotonergic neurotoxicitysupported
Repeated dosing causes hyperthermia but no long-term 5-HT depletion unlike MDMA. npp.2011.304
Unlike MDMA, repeated dosing in rats does not produce long-term serotonergic neurotoxicitysupported
Methylone does not cause long-term 5-HT depletion unlike MDMA despite hyperthermia. 7854_2016_21
Claim in summary — inconclusiveinconclusiveworking →
Following permanent DEA Schedule I classification in 2013, the compound underwent therapeutic rediscovery: a Phase 2 randomized controlled trial (IMPACT-1) demonstrated a placebo-adjusted CAPS-5 improvement of −9.64 points for PTSD, leading to FDA Breakthrough Therapy Designation in July 2025 and a Priority Review Voucher in April 2026.partially supported
Primary endpoint met: CAPS-5 improvement -9.64 points on Day 64. jamapsychiatry.2025.4625
Methylone functions as a substrate (releaser) at the dopamine, norepinephrine, and serotonin transporters while simultaneously inhibiting monoamine reuptakesupported
Methylone, mephedrone, ethylone, butylone act as non-selective monoamine uptake inhibitors similar to cocaine. Mephedrone, methylone, ethylone and butylone also induced 5-HT release similar to MDMA. j.1476-5381.2012.02145.x
Methylone functions as a substrate (releaser) at the dopamine, norepinephrine, and serotonin transporters while simultaneously inhibiting monoamine reuptakesupported
Methylone and mephedrone are nonselective substrates for plasma membrane monoamine transporters, similar to MDMA in potency and selectivity. npp.2011.304
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — not_supportednot supportedworking →
The β-keto group abolishes TAAR1 activity present in MDMA and reduces lipophilicity, while preserving high blood-brain barrier permeability (serum:brain ratio 1:7.97 in rats).partially supported
Both drugs readily penetrated brain with serum:brain ratio 1:7.97. fpsyt.2017.00232
The experiential profile — reported in review literature rather than controlled human studies — includes empathogenic warmth, psychomotor stimulation, euphoria, and enhanced sociability, resembling MDMA but shorter in duration and reportedly lower in intensitysupported
Desired effects: increased energy, empathy, libido. Cardiovascular/psychiatric adverse effects. sar.s37257
Cardiovascular toxicity is the primary acute safety concern: sudden cardiac death has been documented in both predisposed and previously healthy individuals, and blood methylone concentration does not reliably predict lethalitysupported
First reported case of sudden cardiac death associated with methylone in a previously healthy 19-year-old. paf.0b013e31827ab5da
Cardiovascular toxicity is the primary acute safety concern: sudden cardiac death has been documented in both predisposed and previously healthy individuals, and blood methylone concentration does not reliably predict lethalitysupported
Fatal methylone case in a 16-year-old with cardiac malformation. oh.2012.29310
Cardiovascular toxicity is the primary acute safety concern: sudden cardiac death has been documented in both predisposed and previously healthy individuals, and blood methylone concentration does not reliably predict lethalitysupported
Lethal concentrations cannot be established. 1556-4029.13316
Hyperthermia risk increases markedly in crowded environmentssupported
Methylone dose-dependently increased locomotion and induced hyperthermia (more pronounced in group-housed conditions). fpsyt.2017.00232
Rodent self-administration demonstrates reinforcing effects comparable to MDMA but without the dose escalation seen with cocaine or methamphetamine, suggesting moderate abuse liabilitysupported
Long access did not lead to escalated intake unlike cocaine. Abuse potential similar to or greater than MDMA but lower compulsive use potential than prototypical stimulants. pmid:24244886
pharmacokinetic-detail7 · 6 ok
In rodent studies, a dose of 40 mg/kg s.c. proved surprisingly lethal to some animals, indicating a steep dose-response curve at high doses.supported
40 mg/kg s.c. lethal to some animals. Short duration of action. fpsyt.2017.00232
The most comprehensive pharmacokinetic characterization of methylone derives from rat studies following subcutaneous administration:supported
Serum and brain levels of methylone and nor-methylone peaked at 30 min after s.c. administration. Both drugs readily penetrated brain with serum:brain ratio 1:7.97. fpsyt.2017.00232
The 1:7.97 serum:brain ratio indicates highly preferential CNS accumulation, and the coincidence of peak brain concentration with maximum behavioral effects confirms rapid central distributionsupported
Both drugs readily penetrated brain with serum:brain ratio 1:7.97. Methylone dose-dependently increased locomotion and induced hyperthermia. fpsyt.2017.00232
Methylone's two enantiomers exhibit distinct pharmacokinetic and toxicological profiles. S-(−)-methylone demonstrates greater absorption across Caco-2 intestinal cell monolayers, suggesting enantioselective oral bioavailability favoring this enantiomersupported
S-(-)-methylone is the most absorbed enantiomer in Caco-2 intestinal cell model. Enantioselectivity in intestinal permeability first demonstrated for this cathinone class. j.taap.2020.114970
Two primary metabolic pathways are characterized:supported
N-demethylation or opening of the 3,4-methylenedioxy ring via O-demethylenation gives rise to pharmacologically active metabolites of methylone. 0269881119844185
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
The Phase 2 PTSD trial (IMPACT-1) employed four oral doses separated by one week, suggesting the acute effect duration is manageable within a single clinical session.supported
65 patients with severe PTSD, 4 oral doses separated by one week. jamapsychiatry.2025.4625
comparative-pharmacology6 · 4 ok
The key therapeutic distinction is neurotoxicity: repeated methylone dosing (3.0 and 10.0 mg/kg s.c.) in rats does not produce the long-term depletion of cortical or striatal serotonin that characterizes MDMA neurotoxicitysupported
Repeated dosing causes hyperthermia but no long-term 5-HT depletion unlike MDMA. npp.2011.304
The key therapeutic distinction is neurotoxicity: repeated methylone dosing (3.0 and 10.0 mg/kg s.c.) in rats does not produce the long-term depletion of cortical or striatal serotonin that characterizes MDMA neurotoxicitysupported
Methylone does not cause long-term 5-HT depletion unlike MDMA despite hyperthermia. 7854_2016_21
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Compared to mephedrone (4-methylmethcathinone), methylone shares the "cocaine-MDMA mixed" profile — both are transporter substrates rather than pure uptake blockerssupported
Methylone, mephedrone, ethylone, butylone act as non-selective monoamine uptake inhibitors similar to cocaine. Mephedrone, methylone, ethylone and butylone also induced 5-HT release similar to MDMA. j.1476-5381.2012.02145.x
Structure-activity relationship analysis indicates that the methylenedioxy substitution on the cathinone scaffold is the primary determinant of entactogenic character: it shifts selectivity toward serotonergic activity relative to unsubstituted cathinones.supported
Updated SAR review of 209+ synthetic cathinones... Methylone's 3,4-methylenedioxy ring substitution confers MDMA-like entactogen profile. acsptsci.4c00299
neuroscience6 · 4 ok
Claim in neuroscience — inconclusiveinconclusiveworking →
DAT substrate activity drives dopamine efflux in the nucleus accumbens, producing the stimulant and euphoric components of the methylone experience. In vivo microdialysis confirms dose-dependent extracellular dopamine elevation, though the magnitude is less than that produced by methamphetamine — consistent with methylone's intermediate position between pure stimulants and pure entactogens.supported
IV administration increases extracellular DA and 5-HT in rat nucleus accumbens. npp.2011.304
The behavioral evidence supports this: methylone produces rapid and durable improvements in fear extinction recall, with NET activity (not SERT) identified as the critical mediator for this behavioral effect.supported
Long-lasting effects on fear extinction learning and memory observed. NET activity required for behavioral effect (blocked by reboxetine). s41386-025-02206-z
Claim in neuroscience — inconclusiveinconclusiveworking →
The characterization of methylone as a neuroplastogen aligns with the broader psychoplastogen hypothesis — the proposal that rapid-acting psychiatric treatments (including ketamine, MDMA, and classical psychedelics) share a common downstream mechanism of structural and functional neural plasticity, mediated through BDNF-trkB-mTOR signaling cascadessupported
Described as highly selective rapid-acting neuroplastogen releasing 5-HT, NE, DA without 5-HT2A activity. jamapsychiatry.2025.4625
Methylone's enhancement of fear extinction recall is directly relevant to reconsolidation-based models of PTSD therapysupported
Long-lasting effects on fear extinction learning and memory observed... Supports mechanism as rapid-acting neuroplastogen for PTSD. s41386-025-02206-z
receptor-pharmacology5 · 4 ok
Specific IC₅₀ values for uptake inhibition and EC₅₀ values for substrate-induced release have been reported in full-text publications, though numerical values available from abstracts are limitedsupported
Designer beta-keto amphetamines pharmacology characterized. Methylone, mephedrone, ethylone, butylone act as non-selective monoamine uptake inhibitors similar to cocaine. j.1476-5381.2012.02145.x
Specific IC₅₀ values for uptake inhibition and EC₅₀ values for substrate-induced release have been reported in full-text publications, though numerical values available from abstracts are limitedsupported
Methylone had higher inhibitory potency at uptake than binding and induced release of neurotransmitter from hDAT, hSERT and hNET. j.bcp.2013.04.004
The compound's classification as a "cocaine-MDMA mixed" cathinone reflects its dual action: it inhibits DA and 5-HT uptake with approximately equal potency (similar to cocaine) while also triggering carrier-mediated 5-HT release (similar to MDMA).supported
Methylone, mephedrone, ethylone, butylone act as non-selective monoamine uptake inhibitors similar to cocaine. Mephedrone, methylone, ethylone and butylone also induced 5-HT release similar to MDMA. j.1476-5381.2012.02145.x
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Methylone's roughly equipotent DAT and SERT inhibition, combined with preferential serotonin release, produces an intermediate profilesupported
Methylone classified as MDMA-like cathinone. DA/SERT ratio determines psychotropic vs toxic effects. smw.2015.14043
effects-overview3 · 1 ok
The experience is notably sensitive to ambient temperature and social context: crowded, warm environments amplify both the empathogenic warmth and the physiological risks (particularly hyperthermia), while solitary use tends to foreground the stimulant componentsupported
Methylone dose-dependently increased locomotion and induced hyperthermia (more pronounced in group-housed conditions). fpsyt.2017.00232
Claim in effects-overview — inconclusiveinconclusiveworking →
Claim in effects-overview — inconclusiveinconclusiveworking →
history3 · 0 ok
clinical-evidence2 · 1 ok
NCT05741710 — Safety and efficacy of methylone in PTSD. Status: completed. Results contributed to the Phase 2 development program and were referenced in the JAMA Psychiatry Phase 2 publication.supported
Phase 2 RCT of TSND-201 (methylone) for PTSD. [Scope: NCT05741710 and NCT06215261] jamapsychiatry.2025.4625
Claim in clinical-evidence — inconclusiveinconclusiveworking →
chemistry1 · 1 ok
The enantiomers differ in both pharmacokinetic and toxicological properties: S-(−)-methylone exhibits greater intestinal absorption across Caco-2 cell models, suggesting enantioselective oral bioavailability, while R-(+)-methylone is the more oxidative and cytotoxic enantiomer in dopaminergic SH-SY5Y neuronal cells.supported
S-(-)-methylone is the most absorbed enantiomer in Caco-2 intestinal cell model. Enantioselectivity in intestinal permeability first demonstrated for this cathinone class. j.taap.2020.114970