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MDA

3,4-methylenedioxyamphetamine

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what any key link opens

psx:substance/mda/proposal/duration/114b071b-1c8e-4e1f-bdfb-2c8298d9789a

proposal2026-04-24recordapproved

derived from · upstream

none recorded

feeds · downstream

Closure of psx:substance/mda/proposal/duration/114b071b-1c8e-4e1f-bdfb-2c8298d9789a: 0 upstream, 1 downstream.

psx:substance/mda/proposal/duration/114b071b-1c8e-4e1f-bdfb-2c8298d9789a
└─ derived_from  value/duration/oral/offset@1

indented by distance from this node, not by parentage

1Provenance card

the boundary, as counts

Sources

2910 with DOI

3 strong · 22 moderate · 4 weak

Compilations

12026-04-24T16:04:30.434Z

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

Decisions

32last ruled 2026-06-04

0 awaiting a ruling

Issued documents

42026-10-19T20:32:37.135Z

notice · info card · emergency

Searches

274 with no results

queries and counts on the build

Claims checked

8667 supported

67 supported · 19 not

Correspondence

0received

consent field ships in Phase 4

Edges

273

derivations recorded for this entity

Complete over 29 sources, 1 compilation, and 32 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/mda/archive

2Build

one panel per compilation run

generation run 2026-04-24

67 min completedmodel pipeline-v5plan not recordedrun/68703491…

Selection

results seen112
selected by the model35
consumed as sources29

Verification

claims checked86
supported63
partially supported4
not supported2
inconclusive17
  • record
  • seen / partial
  • working

The model's own caveats

none raised on this run

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
27 searches — query, source, results, what was kept and why
27 searches for this run
#sourcequeryseenkeptrationale
1PubMedmethylenedioxyamphetamine metabolism neurotoxicity role22—
2PubMed · absenceMDA MDMA serotonin syndrome drug interaction tramadol0——
3PubChemCID 161411—
4PubChem · absenceMDA 3,4-methylenedioxyamphetamine01—
5PubMedMDA 3,4-methylenedioxyamphetamine pharmacology receptor binding83—
6PubMedMDA methylenedioxyamphetamine serotonin transporter monoamine release Ki11—
7PubMedmethylenedioxyamphetamine neurotoxicity serotonin dopamine101—
8PubMedMDA methylenedioxyamphetamine hyperthermia overdose death case report11—
9PubMedMDA methylenedioxyamphetamine human pharmacokinetics half-life urine42—
10PubMedMDA methylenedioxyamphetamine cardiovascular blood pressure heart rate74—
11OpenAlexMDA methylenedioxyamphetamine neurotoxicity serotonin axon terminal (citation-sorted)82—
12PubMedMDA methylenedioxyamphetamine 5-HT2A agonist psychedelic mechanism11—
13PubMedMDA drug discrimination amphetamine LSD11—
14PubMed · absenceMDA MDMA serotonin syndrome lethal interaction opioid0——
15PubMedNichols entactogen MDMA MBDB pharmacology class11—
16OpenAlexMDA 3,4-methylenedioxyamphetamine pharmacology (citation-sorted)101—
17PubMedPMID 40999236 (Straumann 2026 MDA vs MDMA RCT)11—
18ClinicalTrials.govmethylenedioxyamphetamine MDA101—
19WebSearchMDA 3,4-methylenedioxyamphetamine Schedule I DEA 1970 legal history scheduling101—
20OpenAlextramadol serotonin syndrome interaction amphetamine MDMA pharmacodynamic51—
21WebFetchWikidoc MDA page13—
22WebSearchMDA UK Canada Australia legal status Misuse of Drugs Act103—
23WebSearchMDA methylenedioxyamphetamine synthesis history 1910 Mannich patent101—
24OpenAlexMDA methylenedioxyamphetamine human study subjective effects entactogen (citation-sorted)80—
25PLoS ONE (WebFetch)Baggott 2010 MDA RCT full data11—
26PubMed + OpenAlex · absenceMultiple final searches for tolerance, dependence, harm reduction MDA-specific00—
27PubMedStraumann 2025 2026 MDA MDMA lysine prodrug crossover NCT0484720611—
86 claims by section — every cited sentence, checked against its source
safety22 · 22 ok
  • The landmark preclinical study by O'Hearn et al. (1988) demonstrated that MDA (20 mg/kg s.c., twice daily for 4 days) caused profound and selective loss of serotonergic (5-HT) axon terminals throughout the rat forebrain, while completely sparing catecholamine axons. MDA produced a greater reduction of 5-HT axons than MDMA at the same dosage — establishing that MDA is more neurotoxic than MDMA on a per-dose basissupported

    MDA/MDMA cause selective serotonergic axon terminal ablation in rat forebrain. MDA more neurotoxic than MDMA at same dose. Catecholamine axons completely spared. pmid:2457659

  • The mechanism is metabolic, not direct: MDA undergoes CYP2D6-mediated O-demethylenation to alpha-methyldopamine (alpha-MeDA), which oxidizes to an ortho-quinone and conjugates with glutathione to form thioether adductssupported

    Neither MDA nor MDMA produces neurotoxicity when injected directly into brain. Alpha-methyldopamine (alpha-MeDA)...their thioether conjugates...produce long-term depletions in serotonin concentrations. pmid:15228153

  • The mechanism is metabolic, not direct: MDA undergoes CYP2D6-mediated O-demethylenation to alpha-methyldopamine (alpha-MeDA), which oxidizes to an ortho-quinone and conjugates with glutathione to form thioether adductssupported

    MDMA and MDA are O-demethylenated to N-Me-alpha-MeDA and alpha-MeDA (catechols) which oxidize to ortho-quinones and conjugate with glutathione. pmid:17467183

  • MDA injected directly into the brain does not produce neurotoxicity, confirming the requirement for peripheral metabolism.supported

    Neither MDA nor MDMA produces neurotoxicity when injected directly into brain. pmid:15228153

  • Temperature dependence: Malberg and Seiden (1998) demonstrated that small (2°C) changes in ambient temperature produce large changes in MDMA/MDA-induced serotonin neurotoxicity in ratssupported

    Small (2°C) changes in ambient temperature produce large changes in MDMA neurotoxicity and core temperature. jneurosci.18-13-05086.1998

  • Bexis and Docherty (2006) compared cardiovascular effects of MDMA, MDA, and MDEA in freely moving rats using radiotelemetrysupported

    MDMA and MDA produced prolonged increases in blood and diastolic pressures; MDA caused the most marked rise. pmid:16491100

  • The pressor effect is mediated by alpha-1A and alpha-1D adrenoceptor agonism — MDA is the most potent alpha-1 agonist in the MDxx series.supported

    MDA most potent at alpha1-adrenoceptors. pmid:16491100

  • In mice, MDA produced potent hyperthermia partially antagonized by bretylium and blocked by haloperidol, implicating both noradrenergic and dopaminergic mechanisms.supported

    MDA had potent hyperthermic effect in mice partially antagonized by bretylium, blocked by haloperidol. pmid:1174022

  • The intravenous LD50 in dogs is 8.1 mg/kg (95% CI: 7.0–9.4 mg/kg), with LD1 ≈ 5 mg/kg and LD99 ≈ 14 mg/kgsupported

    LD50 and 95% CI: 8.1 (7.0-9.4) mg/kg IV. LD1 approx 5 mg/kg, LD99 approx 14 mg/kg. pmid:3753103

  • At lethal IV doses, death was preceded by hyperthermia, tachycardia, and hypertension progressing to cardiovascular depression and respiratory failuresupported

    High IV dose of MDA (20 mg/kg) in dogs elevated body temperature, heart rate, blood pressure initially then depression and death. pmid:3699443

  • Chlorpromazine (10 mg/kg IV) administered after MDA overdose led to stabilization and 48-hour survival in dogs.supported

    Chlorpromazine (10 mg/kg IV) after MDA showed stabilization and 48h survival. pmid:3699443

  • De Letter et al. (2006) reviewed amphetamine-related fatalities in Ghent, Belgium from 1976–2004supported

    In 34 fatalities, amphetamines were involved (including MDA). pmid:16454462

  • The Straumann et al. (2026) RCT documented significantly greater "fear" and "bad drug effects" with MDA compared to MDMA at equimolar dosessupported

    MDA induced greater stimulant effects, more bad drug effects, more fear, more visual alterations. s41386-025-02248-3

  • MDA's greater stimulant and adverse effect burden compared to MDMA suggests that compulsive use patterns are pharmacologically plausible via dopaminergic reinforcement, but the elevated fear and dysphoria may paradoxically limit compulsive redosingsupported

    MDA induced greater stimulant effects, more bad drug effects, more fear, more visual alterations. s41386-025-02248-3

  • In severe cases, serotonin syndrome manifests as hyperthermia, muscle rigidity, clonus, autonomic instability, and multiple organ failure.supported

    Serotonin toxicity characterised by neuromuscular excitation (clonus, hyperreflexia, myoclonus, rigidity), autonomic stimulation (hyperthermia, tachycardia, diaphoresis). j.1326-5377.2007.tb01282.x

  • Tramadol: Tramadol inhibits SERT and NET at clinically relevant concentrationssupported

    Opioids may inhibit the SERT and NET. Tramadol SERT inhibition may contribute to serotonin syndrome risk. bph.14105

  • Fluoxetine, paroxetine, quinidine, bupropion, and other CYP2D6 inhibitors reduce MDA metabolism, substantially increasing plasma MDA concentrations and toxicity risksupported

    MDMA is a potent mechanism-based inhibitor (MBI) of CYP2D6...CYP2D6 inactivation relevant to MDA metabolism. pmid:16478752

  • The norepinephrine transporter inhibitor reboxetine reduces MDMA's cardiovascular and stimulant effects by blocking NET-mediated norepinephrine releasesupported

    Reboxetine reduced MDMA effects including elevations in plasma NE, blood pressure and heart rate, drug high, stimulation...NE transporter-mediated NE release has critical role in cardiovascular and stimulant-like effects of MDMA. clpt.2011.78

  • Cardiovascular disease and hypertension: MDA is the most potent pressor agent in the MDxx seriessupported

    MDA caused the most marked rise. MDA most potent at alpha1-adrenoceptors. pmid:16491100

  • Hepatic impairment: MDA metabolism is CYP2D6/CYP3A4 dependentsupported

    demethylenation (CYP2D6 or CYP3A2/4) pmid:10720722

  • Mechanistic basis for lethal serotonin toxicity is established.supported

    Tramadol SERT inhibition may contribute to serotonin syndrome risk. bph.14105

  • Mechanistic basis for lethal serotonin toxicity is established.supported

    Severe serotonin toxicity only occurs with combinations of drugs acting at different sites. j.1326-5377.2007.tb01282.x

pharmacology19 · 15 ok
  • Claim in pharmacology — not_supportednot supportedworking →

  • Claim in pharmacology — inconclusiveinconclusiveworking →

  • Kolaczynska et al. (2022) established that MDA inhibits NET with the greatest potency among the three transporters and preferentially inhibits serotonin over dopamine uptakesupported

    MDA, its fluorinated analogs...inhibited NET with the greatest potency and preferentially inhibited 5-HT vs. dopamine uptake. j.euroneuro.2022.03.006

  • The potency order for dopamine release from striatal synaptosomes is MDA > MDMA > MDEA = MDBA, while MDA and MDMA are equipotent at inducing serotonin release from cortical and hippocampal preparationssupported

    MDA, MDMA and MDEA were equipotent at inducing [3H]5-HT release from frontal cortex/hippocampal synaptosomes...The potency order for inducing [3H]DA release from striatal synaptosomes was MDA > MDMA > MDEA = MDBA. pmid:11371001

  • The potency order for dopamine release from striatal synaptosomes is MDA > MDMA > MDEA = MDBA, while MDA and MDMA are equipotent at inducing serotonin release from cortical and hippocampal preparationssupported

    MDA, MDMA and MDEA were equipotent at inducing [3H]5-HT release...The potency order for inducing [3H]DA release from striatal synaptosomes was MDA > MDMA > MDEA = MDBA. pmid:11371001

  • This greater dopaminergic releasing activity underlies MDA's more pronounced stimulant profile relative to MDMA, a difference confirmed in human subjects.supported

    MDA induced greater stimulant effects, more bad drug effects, more fear, more visual alterations. s41386-025-02248-3

  • Unlike MDMA, MDA also binds and activates the 5-HT₂A receptor directly, with affinity in the low-micromolar range (Ki ≤ 10 µM in radioligand binding assays; partial or full agonist in functional activation assays)supported

    Most compounds bound to 5-HT2A and 5-HT2C receptors (Ki ≤ 10 μM) and several substances activated the 5-HT2A and 5-HT2B receptor as partial or full agonists. j.euroneuro.2022.03.006

  • Drug discrimination studies confirm this dual character: MDA substitutes for both LSD and amphetamine in trained animals, while MDMA is primarily amphetamine-like at typical dosessupported

    MDMA is apparently 'amphetamine-like' and not 'LSD-like' while MDA is apparently both 'LSD-like' and 'amphetamine-like.' pmid:1979215

  • The MDMA discriminative cue generalizes completely to MDA, confirming shared entactogen-class properties.supported

    MDMA cue completely generalized to MDA but not to LSD or DOM. pmid:2898791

  • Claim in pharmacology — inconclusiveinconclusiveworking →

  • Plasma elimination half-life (geometric mean) is 8.4 hours, measured in the same crossover RCT at 92 mg oral (for comparison, MDMA half-life was 7.3 hours under identical conditions)supported

    Plasma half-life: MDMA 7.3h, MDA 8.4h. s41386-025-02248-3

  • MDA undergoes hepatic metabolism through two primary pathways:supported

    demethylenation (CYP2D6 or CYP3A2/4) followed by COMT methylation and/or glucuronide/sulfate conjugation; N-dealkylation and deamination to benzoic acid derivatives. pmid:10720722

  • Claim in pharmacology — inconclusiveinconclusiveworking →

  • Poor CYP2D6 metabolizers and individuals taking CYP2D6 inhibitors (fluoxetine, paroxetine, quinidine) will experience elevated MDA plasma concentrations and increased toxicity risksupported

    MDMA is a potent mechanism-based inhibitor (MBI) of CYP2D6...CYP2D6 inactivation relevant to MDA metabolism. pmid:16478752

  • These thioether metabolites cross the blood-brain barrier, stimulate acute monoamine release, and cause long-term serotonergic neuronal death, elevated GFAP expression (an astrogliosis marker), and microglial activationsupported

    their thioether conjugates stimulate acute release of serotonin, dopamine, and norepinephrine and produce long-term depletions in serotonin concentrations, elevations in GFAP expression, and activation of microglial cells. pmid:15228153

  • These thioether metabolites cross the blood-brain barrier, stimulate acute monoamine release, and cause long-term serotonergic neuronal death, elevated GFAP expression (an astrogliosis marker), and microglial activationsupported

    Thioether MDMA metabolites are strong neurotoxins, significantly more than their parent catechols...Hyperthermia (40°C) accelerated neuronal death. pmid:17467183

  • Critically, MDA does not produce neurotoxicity when injected directly into the brain — only when administered peripherally, demonstrating that hepatic metabolism to these reactive intermediates is required for neurotoxicitysupported

    Neither MDA nor MDMA produces neurotoxicity when injected directly into brain. pmid:15228153

  • Alpha-MeDA is more neurotoxic than MDA itself, and the glutathione-thioether conjugates are the most toxic species in the pathway.partially supported

    Thioether MDMA metabolites are strong neurotoxins, significantly more than their parent catechols. N-Me-alpha-MeDA and alpha-MeDA are more neurotoxic than MDMA. pmid:17467183

  • MDA is produced in vivo by N-demethylation of MDMA at a plasma ratio of approximately 3–5:100 (MDA:MDMA)supported

    MDMA biotransformed into MDA; plasma MDA:MDMA ratio 3-5/100 in monkeys, similar to humans. pmid:15999148

summary13 · 11 ok
  • It produces stimulant, entactogenic, and psychedelic effects over a total duration of approximately 5–8 hours (mean 6.1 ± 0.5 hours at 92 mg oral), placing it at the intersection of three pharmacological classes — a profile shared by few other compounds.supported

    MDA produced stronger/longer-lasting effects (6.1±0.5h vs 4.1±0.4h). MDA induced greater stimulant effects...more visual alterations. s41386-025-02248-3

  • It served as a conceptual anchor for David Nichols' 1986 coinage of the term "entactogen"supported

    Seminal paper coining the term 'entactogen' for a new pharmacological class including MDA and MDMA, distinguishing them from classic hallucinogens and stimulants. pmid:2880944

  • No clinical trials have investigated MDA as a primary therapeutic agent; the compound's current research significance lies in comparative pharmacology with mdma, where a 2026 head-to-head RCT established MDA's distinct psychedelic and adverse-effect profile.supported

    MDA (92mg) vs MDMA (100mg) equimolar crossover. MDA induced greater stimulant effects, more bad drug effects, more fear, more visual alterations. NCT04847206. s41386-025-02248-3

  • MDA acts as a substrate-type releaser at the serotonin, dopamine, and norepinephrine transporters, with greatest potency at NET and greater dopaminergic releasing activity than MDMApartially supported

    MDA, its fluorinated analogs...inhibited NET with the greatest potency and preferentially inhibited 5-HT vs. dopamine uptake. j.euroneuro.2022.03.006

  • MDA acts as a substrate-type releaser at the serotonin, dopamine, and norepinephrine transporters, with greatest potency at NET and greater dopaminergic releasing activity than MDMApartially supported

    The potency order for inducing [3H]DA release from striatal synaptosomes was MDA > MDMA > MDEA = MDBA. pmid:11371001

  • Claim in summary — not_supportednot supportedworking →

  • Claim in summary — inconclusiveinconclusiveworking →

  • Set and setting modulate the balance between prosocial warmth and anxiety, a dynamic confirmed by the elevated "fear" and "bad drug effects" scores reported under controlled conditions.supported

    MDA induced greater stimulant effects, more bad drug effects, more fear, more visual alterations. s41386-025-02248-3

  • In preclinical models, it produces greater selective serotonergic axon terminal ablation at equivalent doses, mediated by neurotoxic thioether metabolites of alpha-methyldopamine formed via CYP2D6supported

    MDA/MDMA cause selective serotonergic axon terminal ablation in rat forebrain. MDA more neurotoxic than MDMA at same dose. Catecholamine axons completely spared. pmid:2457659

  • In preclinical models, it produces greater selective serotonergic axon terminal ablation at equivalent doses, mediated by neurotoxic thioether metabolites of alpha-methyldopamine formed via CYP2D6supported

    Alpha-methyldopamine (alpha-MeDA) and N-methyl-alpha-MeDA are metabolites of both MDA and MDMA; their thioether conjugates...produce long-term depletions in serotonin concentrations, elevations in GFAP expression. pmid:15228153

  • In preclinical models, it produces greater selective serotonergic axon terminal ablation at equivalent doses, mediated by neurotoxic thioether metabolites of alpha-methyldopamine formed via CYP2D6supported

    MDMA and MDA are O-demethylenated to N-Me-alpha-MeDA and alpha-MeDA (catechols) which oxidize to ortho-quinones and conjugate with glutathione. Thioether MDMA metabolites are strong neurotoxins. pmid:17467183

  • Cardiovascular risk is elevated: MDA is the most potent pressor agent among the MDxx compounds, acting through alpha-1 adrenoceptor agonismsupported

    MDA caused the most marked rise [in blood pressure]. MDA most potent at alpha1-adrenoceptors. pmid:16491100

  • Ambient temperature strongly modulates neurotoxicity — small increases in environmental heat dramatically amplify serotonergic damagesupported

    Small (2°C) changes in ambient temperature produce large changes in MDMA neurotoxicity and core temperature. jneurosci.18-13-05086.1998

receptor-pharmacology9 · 8 ok
  • Kolaczynska et al. (2022) characterized the transporter potency profile: MDA inhibits NET with the greatest potency, followed by SERT, with DAT inhibition being weakestsupported

    MDA...inhibited NET with the greatest potency and preferentially inhibited 5-HT vs. dopamine uptake. j.euroneuro.2022.03.006

  • This triple-releasing profile is shared across the MDxx series, but MDA's relative dopaminergic potency exceeds that of MDMA: the rank order for dopamine release from striatal synaptosomes is MDA > MDMA > MDEA.supported

    The potency order for inducing [3H]DA release from striatal synaptosomes was MDA > MDMA > MDEA = MDBA. pmid:11371001

  • Kolaczynska et al. (2022) reported Ki ≤ 10 µM in radioligand binding and partial-to-full agonist activity in functional assayssupported

    Most compounds bound to 5-HT2A and 5-HT2C receptors (Ki ≤ 10 μM) and several substances activated the 5-HT2A and 5-HT2B receptor as partial or full agonists. j.euroneuro.2022.03.006

  • This 5-HT₂A agonism is pharmacologically confirmed in vivo: Teitler et al. (1990) demonstrated that MDA is both "LSD-like" and "amphetamine-like" in drug discrimination paradigms, a dual substitution pattern that requires 5-HT₂A activation (for the LSD cue) in addition to monoamine release (for the amphetamine cue)supported

    MDA is apparently both 'LSD-like' and 'amphetamine-like'...The data...strongly implicate the brain 5HT2 receptor as the site-of-action of the hallucinogenic PIAs and LSD. pmid:1979215

  • MDA binds the 5-HT₂C receptor (Ki ≤ 10 µM) and activates it as a partial or full agonist. 5-HT₂C activation generally opposes dopaminergic transmission in mesolimbic circuits and may contribute to appetite suppression and anxiogenic effects.partially supported

    Most compounds bound to 5-HT2A and 5-HT2C receptors (Ki ≤ 10 μM) and several substances activated the 5-HT2A and 5-HT2B receptor as partial or full agonists. j.euroneuro.2022.03.006

  • MDA is the most potent compound among the MDxx series at alpha-1A and alpha-1D adrenoceptorssupported

    MDA most potent at alpha1-adrenoceptors. pmid:16491100

  • This alpha-1 agonism is the primary mechanism for MDA's pressor effects — the most marked blood pressure elevation among MDMA, MDA, and MDEA in radiotelemetry studiessupported

    MDMA and MDA produced prolonged increases in blood and diastolic pressures; MDA caused the most marked rise. MDA most potent at alpha1-adrenoceptors. pmid:16491100

  • Claim in receptor-pharmacology — inconclusiveinconclusiveworking →

  • MDA modulates human GABA-A receptors (α₁β₂γ₂ subunit composition) in a bidirectional, occupancy-dependent manner: inhibition at low receptor occupancy and potentiation at high occupancysupported

    MDMA and its metabolite MDA both inhibited the GABA-evoked current at low receptor occupancy. However...MDA induced a potentiation. j.neuro.2011.05.016

neuroscience6 · 2 ok
  • MDA's equipotent serotonin release relative to MDMA suggests comparable engagement of these circuits, though the simultaneous 5-HT₂A agonism may modulate the qualitative character of the experience.supported

    MDA, MDMA and MDEA were equipotent at inducing [3H]5-HT release from frontal cortex/hippocampal synaptosomes. pmid:11371001

  • Claim in neuroscience — inconclusiveinconclusiveworking →

  • Claim in neuroscience — inconclusiveinconclusiveworking →

  • Claim in neuroscience — inconclusiveinconclusiveworking →

  • The greater stimulant effects of MDA relative to MDMA in human subjects reflect this enhanced catecholaminergic profile.supported

    MDA induced greater stimulant effects, more bad drug effects, more fear, more visual alterations. s41386-025-02248-3

  • Claim in neuroscience — inconclusiveinconclusiveworking →

pharmacokinetic-detail5 · 2 ok
  • Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →

  • Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →

  • Like MDMA, MDA is expected to exhibit mechanism-based (irreversible) inhibition of CYP2D6, meaning the enzyme that metabolizes MDA is destroyed in the processsupported

    MDMA is a potent mechanism-based inhibitor (MBI) of CYP2D6, causing quasi-irreversible inhibition in vitro...CYP2D6 inactivation relevant to MDA metabolism. pmid:16478752

  • Phase I metabolism proceeds through two principal routes:supported

    Phase I and II metabolites of MDA identified in human urine: demethylenation (CYP2D6 or CYP3A2/4)...N-dealkylation and deamination to benzoic acid derivatives. pmid:10720722

  • Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →

clinical-evidence3 · 2 ok
  • The only published RCT specifically designed around MDA's psychedelic properties:supported

    RCT investigating mechanisms of drug-induced visions using MDA in humans. Very few serotonergic hallucinogens have been studied in humans in decades. journal.pone.0014074

  • Claim in clinical-evidence — inconclusiveinconclusiveworking →

  • The definitive comparative human pharmacology study:supported

    N=23 healthy participants. MDA (92mg) vs MDMA (100mg) equimolar crossover...Plasma half-life: MDMA 7.3h, MDA 8.4h. s41386-025-02248-3

comparative-pharmacology3 · 2 ok
  • In the dopamine release rank order, MDEA = MDBA and both fall below MDMA, which falls below MDAsupported

    The potency order for inducing [3H]DA release from striatal synaptosomes was MDA > MDMA > MDEA = MDBA. pmid:11371001

  • Claim in comparative-pharmacology — inconclusiveinconclusiveworking →

  • Schindler et al. (2014) demonstrated that MDA is a cardiovascular-active MDMA metabolite, contributing to the pressor and tachycardic effects observed during MDMA sessionssupported

    Cardiovascular effects of MDMA and its metabolites in conscious rats. Metabolites including MDA contribute to cardiovascular effects of MDMA. bph.12423

chemistry2 · 0 ok
  • Claim in chemistry — inconclusiveinconclusiveworking →

  • Claim in chemistry — inconclusiveinconclusiveworking →

history2 · 2 ok
  • In 1986, David Nichols published a landmark paper coining the term "entactogen" — literally "touching within" — to describe a novel pharmacological class encompassing MDA, MDMA, and MBDB, distinguished from both classical hallucinogens and amphetamine-type stimulantssupported

    Seminal paper coining the term 'entactogen' for a new pharmacological class including MDA and MDMA, distinguishing them from classic hallucinogens and stimulants. pmid:2880944

  • The most significant modern study is a Phase 1 trial at the University Hospital Basel (NCT04847206, completed) that included MDA as a comparator arm alongside MDMA and their lysine prodrugs, generating the definitive head-to-head human data published by Straumann et al. in 2026supported

    N=23 healthy participants. MDA (92mg) vs MDMA (100mg) equimolar crossover...NCT04847206. s41386-025-02248-3

effects-overview1 · 1 ok
  • The anxiogenic potential is higher than with MDMA — fear and dysphoria are reported even in controlled settings — making psychological preparation and environment more consequential.supported

    MDA induced greater stimulant effects, more bad drug effects, more fear, more visual alterations. s41386-025-02248-3

legal-status1 · 0 ok
  • Claim in legal-status — inconclusiveinconclusiveworking →

3Sources

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

Sources 1 to 30
yearsourcetierstatusfeeds
2026Acute effects of MDMA, MDA, lysine-MDMA, and lysine-MDA in a randomized, double-blind, placebo-controlled, crossover trial in healthy participantsStraumann I, Vizeli P, Avedisian I, et al. · Neuropsychopharmacologydoi:10.1038/s41386-025-02248-3strongconsumed8 sections
2024MDA Legal and Scheduling Historyurl:755ecf5f019fcddfweakconsumedcited only
20233,4-Methylenedioxyamphetamine - Wikidocurl:92de597bb05858e8weakconsumedcited only
2022Pharmacological characterization of 3,4-methylenedioxyamphetamine (MDA) analogs and two amphetamine-based compounds: N,α-DEPEA and DPIAKolaczynska KE, Ducret P, Trachsel D, Hoener MC, Liechti ME, Luethi D · European Neuropsychopharmacologydoi:10.1016/j.euroneuro.2022.03.006moderateconsumed4 sections
2018Opioid-induced inhibition of the human 5-HT and noradrenaline transporters in vitro: link to clinical reports of serotonin syndromeRickli A, Liakoni E, Hoener MC, Liechti ME · British Journal of Pharmacologydoi:10.1111/bph.14105moderateconsumed1 section
2014Effects of 3,4-methylenedioxymethamphetamine (MDMA) and its main metabolites on cardiovascular function in conscious ratsSchindler CW, Thorndike EB, Blough BE, Tella SR, Goldberg SR, Baumann MH · British Journal of Pharmacologydoi:10.1111/bph.12423moderateconsumed1 section
2012An unusual clandestine laboratory synthesis of 3,4-methylenedioxyamphetamine (MDA)Dal Cason TA, Corbett CA, Poole PK, et al. · Forensic Science Internationaldoi:10.1016/j.forsciint.2012.10.002weakconsumed1 section
2011Modulation of human GABAA receptor function: a novel mode of action of drugs of abuseHondebrink L, Meulenbelt J, van Kleef RG, van den Berg M, Westerink RH · Neurotoxicologydoi:10.1016/j.neuro.2011.05.016moderateconsumed1 section
2011The norepinephrine transporter inhibitor reboxetine reduces stimulant effects of MDMA ("ecstasy") in humansHysek CM, Simmler LD, Ineichen M, Grouzmann E, Hoener MC, Brenneisen R, Huwyler J, Liechti ME · Clinical Pharmacology and Therapeuticsdoi:10.1038/clpt.2011.78strongconsumed1 section
2010Investigating the mechanisms of hallucinogen-induced visions using 3,4-methylenedioxyamphetamine (MDA): a randomized controlled trial in humansBaggott MJ, Siegrist JD, Galloway GP, Robertson LC, Coyle JR, Mendelson JE · PLoS ONEdoi:10.1371/journal.pone.0014074strongconsumed4 sections
2007Neurotoxicity mechanisms of thioether ecstasy metabolitesCapela JP, Macedo C, Branco PS, et al. · Neurosciencepmid:17467183moderateconsumed3 sections
2007Serotonin toxicity: a practical approach to diagnosis and treatmentIsbister GK, Buckley NA, Whyte IM · The Medical Journal of Australiadoi:10.5694/j.1326-5377.2007.tb01282.xmoderateconsumed1 section
2006Amphetamines as potential inducers of fatalities: a review in the district of Ghent from 1976-2004De Letter EA, Piette MH, Lambert WE, Cordonnier JA · Medicine, Science, and the Lawpmid:16454462weakconsumed1 section
2006Effects of MDMA, MDA and MDEA on blood pressure, heart rate, locomotor activity and body temperature in the rat involve alpha-adrenoceptorsBexis S, Docherty JR · British Journal of Pharmacologypmid:16491100moderateconsumed4 sections
2006Pharmacokinetic profile of single and repeated oral doses of MDMA in squirrel monkeys: relationship to lasting effects on brain serotonin neuronsMechan A, Yuan J, Hatzidimitriou G, Irvine RJ, McCann UD, Ricaurte GA · Neuropsychopharmacologypmid:15999148moderateconsumed1 section
2006The impact of experimental design on assessing mechanism-based inactivation of CYP2D6 by MDMA (Ecstasy)Van LM, Heydari A, Yang J, et al. · Journal of Psychopharmacologypmid:16478752moderateconsumed3 sections
2004Human pharmacology of MDMA: pharmacokinetics, metabolism, and dispositionde la Torre R, Farré M, Roset PN, Pizarro N, Abanades S, Segura M, Segura J, Camí J · Therapeutic Drug Monitoringpmid:15228154moderateconsumed2 sections
2004Stereochemical analysis of 3,4-methylenedioxymethamphetamine and its main metabolites in human samples including the catechol-type metabolitePizarro N, Farré M, Pujadas M, Peiró AM, Roset PN, Joglar J, de la Torre R · Drug Metabolism and Dispositionpmid:15319342moderateconsumed1 section
2004The role of metabolism in 3,4-(+)-methylenedioxyamphetamine and 3,4-(+)-methylenedioxymethamphetamine (ecstasy) toxicityMonks TJ, Jones DC, Bai F, Lau SS · Therapeutic Drug Monitoringpmid:15228153moderateconsumed3 sections
2001Behavioural, hyperthermic and neurotoxic effects of 3,4-methylenedioxymethamphetamine analogues in the Wistar ratO'Loinsigh ED, Boland G, Kelly JP, O'Boyle KM · Progress in Neuro-Psychopharmacology & Biological Psychiatrypmid:11371001moderateconsumed5 sections
2000Toxicokinetics and analytical toxicology of amphetamine-derived designer drugs ('Ecstasy')Maurer HH, Bickeboeller-Friedrich J, Kraemer T, Peters FT · Toxicology Letterspmid:10720722moderateconsumed3 sections
1998Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the RatMalberg JE, Seiden LS · Journal of Neurosciencedoi:10.1523/jneurosci.18-13-05086.1998moderateconsumed2 sections
1990Receptor pharmacology of MDMA and related hallucinogensTeitler M, Leonhardt S, Appel NM, De Souza EB, Glennon RA · Annals of the New York Academy of Sciencespmid:1979215moderateconsumed2 sections
1988Drug discrimination studies with MDMA and amphetamineOberlender R, Nichols DE · Psychopharmacologypmid:2898791moderateconsumed2 sections
1988Ring-substituted amphetamine interactions with neurotransmitter receptor binding sites in human cortexPierce PA, Peroutka SJ · Neuroscience Letterspmid:2906416moderateconsumed1 section
1986Differences between the mechanism of action of MDMA, MBDB, and the classic hallucinogens. Identification of a new therapeutic class: entactogensNichols DE · Journal of Psychoactive Drugspmid:2880944moderateconsumed2 sections
1986Effects of an i.v. lethal dose of 3,4-methylenedioxyamphetamine (MDA) in the dog and antagonism by chlorpromazineDavis WM, Catravas JD, Waters IW · General Pharmacologypmid:3699443moderateconsumed1 section
1986Effects of anesthesia and phenoxybenzamine on responses of dogs to IV subtoxic doses of 3,4-methylenedioxyamphetamine (MDA)Waters IW, Catravas JD, Davis WM · Archives Internationales de Pharmacodynamie et de Therapiepmid:3753103moderateconsumed1 section
1975Comparison of cardiovascular, hyperthermic, and toxic effects of para-methoxyamphetamine (PMA) and 3,4-methylenedioxyamphetamine (MDA)Nichols DE, Ilhan M, Long JP · Archives Internationales de Pharmacodynamie et de Therapiepmid:1174022moderateconsumed1 section
—Searched PubChem for "MDA 3,4-methylenedioxyamphetamine" — no resultsabsenceno results—
Show all 33 sources — 3 more
Sources 31 to 33
yearsourcetierstatusfeeds
—Searched PubMed + OpenAlex for "Multiple final searches for tolerance, dependence, harm reduction MDA-specific" — no resultsabsenceno results—
—Searched PubMed for "MDA MDMA serotonin syndrome drug interaction tramadol" — no resultsabsenceno results—
—Searched PubMed for "MDA MDMA serotonin syndrome lethal interaction opioid" — no resultsabsenceno results—

4Docket

one filing per activity — decisions, correspondence, reports

  1. 0012026-04-24revisionRevision 1

    Initial LLM generation (v5 pipeline, wiki)

    psx:substance/mda/version/1
  2. 0022026-06-04proposal30 value proposals approved together

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

    30 items in this filing

    • dose_tier · light
    • dose_tier · common
    • dose_tier · strong
    • dose_tier · heavy
    • timeline · oral · onset
    • timeline · oral · come_up
    • timeline · oral · peak
    • timeline · oral · plateau
    • 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
    • contraindication · cardiovascular
    • contraindication · cardiovascular
    • contraindication · psychiatric
    • contraindication · psychiatric
    • contraindication · hepatic
    • contraindication · pregnancy_breastfeeding
    • contraindication · other
    • contraindication · other
    psx:substance/mda/proposal/dose_tier/f23115cc-ee7b-4079-9df5-a583156621f5
  3. 0032026-06-04publicationPublication — backfill

5Issued documents

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

Issued documents
documentcontent hashissuedfrom versionsuperseded
info_carde5df8902dea3eae710fae73a…2026-10-19 20:32Revision 1current
emergency47cf1475db8db7f236c6a01a…2026-09-04 04:30Revision 1current
info_card8d537c5ea1076cd57004b747…2026-09-04 04:30Revision 1superseded2026-10-19
noticec5e98aeaee016efdd2256258…2026-09-04 04:30Revision 1current