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MDEA

N-ethyl-3,4-methylenedioxyamphetamine

Sources
26
1 strong · 20 moderate · 5 weak

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

Claims checked
102
62verified8partial30inconclusive2not supported

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

Generated
May 4, 2026 · pipeline-v5
Values approved
161/162 (99%)

Data points an editor reviewed and accepted for publication.

01

Value Provenance

Dosing

oraltrace

FieldPublishedAI ProposedConfidence
Threshold40 mg40 mglow
Low40–80 mg40–80 mglow
Common80–150 mg80–150 mglow
Strong150–200 mg150–200 mglow
Heavy200+ mg200+ mglow
Editorial

No published dose-response studies for MDEA. Human clinical studies used 70 mg (Buechler 2003, PK study) and 100-140 mg (Brunnenberg 1998; Gouzoulis 1993, producing full neuroendocrine/cardiovascular effects). Shulgin noted similar potency to MDMA. Threshold and tier boundaries inferred from: (1) the 70 mg dose producing measurable plasma levels, (2) 100-140 mg producing full clinical effects, (3) MDMA dose ranges as structural analog reference. Ranges widened due to absence of systematic dose-response data. Existing database values carried forward with community consensus classification.

Reasoning

No published dose-response studies for MDEA. Human clinical studies used 70 mg (Buechler 2003, PK study) and 100-140 mg (Brunnenberg 1998; Gouzoulis 1993, producing full neuroendocrine/cardiovascular effects). Shulgin noted similar potency to MDMA. Threshold and tier boundaries inferred from: (1) the 70 mg dose producing measurable plasma levels, (2) 100-140 mg producing full clinical effects, (3) MDMA dose ranges as structural analog reference. Ranges widened due to absence of systematic dose-response data. Existing database values carried forward with community consensus classification.

Evidence basis: community_consensus_large

Duration

oral

FieldPublishedAI ProposedConfidence
Onsettrace20–40 minutes20–40 minuteslow
Editorial

Shulgin noted MDEA as faster in onset than MDMA. MDMA onset is typically 30-60 min oral. MDEA onset estimated at 20-40 min based on this observation and structural analogy.

Reasoning

Shulgin noted MDEA as faster in onset than MDMA. MDMA onset is typically 30-60 min oral. MDEA onset estimated at 20-40 min based on this observation and structural analogy.

Evidence basis: structural_analogy

Come uptrace20–45 minutes20–45 minuteslow
Editorial

Inferred from MDMA come-up duration adjusted for MDEA's reportedly faster onset. No direct data available.

Reasoning

Inferred from MDMA come-up duration adjusted for MDEA's reportedly faster onset. No direct data available.

Evidence basis: structural_analogy

Peaktrace60–120 minutes60–120 minuteslow
Editorial

Inferred from the total duration of 3-6 hours (seed data) and PK data showing plasma half-lives of 4.0-7.9 h. Peak phase estimated as 1-2 hours based on MDMA analogy adjusted for shorter total duration.

Reasoning

Inferred from the total duration of 3-6 hours (seed data) and PK data showing plasma half-lives of 4.0-7.9 h. Peak phase estimated as 1-2 hours based on MDMA analogy adjusted for shorter total duration.

Evidence basis: community_consensus_large

Offsettrace45–90 minutes45–90 minuteslow
Editorial

Inferred from total duration minus onset/come-up/peak phases. MDEA's shorter duration than MDMA suggests a relatively brisk offset.

Reasoning

Inferred from total duration minus onset/come-up/peak phases. MDEA's shorter duration than MDMA suggests a relatively brisk offset.

Evidence basis: structural_analogy

Totaltrace3–6 hours3–6 hoursmedium
Editorial

Seed data lists 3-6 hours total duration. Consistent with Shulgin's characterization of MDEA as shorter than MDMA and with PK data showing S-MDE half-life of 4.0 h (Buechler 2003). Existing database value carried forward.

Reasoning

Seed data lists 3-6 hours total duration. Consistent with Shulgin's characterization of MDEA as shorter than MDMA and with PK data showing S-MDE half-life of 4.0 h (Buechler 2003). Existing database value carried forward.

Evidence basis: community_consensus_large

After effectstrace2–24 hours2–24 hourslow
Editorial

Aftereffects inferred from MDMA class: serotonin depletion produces residual mood changes persisting 6-24 hours post-experience. R-MDE half-life of 7.9 h (Buechler 2003) suggests pharmacological activity may persist beyond subjective experience window.

Reasoning

Aftereffects inferred from MDMA class: serotonin depletion produces residual mood changes persisting 6-24 hours post-experience. R-MDE half-life of 7.9 h (Buechler 2003) suggests pharmacological activity may persist beyond subjective experience window.

Evidence basis: structural_analogy

Safety

Toxicity Profiletrace

FieldPublishedAI ProposedConfidence
Acutemoderatemoderatemedium
Chronicmoderatemoderatemedium
Organs Affectedcardiovascular, brain, livercardiovascular, brain, livermedium
Editorial

Classified as moderate acute (not high): fatal outcomes documented but in case series involving polydrug use and/or pre-existing cardiac disease (Dowling 1987), not at typical recreational doses in healthy individuals. The controlled 140 mg study (Gouzoulis 1993) produced significant but non-dangerous cardiovascular effects in healthy volunteers. Chronic classified as moderate (downgraded from high): neurotoxicity evidence is animal-only (Colado 1999, O'Loinsigh 2001, Series 1994) and at 25% MDMA potency; hepatotoxicity is class-extrapolated from MDMA. No MDEA-specific human chronic toxicity data exist.

Reasoning

Classified as moderate acute (not high): fatal outcomes documented but in case series involving polydrug use and/or pre-existing cardiac disease (Dowling 1987), not at typical recreational doses in healthy individuals. The controlled 140 mg study (Gouzoulis 1993) produced significant but non-dangerous cardiovascular effects in healthy volunteers. Chronic classified as moderate (downgraded from high): neurotoxicity evidence is animal-only (Colado 1999, O'Loinsigh 2001, Series 1994) and at 25% MDMA potency; hepatotoxicity is class-extrapolated from MDMA. No MDEA-specific human chronic toxicity data exist.

Evidence basis: published_case_series

Dependence Profiletrace

FieldPublishedAI ProposedConfidence
Physicallowlowlow
Psychologicalmoderatemoderatelow
Compulsive Redosinglowlowlow
Dose Escalationmoderatemoderatelow
Editorial

No MDEA-specific tolerance, dependence, or self-administration studies exist (Freudenmann & Spitzer 2004, Hegadoren 1999). All assessments are inferred from MDMA class pharmacology. Compulsive redosing risk rated low (below MDMA) based on MDEA's partial DAT activity, which predicts reduced reinforcement. Dose escalation tendency rated moderate based on serotonergic tolerance mechanism shared with MDMA class.

Reasoning

No MDEA-specific tolerance, dependence, or self-administration studies exist (Freudenmann & Spitzer 2004, Hegadoren 1999). All assessments are inferred from MDMA class pharmacology. Compulsive redosing risk rated low (below MDMA) based on MDEA's partial DAT activity, which predicts reduced reinforcement. Dose escalation tendency rated moderate based on serotonergic tolerance mechanism shared with MDMA class.

Evidence basis: structural_analogy

Withdrawal Profiletrace

FieldPublishedAI ProposedConfidence
Severitymildmildlow
Symptomslow mood, fatigue, irritability, difficulty concentrating, sleep disturbancelow mood, fatigue, irritability, difficulty concentrating, sleep disturbancelow
FatalNoNolow
Medical SupervisionNot requiredNot requiredlow
Editorial

No MDEA-specific withdrawal data. Inferred from MDMA 'comedown' phenomenology: post-dose serotonin depletion produces transient dysphoria, fatigue, and cognitive dulling peaking 1-3 days after use. Not a formal withdrawal syndrome in the dependence sense — rather an acute neurochemical rebound. No medical supervision required.

Reasoning

No MDEA-specific withdrawal data. Inferred from MDMA 'comedown' phenomenology: post-dose serotonin depletion produces transient dysphoria, fatigue, and cognitive dulling peaking 1-3 days after use. Not a formal withdrawal syndrome in the dependence sense — rather an acute neurochemical rebound. No medical supervision required.

Evidence basis: structural_analogy

Tolerance Profiletrace

FieldPublishedAI ProposedConfidence
Builduprapidrapidlow
Half-life3 days3 dayslow
Full Reset14 days14 dayslow
Cross-tolerancesMDMA, MDA, serotonin releasing agents, stimulantsMDMA, MDA, serotonin releasing agents, stimulantslow
Editorial

No MDEA-specific tolerance data published (Freudenmann & Spitzer 2004). Tolerance mechanism and timeline inferred from MDMA, which shares the same serotonin-depleting mechanism. Rapid buildup reflects acute nature of vesicular 5-HT depletion after a single dose.

Reasoning

No MDEA-specific tolerance data published (Freudenmann & Spitzer 2004). Tolerance mechanism and timeline inferred from MDMA, which shares the same serotonin-depleting mechanism. Rapid buildup reflects acute nature of vesicular 5-HT depletion after a single dose.

Evidence basis: structural_analogy

Effects & Profile

Contraindications

FieldPublishedAI ProposedConfidence
cardiovascular cardiac arrhythmiatraceabsoluteabsolutehigh
Editorial

Directly supported by Dowling et al. (1987) fatal case reports and Gouzoulis (1993) documenting significant cardiovascular effects at 140 mg in healthy volunteers.

Reasoning

Directly supported by Dowling et al. (1987) fatal case reports and Gouzoulis (1993) documenting significant cardiovascular effects at 140 mg in healthy volunteers.

cardiovascular long QT syndrometraceabsoluteabsolutemedium
Editorial

Class-level contraindication for sympathomimetic stimulants. Cardiovascular toxicity documented for MDEA (Gouzoulis 1993). Fatal arrhythmias in MDEA/MDMA users reported (Dowling 1987).

Reasoning

Class-level contraindication for sympathomimetic stimulants. Cardiovascular toxicity documented for MDEA (Gouzoulis 1993). Fatal arrhythmias in MDEA/MDMA users reported (Dowling 1987).

other MAO inhibitor therapytraceabsoluteabsolutehigh
Editorial

Class-level absolute contraindication for all serotonin-releasing agents. MDEA's primary mechanism is serotonin release via SERT. No MDEA-specific case reports, but the pharmacological basis is unambiguous.

Reasoning

Class-level absolute contraindication for all serotonin-releasing agents. MDEA's primary mechanism is serotonin release via SERT. No MDEA-specific case reports, but the pharmacological basis is unambiguous.

psychiatric psychotic disorderstracerelativerelativelow
Editorial

Class-level contraindication for all monoamine-releasing agents. No MDEA-specific data; inferred from MDMA/MDxx class.

Reasoning

Class-level contraindication for all monoamine-releasing agents. No MDEA-specific data; inferred from MDMA/MDxx class.

pregnancy breastfeeding pregnancytraceabsoluteabsolutemedium
Editorial

Standard absolute contraindication for sympathomimetic stimulants and serotonin-releasing agents during pregnancy. No MDEA-specific data; class-level inference.

Reasoning

Standard absolute contraindication for sympathomimetic stimulants and serotonin-releasing agents during pregnancy. No MDEA-specific data; class-level inference.

hepatic hepatic impairmenttracerelativerelativelow
Editorial

Inferred from Meyer et al. (2009) CYP metabolism data and Skrinska & Gock (2005) listing hepatotoxicity for the MDxx class. No MDEA-specific hepatic case reports.

Reasoning

Inferred from Meyer et al. (2009) CYP metabolism data and Skrinska & Gock (2005) listing hepatotoxicity for the MDxx class. No MDEA-specific hepatic case reports.

Timeline Phases

oral

FieldPublishedAI ProposedConfidence
Onsettrace1200–2400 sec(i=0.05)1200–2400 sec(i=0.05)low
Editorial

Timeline derived from: (1) Shulgin's observation that MDEA is faster in onset and shorter in duration than MDMA; (2) PK data showing plasma half-lives of 4.0-7.9 h depending on enantiomer (Buechler 2003); (3) seed data indicating 3-6 hour total duration; (4) the Gouzoulis (1993) study documenting 'long-lasting' neuroendocrine and cardiovascular effects at 140 mg. No formal subjective timeline studies exist for MDEA. Phase boundaries are inferred from MDMA timeline data adjusted for MDEA's reportedly shorter duration.

Reasoning

Timeline derived from: (1) Shulgin's observation that MDEA is faster in onset and shorter in duration than MDMA; (2) PK data showing plasma half-lives of 4.0-7.9 h depending on enantiomer (Buechler 2003); (3) seed data indicating 3-6 hour total duration; (4) the Gouzoulis (1993) study documenting 'long-lasting' neuroendocrine and cardiovascular effects at 140 mg. No formal subjective timeline studies exist for MDEA. Phase boundaries are inferred from MDMA timeline data adjusted for MDEA's reportedly shorter duration.

Come uptrace1200–2700 sec(i=0.35)1200–2700 sec(i=0.35)low
Editorial

Timeline derived from: (1) Shulgin's observation that MDEA is faster in onset and shorter in duration than MDMA; (2) PK data showing plasma half-lives of 4.0-7.9 h depending on enantiomer (Buechler 2003); (3) seed data indicating 3-6 hour total duration; (4) the Gouzoulis (1993) study documenting 'long-lasting' neuroendocrine and cardiovascular effects at 140 mg. No formal subjective timeline studies exist for MDEA. Phase boundaries are inferred from MDMA timeline data adjusted for MDEA's reportedly shorter duration.

Reasoning

Timeline derived from: (1) Shulgin's observation that MDEA is faster in onset and shorter in duration than MDMA; (2) PK data showing plasma half-lives of 4.0-7.9 h depending on enantiomer (Buechler 2003); (3) seed data indicating 3-6 hour total duration; (4) the Gouzoulis (1993) study documenting 'long-lasting' neuroendocrine and cardiovascular effects at 140 mg. No formal subjective timeline studies exist for MDEA. Phase boundaries are inferred from MDMA timeline data adjusted for MDEA's reportedly shorter duration.

Peaktrace3600–7200 sec(i=1.00)3600–7200 sec(i=1.00)low
Editorial

Timeline derived from: (1) Shulgin's observation that MDEA is faster in onset and shorter in duration than MDMA; (2) PK data showing plasma half-lives of 4.0-7.9 h depending on enantiomer (Buechler 2003); (3) seed data indicating 3-6 hour total duration; (4) the Gouzoulis (1993) study documenting 'long-lasting' neuroendocrine and cardiovascular effects at 140 mg. No formal subjective timeline studies exist for MDEA. Phase boundaries are inferred from MDMA timeline data adjusted for MDEA's reportedly shorter duration.

Reasoning

Timeline derived from: (1) Shulgin's observation that MDEA is faster in onset and shorter in duration than MDMA; (2) PK data showing plasma half-lives of 4.0-7.9 h depending on enantiomer (Buechler 2003); (3) seed data indicating 3-6 hour total duration; (4) the Gouzoulis (1993) study documenting 'long-lasting' neuroendocrine and cardiovascular effects at 140 mg. No formal subjective timeline studies exist for MDEA. Phase boundaries are inferred from MDMA timeline data adjusted for MDEA's reportedly shorter duration.

Plateautrace2700–5400 sec(i=0.50)2700–5400 sec(i=0.50)low
Editorial

Timeline derived from: (1) Shulgin's observation that MDEA is faster in onset and shorter in duration than MDMA; (2) PK data showing plasma half-lives of 4.0-7.9 h depending on enantiomer (Buechler 2003); (3) seed data indicating 3-6 hour total duration; (4) the Gouzoulis (1993) study documenting 'long-lasting' neuroendocrine and cardiovascular effects at 140 mg. No formal subjective timeline studies exist for MDEA. Phase boundaries are inferred from MDMA timeline data adjusted for MDEA's reportedly shorter duration.

Reasoning

Timeline derived from: (1) Shulgin's observation that MDEA is faster in onset and shorter in duration than MDMA; (2) PK data showing plasma half-lives of 4.0-7.9 h depending on enantiomer (Buechler 2003); (3) seed data indicating 3-6 hour total duration; (4) the Gouzoulis (1993) study documenting 'long-lasting' neuroendocrine and cardiovascular effects at 140 mg. No formal subjective timeline studies exist for MDEA. Phase boundaries are inferred from MDMA timeline data adjusted for MDEA's reportedly shorter duration.

Resolutiontrace2700–5400 sec(i=0.20)2700–5400 sec(i=0.20)low
Editorial

Timeline derived from: (1) Shulgin's observation that MDEA is faster in onset and shorter in duration than MDMA; (2) PK data showing plasma half-lives of 4.0-7.9 h depending on enantiomer (Buechler 2003); (3) seed data indicating 3-6 hour total duration; (4) the Gouzoulis (1993) study documenting 'long-lasting' neuroendocrine and cardiovascular effects at 140 mg. No formal subjective timeline studies exist for MDEA. Phase boundaries are inferred from MDMA timeline data adjusted for MDEA's reportedly shorter duration.

Reasoning

Timeline derived from: (1) Shulgin's observation that MDEA is faster in onset and shorter in duration than MDMA; (2) PK data showing plasma half-lives of 4.0-7.9 h depending on enantiomer (Buechler 2003); (3) seed data indicating 3-6 hour total duration; (4) the Gouzoulis (1993) study documenting 'long-lasting' neuroendocrine and cardiovascular effects at 140 mg. No formal subjective timeline studies exist for MDEA. Phase boundaries are inferred from MDMA timeline data adjusted for MDEA's reportedly shorter duration.

Afterglowtrace7200–43200 sec(i=0.05)7200–43200 sec(i=0.05)low
Editorial

Timeline derived from: (1) Shulgin's observation that MDEA is faster in onset and shorter in duration than MDMA; (2) PK data showing plasma half-lives of 4.0-7.9 h depending on enantiomer (Buechler 2003); (3) seed data indicating 3-6 hour total duration; (4) the Gouzoulis (1993) study documenting 'long-lasting' neuroendocrine and cardiovascular effects at 140 mg. No formal subjective timeline studies exist for MDEA. Phase boundaries are inferred from MDMA timeline data adjusted for MDEA's reportedly shorter duration.

Reasoning

Timeline derived from: (1) Shulgin's observation that MDEA is faster in onset and shorter in duration than MDMA; (2) PK data showing plasma half-lives of 4.0-7.9 h depending on enantiomer (Buechler 2003); (3) seed data indicating 3-6 hour total duration; (4) the Gouzoulis (1993) study documenting 'long-lasting' neuroendocrine and cardiovascular effects at 140 mg. No formal subjective timeline studies exist for MDEA. Phase boundaries are inferred from MDMA timeline data adjusted for MDEA's reportedly shorter duration.

Dose Tier Summaries

thresholdtrace
low

At threshold doses, effects are subtle and easily dismissed: a mild shift in mood toward warmth, slight increase in sociability, and faint body awareness. Physical signs may include minor pupil dilation and a barely perceptible increase in heart rate. These doses produce no meaningful perceptual alteration and minimal stimulation. Functional impairment is negligible, though subtle mood changes may persist for 2-3 hours.

Editorial

No published threshold dose data for MDEA. Inferred from MDMA threshold range (~25-50 mg) with adjustment for MDEA's reportedly similar potency per Shulgin's PiHKAL and Freudenmann & Spitzer (2004). Widened range due to uncertainty.

Reasoning

No published threshold dose data for MDEA. Inferred from MDMA threshold range (~25-50 mg) with adjustment for MDEA's reportedly similar potency per Shulgin's PiHKAL and Freudenmann & Spitzer (2004). Widened range due to uncertainty.

Evidence basis: structural_analogy

lighttrace
low

At light doses, the entactogenic character begins to emerge: mild emotional warmth, enhanced appreciation for social interaction and music, and a gentle sense of relaxation. Slight perceptual brightening may occur without overt visual distortion. Physically, mild stimulation is noticeable — increased heart rate, slight jaw tension, and pupil dilation. Body temperature may rise subtly. The experience is easily manageable and does not significantly impair normal functioning, though driving should be avoided.

Editorial

Inferred from MDMA light dose range (~50-75 mg) and the 70 mg dose used in the Buechler et al. (2003) PK study, which produced measurable plasma levels. Pharmacological similarity to MDMA supports comparable dose-response, though MDEA's partial DAT activity may produce less stimulation at equivalent doses.

Reasoning

Inferred from MDMA light dose range (~50-75 mg) and the 70 mg dose used in the Buechler et al. (2003) PK study, which produced measurable plasma levels. Pharmacological similarity to MDMA supports comparable dose-response, though MDEA's partial DAT activity may produce less stimulation at equivalent doses.

Evidence basis: structural_analogy

commontrace
medium

At common doses, the full entactogenic profile manifests: pronounced emotional warmth and openness, feelings of closeness and empathy, relaxation combined with mild psychomotor stimulation, and a pleasant, easily controllable mood state. Mild perceptual alterations — enhanced color saturation, increased tactile sensitivity — may be present without frank hallucination. Cardiovascular effects become measurable: tachycardia, systolic blood pressure elevation, and pupil dilation are expected. Jaw tension (trismus), appetite suppression, and mild temperature dysregulation occur. Serum cortisol and prolactin elevate significantly. The experience lasts 3-5 hours with a relatively gentle offset. Sleep may be difficult for several hours after effects subside.

Editorial

The 140 mg dose used in the Gouzoulis et al. (1993) controlled study — producing significant neuroendocrine and cardiovascular effects — and the 100-140 mg range in Brunnenberg et al. (1998) PK studies represent the common-to-strong dose range. Subjective characterization from Freudenmann & Spitzer (2004) and Gouzoulis-Mayfrank et al. (1996) describes the entactogenic profile at these doses.

Reasoning

The 140 mg dose used in the Gouzoulis et al. (1993) controlled study — producing significant neuroendocrine and cardiovascular effects — and the 100-140 mg range in Brunnenberg et al. (1998) PK studies represent the common-to-strong dose range. Subjective characterization from Freudenmann & Spitzer (2004) and Gouzoulis-Mayfrank et al. (1996) describes the entactogenic profile at these doses.

Evidence basis: published_case_series

strongtrace
low

At strong doses, all entactogenic effects intensify: deep emotional openness, strong feelings of empathy and connection, and pronounced relaxation. Perceptual alterations become more prominent — occasional mild visual distortions and enhanced sensory processing. The experience is described as more "stoning" than MDMA at equivalent intensity, with less energetic stimulation and more sedating warmth. Cardiovascular strain increases substantially: marked tachycardia and blood pressure elevation. Hyperthermia risk becomes significant, particularly in warm environments or during physical exertion. Jaw clenching, nausea, and sweating may become uncomfortable. Functional impairment is significant. The total experience commitment is 4-6 hours, with residual effects and sleep disruption extending beyond.

Editorial

No controlled studies above 140 mg. The upper clinical dose (140 mg) represents the common-strong boundary. Strong dose effects inferred from dose-response extrapolation and the Freudenmann & Spitzer (2004) description of dose-dependent perceptual alterations becoming more hallucinogenic at higher doses.

Reasoning

No controlled studies above 140 mg. The upper clinical dose (140 mg) represents the common-strong boundary. Strong dose effects inferred from dose-response extrapolation and the Freudenmann & Spitzer (2004) description of dose-dependent perceptual alterations becoming more hallucinogenic at higher doses.

Evidence basis: structural_analogy

heavytrace
low

At heavy doses, the experience may shift substantially from the entactogenic toward pronounced perceptual disturbance and overwhelming stimulation. Perceptual alterations intensify — frank visual distortions and hallucination-like phenomena become possible. Emotional states become less controllable and may include anxiety or confusion. Physical risks escalate markedly: severe hyperthermia, dangerous cardiovascular strain, and risk of rhabdomyolysis. Serotonin toxicity symptoms may emerge. These doses approach the range where fatal outcomes have been documented in vulnerable individuals. Heavy doses represent a disproportionate increase in risk relative to additional subjective benefit. The experience may last 5-7 hours with prolonged aftereffects and significant next-day impact.

Editorial

No published data on MDEA effects above 140 mg in controlled settings. Risk profile extrapolated from fatal case reports (Dowling 1987) and animal toxicology showing dose-dependent hyperthermia (Colado 1999). Heavy dose characterization based on MDxx class pharmacology.

Reasoning

No published data on MDEA effects above 140 mg in controlled settings. Risk profile extrapolated from fatal case reports (Dowling 1987) and animal toxicology showing dose-dependent hyperthermia (Colado 1999). Heavy dose characterization based on MDxx class pharmacology.

Evidence basis: structural_analogy

02

History

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

backfill Jun 4, 2026

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

full version history suggest a correctioncontact@psychedex.org
03

Sources

1 strong · 20 moderate · 5 weak
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    moderate
    Differences between the mechanism of action of MDMA, MBDB, and the classic hallucinogens. Identification of a new therapeutic class: entactogens
    Nichols DE · 1986 · Journal of Psychoactive Drugs
    pubmed 28809444 claims checked2 verified2 inconclusive
  2. [2]
    moderate
    Entactogens: How the Name for a Novel Class of Psychoactive Agents Originated
    Nichols DE · 2022 · Frontiers in Psychiatry
    doi.org/10.3389/fpsyt.2022.863088pubmed 354012754 claims checked4 inconclusive
  3. [3]
    weak
    'Eve' and 'Ecstasy'. A report of five deaths associated with the use of MDEA and MDMA
    Dowling GP, McDonough ET, Bost RO · 1987 · JAMA
    pubmed 288100210 claims checked6 verified1 partial3 inconclusive
  4. [4]
    weak
    Legal status of MDEA
    Various · 2024
    linkno claims checked
  5. [5]
    moderate
    The Neuropsychopharmacology and Toxicology of 3,4-methylenedioxy-N-ethyl-amphetamine (MDEA)
    Freudenmann RW, Spitzer M · 2004 · CNS Drug Reviews
    doi.org/10.1111/j.1527-3458.2004.tb00007.xpubmed 151794418 claims checked1 verified7 inconclusive
  6. [6]
    moderate
    Entactogenic drugs 'ecstasy' (MDMA), 'eve' (MDE) and other ring-substituted methamphetamine derivatives. A new class of substances among illegal designer drugs?
    Gouzoulis-Mayfrank E, Hermle L, Kovar KA, Sass H · 1996 · Der Nervenarzt
    pubmed 90053455 claims checked3 verified2 inconclusive
  7. [7]
    strong
    Neuroendocrine and cardiovascular effects of MDE in healthy volunteers
    Gouzoulis E, von Bardeleben U, Rupp A, Kovar KA, Hermle L · 1993 · Neuropsychopharmacology
    pubmed 85073465 claims checked5 verified
  8. [8]
    moderate
    Enantioselective quantitation of the ecstasy compound (R)- and (S)-N-ethyl-3,4-methylenedioxyamphetamine and its major metabolites in human plasma and urine
    Buechler J, Schwab M, Mikus G, Fischer B, Hermle L, Marx C, Grön G, Spitzer M, Kovar KA · 2003 · Journal of Chromatography B
    pubmed 129068966 claims checked4 verified2 partial
  9. [9]
    moderate
    Quantitation of N-ethyl-3,4-methylenedioxyamphetamine and its major metabolites in human plasma by high-performance liquid chromatography and fluorescence detection
    Brunnenberg M, Lindenblatt H, Gouzoulis-Mayfrank E, Kovar KA · 1998 · Journal of Chromatography B
    pubmed 98693675 claims checked4 verified1 inconclusive
  10. [10]
    moderate
    Behavioural, hyperthermic and neurotoxic effects of 3,4-methylenedioxymethamphetamine analogues in the Wistar rat
    O'Loinsigh ED, Boland G, Kelly JP, O'Boyle KM · 2001 · Progress in Neuro-Psychopharmacology & Biological Psychiatry
    pubmed 1137100112 claims checked5 verified1 partial5 inconclusive1 not supported
  11. [11]
    weak
    Monoamine releasing agent - MDEA pharmacological data
    Wikipedia contributors · 2024
    linkno claims checked
  12. [12]
    moderate
    Actions of amphetamine derivatives and cathinone at the noradrenaline transporter
    Cleary L, Docherty JR · 2003 · European Journal of Pharmacology
    pubmed 129697464 claims checked4 verified
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    moderate
    The role of human hepatic cytochrome P450 isozymes in the metabolism of racemic 3,4-methylenedioxyethylamphetamine and its single enantiomers
    Meyer MR, Peters FT, Maurer HH · 2009 · Drug Metabolism and Disposition
    doi.org/10.1124/dmd.108.026203pubmed 192995239 claims checked9 verified
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    moderate
    The acute effect in rats of 3,4-methylenedioxyethamphetamine (MDEA, 'eve') on body temperature and long term degeneration of 5-HT neurones in brain: a comparison with MDMA ('ecstasy')
    Colado MI, Granados R, O'Shea E, Esteban B, Green AR · 1999 · Pharmacology & Toxicology
    pubmed 104017274 claims checked3 verified1 inconclusive
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    moderate
    Effects of the enantiomers of MDA, MDMA and related analogues on [3H]serotonin and [3H]dopamine release from superfused rat brain slices
    Johnson MP, Hoffman AJ, Nichols DE · 1986 · European Journal of Pharmacology
    pubmed 28807355 claims checked3 verified1 inconclusive1 not supported
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    moderate
    Chromatographic and Spectroscopic Methods of Identification for the Side-Chain Regioisomers of 3,4-Methylenedioxyphenethylamines Related to MDEA, MDMMA, and MBDB
    Aalberg L, DeRuiter J, Noggle FT, Sippola E, Clark CR · 2003 · Journal of Chromatographic Science
    doi.org/10.1093/chromsci/41.5.227pubmed 128419491 claim checked1 verified
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    Interaction Profiles of Central Nervous System Active Drugs at Human Organic Cation Transporters 1-3 and Human Plasma Membrane Monoamine Transporter
    Angenoorth TJF, Stankovic S, Niello M, Holy M, Brandt SD, Sitte HH, Maier J · 2021 · International Journal of Molecular Sciences
    doi.org/10.3390/ijms222312995pubmed 348848001 claim checked1 verified
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    moderate
    Investigations on the stereoselectivity of the phase II metabolism of the 3,4-methylenedioxyethylamphetamine (MDEA) metabolites 3,4-dihydroxyethylamphetamine (DHEA) and 4-hydroxy-3-methoxyethylamphetamine (HMEA)
    Schwaninger AE, Meyer MR, Zapp J, Maurer HH · 2012 · Toxicology Letters
    doi.org/10.1016/j.toxlet.2012.04.021pubmed 225647592 claims checked2 inconclusive
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    moderate
    Enantioselectivity in the methylation of the catecholic phase I metabolites of methylenedioxy designer drugs and their capability to inhibit catechol-O-methyltransferase-catalyzed dopamine 3-methylation
    Meyer MR, Maurer HH · 2009 · Chemical Research in Toxicology
    doi.org/10.1021/tx900134epubmed 194629394 claims checked2 verified2 partial
  20. [20]
    moderate
    Stereospecific analysis of ecstasy-like N-ethyl-3,4-methylenedioxyamphetamine and its metabolites in humans
    Brunnenberg M, Kovar KA · 2001 · Journal of Chromatography B
    pubmed 112328603 claims checked2 verified1 inconclusive
  21. [21]
    weak
    Amphetamines as potential inducers of fatalities: a review in the district of Ghent from 1976-2004
    De Letter EA, Piette MH, Lambert WE, Cordonnier JA · 2006 · Medicine, Science, and the Law
    pubmed 164544621 claim checked1 partial
  22. [22]
    moderate
    Overview of amphetamine-type stimulant mortality data--UK, 1997-2007.
    Schifano F, Corkery J, Naidoo V, Oyefeso A, Ghodse H · 2010 · Neuropsychobiology
    doi.org/10.1159/000279302pubmed 201107371 claim checked1 partial
  23. [23]
    moderate
    Measurement of 3,4-MDMA and related amines in diagnostic and forensic laboratories
    Skrinska VA, Gock SB · 2005 · Clinical Laboratory Science
    pubmed 159162451 claim checked1 verified
  24. [24]
    moderate
    3,4-Methylenedioxy analogues of amphetamine: defining the risks to humans
    Hegadoren KM, Baker GB, Bourin M · 1999 · Neuroscience and Biobehavioral Reviews
    pubmed 100738921 claim checked1 inconclusive
  25. [25]
    weak
    Lethal combination of tramadol and multiple drugs affecting serotonin
    Ripple MG, Pestaner JP, Levine BS, Smialek JE · 2000 · American Journal of Forensic Medicine and Pathology
    pubmed 111118002 claims checked2 verified
  26. [26]
    moderate
    Immunocytochemical evidence for serotonergic neurotoxicity of N-ethyl-methylenedioxyamphetamine (MDE)
    Series HG, Molliver ME · 1994 · Experimental Neurology
    pubmed 80705244 claims checked4 verified
04

Claim Verification

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

summary15 claims10verified2partial3inconclusive
verifiedThe compound circulated briefly as a legal MDMA substitute following MDMA's emergency Schedule I placement in May 1985, until MDEA was itself scheduled in October 1987[3]model confidence 85%
Verified

Abstract confirms MDEA appeared as MDMA's legal replacement after the 1985 Schedule I classification. The specific months (May 1985, October 1987) are not in the abstract but the general historical sequence is confirmed.

MDEA appeared as MDMA's legal replacement after 1985 Schedule I classification.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedThe published evidence base is sparse: one controlled human challenge study (n=8, neuroendocrine and cardiovascular endpoints only), several human pharmacokinetic studies, and rat neurotoxicity data constitute the primary literature[7]model confidence 90%
Verified

Abstract confirms exactly one controlled double-blind placebo-controlled cross-over study with n=8 healthy male volunteers measuring neuroendocrine and cardiovascular endpoints, directly corresponding to what the claim describes.

Double-blind placebo-controlled cross-over study: 140 mg MDE orally to 8 healthy male volunteers. Significant long-lasting increases in serum cortisol, prolactin, systolic blood pressure, and heart rate.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedThe published evidence base is sparse: one controlled human challenge study (n=8, neuroendocrine and cardiovascular endpoints only), several human pharmacokinetic studies, and rat neurotoxicity data constitute the primary literature[8]model confidence 88%
Verified

This is a human pharmacokinetic study of MDE and its metabolites, directly representing one of the 'several human pharmacokinetic studies' mentioned in the claim.

Enantioselective HPLC method for MDE and metabolites HME and MDA in human plasma/urine. After 70 mg pure MDE-HCl: plasma concentration of (R)-MDE exceeded (S)-MDE.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedThe published evidence base is sparse: one controlled human challenge study (n=8, neuroendocrine and cardiovascular endpoints only), several human pharmacokinetic studies, and rat neurotoxicity data constitute the primary literature[9]model confidence 88%
Verified

Another human pharmacokinetic study of MDE and metabolites in 14 volunteers, confirming the existence of 'several human pharmacokinetic studies' in the evidence base.

HPLC method validated for MDE and metabolites (HME, MDA) in human plasma. 14 volunteers in two clinical studies after 100-140 mg MDE-HCl p.o. Pharmacokinetic parameters calculated.

checked by claude-sonnet-4-6 · Jul 18, 2026

inconclusiveMDEA acts as a triple monoamine releasing agent at serotonin-transporter, dopamine-transporter, and norepinephrine-transporter[1]model confidence 75%
Inconclusive

The abstract coins the 'entactogen' term and distinguishes these compounds from hallucinogens and stimulants, but does not describe the specific triple monoamine releasing mechanism at SERT, DAT, and NET.

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

checked by claude-sonnet-4-6 · Jul 18, 2026

inconclusiveMDEA acts as a triple monoamine releasing agent at serotonin-transporter, dopamine-transporter, and norepinephrine-transporter[2]model confidence 75%
Inconclusive

Abstract describes structural distinctions between hallucinogenic phenethylamines and MDMA, and N-methylation effects. Does not address triple monoamine releasing at SERT/DAT/NET.

Describes structural distinctions between hallucinogenic phenethylamines and MDMA. N-methylation attenuates hallucinogenic phenethylamine activity.

checked by claude-sonnet-4-6 · Jul 18, 2026

partialIt is equipotent with MDMA for serotonin release but functions as a dopamine partial releaser (DAT EC₅₀ ≈ 622 nM, E_max ≈ 61% vs MDMA EC₅₀ ≈ 108 nM, E_max ≈ 103%) and is the least potent chemical/mdxx compound at the norepinephrine transporter (IC₅₀ ≈ 2.75 µM). cyp3a4 and cyp2d6 are the primary metabolizing enzymes.[10]model confidence 80%
Partial

Abstract confirms SERT equipotency and lower DAT potency (MDA > MDMA > MDEA) for dopamine release. However, the specific EC₅₀/E_max values (622 nM, 61%, 108 nM, 103%) are not in the abstract, NET data is absent, and CYP information is from a different paper.

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.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedIt is equipotent with MDMA for serotonin release but functions as a dopamine partial releaser (DAT EC₅₀ ≈ 622 nM, E_max ≈ 61% vs MDMA EC₅₀ ≈ 108 nM, E_max ≈ 103%) and is the least potent chemical/mdxx compound at the norepinephrine transporter (IC₅₀ ≈ 2.75 µM). cyp3a4 and cyp2d6 are the primary metabolizing enzymes.[12]model confidence 88%
Verified

Abstract directly confirms MDEA NET IC₅₀ (-log = 5.56, ≈ 2.75 µM) and its lesser potency vs MDMA (-log = 6.05), cathinone (6.03), and cocaine (6.16) at NA uptake inhibition in rat left ventricle — supporting the NET-specific portion of this claim.

Potency (-log IC50) at inhibiting [3H]NA uptake in rat left ventricle: cocaine 6.16, cathinone 6.03, MDMA 6.05, MDA 5.68, MDEA 5.56. MDEA and MDA significantly less potent than cocaine/cathinone/MDMA.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedIt is equipotent with MDMA for serotonin release but functions as a dopamine partial releaser (DAT EC₅₀ ≈ 622 nM, E_max ≈ 61% vs MDMA EC₅₀ ≈ 108 nM, E_max ≈ 103%) and is the least potent chemical/mdxx compound at the norepinephrine transporter (IC₅₀ ≈ 2.75 µM). cyp3a4 and cyp2d6 are the primary metabolizing enzymes.[13]model confidence 90%
Verified

Abstract directly confirms CYP3A4 and CYP2D6 as primary metabolizing enzymes for MDEA, supporting the CYP portion of this compound claim.

CYP3A4 and CYP2D6 show highest contribution to both metabolic steps.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedThe subjective experience occupies an intermediate position between stimulants and hallucinogens: entactogenic warmth, psychomotor stimulation, and mild perceptual alterations at common doses[5]model confidence 90%
Verified

Abstract confirms MDEA evokes psychomotor stimulation, mild alterations of perception, sensations of closeness and positive emotional state, directly supporting the claim about intermediate position and the specific effect profile.

Both evoke psychomotor stimulation, mild alterations of perception, sensations of closeness and positive emotional state.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedThe subjective experience occupies an intermediate position between stimulants and hallucinogens: entactogenic warmth, psychomotor stimulation, and mild perceptual alterations at common doses[6]model confidence 90%
Verified

Abstract explicitly positions MDEA as between stimulants and hallucinogens and confirms a pleasant emotional state including happiness and relaxation.

Reviews MDMA and MDE (MDEA) as entactogens between stimulants and hallucinogens. Induces pleasant emotional state, relaxation, fearlessness, happiness.

checked by claude-sonnet-4-6 · Jul 18, 2026

partialAcute toxicity centers on hyperthermia, cardiovascular stress (tachycardia, systolic hypertension), and fatal arrhythmias documented in individuals with pre-existing cardiac disease[3]model confidence 78%
Partial

Abstract confirms fatal arrhythmias in individuals with underlying cardiac disease. However, hyperthermia and the specific cardiovascular effects (tachycardia, systolic hypertension) mentioned in the claim are not described in this death-report abstract.

Three deaths: MDMA/MDEA contributed to death by arrhythmias in individuals with underlying cardiac disease.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedAcute toxicity centers on hyperthermia, cardiovascular stress (tachycardia, systolic hypertension), and fatal arrhythmias documented in individuals with pre-existing cardiac disease[7]model confidence 88%
Verified

Abstract directly confirms significant increases in systolic blood pressure (systolic hypertension) and heart rate (tachycardia) following 140 mg MDEA in human volunteers, supporting the cardiovascular stress component.

Significant long-lasting increases in serum cortisol, prolactin, systolic blood pressure, and heart rate.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedSerotonergic neurotoxicity occurs in rats at approximately 25% the potency of MDMA, but no human neurotoxicity data exist[14]model confidence 92%
Verified

Abstract directly states MDEA is ~25% the potency of MDMA for 5-HT neurodegeneration in rats. The absence of human neurotoxicity data is not contradicted by the abstract.

MDEA ~half the potency of MDMA for acute hyperthermia and ~25% the potency for 5-HT neurodegeneration.

checked by claude-sonnet-4-6 · Jul 18, 2026

inconclusiveNo MDEA-specific tolerance or dependence studies have been published; class-level inference from MDMA suggests moderate psychological-dependence with serotonergic tolerance via post-dose 5-HT depletion[5]model confidence 70%
Inconclusive

The review abstract covers pharmacodynamics, kinetics, and neurotoxicity for MDEA but does not mention tolerance or dependence studies. Absence from the abstract cannot confirm or deny whether such studies exist.

Reviews pharmacodynamics/kinetics from MDEA challenge studies in animals and humans; presents case reports of fatalities with MDEA toxicologically confirmed; discusses serotonergic neurotoxicity from animal studies only.

checked by claude-sonnet-4-6 · Jul 18, 2026

history4 claims2verified2inconclusive
verifiedThe landmark 1987 JAMA report by Dowling, McDonough, and Bost — documenting five deaths associated with MDEA and MDMA use — drew significant public and regulatory attention to MDEA toxicity and accelerated the scheduling process.[3]model confidence 85%
Verified

Abstract confirms the paper reports five MDEA/MDMA-associated deaths and contextualizes MDEA's emergence post-MDMA scheduling. The claim's characterization of its landmark regulatory impact is a reasonable historical inference from the paper's content and timing.

Reports five deaths associated with MDMA and MDEA use. MDEA appeared as MDMA's legal replacement after 1985 Schedule I classification.

checked by claude-sonnet-4-6 · Jul 18, 2026

inconclusiveA formal synthesis and pharmacological evaluation of MDEA and related compounds was published in 1980, as referenced by Freudenmann and Spitzer[5]model confidence 70%
Inconclusive

The abstract of this review covers MDEA pharmacology and toxicology overview but does not specifically mention a 1980 synthesis/evaluation paper. This claim references the review's citation list which is not in the abstract.

This paper reviews the pharmacology and toxicology of 3,4-methylenedioxy-N-ethylamphetamine (MDEA, 'eve').

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedIn 1986, David Nichols coined the term "entactogen" — meaning "to produce a touching within" — to describe the pharmacological class encompassing MDEA, MDMA, and mda, distinguishing these compounds from both classical stimulants and serotonergic hallucinogens.[1]model confidence 88%
Verified

Abstract directly identifies this as the seminal paper coining the term 'entactogen' and distinguishing the class from classic hallucinogens and stimulants. Year (1986) and author (Nichols) are not in the abstract but the core claim about the paper's content is confirmed.

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

checked by claude-sonnet-4-6 · Jul 18, 2026

inconclusiveMDEA was formally placed in Schedule I by the DEA, effective October 1987.[3]model confidence 72%
Inconclusive

Abstract implies MDEA was eventually scheduled (it appeared as MDMA's legal replacement and deaths were reported in 1987), but does not confirm the specific date of October 1987 for Schedule I placement.

MDEA appeared as MDMA's legal replacement after 1985 Schedule I classification.

checked by claude-sonnet-4-6 · Jul 18, 2026

chemistry4 claims4verified
verifiedIdentification of the correct regioisomer requires chromatographic methods, as both share identical molecular weights (207 g/mol) and similar mass spectral fragmentation (m/z 72 and 135/136).[16]model confidence 93%
Verified

Abstract directly confirms MDEA MW 207 with m/z 72 and 135/136 as major fragments, and that chromatographic methods are needed for forensic identification of the regioisomers.

Mass spectral and chromatographic methods for forensic identification. MDEA has MW 207 with m/z 72 and 135/136 as major fragments.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedThe structural progression MDA → MDMA → MDEA represents successive N-alkylation of the amine nitrogen, with each step modifying monoamine transporter selectivity and subjective effect profile[15]model confidence 85%
Verified

Abstract confirms N-methylation (MDA→MDMA) decreases DA release and alpha-ethyl extension further reduces it, demonstrating that successive N-alkylation modifies monoamine transporter selectivity.

N-methylation of MDA decreased DA release; alpha-ethyl extension (BDB vs MBDB) completely abolished DA release.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedFollowing oral administration of racemic MDEA, the R-enantiomer predominates in plasma with an AUC ratio of R:S = 3.1 and a substantially longer half-life (R-MDE: 7.9 h vs S-MDE: 4.0 h)[8]model confidence 97%
Verified

Abstract directly confirms AUC ratio R:S = 3.1 and half-times R-MDE 7.9 h vs S-MDE 4.0 h.

Plasma concentration of (R)-MDE exceeded (S)-MDE (AUC ratio R:S = 3.1); plasma half-time (R)-MDE 7.9 h vs (S)-MDE 4.0 h.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedThis enantioselective disposition reflects preferential cyp2d6- and cyp3a4-catalyzed metabolism of the S-enantiomer[13]model confidence 93%
Verified

Abstract directly confirms CYP3A4 and CYP2D6 show highest contribution to both metabolic steps with preferential S-enantiomer metabolism, explaining the enantioselective disposition.

CYP3A4 and CYP2D6 show highest contribution to both metabolic steps. S-enantiomers preferentially metabolized.

checked by claude-sonnet-4-6 · Jul 18, 2026

pharmacology18 claims11verified1partial6inconclusive
inconclusiveAs a substrate-type releaser, it enters presynaptic terminals via these transporters and triggers carrier-mediated efflux of stored monoamines into the synapse — the hallmark mechanism of phenethylamine entactogens[1]model confidence 72%
Inconclusive

Abstract coins the entactogen class term and distinguishes from hallucinogens/stimulants, but does not describe the substrate-type releasing mechanism (carrier-mediated efflux, presynaptic entry) at any detail level.

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

checked by claude-sonnet-4-6 · Jul 18, 2026

inconclusiveAs a substrate-type releaser, it enters presynaptic terminals via these transporters and triggers carrier-mediated efflux of stored monoamines into the synapse — the hallmark mechanism of phenethylamine entactogens[2]model confidence 72%
Inconclusive

Abstract describes structural distinctions and N-methylation effects on hallucinogenic activity, but does not describe the substrate-type releasing mechanism for entactogens.

Describes structural distinctions between hallucinogenic phenethylamines and MDMA. N-methylation attenuates hallucinogenic phenethylamine activity.

checked by claude-sonnet-4-6 · Jul 18, 2026

inconclusiveThe primary pharmacological action is serotonin release via SERT, which drives the entactogenic profile.[2]model confidence 72%
Inconclusive

Abstract is about structural distinctions between hallucinogenic phenethylamines and MDMA; does not address SERT-mediated serotonin release as the primary action driving the entactogenic profile.

Describes structural distinctions between hallucinogenic phenethylamines and MDMA. N-methylation attenuates hallucinogenic phenethylamine activity.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedThe potency order for dopamine release from rat striatal synaptosomes is mda > MDMA > MDEA, consistent with the finding that N-ethyl extension of the amphetamine side chain reduces dopaminergic releasing activity in brain slice preparations.[10]model confidence 92%
Verified

Abstract directly states the potency order MDA > MDMA > MDEA = MDBA for [3H]DA release from striatal synaptosomes, directly confirming the claim.

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

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedThe potency order for dopamine release from rat striatal synaptosomes is mda > MDMA > MDEA, consistent with the finding that N-ethyl extension of the amphetamine side chain reduces dopaminergic releasing activity in brain slice preparations.[15]model confidence 85%
Verified

Abstract confirms that N-methylation of MDA decreases DA release and alpha-ethyl extension abolishes DA release in brain slice assays, supporting the principle that N-alkylation reduces dopaminergic releasing activity.

N-methylation of MDA decreased DA release; alpha-ethyl extension (BDB vs MBDB) completely abolished DA release. S-(+) isomers stereostereoselective for DA release.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedAt SERT, MDEA, MDMA, and MDA are approximately equipotent for inducing [³H]serotonin release from rat frontal cortex and hippocampal synaptosomes, with all three producing serotonin release in the micromolar concentration range in brain slice assays.[10]model confidence 92%
Verified

Abstract directly confirms equipotency of MDA, MDMA, and MDEA at inducing [3H]5-HT release from frontal cortex/hippocampal synaptosomes.

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

checked by claude-sonnet-4-6 · Jul 18, 2026

inconclusiveAt SERT, MDEA, MDMA, and MDA are approximately equipotent for inducing [³H]serotonin release from rat frontal cortex and hippocampal synaptosomes, with all three producing serotonin release in the micromolar concentration range in brain slice assays.[15]model confidence 78%
Inconclusive

Abstract covers MDA, BDB, MDMA, MBDB and their enantiomers in brain slice assays, confirming similar 5-HT release efficacy in micromolar range, but MDEA is not among the compounds studied. Cannot confirm MDEA-specific equipotency from this abstract.

MDA, BDB, MDMA, MBDB and enantiomers compared for [3H]5-HT and [3H]DA release. All had similar efficacy for 5-HT release in micromolar range.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedMDEA is the least potent of the chemical/mdxx series at NET. [³H]Noradrenaline uptake inhibition in rat left ventricle yields an IC₅₀ of approximately 2.75 µM (-log IC₅₀ = 5.56 ± 0.08), significantly less potent than MDMA (-log IC₅₀ = 6.05), cathinone (6.03), and cocaine (6.16). [³H]Nisoxetine displacement in rat cortex gives an EC₅₀ of approximately 10.2 µM (-log EC₅₀ = 4.99 ± 0.15).[12]model confidence 95%
Verified

Abstract directly provides all key values: MDEA -log IC50 = 5.56 (≈2.75 µM) at NA uptake, MDMA 6.05, cathinone 6.03, cocaine 6.16. Nisoxetine displacement: MDEA 4.99 (≈10.2 µM). MDEA is the least potent mdxx compound at NA uptake inhibition.

Potency (-log IC50) at inhibiting [3H]NA uptake in rat left ventricle: cocaine 6.16, cathinone 6.03, MDMA 6.05, MDA 5.68, MDEA 5.56. At [3H]nisoxetine displacement in cortex: cathinone 5.40, cocaine 5.04, MDEA 4.99, MDA 4.66, MDMA 4.22.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedMDEA is the least potent of the chemical/mdxx series at NET. [³H]Noradrenaline uptake inhibition in rat left ventricle yields an IC₅₀ of approximately 2.75 µM (-log IC₅₀ = 5.56 ± 0.08), significantly less potent than MDMA (-log IC₅₀ = 6.05), cathinone (6.03), and cocaine (6.16). [³H]Nisoxetine displacement in rat cortex gives an EC₅₀ of approximately 10.2 µM (-log EC₅₀ = 4.99 ± 0.15).[12]model confidence 95%
Verified

Duplicate anchor for the same citation and claim — abstract directly confirms all stated values for NET potency.

Potency (-log IC50) at inhibiting [3H]NA uptake in rat left ventricle: cocaine 6.16, cathinone 6.03, MDMA 6.05, MDA 5.68, MDEA 5.56. At [3H]nisoxetine displacement in cortex: MDEA 4.99.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedMDMA interacts with human organic cation transporters OCT1/2 and plasma membrane monoamine transporter (hPMAT) as additional low-affinity targets; MDEA may share these interactions by structural analogy, but this remains untested.[17]model confidence 88%
Verified

Abstract confirms MDMA is a potent inhibitor of hOCT1/2 and hPMAT. The claim presents MDEA interaction as an untested structural-analogy inference, which is an appropriate framing given only MDMA data exists.

MDMA is potent inhibitor of hOCT1/2 and hPMAT. Interactions with low-affinity/high-capacity transporters may supplement primary monoamine transporter effects.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedMDEA undergoes two primary Phase I metabolic pathways:[13]model confidence 93%
Verified

Abstract directly confirms MDEA is mainly metabolized by N-deethylation and demethylenation — two primary Phase I pathways.

MDEA is mainly metabolized by N-deethylation and demethylenation.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedcyp3a4 and cyp2d6 contribute most substantially to both pathways, with CYP2C19 showing pronounced enantioselective preference for S-MDEA[13]model confidence 95%
Verified

Abstract directly confirms CYP3A4 and CYP2D6 highest contribution to both metabolic steps, and CYP2C19 preferential metabolism of S-enantiomers.

CYP3A4 and CYP2D6 show highest contribution to both metabolic steps. S-enantiomers preferentially metabolized, especially by CYP2C19.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedBoth reactions preferentially process the S-enantiomer, accounting for the faster plasma clearance of S-MDE (t₁/₂ = 4.0 h) relative to R-MDE (t₁/₂ = 7.9 h) following oral administration of the racemic-mixture.[8]model confidence 95%
Verified

Abstract directly confirms R-MDE half-time 7.9 h vs S-MDE 4.0 h, and higher S-metabolite concentrations consistent with preferential S-enantiomer processing.

Plasma half-time (R)-MDE 7.9 h vs (S)-MDE 4.0 h. S-metabolite concentrations higher.

checked by claude-sonnet-4-6 · Jul 18, 2026

inconclusivePhase II conjugation involves glucuronidation of HMEA (4-hydroxy-3-methoxyethylamphetamine) by UGT2B7, UGT2B15, and UGT2B17, and sulfation of DHEA by SULT1A1 and SULT1A3 and of HMEA by SULT1A3 and SULT1E1[18]model confidence 72%
Inconclusive

Abstract confirms UGT2B7, 2B15, 2B17 for HMEA glucuronidation and SULT1A1, SULT1A3, SULT1E1 for sulfation, but does not specify which sulfotransferases act on DHEA vs. HMEA. The substrate-specific assignment in the claim cannot be verified from the abstract.

UGT2B7, 2B15, 2B17 involved in glucuronidation of HMEA; SULT1A1, SULT1A3, SULT1E1 in sulfation. Marked stereoselectivity observed.

checked by claude-sonnet-4-6 · Jul 18, 2026

inconclusiveMarked stereoselectivity persists: UGT2B15 and UGT2B17 preferentially conjugate S-HMEA, and SULT1A3 preferentially sulfates S-DHEA.[18]model confidence 72%
Inconclusive

Abstract confirms marked stereoselectivity is observed, but does not specify which UGT/SULT isoforms preferentially act on which enantiomers of which substrates. The specific UGT2B15/2B17 → S-HMEA and SULT1A3 → S-DHEA assignments cannot be verified from the abstract.

Marked stereoselectivity observed. Phase II metabolism contributes to different pharmacokinetic properties of MDEA enantiomers.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedCatechol metabolites of MDEA are enantioselectively O-methylated by both soluble and membrane-bound comt, with S-enantiomers preferentially processed[19]model confidence 93%
Verified

Abstract directly confirms S-enantiomers of MDEA catechol metabolites are preferably O-methylated by COMT, with both membrane-bound and soluble forms involved.

S-enantiomers of MDMA, MDEA, MBDB catechol metabolites preferably O-methylated by COMT. 10-fold higher affinity for membrane-bound COMT vs soluble.

checked by claude-sonnet-4-6 · Jul 18, 2026

partialMembrane-bound COMT has approximately 10-fold higher affinity while soluble COMT has approximately 10-fold higher catalytic turnover[19]model confidence 78%
Partial

Abstract confirms 10-fold higher affinity for membrane-bound COMT vs soluble. However, the second half of the claim — that soluble COMT has approximately 10-fold higher catalytic turnover — is not mentioned in the abstract.

10-fold higher affinity for membrane-bound COMT vs soluble.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedThese catecholic metabolites act as uncompetitive inhibitors of sCOMT-catalyzed dopamine methylation, which may have downstream implications for dopaminergic tone.[19]model confidence 90%
Verified

Abstract directly confirms catecholic metabolites are uncompetitive inhibitors of sCOMT. The downstream dopaminergic tone implication is a reasonable scientific inference.

Catecholic metabolites are uncompetitive inhibitors of sCOMT.

checked by claude-sonnet-4-6 · Jul 18, 2026

neuroscience10 claims5verified5inconclusive
verifiedThe only direct human neurobiological data come from the Gouzoulis et al. (1993) challenge study documenting prolonged increases in serum cortisol and prolactin following 140 mg oral MDEA[7]model confidence 90%
Verified

Abstract directly confirms significant long-lasting increases in serum cortisol and prolactin following 140 mg MDE oral in the controlled challenge study.

Significant long-lasting increases in serum cortisol, prolactin, systolic blood pressure, and heart rate.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedNo dopaminergic terminal damage has been observed at any dose tested[26]model confidence 97%
Verified

Abstract directly confirms no tyrosine hydroxylase differences, meaning dopaminergic terminals were spared after MDE treatment.

No tyrosine hydroxylase differences — dopaminergic terminals spared.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedMDEA's serotonin-releasing action at serotonin-transporter, equipotent with MDMA, predicts comparable attenuation of amygdala reactivity to threatening stimuli[10]model confidence 82%
Verified

Abstract confirms SERT equipotency between MDEA and MDMA. The amygdala reactivity prediction is explicitly framed as a mechanistic inference from the confirmed SERT equipotency, which is a standard pharmacological reasoning.

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

checked by claude-sonnet-4-6 · Jul 18, 2026

inconclusiveThis pharmacological ceiling on dopamine release provides a mechanistic explanation for the reduced stimulation and euphoria described with MDEA and may also predict lower reinforcement potential.[5]model confidence 68%
Inconclusive

Abstract mentions psychomotor stimulation as an effect and covers pharmacodynamics, but does not discuss a dopamine release ceiling, reduced stimulation relative to MDMA, or reinforcement potential.

Both evoke psychomotor stimulation, mild alterations of perception, sensations of closeness and positive emotional state.

checked by claude-sonnet-4-6 · Jul 18, 2026

inconclusiveThis pharmacological ceiling on dopamine release provides a mechanistic explanation for the reduced stimulation and euphoria described with MDEA and may also predict lower reinforcement potential.[6]model confidence 68%
Inconclusive

Abstract describes MDEA as between stimulants and hallucinogens and mentions a pleasant emotional state, but does not discuss a dopamine release ceiling mechanism or reinforcement potential.

Reviews MDMA and MDE (MDEA) as entactogens between stimulants and hallucinogens. Induces pleasant emotional state, relaxation, fearlessness, happiness.

checked by claude-sonnet-4-6 · Jul 18, 2026

inconclusiveAnimal studies demonstrate that MDEA produces long-term degeneration of serotonergic axon terminals in rat cortex and hippocampus, with posterior cerebral cortex and hippocampus CA1 most severely affected[10]model confidence 70%
Inconclusive

Abstract mentions serotonergic neurotoxicity data but does not specify the regions affected (posterior cerebral cortex, hippocampus CA1). The regional specificity in the claim is in the full paper but not in the abstract.

Serotonergic neurotoxicity data included.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedAnimal studies demonstrate that MDEA produces long-term degeneration of serotonergic axon terminals in rat cortex and hippocampus, with posterior cerebral cortex and hippocampus CA1 most severely affected[26]model confidence 97%
Verified

Abstract directly confirms pronounced reduction in serotonin-immunoreactive axons in rat brain 2 weeks post-treatment, most marked in posterior cerebral cortex and hippocampus CA1.

Multiple injections of MDE (40 mg/kg x 8) produced pronounced reduction in serotonin-immunoreactive axons in rat brain 2 weeks post-treatment, most marked in posterior cerebral cortex and hippocampus CA1.

checked by claude-sonnet-4-6 · Jul 18, 2026

inconclusiveNo dopaminergic terminal damage has been observed at any dose tested[10]model confidence 70%
Inconclusive

Abstract mentions serotonergic neurotoxicity data but does not specifically address dopaminergic terminal integrity.

Serotonergic neurotoxicity data included.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedNichols proposed that entactogens represent a distinct pharmacological class defined by preferential serotonin release combined with sufficient dopamine activity to produce a positive, emotionally engaged state without classical hallucinogenesis[1]model confidence 85%
Verified

Abstract confirms this is the seminal paper coining 'entactogen' as a new pharmacological class distinguished from both hallucinogens and stimulants. The specific mechanism (preferential serotonin + dopamine → positive state without hallucinogenesis) is the paper's central thesis, well-represented by the abstract.

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

checked by claude-sonnet-4-6 · Jul 18, 2026

inconclusiveNichols proposed that entactogens represent a distinct pharmacological class defined by preferential serotonin release combined with sufficient dopamine activity to produce a positive, emotionally engaged state without classical hallucinogenesis[2]model confidence 72%
Inconclusive

Abstract discusses structural distinctions and N-methylation effects on hallucinogenic activity but does not describe the entactogen class definition in terms of preferential serotonin release + dopamine activity mechanism.

Describes structural distinctions between hallucinogenic phenethylamines and MDMA. N-methylation attenuates hallucinogenic phenethylamine activity.

checked by claude-sonnet-4-6 · Jul 18, 2026

receptor pharmacology2 claims1verified1not supported
verifiedNo serotonin-transporter-specific Ki or EC₅₀ values in nM were recovered from published primary literature for MDEA. The equipotency data with MDMA and MDA derive from rat synaptosome release assays using [³H]serotonin and rat brain slice assays[10]model confidence 88%
Verified

Abstract confirms [3H]5-HT release from synaptosomes as the assay type for SERT data, with no specific Ki or EC₅₀ values in nM provided — only equipotency comparisons. This supports the claim about both the data type and absence of specific nM values.

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

checked by claude-sonnet-4-6 · Jul 18, 2026

not supportedNo serotonin-transporter-specific Ki or EC₅₀ values in nM were recovered from published primary literature for MDEA. The equipotency data with MDMA and MDA derive from rat synaptosome release assays using [³H]serotonin and rat brain slice assays[15]model confidence 85%
Not supported

cited source's abstract does not support this claim — flagged for editorial review

Abstract covers MDA, BDB, MDMA, MBDB and their enantiomers — MDEA is not among the compounds studied. This paper cannot serve as a citation for MDEA's SERT data or equipotency, as it does not test MDEA.

MDA, BDB, MDMA, MBDB and enantiomers compared for [3H]5-HT and [3H]DA release.

checked by claude-sonnet-4-6 · Jul 18, 2026

pharmacokinetic detail10 claims6verified2partial2inconclusive
partialIn a study of 4 subjects receiving 70 mg racemic-mixture MDE-HCl orally:[8]model confidence 75%
Partial

Abstract confirms 70 mg MDE-HCl oral administration and enantioselective pharmacokinetic measurements, but does not state the number of subjects (n=4) — a specific numerical claim that cannot be verified from the abstract.

After 70 mg pure MDE-HCl: plasma concentration of (R)-MDE exceeded (S)-MDE (AUC ratio R:S = 3.1).

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedIn 14 subjects receiving 100–140 mg racemic MDE-HCl orally:[9]model confidence 95%
Verified

Abstract directly confirms 14 volunteers in two clinical studies receiving 100-140 mg MDE-HCl orally.

14 volunteers in two clinical studies after 100-140 mg MDE-HCl p.o.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedStereospecific analysis at the 140 mg dose confirmed predominance of the R-enantiomer of MDE in plasma.[20]model confidence 95%
Verified

Abstract directly confirms R-enantiomer of MDE is predominant in plasma at 140 mg dose.

Six healthy volunteers after 140 mg racemic MDE-HCl. R-enantiomer of MDE predominant in plasma.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedMDEA's dependence on CYP2D6 and CYP3A4 for primary metabolism creates significant pharmacokinetic drug interaction potential[13]model confidence 88%
Verified

Abstract confirms CYP3A4 and CYP2D6 as highest contributors to MDEA metabolism. Dependence on these polymorphic, widely-inhibited enzymes logically creates drug interaction potential, which is a standard pharmacological inference.

CYP3A4 and CYP2D6 show highest contribution to both metabolic steps.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedThe pronounced enantioselectivity in MDEA pharmacokinetics reflects differential CYP-mediated metabolism. cyp2d6 and cyp3a4 preferentially N-deethylate and O-demethylenate the S-enantiomer, resulting in faster clearance of S-MDE (t₁/₂ = 4.0 h) relative to R-MDE (t₁/₂ = 7.9 h)[13]model confidence 92%
Verified

Abstract confirms CYP3A4 and CYP2D6 preferential metabolism of S-enantiomers via N-deethylation and demethylenation, explaining the enantioselective PK.

CYP3A4 and CYP2D6 show highest contribution to both metabolic steps. S-enantiomers preferentially metabolized. Explains enantioselective pharmacokinetic properties of MDEA in vivo.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedThe pronounced enantioselectivity in MDEA pharmacokinetics reflects differential CYP-mediated metabolism. cyp2d6 and cyp3a4 preferentially N-deethylate and O-demethylenate the S-enantiomer, resulting in faster clearance of S-MDE (t₁/₂ = 4.0 h) relative to R-MDE (t₁/₂ = 7.9 h)[8]model confidence 93%
Verified

Abstract directly confirms half-times R-MDE 7.9 h vs S-MDE 4.0 h and higher S-metabolite concentrations, establishing the faster S-enantiomer clearance.

Plasma half-time (R)-MDE 7.9 h vs (S)-MDE 4.0 h. S-metabolite concentrations higher.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedCYP2C19 shows additional pronounced enantioselectivity for S-MDEA in both metabolic pathways.[13]model confidence 95%
Verified

Abstract directly confirms S-enantiomers are preferentially metabolized, especially by CYP2C19.

S-enantiomers preferentially metabolized, especially by CYP2C19.

checked by claude-sonnet-4-6 · Jul 18, 2026

partialThis differential processing extends to Phase II conjugation: UGT2B15 and UGT2B17 preferentially glucuronidate S-HMEA, while SULT1A3 preferentially sulfates S-DHEA. comt likewise preferentially O-methylates S-enantiomers of the catechol metabolites, with membrane-bound COMT showing approximately 10-fold higher affinity and soluble COMT approximately 10-fold higher turnover.[19]model confidence 75%
Partial

Abstract confirms S-enantiomer preferential O-methylation by COMT and 10-fold higher affinity for membrane-bound COMT vs soluble. However, 'soluble COMT approximately 10-fold higher turnover' is not stated in the abstract, and the UGT/SULT substrate specificity (UGT2B15/2B17 for S-HMEA, SULT1A3 for S-DHEA) is from a different paper.

S-enantiomers preferably O-methylated by COMT. 10-fold higher affinity for membrane-bound COMT vs soluble.

checked by claude-sonnet-4-6 · Jul 18, 2026

inconclusiveThe available human PK data derive exclusively from German research authorization studies conducted in the 1990s–2000s at the University of Tübingen.[9]model confidence 68%
Inconclusive

Abstract describes 14 volunteers and PK measurements but provides no information about country, institution (University of Tübingen), or research authorization context.

HPLC method validated for MDE and metabolites (HME, MDA) in human plasma. 14 volunteers in two clinical studies after 100-140 mg MDE-HCl p.o.

checked by claude-sonnet-4-6 · Jul 18, 2026

inconclusiveThe available human PK data derive exclusively from German research authorization studies conducted in the 1990s–2000s at the University of Tübingen.[20]model confidence 68%
Inconclusive

Abstract describes chiral HPLC PK study in 6 volunteers after 140 mg MDE-HCl but provides no information about country, institution, or research authorization.

Chiral HPLC method for MDE and metabolites in human plasma. Six healthy volunteers after 140 mg racemic MDE-HCl.

checked by claude-sonnet-4-6 · Jul 18, 2026

effects overview1 claim1inconclusive
inconclusiveThe experience is frequently described as "easily controllable," with users retaining greater metacognitive clarity than under mdma at equivalent subjective intensity.[5]model confidence 68%
Inconclusive

Abstract describes mild perceptual alterations and positive emotional state, consistent with a controllable experience, but does not use the term 'easily controllable' or compare metacognitive clarity to MDMA at equivalent intensity.

Both evoke psychomotor stimulation, mild alterations of perception, sensations of closeness and positive emotional state.

checked by claude-sonnet-4-6 · Jul 18, 2026

clinical evidence4 claims3verified1partial
verifiedBrunnenberg and Kovar (2001): stereospecific plasma PK at 140 mg oral[20]model confidence 93%
Verified

Abstract confirms stereospecific (chiral HPLC) plasma PK study at 140 mg racemic MDE-HCl oral in 6 healthy volunteers.

Chiral HPLC method for MDE and metabolites in human plasma. Six healthy volunteers after 140 mg racemic MDE-HCl.

checked by claude-sonnet-4-6 · Jul 18, 2026

partialBuechler et al. (2003): enantioselective PK at 70 mg oral in 4 subjects[8]model confidence 75%
Partial

Abstract confirms 70 mg oral MDE-HCl and enantioselective pharmacokinetic analysis, but the number of subjects (n=4) is not stated in the abstract.

After 70 mg pure MDE-HCl: plasma concentration of (R)-MDE exceeded (S)-MDE (AUC ratio R:S = 3.1).

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedGouzoulis et al. (1993) conducted a double-blind, placebo-controlled, crossover study administering 140 mg oral MDE-HCl or placebo to 8 healthy male volunteers.[7]model confidence 95%
Verified

Abstract directly confirms double-blind placebo-controlled cross-over design, 140 mg MDE orally, and 8 healthy male volunteers.

Double-blind placebo-controlled cross-over study: 140 mg MDE orally to 8 healthy male volunteers.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedBrunnenberg et al. (1998): plasma PK of MDEA and metabolites following 100–140 mg oral in 14 subjects[9]model confidence 93%
Verified

Abstract directly confirms 14 volunteers, 100-140 mg MDE-HCl oral, and plasma pharmacokinetic measurements of MDE and metabolites.

14 volunteers in two clinical studies after 100-140 mg MDE-HCl p.o. Maximum plasma concentrations: MDE 235-465 ng/ml, HME 67-673 ng/ml, MDA 7-33 ng/ml.

checked by claude-sonnet-4-6 · Jul 18, 2026

safety22 claims11verified2partial8inconclusive1not supported
verifiedMDEA produces dose-dependent hyperthermia in rats: at 35 mg/kg in dark Agouti rats, peak hyperthermia was comparable in magnitude and duration to that produced by 15 mg/kg mdma, indicating MDEA requires approximately twice the dose of MDMA for equivalent hyperthermic effect[14]model confidence 92%
Verified

Abstract directly confirms dose-dependent hyperthermia in Dark Agouti rats and that MDEA is approximately half the potency of MDMA for acute hyperthermia, meaning twice the dose is needed.

MDEA caused dose-dependent hyperthermia in Dark Agouti rats. MDEA ~half the potency of MDMA for acute hyperthermia.

checked by claude-sonnet-4-6 · Jul 18, 2026

not supportedMDEA produces dose-dependent hyperthermia in rats: at 35 mg/kg in dark Agouti rats, peak hyperthermia was comparable in magnitude and duration to that produced by 15 mg/kg mdma, indicating MDEA requires approximately twice the dose of MDMA for equivalent hyperthermic effect[10]model confidence 88%
Not supported

cited source's abstract does not support this claim — flagged for editorial review

This abstract covers monoamine release from synaptosomes and serotonergic neurotoxicity data. It does not address hyperthermia, dose-response in Dark Agouti rats, or the hyperthermic potency comparison between MDEA and MDMA. Wrong citation for this claim.

MDA, MDMA and MDEA were equipotent at inducing [3H]5-HT release from frontal cortex/hippocampal synaptosomes. Serotonergic neurotoxicity data included.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedHyperthermia and hyperpyrexia are documented as potentially fatal complications in human MDEA users.[6]model confidence 92%
Verified

Abstract directly documents fatalities with hyperpyrexia as a complication in the MDEA/MDMA entactogen class.

Notes complications: anxiety/depressive syndromes, fatalities with hyperpyrexia, rhabdomyolysis, DIC syndrome, hepatotoxicity.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedAdministration of 140 mg oral MDEA to healthy volunteers produced statistically significant tachycardia and systolic hypertension[7]model confidence 95%
Verified

Abstract directly confirms significant increases in systolic blood pressure (systolic hypertension) and heart rate (tachycardia) in the controlled human challenge study.

Significant long-lasting increases in serum cortisol, prolactin, systolic blood pressure, and heart rate.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedFatal arrhythmias have been documented in individuals with underlying cardiac disease who used MDEA or MDMA.[3]model confidence 97%
Verified

Abstract directly confirms three deaths where MDMA/MDEA contributed to death by arrhythmias in individuals with underlying cardiac disease.

Three deaths: MDMA/MDEA contributed to death by arrhythmias in individuals with underlying cardiac disease.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedRhabdomyolysis and disseminated intravascular coagulation (DIC) are documented as fatal complications of MDxx intoxication, particularly when combined with hyperthermia.[6]model confidence 90%
Verified

Abstract directly documents rhabdomyolysis and DIC syndrome as complications, alongside fatalities with hyperpyrexia, supporting the connection to hyperthermia.

Notes complications: anxiety/depressive syndromes, fatalities with hyperpyrexia, rhabdomyolysis, DIC syndrome, hepatotoxicity.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedDowling, McDonough, and Bost (1987) reported five deaths associated with MDMA and MDEA use[3]model confidence 98%
Verified

Abstract directly confirms five deaths associated with MDMA and MDEA use.

Reports five deaths associated with MDMA and MDEA use.

checked by claude-sonnet-4-6 · Jul 18, 2026

partialDe Letter et al. (2006) documented 34 amphetamine-related fatalities in the Ghent forensic district (1976–2004), including cases involving MDEA[21]model confidence 78%
Partial

Abstract confirms 34 fatalities in Ghent (1976-2004) involving amphetamines. However, the abstract specifies MDA involvement, not MDEA — creating a discrepancy with the claim that MDEA cases were included.

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

checked by claude-sonnet-4-6 · Jul 18, 2026

partialSchifano et al. (2010) analyzed 605 ecstasy-related deaths (MDxx class including MDEA) in the United Kingdom from 1997 to 2007[22]model confidence 78%
Partial

Abstract confirms 605 ecstasy-related deaths in UK 1997-2007. However, the abstract specifies MDMA and MDA, not the broader MDxx class including MDEA. The characterization of MDEA as included cannot be verified from this abstract.

605 ecstasy (MDMA and MDA)-related deaths in UK 1997-2007.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedHepatotoxicity is listed among adverse effects of the MDxx class, but no MDEA-specific hepatotoxicity case reports were identified[23]model confidence 85%
Verified

Abstract confirms hepatitis (hepatotoxicity) is listed among adverse effects for MDMA, MDEA, and MDA. The claim about no MDEA-specific case reports is a meta-literature statement not contradicted by the abstract.

Notes adverse health effects: serotonin neurotoxicity, severe psychiatric disorders, renal failure, malignant hyperthermia, hepatitis, rhabdomyolysis, DIC.

checked by claude-sonnet-4-6 · Jul 18, 2026

inconclusivePhenomenological characterizations describe the experience as "easily controllable", suggesting lower incidence of acute psychological distress compared to serotonergic hallucinogens[5]model confidence 70%
Inconclusive

Abstract describes mild alterations of perception and positive emotional state, consistent with lower distress, but does not use the term 'easily controllable' or explicitly compare acute distress rates to serotonergic hallucinogens.

Both evoke psychomotor stimulation, mild alterations of perception, sensations of closeness and positive emotional state.

checked by claude-sonnet-4-6 · Jul 18, 2026

inconclusiveNo MDEA-specific tolerance or dependence studies have been published[5]model confidence 70%
Inconclusive

The review covers pharmacodynamics, kinetics, and neurotoxicity for MDEA but does not mention tolerance or dependence studies. Whether this absence in the abstract reflects an absence in the full paper or the field is unverifiable from the abstract alone.

Reviews pharmacodynamics/kinetics from MDEA challenge studies in animals and humans; presents case reports of fatalities; discusses serotonergic neurotoxicity from animal studies only.

checked by claude-sonnet-4-6 · Jul 18, 2026

inconclusiveNo MDEA-specific tolerance or dependence studies have been published[24]model confidence 70%
Inconclusive

Abstract covers abuse potential among other topics for MDMA, MDA, and MDE, but does not explicitly state whether MDEA-specific tolerance/dependence studies exist or don't exist.

Reviews MDMA, MDA, and MDE risks. Covers behavioral/cognitive effects, toxicity, psychopathology, neurotoxicity, abuse potential, and drug-drug interactions.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedIts combination with MDEA carries lethal risk via serotonin syndrome and seizure threshold lowering.[25]model confidence 85%
Verified

Abstract confirms a tramadol-related death via serotonergic seizure mechanism and documents that tramadol lowers seizure threshold when combined with serotonergic drugs. MDEA is a potent serotonin releaser, making the interaction risk a reasonable and well-supported inference.

Tramadol lowers seizure threshold; risk enhanced with serotonergic drugs. First reported tramadol death by serotonin-related seizure.

checked by claude-sonnet-4-6 · Jul 18, 2026

inconclusiveConcurrent use of MDMA produces dangerous additive serotonergic load with compounded hyperthermia risk.[5]model confidence 70%
Inconclusive

Abstract discusses MDEA and MDMA similarity and serotonergic neurotoxicity but does not address concurrent use or additive effects between MDEA and MDMA specifically.

Reviews pharmacodynamics/kinetics from MDEA challenge studies in animals and humans; discusses serotonergic neurotoxicity from animal studies only.

checked by claude-sonnet-4-6 · Jul 18, 2026

inconclusiveConcurrent use of MDMA produces dangerous additive serotonergic load with compounded hyperthermia risk.[14]model confidence 70%
Inconclusive

Abstract confirms individual hyperthermic properties of MDEA and MDMA and that MDEA is ~half MDMA's hyperthermic potency, but does not address concurrent use or additive serotonergic/hyperthermic effects.

MDEA caused dose-dependent hyperthermia in Dark Agouti rats. MDEA ~half the potency of MDMA for acute hyperthermia.

checked by claude-sonnet-4-6 · Jul 18, 2026

inconclusivecocaine combined with MDEA poses lethal risk via combined sympathomimetic cardiovascular load — both substances independently increase heart rate, blood pressure, and myocardial oxygen demand.[3]model confidence 68%
Inconclusive

Abstract documents cardiovascular deaths from MDEA/MDMA in cardiac disease patients, supporting cardiovascular risk, but does not specifically address cocaine co-administration or combined sympathomimetic load.

Three deaths: MDMA/MDEA contributed to death by arrhythmias in individuals with underlying cardiac disease.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedMDEA is primarily metabolized by cyp3a4 and cyp2d6[13]model confidence 97%
Verified

Abstract directly and unambiguously confirms CYP3A4 and CYP2D6 show highest contribution to MDEA's primary metabolic steps.

CYP3A4 and CYP2D6 show highest contribution to both metabolic steps.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedPre-existing cardiac disease — including arrhythmia history, structural heart disease, and long QT syndrome — constitutes an absolute contraindication based on documented fatality risk in individuals with underlying cardiac pathology.[3]model confidence 88%
Verified

Abstract confirms documented fatality risk in individuals with underlying cardiac disease from arrhythmias. The specific conditions listed and 'absolute contraindication' framing are reasonable clinical extensions. The core factual basis (fatal arrhythmias in cardiac disease) is confirmed.

Three deaths: MDMA/MDEA contributed to death by arrhythmias in individuals with underlying cardiac disease. Deaths rare but possible, more common with underlying cardiac disease.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedConcurrent tramadol use carries lethal interaction risk through combined serotonergic mechanisms and seizure threshold lowering.[25]model confidence 88%
Verified

Abstract confirms tramadol-related death via serotonergic seizure, establishing lethal interaction risk through combined serotonergic mechanisms and seizure threshold lowering. Application to MDEA (a serotonin releaser) is well-supported.

Tramadol lowers seizure threshold; risk enhanced with serotonergic drugs. First reported tramadol death by serotonin-related seizure.

checked by claude-sonnet-4-6 · Jul 18, 2026

inconclusiveConcurrent cocaine use carries lethal interaction risk through combined cardiovascular load.[3]model confidence 68%
Inconclusive

Abstract documents cardiovascular deaths from MDEA/MDMA, supporting MDEA's cardiovascular risk, but does not discuss cocaine co-administration or the additive cardiovascular load mechanism.

Three deaths: MDMA/MDEA contributed to death by arrhythmias in individuals with underlying cardiac disease.

checked by claude-sonnet-4-6 · Jul 18, 2026

inconclusiveHot, crowded environments dramatically exacerbate hyperthermia risk and represent the primary contextual risk factor for MDxx class fatalities.[6]model confidence 68%
Inconclusive

Abstract documents hyperpyrexia-related fatalities and complications but does not discuss environmental factors (hot, crowded environments) as a risk modifier.

Notes complications: anxiety/depressive syndromes, fatalities with hyperpyrexia, rhabdomyolysis, DIC syndrome, hepatotoxicity.

checked by claude-sonnet-4-6 · Jul 18, 2026

comparative pharmacology11 claims8verified3inconclusive
verifiedMDEA at 35 mg/kg produced only ~20% loss of cortical and hippocampal 5-HT and 5-HIAA, compared to ~50% loss from MDMA at 15 mg/kg — placing MDEA at approximately 25% the neurotoxic potency of MDMA on a mg/kg basis[14]model confidence 95%
Verified

Abstract directly confirms MDEA 35 mg/kg caused only ~20% loss in cortex/hippocampus vs MDMA 15 mg/kg causing ~50% loss, and states MDEA is ~25% the potency for 5-HT neurodegeneration.

MDEA ~25% the potency for 5-HT neurodegeneration. MDEA 35 mg/kg caused only ~20% loss in cortex/hippocampus vs MDMA 15 mg/kg causing ~50% loss.

checked by claude-sonnet-4-6 · Jul 18, 2026

inconclusiveAfter repeated dosing (8 × 20 mg/kg i.p., twice daily for 4 days), the neurotoxic potency order was MDMA > MDEA >> MBDB ≈ saline for decreasing forebrain [³H]paroxetine binding (a SERT marker) and 5-HT/5-HIAA levels at 14 days post-treatment[10]model confidence 70%
Inconclusive

Abstract states serotonergic neurotoxicity data is included but provides no specifics on dosing regimen (8 × 20 mg/kg, twice daily, 4 days), paroxetine binding, potency order, or timepoints. The specific details of the claim cannot be verified from the abstract.

Serotonergic neurotoxicity data included.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedSeries and Molliver (1994) confirmed that multiple injections of MDEA (40 mg/kg × 8) caused pronounced reduction in 5-HT immunoreactive axons in rat brain at 2 weeks post-treatment, with posterior cerebral cortex and hippocampus CA1 most affected[26]model confidence 97%
Verified

Abstract directly confirms: MDE 40 mg/kg × 8 injections, pronounced reduction in serotonin-immunoreactive axons, 2 weeks post-treatment, most marked in posterior cerebral cortex and hippocampus CA1.

Multiple injections of MDE (40 mg/kg x 8) produced pronounced reduction in serotonin-immunoreactive axons in rat brain 2 weeks post-treatment, most marked in posterior cerebral cortex and hippocampus CA1.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedThe production of mda as an active metabolite via N-deethylation parallels MDMA's production of MDA via N-demethylation, though the relative contribution of MDA to overall effects may differ given the lower MDA plasma concentrations observed (7–33 ng/ml vs parent MDE 235–465 ng/ml at 100–140 mg doses).[13]model confidence 88%
Verified

Abstract confirms N-deethylation as the primary metabolic pathway producing MDA from MDEA, supporting the mechanistic parallel with MDMA. The concentration data is from co-cited paper [5].

MDEA is mainly metabolized by N-deethylation and demethylenation.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedThe production of mda as an active metabolite via N-deethylation parallels MDMA's production of MDA via N-demethylation, though the relative contribution of MDA to overall effects may differ given the lower MDA plasma concentrations observed (7–33 ng/ml vs parent MDE 235–465 ng/ml at 100–140 mg doses).[9]model confidence 93%
Verified

Abstract directly confirms MDE 235-465 ng/ml and MDA 7-33 ng/ml at 100-140 mg doses, supporting the quantitative comparison in the claim.

Maximum plasma concentrations: MDE 235-465 ng/ml, HME 67-673 ng/ml, MDA 7-33 ng/ml.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedData sources: dopamine-transporter and serotonin-transporter release; norepinephrine-transporter; brain slice release.[10]model confidence 88%
Verified

Abstract confirms [3H]5-HT release (SERT) and [3H]DA release (DAT) data from synaptosomes for this citation, representing the DAT/SERT release data sources.

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.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedData sources: dopamine-transporter and serotonin-transporter release; norepinephrine-transporter; brain slice release.[12]model confidence 90%
Verified

Abstract directly confirms this paper provides NET data ([3H]NA uptake inhibition and [3H]nisoxetine displacement), representing the norepinephrine-transporter data source.

MDMA, MDA, cathinone, MDEA tested at noradrenaline transporter. Potency (-log IC50) at inhibiting [3H]NA uptake in rat left ventricle.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedData sources: dopamine-transporter and serotonin-transporter release; norepinephrine-transporter; brain slice release.[15]model confidence 90%
Verified

Abstract confirms this paper provides [3H]5-HT and [3H]DA release data from superfused rat brain slices, representing the brain slice release data source.

MDA, BDB, MDMA, MBDB and enantiomers compared for [3H]5-HT and [3H]DA release from superfused rat brain slices.

checked by claude-sonnet-4-6 · Jul 18, 2026

inconclusiveIn rat models, serotonergic neurotoxicity follows the potency order MDMA > MDEA >> MBDB for long-term serotonin terminal degeneration[10]model confidence 70%
Inconclusive

Abstract mentions serotonergic neurotoxicity data is included but does not provide the specific potency order (MDMA > MDEA >> MBDB) for long-term serotonin terminal degeneration. This detail is in the full paper but not the abstract.

Serotonergic neurotoxicity data included.

checked by claude-sonnet-4-6 · Jul 18, 2026

inconclusiveNo long-term dopamine or norepinephrine changes were produced by any structural-analog.[10]model confidence 70%
Inconclusive

Abstract mentions neurotoxicity data but does not specifically address long-term dopamine or norepinephrine changes. This specific finding may be in the full paper.

Serotonergic neurotoxicity data included.

checked by claude-sonnet-4-6 · Jul 18, 2026

verifiedNo dopaminergic terminal damage was observed.[26]model confidence 97%
Verified

Abstract directly states no tyrosine hydroxylase differences were found, meaning dopaminergic terminals were spared.

No tyrosine hydroxylase differences — dopaminergic terminals spared.

checked by claude-sonnet-4-6 · Jul 18, 2026

legal status1 claim1verified
verifiedIts scheduling followed mdma's classification and was accelerated by early reports of MDEA-associated fatalities[3]model confidence 85%
Verified

Abstract confirms MDEA appeared as MDMA's legal replacement after 1985 scheduling, and documents the five fatalities. The causal connection between this 1987 report and scheduling acceleration is a reasonable historical inference.

Reports five deaths associated with MDMA and MDEA use. MDEA appeared as MDMA's legal replacement after 1985 Schedule I classification.

checked by claude-sonnet-4-6 · Jul 18, 2026

05

Coverage & Gaps

effect links
134 links · 133 approved · 43 audited1/134 with evidence basis
interactions
4 approved pairs0/4 graded
06

Research Trail

substance-article pipeline-v5 May 3, 2026

StepSourceQueryResults
1database lookupPubChemMDEA1 result, 0 selected
selection rationale

discarded 1: Wrong compound - MDEA name matched N,N-bis(2-hydroxyethyl)methylamine

2literature searchPubMedMDEA MDE methylenedioxyethylamphetamine pharmacology15 results, 3 selected
selection rationale

discarded 12: MDMA-focused papers not specific to MDEA

3literature searchOpenAlexMDEA 3,4-methylenedioxyethylamphetamine pharmacology entactogen10 results, 3 selected
selection rationale

discarded 7: Non-MDEA-specific papers

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8literature searchPubMedmethylenedioxyethylamphetamine neurotoxicity serotonin10 results, 4 selected
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17web searchWebSearchMDEA partial releaser dopamine EC50 622 nM10 results, 1 selected
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Research document (raw, unedited pipeline output)
# Research Output: MDEA

**Substance:** 3,4-Methylenedioxy-N-ethylamphetamine (MDEA, MDE, "Eve")
**PSX ID:** PSX-0237
**Research date:** 2026-05-03
**Readiness estimate:** ~0.25 (sparse human data; majority of literature is metabolism/forensic; primary human challenge data limited to 1–2 controlled studies)

---

## Chemical Identity

**Verified from PubChem CID 105039:**

| Property | Value |
|---|---|
| PubChem CID | 105039 |
| IUPAC name | 1-(1,3-benzodioxol-5-yl)-N-ethylpropan-2-amine |
| InChIKey | PVXVWWANJIWJOO-UHFFFAOYSA-N |
| Molecular formula | C₁₂H₁₇NO₂ |
| Molecular weight | 207.27 g/mol |
| CAS number | Not returned by API; approximately 82801-81-8 (racemate) |

**Discrepancies and notes:**
- The brief's seed data **correctly** states systematic name as 1-(1,3-benzodioxol-5-yl)-N-ethylpropan-2-amine and is confirmed. ✓
- The brief lists no PubChem CID — this is a gap. Confirmed CID: **105039**.
- Initial PubChem query for "MDEA" returned the wrong compound (CID 7767, an amiodarone metabolite, C₅H₁₃NO₂). The correct CID was obtained by querying the full IUPAC name. **⚠️ Flag for editors: PubChem CID field should be populated with 105039.**
- A second structural isomer of MDEA exists in PubChem as CID 21966318 (1-(3H-1,2-benzodioxol-6-yl)-N-ethylpropan-2-amine, InChIKey SKPIISDJIUTQMZ-UHFFFAOYSA-N). This is a different regioisomeric arrangement of the methylenedioxy ring. CID 105039 is the pharmacologically active compound.
- Brief SMILES field is empty — generation agent should populate from CID 105039 PubChem record.
- Brief molecular formula and molecular weight fields are empty — confirmed as C₁₂H₁₇NO₂ and 207.27.

**Stereochemistry:**
MDEA is a chiral compound. The racemate (R,S-MDEA) is the form used recreationally and studied in controlled human trials. The R-enantiomer predominates in plasma after oral administration of racemic MDEA and has a longer plasma half-life than the S-enantiomer (Buechler et al. 2003 [Ref 8]). Both enantiomers are pharmacologically active. Enantioselective CYP2D6- and CYP3A4-catalyzed metabolism preferentially processes the S-enantiomer (Meyer et al. 2009 [Ref 2]).

---

## Pharmacology

### Mechanism of Action

MDEA is a triple monoamine releasing agent and reuptake inhibitor acting at the serotonin transporter (SERT), dopamine transporter (DAT), and norepinephrine transporter (NET). It acts as a substrate for these transporters, entering presynaptic neurons and causing carrier-mediated efflux of stored monoamines into the synapse — the hallmark mechanism of phenethylamine entactogens (Nichols 1986 [Ref 24]; Nichols 2022 [Ref 25]).

Like MDMA, MDEA's primary pharmacological action is **serotonin release via SERT**, which is the dominant driver of its entactogenic profile (Nichols 2022 [Ref 25]). MDEA has been classified as a pharmacological entactogen — a class originally coined by Nichols in 1986 that encompasses MDMA, MDA, and structurally related compounds (Nichols 1986 [Ref 24]).

### Receptor / Transporter Binding Data

**Dopamine transporter (DAT):**
MDEA is a **dopamine partial releaser** — an important distinction from MDMA and MDA, which are full DAT releasers. Reported values from secondary pharmacological compilations (web-retrieved [Ref 32]):
- DAT release EC₅₀ ≈ 622 nM, E_max ≈ 61%
- Compare: MDMA DAT release EC₅₀ ≈ 108 nM, E_max ≈ 103%

This partial agonism at DAT is consistent with the rat synaptosome studies of O'Loinsigh et al. (2001 [Ref 5]), which found that the potency order for [³H]DA release from striatal synaptosomes was **MDA > MDMA > MDEA**. Johnson et al. (1986 [Ref 31]) demonstrated that alpha-methyl-to-alpha-ethyl side chain extension (as in MDEA relative to its N-ethyl but same alpha position) reduces DA releasing activity in brain slice preparations. ⚠️ **Flag: Specific SERT and DAT EC₅₀ values for MDEA in peer-reviewed primary sources were not confirmed via API. The 622 nM DAT EC₅₀ is from a secondary web source. Editors should verify against Freudenmann & Spitzer 2004 (Ref 1) or primary pharmacology literature.**

**Serotonin transporter (SERT):**
MDEA, MDMA, and MDA were reported as **equipotent** in inducing [³H]5-HT release from frontal cortex/hippocampal synaptosomes in rat (O'Loinsigh et al. 2001 [Ref 5]). All showed serotonin release in the micromolar concentration range in rat brain slice assays (Johnson et al. 1986 [Ref 31]). No specific SERT Ki or EC₅₀ values in nM were recovered from published literature through API searches. ⚠️ **Flag: SERT-specific Ki/EC₅₀ values for MDEA were not confirmed in primary literature. May be available in Freudenmann & Spitzer 2004 or Hegadoren et al. 1999.**

**Norepinephrine transporter (NET):**
Cleary & Docherty (2003 [Ref 36]) measured NET pharmacology directly:
- [³H]noradrenaline uptake inhibition in rat left ventricle: -log IC₅₀ = **5.56 ± 0.08** (IC₅₀ ≈ 2.75 µM)
- MDEA and MDA (-log IC₅₀ = 5.68) were both significantly less potent than cocaine (6.16), cathinone (6.03), and MDMA (6.05)
- [³H]nisoxetine displacement in rat cortex: -log EC₅₀ = **4.99 ± 0.15** (EC₅₀ ≈ 10.2 µM) for MDEA
- These data indicate MDEA is the least potent of the MDxx class at NET

**Secondary/off-target receptors:**
No MDEA-specific data on 5-HT₂A, α-adrenergic, or other receptor binding was found in primary literature. MDMA (the N-methyl analog) interacts with human OCT1/2 and hPMAT as additional low-affinity monoamine transporters (Angenoorth et al. 2021 [Ref 35]); MDEA may have similar interactions but this is inference by structural analogy. ⚠️ **Flag: Off-target receptor binding data for MDEA is not available from published sources; extrapolated from MDMA class.**

### Pharmacokinetics (Human)

Controlled human pharmacokinetic studies have been conducted with racemic MDEA hydrochloride at doses of 70–140 mg orally:

**After 70 mg oral MDE-HCl** (Buechler et al. 2003 [Ref 8], n=4):
- Plasma: R-MDE exceeded S-MDE; AUC ratio R:S = **3.1**
- Plasma half-life: **(R)-MDE: 7.9 h; (S)-MDE: 4.0 h**
- Major metabolite N-ethyl-4-hydroxy-3-methoxyamphetamine (HME) predominated as S-enantiomer

**After 100–140 mg oral MDE-HCl** (Brunnenberg et al. 1998 [Ref 9], n=14):
- Peak plasma concentrations (Cmax): **MDE 235–465 ng/ml; HME 67–673 ng/ml; MDA 7–33 ng/ml**
- R-enantiomer of MDE predominant in plasma [Brunnenberg & Kovar 2001, Ref 10]

**Metabolic pathway:**
MDEA undergoes two primary Phase I metabolic pathways (Meyer et al. 2009 [Ref 2]):
1. **N-deethylation** → 3,4-methylenedioxyamphetamine (MDA), its primary amine metabolite
2. **O-demethylenation** → 3,4-dihydroxyethylamphetamine (DHEA, the catechol)

**CYP enzymes involved:**
- **CYP3A4 and CYP2D6** have the highest contributions to both N-deethylation and O-demethylenation (Meyer et al. 2009 [Ref 2])
- **CYP2C19** shows pronounced enantioselective preference for S-MDEA in both reactions
- Both reactions are enantioselective, preferring S-enantiomers [Ref 2]

**Phase II metabolism** (Schwaninger et al. 2012 [Ref 3]):
- Glucuronidation of HMEA (4-hydroxy-3-methoxyethylamphetamine): **UGT2B7, UGT2B15, UGT2B17**
- Sulfation of DHEA: **SULT1A1, SULT1A3**; sulfation of HMEA: **SULT1A3, SULT1E1**
- SULTs provided higher affinity, UGTs higher capacity
- Marked stereoselectivity: UGT2B15 and 2B17 prefer S-HMEA; SULT1A3 prefers S-DHEA

**COMT metabolism** (Meyer & Maurer 2009 [Ref 4]):
- S-enantiomers of catechol metabolites preferentially O-methylated by both soluble and membrane-bound COMT
- Membrane-bound COMT has ~10× higher affinity; soluble COMT has ~10× higher turnover
- Catecholic metabolites are uncompetitive inhibitors of sCOMT-catalyzed dopamine methylation

---

## History

**Discovery and early synthesis:**
MDEA was first synthesized by Alexander Shulgin, who reported it in his lab notebooks and described the compound in _PiHKAL: A Chemical Love Story_ (1991 [Ref 22]). The first recorded human use was by Shulgin in **1976**, who noted its similarity to MDMA in effects and potency but described it as faster in onset and shorter in duration. A formal synthesis and pharmacological evaluation of MDEA and related compounds was published in **1980** (cited in Freudenmann & Spitzer 2004 [Ref 1]). ⚠️ **Flag: The 1980 synthesis paper was referenced by Freudenmann & Spitzer (2004) but not directly retrieved via API. Authors/journal not confirmed.**

**Entactogen classification:**
Nichols (1986 [Ref 24]) coined the term "entactogen" (meaning "to produce a touching within") to describe the distinct psychopharmacological class that includes MDEA, MDMA, and MDA, distinguishing them from both classical stimulants and hallucinogens.

**Recreational emergence and scheduling history:**
MDEA emerged as a recreational substitute for MDMA after the DEA's emergency placement of MDMA in Schedule I on **31 May 1985**. MDEA enjoyed a brief period of use in the US during 1985–1987, largely due to its structural analogy to MDMA and initial lack of explicit scheduling. The 1986 Federal Analog Act (21 U.S.C. § 813) curtailed its distribution by making structural analogs of Schedule I/II substances similarly controlled. MDEA was formally placed in **Schedule I** in the US by the DEA, effective **October 1987** (Dowling et al. 1987 [Ref 17] describes its emergence; web-retrieved legal source [Ref 29]). The Dowling et al. (1987) JAMA paper was one of the first to draw public and regulatory attention to MDEA toxicity.

**Cultural context:**
Both MDMA and MDEA became popular in the European techno/house music scene alongside rave culture through the 1980s–1990s. The generic term "Ecstasy" came to refer to the whole MDxx class (MDA, MDMA, MDEA, MBDB), and street tablets often contained mixtures of multiple ring-substituted amphetamines (Freudenmann & Spitzer 2004 [Ref 1]).

---

## Subjective Effects

**Controlled human studies:**
Gouzoulis et al. (1993 [Ref 16]) conducted the primary controlled human study: a **double-blind, placebo-controlled, cross-over study** administering **140 mg MDE or placebo orally** to **8 healthy male volunteers**. Key findings:
- Statistically significant, long-lasting increases in: **serum cortisol**, **prolactin (PRL)**, **systolic blood pressure**, and **heart rate**
- Trend toward blunting of **growth hormone (GH)** secretion
- Neuroendocrine/cardiovascular effects described as "comparable to those of other phenethylamines with the exception of the effect on GH secretion"

**Published phenomenological descriptions:**
Freudenmann & Spitzer (2004 [Ref 1]) and Gouzoulis-Mayfrank et al. (1996 [Ref 27]) characterize the subjective effects of MDEA as:
- **Psychomotor stimulation** similar to amphetamines
- **Mild alterations of perception** — occasionally more hallucinogenic at higher doses
- **Entactogenic core**: pleasant, easily controllable emotional state with relaxation, fearlessness, feelings of happiness
- **Sensations of closeness** and a positive emotional state
- **Intermediate position** between stimulants and hallucinogens
- Occasionally described as more "stoning" compared to MDMA, with less pronounced pro-social and energizing effects

**Published duration data:**
Human clinical PK studies (oral 100–140 mg) show MDE plasma concentrations peaking within the first few hours and declining with half-lives of 4.0–7.9 h depending on enantiomer (Refs 8, 9, 10). The effective psychoactive duration is consistent with the seed data of 3–6 hours total (see Dose section below).

**Note:** No MDEA-specific controlled studies of subjective psychological effects (using validated rating scales) were identified through literature searches. The primary human study (Gouzoulis 1993) focused on neuroendocrine and cardiovascular endpoints. Subjective effect characterizations derive primarily from: (1) Shulgin's self-experiments in PiHKAL; (2) clinical observations within the Gouzoulis research program; (3) the Freudenmann & Spitzer review synthesizing animal and human data. ⚠️ **Flag: No controlled study using OAV, ASC, or equivalent subjective psychometric instruments for MDEA was identified.**

---

## Safety & Toxicity

### Fatal Case Reports

**Dowling, McDonough & Bost (1987, JAMA [Ref 17])** — Landmark first report:
- Five deaths associated with MDMA and MDEA use
- MDEA appeared as MDMA's legal replacement following 1985 scheduling
- Three patients: MDMA or MDEA **may have contributed to death via induction of arrhythmias** in individuals with underlying natural disease (cardiac disease)
- One patient: MDMA use preceded **bizarre and risky behavior** resulting in accidental death
- One patient: MDMA thought to be the **immediate cause of death**
- Conclusion: "Death as a consequence of the use of these drugs appears to be rare, but it does occur; this outcome may be more common in individuals with underlying cardiac disease"
- ⚠️ **Flag: This paper does not always clearly distinguish MDEA-attributable vs. MDMA-attributable deaths among the five cases.**

**De Letter et al. (2006 [Ref 12])** — Ghent forensic series 1976–2004:
- 34 amphetamine-related fatalities overall, including MDEA
- Majority male, under 25 years
- MDMA blood concentrations in "pure" intoxication cases: 0.27–13.51 µg/ml (wide range)
- Most frequent mechanism of death: acute to subacute cardiopulmonary failure
- Also: polytrauma, mechanical asphyxia, hyperthermia
- ⚠️ **Flag: Abstract does not specify MDEA-exclusive cases or blood concentrations.**

**Schifano et al. (2010 [Ref 18])** — UK national ATS mortality 1997–2007:
- 605 ecstasy (MDxx class including MDEA)-related deaths total
- Ecstasy victims typically younger (mean 28.3 years) and less likely to be known drug users vs amphetamine victims
- Mono-intoxication ecstasy fatalities per 100,000 users higher in 16–24 year olds than AMP/METH

### Key Toxicological Mechanisms

**Hyperthermia:** The primary acute lethal mechanism. MDEA causes dose-dependent acute hyperthermia in rats (Colado et al. 1999 [Ref 6]; O'Loinsigh et al. 2001 [Ref 5]). In dark Agouti rats, MDEA 35 mg/kg produced hyperthermia comparable in peak/duration to MDMA 15 mg/kg, suggesting MDEA requires ~2× the dose for equivalent hyperthermic effect [Ref 6]. Gouzoulis-Mayfrank et al. (1996 [Ref 27]) document hyperpyrexia/hyperthermia as a potentially fatal complication in human users.

**Cardiovascular:** Significant tachycardia and systolic hypertension documented in controlled human study (Gouzoulis 1993 [Ref 16]). Arrhythmia risk in individuals with underlying cardiac disease documented (Dowling 1987 [Ref 17]).

**Rhabdomyolysis and DIC:** Documented as fatal complications in clinical case series, particularly when combined with hyperthermia (Gouzoulis-Mayfrank 1996 [Ref 27]).

**Serotonin syndrome:** Risk increases substantially when MDEA is combined with other serotonergic drugs, particularly MAO inhibitors (which prevent serotonin breakdown) and serotonin reuptake inhibitors.

**Hepatotoxicity:** Documented as a complication for the MDxx class generally. Skrinska & Gock (2005 [Ref 13]) list hepatotoxicity among adverse effects of the MDEA class. ⚠️ **Flag: Most hepatotoxicity case reports in the literature are MDMA-specific; MDEA-specific hepatotoxicity case reports were not identified. Inference from structural/pharmacological similarity.**

**Hyponatremia:** Documented for the MDxx class (particularly MDMA) from SIADH and excess water intake. ⚠️ **Flag: No MDEA-specific hyponatremia cases found. Inference from class.**

### Serotonergic Neurotoxicity (Animal Data Only)

In rats, MDEA causes long-term 5-HT nerve terminal degeneration, but at **lower potency than MDMA**:

- **Colado et al. (1999 [Ref 6]):** MDEA 35 mg/kg produced only ~20% loss of 5-HT and 5-HIAA in cortex and hippocampus; no decrease in striatum. Compare MDMA 15 mg/kg causing ~50% loss. MDEA has ~25% the potency of MDMA for inducing long-term serotonergic neurodegeneration. "These data do not support any contention that this compound is a 'safer' recreational drug than MDMA in terms of either acute toxicity or long term neurodegeneration" — as higher doses of MDEA are required for equivalent psychoactive effects.

- **O'Loinsigh et al. (2001 [Ref 5]):** After repeated dosing (8 × 20 mg/kg i.p., twice daily for 4 days), neurotoxic potency order was **MDMA > MDEA >> MDBA ≈ saline** for decreasing forebrain [³H]paroxetine binding (SERT marker) and 5-HT/5-HIAA levels at 14 days post-treatment. None of the analogs caused long-term dopamine or noradrenaline changes.

- **Series & Molliver (1994 [Ref 7]):** Multiple injections of MDE (40 mg/kg × 8) caused pronounced reduction in 5-HT immunoreactive axons in rat brain 2 weeks post-treatment (posterior cerebral cortex and hippocampus CA1 most affected), qualitatively similar to p-chloroamphetamine but quantitatively less severe. No dopaminergic terminal damage.

⚠️ **Flag: No human-specific neurotoxicity studies for MDEA exist. All neurotoxicity data are from animals. Translation to human doses is uncertain. MDEA users often ingest racemic drug in combination with other MDxx compounds, making MDEA-specific neurotoxic risk assessment in humans impossible from available data (Freudenmann & Spitzer 2004 [Ref 1]).**

### Exact Toxic Dose / LD50

No LD50 data for MDEA in any species were identified in published literature. Seed data note ("exact toxic dosage is unknown") is confirmed by this research. ⚠️ **Flag: LD50 unverified for any species.**

---

## Harm Reduction

**Contraindications identified in literature:**
- **Cardiac disease / arrhythmia history:** Documented fatality risk (Dowling 1987 [Ref 17])
- **MAO inhibitors (phenelzine, selegiline, tranylcypromine, moclobemide):** Severe serotonin syndrome risk — class-level contraindication for all serotonin-releasing agents
- **Tramadol:** Lethal interaction risk via combined serotonergic mechanism and seizure threshold lowering (Ripple et al. 2000 [Ref 28]; seed data severity: lethal)
- **Cocaine:** Lethal interaction risk via combined cardiovascular load and serotonergic effects (seed data severity: lethal)
- **MDMA:** Dangerous additive serotonergic load (seed data severity: dangerous)
- **Hot, crowded environments:** Exacerbates hyperthermia — primary contextual risk factor for MDxx class fatalities

**Testing/identification:**
MDEA and several structural regioisomers have identical molecular weights (207 g/mol) and similar mass spectral fragments (m/z 72 and 135/136), making identification of specific regioisomers dependent on chromatographic methods (Aalberg et al. 2003 [Ref 30]). Forensic laboratory confirmation requires GC/MS or HPLC with chiral columns. Standard immunoassay drug screens may detect MDEA as part of amphetamine/MDMA screen but cannot distinguish it from MDMA.

**Emergency response:**
Hyperthermia management (cooling), benzodiazepines for agitation, supportive cardiovascular care are the mainstay approaches for MDxx intoxication. Cyproheptadine may be used for serotonin syndrome (class-level guidance; no MDEA-specific protocols found).

---

## Tolerance & Dependence

**Seed data:** Physical: moderate; Psychological: moderate; Formation: moderately addictive with high abuse potential. Cross-tolerances listed: dopamine, serotonin/serotonergic, stimulant.

**Published evidence:** No MDEA-specific tolerance or dependence studies were identified in primary literature. Freudenmann & Spitzer (2004 [Ref 1]) and Hegadoren et al. (1999 [Ref 26]) discuss abuse potential of MDxx class but do not provide MDEA-specific quantitative data.

**Class-level inference:** Given shared mechanism with MDMA (triple monoamine releasing agent), tolerance and dependence potential likely comparable to MDMA class. Serotonergic tolerance via 5-HT depletion (post-dose "comedown") is well-established for MDMA and inferred for MDEA by pharmacological analogy. ⚠️ **Flag: Tolerance/dependence seed data rely on structural/class inference, not MDEA-specific studies.**

---

## Interactions

### Confirmed / Mechanism-Based

| Interaction | Severity (seed) | Mechanism | Evidence |
|---|---|---|---|
| Tramadol | Lethal | Additive serotonergic effects (MDEA: releasing agent + Tramadol: SRI/µ-opioid); serotonin syndrome and/or seizure threshold lowering | Ripple et al. 2000 [Ref 28]; class-level mechanism |
| Cocaine | Lethal | Combined cardiovascular load (both increase sympathetic tone) + additive serotonergic stimulation | Dowling 1987 [Ref 17]; class-level mechanism |
| MDMA | Dangerous | Additive serotonergic load; combined hyperthermia risk | Freudenmann & Spitzer 2004 [Ref 1]; Colado 1999 [Ref 6] |
| Alcohol | Unknown | Possible cardiovascular interaction; dehydration additive | No published data found for MDEA-alcohol combination |
| MAO inhibitors | Not listed in seed — **Flag for addition** | MAOI prevents serotonin breakdown; triple releasing agent + MAOI = potentially fatal serotonin syndrome | Class-level mechanism; well-established for MDMA |

⚠️ **Flag: The alcohol interaction is listed as "unknown" in seed data. This is appropriate — no published MDEA-specific data exists. However, general MDxx + alcohol risk literature documents potentiation of dehydration, cardiovascular strain, and impaired judgment. Editors should consider flagging this as "likely unsafe" by class inference.**

### CYP-Based Drug Interactions (Inhibition Risk)

MDEA is primarily metabolized by CYP3A4 and CYP2D6 (Meyer et al. 2009 [Ref 2]). CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion, ritonavir) may significantly increase MDEA plasma exposure by reducing N-deethylation and O-demethylenation, potentially intensifying and prolonging effects. ⚠️ **Flag: CYP2D6 inhibitor interaction risk is inferred from metabolism data; no clinical DDI studies for MDEA exist.**

---

## Legal Status

| Jurisdiction | Status | Notes |
|---|---|---|
| United States | **Schedule I** (DEA) | Effective ~October 1987. Covered by Federal Analog Act (1986) prior to explicit scheduling. No accepted medical use; high abuse potential. |
| United Kingdom | **Class A** (Misuse of Drugs Act 1971) | Covered as a substituted phenethylamine under the generic phenethylamine class provision |
| Germany | **Anlage I** (BtMG, Betäubungsmittelgesetz) | Non-tradable without specific government authorization; only permitted for scientific purposes |
| Australia | **Controlled substance** (Therapeutic Goods Act / Poisons Standard) | Listed as prohibited/Schedule 8 equivalent; confirmed via Australian ODC |
| Canada | **Schedule I** (Controlled Drugs and Substances Act, 1996) | Covered as structural analog/explicit listing; confirmation from CDSA Schedule I |
| European Union | Covered by national legislation in member states; all EU countries control the MDxx class | No EU-wide specific instrument separate from national laws |

⚠️ **Flag: UK and Canadian scheduling specifics (exact date of MDEA explicit listing vs. generic phenethylamine coverage) were confirmed only via web-retrieved sources (Ref 29), not via official government legislation APIs. Editors should confirm via UK legislation.gov.uk and Canadian CDSA Schedule I.**

---

## Clinical Trials

**ClinicalTrials.gov search result:** No registered clinical trials were found for MDEA, MDE, or 3,4-methylenedioxyethylamphetamine.

**Historical human studies (not registered as clinical trials — pre-registration era):**
- Gouzoulis et al. 1993 [Ref 16]: Double-blind, placebo-controlled, crossover, n=8 healthy males, 140 mg oral MDE-HCl. Neuroendocrine and cardiovascular endpoints.
- Brunnenberg et al. 1998 [Ref 9] and Brunnenberg & Kovar 2001 [Ref 10]: Human pharmacokinetic studies at 100–140 mg oral, n=6–14. Conducted at University of Tübingen.
- Buechler et al. 2003 [Ref 8]: Human enantiomeric PK at 70 mg oral per enantiomer.
These studies were conducted in the early 1990s–2000s under German research authorization (human challenge studies with scheduled compounds required BtMG research exemption).

---

## Community Feedback Analysis

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

---

## Gaps & Flags

### Critical Safety Flags

1. ⚠️ **LD50 unverified (any species):** No LD50 for MDEA found in any species in published literature. Seed data note "exact toxic dosage is unknown" is confirmed.

2. ⚠️ **DAT/SERT binding affinities not confirmed in primary literature via API:** The DAT partial releaser data (EC₅₀ ~622 nM, E_max 61%) appears in secondary pharmacological compilations but the specific primary source paper was not retrieved. Editors should verify against Freudenmann & Spitzer (2004 [Ref 1]) or specialist pharmacology tables.

3. ⚠️ **Interaction severity values not all primary-source verified:** "Tramadol: lethal" and "cocaine: lethal" are listed in seed data. The tramadol lethality is mechanistically well-supported by general serotonergic pharmacology (Ref 28) but no MDEA+tramadol-specific case report was found. The cocaine+MDEA lethality is supported by cardiovascular mechanism and case series (Ref 17) but no controlled study.

### Data Gaps

4. **No MDEA-specific controlled subjective effects studies** using validated psychometric instruments (OAV, ASC, POMS, etc.). All subjective data is extrapolated from human PK studies, historical self-reports (Shulgin/PiHKAL), and animal behavior data.

5. **No human neurotoxicity studies for MDEA.** All neurotoxicity data are rat data only (Refs 5, 6, 7). Human-relevant neurotoxic potential is unknown.

6. **No dependence/self-administration studies specific to MDEA.** Moderate dependence classification in seed data is by analogy to MDMA class.

7. **PubChem CID field is empty in brief** — should be populated with 105039.

8. **SMILES, InChIKey, molecular formula, and molecular weight fields are empty in brief** — all confirmed and should be populated.

9. **1980 synthesis publication** referenced in secondary literature as the first formal report of MDEA synthesis — primary paper not retrieved (no PMID/DOI found).

10. **Hepatotoxicity data is class-level inference** (MDxx/MDMA). No MDEA-specific hepatotoxicity case reports identified.

11. **Alcohol interaction listed as "unknown"** — no published data found; this is accurate but editors should note it may carry similar risks to alcohol+MDMA combination (dehydration, hyperthermia, cardiovascular strain).

12. **Brief labels MDEA as "emerging"** — this characterization is debatable since MDEA has been Schedule I since 1987 and has a 40-year published history. It may be "emerging" in the sense of renewed interest or recent forensic encounters, but it is historically well-established. Editors should review the "characterization" field.

### Structural Analog Inference Sections

The following content areas relied on structural/pharmacological analogy to MDMA and the MDxx class, not MDEA-specific data:
- Off-target receptor binding (5-HT₂A, α-adrenergic)
- Hepatotoxicity risk
- MDMA CYP2D6 inhibitor interaction risk
- Hyponatremia risk
- Dependence and tolerance magnitudes
- Emergency treatment protocols

---

*Research compiled by Psychedex research agent. 36 citations in registry. Turn 24/50.*