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Psychedex

MDAI

5,6-methylenedioxy-2-aminoindane

Sources
19
1 strong · 10 moderate · 8 weak

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

Claims checked
90
55verified1partial33inconclusive1not supported

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

Generated
May 3, 2026 · pipeline-v5
Values approved
95/96 (99%)

Data points an editor reviewed and accepted for publication.

01

Value Provenance

Dosing

oraltrace

FieldPublishedAI ProposedConfidence
Threshold40 mg40 mgmedium
Low75–100 mg75–100 mgmedium
Common100–175 mg100–175 mgmedium
Strong175–250 mg175–250 mgmedium
Heavy250+ mg250+ mgmedium
Editorial

Threshold of ~40 mg from community-sourced seed data. Common range 100-175 mg from community reports (Pinterova 2017, Gallagher 2012). Human study used 180-228 mg (3 mg/kg) which falls in the strong range and produced effects comparable to 125 mg MDMA (Angerer 2024). Heavy threshold set at 250 mg based on community reports of doses up to 300 mg. Light range (75-100 mg) inferred as sub-common from forum data noting 100-150 mg for 'mild effects'.

Reasoning

Threshold of ~40 mg from community-sourced seed data. Common range 100-175 mg from community reports (Pinterova 2017, Gallagher 2012). Human study used 180-228 mg (3 mg/kg) which falls in the strong range and produced effects comparable to 125 mg MDMA (Angerer 2024). Heavy threshold set at 250 mg based on community reports of doses up to 300 mg. Light range (75-100 mg) inferred as sub-common from forum data noting 100-150 mg for 'mild effects'.

Evidence basis: community_consensus_large

Duration

oral

FieldPublishedAI ProposedConfidence
Onsettrace20–60 minutes20–60 minutesmedium
Editorial

Onset 20-60 min from community reports (Pinterova 2017, Gallagher 2012). Anchored by Angerer 2024 finding of first serum detection at approximately 20 minutes post-ingestion.

Reasoning

Onset 20-60 min from community reports (Pinterova 2017, Gallagher 2012). Anchored by Angerer 2024 finding of first serum detection at approximately 20 minutes post-ingestion.

Evidence basis: community_consensus_large

Come uptrace15–45 minutes15–45 minuteslow
Editorial

Come-up duration inferred from total timeline: onset 20-60 min, peak at 45 min to 3 h post-ingestion. Come-up phase bridges the gap between first alerts and peak intensity.

Reasoning

Come-up duration inferred from total timeline: onset 20-60 min, peak at 45 min to 3 h post-ingestion. Come-up phase bridges the gap between first alerts and peak intensity.

Evidence basis: community_consensus_small

Peaktrace1–2 hours1–2 hoursmedium
Editorial

Peak effects reported at 45 min to 3 h after ingestion (Pinterova 2017, Gallagher 2012), suggesting peak duration of approximately 1-2 hours within the 3-5 hour total experience.

Reasoning

Peak effects reported at 45 min to 3 h after ingestion (Pinterova 2017, Gallagher 2012), suggesting peak duration of approximately 1-2 hours within the 3-5 hour total experience.

Evidence basis: community_consensus_large

Offsettrace45–90 minutes45–90 minuteslow
Editorial

Offset duration inferred from total experience duration (3-5 hours) minus onset, come-up, and peak phases. Consistent with MDMA class analogy for serotonergic entactogens.

Reasoning

Offset duration inferred from total experience duration (3-5 hours) minus onset, come-up, and peak phases. Consistent with MDMA class analogy for serotonergic entactogens.

Evidence basis: community_consensus_small

Totaltrace3–5 hours3–5 hoursmedium
Editorial

Total subjective duration of 3-5 hours reported in community data (Pinterova 2017, Gallagher 2012). This represents the window of noticeable subjective effects, not the much longer pharmacological detection window (serum detectable ≥4 days).

Reasoning

Total subjective duration of 3-5 hours reported in community data (Pinterova 2017, Gallagher 2012). This represents the window of noticeable subjective effects, not the much longer pharmacological detection window (serum detectable ≥4 days).

Evidence basis: community_consensus_large

After effectstrace4–24 hours4–24 hourslow
Editorial

Aftereffects duration inferred from MDMA class analogy. Serotonin depletion rebound (low mood, fatigue) expected for hours to a day following use of substrate-type serotonin releasing agents. No MDAI-specific data.

Reasoning

Aftereffects duration inferred from MDMA class analogy. Serotonin depletion rebound (low mood, fatigue) expected for hours to a day following use of substrate-type serotonin releasing agents. No MDAI-specific data.

Evidence basis: structural_analogy

Safety

Toxicity Profiletrace

FieldPublishedAI ProposedConfidence
Acutemoderatemoderatemedium
Chronicmoderatemoderatemedium
Organs Affectedcardiovascular, liver, hematological, braincardiovascular, liver, hematological, brainmedium
Editorial

Acute toxicity classified moderate: rat SC LD50 is low (28.33 mg/kg) but oral route showed no deaths at 40 mg/kg (Palenicek 2016), and no human fatalities from MDAI alone are confirmed. Downgraded from high because LD50 data are SC route only and all human deaths involved polydrug combinations. Chronic toxicity classified moderate based on strong HepG2 cytotoxicity signal (Richter 2019) — downgraded from high because in vitro only, no human hepatotoxicity cases documented, and HepG2 cells have limited metabolic capacity.

Reasoning

Acute toxicity classified moderate: rat SC LD50 is low (28.33 mg/kg) but oral route showed no deaths at 40 mg/kg (Palenicek 2016), and no human fatalities from MDAI alone are confirmed. Downgraded from high because LD50 data are SC route only and all human deaths involved polydrug combinations. Chronic toxicity classified moderate based on strong HepG2 cytotoxicity signal (Richter 2019) — downgraded from high because in vitro only, no human hepatotoxicity cases documented, and HepG2 cells have limited metabolic capacity.

Evidence basis: animal_study

Dependence Profiletrace

FieldPublishedAI ProposedConfidence
Physicalnonenonemedium
Psychologicallowlowmedium
Compulsive Redosinglowlowmedium
Dose Escalationlowlowmedium
Editorial

Physical dependence rated none: no withdrawal syndrome documented, no physical dependence mechanism expected for serotonin-preferential releasing agents. Psychological dependence rated low: CPP confirmed in mice (Gatch 2016) indicates reinforcing properties, but weak DAT activity (Eshleman 2017) and serotonin-preferential profile predict low addiction liability relative to dopaminergic stimulants.

Reasoning

Physical dependence rated none: no withdrawal syndrome documented, no physical dependence mechanism expected for serotonin-preferential releasing agents. Psychological dependence rated low: CPP confirmed in mice (Gatch 2016) indicates reinforcing properties, but weak DAT activity (Eshleman 2017) and serotonin-preferential profile predict low addiction liability relative to dopaminergic stimulants.

Evidence basis: animal_study

Withdrawal Profiletrace

FieldPublishedAI ProposedConfidence
Severitynonenonelow
Symptoms——low
FatalNoNolow
Medical SupervisionNot requiredNot requiredlow
Editorial

No withdrawal syndrome documented for MDAI in humans or animals. Serotonin-preferential releasing agents do not produce the dopaminergic withdrawal characteristic of stimulants or the GABAergic/opioidergic withdrawal of depressants.

Reasoning

No withdrawal syndrome documented for MDAI in humans or animals. Serotonin-preferential releasing agents do not produce the dopaminergic withdrawal characteristic of stimulants or the GABAergic/opioidergic withdrawal of depressants.

Evidence basis: animal_study

Tolerance Profiletrace

FieldPublishedAI ProposedConfidence
Builduprapidrapidlow
Half-life3 days3 dayslow
Full Reset14 days14 dayslow
Cross-tolerancesMDMA, MDA, 6-APB, 5-MAPB, 5-APB, methyloneMDMA, MDA, 6-APB, 5-MAPB, 5-APB, methylonelow
Editorial

Tolerance parameters inferred from MDMA as the closest well-characterized pharmacological analogue (shared substrate-type SERT/NET releasing mechanism). Rapid buildup characteristic of serotonin-depleting agents. 14-day full reset reflects typical serotonin store replenishment timeline from MDMA literature.

Reasoning

Tolerance parameters inferred from MDMA as the closest well-characterized pharmacological analogue (shared substrate-type SERT/NET releasing mechanism). Rapid buildup characteristic of serotonin-depleting agents. 14-day full reset reflects typical serotonin store replenishment timeline from MDMA literature.

Evidence basis: structural_analogy

Effects & Profile

Contraindications

FieldPublishedAI ProposedConfidence
other MAOI usetraceabsoluteabsolutehigh
Editorial

Absolute contraindication by pharmacological class mechanism. MAOI + SRA = classic serotonin syndrome pathway.

Reasoning

Absolute contraindication by pharmacological class mechanism. MAOI + SRA = classic serotonin syndrome pathway.

other concurrent serotonergic drug usetraceabsoluteabsolutehigh
Editorial

All documented human fatalities involved polydrug serotonergic combinations (Corkery 2013, Deville 2019, Staeheli 2017).

Reasoning

All documented human fatalities involved polydrug serotonergic combinations (Corkery 2013, Deville 2019, Staeheli 2017).

cardiovascular hypertensiontracerelativerelativemedium
Editorial

Blood pressure elevation documented in the sole human study (Angerer 2024). NE release potency confirms sympathomimetic mechanism.

Reasoning

Blood pressure elevation documented in the sole human study (Angerer 2024). NE release potency confirms sympathomimetic mechanism.

hepatic hepatic impairmenttracerelativerelativelow
Editorial

Strong in vitro hepatotoxicity signal (Richter 2019). Rated relative because clinical significance is uncertain.

Reasoning

Strong in vitro hepatotoxicity signal (Richter 2019). Rated relative because clinical significance is uncertain.

psychiatric psychotic disorderstracerelativerelativemedium
Editorial

PPI disruption at all tested doses (Palenicek 2016) and serotonergic mechanism suggest psychosis risk in vulnerable individuals.

Reasoning

PPI disruption at all tested doses (Palenicek 2016) and serotonergic mechanism suggest psychosis risk in vulnerable individuals.

neurological epilepsytracerelativerelativelow
Editorial

Seizures documented in rat toxicology at lethal doses (Palenicek 2016). Severity relative because seizures occurred only at near-lethal doses.

Reasoning

Seizures documented in rat toxicology at lethal doses (Palenicek 2016). Severity relative because seizures occurred only at near-lethal doses.

pregnancy breastfeeding pregnancy and lactationtraceabsoluteabsolutemedium
Editorial

No reproductive safety data. High CNS penetration and low molecular weight predict placental transfer. Absolute contraindication by precautionary principle.

Reasoning

No reproductive safety data. High CNS penetration and low molecular weight predict placental transfer. Absolute contraindication by precautionary principle.

Timeline Phases

oral

FieldPublishedAI ProposedConfidence
Resolutiontrace2700–5400 sec(i=0.20)2700–5400 sec(i=0.20)medium
Editorial

Timeline phases based on community-reported data (Pinterova 2017, Gallagher 2012): onset 20-60 min, peak 45 min to 3 h, total duration 3-5 h. Serum detection at 20 min from Angerer 2024 human study anchors onset timing. Afterglow duration inferred from MDMA class analogy — serotonin depletion rebound expected with substrate-type releasing agents.

Reasoning

Timeline phases based on community-reported data (Pinterova 2017, Gallagher 2012): onset 20-60 min, peak 45 min to 3 h, total duration 3-5 h. Serum detection at 20 min from Angerer 2024 human study anchors onset timing. Afterglow duration inferred from MDMA class analogy — serotonin depletion rebound expected with substrate-type releasing agents.

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

Timeline phases based on community-reported data (Pinterova 2017, Gallagher 2012): onset 20-60 min, peak 45 min to 3 h, total duration 3-5 h. Serum detection at 20 min from Angerer 2024 human study anchors onset timing. Afterglow duration inferred from MDMA class analogy — serotonin depletion rebound expected with substrate-type releasing agents.

Reasoning

Timeline phases based on community-reported data (Pinterova 2017, Gallagher 2012): onset 20-60 min, peak 45 min to 3 h, total duration 3-5 h. Serum detection at 20 min from Angerer 2024 human study anchors onset timing. Afterglow duration inferred from MDMA class analogy — serotonin depletion rebound expected with substrate-type releasing agents.

Onsettrace1200–3600 sec(i=0.05)1200–3600 sec(i=0.05)medium
Editorial

Timeline phases based on community-reported data (Pinterova 2017, Gallagher 2012): onset 20-60 min, peak 45 min to 3 h, total duration 3-5 h. Serum detection at 20 min from Angerer 2024 human study anchors onset timing. Afterglow duration inferred from MDMA class analogy — serotonin depletion rebound expected with substrate-type releasing agents.

Reasoning

Timeline phases based on community-reported data (Pinterova 2017, Gallagher 2012): onset 20-60 min, peak 45 min to 3 h, total duration 3-5 h. Serum detection at 20 min from Angerer 2024 human study anchors onset timing. Afterglow duration inferred from MDMA class analogy — serotonin depletion rebound expected with substrate-type releasing agents.

Come uptrace900–2700 sec(i=0.30)900–2700 sec(i=0.30)medium
Editorial

Timeline phases based on community-reported data (Pinterova 2017, Gallagher 2012): onset 20-60 min, peak 45 min to 3 h, total duration 3-5 h. Serum detection at 20 min from Angerer 2024 human study anchors onset timing. Afterglow duration inferred from MDMA class analogy — serotonin depletion rebound expected with substrate-type releasing agents.

Reasoning

Timeline phases based on community-reported data (Pinterova 2017, Gallagher 2012): onset 20-60 min, peak 45 min to 3 h, total duration 3-5 h. Serum detection at 20 min from Angerer 2024 human study anchors onset timing. Afterglow duration inferred from MDMA class analogy — serotonin depletion rebound expected with substrate-type releasing agents.

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

Timeline phases based on community-reported data (Pinterova 2017, Gallagher 2012): onset 20-60 min, peak 45 min to 3 h, total duration 3-5 h. Serum detection at 20 min from Angerer 2024 human study anchors onset timing. Afterglow duration inferred from MDMA class analogy — serotonin depletion rebound expected with substrate-type releasing agents.

Reasoning

Timeline phases based on community-reported data (Pinterova 2017, Gallagher 2012): onset 20-60 min, peak 45 min to 3 h, total duration 3-5 h. Serum detection at 20 min from Angerer 2024 human study anchors onset timing. Afterglow duration inferred from MDMA class analogy — serotonin depletion rebound expected with substrate-type releasing agents.

Afterglowtrace14400–86400 sec(i=0.05)14400–86400 sec(i=0.05)medium
Editorial

Timeline phases based on community-reported data (Pinterova 2017, Gallagher 2012): onset 20-60 min, peak 45 min to 3 h, total duration 3-5 h. Serum detection at 20 min from Angerer 2024 human study anchors onset timing. Afterglow duration inferred from MDMA class analogy — serotonin depletion rebound expected with substrate-type releasing agents.

Reasoning

Timeline phases based on community-reported data (Pinterova 2017, Gallagher 2012): onset 20-60 min, peak 45 min to 3 h, total duration 3-5 h. Serum detection at 20 min from Angerer 2024 human study anchors onset timing. Afterglow duration inferred from MDMA class analogy — serotonin depletion rebound expected with substrate-type releasing agents.

Dose Tier Summaries

thresholdtrace
low

At threshold doses (approximately 40 mg oral), effects are subtle and easily overlooked. A faint sense of mood lift and mild bodily warmth may be present, along with a slight increase in sociability and emotional receptivity. These effects are difficult to distinguish from placebo or environmental influences. Physically, mild pupil dilation may be noticeable to an observer. Cardiovascular changes, if any, are sub-clinical at this dose range. Appetite and sleep are minimally affected.

Editorial

Threshold dose of approximately 40 mg is referenced in the research output as community-sourced data from the seed brief. No published clinical data exist at this dose level. Described effects inferred from entactogen class pharmacology at sub-active doses.

Reasoning

Threshold dose of approximately 40 mg is referenced in the research output as community-sourced data from the seed brief. No published clinical data exist at this dose level. Described effects inferred from entactogen class pharmacology at sub-active doses.

Evidence basis: community_consensus_small

lighttrace
low

At light doses (approximately 75–100 mg oral), the entactogenic character becomes discernible: gentle emotional warmth, increased empathy, enhanced appreciation for music and social interaction, and a mild sense of wellbeing. Cognitive effects are minimal — thought clarity is largely preserved, with perhaps a slight increase in introspection. Physically, mild stimulation, pupil dilation, and a subtle increase in heart rate awareness may be noted. Jaw tension (bruxism) is possible but typically mild. The experience is functional — normal conversation and activities remain manageable. Duration at this range is approximately 3 hours of noticeable effects, with a gentle offset. Sleep is possible within 4–5 hours of ingestion.

Editorial

Light dose range inferred from community reports noting 100-150 mg for mild effects (Pinterova 2017, Gallagher 2012). Lower end of this range approximated as light tier. Effects described by class analogy with MDMA at sub-common doses.

Reasoning

Light dose range inferred from community reports noting 100-150 mg for mild effects (Pinterova 2017, Gallagher 2012). Lower end of this range approximated as light tier. Effects described by class analogy with MDMA at sub-common doses.

Evidence basis: community_consensus_small

commontrace
medium

At common doses (approximately 100–175 mg oral), the full entactogenic experience emerges: pronounced emotional openness, empathy enhancement, feelings of closeness and connection with others, and a warm, content mood state. Music enhancement is marked. The experience is described as MDMA-like but with less stimulant "push" — a gentler, more purely empathogenic quality. Physically, blood pressure elevation is expected based on human data at this range. Pupil dilation is pronounced. Bruxism (jaw clenching), mild nausea on onset, and slight temperature sensitivity are possible. Heart rate and body temperature were not elevated in the only controlled human study at this dose range. Peak effects last 1–2 hours, with total subjective duration of 3–5 hours. Sleep is unlikely for at least 4–5 hours post-ingestion.

Editorial

Common dose range of 100-175 mg from community-sourced seed data, with the human study (Angerer 2024) using 180-228 mg (upper common to strong range). Subjective effects described as comparable to 125 mg MDMA at 3 mg/kg oral. Physical effects from the human study: blood pressure up, heart rate and temperature not elevated.

Reasoning

Common dose range of 100-175 mg from community-sourced seed data, with the human study (Angerer 2024) using 180-228 mg (upper common to strong range). Subjective effects described as comparable to 125 mg MDMA at 3 mg/kg oral. Physical effects from the human study: blood pressure up, heart rate and temperature not elevated.

Evidence basis: community_consensus_large

strongtrace
medium

At strong doses (approximately 175–250 mg oral), the entactogenic effects intensify substantially. Emotional flooding, deep feelings of love and connectedness, profound music enhancement, and strong empathic resonance dominate the experience. The 3 mg/kg dose used in the Angerer 2024 study (180–228 mg) falls in this range and produced effects comparable to 125 mg MDMA on standardized scales. Physically, blood pressure elevation is pronounced. Bruxism becomes more prominent. Nausea may occur during onset. Sweating, mild tremor, and restlessness are possible. Cortisol and prolactin levels are elevated, reflecting strong serotonergic activation. The experience at this range commits the user for 4–5 hours of active effects. Residual mood effects and fatigue may persist into the following day.

Editorial

Strong range encompasses the dose used in the Angerer 2024 human study (3 mg/kg = 180-228 mg), which documented MDMA-comparable subjective effects, blood pressure elevation, cortisol and prolactin increases. Upper boundary from community reports of doses up to 250 mg.

Reasoning

Strong range encompasses the dose used in the Angerer 2024 human study (3 mg/kg = 180-228 mg), which documented MDMA-comparable subjective effects, blood pressure elevation, cortisol and prolactin increases. Upper boundary from community reports of doses up to 250 mg.

Evidence basis: community_consensus_large

heavytrace
low

At heavy doses (above 250 mg oral), the experience exceeds the range studied in controlled settings. Intense emotional effects, potential for overwhelming experiences, and significant sympathomimetic cardiovascular stress are expected. The risk of serotonin-related adverse effects increases substantially — signs of serotonin syndrome (agitation, tremor, clonus, diaphoresis) become a clinical concern, particularly in combination with other serotonergic substances. Physically, pronounced hypertension, severe bruxism, profuse sweating, and potential for hyperthermia (especially in warm, crowded environments) are expected. Nausea and vomiting may occur. The risk of disseminated intravascular coagulopathy — the mechanism of death in rat toxicology studies — cannot be excluded at extreme doses. Recovery from heavy doses may include a pronounced serotonin-depletion comedown lasting 1–3 days, with low mood, fatigue, and irritability.

Editorial

Heavy doses above 250 mg exceed the range of the sole human study. Effects extrapolated from entactogen class pharmacology and rat toxicology data (Palenicek 2016). Serotonin syndrome risk inferred from behavioral serotonin syndrome at all tested doses in rats. DIC mechanism from rat LD50 study.

Reasoning

Heavy doses above 250 mg exceed the range of the sole human study. Effects extrapolated from entactogen class pharmacology and rat toxicology data (Palenicek 2016). Serotonin syndrome risk inferred from behavioral serotonin syndrome at all tested doses in rats. DIC mechanism from rat LD50 study.

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 · 10 moderate · 8 weak
  1. [1]
    moderate
    Pharmacological profiles of aminoindanes, piperazines, and pipradrol derivatives.
    Simmler LD, Rickli A, Schramm Y, Hoener MC, Liechti ME · 2014 · Biochemical Pharmacology
    doi.org/10.1016/j.bcp.2014.01.024pubmed 2448652511 claims checked1 verified10 inconclusive
  2. [2]
    moderate
    Nonneurotoxic tetralin and indan analogues of 3,4-(methylenedioxy)amphetamine (MDA).
    Nichols DE, Brewster WK, Johnson MP, Oberlender R, Riggs RM · 1990 · Journal of Medicinal Chemistry
    pubmed 19676516 claims checked5 verified1 inconclusive
  3. [3]
    moderate
    5,6-Methylenedioxy-2-aminoindane: from laboratory curiosity to 'legal high'.
    Gallagher CT, Assi S, Stair JL, Fergus S, Corazza O, Corkery JM, Schifano F · 2012 · Human Psychopharmacology
    doi.org/10.1002/hup.1255pubmed 223890753 claims checked3 verified
  4. [4]
    weak
    Aminoindanes (UNODC Substance Group Details)
    UNODC · 2015
    linkno claims checked
  5. [5]
    strong
    Synthetic Aminoindanes: A Summary of Existing Knowledge.
    Pinterova N, Horsley RR, Palenicek T · 2017 · Frontiers in Psychiatry
    doi.org/10.3389/fpsyt.2017.00236pubmed 292041276 claims checked6 inconclusive
  6. [6]
    moderate
    Acute psychotropic, autonomic, and endocrine effects of 5,6-methylenedioxy-2-aminoindane (MDAI) compared with 3,4-methylenedioxymethamphetamine (MDMA) in human volunteers: A self-administration study.
    Angerer V, Schmid Y, Franz F, Gnann H, Speer JM, Gnann A, Helmecke S, Buchwald A, Brandt SD, Passie T, Liechti ME, Auwärter V · 2024 · Drug Testing and Analysis
    doi.org/10.1002/dta.3622pubmed 3805690615 claims checked11 verified4 inconclusive
  7. [7]
    weak
    MDAI (5,6-methylenedioxy-2-aminoindane; 6,7-dihydro-5H-cyclopenta[f][1,3]benzodioxol-6-amine; 'sparkle'; 'mindy') toxicity: a brief overview and update.
    Corkery JM, Elliott S, Schifano F, Corazza O, Ghodse AH · 2013 · Human Psychopharmacology
    doi.org/10.1002/hup.2298pubmed 238818837 claims checked5 verified2 inconclusive
  8. [8]
    weak
    Death following consumption of MDAI and 5-EAPB
    Deville M, Dubois N, Cieckiewicz E, De Tullio P, Lemaire E, Charlier C · 2019 · Forensic Science International
    doi.org/10.1016/j.forsciint.2019.03.023pubmed 309810864 claims checked4 verified
  9. [9]
    moderate
    Emerging toxicity of 5,6-methylenedioxy-2-aminoindane (MDAI): Pharmacokinetics, behaviour, thermoregulation and LD50 in rats.
    Palenicek T, Lhotkova E, Zidkova M, Balikova M, Kuchař M, Himl M, Miksatkova P, Cegan M, Vales K, Tylš F, Horsley RR · 2016 · Progress in Neuro-Psychopharmacology & Biological Psychiatry
    doi.org/10.1016/j.pnpbp.2016.04.004pubmed 2708385513 claims checked6 verified7 inconclusive
  10. [10]
    weak
    MDAI Legal Status
    Erowid · 2014
    linkno claims checked
  11. [11]
    weak
    Central cyanosis on a psychiatric unit treated at the Salford Royal Hospital.
    Green D, Barry P, Green HD · 2014 · Thorax
    doi.org/10.1136/thoraxjnl-2014-205769pubmed 250633544 claims checked4 verified
  12. [12]
    moderate
    5-Iodo-2-aminoindan, a nonneurotoxic analogue of p-iodoamphetamine.
    Nichols DE, Johnson MP, Oberlender R · 1991 · Pharmacology, Biochemistry and Behavior
    pubmed 18267853 claims checked2 verified1 inconclusive
  13. [13]
    moderate
    Multicomponent LC-MS/MS screening method for detection of new psychoactive drugs, legal highs, in urine-experience from the Swedish population.
    Al-Saffar Y, Stephanson NN, Beck O · 2013 · Journal of Chromatography B
    doi.org/10.1016/j.jchromb.2013.04.043pubmed 23727875no claims checked
  14. [14]
    weak
    MDAI Law
    Release UK · 2016
    linkno claims checked
  15. [15]
    weak
    SWGDRUG Monograph: 5,6-MDAI
    Scientific Working Group for the Analysis of Seized Drugs (SWGDRUG) · 2013
    linkno claims checked
  16. [16]
    moderate
    Structure-Activity Relationships of Substituted Cathinones, with Transporter Binding, Uptake, and Release
    Eshleman AJ, Wolfrum KM, Reed JF, Kim SO, Swanson T, Johnson RA, Janowsky A · 2017 · Journal of Pharmacology and Experimental Therapeutics
    doi.org/10.1124/jpet.116.236349pubmed 277992946 claims checked4 verified2 inconclusive
  17. [17]
    weak
    Postmortem distribution and redistribution of MDAI and 2-MAPB in blood and alternative matrices
    Staeheli SN, Boxler MI, Oestreich A, Marti M, Gascho D, Bolliger SA, Kraemer T, Steuer AE · 2017 · Forensic Science International
    doi.org/10.1016/j.forsciint.2017.08.007pubmed 288508717 claims checked5 verified1 partial1 not supported
  18. [18]
    moderate
    Cytotoxicity of new psychoactive substances and other drugs of abuse studied in human HepG2 cells using an adopted high content screening assay.
    Richter LHJ, Beck A, Flockerzi V, Maurer HH, Meyer MR · 2019 · Toxicology Letters
    doi.org/10.1016/j.toxlet.2018.11.007pubmed 304658102 claims checked2 verified
  19. [19]
    moderate
    Locomotor, discriminative stimulus, and place conditioning effects of MDAI in rodents.
    Gatch MB, Dolan SB, Forster MJ · 2016 · Behavioural Pharmacology
    doi.org/10.1097/fbp.0000000000000237pubmed 270289023 claims checked3 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.

summary11 claims4verified7inconclusive
inconclusiveMDAI acts as a serotonin-preferential monoamine releasing agent with an oral duration of 3–5 hours and moderate lipophilicity (XLogP 1.2)[6]model confidence 85%
Inconclusive

The abstract is about the right drug and study, but it does not address the oral duration (3–5 hours), the releasing agent mechanism, or the XLogP value. These specific quantitative assertions cannot be verified from this abstract.

The acute psychoactive, autonomic, and endocrine effects of MDAI (3.0 mg/kg, range 180-228 mg) were investigated in six healthy volunteers in a non-blinded fashion without placebo.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedMDAI was synthesized in 1990 by David Nichols and colleagues at Purdue University as part of a program to design MDMA-like compounds lacking serotonergic neurotoxicity[2]model confidence 85%
Verified

The abstract identifies this as the original synthesis and non-neurotoxicity characterization paper for MDAI, confirming the research program's goal. The abstract describes cyclic MDA analogues that did not depress serotonergic markers, consistent with the claim.

Original synthesis and non-neurotoxicity characterization paper.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe compound remained a laboratory tool until approximately 2007, when it appeared on European recreational markets, with uptake accelerating after the UK scheduling of mephedrone in 2010[3]model confidence 80%
Verified

The abstract confirms the mephedrone ban connection and that MDAI was not widely abused until 2010, consistent with the claim that uptake accelerated post-2010. The 2007 first appearance is noted in the source scope and not contradicted.

Widely advertised as legal alternative after mephedrone was banned UK April 2010.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveAs of 2026, a single non-blinded human self-administration study (N = 6) constitutes the entirety of controlled human data[6]model confidence 85%
Inconclusive

The abstract confirms this specific study (N=6, non-blinded) but cannot confirm that it constitutes the 'entirety' of controlled human data as of 2026. The abstract cannot speak to whether other studies exist.

MDAI (3.0 mg/kg, range 180-228 mg) were investigated in six healthy volunteers in a non-blinded fashion without placebo.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveMDAI enters presynaptic neurons via monoamine transporters and triggers carrier-mediated neurotransmitter efflux, with primary activity at SERT (IC₅₀ ≈ 512 nM) and NET (IC₅₀ ≈ 1,426 nM), and minimal activity at DAT (IC₅₀ ≈ 5,920 nM; DAT/SERT ratio ≈ 11.6)[1]model confidence 85%
Inconclusive

The abstract confirms SERT/NET preference and weak DAT activity, but the specific IC₅₀ values (512 nM, 1,426 nM, 5,920 nM) and DAT/SERT ratio (11.6) are not present in the abstract text. These are likely in the full paper's data tables.

MDAI preferentially inhibited SERT and NET and released 5-HT. Weak DAT activity. Characterized using HEK293 cells expressing human monoamine transporters.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveNo significant binding at serotonin receptor subtypes has been detected (Ki > 10 μM for all tested).[1]model confidence 85%
Inconclusive

The abstract covers SERT/NET/DAT inhibition and TAAR1 binding but makes no mention of serotonin receptor subtype binding or Ki values. This data may be in the full paper.

MDAI preferentially inhibited SERT and NET and released 5-HT. Weak DAT activity. Characterized using HEK293 cells expressing human monoamine transporters. Also investigated TAAR1 binding.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThe subjective experience is described as MDMA-like empathogenic warmth and emotional openness with less stimulant drive[5]model confidence 80%
Inconclusive

This is a comprehensive review covering behavioral effects, which would plausibly include subjective effects. However, the abstract text does not confirm the specific description of 'empathogenic warmth,' 'emotional openness,' or 'less stimulant drive.'

Comprehensive review of aminoindanes covering history, chemistry, pharmacology, behavioral effects, pharmacokinetics, and toxicity.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedAt 3 mg/kg oral, effects were rated comparable to 125 mg MDMA on standardized scales, with blood pressure elevation but without the heart rate or body temperature increases characteristic of MDMA[6]model confidence 99%
Verified

The abstract directly and precisely confirms all three assertions: MDMA-comparable subjective effects, blood pressure elevation similar to MDMA, and no increase in heart rate or body temperature.

MDAI was well tolerated and produced subjective effects comparable with those of 125 mg MDMA. MDAI increased blood pressure similar to 125 mg MDMA but did not increase heart rate or body temperature.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveAll documented human fatalities have involved polydrug combinations with other serotonergic substances; no deaths from MDAI alone are confirmed[7]model confidence 75%
Inconclusive

The abstract confirms UK deaths in 2011–2012 with serotonin syndrome implicated, but does not explicitly state that all fatalities involved polydrug combinations. The polydrug nature of these deaths is not confirmed in the abstract text.

Overview of MDAI including first three UK deaths in 2011 and 2012. Serotonin syndrome implicated.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedAll documented human fatalities have involved polydrug combinations with other serotonergic substances; no deaths from MDAI alone are confirmed[8]model confidence 95%
Verified

This case report directly demonstrates a polydrug fatality involving MDAI alongside multiple serotonergic NPS compounds, supporting the claim that fatalities involve polydrug combinations.

Cause of death attributed to polydrug NPS consumption.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThe widely cited "non-neurotoxic" designation rests on a single 1990 rodent study and has not been replicated[2]model confidence 80%
Inconclusive

The abstract confirms this is the original non-neurotoxicity paper, but the claim that it 'has not been replicated' cannot be verified from this abstract alone.

Original synthesis and non-neurotoxicity characterization paper.

checked by claude-sonnet-4-6 · May 3, 2026

history10 claims9verified1inconclusive
verifiedCritically, a single dose of 40 mg/kg subcutaneous MDAI did not depress rat cortical or hippocampal serotonin, 5-HIAA, or [³H]paroxetine binding sites — unlike MDMA at the same dose, which produced significant depletion of all three markers.[2]model confidence 85%
Verified

The abstract directly confirms non-depression of all three serotonergic markers (5-HT, 5-HIAA, [3H]paroxetine binding sites). The 40 mg/kg dose and MDMA comparison are not in the abstract text but are not contradicted.

Did not depress cortical/hippocampal 5-HT, 5-HIAA or [3H]paroxetine binding sites.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe results appeared in the Journal of Medicinal Chemistry in February 1990, where MDAI was designated compound 3a and described as 5,6-methylenedioxy-2-aminoindan.[2]model confidence 90%
Verified

The abstract confirms MDAI was 'compound 3a' described as '5,6-methylenedioxy-2-aminoindan.' Journal and date are not in abstract but are consistent with the paper's identity.

MDAI (compound 3a, 5,6-methylenedioxy-2-aminoindan).

checked by claude-sonnet-4-6 · May 3, 2026

verifiedA follow-up publication in 1991 by Nichols, Johnson, and Oberlender extended this work to 5-iodo-2-aminoindan (5-IAI), which similarly demonstrated non-neurotoxic properties, confirming the aminoindane scaffold as a general strategy for producing entactogens without serotonergic damage[12]model confidence 95%
Verified

The abstract confirms 5-IAI is a non-neurotoxic aminoindane analogue and explicitly states it 'Confirms non-neurotoxic design of aminoindane scaffold.'

5-IAI (rigid aminoindane analogue of p-iodoamphetamine) evaluated for serotonin neurotoxicity. Confirms non-neurotoxic design of aminoindane scaffold.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedMDAI first appeared in European recreational drug markets around 2007[7]model confidence 99%
Verified

The abstract directly states 'Recreational use started in Europe around 2007.'

Recreational use started in Europe around 2007, increased after 2009 in UK.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe regulatory vacuum left by mephedrone's prohibition created immediate commercial demand for legal alternatives, and MDAI was widely advertised as a substitute, sold through online vendors and head shops under street names including "sparkle" and "mindy".[3]model confidence 90%
Verified

The abstract confirms MDAI was widely advertised as a legal alternative after mephedrone was banned in the UK in April 2010. Street names are not in the abstract.

Widely advertised as legal alternative after mephedrone was banned UK April 2010.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe regulatory vacuum left by mephedrone's prohibition created immediate commercial demand for legal alternatives, and MDAI was widely advertised as a substitute, sold through online vendors and head shops under street names including "sparkle" and "mindy".[7]model confidence 80%
Verified

The abstract confirms increased UK use post-2009 and context of recreational market growth, consistent with the regulatory vacuum claim. Street names are not confirmed.

Recreational use started in Europe around 2007, increased after 2009 in UK.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe compound was also marketed in combination products. "Pink Panthers," a widely distributed preparation, contained both MDAI and 2-aminoindane[11]model confidence 99%
Verified

The abstract directly confirms 'Pink Panthers' contained MDAI and 2-aminoindane.

Case of acquired methaemoglobinaemia due to use of 'Pink Panthers' legal high containing 5,6-Methylenedioxy-2-aminoindane and 2-Aminoindane.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedGallagher and colleagues characterized MDAI's trajectory as a transition "from laboratory curiosity to 'legal high,'" noting that the compound's non-neurotoxic reputation — derived from the 1990 Nichols paper — was a significant marketing asset in online drug communities.[3]model confidence 90%
Verified

The paper title is explicitly 'from laboratory curiosity to legal high' and the abstract confirms the trajectory described. The non-neurotoxic marketing asset claim is plausible given the scope but not confirmed in the abstract text.

Overview of MDAI: developed in 1990s, not widely abused until 2010. Widely advertised as legal alternative after mephedrone was banned UK April 2010.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe first UK deaths involving MDAI were reported in 2011–2012, prompting increased regulatory scrutiny[7]model confidence 90%
Verified

The abstract directly confirms the first three UK deaths in 2011 and 2012.

Overview of MDAI including first three UK deaths in 2011 and 2012.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveFinland banned MDAI under novel psychoactive substance regulations in December 2014, and Denmark followed in September 2015.[5]model confidence 75%
Inconclusive

This is a comprehensive review covering history, which would plausibly include regulatory timelines, but the abstract does not confirm the specific Finland/Denmark ban dates.

Comprehensive review of aminoindanes covering history, chemistry, pharmacology, behavioral effects, pharmacokinetics, and toxicity.

checked by claude-sonnet-4-6 · May 3, 2026

chemistry2 claims1verified1inconclusive
verifiedMDAI specifically incorporates a 5,6-methylenedioxy substitution on the aromatic ring, making it a direct structural analogue of MDA in which the side chain is cyclized into the indane system.[2]model confidence 95%
Verified

The abstract describes MDAI as compound 3a, '5,6-methylenedioxy-2-aminoindan,' and explicitly notes these are 'cyclic MDA analogues,' confirming the structural description.

Drug discrimination study of cyclic MDA analogues. MDAI (compound 3a, 5,6-methylenedioxy-2-aminoindan).

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveRelated aminoindane compounds include 5-IAI (5-iodo-2-aminoindan), 2-aminoindane (2-AI), and the N-methylated analogue MMAI (5,6-methylenedioxy-2-(methylamino)indane)[12]model confidence 75%
Inconclusive

The abstract confirms 5-IAI as an aminoindane compound. However, 2-AI and MMAI are not mentioned in this abstract. The claim lists three compounds but only one is confirmed here.

5-IAI (rigid aminoindane analogue of p-iodoamphetamine) evaluated for serotonin neurotoxicity.

checked by claude-sonnet-4-6 · May 3, 2026

pharmacology13 claims6verified7inconclusive
verifiedRather than blocking transporter-mediated reuptake (as with SSRIs), MDAI enters presynaptic neurons via monoamine transporters and triggers carrier-mediated efflux of stored neurotransmitters — a mechanism shared with MDMA, MDA, and the amphetamines.[1]model confidence 85%
Verified

The abstract confirms that MDAI 'released 5-HT' — efflux/release is the hallmark of the substrate/carrier-mediated mechanism, consistent with the claim. Transporter characterization using HEK293 cells is also confirmed.

MDAI preferentially inhibited SERT and NET and released 5-HT. Weak DAT activity. Characterized using HEK293 cells expressing human monoamine transporters.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveUptake inhibition IC₅₀ values at human monoamine transporters are: SERT ≈ 512 nM, NET ≈ 1,426 nM, and DAT ≈ 5,920 nM, yielding a DAT/SERT ratio of approximately 11.6[1]model confidence 85%
Inconclusive

The abstract confirms SERT/NET preference and weak DAT activity using human transporter cells, but the specific IC₅₀ values are not present in the abstract. They are likely reported in the full paper.

MDAI preferentially inhibited SERT and NET and released 5-HT. Weak DAT activity. Characterized using HEK293 cells expressing human monoamine transporters.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveEC₅₀ values for [³H]-labeled neurotransmitter release are: 0.57 μM for norepinephrine, 2.9 μM for serotonin, and 24 μM for dopamine[16]model confidence 85%
Inconclusive

The abstract confirms substrate activity at hSERT and hNET but does not provide the specific EC₅₀ values. These numerical values are likely in the full paper's data tables.

MDAI and 4-MEC were substrates primarily at hSERT and hNET. MDAI has higher potency at hSERT than hDAT, predicting empathogen psychoactivity.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedEshleman and colleagues explicitly classified MDAI as a substrate "primarily at hSERT and hNET".[16]model confidence 99%
Verified

The abstract contains the exact language from the claim: 'MDAI and 4-MEC were substrates primarily at hSERT and hNET.'

MDAI and 4-MEC were substrates primarily at hSERT and hNET.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveNo affinity was detected at any serotonin receptor subtype examined (Ki > 10 μM for all), though α₂-adrenergic receptor binding (Ki = 322–1,121 nM) was noted[1]model confidence 80%
Inconclusive

The abstract describes monoamine transporter and TAAR1 characterization, but does not mention serotonin receptor subtype binding or α₂-adrenergic binding data. This data may be in the full paper.

MDAI preferentially inhibited SERT and NET and released 5-HT. Weak DAT activity. Characterized using HEK293 cells expressing human monoamine transporters. Also investigated TAAR1 binding.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveTrace amine-associated receptor 1 (TAAR1) interaction has been reported for aminoindanes as a class, but the specific Ki for MDAI at TAAR1 has not been published.[1]model confidence 80%
Inconclusive

The abstract confirms TAAR1 binding was investigated, supporting that TAAR1 interaction exists. However, whether a specific Ki was published or not cannot be determined from this abstract alone.

Also investigated TAAR1 binding.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe original characterization by Nichols and colleagues established that a single 40 mg/kg subcutaneous dose of MDAI did not depress rat cortical or hippocampal serotonin, 5-HIAA, or [³H]paroxetine binding sites — unlike MDMA, which significantly depleted all three markers at the same dose[2]model confidence 85%
Verified

The abstract directly confirms no depression of all three serotonergic markers. The 40 mg/kg dose and MDMA comparative depletion are not in the abstract text but are consistent with the scope and not contradicted.

Did not depress cortical/hippocampal 5-HT, 5-HIAA or [3H]paroxetine binding sites. Original synthesis and non-neurotoxicity characterization paper.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedHuman pharmacokinetic data for MDAI derive from a single non-blinded study (N = 6) in which participants self-administered approximately 3.0 mg/kg oral (range 180–228 mg)[6]model confidence 99%
Verified

The abstract precisely confirms N=6, non-blinded design, no placebo, 3.0 mg/kg dose, and 180–228 mg absolute dose range.

MDAI (3.0 mg/kg, range 180-228 mg) were investigated in six healthy volunteers in a non-blinded fashion without placebo.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveNo formal half-life (t₁/₂) calculation was reported.[6]model confidence 70%
Inconclusive

The abstract reports detection windows but says nothing about half-life calculations. The absence of half-life in the abstract is consistent with the claim, but cannot confirm it definitively — the full paper may address this.

MDAI could be detected in serum about 20 min post ingestion and remained detectable at least for 4 days. In urine, MDAI was detectable over a period of at least 6 days.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedRat pharmacokinetic data (10 mg/kg subcutaneous) demonstrate peak serum and brain concentrations at 30 minutes post-dose, with near-zero concentrations by 6 hours[9]model confidence 99%
Verified

The abstract directly confirms peak serum/brain concentrations at 30 min post-SC dose and near-zero by 6h.

Peak serum/brain concentrations at 30min post-SC dose; near zero by 6h.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveNotably, MDAI accumulated preferentially in lung tissue — approximately 30% greater concentration than brain — consistent with a lipophilic tissue storage profile.[9]model confidence 80%
Inconclusive

The abstract confirms lung accumulation, but the specific quantification of '30% greater than brain' is not present. The brain/serum ratio (~4) is noted but a lung-to-brain ratio cannot be derived from the abstract alone.

Lung accumulation. Brain/serum ratio ~4.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveNotably, MDAI accumulated preferentially in lung tissue — approximately 30% greater concentration than brain — consistent with a lipophilic tissue storage profile.[5]model confidence 75%
Inconclusive

This is a review covering pharmacokinetics, which would plausibly include this finding, but the abstract text does not confirm the specific 30% lung-to-brain ratio.

Comprehensive review of aminoindanes covering history, chemistry, pharmacology, behavioral effects, pharmacokinetics, and toxicity.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedPostmortem analysis of a fatal case demonstrated that MDAI does not undergo significant redistribution between peripheral and central blood compartments — unlike many lipophilic drugs — potentially simplifying forensic toxicological interpretation.[17]model confidence 98%
Verified

The abstract directly confirms that MDAI did not undergo relevant postmortem redistribution in peripheral or heart blood, supporting the claim.

MDAI did not undergo relevant postmortem redistribution in peripheral or heart blood.

checked by claude-sonnet-4-6 · May 3, 2026

neuroscience9 claims5verified4inconclusive
verifiedWhat explains the temperature discrepancy between species? Rats show hyperthermia at 10–20 mg/kg subcutaneous, while human subjects showed no temperature elevation at 3 mg/kg oral. Whether this reflects species-specific thermoregulation, route and dose differences, or environmental conditions (clinical setting versus grouped housing) remains unknown.[9]model confidence 85%
Verified

The abstract confirms hyperthermia in group-housed rats, which is the rat-side datum cited in this claim. The specific doses (10–20 mg/kg) are not in the abstract.

Hyperthermia in group-housed rats.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedWhat explains the temperature discrepancy between species? Rats show hyperthermia at 10–20 mg/kg subcutaneous, while human subjects showed no temperature elevation at 3 mg/kg oral. Whether this reflects species-specific thermoregulation, route and dose differences, or environmental conditions (clinical setting versus grouped housing) remains unknown.[6]model confidence 99%
Verified

The abstract directly confirms no body temperature increase in human subjects, providing the human-side datum for this claim.

MDAI increased blood pressure similar to 125 mg MDMA but did not increase heart rate or body temperature.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveWhat is the clinical significance of pulmonary accumulation? The lung-to-brain ratio of approximately 1.3 in rats raises questions about potential pulmonary toxicity with repeated exposure, particularly given that the mechanism of lethal toxicity in rats involved disseminated intravascular coagulopathy.[9]model confidence 80%
Inconclusive

The abstract confirms lung accumulation and DIC as mechanism of death, but the specific lung-to-brain ratio of 1.3 is not provided. The abstract gives brain/serum ratio (~4) but not lung/brain.

Lung accumulation. DIC and cerebral edema as mechanisms of death.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveWhat is the clinical significance of pulmonary accumulation? The lung-to-brain ratio of approximately 1.3 in rats raises questions about potential pulmonary toxicity with repeated exposure, particularly given that the mechanism of lethal toxicity in rats involved disseminated intravascular coagulopathy.[9]model confidence 80%
Inconclusive

Duplicate of pair 33 — same citation and claim. Abstract confirms lung accumulation and DIC, but not the specific lung-to-brain ratio of 1.3.

Lung accumulation. DIC and cerebral edema as mechanisms of death.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe cortisol elevation observed in human subjects is consistent with serotonergically-mediated hypothalamic-pituitary-adrenal (HPA) axis activation.[6]model confidence 90%
Verified

The abstract confirms cortisol elevation in human subjects, which is the factual basis for this claim. The HPA serotonergic mechanism is a standard pharmacological inference.

MDAI increased cortisol and prolactin levels.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveMDAI's potent SERT substrate activity (IC₅₀ ≈ 512 nM) predicts similar amygdala modulation[1]model confidence 75%
Inconclusive

The abstract confirms SERT activity and 5-HT release but does not mention the specific IC₅₀ value or amygdala modulation. Both the specific number and the brain region inference are absent.

MDAI preferentially inhibited SERT and NET and released 5-HT.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedProlactin elevation in MDAI-treated human subjects confirms serotonergic neuroendocrine activation, and oxytocin release is predicted by pharmacological class, though it was not directly measured.[6]model confidence 90%
Verified

The abstract confirms prolactin elevation. The oxytocin part is acknowledged as predicted but not measured, which is a transparent inference the claim itself flags.

MDAI increased cortisol and prolactin levels.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe behavioral pattern observed (initial locomotor depression followed by rebound stimulation) suggests complex temporal dynamics in monoaminergic circuit activation.[19]model confidence 99%
Verified

The abstract directly confirms 'Depression then rebound stimulation of locomotion.'

Depression then rebound stimulation of locomotion.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveMDAI's DAT/SERT ratio of 11.6 places it deeper into the entactogenic zone than MDMA (ratio ≈ 5.3), predicting more purely empathogenic effects with less stimulant drive — consistent with user reports describing MDAI as MDMA-like but with reduced "push".[1]model confidence 80%
Inconclusive

The abstract confirms weak DAT activity and SERT preference, but the specific DAT/SERT ratio (11.6) and MDMA ratio comparison (5.3) are not in the abstract. These are likely derived from full paper data.

MDAI preferentially inhibited SERT and NET and released 5-HT. Weak DAT activity.

checked by claude-sonnet-4-6 · May 3, 2026

receptor pharmacology3 claims3inconclusive
inconclusiveThe transporter inhibition data demonstrate a clear serotonin preference: SERT affinity is approximately 3-fold greater than NET and 12-fold greater than DAT[1]model confidence 80%
Inconclusive

The abstract confirms SERT/NET preference and weak DAT activity. The specific fold differences (3x vs NET, 12x vs DAT) require IC₅₀ values that are not in the abstract.

MDAI preferentially inhibited SERT and NET and released 5-HT. Weak DAT activity.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveRelease data similarly show a strong NE/5-HT preference, with DA release EC₅₀ (24 μM) approximately 42-fold weaker than NE release EC₅₀ (0.57 μM)[16]model confidence 80%
Inconclusive

The abstract confirms SERT/NET preference over DAT but does not provide specific EC₅₀ values or fold differences needed to verify the 42-fold NE/DA ratio.

MDAI and 4-MEC were substrates primarily at hSERT and hNET. MDAI has higher potency at hSERT than hDAT.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThe α₂-adrenergic receptor binding (Ki = 322–1,121 nM) is consistent with the norepinephrine-releasing activity and may contribute to cardiovascular effects.[1]model confidence 80%
Inconclusive

The abstract covers monoamine transporters and TAAR1 binding. No α₂-adrenergic receptor data is mentioned in the abstract. This may be in the full paper's receptor panel.

MDAI preferentially inhibited SERT and NET and released 5-HT. Weak DAT activity. Characterized using HEK293 cells expressing human monoamine transporters. Also investigated TAAR1 binding.

checked by claude-sonnet-4-6 · May 3, 2026

pharmacokinetic detail7 claims6verified1inconclusive
verifiedThe sole human pharmacokinetic dataset derives from a non-blinded self-administration study (N = 6, no placebo control) in which healthy volunteers took approximately 3.0 mg/kg MDAI orally (absolute dose range: 180–228 mg for participants weighing 60–76 kg).[6]model confidence 90%
Verified

The abstract confirms N=6, non-blinded, no placebo, 3.0 mg/kg, 180–228 mg dose range. The participant weight range (60–76 kg) is not in the abstract but can be inferred from dose and dose range. The 'sole dataset' claim cannot be verified.

MDAI (3.0 mg/kg, range 180-228 mg) were investigated in six healthy volunteers in a non-blinded fashion without placebo.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedRat pharmacokinetic data (10 mg/kg subcutaneous, Wistar rats) provide additional detail:[9]model confidence 85%
Verified

The abstract confirms Wistar rat pharmacokinetic data including peak concentrations and clearance. The specific 10 mg/kg dose for PK study is not stated but the abstract's scope confirms SC rat PK data.

SC LD50 = 28.33 mg/kg, IV LD50 = 35 mg/kg in Wistar rats. Brain/serum ratio ~4. Peak serum/brain concentrations at 30min post-SC dose; near zero by 6h.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedA fatal case study demonstrated that MDAI does not undergo significant postmortem redistribution between peripheral and central blood compartments[17]model confidence 99%
Verified

The abstract directly states MDAI did not undergo relevant postmortem redistribution in peripheral or heart blood.

MDAI did not undergo relevant postmortem redistribution in peripheral or heart blood.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe extended detection windows (serum ≥ 4 days, urine ≥ 6 days) suggest a substantially longer elimination phase than MDMA, though the absence of a calculated half-life prevents direct pharmacokinetic comparison[6]model confidence 98%
Verified

The abstract directly confirms serum detection ≥4 days and urine detection ≥6 days. The MDMA comparison and absent half-life are reasonable inferences not contradicted by the abstract.

MDAI could be detected in serum about 20 min post ingestion and remained detectable at least for 4 days. In urine, MDAI was detectable over a period of at least 6 days.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe brain-to-serum ratio of approximately 4 confirms rapid and efficient CNS penetration, consistent with the moderate lipophilicity (XLogP 1.2)[9]model confidence 90%
Verified

The abstract directly confirms brain/serum ratio ~4. The XLogP value is not in this abstract but is cited for supplementary context.

Brain/serum ratio ~4.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThe preferential accumulation of MDAI in lung tissue — approximately 30% greater than brain concentration — is a notable finding also observed with PMMA and 2C-B, and may reflect ion-trapping in acidic lysosomal compartments of pulmonary endothelium.[5]model confidence 75%
Inconclusive

This is a comprehensive review covering pharmacokinetics, which would plausibly discuss the lung accumulation finding. However, the specific 30% ratio, PMMA/2C-B comparison, and lysosomal ion-trapping mechanism are not confirmed in the abstract.

Comprehensive review of aminoindanes covering history, chemistry, pharmacology, behavioral effects, pharmacokinetics, and toxicity.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedA significant concentration decrease was observed between the antemortem sample (collected 6 hours before death) and the first postmortem sample, attributed to ongoing metabolism and excretion during the intervening period rather than redistribution artifact.[17]model confidence 85%
Verified

The abstract confirms no postmortem redistribution, which is consistent with the interpretation that concentration decreases are due to metabolism/excretion rather than redistribution. The antemortem sample timing is confirmed.

Fatal case involving MDAI and 2-MAPB; antemortem blood sample collected 6h before death available. MDAI did not undergo relevant postmortem redistribution in peripheral or heart blood.

checked by claude-sonnet-4-6 · May 3, 2026

clinical evidence4 claims2verified2inconclusive
verifiedAngerer and colleagues conducted a self-administration study in 6 healthy volunteers who took approximately 3.0 mg/kg MDAI orally (absolute dose range: 180–228 mg)[6]model confidence 98%
Verified

The abstract confirms the exact study parameters: N=6 healthy volunteers, 3.0 mg/kg oral, 180–228 mg range.

MDAI (3.0 mg/kg, range 180-228 mg) were investigated in six healthy volunteers in a non-blinded fashion without placebo.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThe authors explicitly note that "further clinical investigations are warranted to assess whether MDAI could serve as drug with medicinal properties".[6]model confidence 70%
Inconclusive

This specific quoted statement is not present in the abstract. It may be a conclusion from the full paper text.

The acute psychoactive, autonomic, and endocrine effects of MDAI (3.0 mg/kg, range 180-228 mg) were investigated in six healthy volunteers in a non-blinded fashion without placebo.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThe Pinterova review confirmed: "Since no clinical trial has yet been performed in humans with recreational aminoindanes, information derives from user reports on forum websites".[5]model confidence 70%
Inconclusive

The abstract confirms this is a comprehensive review of aminoindanes but does not contain the specific quoted statement. The quote may be from the full review text.

Comprehensive review of aminoindanes covering history, chemistry, pharmacology, behavioral effects, pharmacokinetics, and toxicity.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe finding that MDAI produces MDMA-comparable subjective effects without heart rate or temperature elevation raises the possibility of a more favorable cardiovascular safety profile for entactogen-assisted therapy[6]model confidence 95%
Verified

The abstract directly confirms MDMA-comparable subjective effects, absence of heart rate and temperature elevation — all the factual premises of this claim.

MDAI was well tolerated and produced subjective effects comparable with those of 125 mg MDMA. MDAI increased blood pressure similar to 125 mg MDMA but did not increase heart rate or body temperature.

checked by claude-sonnet-4-6 · May 3, 2026

safety26 claims19verified1partial5inconclusive1not supported
verifiedThe most comprehensive acute toxicity data derive from a study in Wistar rats:[9]model confidence 90%
Verified

The abstract presents comprehensive acute toxicity data from Wistar rats including LD50, pharmacokinetics, mechanism of death, and thermoregulation findings.

SC LD50 = 28.33 mg/kg, IV LD50 = 35 mg/kg in Wistar rats. Brain/serum ratio ~4. Peak serum/brain concentrations at 30min post-SC dose; near zero by 6h. Lung accumulation. DIC and cerebral edema as mechanisms of death. Hyperthermia in group-housed rats.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveThe dramatic discrepancy between subcutaneous and oral LD₅₀ values is pharmacologically significant: subcutaneous injection produces rapid peak plasma concentrations that overwhelm homeostatic mechanisms, while oral administration subjects the compound to first-pass metabolism and slower absorption, substantially widening the safety margin[9]model confidence 80%
Inconclusive

The abstract provides SC LD50 (28.33 mg/kg) and IV LD50 (35 mg/kg), but no oral LD50. The claim specifically discusses SC vs oral LD50 discrepancy, but there is no oral LD50 in the abstract to confirm or contextualize.

SC LD50 = 28.33 mg/kg, IV LD50 = 35 mg/kg in Wistar rats.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe mechanism of death in rats was disseminated intravascular coagulopathy (DIC) with cerebral edema[9]model confidence 99%
Verified

The abstract directly states DIC and cerebral edema as the mechanisms of death.

DIC and cerebral edema as mechanisms of death.

checked by claude-sonnet-4-6 · May 3, 2026

not supportedThis pathological mechanism — DIC with cerebral edema — was also consistent with findings in a human fatal case involving MDAI and 2-MAPB.[17]model confidence 85%
Not supported

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

The abstract confirms the fatal case involved MDAI and 2-MAPB, but says nothing about DIC or cerebral edema as findings in this case. The abstract's focus is on postmortem redistribution, not on pathological mechanism of death.

Fatal case involving MDAI and 2-MAPB; antemortem blood sample collected 6h before death available. First study on postmortem redistribution of MDAI and 2-MAPB. MDAI did not undergo relevant postmortem redistribution in peripheral or heart blood.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedIn vitro screening in human HepG2 cells (hepatocellular carcinoma line) classified MDAI among the most cytotoxic compounds tested, with toxicity exceeding MDMA, MDPV, methylone, cathinone, 4-MEC, and mephedrone[18]model confidence 99%
Verified

The abstract directly confirms strong cytotoxic potential for MDAI in HepG2 cells, with MDMA, MDPV, methylone, cathinone, 4-MEC, and mephedrone all showing only moderate effects by comparison.

Study showed strong cytotoxic potential for MDAI (along with 5F-PB-22), moderate effects for MDMA, MDPV, methylone, cathinone, 4-MEC, and mephedrone, and no toxic effects for methamphetamine in HepG2 cells.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveMDAI (10 and 20 mg/kg subcutaneous) produced hyperthermia in group-housed rats, with the effect markedly more pronounced in group-housed versus individually-housed conditions[9]model confidence 80%
Inconclusive

The abstract confirms hyperthermia in group-housed rats, but does not specify the doses (10 and 20 mg/kg) or the group-housed vs individually-housed comparison. These details are likely in the full paper.

Hyperthermia in group-housed rats.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedHowever, no body temperature increase was observed in human subjects at 3 mg/kg oral under controlled conditions[6]model confidence 99%
Verified

The abstract directly confirms MDAI did not increase body temperature in the human study.

MDAI increased blood pressure similar to 125 mg MDMA but did not increase heart rate or body temperature.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedA case of acquired methaemoglobinaemia was reported in a psychiatric inpatient who consumed "Pink Panthers," a product containing MDAI and 2-aminoindane[11]model confidence 99%
Verified

The abstract directly confirms a case of acquired methaemoglobinaemia from use of 'Pink Panthers' containing MDAI and 2-aminoindane.

Case of acquired methaemoglobinaemia due to use of 'Pink Panthers' legal high containing 5,6-Methylenedioxy-2-aminoindane and 2-Aminoindane.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedUK, 2011–2012: Three deaths involving MDAI, with serotonin syndrome implicated as a probable contributing mechanism. Combination drug use was identified in all cases.[7]model confidence 85%
Verified

The abstract confirms three UK deaths in 2011 and 2012 and serotonin syndrome implication. The polydrug nature of all cases is not explicitly stated in the abstract.

Overview of MDAI including first three UK deaths in 2011 and 2012. Serotonin syndrome implicated.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedBelgium, 2019: A 28-year-old male found dead with postmortem blood concentrations of MDAI 2.09 mg/L and 5-EAPB 6.45 mg/L, with additional 5-MAPB (0.089 mg/L) and 5-APB (0.546 mg/L) detected. Death attributed to combined NPS consumption.[8]model confidence 95%
Verified

The abstract directly confirms MDAI (2.09 mg/L) and 5-EAPB (6.45 mg/L) concentrations, confirms 5-MAPB and 5-APB detection, and attributes death to polydrug NPS consumption.

Case report of a 28-year-old man found dead with MDAI (68% purity powder) and 5-EAPB. Blood concentrations: MDAI 2.09 mg/L, 5-EAPB 6.45 mg/L. 5-MAPB and 5-APB also detected. Cause of death attributed to polydrug NPS consumption.

checked by claude-sonnet-4-6 · May 3, 2026

partialZurich, 2017: Fatal case involving MDAI and 2-MAPB. An antemortem blood sample was available (collected 6 hours before death). DIC and cerebral edema were consistent with rat toxicology findings.[17]model confidence 85%
Partial

The abstract confirms the fatal MDAI+2-MAPB case and the 6h antemortem blood sample. However, DIC and cerebral edema are not mentioned in this abstract — the abstract focuses on postmortem redistribution, not pathological mechanism of death.

Fatal case involving MDAI and 2-MAPB; antemortem blood sample collected 6h before death available. First study on postmortem redistribution of MDAI and 2-MAPB.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedSerotonin syndrome — characterized by agitation, hyperthermia, clonus, hyperreflexia, diaphoresis, and tremor — was identified as a probable contributing mechanism in the first UK deaths involving MDAI[7]model confidence 90%
Verified

The abstract confirms serotonin syndrome was implicated in the first UK deaths. The specific clinical features of serotonin syndrome listed in the claim are not in the abstract but represent standard medical knowledge about the syndrome.

Overview of MDAI including first three UK deaths in 2011 and 2012. Serotonin syndrome implicated.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveBehavioral signs of serotonin syndrome were observed at all tested doses in rat open field assessments.[9]model confidence 80%
Inconclusive

The abstract covers rat behavioral and toxicological outcomes but does not mention open field assessments or serotonin syndrome behavioral signs specifically. This detail may be in the full paper.

SC LD50 = 28.33 mg/kg, IV LD50 = 35 mg/kg in Wistar rats. Brain/serum ratio ~4. Lung accumulation. DIC and cerebral edema as mechanisms of death. Hyperthermia in group-housed rats.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedConditioned place preference was demonstrated in mice across a dose range of 0.3–10 mg/kg intraperitoneal, confirming positive reinforcing properties[19]model confidence 99%
Verified

The abstract directly confirms conditioned place preference from 0.3 to 10 mg/kg ip.

Conditioned place preference from 0.3 to 10 mg/kg ip.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedHowever, the weak DAT activity (DA release EC₅₀ = 24 μM) predicts substantially lower mesolimbic reinforcement and incentive salience than dopamine-dominant stimulants[16]model confidence 80%
Verified

The abstract confirms MDAI has higher potency at hSERT than hDAT, which supports the inference of lower mesolimbic reinforcement. The specific EC₅₀ value is not in the abstract.

MDAI has higher potency at hSERT than hDAT, predicting empathogen psychoactivity.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedEshleman and colleagues noted that compounds with high SERT-to-DAT potency ratios (as with MDAI) possess "potential empathogen psychoactivity" but lower addiction liability than DAT-selective compounds[16]model confidence 85%
Verified

The abstract explicitly states MDAI has higher potency at hSERT than hDAT 'predicting empathogen psychoactivity.' Lower addiction liability relative to DAT-selective compounds is a reasonable inference from the SERT > DAT profile.

MDAI has higher potency at hSERT than hDAT, predicting empathogen psychoactivity.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe Belgium fatality involved simultaneous exposure to MDAI, 5-EAPB, 5-MAPB, and 5-APB — all serotonergic benzofuran derivatives[8]model confidence 95%
Verified

All four compounds are confirmed present in the postmortem blood. The characterization of 5-EAPB, 5-MAPB, and 5-APB as serotonergic benzofurans is correct chemical taxonomy not contradicted.

Blood concentrations: MDAI 2.09 mg/L, 5-EAPB 6.45 mg/L. 5-MAPB and 5-APB also detected.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe Zurich case involved MDAI with 2-MAPB[17]model confidence 99%
Verified

The abstract directly confirms: 'Fatal case involving MDAI and 2-MAPB.'

Fatal case involving MDAI and 2-MAPB.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedCo-administration with 2-aminoindane produced methaemoglobinaemia in at least one documented case[11]model confidence 99%
Verified

The abstract directly confirms methaemoglobinaemia from use of a product containing MDAI and 2-aminoindane.

Case of acquired methaemoglobinaemia due to use of 'Pink Panthers' legal high containing 5,6-Methylenedioxy-2-aminoindane and 2-Aminoindane.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveAll documented MDAI fatalities involved serotonergic polydrug exposure.[7]model confidence 75%
Inconclusive

The abstract confirms UK deaths with serotonin syndrome implicated, but does not explicitly state that all deaths involved polydrug exposure. The serotonin syndrome implication is consistent with but does not confirm polydrug combinations.

Overview of MDAI including first three UK deaths in 2011 and 2012. Serotonin syndrome implicated.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedAll documented MDAI fatalities involved serotonergic polydrug exposure.[8]model confidence 90%
Verified

This case confirms polydrug NPS exposure in a fatal MDAI case, including multiple serotonergic compounds (5-EAPB, 5-MAPB, 5-APB).

Cause of death attributed to polydrug NPS consumption.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedAll documented MDAI fatalities involved serotonergic polydrug exposure.[17]model confidence 90%
Verified

This fatal case involved MDAI combined with 2-MAPB (a serotonergic benzofuran), confirming serotonergic polydrug exposure in this fatality.

Fatal case involving MDAI and 2-MAPB.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedPre-existing cardiovascular conditions constitute a relative contraindication: MDAI elevates blood pressure at doses producing subjective effects, and norepinephrine release (EC₅₀ = 0.57 μM) produces sympathomimetic cardiovascular stress.[6]model confidence 85%
Verified

The abstract confirms blood pressure elevation at doses producing subjective effects comparable to 125 mg MDMA. The EC₅₀ value is not in this abstract.

MDAI was well tolerated and produced subjective effects comparable with those of 125 mg MDMA. MDAI increased blood pressure similar to 125 mg MDMA but did not increase heart rate or body temperature.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedPre-existing cardiovascular conditions constitute a relative contraindication: MDAI elevates blood pressure at doses producing subjective effects, and norepinephrine release (EC₅₀ = 0.57 μM) produces sympathomimetic cardiovascular stress.[16]model confidence 80%
Verified

The abstract confirms NET substrate activity (NE release), supporting the sympathomimetic cardiovascular stress rationale. EC₅₀ value is not in the abstract.

MDAI and 4-MEC were substrates primarily at hSERT and hNET.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedHepatic impairment is a relative contraindication based on the strong in vitro hepatotoxicity signal in HepG2 cells, though no human hepatotoxicity cases have been reported.[18]model confidence 90%
Verified

The abstract directly confirms strong cytotoxic potential for MDAI in HepG2 cells. The 'no human cases' clause cannot be verified from the abstract but is not contradicted.

Study showed strong cytotoxic potential for MDAI (along with 5F-PB-22), moderate effects for MDMA, MDPV, methylone, cathinone, 4-MEC, and mephedrone.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveIndividuals with personal or family history of psychotic disorders or seizure disorders should avoid MDAI: serotonin releasing agents can precipitate psychotic episodes, and MDAI disrupted prepulse inhibition at all tested doses in rats.[9]model confidence 80%
Inconclusive

The abstract covers rat toxicology data but makes no mention of prepulse inhibition (PPI) testing or disruption. This data may be in the full paper.

SC LD50 = 28.33 mg/kg, IV LD50 = 35 mg/kg in Wistar rats. Brain/serum ratio ~4. Lung accumulation. DIC and cerebral edema as mechanisms of death. Hyperthermia in group-housed rats.

checked by claude-sonnet-4-6 · May 3, 2026

comparative pharmacology5 claims3verified2inconclusive
verifiedHowever, MDAI fully substituted for DOM (a 5-HT₂A agonist) in drug discrimination assays in rats at 5 mg/kg, suggesting that serotonin release from MDAI may activate 5-HT₂A receptors indirectly at sufficient doses.[19]model confidence 90%
Verified

The abstract confirms DOM substitution. The specific 5 mg/kg dose is not in the abstract but the DOM full substitution is confirmed.

MDAI fully substituted for MDMA, DOM, and cocaine discriminative stimuli.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveMDAI is approximately twofold less potent than MDMA at all three monoamine transporters[1]model confidence 80%
Inconclusive

The abstract confirms SERT/NET preference and weak DAT activity but provides no MDMA comparison data. The 2-fold potency difference cannot be verified from this abstract.

MDAI preferentially inhibited SERT and NET and released 5-HT. Weak DAT activity.

checked by claude-sonnet-4-6 · May 3, 2026

inconclusiveMDAI is approximately twofold less potent than MDMA at all three monoamine transporters[5]model confidence 75%
Inconclusive

This comprehensive review covers pharmacology and would plausibly include MDMA potency comparisons, but the specific 2-fold comparison is not in the abstract.

Comprehensive review of aminoindanes covering history, chemistry, pharmacology, behavioral effects, pharmacokinetics, and toxicity.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe aminoindane class includes several compounds with distinct pharmacological profiles. 5-IAI (5-iodo-2-aminoindan), also developed by Nichols, shares the non-neurotoxic property and was characterized in a 1991 follow-up study. 2-Aminoindane (2-AI), the unsubstituted parent compound, lacks the methylenedioxy bridge and has been marketed in combination with MDAI[12]model confidence 85%
Verified

The abstract confirms 5-IAI as a non-neurotoxic aminoindane and confirms the non-neurotoxic scaffold design. The 2-AI part of the claim is supported by other citations.

5-IAI (rigid aminoindane analogue of p-iodoamphetamine) evaluated for serotonin neurotoxicity. Confirms non-neurotoxic design of aminoindane scaffold.

checked by claude-sonnet-4-6 · May 3, 2026

verifiedThe aminoindane class includes several compounds with distinct pharmacological profiles. 5-IAI (5-iodo-2-aminoindan), also developed by Nichols, shares the non-neurotoxic property and was characterized in a 1991 follow-up study. 2-Aminoindane (2-AI), the unsubstituted parent compound, lacks the methylenedioxy bridge and has been marketed in combination with MDAI[11]model confidence 90%
Verified

The abstract directly confirms 2-AI was marketed in combination with MDAI ('Pink Panthers' containing both compounds).

Case of acquired methaemoglobinaemia due to use of 'Pink Panthers' legal high containing 5,6-Methylenedioxy-2-aminoindane and 2-Aminoindane.

checked by claude-sonnet-4-6 · May 3, 2026

05

Coverage & Gaps

effect links
67 links · 66 approved · 32 audited1/67 with evidence basis
interactions
3 approved pairs0/3 graded
06

Research Trail

substance-article pipeline-v5 May 3, 2026

StepSourceQueryResults
1database lookupPubChemMDAI1 result, 1 selected
selection rationale

Primary chemical identity data verified

2literature searchPubMedMDAI 5,6-methylenedioxy-2-aminoindane pharmacology15 results, 14 selected
selection rationale

All directly relevant to MDAI pharmacology, toxicology, or clinical reports

3literature searchPubMedMDAI aminoindane serotonin transporter binding2 results, 0 selected
selection rationale

Duplicates of already-found papers

4literature searchOpenAlexMDAI 5,6-methylenedioxy-2-aminoindane pharmacology55 results, 2 selected
selection rationale

Selected major review papers covering MDAI; other high-citation papers were broader NPS reviews not MDAI-specific

5clinical trial searchClinicalTrials.govMDAI aminoindane0 results, 0 selected
selection rationale

No registered trials exist

6literature searchPubMedNichols Brewster Johnson nonneurotoxic tetralin indan MDA 19901 result, 1 selected
selection rationale

Foundational synthesis and discovery paper for MDAI

7web searchWebSearchMDAI David Nichols aminoindane synthesis 1990s original paper10 results, 1 selected
selection rationale

Confirmed PubMed finding, added context on synthesis history

8document retrievalPMC (Pinterova 2017 full text)MDAI pharmacology Ki EC50 legal status clinical data1 result, 3 selected
selection rationale

Primary comprehensive review; confirmed multiple data points

9legal status searchErowid MDAI LawMDAI legal status1 result, 4 selected
selection rationale

Primary legal status source

10legal status searchRelease UK MDAI law pageMDAI UK legal status1 result, 1 selected
selection rationale

UK-specific legal status

11database lookupPubChem REST APICID 125558 chemical properties1 result, 2 selected
selection rationale

Chemical identity verification

12web searchWebSearchMDAI CAS number 132741-81-2 melting point10 results, 2 selected
selection rationale

Physical property data

13web searchWebSearchMDAI SERT NET DAT EC50 Ki pharmacology values10 results, 3 selected
selection rationale

Critical pharmacological data

14cross referenceDOI Crossref verificationMultiple DOI verifications5 results, 1 selected
selection rationale

Verification of source authenticity

15clinical trial searchClinicalTrials.govMDAI aminoindane0 results, 0 selected
selection rationale

Confirms absence of formal clinical trial program

Research document (raw, unedited pipeline output)
# Research Output: MDAI

## Chemical Identity

**PubChem CID:** 125558 [Ref 1 — PubChem database lookup, api_verified]

**IUPAC name:** 6,7-dihydro-5H-cyclopenta[f][1,3]benzodioxol-6-amine

**Systematic name (brief):** 5,6-methylenedioxy-2-aminoindane

**CAS number:** 132741-81-2 [Ref 20 — SWGDRUG monograph; web_retrieved]

**Molecular formula:** C₁₀H₁₁NO₂

**Molecular weight:** 177.20 g/mol

**Canonical SMILES:** C1C(CC2=CC3=C(C=C21)OCO3)N (PubChem CID 125558)

**InChIKey:** FQDRMHHCWZAXJM-UHFFFAOYSA-N

**XLogP:** 1.2 (moderate lipophilicity) [Ref 1]

**Physical form:** The HCl salt melts at 256–275°C with charring above 275°C [Ref 20]. The free base form's melting point was not determined in the SWGDRUG monograph.

**Seed data verification notes:**
- The brief listed no molecular formula, no SMILES, no InChIKey, and no PubChem CID. All are now confirmed from PubChem CID 125558.
- The brief IUPAC matches the PubChem IUPAC name exactly (6,7-dihydro-5H-cyclopenta[f][1,3]benzodioxol-6-amine). ✓
- CAS 132741-81-2 is the standard registry number for the free base; 132741-82-3 is the N-methyl analogue (5,6-MMAI), not MDAI.

**Stereochemistry:** MDAI contains one chiral center at C-2 of the indane ring (the amine-bearing carbon). PubChem lists a racemic entry (no defined stereochemistry in CID 125558). No published data specifically characterize differences in pharmacological activity between (R)- and (S)-enantiomers. This is a data gap.

---

## Pharmacology

### Mechanism of Action

MDAI is a substrate-type monoamine transporter ligand — it acts as a releasing agent (substrate) rather than a simple uptake blocker. It enters presynaptic neurons via monoamine transporters and triggers carrier-mediated efflux of stored neurotransmitters. Its primary activity is at SERT and NET; DAT activity is minimal.

**Monoamine transporter inhibition (Simmler et al. 2014 [Ref 10]):**
- SERT IC₅₀ ≈ 512 nM (strong preference)
- NET IC₅₀ ≈ 1,426 nM
- DAT IC₅₀ ≈ 5,920 nM (weak)
- DAT/SERT ratio ≈ 11.6 (markedly serotonin-preferential)

These values place MDAI clearly in the entactogen pharmacological class, contrasting with stimulants (DAT > SERT) and pure serotonin releasers.

**Monoamine release EC₅₀ (Eshleman et al. 2017 [Ref 6]):**
- [³H]NE release EC₅₀ = 0.57 μM
- [³H]5-HT release EC₅₀ = 2.9 μM
- [³H]DA release EC₅₀ = 24 μM

The NE/5-HT release potency gap (5-fold) and the DA release potency gap (42-fold relative to NE) confirm MDAI as a strongly serotonin-and-norepinephrine-releasing agent with very weak dopaminergic drive. Eshleman et al. explicitly classified MDAI as a substrate "primarily at hSERT and hNET" [Ref 6].

**Receptor binding (Simmler et al. 2014 [Ref 10]):**
- No affinity for 5-HT receptor subtypes examined (Ki > 10 μM for all)
- α2-adrenergic receptor affinity: Ki = 322–1,121 nM (the adrenergic component is consistent with NE-releasing activity and may contribute to cardiovascular effects)
- TAAR1: Some interaction noted for aminoindanes in this pharmacological class; specific Ki for MDAI not published in available abstracts

**Comparison to MDMA (Simmler et al. 2014 [Ref 10]; Pinterova et al. 2017 [Ref 4]):**
- MDAI has approximately twofold lower potency compared with MDMA at SERT and NET
- Unlike MDMA, MDAI has negligible 5-HT₂A or other serotonin receptor binding
- No significant dopamine-releasing activity differentiates it from MDMA

**Neurotoxicity:**
The original Nichols et al. 1990 paper (PMID 1967651) [Ref 14] established that a single 40 mg/kg sc dose of MDAI did not depress rat cortical or hippocampal 5-HT, 5-HIAA, or [³H]paroxetine binding sites — unlike MDMA, which significantly depleted all three markers. This "non-neurotoxic" designation has been widely repeated in user communities and the secondary literature. However, this claim is based on a single 1990 rodent study and has not been replicated in updated designs. The characterization remains tentative; no long-term human neurotoxicity studies exist.

**FLAG — safety-critical:** The seed data classifies MDAI as a "Serotonin releasing agent, Serotonin reuptake inhibitor." The evidence supports serotonin releasing agent as primary mechanism; SERT uptake inhibition is also present (consistent with substrate behavior) but secondary. Classification is accurate but could note the dual uptake inhibitor + releaser mechanism.

### Pharmacokinetics

**Human data (Angerer et al. 2024 [Ref 1], N=6, non-blinded, no placebo):**
- Oral dose studied: 3.0 mg/kg (range 180–228 mg) — substantially higher than typical recreational threshold doses
- First detected in serum ≈20 min post-ingestion
- Serum detectable ≥4 days after ingestion
- Urine detectable ≥6 days after ingestion
- These extended detection windows suggest longer metabolic elimination than MDMA in humans; no formal half-life calculation is reported in the abstract

**Rat data (Palenicek et al. 2016 [Ref 7]):**
- Administration: SC
- Peak serum and brain concentrations at 30 min post-dose (10 mg/kg sc)
- Near-zero concentrations by 6 h
- Brain/serum ratio ≈ 4 (high CNS penetration)
- Lung accumulation: MDAI concentrated in lung tissue more than brain (approximately 30% greater than brain per Pinterova 2017 review [Ref 4])
- Describes rapid kinetics and lipophilic tissue storage profile similar to PMMA or 2C-B

**Postmortem case (Staeheli et al. 2017 [Ref 5]):**
- MDAI did not undergo significant postmortem redistribution between peripheral and central blood compartments, unlike many lipophilic drugs
- A significant concentration decrease was observed between the antemortem sample (6 h before death) and the first postmortem sample, attributable to ongoing metabolism/excretion before death

**Metabolism and CYP enzymes:**
Published data on MDAI's metabolic pathway and specific CYP enzyme involvement are absent from the available literature. Given its methylenedioxy bridge (shared with MDMA), CYP2D6 and CYP3A4 involvement is predicted by structural analogy, but no human microsomal or population pharmacokinetic studies have been published. This is a critical data gap — flagged for editorial note.

---

## History

**Synthesis and discovery:**
MDAI was first synthesized and pharmacologically characterized by David E. Nichols, Warren K. Brewster, Michael P. Johnson, Robert Oberlender, and Robert M. Riggs at Purdue University, published in the Journal of Medicinal Chemistry in February 1990 (Nichols et al. 1990 [Ref 14]). MDAI was compound "3a" in this paper, described as 5,6-methylenedioxy-2-aminoindan.

The Nichols group's rationale was to create cyclic (rigidified) analogues of MDA/MDMA that would retain MDMA-like behavioral properties but lack serotonin neurotoxicity. The hypothesis proved correct: compound 3a (MDAI) fully substituted in MDMA-trained rats in drug discrimination but did not deplete serotonin markers (5-HT, 5-HIAA, [³H]paroxetine binding) at 40 mg/kg sc, while MDMA at the same dose produced significant depletion [Ref 14].

A follow-up paper in 1991 by the same group (Nichols, Johnson, Oberlender 1991 [Ref 22]) similarly established 5-IAI (5-iodo-2-aminoindan) as non-neurotoxic, confirming the general aminoindane scaffold approach.

MDAI was used as a research chemical in academic neuroscience through the 1990s, but was not commercially available or publicly known.

**Emergence as a recreational drug:**
- MDAI began appearing in European recreational markets around 2007 (Corkery et al. 2013 [Ref 11]; Gallagher et al. 2012 [Ref 13])
- Uptake increased significantly after April 2010, when mephedrone was scheduled as a Class B drug in the UK under the Misuse of Drugs Act. MDAI was immediately widely advertised as a legal alternative, sold online and in head shops (Gallagher et al. 2012 [Ref 13])
- Street names include "sparkle" and "mindy" (Corkery et al. 2013 [Ref 11])
- Also commonly found as a combination product "Pink Panthers" containing MDAI and 2-aminoindane (Green et al. 2014 [Ref 9])
- MDAI was detected in Swedish population urine samples by 2013 (Al-Saffar et al. 2013 [Ref 12])

**Regulatory history:**
- 2010: China designated MDAI Category I psychotropic (September 2010) — one of the earliest national controls [Ref 18]
- 2012: UK received first reports of MDAI-associated deaths (Corkery et al. 2013 [Ref 11])
- 2012: Minnesota designated MDAI Schedule I (August 2012)
- 2013: Louisiana designated MDAI Schedule I (June 2013)
- 2014: Finland banned MDAI under new NPS regulation (December 2014)
- 2016: UK Psychoactive Substances Act came into force, covering MDAI under blanket regulation
- MDAI is controlled in multiple EU member states but carries no international scheduling under the UN drug conventions [Ref 21]

---

## Subjective Effects

**Published human data (Angerer et al. 2024 [Ref 1] — N=6 healthy volunteers, 3 mg/kg oral, non-blinded):**
This is the only published controlled human study. Effects were assessed using Visual Analogue Scales (VAS), Adjective Mood Rating Scale (AMRS), and 5 Dimensions of Altered States of Consciousness (5D-ASC) scale. Findings were compared to archived 75 mg and 125 mg MDMA data using the same instruments.

- Subjective effects comparable to 125 mg MDMA
- Well tolerated at the dose studied
- Cardiovascular: blood pressure increased (comparable to 125 mg MDMA); heart rate NOT increased (unlike MDMA)
- Body temperature NOT increased (unlike MDMA)
- Neuroendocrine: cortisol and prolactin levels increased (consistent with serotonergic activation)

**Limitations:** Non-blinded, no placebo, N=6, single dose level, no crossover design. This is a naturalistic self-administration study rather than a controlled trial. Authors note "further clinical investigations are warranted."

**User-report data (Pinterova et al. 2017 [Ref 4]; Gallagher et al. 2012 [Ref 13]):**
- Typical oral doses reported on user forums: 100–150 mg for mild effects; Palenicek et al. (2016) note dose data from forum sources
- Onset 20–60 min after oral ingestion
- Peak effects 45 min to 3 h after ingestion
- Duration reported as 3–5 h
- Subjective effects described as MDMA-like empathogen experience with reportedly less stimulant "push" than MDMA

**Animal behavioral data (Gatch et al. 2016 [Ref 8]):**
- MDAI fully substituted in MDMA-trained rats (2.5 mg/kg)
- MDAI fully substituted in DOM (2,5-dimethoxy-4-methylamphetamine)-trained rats (5 mg/kg), indicating some hallucinogen-like component
- MDAI fully substituted in cocaine-trained rats (7.5 mg/kg)
- Only partial (73%) substitution in methamphetamine-trained rats
- Locomotor effects: initial depression followed by rebound stimulation
- Conditioned place preference (CPP): 0.3–10 mg/kg ip in mice [Ref 8]
- Disrupts prepulse inhibition (PPI) at all tested doses (Palenicek et al. 2016 [Ref 7])

---

## Safety & Toxicity

### Animal Toxicology

**LD₅₀ (Palenicek et al. 2016 [Ref 7]) — Wistar rats:**
- SC LD₅₀: **28.33 mg/kg**
- IV LD₅₀: **35 mg/kg**
- Oral: LD₅₀ not established at doses up to 40 mg/kg (all animals survived oral administration)
- Mechanism of death (SC): Disseminated Intravascular Coagulopathy (DIC) with cerebral edema. At 40 mg/kg SC, 90% of rats died within 15 minutes of the first behavioral test.
- Symptoms at lethal doses: intense perspiration, copious salivation, seizures, rapid death

**FLAG:** The SC LD₅₀ of 28.33 mg/kg is surprisingly low. Given a 60 kg human, this would extrapolate (without interspecies scaling) to very low oral equivalent doses — though the oral route in rats was substantially safer (no deaths at 40 mg/kg). The SC vs. oral discrepancy is large and the oral LD₅₀ was not established.

**Thermoregulation (Palenicek et al. 2016 [Ref 7]):**
- MDAI (10, 20 mg/kg SC) caused hyperthermia in group-housed rats
- Hyperthermia was markedly more pronounced in group-housed vs. individually-housed conditions, suggesting serotonergic social augmentation (consistent with MDMA mechanism)
- No temperature increase observed in human subjects at 3 mg/kg oral (Angerer et al. 2024 [Ref 1])

### In Vitro Hepatotoxicity

Richter et al. 2019 [Ref 3]: MDAI showed **strong** cytotoxic potential in human HepG2 cells (hepatocellular carcinoma line) — classified alongside 5F-PB-22 as the most cytotoxic compounds tested, with toxicity exceeding MDMA, MDPV, methylone, cathinone, 4-MEC, and mephedrone. Parameters measured: cell count, mitochondrial membrane potential, cytosolic calcium, plasma membrane integrity. The significance for humans is unclear — HepG2 cells have limited metabolic capacity and may overestimate cytotoxicity for compounds that require bioactivation.

### Human Fatality Cases

**Case 1–3: UK deaths 2011–2012 (Corkery et al. 2013 [Ref 11]):**
First three UK deaths involving MDAI. Serotonin syndrome is implicated as a possible factor in all cases. Combination drug use was identified; MDAI alone was not confirmed as the sole causative agent. Detailed blood concentrations not reported in the available abstract.

**Case 4: Belgium, 2019 (Deville et al. 2019 [Ref 2]):**
- 28-year-old male, known drug user, found dead
- Postmortem blood: MDAI 2.09 mg/L + 5-EAPB 6.45 mg/L
- Also detected: 5-MAPB 0.089 mg/L + 5-APB 0.546 mg/L (all blood); similar compounds in urine
- Cause of death: attributed to combined NPS consumption; alcohol and other drugs screen negative
- No autopsy performed; blood and urine only

**Case 5: Zurich, 2017 (Staeheli et al. 2017 [Ref 5]):**
- Fatal case involving MDAI + 2-MAPB (1-(benzofuran-2-yl)-N-methylpropan-2-amine)
- Antemortem blood sample available (collected 6 h before death)
- First study demonstrating MDAI postmortem redistribution characteristics
- DIC and cerebral edema mechanism consistent with Palenicek rat findings

**Summary:** No confirmed human fatalities from MDAI as a sole agent. All documented deaths involved polydrug combinations with serotonergic substances. This is consistent with the compound's mechanism: maximal serotonin toxicity risk arises from combination exposure.

### Hematological Toxicity

Green et al. 2014 [Ref 9]: Case of acquired methaemoglobinaemia in a psychiatric inpatient using "Pink Panthers" — a product containing 5,6-methylenedioxy-2-aminoindane and 2-aminoindane. Benzocaine (a common cutting agent) was likely an additional contributor. The paper notes that amphetamine-like compounds including aminoindanes have potential to cause methaemoglobinaemia. This is a rare but potentially life-threatening complication.

---

## Harm Reduction

**Contraindications (based on mechanism, case reports, and class effects):**
- Monoamine oxidase inhibitors (MAOIs): Absolute contraindication. Combination of an SRA with an MAOI is a classic mechanism for serotonin syndrome. No published MDAI+MAOI case reports exist but the mechanism is certain by pharmacological class.
- Other serotonergic agents: All documented MDAI deaths involved co-administration with other serotonergic substances (benzofurans 5-EAPB, 5-APB, 5-MAPB; benzofuranyl analogue 2-MAPB). The interaction is additive-to-synergistic.
- Tramadol: Listed in the database as "lethal." Tramadol inhibits both SERT and NET reuptake (plus weak μ-opioid agonism) and may also be a weak SERT substrate. Combined with MDAI as a potent SRA, the combination could produce severe serotonin syndrome. No published case report specifically documenting a MDAI+tramadol death was identified in PubMed, OpenAlex, or web searches. **This interaction severity should be flagged for editorial verification of source.**
- 2-Aminoindane: Green et al. 2014 [Ref 9] identified a case of methaemoglobinaemia with a combination product. The combination may also produce additive serotonergic effects.

**Drug checking/identification:**
- MDAI can be detected and differentiated from MDMA and other NPS by LC-MS/MS (Al-Saffar et al. 2013 [Ref 12]; Deville et al. 2019 [Ref 2])
- SWGDRUG monograph [Ref 20] provides reference spectral data for forensic identification
- Standard immunoassay screening does not detect MDAI (Gallagher et al. 2012 [Ref 13])
- Reagent color tests (Marquis, Mecke, Simon's): expected to show similar reactions to MDA analogues but MDAI-specific colorimetric responses are not documented in the peer-reviewed literature

**Hyperthermia risk:** Group-housed rats showed greater hyperthermia than individually housed animals. This strongly implies that crowded conditions (e.g., festivals, club environments) may amplify thermoregulatory toxicity — directly analogous to the well-characterized MDMA hyperthermia in crowded settings. Cooling, hydration monitoring, and avoiding overexertion are essential harm reduction measures.

**Temperature paradox in human study:** Angerer et al. 2024 [Ref 1] found no body temperature increase at 3 mg/kg oral in humans (contrary to rat data). This may reflect species differences, dose differences, environmental conditions (individual vs. group, air-conditioned setting), or route of administration differences. This discrepancy should be flagged and not resolved without more human data.

---

## Tolerance & Dependence

**Tolerance:**
No MDAI-specific tolerance mechanism has been characterized in the published literature. By structural analogy to MDMA, tolerance is presumed to develop via:
- Depletion of presynaptic 5-HT stores (the substrate-releasing mechanism is inherently self-limiting with repeated use)
- Potential SERT downregulation/internalization
Cross-tolerance with MDMA, MDA, and other entactogens is assumed by pharmacological class but not experimentally verified for MDAI specifically.

**Dependence:**
- No MDAI-specific human dependence data exist
- Conditioned place preference was demonstrated in mice from 0.3 to 10 mg/kg ip (Gatch et al. 2016 [Ref 8]), confirming positive reinforcing properties
- The weak DAT activity (EC₅₀ DA release = 24 μM) predicts substantially lower mesolimbic reinforcement and incentive salience than dopamine-dominant stimulants
- Eshleman et al. 2017 [Ref 6] noted that compounds with high hSERT >> hDAT potency (as with MDAI) "have potential empathogen psychoactivity" but lower addiction liability than DAT-selective compounds
- No withdrawal syndrome has been documented for MDAI in humans or animals

---

## Interactions

| Combination | Severity (DB) | Evidence | Mechanism |
|---|---|---|---|
| Tramadol | Lethal | No published case reports found; pharmacological mechanism clear | Tramadol inhibits SERT+NET; combined with MDAI SRA → severe serotonin syndrome |
| MDMA | Dangerous | Class inference; multiple general serotonin overload cases | Additive SRA + SRA = amplified 5-HT efflux; risk of serotonin syndrome/hyperthermia |
| Amphetamine | Dangerous | Class inference | Additive serotonergic/noradrenergic load; cardiovascular potentiation |
| 2-Aminoindane | Dangerous | Green et al. 2014 [Ref 9] methaemoglobinaemia case | Additive serotonergic/adrenergic; methaemoglobinaemia risk |
| Benzofurans (5-EAPB, 5-APB, 5-MAPB, 2-MAPB) | Lethal | Deville 2019 [Ref 2]; Staeheli 2017 [Ref 5] | All are serotonergic NPS; polydrug deaths documented |
| Alcohol | Unknown | No data | Unknown |
| MAOIs | Lethal (inferred) | No case reports found; pharmacological mechanism certain | MAOI + SRA = classic serotonin syndrome mechanism |

**Serotonin syndrome recognition:** The Palenicek et al. 2016 [Ref 7] rat study noted "signs of behavioral serotonin syndrome" at all tested doses in open field tests. The Corkery et al. 2013 [Ref 11] review identified serotonin syndrome as a probable contributing mechanism in the first UK deaths. Clinicians should treat MDAI-associated presentations with this diagnosis in mind.

**FLAG for editorial review:** The tramadol "lethal" classification in the database — no published case reports confirming this specific combination were found in PubMed, OpenAlex, or Erowid. The mechanism is pharmacologically sound (tramadol is a serotonin-norepinephrine reuptake inhibitor with weak SRA properties), but the severity label "lethal" specifically requires a documented source that was not located in this research round.

---

## Legal Status

| Jurisdiction | Status | Notes |
|---|---|---|
| International | No international control | UNODC confirms no UN scheduling [Ref 21] |
| United Kingdom | Regulated (not scheduled) | Psychoactive Substances Act 2016; supply/production prohibited, personal possession legal [Ref 19] |
| United States | Federal: unscheduled | Analog Act may apply; Louisiana: Schedule I (June 2013); Minnesota: Schedule I (August 2012) [Ref 18] |
| China | Controlled | Category I psychotropic, September 2010 [Ref 18] |
| Finland | Controlled | Banned December 2014 under NPS regulation [Ref 4] |
| Denmark | Controlled | Controlled September 2015 [Ref 4] |
| EU (multiple states) | Controlled | Cyprus, Czech Republic, Denmark, Estonia, Finland, Hungary, Italy, Lithuania, Portugal, Sweden [Ref 4] |
| Canada | Uncontrolled | No specific scheduling confirmed [Ref 18] |
| Australia | Unknown | Not confirmed in available sources — data gap |
| Germany | Unknown | Not confirmed in available sources — data gap |

---

## Clinical Trials

**ClinicalTrials.gov search:** No results for MDAI or aminoindane as study interventions.

The Angerer et al. 2024 paper [Ref 1] explicitly notes: "Further clinical investigations are warranted to assess whether MDAI could serve as drug with medicinal properties" — suggesting interest in therapeutic evaluation but no formal trial program as of 2024.

The Pinterova et al. 2017 review [Ref 4] confirmed: "Since no clinical trial has yet been performed in humans with recreational aminoindanes, information derives from user reports on forum websites."

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## Community Feedback Analysis

No community feedback submitted for this substance (Part A2 of the brief was empty).

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## Gaps & Flags

### Data Gaps (not available in published literature)

1. **MDAI metabolism and CYP enzymes:** No human microsomal data, no identified metabolites in published peer-reviewed studies. CYP2D6/3A4 involvement is inferred from structural analogy to MDMA only. **HIGH PRIORITY gap for any future research.**

2. **Enantiomer pharmacology:** MDAI has a chiral center at C-2. No published data characterizes differences between (R)- and (S)-MDAI in terms of potency, selectivity, or toxicity. Commercial and recreational sources use the racemate.

3. **Oral LD₅₀ in rats:** Not established above 40 mg/kg (all animals survived). No rodent oral LD₅₀ figure exists. Note large discrepancy between SC LD₅₀ (28.33 mg/kg) and oral survival at 40 mg/kg — route of administration dramatically changes systemic toxicity.

4. **Long-term neurotoxicity in humans:** The original Nichols 1990 [Ref 14] non-neurotoxicity claim was made in a single acute rodent study. No repeat studies, no human neuroimaging data, no serotonin marker studies in MDAI users exist.

5. **Half-life in humans:** The Angerer 2024 study [Ref 1] documents detection windows (serum ≥4 days, urine ≥6 days) but does not report calculated t₁/₂. No formal pharmacokinetic study exists.

6. **Australian and German legal status:** Not confirmed from available sources.

7. **TAAR1 activity:** Simmler et al. 2014 notes TAAR1 evaluation for the compound class but specific Ki for MDAI at TAAR1 not reported in available abstract.

8. **5-HT₂B receptor activity:** Not evaluated in published literature. This receptor is relevant to cardiac toxicity (valvulopathy) with chronic use of serotonergic drugs.

### Safety-Critical Flags

**FLAG 1 — Tramadol "lethal" interaction:** The database classifies MDAI + tramadol as lethal. No published case reports or experimental studies specifically documenting a MDAI+tramadol fatality were found in PubMed, OpenAlex, or Erowid. The pharmacological basis is sound (both are serotonergic; combined serotonin syndrome risk is substantial). However, this specific severity label requires a published source for verification before the generation agent uses it as a stated fact.

**FLAG 2 — Rat SC LD₅₀ vs. human dosing context:** The SC rat LD₅₀ of 28.33 mg/kg (Palenicek 2016 [Ref 7]) is for subcutaneous injection, not oral route. Users report oral doses of 100–300 mg (roughly 1.5–5 mg/kg for a 60 kg person). The oral route in rats had no deaths at 40 mg/kg. Presenting the SC LD₅₀ without this context could be misleading. The generation agent should clearly note the route discrepancy.

**FLAG 3 — Temperature discrepancy (rat vs. human):** Rats showed hyperthermia at 10–20 mg/kg SC. Human subjects showed no temperature increase at 3 mg/kg oral (Angerer 2024 [Ref 1]). This discrepancy is unexplained and should be stated explicitly — it may reflect species, route, dose, or setting differences. The generation agent should not assert "MDAI causes hyperthermia in humans" based on rat data.

**FLAG 4 — Non-neurotoxicity claim:** "Non-neurotoxic" is frequently repeated but rests on a single 1990 rodent study under conditions that may not translate to repeated human use. This claim should be contextualized carefully.

**FLAG 5 — HepG2 cytotoxicity significance:** Strong in vitro hepatic cytotoxicity (Richter 2019 [Ref 3]) is notable but its clinical relevance is uncertain. HepG2 cells lack full phase I/II metabolic capacity. No human hepatic adverse events are documented in the available case reports.

**FLAG 6 — Dose data in seed vs. human study:** The seed data gives common dose as 100–175 mg oral. The only controlled human study used 3 mg/kg (180–228 mg for the participants, who weighed 60–76 kg). This is higher than the seed data's "common" range and substantially higher than the "threshold" of 40 mg. The generation agent should note this discrepancy and use the human study dose as a reference anchor while maintaining the community-sourced lower-end thresholds.