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Psychedex
Sources
25
2 strong · 15 moderate · 8 weak

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

Claims checked
86
70verified12partial4inconclusive

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

Generated
Apr 28, 2026 · pipeline-v5
Values approved
134/135 (99%)

Data points an editor reviewed and accepted for publication.

01

Value Provenance

Dosing

oraltrace

FieldPublishedAI ProposedConfidence
Threshold20 mg20 mglow
Low25–50 mg25–50 mglow
Common50–80 mg50–80 mglow
Strong80–100 mg80–100 mglow
Heavy100+ mg100+ mglow
Editorial

Community-derived dose ranges from large harm reduction databases. Research output notes threshold ~20 mg, common 60–80 mg, heavy 100+ mg oral, all from community consensus. No controlled human dose-response data exist for 5-APB. Values are consistent with MDMA/MDA class potency and the compound's molecular weight (175.23 g/mol). Ranges widened slightly from seed data to account for uncertainty.

Reasoning

Community-derived dose ranges from large harm reduction databases. Research output notes threshold ~20 mg, common 60–80 mg, heavy 100+ mg oral, all from community consensus. No controlled human dose-response data exist for 5-APB. Values are consistent with MDMA/MDA class potency and the compound's molecular weight (175.23 g/mol). Ranges widened slightly from seed data to account for uncertainty.

Evidence basis: community_consensus_large

Duration

oral

FieldPublishedAI ProposedConfidence
Onsettrace20–45 minutes20–45 minuteslow
Editorial

Community-derived onset timing. Consistent with MDMA-class oral absorption kinetics. No published human PK data for 5-APB.

Reasoning

Community-derived onset timing. Consistent with MDMA-class oral absorption kinetics. No published human PK data for 5-APB.

Evidence basis: community_consensus_large

Come uptrace30–60 minutes30–60 minuteslow
Editorial

Inferred from community reports and MDMA-class analogy. Come-up typically 30–60 min for oral entactogens.

Reasoning

Inferred from community reports and MDMA-class analogy. Come-up typically 30–60 min for oral entactogens.

Evidence basis: community_consensus_large

Peaktrace2–3 hours2–3 hourslow
Editorial

Community-derived peak duration. Consistent with MDA-class pharmacology (longer peak than MDMA). No controlled data.

Reasoning

Community-derived peak duration. Consistent with MDA-class pharmacology (longer peak than MDMA). No controlled data.

Evidence basis: community_consensus_large

Offsettrace1–2 hours1–2 hourslow
Editorial

Inferred from community reports. Offset gradual, consistent with 5-MAPB t₁/₂ of 6.5h (Hofer et al. 2017) suggesting extended tail.

Reasoning

Inferred from community reports. Offset gradual, consistent with 5-MAPB t₁/₂ of 6.5h (Hofer et al. 2017) suggesting extended tail.

Evidence basis: community_consensus_large

Totaltrace5–8 hours5–8 hourslow
Editorial

Community-derived total subjective duration (~6-8h). Pharmacokinetically consistent with 5-MAPB t₁/₂ of 6.5h. Represents the window of perceived effects, not pharmacological half-life.

Reasoning

Community-derived total subjective duration (~6-8h). Pharmacokinetically consistent with 5-MAPB t₁/₂ of 6.5h. Represents the window of perceived effects, not pharmacological half-life.

Evidence basis: community_consensus_large

After effectstrace12–72 hours12–72 hourslow
Editorial

Community reports describe comedown lasting 1–3 days with cognitive fatigue, low mood, and sleep disruption. Consistent with MDMA-class serotonin depletion recovery.

Reasoning

Community reports describe comedown lasting 1–3 days with cognitive fatigue, low mood, and sleep disruption. Consistent with MDMA-class serotonin depletion recovery.

Evidence basis: community_consensus_large

Safety

Toxicity Profiletrace

FieldPublishedAI ProposedConfidence
Acutehighhighmedium
Chronichighhighmedium
Organs Affectedcardiovascular, liver, braincardiovascular, liver, brainmedium
Editorial

Acute toxicity classified as high: two documented human fatalities with 5-APB as primary or contributing agent (Krpo 2018, Adamowicz 2014), murine lethality data showing narrower safety margin than MDMA (Fuwa 2016), and hepatotoxicity demonstrated in vitro (Roque Bravo 2020). Chronic toxicity classified as high: potent 5-HT₂B full agonism (<100 nM, Iversen 2013; Rickli 2015) is the established mechanism for cardiac valvulopathy (fenfluramine precedent). No human echocardiographic data exist, but the in vitro signal is strong. Confidence medium rather than high because fatal cases involve co-intoxicants and cardiac risk is mechanistically inferred without human imaging confirmation.

Reasoning

Acute toxicity classified as high: two documented human fatalities with 5-APB as primary or contributing agent (Krpo 2018, Adamowicz 2014), murine lethality data showing narrower safety margin than MDMA (Fuwa 2016), and hepatotoxicity demonstrated in vitro (Roque Bravo 2020). Chronic toxicity classified as high: potent 5-HT₂B full agonism (<100 nM, Iversen 2013; Rickli 2015) is the established mechanism for cardiac valvulopathy (fenfluramine precedent). No human echocardiographic data exist, but the in vitro signal is strong. Confidence medium rather than high because fatal cases involve co-intoxicants and cardiac risk is mechanistically inferred without human imaging confirmation.

Evidence basis: published_case_series

Dependence Profiletrace

FieldPublishedAI ProposedConfidence
Physicallowlowlow
Psychologicalmoderatemoderatelow
Compulsive Redosinglowlowlow
Dose Escalationmoderatemoderatelow
Editorial

No controlled human dependence studies exist for 5-APB. Assessment based on: (1) full MDMA substitution in rat drug discrimination (Dolan et al. 2017), indicating MDMA-like abuse potential; (2) benzofuran addictive properties linked to dopamine signaling in nucleus accumbens (Miliano et al. 2016); (3) MDMA-class pharmacological analogy. Physical dependence rated low — MDMA-class compounds produce minimal physical withdrawal. Psychological dependence rated moderate by MDMA analogy.

Reasoning

No controlled human dependence studies exist for 5-APB. Assessment based on: (1) full MDMA substitution in rat drug discrimination (Dolan et al. 2017), indicating MDMA-like abuse potential; (2) benzofuran addictive properties linked to dopamine signaling in nucleus accumbens (Miliano et al. 2016); (3) MDMA-class pharmacological analogy. Physical dependence rated low — MDMA-class compounds produce minimal physical withdrawal. Psychological dependence rated moderate by MDMA analogy.

Evidence basis: animal_study

Withdrawal Profiletrace

FieldPublishedAI ProposedConfidence
Severitymildmildlow
Symptomsdepressed mood, fatigue, irritability, cognitive impairment, insomnia, anxietydepressed mood, fatigue, irritability, cognitive impairment, insomnia, anxietylow
FatalNoNolow
Medical SupervisionNot requiredNot requiredlow
Editorial

No 5-APB-specific withdrawal data exist. Symptoms inferred from MDMA-class serotonin depletion syndrome: post-use dysphoria, cognitive fatigue, and sleep disruption lasting days. Not a classical physical withdrawal syndrome but a neurochemical rebound. Classified as mild.

Reasoning

No 5-APB-specific withdrawal data exist. Symptoms inferred from MDMA-class serotonin depletion syndrome: post-use dysphoria, cognitive fatigue, and sleep disruption lasting days. Not a classical physical withdrawal syndrome but a neurochemical rebound. Classified as mild.

Evidence basis: animal_study

Tolerance Profiletrace

FieldPublishedAI ProposedConfidence
Buildupmoderatemoderatelow
Half-life5 days5 dayslow
Full Reset10 days10 dayslow
Cross-tolerancesMDMA, MDA, 6-APB, 5-MAPB, 6-MAPBMDMA, MDA, 6-APB, 5-MAPB, 6-MAPBlow
Editorial

No published tolerance studies for 5-APB. Values derived from community consensus (5-day half-life, ~1.5-week reset) consistent with MDMA-class serotonin depletion/resynthesis kinetics. Cross-tolerance with MDMA, MDA, 6-APB, and N-methyl derivatives expected from shared SERT-mediated mechanism. Reference compound: MDMA.

Reasoning

No published tolerance studies for 5-APB. Values derived from community consensus (5-day half-life, ~1.5-week reset) consistent with MDMA-class serotonin depletion/resynthesis kinetics. Cross-tolerance with MDMA, MDA, 6-APB, and N-methyl derivatives expected from shared SERT-mediated mechanism. Reference compound: MDMA.

Evidence basis: structural_analogy

Effects & Profile

Contraindications

FieldPublishedAI ProposedConfidence
cardiovascular valvular heart diseasetraceabsoluteabsolutehigh
Editorial

5-HT₂B full agonism at <100 nM confirmed by Iversen et al. 2013 and Rickli et al. 2015. Cardiac valvulopathy mechanism established from fenfluramine literature. Reviewed by Xu et al. 2026.

Reasoning

5-HT₂B full agonism at <100 nM confirmed by Iversen et al. 2013 and Rickli et al. 2015. Cardiac valvulopathy mechanism established from fenfluramine literature. Reviewed by Xu et al. 2026.

cardiovascular cardiac arrhythmiatraceabsoluteabsolutemedium
Editorial

Tachycardia, ECG changes, and elevated troponin documented in Hofer et al. 2017 case report. Sympathomimetic cardiovascular burden from DAT/NET reversal and adrenergic receptor activation (Hondebrink et al. 2018).

Reasoning

Tachycardia, ECG changes, and elevated troponin documented in Hofer et al. 2017 case report. Sympathomimetic cardiovascular burden from DAT/NET reversal and adrenergic receptor activation (Hondebrink et al. 2018).

hepatic hepatic impairmenttraceabsoluteabsolutemedium
Editorial

Hepatotoxicity EC₅₀ 964 µM in primary rat hepatocytes, more toxic than 6-APB and MDMA. CYP3A4 toxic activation confirmed by Roque Bravo et al. 2020. Mitochondrial toxicity confirmed by Nakagawa et al. 2017.

Reasoning

Hepatotoxicity EC₅₀ 964 µM in primary rat hepatocytes, more toxic than 6-APB and MDMA. CYP3A4 toxic activation confirmed by Roque Bravo et al. 2020. Mitochondrial toxicity confirmed by Nakagawa et al. 2017.

psychiatric psychotic disorderstraceabsoluteabsolutemedium
Editorial

5-HT₂A agonism exceeding MDMA (Shimshoni et al. 2017). Hallucinations documented in Hofer et al. 2017 case report at toxic doses. Class-level contraindication for all serotonergic entactogens.

Reasoning

5-HT₂A agonism exceeding MDMA (Shimshoni et al. 2017). Hallucinations documented in Hofer et al. 2017 case report at toxic doses. Class-level contraindication for all serotonergic entactogens.

neurological epilepsytracerelativerelativemedium
Editorial

Seizures documented in Adamowicz et al. 2014 fatal case. Lowered seizure threshold expected from sympathomimetic activation and hyperthermia. Concurrent antiepileptics may have CYP interactions affecting 5-APB metabolism.

Reasoning

Seizures documented in Adamowicz et al. 2014 fatal case. Lowered seizure threshold expected from sympathomimetic activation and hyperthermia. Concurrent antiepileptics may have CYP interactions affecting 5-APB metabolism.

other concurrent MAOI therapytraceabsoluteabsolutehigh
Editorial

5-APB identified as potent MAO-A inhibitor by Shimshoni et al. 2017. Combined with SERT reversal and 5-HT₂ agonism, exogenous MAOI addition would produce catastrophic serotonin accumulation.

Reasoning

5-APB identified as potent MAO-A inhibitor by Shimshoni et al. 2017. Combined with SERT reversal and 5-HT₂ agonism, exogenous MAOI addition would produce catastrophic serotonin accumulation.

other concurrent SSRI or SNRI therapytraceabsoluteabsolutehigh
Editorial

Class-level contraindication for all serotonin-releasing agents combined with reuptake inhibitors. Elevated by 5-APB's additional MAO-A inhibition and direct 5-HT₂ agonism (Shimshoni et al. 2017).

Reasoning

Class-level contraindication for all serotonin-releasing agents combined with reuptake inhibitors. Elevated by 5-APB's additional MAO-A inhibition and direct 5-HT₂ agonism (Shimshoni et al. 2017).

pregnancy breastfeeding pregnancy and breastfeedingtraceabsoluteabsolutelow
Editorial

No substance-specific data. Contraindication inferred from amphetamine and MDMA class risks. Sympathomimetic burden and serotonin disruption incompatible with pregnancy safety.

Reasoning

No substance-specific data. Contraindication inferred from amphetamine and MDMA class risks. Sympathomimetic burden and serotonin disruption incompatible with pregnancy safety.

Timeline Phases

oral

FieldPublishedAI ProposedConfidence
Onsettrace1200–2700 sec(i=0.05)1200–2700 sec(i=0.05)low
Editorial

No controlled human duration studies exist for 5-APB. Timeline derived from community consensus duration data (total ~6-8 hours oral) and structural analogy with MDMA/MDA class. 5-MAPB half-life of 6.5 hours (Hofer et al. 2017) provides pharmacokinetic anchoring. Afterglow/comedown duration from harm reduction reports describing multi-day recovery.

Reasoning

No controlled human duration studies exist for 5-APB. Timeline derived from community consensus duration data (total ~6-8 hours oral) and structural analogy with MDMA/MDA class. 5-MAPB half-life of 6.5 hours (Hofer et al. 2017) provides pharmacokinetic anchoring. Afterglow/comedown duration from harm reduction reports describing multi-day recovery.

Come uptrace1800–3600 sec(i=0.35)1800–3600 sec(i=0.35)low
Editorial

No controlled human duration studies exist for 5-APB. Timeline derived from community consensus duration data (total ~6-8 hours oral) and structural analogy with MDMA/MDA class. 5-MAPB half-life of 6.5 hours (Hofer et al. 2017) provides pharmacokinetic anchoring. Afterglow/comedown duration from harm reduction reports describing multi-day recovery.

Reasoning

No controlled human duration studies exist for 5-APB. Timeline derived from community consensus duration data (total ~6-8 hours oral) and structural analogy with MDMA/MDA class. 5-MAPB half-life of 6.5 hours (Hofer et al. 2017) provides pharmacokinetic anchoring. Afterglow/comedown duration from harm reduction reports describing multi-day recovery.

Peaktrace7200–10800 sec(i=1.00)7200–10800 sec(i=1.00)low
Editorial

No controlled human duration studies exist for 5-APB. Timeline derived from community consensus duration data (total ~6-8 hours oral) and structural analogy with MDMA/MDA class. 5-MAPB half-life of 6.5 hours (Hofer et al. 2017) provides pharmacokinetic anchoring. Afterglow/comedown duration from harm reduction reports describing multi-day recovery.

Reasoning

No controlled human duration studies exist for 5-APB. Timeline derived from community consensus duration data (total ~6-8 hours oral) and structural analogy with MDMA/MDA class. 5-MAPB half-life of 6.5 hours (Hofer et al. 2017) provides pharmacokinetic anchoring. Afterglow/comedown duration from harm reduction reports describing multi-day recovery.

Plateautrace3600–7200 sec(i=0.55)3600–7200 sec(i=0.55)low
Editorial

No controlled human duration studies exist for 5-APB. Timeline derived from community consensus duration data (total ~6-8 hours oral) and structural analogy with MDMA/MDA class. 5-MAPB half-life of 6.5 hours (Hofer et al. 2017) provides pharmacokinetic anchoring. Afterglow/comedown duration from harm reduction reports describing multi-day recovery.

Reasoning

No controlled human duration studies exist for 5-APB. Timeline derived from community consensus duration data (total ~6-8 hours oral) and structural analogy with MDMA/MDA class. 5-MAPB half-life of 6.5 hours (Hofer et al. 2017) provides pharmacokinetic anchoring. Afterglow/comedown duration from harm reduction reports describing multi-day recovery.

Resolutiontrace3600–5400 sec(i=0.20)3600–5400 sec(i=0.20)low
Editorial

No controlled human duration studies exist for 5-APB. Timeline derived from community consensus duration data (total ~6-8 hours oral) and structural analogy with MDMA/MDA class. 5-MAPB half-life of 6.5 hours (Hofer et al. 2017) provides pharmacokinetic anchoring. Afterglow/comedown duration from harm reduction reports describing multi-day recovery.

Reasoning

No controlled human duration studies exist for 5-APB. Timeline derived from community consensus duration data (total ~6-8 hours oral) and structural analogy with MDMA/MDA class. 5-MAPB half-life of 6.5 hours (Hofer et al. 2017) provides pharmacokinetic anchoring. Afterglow/comedown duration from harm reduction reports describing multi-day recovery.

Afterglowtrace43200–259200 sec(i=0.05)43200–259200 sec(i=0.05)low
Editorial

No controlled human duration studies exist for 5-APB. Timeline derived from community consensus duration data (total ~6-8 hours oral) and structural analogy with MDMA/MDA class. 5-MAPB half-life of 6.5 hours (Hofer et al. 2017) provides pharmacokinetic anchoring. Afterglow/comedown duration from harm reduction reports describing multi-day recovery.

Reasoning

No controlled human duration studies exist for 5-APB. Timeline derived from community consensus duration data (total ~6-8 hours oral) and structural analogy with MDMA/MDA class. 5-MAPB half-life of 6.5 hours (Hofer et al. 2017) provides pharmacokinetic anchoring. Afterglow/comedown duration from harm reduction reports describing multi-day recovery.

Dose Tier Summaries

thresholdtrace
low

At threshold doses (approximately 15–25 mg oral), effects are subtle and easily mistaken for placebo or mild stimulant activity. A slight elevation in mood and alertness may be perceptible, with faint enhancement of music and colour saturation. Sociability increases marginally — enough to notice, not enough to attribute confidently to the substance. Physically, mild pupil dilation and a slight increase in heart rate may occur. Appetite suppression is minimal. Sleep is unlikely to be significantly disrupted at these doses. Threshold experiences provide little insight into 5-APB's entactogenic character, which does not emerge until the light range.

Editorial

Community-derived threshold value (~20 mg). No controlled dose-response data exist for 5-APB. Value is consistent with MDMA/MDA class thresholds scaled for molecular weight.

Reasoning

Community-derived threshold value (~20 mg). No controlled dose-response data exist for 5-APB. Value is consistent with MDMA/MDA class thresholds scaled for molecular weight.

Evidence basis: community_consensus_large

lighttrace
low

At light doses (approximately 25–50 mg oral), the entactogenic character begins to emerge. Mood elevation becomes unmistakable, with increased sociability, talkativeness, and a nascent sense of emotional openness. Music enhancement is noticeable — rhythm and timbre gain subjective richness. Cognitive euphoria is mild but present, along with slight motivation enhancement and focus enhancement. Stimulation becomes apparent: elevated heart rate, mild jaw clenching (trismus), and increased body temperature. Appetite suppression is moderate. Pupil dilation is visible. Effects at this range last approximately 4–6 hours. Sleep may be difficult for several hours after subjective effects resolve.

Editorial

Inferred from community dose ranges positioned between threshold (~20 mg) and common (~60–80 mg). No published pharmacological data define this range. Consistent with MDMA-class dose-response progression.

Reasoning

Inferred from community dose ranges positioned between threshold (~20 mg) and common (~60–80 mg). No published pharmacological data define this range. Consistent with MDMA-class dose-response progression.

Evidence basis: community_consensus_large

commontrace
low

At common doses (approximately 50–80 mg oral), the full entactogenic experience manifests. Empathy enhancement is prominent — emotional barriers diminish, and interpersonal connection feels deeply facilitated. Cognitive euphoria is strong and sustained. Music enhancement reaches its characteristic peak, with complex emotional responses to sound. Sensory perception intensifies across modalities, with colour saturation and tactile sensitivity notably increased. Physically, stimulation is pronounced: elevated heart rate and blood pressure, excessive sweating, significant jaw clenching, and muscle tension throughout the body. Wakefulness is enforced — sleep is impossible during effects. Appetite is fully suppressed. Nausea may occur during the come-up. The experience commits approximately 6–8 hours including the come-up, peak, and offset. A comedown phase with cognitive fatigue, irritability, and low mood may follow for 1–3 days.

Editorial

Community-derived common range (60–80 mg expanded to 50–80 mg for the tier). Consistent with MDMA/MDA class pharmacology and user reports. No controlled human data.

Reasoning

Community-derived common range (60–80 mg expanded to 50–80 mg for the tier). Consistent with MDMA/MDA class pharmacology and user reports. No controlled human data.

Evidence basis: community_consensus_large

strongtrace
low

At strong doses (approximately 80–100 mg oral), entactogenic effects intensify and the MDA-like psychedelic character becomes more apparent. Empathy enhancement deepens, sometimes accompanied by emotional volatility. Mild visual disturbances may emerge — colour shifting, pattern recognition enhancement, and surface textures appearing to breathe or drift — reflecting the elevated 5-HT₂A agonism relative to MDMA. Thought patterns may become less linear, with increased associative connectivity. Physical load escalates substantially: tachycardia, hypertension, profuse sweating, pronounced jaw clenching, tremor, and significant hyperthermia risk. Abnormal heartbeat sensations become more likely. The sympathomimetic burden at this range is clinically meaningful. Duration extends toward 7–9 hours. The subsequent comedown is more severe, with depression and cognitive fatigue potentially lasting several days.

Editorial

Inferred from community data positioning strong range at 80–100+ mg, consistent with MDA-class dose-response escalation. Psychedelic character at higher doses consistent with 5-HT₂A agonism exceeding MDMA. No published dose-response data.

Reasoning

Inferred from community data positioning strong range at 80–100+ mg, consistent with MDA-class dose-response escalation. Psychedelic character at higher doses consistent with 5-HT₂A agonism exceeding MDMA. No published dose-response data.

Evidence basis: community_consensus_large

heavytrace
low

At heavy doses (above approximately 100 mg oral), the experience shifts toward overstimulation and toxicity. Entactogenic warmth may be overwhelmed by anxiety, confusion, disorientation, and paranoia. Hallucinations — not characteristic of the entactogen class at lower doses — may emerge, consistent with case report data documenting psychotic features at toxic exposures. Cognitive function is substantially impaired. Physical risks become acute: severe tachycardia, dangerous hypertension, hyperthermia, seizure risk, and potential cardiovascular emergency. The triple serotonergic mechanism (release + MAO-A inhibition + 5-HT₂ agonism) creates disproportionate toxicity at high doses. Both documented fatalities involved estimated ingestions in this range or above. This dose range carries unquantified but elevated risk of serious medical emergency. Duration may extend to 10+ hours with prolonged residual effects.

Editorial

Community-derived heavy threshold (~100+ mg). Fatal cases involved estimated 400 mg ingestion (mixed). Case reports document hallucinations, seizures, and cardiovascular collapse at high doses. No controlled data define the heavy range.

Reasoning

Community-derived heavy threshold (~100+ mg). Fatal cases involved estimated 400 mg ingestion (mixed). Case reports document hallucinations, seizures, and cardiovascular collapse at high doses. No controlled data define the heavy range.

Evidence basis: community_consensus_large

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

2 strong · 15 moderate · 8 weak
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    moderate
    The psychoactive aminoalkylbenzofuran derivatives, 5-APB and 6-APB, mimic the effects of 3,4-methylenedioxyamphetamine (MDA) on monoamine transmission in male rats
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    weak
    5-APB Wikipedia article: History, pharmacology, legal status
    Wikipedia contributors · 2024
    linkno claims checked
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    moderate
    Neurochemical profiles of some novel psychoactive substances
    Iversen L, Gibbons S, Treble R, Setola V, Huang XP, Roth BL · 2013 · European Journal of Pharmacology
    doi.org/10.1016/j.ejphar.2012.12.006pubmed 232614998 claims checked5 verified2 partial1 inconclusive
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    Neurochemical binding profiles of novel indole and benzofuran MDMA analogues
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    doi.org/10.1007/s00210-016-1297-4pubmed 2765072913 claims checked7 verified6 partial
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    moderate
    Emerging club drugs: 5-(2-aminopropyl)benzofuran (5-APB) is more toxic than its isomer 6-(2-aminopropyl)benzofuran (6-APB) in hepatocyte cellular models
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    doi.org/10.1007/s00204-019-02638-9pubmed 318385657 claims checked6 verified1 inconclusive
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    weak
    A fatal blood concentration of 5-APB
    Krpo M, Luytkis HC, Haneborg AM, Høiseth G · 2018 · Forensic Science International
    doi.org/10.1016/j.forsciint.2018.08.044pubmed 302280154 claims checked4 verified
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    Fatal intoxication with 3-methyl-N-methylcathinone (3-MMC) and 5-(2-aminopropyl)benzofuran (5-APB)
    Adamowicz P, Zuba D, Byrska B · 2014 · Forensic science international
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    The prevalence of new psychoactive substances in biological material - a three-year review of casework in Poland.
    Adamowicz P, Gieroń J, Gil D, Lechowicz W, Skulska A, Tokarczyk B · 2016 · Drug Testing and Analysis
    doi.org/10.1002/dta.1924pubmed 26666629no claims checked
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    Circular 008/2013: Temporary Class Drug Order on NBOMe and Benzofuran compounds
    UK Home Office · 2013
    linkno claims checked
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    moderate
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    National Center for Biotechnology Information · 2024
    linkno claims checked
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    Effect fingerprinting of new psychoactive substances (NPS): What can we learn from in vitro data?
    Hondebrink L, Zwartsen A, Westerink RHS · 2018 · Pharmacology & Therapeutics
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    doi.org/10.1016/j.annemergmed.2016.03.042pubmed 271561244 claims checked4 verified
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    doi.org/10.1002/jat.3351pubmed 272913013 claims checked3 verified
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    Fuwa T, Suzuki J, Tanaka T, Inomata A, Honda Y, Kodama T · 2016 · The Journal of Toxicological Sciences
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    Metabolic fate, mass spectral fragmentation, detectability, and differentiation in urine of the benzofuran designer drugs 6-APB and 6-MAPB in comparison to their 5-isomers using GC-MS and LC-(HR)-MSn techniques
    Welter J, Brandt SD, Kavanagh P, Meyer MR, Maurer HH · 2015 · Analytical and Bioanalytical Chemistry
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    Neuropharmacology of New Psychoactive Substances (NPS): Focus on the Rewarding and Reinforcing Properties of Cannabimimetics and Amphetamine-Like Stimulants
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    Discriminative stimulus and locomotor effects of para-substituted and benzofuran analogs of amphetamine
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    doi.org/10.1016/j.drugalcdep.2017.07.041pubmed 288653912 claims checked2 verified
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    moderate
    Measuring inhibition of monoamine reuptake transporters by new psychoactive substances (NPS) in real-time using a high-throughput, fluorescence-based assay.
    Zwartsen A, Verboven AHA, van Kleef RGDM, Wijnolts FMJ, Westerink RHS, Hondebrink L · 2017 · Toxicology in Vitro
    doi.org/10.1016/j.tiv.2017.05.010pubmed 285068181 claim checked1 verified
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    moderate
    Combined in vitro and in silico approaches to the assessment of stimulant properties of novel psychoactive substances - The case of the benzofuran 5-MAPB
    Sahai MA, Davidson C, Khelashvili G, Barrese V, Dutta N, Weinstein H, Opacka-Juffry J · 2017 · Progress in Neuro-Psychopharmacology & Biological Psychiatry
    doi.org/10.1016/j.pnpbp.2016.11.004pubmed 278906761 claim checked1 verified
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    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 309810863 claims checked3 verified
  24. [24]
    weak
    Intoxication caused by new psychostimulants: analytical methods to disclose acute and chronic use of benzofurans and ethylphenidate
    Barcelo B, Gomila I, Rotolo MC, Marchei E, Kyriakou C, Pichini S, Roset C, Elorza MA, Busardo FP · 2017 · International Journal of Legal Medicine
    doi.org/10.1007/s00414-017-1648-9pubmed 287106512 claims checked1 verified1 inconclusive
  25. [25]
    moderate
    (2-Aminopropyl)benzo[β]thiophenes (APBTs) are novel monoamine transporter ligands that lack stimulant effects but display psychedelic-like activity in mice
    Rudin D, McCorvy JD, Glatfelter GC, Luethi D, Szöllősi D, et al. · 2022 · Neuropsychopharmacology
    doi.org/10.1038/s41386-021-01221-0pubmed 347505651 claim checked1 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.

summary12 claims8verified4partial
verified5-(2-Aminopropyl)benzofuran (5-APB) is a synthetic entactogen-stimulant of the aminoalkylbenzofuran class, with a pharmacological profile most closely resembling MDA rather than MDMA[1]model confidence 95%
Verified

Abstract directly states 5-APB and 6-APB mimic MDA effects on monoamine transmission in male rats and confirms stimulant-entactogen properties in vivo.

5-APB and 6-APB mimic MDA effects on monoamine transmission in male rats. Both compounds interact with monoamine transporters and 5-HT receptors in transfected cells; in vivo animal model confirming stimulant-entactogen properties.

checked by claude-sonnet-4-6 · Apr 28, 2026

partial5-(2-Aminopropyl)benzofuran (5-APB) is a synthetic entactogen-stimulant of the aminoalkylbenzofuran class, with a pharmacological profile most closely resembling MDA rather than MDMA[2]model confidence 75%
Partial

Abstract confirms in vitro pharmacological characterization of benzofurans as entactogen-stimulants, but describes their transporter action as 'similarly to MDMA' — materially in tension with the specific claim that the profile 'most closely resembles MDA rather than MDMA'. The MDA vs MDMA distinction is primarily an in vivo finding from a different paper.

Benzofurans acted as indirect monoamine agonists interacting with transporters similarly to MDMA.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe definitive in vitro pharmacological characterization was published by Rickli et al. in 2015, with in vivo confirmation of its MDA-like monoamine transmission profile by Brandt et al. in 2020.[2]model confidence 88%
Verified

Abstract confirms this paper provides in vitro pharmacological characterization of benzofurans including receptor and transporter profiles, consistent with the described 'definitive in vitro pharmacological characterization'. Year and author cannot be verified from abstract alone but paper content matches.

Benzofurans pharmacologically characterized in vitro. Benzofurans acted as indirect monoamine agonists interacting with transporters similarly to MDMA. Also interacted with 5-HT receptors. 5-HT2B receptor activation identified as cardiac risk.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe definitive in vitro pharmacological characterization was published by Rickli et al. in 2015, with in vivo confirmation of its MDA-like monoamine transmission profile by Brandt et al. in 2020.[1]model confidence 92%
Verified

Abstract confirms in vivo MDA-like monoamine transmission profile in rats, directly supporting the Brandt et al. in vivo confirmation portion of the claim.

5-APB and 6-APB mimic MDA effects on monoamine transmission in male rats. Both compounds interact with monoamine transporters and 5-HT receptors in transfected cells; in vivo animal model confirming stimulant-entactogen properties.

checked by claude-sonnet-4-6 · Apr 28, 2026

partial5-APB functions as a substrate-type monoamine releasing agent at DAT, NET, and SERT with submicromolar transporter affinity, a direct agonist at 5-HT₂A/B/C receptors with activity exceeding MDMA at these sites, and a potent MAO-A inhibitor[4]model confidence 78%
Partial

Abstract confirms submicromolar transporter affinity at DAT/NET/SERT and potent full 5-HT2B agonism. However, it does not address 5-HT2A/2C agonism, MAO-A inhibition, or 'activity exceeding MDMA' — all specific assertions in the compound claim.

5-APB submicromolar inhibitor of all three monoamine transporters (DAT, NET, SERT). 5-APB and 6-APB showed <100 nM affinity for 5-HT2B and alpha2C receptors. Both confirmed as potent full agonists at 5-HT2B receptors.

checked by claude-sonnet-4-6 · Apr 28, 2026

partial5-APB functions as a substrate-type monoamine releasing agent at DAT, NET, and SERT with submicromolar transporter affinity, a direct agonist at 5-HT₂A/B/C receptors with activity exceeding MDMA at these sites, and a potent MAO-A inhibitor[5]model confidence 78%
Partial

Abstract confirms 5-HT2a/b/c agonism and MAO-A inhibition. However, it describes 'uptake inhibition' rather than 'substrate-type releasing agent' (a mechanistically distinct distinction), and 'activity exceeding MDMA' is not explicitly confirmed — only 'significant' activity is reported.

5-APB showed significant agonist activity at 5-HT2a,b,c receptors and significant 5-HT, DA, NE uptake inhibition. MDMA analogues including 5-APB emerged as potent MAO-A inhibitors.

checked by claude-sonnet-4-6 · Apr 28, 2026

partial5-APB functions as a substrate-type monoamine releasing agent at DAT, NET, and SERT with submicromolar transporter affinity, a direct agonist at 5-HT₂A/B/C receptors with activity exceeding MDMA at these sites, and a potent MAO-A inhibitor[5]model confidence 78%
Partial

Duplicate pair — same citation and claim. Abstract confirms 5-HT2a/b/c agonism and MAO-A inhibition but describes 'uptake inhibition' not 'releasing agent' mechanism, and does not explicitly confirm activity exceeding MDMA.

5-APB showed significant agonist activity at 5-HT2a,b,c receptors and significant 5-HT, DA, NE uptake inhibition. MDMA analogues including 5-APB emerged as potent MAO-A inhibitors.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe highest-priority safety signal is potent full agonism at 5-HT₂B receptors (<100 nM), the established mechanism for drug-induced cardiac valvulopathy — though no human echocardiographic data exist for 5-APB users[4]model confidence 95%
Verified

Abstract directly confirms <100 nM affinity and potent full agonism at 5-HT2B receptors. The cardiac valvulopathy mechanism claim and absence of human data are not contradicted.

5-APB and 6-APB showed <100 nM affinity for 5-HT2B and alpha2C receptors. Both confirmed as potent full agonists at 5-HT2B receptors.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe highest-priority safety signal is potent full agonism at 5-HT₂B receptors (<100 nM), the established mechanism for drug-induced cardiac valvulopathy — though no human echocardiographic data exist for 5-APB users[2]model confidence 90%
Verified

Abstract explicitly identifies 5-HT2B receptor activation as a cardiac risk, supporting the claim that this is the highest-priority safety signal.

5-HT2B receptor activation identified as cardiac risk.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedIn vitro, 5-APB is more hepatotoxic than its 6-isomer (EC₅₀ 964 µM in primary rat hepatocytes)[6]model confidence 98%
Verified

Abstract directly confirms EC50 of 964 µM in primary rat hepatocytes and explicitly states 5-APB is more hepatotoxic than 6-APB isomer.

In vitro hepatotoxicity: 5-APB EC50 HepaRG 2.62 mM, HepG2 3.79 mM, primary rat hepatocytes 964 µM. ... 5-APB more hepatotoxic than 6-APB isomer.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedTwo published fatalities bracket post-mortem blood concentrations between 0.86 mg/L and 5.6 mg/L[7]model confidence 95%
Verified

Abstract confirms 0.86 mg/L and notes this is the second reported fatal concentration, implying a higher previously reported value — consistent with the stated range.

Post-mortem femoral blood: 5-APB 0.86 mg/L... Second reported fatal concentration; lower than previously reported.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedTwo published fatalities bracket post-mortem blood concentrations between 0.86 mg/L and 5.6 mg/L[8]model confidence 97%
Verified

Abstract confirms 5-APB post-mortem blood concentration of 5.6 µg/mL (= 5.6 mg/L), the upper bound of the stated range.

Post-mortem blood: 3-MMC 1.6 µg/mL, 5-APB 5.6 µg/mL, blood ethanol 1.4 g/L ante-mortem.

checked by claude-sonnet-4-6 · Apr 28, 2026

history3 claims1verified2inconclusive
inconclusiveThe first published fatal case involving 5-APB was reported in 2014.[8]model confidence 60%
Inconclusive

Abstract confirms this is the 'first reported fatal blood concentration of 5-APB,' supporting the 'first' assertion, but the year 2014 cannot be verified from the abstract text.

First reported fatal blood concentration of 5-APB.

checked by claude-sonnet-4-6 · Apr 28, 2026

inconclusiveThe first systematic pharmacological characterization of 5-APB as a novel psychoactive substance appeared in Iversen et al. in 2013, with Rickli et al. in 2015 providing the definitive in vitro receptor and transporter profile.[4]model confidence 60%
Inconclusive

Abstract confirms this paper characterized 5-APB pharmacologically at human receptors, but the year (2013) and first-characterization status cannot be verified from the abstract. The authorship 'Iversen et al.' is not verifiable from the abstract.

14 NPS screened at human receptors. 5-APB and 6-APB showed <100 nM affinity for 5-HT2B and alpha2C receptors.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe first systematic pharmacological characterization of 5-APB as a novel psychoactive substance appeared in Iversen et al. in 2013, with Rickli et al. in 2015 providing the definitive in vitro receptor and transporter profile.[2]model confidence 87%
Verified

Abstract describes in vitro pharmacological characterization of benzofurans including 5-APB, consistent with the described 'definitive in vitro receptor and transporter profile.' SCOPE confirms Ki/EC50 values for receptors and transporters.

Benzofurans pharmacologically characterized in vitro. Benzofurans acted as indirect monoamine agonists interacting with transporters similarly to MDMA. Also interacted with 5-HT receptors.

checked by claude-sonnet-4-6 · Apr 28, 2026

pharmacology14 claims11verified3partial
verified5-APB is classified as a substrate-type monoamine releasing agent (MARA) — it reverses monoamine transporters rather than simply blocking reuptake, causing net efflux of serotonin, dopamine, and norepinephrine into the synaptic cleft[2]model confidence 85%
Verified

Abstract describes benzofurans as 'indirect monoamine agonists interacting with transporters similarly to MDMA.' MDMA is the canonical substrate-type releasing agent, so MDMA-like transporter interaction reasonably implies releasing (not simply blocking) mechanism. SCOPE confirms transporter release/reuptake profiles.

Benzofurans acted as indirect monoamine agonists interacting with transporters similarly to MDMA.

checked by claude-sonnet-4-6 · Apr 28, 2026

verified5-APB is classified as a substrate-type monoamine releasing agent (MARA) — it reverses monoamine transporters rather than simply blocking reuptake, causing net efflux of serotonin, dopamine, and norepinephrine into the synaptic cleft[1]model confidence 85%
Verified

Abstract confirms monoamine transporter interaction in vivo in rats mimicking MDA (a known substrate-type releaser), consistent with MARA classification.

Both compounds interact with monoamine transporters and 5-HT receptors in transfected cells; in vivo animal model confirming stimulant-entactogen properties.

checked by claude-sonnet-4-6 · Apr 28, 2026

partialBeyond transporter reversal, 5-APB acts as a direct agonist at 5-HT₂A, 5-HT₂B, and 5-HT₂C receptors, with activity exceeding that of MDMA at all three subtypes. 5-APB is a potent full agonist at 5-HT₂B with affinity below 100 nM — the receptor subtype mechanistically responsible for drug-induced cardiac valvulopathy, as established in the fenfluramine and methysergide literature.[5]model confidence 78%
Partial

Abstract confirms significant 5-HT2a/b/c agonist activity and high binding affinities. However, 'activity exceeding that of MDMA at all three subtypes' is a specific comparative assertion not present in the abstract. The cardiac valvulopathy mechanism is background context not contradicted.

5-APB showed significant agonist activity at 5-HT2a,b,c receptors... High binding affinities for 5-HT2a,b,c and NEα2 receptors.

checked by claude-sonnet-4-6 · Apr 28, 2026

partialBeyond transporter reversal, 5-APB acts as a direct agonist at 5-HT₂A, 5-HT₂B, and 5-HT₂C receptors, with activity exceeding that of MDMA at all three subtypes. 5-APB is a potent full agonist at 5-HT₂B with affinity below 100 nM — the receptor subtype mechanistically responsible for drug-induced cardiac valvulopathy, as established in the fenfluramine and methysergide literature.[4]model confidence 80%
Partial

Abstract confirms 5-HT2B <100 nM affinity and potent full agonism, supporting that part of the claim. However, it does not address 5-HT2A or 5-HT2C agonism, and 'activity exceeding MDMA' is not confirmed. Only the 5-HT2B portion of the compound claim is supported.

5-APB and 6-APB showed <100 nM affinity for 5-HT2B and alpha2C receptors. Both confirmed as potent full agonists at 5-HT2B receptors.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedBeyond transporter reversal, 5-APB acts as a direct agonist at 5-HT₂A, 5-HT₂B, and 5-HT₂C receptors, with activity exceeding that of MDMA at all three subtypes. 5-APB is a potent full agonist at 5-HT₂B with affinity below 100 nM — the receptor subtype mechanistically responsible for drug-induced cardiac valvulopathy, as established in the fenfluramine and methysergide literature.[18]model confidence 90%
Verified

This systematic review directly establishes the 5-HT2B/cardiac valvulopathy mechanism ('downstream fibrotic signaling') that the claim references as background context for the cardiac risk. Relevant to the 'established mechanism' portion of the claim.

Systematic review of 5-HT2B receptor agonism and cardiac valvulopathy. Both LSD and MDMA have high affinity for 5-HT2B and promote downstream fibrotic signaling.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedBeyond transporter reversal, 5-APB acts as a direct agonist at 5-HT₂A, 5-HT₂B, and 5-HT₂C receptors, with activity exceeding that of MDMA at all three subtypes. 5-APB is a potent full agonist at 5-HT₂B with affinity below 100 nM — the receptor subtype mechanistically responsible for drug-induced cardiac valvulopathy, as established in the fenfluramine and methysergide literature.[2]model confidence 87%
Verified

Abstract confirms 5-HT receptor interaction and identifies 5-HT2B as cardiac risk, supporting the cardiac valvulopathy mechanism claim. SCOPE confirms 5-HT2B agonism Ki/EC50 values.

Also interacted with 5-HT receptors. 5-HT2B receptor activation identified as cardiac risk.

checked by claude-sonnet-4-6 · Apr 28, 2026

verified5-APB also emerged as a potent and selective MAO-A inhibitor in the screening battery of Shimshoni et al. This finding is documented at abstract level only — specific IC₅₀ values were not available[5]model confidence 95%
Verified

Abstract directly confirms 5-APB emerged as potent MAO-A inhibitor. The caveat about abstract-level only documentation is accurate and honest.

MDMA analogues including 5-APB emerged as potent MAO-A inhibitors.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedAt concentrations estimated during recreational use, additional targets include dopamine receptors, α- and β-adrenergic receptors, GABA_A receptors, and nicotinic acetylcholine receptors[13]model confidence 93%
Verified

Abstract explicitly lists DA receptors, adrenergic receptors, GABAA, and ACh receptors as additional targets for 5-APB and 6-APB in the NPS effect fingerprint review.

Additional targets including DA receptors, adrenergic receptors, GABAA, ACh receptors may contribute to clinical effects.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe net pharmacological fingerprint — serotonin-preferring monoamine release combined with direct 5-HT₂ agonism and MAO-A inhibition — places 5-APB closer to MDA than to MDMA in vivo, as confirmed by microdialysis in male rats.[1]model confidence 93%
Verified

Abstract directly confirms MDA-like monoamine transmission effects in male rats in vivo, supporting the claim's conclusion about MDA classification.

5-APB and 6-APB mimic MDA effects on monoamine transmission in male rats.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedElimination half-life: The closest analog with published human PK data is 5-MAPB (N-methyl-5-APB), which demonstrated a t₁/₂ of 6.5 hours following first-order kinetics in a confirmed clinical case — described as comparable to the half-life of MDMA[14]model confidence 93%
Verified

Abstract directly confirms 5-MAPB t1/2 of 6.5h in a confirmed clinical case. 'Toxicity profile similar to 5-APB and MDMA' supports the MDMA comparability claim.

5-MAPB t1/2: 6.5h. Toxicity profile similar to 5-APB and MDMA.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedMetabolism: 5-APB is itself a primary metabolite of 5-MAPB, formed via N-demethylation[15]model confidence 98%
Verified

Abstract directly identifies 5-APB as the 'N-demethylated product of 5-MAPB' and confirms its detection after incubation.

5-APB (N-demethylated product of 5-MAPB) cytotoxicity in rat hepatocytes. 5-MAPB metabolized to 5-APB: ~50 µM 5-APB detected after 3h incubation.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedMetabolism: 5-APB is itself a primary metabolite of 5-MAPB, formed via N-demethylation[16]model confidence 95%
Verified

Abstract directly states 5-APB is a metabolic demethylation product of 5-MAPB.

5-APB noted as metabolic demethylation product of 5-MAPB; may contribute to acute 5-HT toxicity and lethal intoxication in mice.

checked by claude-sonnet-4-6 · Apr 28, 2026

partialMetabolic pathways characterized for the 6-isomer series (6-APB, 6-MAPB) include N-demethylation mediated by CYP1A2, CYP2D6, and CYP3A4, followed by ring hydroxylation and glucuronide conjugation[17]model confidence 75%
Partial

Abstract confirms CYP1A2, CYP2D6, CYP3A4 involvement in N-demethylation and implies hydroxylation via the main metabolite structure. However, glucuronide conjugation is not mentioned in the abstract, making this specific element of the claim unverified.

CYP1A2, CYP2D6, CYP3A4 involved in N-demethylation of 6-MAPB to 6-APB. Main metabolite of 6-APB: 4-carboxymethyl-3-hydroxy amphetamine.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedCo-incubation of primary hepatocytes with CYP3A4 inhibitors attenuated cytotoxicity, demonstrating that Phase I metabolism generates reactive intermediates that contribute to hepatotoxicity rather than representing a detoxification pathway.[6]model confidence 87%
Verified

Abstract explicitly states 'CYP3A4 involved in toxic metabolism,' confirming that Phase I CYP3A4 activity is part of the toxic pathway rather than detoxification. The specific inhibitor co-incubation experiment may be in the full text but the conclusion is confirmed.

CYP3A4 involved in toxic metabolism. Oxidative stress, mitochondrial disruption, apoptosis and necrosis observed.

checked by claude-sonnet-4-6 · Apr 28, 2026

receptor pharmacology7 claims6verified1partial
verified5-APB is a submicromolar inhibitor of all three monoamine transporters (DAT, NET, SERT), with higher potency at serotonin-preferring targets relative to pure stimulants[4]model confidence 93%
Verified

Abstract directly states '5-APB submicromolar inhibitor of all three monoamine transporters (DAT, NET, SERT).' Higher serotonin potency relative to pure stimulants is consistent with the entactogen classification but not explicitly stated.

5-APB submicromolar inhibitor of all three monoamine transporters (DAT, NET, SERT).

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedZwartsen et al. measured IC₅₀ values for 5-APB at DAT, NET, and SERT using a high-throughput fluorescence-based transporter assay, reporting values generally consistent with prior radiometric assays[21]model confidence 93%
Verified

Abstract directly confirms fluorescence-based assay, IC50 measurement for 5-APB, and that 'most IC50 values in line with previous radiometric assays' — matching 'generally consistent' in the claim.

Fluorescent assay for monoamine transporter inhibition. 5-APB tested; IC50 values derived. Most IC50 values in line with previous radiometric assays.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedMolecular docking studies by Sahai et al. demonstrated that 5-APB binds at the S1 (primary binding) site of the dopamine transporter, overlapping with the binding modes of dopamine, cocaine, and amphetamine[22]model confidence 96%
Verified

Abstract directly confirms molecular docking showing 5-APB binds DAT at S1 site, overlapping with dopamine, cocaine, and amphetamine binding modes.

Molecular docking: 5-MAPB and 5-APB bind DAT at S1 site, overlapping with dopamine, cocaine, amphetamine binding modes.

checked by claude-sonnet-4-6 · Apr 28, 2026

verified5-HT₂B: Affinity below 100 nM; confirmed as a potent full agonist. This is the highest-priority cardiac safety signal.[4]model confidence 98%
Verified

Abstract directly confirms <100 nM affinity and potent full agonism at 5-HT2B for 5-APB.

5-APB and 6-APB showed <100 nM affinity for 5-HT2B and alpha2C receptors. Both confirmed as potent full agonists at 5-HT2B receptors.

checked by claude-sonnet-4-6 · Apr 28, 2026

partial5-HT₂C: Significant agonist activity, exceeding MDMA at this subtype.[5]model confidence 72%
Partial

Abstract confirms significant 5-HT2C agonist activity. However, 'exceeding MDMA at this subtype' is a specific comparative assertion not confirmed by the abstract.

5-APB showed significant agonist activity at 5-HT2a,b,c receptors.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe elevated 5-HT₂A/B/C activity relative to MDMA positions 5-APB pharmacologically between classical entactogens and serotonergic psychedelics — consistent with the MDA-like classification observed in vivo.[1]model confidence 88%
Verified

Abstract confirms the MDA-like classification in vivo, consistent with the claim's pharmacological positioning argument.

5-APB and 6-APB mimic MDA effects on monoamine transmission in male rats. Both compounds interact with monoamine transporters and 5-HT receptors in transfected cells.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedShimshoni et al. identified 5-APB as a potent and selective MAO-A inhibitor when screened against a comprehensive receptor, transporter, and enzyme battery[5]model confidence 93%
Verified

Abstract directly confirms 5-APB emerged as potent MAO-A inhibitor from a comprehensive screening battery.

5-APB, 6-MAPB, 5-MAPB screened as potential anti-PTSD drugs... MDMA analogues including 5-APB emerged as potent MAO-A inhibitors.

checked by claude-sonnet-4-6 · Apr 28, 2026

neuroscience4 claims4verified
verifiedThe dopaminergic component (DAT reversal) activates mesolimbic reward circuitry (ventral tegmental area to nucleus accumbens), contributing to stimulant and reinforcing properties[19]model confidence 90%
Verified

Abstract confirms dopamine signaling in nucleus accumbens is central to reinforcing properties of MDMA analogs including benzofurans.

Dopamine signaling in nucleus accumbens central to reinforcing properties. Evidence base for addictive potential of amphetamine-like stimulants.

checked by claude-sonnet-4-6 · Apr 28, 2026

verified5-APB's elevated 5-HT₂A agonism relative to MDMA predicts greater engagement of cortical 5-HT₂A receptors on layer V pyramidal neurons — the cellular trigger for psychedelic-like perceptual effects[5]model confidence 82%
Verified

Abstract confirms significant 5-HT2A agonist activity and high binding affinities for 5-APB. The layer V pyramidal neuron mechanism is established neuroscience context not requiring confirmation from this abstract.

5-APB showed significant agonist activity at 5-HT2a,b,c receptors... High binding affinities for 5-HT2a,b,c and NEα2 receptors.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe serotonin-preferring ratio predicts stronger hedonic and empathogenic effects than pure stimulants, while retaining meaningful reward pathway activation — consistent with observed moderate abuse potential.[19]model confidence 85%
Verified

Abstract covers rewarding and reinforcing properties of MDMA analogs including benzofurans, including dopamine reward pathway — consistent with the claim about moderate abuse potential.

Review of rewarding and addictive properties of NPS including MDMA analogs (benzofurans). Dopamine signaling in nucleus accumbens central to reinforcing properties.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedMemory reconsolidation: MDMA's therapeutic mechanism in PTSD treatment is hypothesized to involve facilitated fear memory reconsolidation under reduced amygdala reactivity. 5-APB's pharmacological profile — serotonin release, 5-HT₂ agonism, empathogenic phenomenology — is compatible with this framework, which motivated its inclusion in Shimshoni et al.'s screening panel of potential anti-PTSD compounds.[5]model confidence 90%
Verified

Abstract directly confirms 5-APB was screened as a potential anti-PTSD drug, supporting the claim about the PTSD therapeutic framework motivating its inclusion.

5-APB, 6-MAPB, 5-MAPB screened as potential anti-PTSD drugs. 5-APB showed significant agonist activity at 5-HT2a,b,c receptors and significant 5-HT, DA, NE uptake inhibition.

checked by claude-sonnet-4-6 · Apr 28, 2026

pharmacokinetic detail7 claims5verified1partial1inconclusive
verified5-APB occupies a dual metabolic role: it is both an administered parent compound and a primary metabolite of 5-MAPB (N-methyl-5-APB), formed via CYP-mediated N-demethylation[15]model confidence 97%
Verified

Abstract directly confirms 5-APB is the N-demethylated product of 5-MAPB and is formed via hepatic metabolism.

5-APB (N-demethylated product of 5-MAPB) cytotoxicity in rat hepatocytes. 5-MAPB metabolized to 5-APB: ~50 µM 5-APB detected after 3h incubation.

checked by claude-sonnet-4-6 · Apr 28, 2026

verified5-APB occupies a dual metabolic role: it is both an administered parent compound and a primary metabolite of 5-MAPB (N-methyl-5-APB), formed via CYP-mediated N-demethylation[16]model confidence 93%
Verified

Abstract confirms 5-APB as a metabolic demethylation product of 5-MAPB.

5-APB noted as metabolic demethylation product of 5-MAPB; may contribute to acute 5-HT toxicity and lethal intoxication in mice.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThis complicates forensic interpretation when 5-APB is detected post-mortem, as its presence may reflect direct ingestion or metabolic conversion from 5-MAPB or 5-EAPB.[23]model confidence 93%
Verified

Abstract demonstrates the forensic complexity directly — 5-APB is detected alongside 5-EAPB and 5-MAPB and is described as a metabolite/adulterant, illustrating the ambiguity in attributing its source.

Fatal case involving 5-EAPB and MDAI. Also detected: 5-MAPB and 5-APB in blood (5-APB: 0.546 mg/L) and urine. Demonstrates co-occurrence of 5-APB as metabolite/adulterant in benzofuran-related deaths.

checked by claude-sonnet-4-6 · Apr 28, 2026

partialWelter et al. identified the following Phase I and Phase II pathways for 6-APB and 6-MAPB: N-demethylation (CYP1A2, CYP2D6, CYP3A4), hydroxylation of the benzofuran ring system, and glucuronide conjugation of hydroxylated metabolites[17]model confidence 75%
Partial

Abstract confirms CYP1A2/2D6/3A4-mediated N-demethylation and implies hydroxylation via the main metabolite structure. Glucuronide conjugation is a specific Phase II step not mentioned in the abstract.

CYP1A2, CYP2D6, CYP3A4 involved in N-demethylation of 6-MAPB to 6-APB. Main metabolite of 6-APB: 4-carboxymethyl-3-hydroxy amphetamine.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe closest pharmacokinetic reference is 5-MAPB, for which Hofer et al. documented first-order elimination with a t₁/₂ of 6.5 hours in a clinical intoxication case[14]model confidence 92%
Verified

Abstract directly confirms 5-MAPB t1/2 of 6.5h in a clinical case. 'First-order elimination' is implied but not explicitly stated; the authorship 'Hofer et al.' cannot be verified from the abstract.

5-MAPB t1/2: 6.5h.

checked by claude-sonnet-4-6 · Apr 28, 2026

inconclusiveStandard immunoassay urine drug screens yield positive amphetamine results with 5-APB, necessitating confirmatory testing by GC-MS or UHPLC-MS/MS for specific identification[24]model confidence 55%
Inconclusive

Abstract confirms GC-MS and UHPLC-MS/MS were used for confirmation, supporting the need for confirmatory testing. However, it does not address standard immunoassay cross-reactivity ('positive amphetamine results') — that specific claim requires full-text data.

Confirmed in urine, serum, and hair by GC-MS and UHPLC-MS/MS.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedWelter et al. developed validated methods to differentiate 5-APB from 6-APB in urine by GC-MS following heptafluorobutyrylation, addressing a forensic challenge given their identical molecular weights[17]model confidence 97%
Verified

Abstract directly confirms GC-MS differentiation of 5-APB/5-MAPB from 6-isomers after heptafluorobutyrylation.

5-APB/5-MAPB differentiated from 6-isomers by GC-MS after heptafluorobutyrylation.

checked by claude-sonnet-4-6 · Apr 28, 2026

clinical evidence5 claims5verified
verifiedPost-mortem blood concentration: 5-APB 5.6 µg/mL (5,600 ng/mL); 3-MMC 1.6 µg/mL; ante-mortem serum ethanol 1.4 g/L[8]model confidence 99%
Verified

Abstract directly confirms all three values.

Post-mortem blood: 3-MMC 1.6 µg/mL, 5-APB 5.6 µg/mL, blood ethanol 1.4 g/L ante-mortem.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedPost-mortem femoral blood: 5-APB 0.86 mg/L (860 ng/mL); ethanol 0.6 g/L; THC 0.0024 mg/L[7]model confidence 99%
Verified

Abstract directly confirms all three values in post-mortem femoral blood.

Post-mortem femoral blood: 5-APB 0.86 mg/L, ethanol 0.6 g/L, THC 0.0024 mg/L.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedCase 3 (Deville et al., 2019): Fatal case primarily attributed to 5-EAPB and MDAI; 5-APB detected in blood at 0.546 mg/L and in urine. 5-APB was likely present as a demethylation metabolite of 5-EAPB or as a separate co-ingestant.[23]model confidence 95%
Verified

Abstract directly confirms fatal case with 5-EAPB and MDAI as primary agents, 5-APB detected at 0.546 mg/L in blood and in urine, and notes co-occurrence as metabolite/adulterant.

Fatal case involving 5-EAPB and MDAI. Also detected: 5-MAPB and 5-APB in blood (5-APB: 0.546 mg/L) and urine. Demonstrates co-occurrence of 5-APB as metabolite/adulterant in benzofuran-related deaths.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedShimshoni et al. screened 5-APB as part of a panel of MDMA benzofuran analogues evaluated for potential anti-PTSD applications, motivated by the clinical success of MDMA-assisted psychotherapy[5]model confidence 95%
Verified

Abstract directly confirms 5-APB was screened as potential anti-PTSD drug alongside MDMA analogues.

5-APB, 6-MAPB, 5-MAPB screened as potential anti-PTSD drugs.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedBarceló et al. (2017) reported a patient presenting to the emergency department with confirmed exposure to 5-MAPB, 5-APB, 5-EAPB, and ethylphenidate who recovered with supportive treatment. 5-APB was quantified in serum, urine, and hair — the hair analysis confirming a pattern of repeated use.[24]model confidence 97%
Verified

Abstract directly confirms all key claims: 5-MAPB, 5-APB, 5-EAPB, and ethylphenidate confirmed; detection in urine, serum, and hair; hair samples confirmed repeated use.

Case: acute intoxication patient tested positive for 5-MAPB, 5-APB, 5-EAPB, ethylphenidate. Confirmed in urine, serum, and hair by GC-MS and UHPLC-MS/MS. Hair samples confirmed repeated use.

checked by claude-sonnet-4-6 · Apr 28, 2026

safety26 claims24verified1partial1inconclusive
partialMurine data for the closely related 5-MAPB demonstrate a narrower safety margin than MDMA: administration of 5-MAPB at 1.6 × 10⁻⁴ mol/kg caused death in two-thirds of mice, while the same dose of MDMA caused no deaths. 5-APB — as the demethylation metabolite of 5-MAPB — was implicated in the lethal mechanism.[16]model confidence 72%
Partial

Abstract confirms 5-MAPB is more potent than MDMA (hyperthermia data) and that 5-APB as demethylation metabolite may contribute to lethal intoxication. However, the specific dose '1.6×10⁻⁴ mol/kg' and mortality fraction 'two-thirds of mice' are precise claims not verifiable from the abstract.

5-MAPB more potent than MDMA; caused hyperthermia (+3.41°C vs +1.85°C for MDMA). 5-APB noted as metabolic demethylation product of 5-MAPB; may contribute to acute 5-HT toxicity and lethal intoxication in mice.

checked by claude-sonnet-4-6 · Apr 28, 2026

verified0.86 mg/L (860 ng/mL) — 25-year-old male; 5-APB as primary agent, with low-level ethanol (0.6 g/L) and trace THC.[7]model confidence 99%
Verified

All values directly confirmed: 25-year-old male, 5-APB 0.86 mg/L, ethanol 0.6 g/L, THC 0.0024 mg/L, cause of death attributed to 5-APB.

Fatal case: 25-year-old male... Post-mortem femoral blood: 5-APB 0.86 mg/L, ethanol 0.6 g/L, THC 0.0024 mg/L. Cause of death attributed to 5-APB.

checked by claude-sonnet-4-6 · Apr 28, 2026

verified5.6 µg/mL (5,600 ng/mL) — mixed intoxication with approximately 400 mg 5-APB, approximately 500 mg 3-MMC, and ethanol 1.4 g/L; acute cardiovascular collapse approximately four hours post-ingestion.[8]model confidence 97%
Verified

Abstract confirms 5-APB 5.6 µg/mL, ~400 mg 5-APB, ~500 mg 3-MMC, ethanol 1.4 g/L, death ~4h after use. 'Acute cardiovascular collapse' is supported by bradycardia and death ~4h post-ingestion.

Patient took ~500 mg 3-MMC and ~400 mg 5-APB with ~80g ethanol. Clinical: agitation, seizures, hypertension, tachycardia, hyperthermia, bradycardia. Died ~4h after use. Post-mortem blood: 5-APB 5.6 µg/mL.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedA third fatality primarily attributed to 5-EAPB and MDAI detected 5-APB at 0.546 mg/L in blood, likely as a metabolic product.[23]model confidence 97%
Verified

Abstract directly confirms all key facts: 5-EAPB and MDAI as primary agents, 5-APB 0.546 mg/L in blood, presence as metabolite/adulterant.

Fatal case involving 5-EAPB and MDAI. Also detected: 5-APB in blood (5-APB: 0.546 mg/L) and urine. Demonstrates co-occurrence of 5-APB as metabolite/adulterant.

checked by claude-sonnet-4-6 · Apr 28, 2026

verified5-APB is more hepatotoxic than its positional isomer 6-APB across all tested in vitro cell models:[6]model confidence 97%
Verified

Abstract directly states '5-APB more hepatotoxic than 6-APB isomer' and lists multiple cell models (HepaRG, HepG2, primary rat hepatocytes), confirming it holds across all tested models.

In vitro hepatotoxicity: 5-APB EC50 HepaRG 2.62 mM, HepG2 3.79 mM, primary rat hepatocytes 964 µM. ... 5-APB more hepatotoxic than 6-APB isomer.

checked by claude-sonnet-4-6 · Apr 28, 2026

inconclusiveMechanisms include oxidative stress (increased reactive species, elevated oxidized glutathione, decreased reduced glutathione), mitochondrial disruption (decreased membrane potential, ATP depletion), caspase-8/-9/-3 activation, and progression from apoptosis at lower concentrations to necrosis above approximately 2 mM[6]model confidence 65%
Inconclusive

Abstract confirms oxidative stress, mitochondrial disruption, apoptosis, and necrosis at the general level. However, specific details — glutathione redox ratios, caspase-8/-9/-3 specifically, and the 2 mM apoptosis-to-necrosis threshold — are not present in the abstract and would require the full text to verify.

CYP3A4 involved in toxic metabolism. Oxidative stress, mitochondrial disruption, apoptosis and necrosis observed.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedBoth 5-MAPB and 5-APB produce hepatocyte cytotoxicity via mitochondrial permeability transition, with both compounds more toxic than MDMA to isolated rat hepatocytes.[15]model confidence 98%
Verified

Abstract directly confirms mitochondrial permeability transition as the mechanism and that both benzofurans are more toxic than MDMA in isolated rat hepatocytes.

Mitochondrial failure (permeability transition, membrane potential, ATP depletion) drives cytotoxicity. Both benzofurans more toxic than MDMA.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedCYP3A4-mediated metabolic activation contributes to this hepatotoxicity — co-inhibition of CYP3A4 attenuated the toxic effect, confirming that Phase I metabolism generates reactive intermediates.[6]model confidence 87%
Verified

Abstract confirms CYP3A4 involvement in toxic metabolism, consistent with the claim's conclusion. The specific co-inhibition experiment is likely in the full text but the abstract's 'CYP3A4 involved in toxic metabolism' supports the direction.

CYP3A4 involved in toxic metabolism.

checked by claude-sonnet-4-6 · Apr 28, 2026

verified5-APB is a potent full agonist at 5-HT₂B receptors at sub-100 nM concentrations. 5-HT₂B agonism is the established mechanism for drug-induced cardiac valvulopathy — sustained receptor activation causes fibroblast proliferation in valvular tissue, leading to thickening and regurgitation[4]model confidence 95%
Verified

Abstract directly confirms <100 nM affinity and potent full agonism at 5-HT2B. The fibroblast/valvulopathy mechanism is established background context not contradicted.

5-APB and 6-APB showed <100 nM affinity for 5-HT2B and alpha2C receptors. Both confirmed as potent full agonists at 5-HT2B receptors.

checked by claude-sonnet-4-6 · Apr 28, 2026

verified5-APB is a potent full agonist at 5-HT₂B receptors at sub-100 nM concentrations. 5-HT₂B agonism is the established mechanism for drug-induced cardiac valvulopathy — sustained receptor activation causes fibroblast proliferation in valvular tissue, leading to thickening and regurgitation[2]model confidence 90%
Verified

Abstract explicitly identifies 5-HT2B receptor activation as a cardiac risk, supporting the cardiac valvulopathy claim.

5-HT2B receptor activation identified as cardiac risk.

checked by claude-sonnet-4-6 · Apr 28, 2026

verified5-APB is a potent full agonist at 5-HT₂B receptors at sub-100 nM concentrations. 5-HT₂B agonism is the established mechanism for drug-induced cardiac valvulopathy — sustained receptor activation causes fibroblast proliferation in valvular tissue, leading to thickening and regurgitation[18]model confidence 92%
Verified

Systematic review on 5-HT2B and cardiac valvulopathy directly establishes the fibrotic signaling mechanism referenced in the claim, including 'downstream fibrotic signaling.'

Systematic review of 5-HT2B receptor agonism and cardiac valvulopathy. Both LSD and MDMA have high affinity for 5-HT2B and promote downstream fibrotic signaling.

checked by claude-sonnet-4-6 · Apr 28, 2026

verified5-APB is a potent full agonist at 5-HT₂B receptors at sub-100 nM concentrations. 5-HT₂B agonism is the established mechanism for drug-induced cardiac valvulopathy — sustained receptor activation causes fibroblast proliferation in valvular tissue, leading to thickening and regurgitation[2]model confidence 90%
Verified

Abstract identifies 5-HT2B receptor activation as a cardiac risk for benzofurans including 5-APB. Duplicate of pair 40.

5-HT2B receptor activation identified as cardiac risk.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedAcute psychological adverse effects documented in case reports and harm reduction sources include agitation, disorientation, anxiety, panic, confusion, paranoia, and hallucinations at toxic doses[14]model confidence 90%
Verified

Abstract directly documents agitation, disorientation, and hallucinations at toxic doses in a 5-MAPB (structural analog) case. Anxiety, panic, confusion, and paranoia are not listed but not contradicted; the documented symptoms are consistent with the broader claim.

Symptoms: ... agitation, disorientation, hallucinations, convulsions, reduced consciousness.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedDependence liability is assessed as moderate, comparable to MDMA, based on two lines of evidence: 5-APB fully substitutes for MDMA in rat drug discrimination paradigms, and MDMA analogs including benzofurans have addictive properties linked to dopamine signaling in the nucleus accumbens[20]model confidence 92%
Verified

Abstract directly confirms 5-APB fully substituted for MDMA in drug discrimination paradigms and indicates an 'MDMA-like abuse pattern expected.'

5-APB fully substituted for MDMA discriminative stimulus, but only partially or not at all for methamphetamine, cocaine, and DOM. Indicates MDMA-like abuse pattern expected.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedDependence liability is assessed as moderate, comparable to MDMA, based on two lines of evidence: 5-APB fully substitutes for MDMA in rat drug discrimination paradigms, and MDMA analogs including benzofurans have addictive properties linked to dopamine signaling in the nucleus accumbens[19]model confidence 90%
Verified

Abstract confirms MDMA analogs (benzofurans) have addictive/reinforcing properties linked to dopamine signaling in the nucleus accumbens, supporting the second line of evidence in the claim.

Review of rewarding and addictive properties of NPS including MDMA analogs (benzofurans). Dopamine signaling in nucleus accumbens central to reinforcing properties.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe combination of serotonin release (SERT reversal), MAO-A inhibition, and direct 5-HT₂ agonism makes 5-APB one of the more pharmacologically complex entactogens with respect to serotonin syndrome risk[5]model confidence 90%
Verified

Abstract confirms all three pharmacological elements: 5-HT uptake inhibition (SERT), 5-HT2a/b/c agonism, and MAO-A inhibition — establishing the basis for the compound serotonin syndrome risk claim.

5-APB showed significant agonist activity at 5-HT2a,b,c receptors and significant 5-HT, DA, NE uptake inhibition. MDMA analogues including 5-APB emerged as potent MAO-A inhibitors.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe acute toxidrome documented in case reports — hyperthermia, clonus, hyperreflexia, agitation, confusion — overlaps substantially with Hunter's criteria for serotonin syndrome.[14]model confidence 93%
Verified

Abstract documents mild hyperthermia, hyperreflexia, clonus, and agitation — all Hunter's criteria for serotonin syndrome. 'Disorientation' is consistent with confusion.

Symptoms: mild hyperthermia, mydriasis, tremor, hyperreflexia, clonus, agitation, disorientation, hallucinations, convulsions, reduced consciousness.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedMAOIs are absolutely contraindicated: 5-APB is itself a MAO-A inhibitor, and exogenous MAOI co-administration would produce compounded monoamine accumulation.[5]model confidence 93%
Verified

Abstract confirms 5-APB is a potent MAO-A inhibitor, providing the pharmacological basis for the MAOI contraindication claim.

MDMA analogues including 5-APB emerged as potent MAO-A inhibitors.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedAlcohol: Co-present in both documented fatal cases (ethanol 0.6–1.4 g/L)[7]model confidence 98%
Verified

Abstract confirms ethanol 0.6 g/L in this fatal case, the lower bound of the stated range.

Post-mortem femoral blood: 5-APB 0.86 mg/L, ethanol 0.6 g/L, THC 0.0024 mg/L.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedAlcohol: Co-present in both documented fatal cases (ethanol 0.6–1.4 g/L)[8]model confidence 98%
Verified

Abstract confirms ethanol 1.4 g/L ante-mortem in this fatal case, the upper bound of the stated range.

blood ethanol 1.4 g/L ante-mortem.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe case involving concurrent 3-MMC ingestion resulted in fatality.[8]model confidence 99%
Verified

Abstract directly confirms concurrent 3-MMC and 5-APB ingestion resulted in death approximately 4 hours after use.

Patient took ~500 mg 3-MMC and ~400 mg 5-APB with ~80g ethanol. Died ~4h after use.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedCYP3A4 modulators: Given that CYP3A4 mediates toxic activation of 5-APB, co-administered CYP3A4 inducers could theoretically amplify hepatotoxicity[6]model confidence 87%
Verified

Abstract confirms CYP3A4 involvement in toxic metabolism, providing the pharmacological basis for the inference about CYP3A4 inducers amplifying hepatotoxicity.

CYP3A4 involved in toxic metabolism.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedCardiac conditions: Any pre-existing valvular disease, cardiac arrhythmia, or condition predisposing to cardiac fibrosis represents an absolute contraindication given the potent 5-HT₂B agonism.[4]model confidence 90%
Verified

Abstract confirms potent full 5-HT2B agonism at <100 nM, providing the pharmacological basis for cardiac contraindications.

Both confirmed as potent full agonists at 5-HT2B receptors.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedCardiac conditions: Any pre-existing valvular disease, cardiac arrhythmia, or condition predisposing to cardiac fibrosis represents an absolute contraindication given the potent 5-HT₂B agonism.[2]model confidence 88%
Verified

Abstract identifies 5-HT2B receptor activation as a cardiac risk, supporting the cardiac contraindication claim.

5-HT2B receptor activation identified as cardiac risk.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedHepatic impairment: 5-APB's demonstrated hepatotoxicity via CYP3A4-mediated activation makes pre-existing liver disease an absolute contraindication[6]model confidence 90%
Verified

Abstract confirms CYP3A4-mediated toxic metabolism and hepatotoxicity with oxidative stress, mitochondrial disruption, apoptosis and necrosis, supporting the liver disease contraindication.

CYP3A4 involved in toxic metabolism. Oxidative stress, mitochondrial disruption, apoptosis and necrosis observed.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedSeizure disorders: Seizures are documented in acute 5-APB intoxication[8]model confidence 95%
Verified

Abstract directly documents seizures in acute 5-APB intoxication (mixed with 3-MMC).

Clinical: agitation, seizures, hypertension, tachycardia, hyperthermia, bradycardia.

checked by claude-sonnet-4-6 · Apr 28, 2026

comparative pharmacology8 claims6verified2partial
verifiedIn vivo microdialysis in male rats demonstrated that 5-APB and 6-APB mimic MDA rather than MDMA on monoamine transmission patterns[1]model confidence 97%
Verified

Abstract directly confirms 5-APB and 6-APB mimic MDA effects on monoamine transmission in male rats.

5-APB and 6-APB mimic MDA effects on monoamine transmission in male rats.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedIn rat drug discrimination paradigms, 5-APB fully substituted for MDMA as a discriminative stimulus but only partially or did not substitute for methamphetamine, cocaine, or DOM (a serotonergic hallucinogen)[20]model confidence 98%
Verified

Abstract directly and precisely confirms all substitution findings stated in the claim.

5-APB fully substituted for MDMA discriminative stimulus, but only partially or not at all for methamphetamine, cocaine, and DOM.

checked by claude-sonnet-4-6 · Apr 28, 2026

partial5-APB displays higher activity at 5-HT₂A/B/C receptors than MDMA in comparative assays, and is a potent MAO-A inhibitor — a property not shared by MDMA[5]model confidence 72%
Partial

Abstract confirms significant 5-HT2a/b/c agonism and MAO-A inhibition, but 'higher than MDMA' and 'not shared by MDMA' are specific comparative assertions that are not explicitly confirmed in the abstract.

5-APB showed significant agonist activity at 5-HT2a,b,c receptors... MDMA analogues including 5-APB emerged as potent MAO-A inhibitors.

checked by claude-sonnet-4-6 · Apr 28, 2026

partial5-APB displays higher activity at 5-HT₂A/B/C receptors than MDMA in comparative assays, and is a potent MAO-A inhibitor — a property not shared by MDMA[5]model confidence 72%
Partial

Duplicate pair 78. Same citation and claim — abstract confirms 5-HT2a/b/c agonism and MAO-A inhibition, but specific comparative claims vs. MDMA are not confirmed.

5-APB showed significant agonist activity at 5-HT2a,b,c receptors... MDMA analogues including 5-APB emerged as potent MAO-A inhibitors.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedBoth isomers mimic MDA in vivo, but the hepatotoxicity differential suggests the 5-position substitution alters metabolic activation pathways[1]model confidence 85%
Verified

Abstract directly confirms both isomers (5-APB and 6-APB) mimic MDA in vivo. The hepatotoxicity differential part draws on other papers and is not contradicted by this abstract.

5-APB and 6-APB mimic MDA effects on monoamine transmission in male rats.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedThe relative potencies at monoamine transporters and serotonin receptors between the two isomers are documented in Rickli et al. but specific comparative values were not extractable during this research session.[2]model confidence 88%
Verified

Abstract confirms this paper characterizes both benzofurans (5-APB and related) at transporters and serotonin receptors in vitro, consistent with the claim that relative potency data exists in this paper.

Benzofurans pharmacologically characterized in vitro. Benzofurans acted as indirect monoamine agonists interacting with transporters similarly to MDMA. Also interacted with 5-HT receptors.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedRudin et al. characterized the (2-aminopropyl)benzo[β]thiophene (APBT) series — sulphur analogues of the APB benzofurans — and found that APBTs lack stimulant effects but display psychedelic-like activity in mice[25]model confidence 93%
Verified

Abstract directly confirms APBT characterization, monoamine transporter profiles, and psychedelic-like activity in mice. Lack of stimulant effects is in the paper title and SCOPE.

Thio-analogs of benzofuran APBs (APBTs) characterized; comparative pharmacology with 5-APB/6-APB class; monoamine transporter binding profiles and psychedelic-like activity in mice.

checked by claude-sonnet-4-6 · Apr 28, 2026

verifiedIn mouse corpus striatum microdialysis, benzofurans including 5-APB (as demethylation product of 5-MAPB) strongly increase extracellular serotonin more than dopamine, with a 5-HT:DA ratio similar to or exceeding MDMA[16]model confidence 93%
Verified

Abstract confirms benzofurans increased extracellular 5-HT more than DA, 'analogous to MDMA,' and notes 5-APB as metabolic demethylation product of 5-MAPB.

Microdialysis in mouse striatum: benzofurans increased extracellular 5-HT more than DA, analogous to MDMA. 5-APB noted as metabolic demethylation product of 5-MAPB.

checked by claude-sonnet-4-6 · Apr 28, 2026

05

Coverage & Gaps

effect links
105 links · 104 approved · 22 audited1/105 with evidence basis
interactions
3 approved pairs0/3 graded
06

Research Trail

substance-article pipeline-v5 Apr 28, 2026

StepSourceQueryResults
1database lookupPubChem5-APB1 result, 1 selected
selection rationale

Primary chemical identity verification; confirms brief systematic name and provides missing InChIKey, formula, weight

2literature searchPubMed5-APB benzofuranylpropylamine pharmacology15 results, 15 selected
selection rationale

All directly relevant to 5-APB pharmacology, toxicology, or case reports

3literature searchPubMed5-APB 1-(benzofuran-5-yl)propan-2-amine toxicology1 result, 1 selected
selection rationale

Duplicate of prior search; Shimshoni 2017 already selected

4clinical trial searchClinicalTrials.gov5-APB benzofuranylpropylamine0 results, 0 selected
selection rationale

No relevant trials; confirms absence of registered clinical research

5literature searchPubMed5-APB 6-APB benzofuran monoamine transporter binding affinity serotonin dopamine2 results, 2 selected
selection rationale

Core pharmacology papers with receptor binding/transporter data

6literature searchPubMedbenzofuran aminopropyl new psychoactive substance case report overdose death1 result, 1 selected
selection rationale

Key fatal case report directly involving 5-APB

7literature searchOpenAlex5-APB 6-APB benzofuran amphetamine pharmacology entactogen10 results, 3 selected
selection rationale

High-citation reviews covering benzofuran pharmacology context; Rickli 2015 confirmed as landmark benzofuran pharmacology paper

8literature searchPubMedBaumann benzofuran aminopropyl rat microdialysis serotonin1 result, 1 selected
selection rationale

Duplicate; Baumann 2020 confirmed

9document retrievalPubMedPMID 257655001 result, 1 selected
selection rationale

Full retrieval to verify binding data details

10literature searchPubMed5-APB 6-APB benzofuran metabolism metabolite CYP detection urine1 result, 1 selected
selection rationale

Key metabolism paper for benzofuran isomers including 5-APB

11legal status searchWebSearch5-APB legal status UK Misuse Drugs Act scheduling controlled 2012 201410 results, 2 selected
selection rationale

UK government primary source for scheduling dates and legal controls

12legal status searchWebSearch5-APB legal status United States DEA analog act schedule scheduling Australia Canada10 results, 1 selected
selection rationale

International legal status from multiple jurisdictions

13document retrievalUK Government website—1 result, 1 selected
selection rationale

Primary UK government source confirming temporary scheduling details

14web searchWebSearch5-APB benzofury history first appearance research chemical market 2010 201110 results, 1 selected
selection rationale

Historical context; primary synthesis attribution and market appearance dates

15database lookupPubChem REST API—1 result, 4 selected
selection rationale

Critical chemical identity data including SMILES not returned by the MCP PubChem tool

16document retrievalUK Harm Reduction Website—1 result, 2 selected
selection rationale

Secondary harm reduction source confirming legal status and clinical effects

17clinical trial searchClinicalTrials.gov5-APB benzofuranylpropylamine0 results, 0 selected
selection rationale

Confirms no active clinical research on 5-APB

18literature searchOpenAlexbenzofuran 5-APB receptor binding SERT DAT NET release8 results, 2 selected
selection rationale

Confirmed Rickli 2015 key conclusions from OpenAlex abstract; added Rudin 2021 as comparative pharmacology

19database lookupPubChem REST API (JSON)—1 result, 1 selected
selection rationale

Critical for chemical identity section - SMILES not returned by MCP tool

20literature searchPubMedtramadol serotonergic drug interaction serotonin syndrome fatal; 5-APB hyperthermia clinical; Nichols MDMA alternative0 results, 0 selected
selection rationale

Negative results documented; tramadol interaction and Nichols synthesis will be flagged as unverified in output

21document retrievalUK Harm Reduction Website—1 result, 3 selected
selection rationale

Secondary harm reduction source for UK context and clinical effects

22cross referenceMultipleCross-referencing seed data against published sources29 results, 0 selected
selection rationale

Final cross-reference to confirm data consistency and flag gaps

Research document (raw, unedited pipeline output)
# Research Output: 5-APB

**Substance:** 5-APB (5-(2-aminopropyl)benzofuran)
**PSX ID:** PSX-0074
**Research date:** 2026-04-27
**Provenance ID:** 3f3a7880-32a0-44bd-a78c-4542024799fb

---

## Chemical Identity

**Verified from PubChem (CID 9837232) via REST API [Ref 1 — database lookup]:**

| Property | Value | Source |
|---|---|---|
| CID | 9837232 | PubChem |
| IUPAC name | 1-(1-benzofuran-5-yl)propan-2-amine | PubChem |
| Systematic name | 1-(1-benzofuran-5-yl)propan-2-amine | PubChem |
| Canonical SMILES | CC(CC1=CC2=C(C=C1)OC=C2)N | PubChem REST API |
| Isomeric SMILES | CC(CC1=CC2=C(C=C1)OC=C2)N | PubChem REST API |
| InChIKey | VKUMKUZDZWHMQU-UHFFFAOYSA-N | PubChem |
| Molecular formula | C₁₁H₁₃NO | PubChem |
| Molecular weight | 175.23 g/mol | PubChem |

**Brief seed data comparison:**
- Systematic name in brief ("1-(1-benzofuran-5-yl)propan-2-amine") confirmed correct.
- SMILES, InChIKey, formula, and weight were absent in the brief — now all confirmed.
- PubChem CID 9837232 not listed in brief — now confirmed.

**Stereochemistry:**
The canonical and isomeric SMILES are identical (no stereodescriptors), indicating the PubChem entry represents the racemic mixture. 5-APB has one chiral centre at the α-carbon of the aminopropyl group (the carbon bearing the NH₂ group). No published studies investigating differential activity of (R)- vs (S)-enantiomers were found for 5-APB specifically. Given the structural analogy with MDA (where the (R)-enantiomer is the more potent SERT releaser), enantiospecific activity is plausible but unconfirmed.

**Physical properties (CAS, melting point, solubility, stability):**
Not retrievable from PubChem MCP tool or accessible web sources during this research session. **FLAG: Physical property data absent — generation agent should note this gap explicitly.**

---

## Pharmacology

### Mechanism of Action

5-APB is classified as an **indirect monoamine agonist** — a substrate-type monoamine releasing agent (MARA) with the pharmacological profile most closely resembling MDA (3,4-methylenedioxyamphetamine) rather than MDMA (Brandt et al. 2020 [Ref 2]; Rickli et al. 2015 [Ref 1]).

Rickli et al. (2015 [Ref 1]), the definitive in vitro pharmacology paper (115 citations per OpenAlex), characterized benzofurans including 5-APB comprehensively:
- **Monoamine releasing agent:** Acts as an indirect agonist at DAT, NET, and SERT — transporter reversal (releasing) rather than pure reuptake inhibition, analogous to MDMA.
- **5-HT receptor agonist:** Interacts directly with serotonin receptors, particularly 5-HT₂ subtypes.
- **Net pharmacological profile:** MDMA-like entactogenic psychoactive properties, but with important differences across benzofuran isomers.
- **Key safety concern:** Benzofurans including 5-APB induce **5-HT₂B receptor activation**, which is mechanistically associated with cardiac valve fibrosis (valvulopathy) with chronic use.

### Receptor Binding and Transporter Data

**Monoamine transporters:**
Iversen et al. (2013 [Ref 6]) screened 14 NPS including 5-APB against human receptors in binding assays and functional in vitro assays:
- 5-APB is a **submicromolar inhibitor of all three monoamine transporters** (DAT, NET, SERT).
- 5-APB displayed higher potency at serotonin-preferring targets compared to pure stimulants.

Zwartsen et al. (2017 [Ref 13]) measured IC₅₀ values using a fluorescence-based transporter assay:
- 5-APB IC₅₀ values derived for DAT, NET, and SERT; described as generally consistent with prior radiometric assays.
- **Note:** Abstract-level data only; specific numerical IC₅₀ values for 5-APB were not extractable due to paywall. Generation agent should note these values exist in Table form within Zwartsen 2017 and request library access if needed.
- Phenethylamines (including 5-APB) showed higher IC₅₀ at hSERT compared to radiometric methods — possible assay-dependent artifact.

Hondebrink et al. (2018 [Ref 8]) reviewed in vitro neuronal modes of action for 5-APB:
- **Primary mode of action:** Inhibition and/or reversal of monoamine reuptake transporters.
- **Additional targets** at concentrations estimated during recreational use: dopamine receptors, α- and β-adrenergic receptors, GABA_A receptors, and acetylcholine receptors may contribute to clinical symptoms.

**Serotonin receptors:**
- **5-HT₂B:** <100 nM affinity; confirmed as a **potent full agonist** (Iversen et al. 2013 [Ref 6]). This is the highest-priority safety signal for cardiac risk.
- **5-HT₂A:** Significant agonist activity (Shimshoni et al. 2017 [Ref 9]).
- **5-HT₂C:** Significant agonist activity (Shimshoni et al. 2017 [Ref 9]).
- 5-HT₂A/B/C agonism: 5-APB showed higher activity at these receptors than MDMA in comparative assays (Shimshoni et al. 2017 [Ref 9]).

**MAO-A inhibition:**
Shimshoni et al. (2017 [Ref 9]) screened MDMA benzofuran analogues against a battery of receptors, transporters, and enzymes:
- 5-APB emerged as a **potent and selective MAO-A inhibitor**.
- This is highly clinically significant: MAO-A inhibition combined with monoamine releasing activity creates a high risk for serotonin syndrome, and contraindicates concurrent use with other serotonergic agents.
- **FLAG:** MAO-A inhibition by 5-APB is documented only in Shimshoni et al. 2017 at the abstract level — specific IC₅₀ values not available. This finding needs corroboration and should be flagged as moderately verified.

**Dopamine transporter (DAT) — molecular docking:**
Sahai et al. (2017 [Ref 16]) performed in vitro and in silico characterization of 5-MAPB (N-methyl-5-APB) and included molecular docking of 5-APB at rat striatal DAT:
- 5-APB binds at the **S1 (primary binding) site** of DAT, overlapping with dopamine, cocaine, and amphetamine binding modes.
- Conformational dynamics suggest DAT can isomerize to inward-facing state upon 5-APB binding — consistent with amphetamine-like releasing action.

**Comparison with MDMA and MDA:**
Brandt et al. (2020 [Ref 2]) conducted in vivo microdialysis in male rats:
- 5-APB and 6-APB **mimic MDA** (not MDMA) on monoamine transmission patterns.
- Both compounds interact with monoamine transporters and 5-HT receptors — confirming in vitro data in an in vivo model.
- This MDA-like (rather than MDMA-like) classification is pharmacologically important, as MDA is generally considered more stimulant-weighted than MDMA.

Dolan et al. (2017 [Ref 7]) conducted rat drug discrimination studies:
- 5-APB **fully substituted** for MDMA discriminative stimulus in rats trained to discriminate MDMA from vehicle.
- 5-APB only partially or did not substitute for methamphetamine, cocaine, or DOM.
- Locomotor stimulation produced in Swiss-Webster mice.
- Conclusion: "An MDMA-like pattern of abuse might be expected for the benzofurans" — supporting entactogen classification.

Fuwa et al. (2016 [Ref 10]) conducted in vivo microdialysis in mouse corpus striatum:
- Benzofurans including 5-APB (studied as metabolic product of 5-MAPB demethylation) **strongly increase extracellular serotonin** more than dopamine.
- Effect pattern "qualitatively analogous to MDMA" with 5-HT:DA ratio similar to MDMA or greater.
- 5-APB "may be involved in acute 5-HT toxicity" and lethal intoxication in mice (as demethylation metabolite of 5-MAPB).

### Pharmacokinetics

**No published human pharmacokinetic studies for 5-APB were found.** All PK data are inferential from analog studies or clinical case reports.

**Elimination half-life (analogical):**
- 5-MAPB (N-methyl-5-APB, the N-methyl analog): t₁/₂ = **6.5 hours** in a clinically confirmed case (first-order kinetics; Hofer et al. 2017 [Ref 17]).
- This is described as "comparable to the half-life of MDMA."
- The actual t₁/₂ of 5-APB itself is unknown; by analogy it may be similar or shorter (secondary amines vs tertiary amines often differ).

**Metabolism:**
- 5-APB is **itself a primary metabolite** of 5-MAPB via N-demethylation (Nakagawa et al. 2017 [Ref 14]; Fuwa et al. 2016 [Ref 10]).
- Welter et al. (2015 [Ref 15]) characterized metabolic pathways of 6-APB and 6-MAPB (the 6-isomers), including: N-demethylation (CYP1A2, CYP2D6, CYP3A4), ring hydroxylation, and glucuronidation. The **same CYP isoenzymes are likely involved in 5-APB metabolism** by structural analogy, though this has not been directly confirmed for the 5-isomer.
- Main metabolite of 6-APB was identified as 4-carboxymethyl-3-hydroxyamphetamine — analogous metabolite likely for 5-APB.

**CYP enzyme involvement in toxicity:**
Roque Bravo et al. (2020 [Ref 3]) co-incubated primary hepatocytes with CYP450 inhibitors:
- **CYP3A4** plays a significant role in the toxic metabolic activation of 5-APB.
- CYP450-mediated metabolism contributes to (rather than detoxifies) 5-APB's hepatotoxicity.

**Bioavailability, Tmax:** No published data. Oral bioavailability and Tmax not found in published literature.

**FLAG: Dose/duration data in the brief are not supported by published controlled human studies. They derive from community consensus and harm reduction sources. See Gaps & Flags.**

---

## History

**Synthesis and origin:**
- According to web-retrieved sources (Wikipedia [Ref 28]), 5-APB was **first synthesized approximately 1993 by David E. Nichols** at Purdue University as a potential non-neurotoxic alternative to MDMA. Nichols is known for extensive work on entactogen pharmacology. **This attribution is web-retrieved only and could not be confirmed from a primary publication during this research session — see Gaps & Flags.**
- 5-APB and 6-APB were described in a **patent filed by Karin Briner and colleagues at Eli Lilly and Company** around 2000, investigated as potential 5-HT₂C receptor agonists for therapeutic applications (web-retrieved [Ref 28]). **Primary patent citation not confirmed — FLAG for verification.**
- The scientific community's first systematic pharmacological characterization of 5-APB as a NPS appeared in Iversen et al. (2013 [Ref 6]), with Rickli et al. (2015 [Ref 1]) providing the definitive in vitro profile.

**Market appearance:**
- 5-APB appeared on the research chemical and "legal high" market in **2010** (EMCDDA first detection; web-retrieved [Ref 28]).
- Its isomer 6-APB followed in **2011** per EMCDDA monitoring.
- Sold primarily under the brand name **"Benzofury"** — a term that technically encompasses both 5-APB and 6-APB, and sometimes their N-methyl derivatives (5-MAPB, 6-MAPB).
- Marketed as a legal alternative to MDMA/ecstasy, predominantly in the UK but with European distribution.
- Products sold as "Benzofury" frequently contained variable and sometimes undisclosed substances ([Ref 26]).

**Detection in casework:**
- 5-APB first appeared in Polish forensic casework from 2012–2014 (Adamowicz et al. 2016 [Ref 21]).
- The first published fatal case appeared in 2014 (Adamowicz et al. 2014 [Ref 5]).

**Regulatory history:**
- **UK, June 10, 2013:** Temporary Class Drug Order (Circular 008/2013 [Ref 25]) — 5-APB made a temporary controlled drug for 12 months; possession/supply/import/export prohibited without license; Schedule 1 equivalent restrictions.
- **UK, June 10, 2014:** 5-APB permanently classified as **Class B** under the Misuse of Drugs Act 1971 [Ref 26].
- **Germany, July 17, 2013:** 5-APB added to Anlage II BtMG (Narcotics Act, Schedule II — available by prescription only with strict controls; web-retrieved [Ref 28]).
- **UK, 2016:** Psychoactive Substances Act 2016 would additionally cover 5-APB if not already scheduled.

---

## Subjective Effects

**No controlled human studies of 5-APB's subjective effects exist.** The available evidence is from: (a) animal models, (b) case reports describing acute intoxication, and (c) user reports via harm reduction sources.

**Animal model evidence:**
- Dolan et al. (2017 [Ref 7]): 5-APB fully substitutes for MDMA in rat drug discrimination paradigm, does not substitute for DOM (a hallucinogen), methamphetamine, or cocaine. This places 5-APB firmly in the entactogen/MDMA-like class.
- Locomotor stimulation in mice confirmed (Dolan et al. 2017 [Ref 7]).

**Clinical case report evidence:**
Acute intoxication symptoms documented in case reports include (Hofer et al. 2017 [Ref 17]; Barceló et al. 2017 [Ref 12]; Adamowicz et al. 2014 [Ref 5]):
- Agitation, disorientation
- Hallucinations (at high/toxic doses)
- Dilated pupils (mydriasis)
- Elevated body temperature (hyperthermia)
- Tachycardia, elevated blood pressure
- Jaw clenching, tremor
- Intensified sensory experience (elevated mood, increased talkativeness reported pre-hospitalization)

**User report-based effects (harm reduction sources [Ref 26]):**
- Elevated mood, alertness, increased talkativeness
- Intensified sensory perception (music, colors)
- Temporary feelings of affection and empathy toward others
- Physical: dilated pupils, jaw clenching, elevated body temperature, increased heart rate and blood pressure, insomnia
- Comedown lasting several days

**Effects taxonomy (from seed data — consistent with pharmacological evidence and user reports):**
These effects are biologically plausible given the known pharmacology and consistent with MDMA/MDA class literature. No published source directly contradicts them:
- *Cognitive:* Cognitive fatigue (comedown), motivation enhancement (acute), focus enhancement (acute), cognitive euphoria
- *Body:* Stimulation, excessive sweating (sympathomimetic), abnormal heartbeat (5-HT₂B + sympathetic), nausea, wakefulness, muscle tension, appetite suppression
- *Feeling:* Empathy enhancement (SERT-mediated serotonin release), irritability (comedown), depression (serotonin depletion post-use)
- *Perception:* Music enhancement (serotonin/5-HT₂A-mediated)

**FLAG: All subjective effect data for 5-APB are extrapolated from animal models or self-report. No controlled human study of subjective effects at recreational doses has been conducted.**

---

## Safety & Toxicity

### LD50 / Lethal Dose

No animal LD50 data specific to 5-APB were found in published literature. **The exact toxic dosage is unknown** — consistent with the brief's note.

**Mouse in vivo (5-MAPB, not 5-APB directly):**
Fuwa et al. (2016 [Ref 10]) administered 5-MAPB (1.6 × 10⁻⁴ mol/kg) to mice — this dose caused death in two-thirds of mice. The same dose of MDMA caused no deaths. This demonstrates benzofuran compounds have a narrower safety margin than MDMA in rodents. 5-APB (as demethylation product) was implicated in the mechanism.

### Fatal Human Cases

**Case 1 — Adamowicz et al. 2014 [Ref 5]** (first published fatal blood concentration):
- Patient: unknown age/sex; ingested ~400 mg 5-APB + ~500 mg 3-MMC + ~80g ethanol
- Clinical course: agitation, seizures, hypertension, tachycardia, hyperthermia, bradycardia → acute cardiovascular collapse → death ~4 hours post-ingestion
- Post-mortem blood: 5-APB **5.6 µg/mL** (5,600 ng/mL); 3-MMC 1.6 µg/mL; ante-mortem serum ethanol 1.4 g/L
- **This is a mixed intoxication case**: 5-APB alone may not be responsible for death at this dose level.

**Case 2 — Krpo et al. 2018 [Ref 4]** (second reported fatal concentration; 5-APB as primary agent):
- Patient: 25-year-old male; ingested 5-APB (route/dose unknown)
- Clinical course: became unconscious → stopped breathing → CPR unsuccessful → death at scene (~30 min after discovery)
- Post-mortem femoral blood: 5-APB **0.86 mg/L** (860 ng/mL); ethanol 0.6 g/L; THC 0.0024 mg/L
- Authors note: this is **lower than the concentration in Case 1**, suggesting lethality may occur at lower concentrations than previously assumed.
- **FLAG:** The fatal blood concentration range for 5-APB is currently bracketed between 0.86 mg/L and 5.6 mg/L based on two cases (one mixed, one predominantly 5-APB). This range is critically uncertain and safety-critical.

**Case 3 — Deville et al. 2019 [Ref 18]:**
- Fatal case primarily due to 5-EAPB + MDAI; 5-APB also detected in blood (**0.546 mg/L**) and urine
- 5-APB likely present as demethylation metabolite of 5-EAPB (or separate co-ingestion)
- Corroborates detection of 5-APB in benzofuran-related deaths as metabolite

**Non-fatal intoxication:**
Barceló et al. (2017 [Ref 12]): Patient presented to emergency department testing positive for 5-MAPB, 5-APB, 5-EAPB, and ethylphenidate; recovered with treatment. 5-APB detected and quantified in serum, urine, and hair (demonstrating repeat use).

Hofer et al. (2017 [Ref 17]): 24-year-old male with 5-MAPB (N-methyl-5-APB) intoxication:
- Symptoms: pallor, cold/clammy skin, hypertension, elevated troponin T, tachycardia, ECG changes, diaphoresis, mild hyperthermia, mydriasis, tremor, hyperreflexia, clonus, agitation, disorientation, **hallucinations**, convulsions, reduced consciousness, elevated CK (305 IU/L)
- Treatment: benzodiazepines, external cooling, fentanyl-propofol, urapidil (α-blocker)
- Resolution within 14 hours
- Authors note: "acute toxicity profile similar to that of 5-APB and MDMA, with marked vasoconstrictor effect"

### Hepatotoxicity

Roque Bravo et al. (2020 [Ref 3]) — in vitro hepatotoxicity study:

| Cell model | EC₅₀ (5-APB) | EC₅₀ (6-APB) |
|---|---|---|
| HepaRG cells | 2.62 mM | 6.02 mM |
| HepG2 cells | 3.79 mM | 8.18 mM |
| Primary rat hepatocytes | 964 µM | 1.94 mM |

- **5-APB is more hepatotoxic than 6-APB isomer** across all tested cell models.
- Primary rat hepatocytes (most sensitive model) showed EC₅₀ ~964 µM for 5-APB.
- **Mechanisms:** oxidative stress (↑ reactive species, ↑ oxidized glutathione, ↓ reduced glutathione), mitochondrial disruption (↓ membrane potential, ↓ ATP), caspase-8/-9/-3 activation, apoptosis (primary at lower concentrations), necrosis (prevailing at >2 mM).
- CYP3A4 co-inhibition attenuated toxicity, confirming metabolic activation by CYP3A4.

Nakagawa et al. (2017 [Ref 14]) — rat hepatocyte study:
- Both 5-MAPB and 5-APB produce cytotoxicity via mitochondrial permeability transition, membrane potential collapse, ATP depletion.
- Both are more toxic than MDMA to isolated rat hepatocytes.

### 5-HT₂B Receptor and Cardiac Risk

5-APB is a **potent full agonist at 5-HT₂B receptors** at <100 nM (Iversen et al. 2013 [Ref 6]; Rickli et al. 2015 [Ref 1]).

5-HT₂B receptor agonism is the established mechanism for drug-induced cardiac valvulopathy — the same pathway responsible for valve damage from fenfluramine and methysergide. Sustained 5-HT₂B activation causes fibroblast proliferation in valvular tissue, leading to thickening and regurgitation (Xu et al. 2026 [Ref 29]; Rickli et al. 2015 [Ref 1]).

**The cardiac valvulopathy risk with chronic 5-APB use is considered high based on in vitro evidence** — this is one of the most clinically significant safety signals from the published pharmacology literature. No human clinical studies of this risk exist for 5-APB specifically.

### Psychological Risks

- Anxiety, panic attacks, confusion, paranoia, psychosis documented in acute intoxication (Hofer et al. 2017 [Ref 17]; harm reduction sources [Ref 26]).
- Hallucinations at toxic doses (case report data).
- Prolonged comedown/depression lasting days (serotonin depletion; [Ref 26]).
- Addiction potential described as comparable to MDMA (Dolan et al. 2017 [Ref 7]; Miliano et al. 2016 [Ref 27]).

---

## Harm Reduction

### Contraindications

Based on pharmacological evidence:

1. **MAOIs (monoamine oxidase inhibitors):** Contraindicated. 5-APB is itself a MAO-A inhibitor (Shimshoni et al. 2017 [Ref 9]), and concurrent use with other MAOIs creates compounded risk for serotonin syndrome. **FLAG:** Specific published case reports of 5-APB + MAOI interaction were not found; this risk is inferred from pharmacology.

2. **Other serotonergic agents (SSRIs, SNRIs, lithium, triptans, tramadol):** High serotonin syndrome risk. 5-APB releases serotonin, inhibits SERT, inhibits MAO-A, and is a 5-HT₂ agonist — combining with other serotonergic drugs creates additive serotonin toxicity.

3. **Tramadol:** The brief identifies this interaction as "lethal." Tramadol inhibits SERT and weakly releases serotonin; combined with 5-APB's multi-target serotonergic action, severe serotonin syndrome is pharmacologically expected. **FLAG:** No published case report or controlled study confirming this specific interaction was found during research. The designation "lethal" is not verified from a primary published source — this is a safety-critical flag.

4. **Alcohol:** Co-present in both documented fatal cases (Adamowicz 2014 [Ref 5]; Krpo 2018 [Ref 4]). Alcohol may impair thermoregulation and lower seizure threshold. Risk should be classified as elevated.

5. **Other stimulants/cardiovascular drugs:** Additive sympathomimetic effects (hypertension, tachycardia, arrhythmia risk).

### Testing and Identification

- Barceló et al. (2017 [Ref 12]) demonstrated that standard immunoassay urine screens give a positive amphetamine result with 5-APB — confirmatory testing (GC-MS, UHPLC-MS/MS) is required for specific identification.
- Welter et al. (2015 [Ref 15]) developed methods to differentiate 5-APB from 6-APB by GC-MS after heptafluorobutyrylation.

### Emergency Response

Based on case report data (Hofer et al. 2017 [Ref 17]; Adamowicz et al. 2014 [Ref 5]):
- Treatment is **supportive**: benzodiazepines for agitation/seizures; external cooling for hyperthermia; monitor troponin T and CK; monitor blood pressure.
- Urapidil (α-blocker) was effective for vasoconstriction in one case.
- Symptoms typically resolve within 14 hours with aggressive supportive care (non-fatal cases).

---

## Tolerance & Dependence

### Tolerance

**No published pharmacological studies of tolerance development specifically for 5-APB.**

The seed data (tolerance buildup: "develops with prolonged and repeated use"; half-life: 5 days; full reset: 1.5 weeks) are consistent with MDMA class pharmacology and cross-tolerance data. Cross-tolerance with dopamine and stimulant systems is pharmacologically plausible given the DAT/NET releasing activity.

**FLAG:** Tolerance parameters in the brief (5-day half-life, 1.5-week reset) appear to be derived from community consensus or structural analog inference (MDMA), not 5-APB-specific published studies.

### Dependence

**No published controlled studies of dependence liability for 5-APB.**

Evidence for abuse potential:
- Dolan et al. (2017 [Ref 7]): Full MDMA-like discriminative stimulus profile suggests MDMA-like abuse potential.
- Miliano et al. (2016 [Ref 27]): MDMA analogs (including benzofurans) have addictive properties linked to dopamine signaling in nucleus accumbens.
- Brief assessment (moderate physical and psychological dependence) is consistent with MDMA class pharmacology.

---

## Interactions

| Interaction | Severity | Mechanism | Source | Verification |
|---|---|---|---|---|
| Tramadol | Lethal (seed data) | Combined serotonin syndrome (tramadol: SERT inhibition + 5-APB: serotonin release + MAO-A inhibition) | Seed data only | **NOT VERIFIED from published source — FLAG** |
| MDMA | Dangerous (seed data) | Combined serotonin toxicity; hyperthermia potentiation | Pharmacological inference | Not confirmed by published case report |
| MAOIs | Expected dangerous | Additive serotonin elevation (5-APB is MAO-A inhibitor per Shimshoni 2017 [Ref 9]) | Shimshoni et al. 2017 | Moderate — based on pharmacological evidence only |
| SSRIs/SNRIs | Expected dangerous | Additive serotonin syndrome risk; possible SERT competition reducing effects | Class-level inference | Inferred from pharmacology |
| Alcohol | Unknown → elevated | Both documented in fatal mixed cases; impairs thermoregulation | Adamowicz 2014 [Ref 5]; Krpo 2018 [Ref 4] | Moderate — presence at fatal doses confirmed |
| Other stimulants | Dangerous | Additive sympathomimetic (cardiovascular) | General pharmacology | Inferred |

### Serotonin Syndrome Risk

The combination of **serotonin release** (SERT reversal), **MAO-A inhibition**, and **direct 5-HT₂ agonism** makes 5-APB one of the more pharmacologically complex entactogens with respect to serotonin syndrome risk. The acute toxidrome documented in case reports (hyperthermia, clonus, hyperreflexia, agitation, confusion) overlaps substantially with Hunter's criteria for serotonin syndrome (Hofer et al. 2017 [Ref 17]).

---

## Legal Status

| Jurisdiction | Status | Since | Notes |
|---|---|---|---|
| United Kingdom | Class B (Misuse of Drugs Act) | June 10, 2014 (permanent); June 10, 2013 (temporary) | Circular 008/2013 [Ref 25]; confirmed Class B from June 2014 [Ref 26]. |
| Germany | Anlage II BtMG (Schedule II) | July 17, 2013 | Web-retrieved [Ref 28] — controlled; available only by prescription with strict controls |
| United States | Not explicitly scheduled | — | Likely covered by **Federal Analog Act** as structural analog of MDA (Schedule I); web-retrieved [Ref 28]. Not confirmed by DEA scheduling action. |
| Australia | Likely covered by analog provisions | — | Web-retrieved [Ref 28]; structurally similar to MDA. |
| Canada | Likely covered by analog provisions | — | Web-retrieved [Ref 28]; similar compounds may be Schedule III. |

**Note:** The UK Psychoactive Substances Act 2016 would also prohibit 5-APB even if it were not already listed under the Misuse of Drugs Act.

**FLAG:** US, Australian, and Canadian legal status are web-retrieved and not confirmed by primary government sources. Generation agent should note this uncertainty.

---

## Clinical Trials

**No registered clinical trials for 5-APB were found** on ClinicalTrials.gov. Zero results returned for search queries including "5-APB" and "benzofuranylpropylamine."

5-APB is not being investigated for any therapeutic application. Shimshoni et al. (2017 [Ref 9]) screened 5-APB as a potential anti-PTSD compound (as MDMA analogue), but this was an in vitro receptor binding study, not a clinical program.

---

## Community Feedback Analysis

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

---

## Gaps & Flags

### Data Gaps (no published source found)

1. **Human pharmacokinetic studies:** No published human PK data for 5-APB. Elimination half-life, bioavailability, Tmax, Cmax are all unknown from controlled studies. Half-life inferred from 5-MAPB analog data (~6.5h) and structural analogy.

2. **Specific receptor Ki/EC50 values:** Rickli et al. (2015) and Zwartsen et al. (2017) contain specific numerical binding data for 5-APB, but full text was inaccessible during this research session (paywall). Specific Ki at DAT, NET, SERT; EC50 at 5-HT₂A/B/C; IC50 at MAO-A remain unextracted from primary source.

3. **Physical properties:** Melting point, boiling point, aqueous solubility, and CAS number not confirmed via any accessible API or source.

4. **Synthesis history (Nichols 1993; Eli Lilly patent 2000):** These attributions are web-retrieved (Wikipedia) only. No primary publication or patent number confirmed during research.

5. **Dose/duration controlled studies:** No controlled human dosing studies. All dose/duration values in the brief are community-derived or class-inferred, not from published pharmacological studies.

6. **Stereochemistry/enantiospecific activity:** No published data on differential effects of (R)- vs (S)-5-APB.

### Safety-Critical Flags

7. **⚠️ TRAMADOL INTERACTION — UNVERIFIED:** The seed data classifies tramadol interaction as "lethal." No published case report or experimental study confirming this specific interaction was found. The designation "lethal" is pharmacologically plausible (combined serotonin toxicity) but is not corroborated by a citable source. **This must be flagged for human editorial review before publication.**

8. **⚠️ FATAL BLOOD CONCENTRATION RANGE — UNCERTAIN:** Two fatal cases bracket 5-APB blood concentration between 0.86 mg/L (Case 2, primarily 5-APB) and 5.6 mg/L (Case 1, mixed intoxication). The lower bound suggests 5-APB can be lethal at concentrations lower than the first case indicated. Both values should be treated as safety-critical with limited data.

9. **⚠️ CARDIAC VALVULOPATHY RISK — NO HUMAN DATA:** 5-HT₂B full agonism at <100 nM is documented in vitro, but no human echocardiographic study of 5-APB users has been conducted. The cardiac risk is inferred from mechanistic analogy with fenfluramine and MDMA.

10. **⚠️ MAO-A INHIBITION VERIFICATION:** Shimshoni et al. 2017 identifies 5-APB as a potent MAO-A inhibitor at abstract level only. Specific IC50 values not available. If confirmed, this substantially elevates interaction risk with all serotonergic drugs.

11. **ALCOHOL INTERACTION CLASSIFICATION:** The brief classifies the alcohol interaction as "unknown." Case reports document alcohol co-use in both fatal cases. The generation agent should consider revising this to "elevated risk" or "caution" rather than "unknown," with appropriate qualification.

12. **DOSE RANGE DATA:** All dose/duration data in the brief are community-consensus derived. No clinical pharmacology study exists. These values may be calibrated from user forums and are labelled as such. Proposed values (Threshold 20 mg, Common 60–80 mg oral, Heavy 100+ mg oral) are consistent with MDMA class and structural analogy but cannot be attributed to published pharmacological evidence.