Skip to main content
Psychedex
Sources
20
1 strong · 13 moderate · 6 weak

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

Claims checked
75
68verified7inconclusive

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

Generated
Apr 21, 2026 · pipeline-v5
Values approved
219/221 (99%)

Data points an editor reviewed and accepted for publication.

01

Value Provenance

Dosing

oraltrace

FieldPublishedAI ProposedConfidence
Threshold15 mg15 mglow
Low30–60 mg30–60 mglow
Common60–90 mg60–90 mglow
Strong90–120 mg90–120 mglow
Heavy120+ mg120+ mglow
Editorial

Dose ranges from community consensus sources (PsychonautWiki): threshold 15 mg, light 30-60 mg, common 60-90 mg, strong 90-120 mg, heavy 120+ mg. No controlled human dosing studies exist for 6-APB. These values are carried forward from existing community-curated database values.

Reasoning

Dose ranges from community consensus sources (PsychonautWiki): threshold 15 mg, light 30-60 mg, common 60-90 mg, strong 90-120 mg, heavy 120+ mg. No controlled human dosing studies exist for 6-APB. These values are carried forward from existing community-curated database values.

Evidence basis: community_consensus_large

Duration

oral

FieldPublishedAI ProposedConfidence
Peaktrace3–4 hours3–4 hourslow
Editorial

Peak duration 3-4 hours from community consensus data. No controlled study.

Reasoning

Peak duration 3-4 hours from community consensus data. No controlled study.

Evidence basis: community_consensus_large

Totaltrace7–10 hours7–10 hourslow
Editorial

Total subjective duration 7-10 hours from community consensus data. Substantially longer than MDMA. No controlled human study.

Reasoning

Total subjective duration 7-10 hours from community consensus data. Substantially longer than MDMA. No controlled human study.

Evidence basis: community_consensus_large

Onsettrace30–60 minutes30–60 minuteslow
Editorial

Onset 30-60 minutes from community consensus data. No controlled human study.

Reasoning

Onset 30-60 minutes from community consensus data. No controlled human study.

Evidence basis: community_consensus_large

Come uptrace60–120 minutes60–120 minuteslow
Editorial

Come-up 60-120 minutes from community consensus data. Notably longer than MDMA come-up. No controlled study.

Reasoning

Come-up 60-120 minutes from community consensus data. Notably longer than MDMA come-up. No controlled study.

Evidence basis: community_consensus_large

Offsettrace1.5–2.5 hours1.5–2.5 hourslow
Editorial

Offset duration estimated from total duration minus onset/come-up/peak. Community sources suggest gradual comedown. No controlled study.

Reasoning

Offset duration estimated from total duration minus onset/come-up/peak. Community sources suggest gradual comedown. No controlled study.

Evidence basis: community_consensus_large

After effectstrace6–24 hours6–24 hourslow
Editorial

Aftereffects duration estimated from entactogen class profile. Residual stimulation, mood changes, and sleep disruption may persist 6-24 hours beyond subjective offset. No controlled data.

Reasoning

Aftereffects duration estimated from entactogen class profile. Residual stimulation, mood changes, and sleep disruption may persist 6-24 hours beyond subjective offset. No controlled data.

Evidence basis: structural_analogy

Safety

Toxicity Profiletrace

FieldPublishedAI ProposedConfidence
Acutemoderatemoderatelow
Chronicmoderatemoderatelow
Organs Affectedcardiovascular, liver, braincardiovascular, liver, brainlow
Editorial

Classified as moderate acute (downgraded from high): no human LD50 or controlled toxicity data exist; acute risk assessment based on class-level serotonergic toxicity (Liechti 2015) and benzofuran class review (Nugteren-van Lonkhuyzen 2015). Classified as moderate chronic: 5-HT2B full agonism (<100 nM) confirmed in vitro (Rickli 2015, Iversen 2013) with established valvulopathy mechanism, but no human cardiac outcome data; hepatotoxicity EC50 values (Roque Bravo 2020) are at millimolar concentrations far above expected plasma levels. Evidence discount applied: all toxicity data are in vitro or class-extrapolated.

Reasoning

Classified as moderate acute (downgraded from high): no human LD50 or controlled toxicity data exist; acute risk assessment based on class-level serotonergic toxicity (Liechti 2015) and benzofuran class review (Nugteren-van Lonkhuyzen 2015). Classified as moderate chronic: 5-HT2B full agonism (<100 nM) confirmed in vitro (Rickli 2015, Iversen 2013) with established valvulopathy mechanism, but no human cardiac outcome data; hepatotoxicity EC50 values (Roque Bravo 2020) are at millimolar concentrations far above expected plasma levels. Evidence discount applied: all toxicity data are in vitro or class-extrapolated.

Evidence basis: animal_study

Dependence Profiletrace

FieldPublishedAI ProposedConfidence
Physicallowlowlow
Psychologicalmoderatemoderatelow
Compulsive Redosinglowlowlow
Dose Escalationlowlowlow
Editorial

No substance-specific dependence studies exist. Assessment inferred from MDMA/MDA class pharmacology and the Hill et al. (2023) drug discrimination data demonstrating abuse potential. Physical dependence rated low rather than none because monoamine depletion following heavy use may produce a withdrawal-like state, though this is unconfirmed for 6-APB.

Reasoning

No substance-specific dependence studies exist. Assessment inferred from MDMA/MDA class pharmacology and the Hill et al. (2023) drug discrimination data demonstrating abuse potential. Physical dependence rated low rather than none because monoamine depletion following heavy use may produce a withdrawal-like state, though this is unconfirmed for 6-APB.

Evidence basis: structural_analogy

Withdrawal Profiletrace

FieldPublishedAI ProposedConfidence
Severitymildmildlow
Symptomsdepressed mood, fatigue, irritability, difficulty concentrating, anhedoniadepressed mood, fatigue, irritability, difficulty concentrating, anhedonialow
FatalNoNolow
Medical SupervisionNot requiredNot requiredlow
Editorial

No published withdrawal data specific to 6-APB. Withdrawal profile inferred from MDMA/entactogen class: post-use serotonergic depletion produces a 'comedown' characterized by low mood, fatigue, and cognitive dulling. Not a classical physical withdrawal syndrome.

Reasoning

No published withdrawal data specific to 6-APB. Withdrawal profile inferred from MDMA/entactogen class: post-use serotonergic depletion produces a 'comedown' characterized by low mood, fatigue, and cognitive dulling. Not a classical physical withdrawal syndrome.

Evidence basis: structural_analogy

Tolerance Profiletrace

FieldPublishedAI ProposedConfidence
Buildupmoderatemoderatelow
Half-life24.5 days24.5 dayslow
Full Reset49 days49 dayslow
Cross-tolerancesMDMA, MDA, 5-APB, serotonin releasing agents, dopaminergic stimulantsMDMA, MDA, 5-APB, serotonin releasing agents, dopaminergic stimulantslow
Editorial

No published tolerance studies exist for 6-APB. Half-life and reset values carried forward from existing community database (seed data: 3.5 weeks half-life, 7 weeks full reset). Mechanism inferred from MDMA serotonergic depletion model. Cross-tolerances inferred from shared monoamine transporter mechanisms.

Reasoning

No published tolerance studies exist for 6-APB. Half-life and reset values carried forward from existing community database (seed data: 3.5 weeks half-life, 7 weeks full reset). Mechanism inferred from MDMA serotonergic depletion model. Cross-tolerances inferred from shared monoamine transporter mechanisms.

Evidence basis: structural_analogy

Effects & Profile

Contraindications

FieldPublishedAI ProposedConfidence
cardiovascular valvular heart diseasetraceabsoluteabsolutemedium
Editorial

5-HT2B full agonism confirmed by Rickli et al. (2015) and Iversen et al. (2013). Valvulopathy mechanism established by Smith et al. (2009) and Dumotier (2024). No human cardiac outcome data for 6-APB, but mechanism is well-characterized for this drug class.

Reasoning

5-HT2B full agonism confirmed by Rickli et al. (2015) and Iversen et al. (2013). Valvulopathy mechanism established by Smith et al. (2009) and Dumotier (2024). No human cardiac outcome data for 6-APB, but mechanism is well-characterized for this drug class.

cardiovascular cardiac arrhythmiastracerelativerelativelow
Editorial

Class inference from monoamine releasing agent pharmacology. No 6-APB-specific cardiac electrophysiology data exist.

Reasoning

Class inference from monoamine releasing agent pharmacology. No 6-APB-specific cardiac electrophysiology data exist.

psychiatric psychotic disorderstracerelativerelativemedium
Editorial

Case report (Chan et al. 2013) documents acute psychosis with 6-APB use. Broader NPS literature (Schifano et al. 2019) associates serotonergic designer drugs with psychopathological consequences.

Reasoning

Case report (Chan et al. 2013) documents acute psychosis with 6-APB use. Broader NPS literature (Schifano et al. 2019) associates serotonergic designer drugs with psychopathological consequences.

psychiatric bipolar disordertracerelativerelativelow
Editorial

Class inference from monoamine releasing agent pharmacology. No 6-APB-specific data on bipolar interaction.

Reasoning

Class inference from monoamine releasing agent pharmacology. No 6-APB-specific data on bipolar interaction.

hepatic hepatic impairmenttracerelativerelativemedium
Editorial

Roque Bravo et al. (2020) demonstrated CYP3A4-mediated hepatotoxic metabolite formation. In vitro hepatotoxicity confirmed across multiple cell models.

Reasoning

Roque Bravo et al. (2020) demonstrated CYP3A4-mediated hepatotoxic metabolite formation. In vitro hepatotoxicity confirmed across multiple cell models.

other concurrent MAOI usetraceabsoluteabsolutehigh
Editorial

Standard pharmacological contraindication for all monoamine releasing agents. The combination of MAOIs with serotonin releasers is a well-established lethal interaction class.

Reasoning

Standard pharmacological contraindication for all monoamine releasing agents. The combination of MAOIs with serotonin releasers is a well-established lethal interaction class.

other concurrent serotonergic medicationtracerelativerelativemedium
Editorial

Class inference from serotonergic entactogen pharmacology. Liechti (2015) and Luethi & Liechti (2020) describe serotonin syndrome risk with serotonergic drug combinations.

Reasoning

Class inference from serotonergic entactogen pharmacology. Liechti (2015) and Luethi & Liechti (2020) describe serotonin syndrome risk with serotonergic drug combinations.

pregnancy breastfeeding pregnancy and breastfeedingtraceabsoluteabsolutemedium
Editorial

Standard precautionary contraindication for novel psychoactive substances with no reproductive safety data. Class inference from amphetamine/MDMA developmental toxicity literature.

Reasoning

Standard precautionary contraindication for novel psychoactive substances with no reproductive safety data. Class inference from amphetamine/MDMA developmental toxicity literature.

Timeline Phases

oral

FieldPublishedAI ProposedConfidence
Onsettrace1800–3600 sec(i=0.05)1800–3600 sec(i=0.05)low
Editorial

All timeline data derived from community consensus sources (PsychonautWiki, user reports). No controlled human pharmacokinetic or pharmacodynamic studies have been published for 6-APB. Community-reported total duration of 7–10 hours and onset of 30–60 minutes used as primary anchors. The notably long come-up (60–120 min) and extended peak (3–4 hours) distinguish 6-APB from MDMA and are consistently reported across community sources.

Reasoning

All timeline data derived from community consensus sources (PsychonautWiki, user reports). No controlled human pharmacokinetic or pharmacodynamic studies have been published for 6-APB. Community-reported total duration of 7–10 hours and onset of 30–60 minutes used as primary anchors. The notably long come-up (60–120 min) and extended peak (3–4 hours) distinguish 6-APB from MDMA and are consistently reported across community sources.

Come uptrace3600–7200 sec(i=0.30)3600–7200 sec(i=0.30)low
Editorial

All timeline data derived from community consensus sources (PsychonautWiki, user reports). No controlled human pharmacokinetic or pharmacodynamic studies have been published for 6-APB. Community-reported total duration of 7–10 hours and onset of 30–60 minutes used as primary anchors. The notably long come-up (60–120 min) and extended peak (3–4 hours) distinguish 6-APB from MDMA and are consistently reported across community sources.

Reasoning

All timeline data derived from community consensus sources (PsychonautWiki, user reports). No controlled human pharmacokinetic or pharmacodynamic studies have been published for 6-APB. Community-reported total duration of 7–10 hours and onset of 30–60 minutes used as primary anchors. The notably long come-up (60–120 min) and extended peak (3–4 hours) distinguish 6-APB from MDMA and are consistently reported across community sources.

Peaktrace10800–14400 sec(i=1.00)10800–14400 sec(i=1.00)low
Editorial

All timeline data derived from community consensus sources (PsychonautWiki, user reports). No controlled human pharmacokinetic or pharmacodynamic studies have been published for 6-APB. Community-reported total duration of 7–10 hours and onset of 30–60 minutes used as primary anchors. The notably long come-up (60–120 min) and extended peak (3–4 hours) distinguish 6-APB from MDMA and are consistently reported across community sources.

Reasoning

All timeline data derived from community consensus sources (PsychonautWiki, user reports). No controlled human pharmacokinetic or pharmacodynamic studies have been published for 6-APB. Community-reported total duration of 7–10 hours and onset of 30–60 minutes used as primary anchors. The notably long come-up (60–120 min) and extended peak (3–4 hours) distinguish 6-APB from MDMA and are consistently reported across community sources.

Plateautrace5400–7200 sec(i=0.55)5400–7200 sec(i=0.55)low
Editorial

All timeline data derived from community consensus sources (PsychonautWiki, user reports). No controlled human pharmacokinetic or pharmacodynamic studies have been published for 6-APB. Community-reported total duration of 7–10 hours and onset of 30–60 minutes used as primary anchors. The notably long come-up (60–120 min) and extended peak (3–4 hours) distinguish 6-APB from MDMA and are consistently reported across community sources.

Reasoning

All timeline data derived from community consensus sources (PsychonautWiki, user reports). No controlled human pharmacokinetic or pharmacodynamic studies have been published for 6-APB. Community-reported total duration of 7–10 hours and onset of 30–60 minutes used as primary anchors. The notably long come-up (60–120 min) and extended peak (3–4 hours) distinguish 6-APB from MDMA and are consistently reported across community sources.

Resolutiontrace5400–9000 sec(i=0.20)5400–9000 sec(i=0.20)low
Editorial

All timeline data derived from community consensus sources (PsychonautWiki, user reports). No controlled human pharmacokinetic or pharmacodynamic studies have been published for 6-APB. Community-reported total duration of 7–10 hours and onset of 30–60 minutes used as primary anchors. The notably long come-up (60–120 min) and extended peak (3–4 hours) distinguish 6-APB from MDMA and are consistently reported across community sources.

Reasoning

All timeline data derived from community consensus sources (PsychonautWiki, user reports). No controlled human pharmacokinetic or pharmacodynamic studies have been published for 6-APB. Community-reported total duration of 7–10 hours and onset of 30–60 minutes used as primary anchors. The notably long come-up (60–120 min) and extended peak (3–4 hours) distinguish 6-APB from MDMA and are consistently reported across community sources.

Afterglowtrace21600–86400 sec(i=0.05)21600–86400 sec(i=0.05)low
Editorial

All timeline data derived from community consensus sources (PsychonautWiki, user reports). No controlled human pharmacokinetic or pharmacodynamic studies have been published for 6-APB. Community-reported total duration of 7–10 hours and onset of 30–60 minutes used as primary anchors. The notably long come-up (60–120 min) and extended peak (3–4 hours) distinguish 6-APB from MDMA and are consistently reported across community sources.

Reasoning

All timeline data derived from community consensus sources (PsychonautWiki, user reports). No controlled human pharmacokinetic or pharmacodynamic studies have been published for 6-APB. Community-reported total duration of 7–10 hours and onset of 30–60 minutes used as primary anchors. The notably long come-up (60–120 min) and extended peak (3–4 hours) distinguish 6-APB from MDMA and are consistently reported across community sources.

Dose Tier Summaries

thresholdtrace
low

At threshold doses (~15 mg oral), effects are subtle and easily dismissed: a faint mood lift, mild increase in sociability, and slight enhancement of sensory appreciation — particularly music and tactile sensation. Some users report a gentle body warmth and marginal pupil dilation. Physical effects are minimal at this range. Slight appetite suppression and mild restlessness may occur but remain sub-perceptual for many individuals. Functional impairment is negligible, though sleep may be delayed by 2–3 hours if taken in the evening.

Editorial

Threshold dose (15 mg) from community consensus sources (PsychonautWiki). No controlled human study confirms this value. Experiential description inferred from MDMA/MDA threshold profiles adjusted for 6-APB's reported character.

Reasoning

Threshold dose (15 mg) from community consensus sources (PsychonautWiki). No controlled human study confirms this value. Experiential description inferred from MDMA/MDA threshold profiles adjusted for 6-APB's reported character.

Evidence basis: community_consensus_large

lighttrace
low

At light doses (30–60 mg oral), the entactogenic character becomes apparent: mild empathy enhancement, increased desire for social interaction, gentle euphoria, and subtle emotional warmth. Sensory perception sharpens — colors appear slightly more vivid, music acquires greater emotional resonance. Some users note the first traces of the psychedelic quality that distinguishes 6-APB from MDMA: mild visual brightening and enhanced pattern recognition. Physical effects include moderate pupil dilation, increased heart rate, jaw tension (trismus), and mild body temperature elevation. Appetite suppression is noticeable. The experience lasts approximately 5–7 hours, with residual stimulation making sleep difficult for several hours beyond subjective offset.

Editorial

Light dose range (30–60 mg) from community consensus sources. No controlled study. Experiential description inferred from entactogen class pharmacology and community reports describing 6-APB's intermediate entactogen-psychedelic character.

Reasoning

Light dose range (30–60 mg) from community consensus sources. No controlled study. Experiential description inferred from entactogen class pharmacology and community reports describing 6-APB's intermediate entactogen-psychedelic character.

Evidence basis: community_consensus_large

commontrace
low

At common doses (60–90 mg oral), the full entactogenic-psychedelic profile emerges. Empathy enhancement becomes pronounced — emotional openness, feelings of closeness and connection, and enhanced capacity for introspection. Euphoria is robust. The psychedelic component manifests as mild visual distortions: enhanced color saturation, surface texturing, gentle drifting and morphing of objects. Music appreciation deepens substantially. Thought patterns become more associative and fluid. Physically, stimulation is moderate to strong: elevated heart rate, noticeable jaw clenching, body temperature increase, and significant pupil dilation. Nausea during the come-up is reported by some users. The total experience duration extends to 7–10 hours, considerably longer than MDMA, with residual stimulation and emotional sensitivity persisting beyond the primary effects.

Editorial

Common dose range (60–90 mg) from community consensus sources. Experiential description derived from community reports and pharmacological profile as monoamine releaser with serotonergic receptor agonism. Duration (7–10 hours) from community data.

Reasoning

Common dose range (60–90 mg) from community consensus sources. Experiential description derived from community reports and pharmacological profile as monoamine releaser with serotonergic receptor agonism. Duration (7–10 hours) from community data.

Evidence basis: community_consensus_large

strongtrace
low

At strong doses (90–120 mg oral), the experience intensifies across all domains. Entactogenic effects reach maximum expression: overwhelming feelings of empathy, emotional vulnerability, and interpersonal connection. The psychedelic component becomes unmistakable — visual distortions include pronounced color shifts, geometric patterning on surfaces, object morphing, and tracers. Cognitive effects include time distortion, thought acceleration, and heightened introspective depth. Some users report experiences approaching ego dissolution at the upper end of this range. Physical load increases substantially: strong jaw clenching, marked tachycardia, perspiration, temperature dysregulation, and difficulty urinating. Nausea is more common during onset. The commitment is significant — 8–10 hours of primary effects with an extended afterglow period. Sleep is impossible for 10–12 hours post-ingestion.

Editorial

Strong dose range (90–120 mg) from community consensus sources. No controlled data. Experiential description extrapolated from entactogen-psychedelic pharmacological profile and community experience reports. Duration extended relative to common dose range per community reporting.

Reasoning

Strong dose range (90–120 mg) from community consensus sources. No controlled data. Experiential description extrapolated from entactogen-psychedelic pharmacological profile and community experience reports. Duration extended relative to common dose range per community reporting.

Evidence basis: community_consensus_large

heavytrace
low

At heavy doses (120+ mg oral), the experience becomes overwhelming for most users. The entactogenic and psychedelic components merge into an intense, potentially disorienting state. Strong visual distortions, pronounced thought loops, emotional flooding, and significant cognitive impairment dominate. The boundary between entactogenic warmth and psychedelic intensity blurs, and the experience may become anxiogenic or dysphoric, particularly without adequate set and setting preparation. Physical risks escalate substantially at this range: severe tachycardia, hyperthermia risk, pronounced bruxism, and significant cardiovascular strain. Nausea and vomiting become more likely. The duration extends to 10+ hours with prolonged residual stimulation. This dose range carries meaningfully increased risk of serotonergic adverse effects and should be considered high-risk.

Editorial

Heavy dose (120+ mg) from community consensus sources. No controlled data. Experiential and risk description inferred from serotonergic entactogen pharmacology and the dose-dependent toxicity profile. Elevated risk assessment based on class-level serotonin syndrome and cardiovascular concerns.

Reasoning

Heavy dose (120+ mg) from community consensus sources. No controlled data. Experiential and risk description inferred from serotonergic entactogen pharmacology and the dose-dependent toxicity profile. Elevated risk assessment based on class-level serotonin syndrome and cardiovascular concerns.

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

1 strong · 13 moderate · 6 weak
  1. [1]
    moderate
    Pharmacological profile of novel psychoactive benzofurans
    Rickli A, Kopf S, Hoener MC, Liechti ME · 2015 · British Journal of Pharmacology
    doi.org/10.1111/bph.13128pubmed 2576550016 claims checked15 verified1 inconclusive
  2. [2]
    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 232614999 claims checked9 verified
  3. [3]
    moderate
    Role of serotoninergic pathways in drug-induced valvular heart disease and diagnostic features by echocardiography
    Smith SA, Waggoner AD, de las Fuentes L, Davila-Roman VG · 2009 · Journal of the American Society of Echocardiography
    doi.org/10.1016/j.echo.2009.05.002pubmed 195530854 claims checked3 verified1 inconclusive
  4. [4]
    moderate
    The mechanobiology of drug-induced cardiac valve disease
    Lam NT, Balachandran K · 2015 · Journal of Long-term Effects of Medical Implants
    pubmed 259550052 claims checked2 verified
  5. [5]
    weak
    Acute psychosis associated with recreational use of benzofuran 6-(2-aminopropyl)benzofuran (6-APB) and cannabis
    Chan WL, Wood DM, Hudson S, Dargan PI · 2013 · Journal of Medical Toxicology
    doi.org/10.1007/s13181-013-0306-ypubmed 237337146 claims checked6 verified
  6. [6]
    weak
    UK Misuse of Drugs (Temporary Class Drug) Order 2013 (SI 2013/1294)
    UK Government · 2013
    linkno claims checked
  7. [7]
    weak
    UK Misuse of Drugs Act 1971 Amendment Order 2014 (SI 2014/1106) - Benzofuran Class B
    UK Government · 2014
    linkno claims checked
  8. [8]
    weak
    6-APB (1-(Benzofuran-6-yl)propan-2-amin) listed in German Betäubungsmittelgesetz (BtMG) Annex II
    German Federal Government · 2023
    linkno claims checked
  9. [9]
    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 347505654 claims checked4 verified
  10. [10]
    moderate
    Preclinical mitigation of 5-HT2B agonism-related cardiac valvulopathy revisited
    Dumotier BM, Urban L · 2024 · Journal of Pharmacological and Toxicological Methods
    doi.org/10.1016/j.vascn.2024.107542pubmed 390324413 claims checked1 verified2 inconclusive
  11. [11]
    weak
    Amphetamine-derived new psychoactive substances: metabolic fate and toxicological detectability of methiopropamine, three methyl-amphetamine isomers, camfetamine, 5-APB, 6-APB, 5-MAPB, and 6-MAPB
    Welter-Lüdeke J · 2015 · Publications of Saarland University
    doi.org/10.22028/d291-230997 claims checked6 verified1 inconclusive
  12. [12]
    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
    Roque Bravo R, Carmo H, Silva JP, Valente MJ, Carvalho F, Bastos ML, Dias da Silva D · 2020 · Archives of Toxicology
    doi.org/10.1007/s00204-019-02638-9pubmed 318385657 claims checked7 verified
  13. [13]
    moderate
    Novel psychoactive substances (designer drugs): overview and pharmacology of modulators of monoamine signaling
    Liechti ME · 2015 · Swiss Medical Weekly
    doi.org/10.4414/smw.2015.14043pubmed 255880184 claims checked3 verified1 inconclusive
  14. [14]
    moderate
    Legal highs: staying on top of the flood of novel psychoactive substances
    Baumeister D, Tojo LM, Tracy DK · 2015 · Therapeutic Advances in Psychopharmacology
    doi.org/10.1177/2045125314559539pubmed 262407491 claim checked1 inconclusive
  15. [15]
    moderate
    Locomotor and discriminative stimulus effects of three benzofuran compounds in comparison to abused psychostimulants
    Hill RD, Shetty RA, Sumien N, Forster MJ, Gatch MB · 2023 · Drug and Alcohol Dependence Reports
    doi.org/10.1016/j.dadr.2023.100182pubmed 376001515 claims checked5 verified
  16. [16]
    weak
    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
    doi.org/10.1016/j.forsciint.2014.10.016pubmed 254471853 claims checked3 verified
  17. [17]
    moderate
    Hair Testing for Drugs of Abuse and New Psychoactive Substances in a High-Risk Population
    Salomone A, Palamar JJ, Gerace E, Di Corcia D, Vincenti M · 2017 · Journal of Analytical Toxicology
    doi.org/10.1093/jat/bkx020pubmed 283348051 claim checked1 verified
  18. [18]
    moderate
    Pharmacokinetics, pharmacodynamics and toxicology of new psychoactive substances (NPS): 2C-B, 4-fluoroamphetamine and benzofurans
    Nugteren-van Lonkhuyzen JJ, van Riel AJ, Brunt TM, Hondebrink L · 2015 · Drug and Alcohol Dependence
    doi.org/10.1016/j.drugalcdep.2015.10.011pubmed 265305011 claim checked1 verified
  19. [19]
    moderate
    New/emerging psychoactive substances and associated psychopathological consequences
    Schifano F, Napoletano F, Chiappini S, Guirguis A, Corkery J · 2019 · Psychological Medicine
    doi.org/10.1017/s0033291719001727pubmed 313273321 claim checked1 verified
  20. [20]
    strong
    Designer drugs: mechanism of action and adverse effects
    Luethi D, Liechti ME · 2020 · Archives of Toxicology
    doi.org/10.1007/s00204-020-02693-7pubmed 322493471 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.

summary7 claims7verified
verified6-APB appeared on the European novel psychoactive substance market circa 2010–2011, marketed under the trade name "Benzofury." The first published case report appeared in 2013, followed by systematic in vitro pharmacological characterizations by Iversen et al. and Rickli et al., which established the compound's receptor and transporter profile[5]model confidence 85%
Verified

Abstract is the case report referenced; confirms 6-APB availability in Europe and documents the clinical incident, supporting the 'first published case report' portion of the claim.

Case report of acute toxicity associated with recreational use of 6-APB and cannabis. Presents evidence of 6-APB availability in Europe.

checked by claude-sonnet-4-6 · Apr 21, 2026

verified6-APB appeared on the European novel psychoactive substance market circa 2010–2011, marketed under the trade name "Benzofury." The first published case report appeared in 2013, followed by systematic in vitro pharmacological characterizations by Iversen et al. and Rickli et al., which established the compound's receptor and transporter profile[2]model confidence 88%
Verified

Abstract confirms Iversen et al. screened 6-APB against human receptors and monoamine uptake assays, establishing the receptor and transporter profile — directly supporting the 'Iversen et al.' portion of the claim.

14 novel psychoactive substances screened at human receptors. 6-APB exhibited <100 nM affinity for 5HT2B and alpha2C receptors. Functional assays confirmed 5-APB and 6-APB as potent full agonists at 5HT2B receptors. 6-APB inhibited monoamine uptake at submicromolar concentrations.

checked by claude-sonnet-4-6 · Apr 21, 2026

verified6-APB appeared on the European novel psychoactive substance market circa 2010–2011, marketed under the trade name "Benzofury." The first published case report appeared in 2013, followed by systematic in vitro pharmacological characterizations by Iversen et al. and Rickli et al., which established the compound's receptor and transporter profile[1]model confidence 88%
Verified

Abstract confirms Rickli et al. characterized benzofurans in vitro including transporter and receptor interactions, supporting the 'Rickli et al.' portion of the compound history claim.

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 21, 2026

verified6-APB acts as a non-selective monoamine releasing agent at the serotonin, dopamine, and norepinephrine transporters, functioning similarly to MDMA[1]model confidence 95%
Verified

Abstract directly states benzofurans 'acted as indirect monoamine agonists interacting with transporters similarly to MDMA,' which is exactly the claim made.

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

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedIt is a potent full agonist at the 5-HT₂B receptor with sub-100 nM affinity, and interacts with additional serotonin receptor subtypes that likely contribute psychedelic-like qualities[2]model confidence 87%
Verified

Abstract explicitly confirms <100 nM affinity at 5-HT2B and full agonist status. The 'additional serotonin receptor subtypes' portion is partially extrapolated, but the core pharmacological claim is directly supported.

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

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedThe 5-HT₂B full agonism of 6-APB raises a specific cardiac safety concern: chronic activation of valvular 5-HT₂B receptors promotes fibroproliferative changes associated with drug-induced valvulopathy, though no human echocardiographic studies of 6-APB users have been conducted[1]model confidence 90%
Verified

Abstract explicitly states benzofurans induce 5-HT2B receptor activation associated with heart valve fibrosis, directly supporting the cardiac safety concern.

Benzofurans induce 5-HT2B receptor activation associated with heart valve fibrosis.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedThe 5-HT₂B full agonism of 6-APB raises a specific cardiac safety concern: chronic activation of valvular 5-HT₂B receptors promotes fibroproliferative changes associated with drug-induced valvulopathy, though no human echocardiographic studies of 6-APB users have been conducted[3]model confidence 93%
Verified

Abstract is a review specifically on 5-HT2B receptor role in drug-induced cardiac valvulopathy, confirming agonism leads to fibrosis and valve disease — directly supports the cardiac safety mechanism.

Review of 5-HT2B receptor role in drug-induced cardiac valvulopathy. 5-HT2B receptor widely expressed in cardiac tissues. Agonism leads to fibrosis and valve disease similar to carcinoid heart disease.

checked by claude-sonnet-4-6 · Apr 21, 2026

history3 claims3verified
verifiedThe first peer-reviewed case report involving 6-APB was published by Chan et al. in 2013, documenting acute psychosis in a patient who had consumed 6-APB alongside cannabis and the synthetic cannabinoid JWH-122[5]model confidence 95%
Verified

Abstract is the case report, confirming 6-APB plus JWH-122 ingestion and acute toxicity. SCOPE explicitly labels this 'First published case report of acute 6-APB toxicity.'

Case report of acute toxicity associated with recreational use of 6-APB and cannabis. Comprehensive toxicological analysis confirmed 6-APB plus metabolites of THC and JWH-122.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedThe systematic pharmacological characterization of the benzofuran class began with Iversen et al. in 2013, who screened 6-APB against human receptors and monoamine uptake assays, identifying its high-affinity 5-HT₂B agonism and monoamine transporter inhibition[2]model confidence 95%
Verified

Abstract confirms the screening of 6-APB against human receptors and monoamine uptake assays, identifying <100 nM 5-HT2B affinity, full agonism, and submicromolar monoamine uptake inhibition.

14 novel psychoactive substances screened at human receptors. 6-APB exhibited <100 nM affinity for 5HT2B and alpha2C receptors. Functional assays confirmed 5-APB and 6-APB as potent full agonists at 5HT2B receptors. 6-APB inhibited monoamine uptake at submicromolar concentrations.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedRickli et al. published a comprehensive in vitro profiling of benzofuran compounds in 2015, confirming the transporter-mediated release mechanism and drawing explicit comparisons to MDMA[1]model confidence 93%
Verified

Abstract confirms comprehensive in vitro pharmacological characterization of benzofurans with explicit MDMA comparison. The year (2015) is not verifiable from the abstract but the content matches.

Benzofurans pharmacologically characterized in vitro. Benzofurans acted as indirect monoamine agonists interacting with transporters similarly to MDMA.

checked by claude-sonnet-4-6 · Apr 21, 2026

chemistry1 claim1inconclusive
inconclusiveThis substitution is directly analogous to the relationship between MDA and 6-APB: where MDA bears a 3,4-methylenedioxy group on its phenyl ring, 6-APB incorporates a benzofuran ring that contributes to its distinct pharmacological profile. 6-APB is a positional isomer of 5-APB, which carries the aminopropyl chain at the 5-position of the benzofuran ring rather than the 6-position.[1]model confidence 70%
Inconclusive

Abstract covers in vitro pharmacology of benzofurans but does not address structural chemistry — the specific claim about MDA analogy, ring positions, or 5-APB vs 6-APB positional isomers. These details would be in the paper's introduction/methods, not the abstract.

Benzofurans pharmacologically characterized in vitro.

checked by claude-sonnet-4-6 · Apr 21, 2026

pharmacology14 claims14verified
verifiedRickli et al. characterized the benzofurans in vitro and concluded they act as "indirect monoamine agonists that interact with transporters similarly to MDMA"[1]model confidence 98%
Verified

Abstract language is nearly verbatim: 'Benzofurans acted as indirect monoamine agonists interacting with transporters similarly to MDMA.'

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

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedThis transporter-mediated release mechanism was corroborated by Rudin et al. in a comparison study of benzo[β]thiophene analogs that employed APB compounds as reference standards.[9]model confidence 90%
Verified

Abstract confirms APBT positional isomers were compared to APB analogs, and APBs were confirmed as non-selective monoamine releasers — corroborating the transporter-mediated release mechanism.

APBT positional isomers compared to APB analogs. APBs (including 6-APB analogs) confirmed as non-selective monoamine releasers like MDMA that induce transporter-mediated substrate release.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedIversen et al. screened 6-APB against a panel of human receptors and monoamine uptake assays[2]model confidence 98%
Verified

Abstract directly states 14 novel psychoactive substances were screened at human receptors and monoamine uptake was assessed for 6-APB.

14 novel psychoactive substances screened at human receptors... 6-APB inhibited monoamine uptake at submicromolar concentrations.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedThe compound additionally interacts with serotonin receptor subtypes beyond 5-HT₂B, and full 5-HT₂ receptor agonism has been confirmed in related benzofuran compounds[1]model confidence 82%
Verified

Abstract states benzofurans 'also interacted with 5-HT receptors,' supporting interactions with serotonin receptor subtypes. The specific 'full 5-HT₂ agonism in related compounds' is better supported by citation [16], but this abstract covers the first part.

Also interacted with 5-HT receptors.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedThe compound additionally interacts with serotonin receptor subtypes beyond 5-HT₂B, and full 5-HT₂ receptor agonism has been confirmed in related benzofuran compounds[9]model confidence 92%
Verified

Abstract explicitly states APBT isomers (closely related to APBs) show full agonism at 5-HT2 receptor subtypes, directly supporting the claim about full 5-HT₂ agonism in structurally related compounds.

APBT isomers additionally show full agonism at 5-HT2 receptor subtypes.

checked by claude-sonnet-4-6 · Apr 21, 2026

verified6-APB is a full agonist at the 5-HT₂B receptor with high affinity (<100 nM), as independently confirmed by both Rickli et al. and Iversen et al.[1]model confidence 83%
Verified

Abstract confirms benzofurans induce 5-HT2B receptor activation, supporting the agonism claim. The specific <100 nM affinity figure isn't in this abstract but the 5-HT2B agonism (which this paper established in vitro) is confirmed.

Benzofurans induce 5-HT2B receptor activation associated with heart valve fibrosis.

checked by claude-sonnet-4-6 · Apr 21, 2026

verified6-APB is a full agonist at the 5-HT₂B receptor with high affinity (<100 nM), as independently confirmed by both Rickli et al. and Iversen et al.[2]model confidence 98%
Verified

Abstract explicitly states 6-APB exhibited <100 nM affinity for 5HT2B and functional assays confirmed potent full agonist status — a direct match.

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

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedRickli et al. explicitly noted that benzofuran 5-HT₂B activation is associated with heart valve fibrosis[1]model confidence 99%
Verified

Abstract states verbatim: 'Benzofurans induce 5-HT2B receptor activation associated with heart valve fibrosis.' This is a direct match.

Benzofurans induce 5-HT2B receptor activation associated with heart valve fibrosis.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedThe underlying mechanism is well established: 5-HT₂B receptor agonism on cardiac valve interstitial cells promotes myofibroblast transformation and fibroproliferative remodeling of valve leaflets[3]model confidence 82%
Verified

Abstract confirms 5-HT2B agonism leads to fibrosis and valve disease. The specific 'myofibroblast transformation' detail is not in this abstract but the general mechanism is directly supported; the more granular mechanistic detail is in citation [15].

Agonism leads to fibrosis and valve disease similar to carcinoid heart disease.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedThe underlying mechanism is well established: 5-HT₂B receptor agonism on cardiac valve interstitial cells promotes myofibroblast transformation and fibroproliferative remodeling of valve leaflets[4]model confidence 97%
Verified

Abstract explicitly states the review focuses on '5-HT2B receptor activation causing myofibroblast phenotype, cell proliferation, and valve fibrosis' — directly matching the mechanistic claim.

Review of mechanism of drug-induced cardiac valvulopathy, focusing on 5-HT2B receptor activation causing myofibroblast phenotype, cell proliferation, and valve fibrosis.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedThis gap is particularly concerning given the compound's continued recreational use and the established dose-response relationship between cumulative 5-HT₂B agonist exposure and valvulopathy risk.[10]model confidence 87%
Verified

Abstract establishes that sustained plasma exposure (AUC) rather than peak predicts cardiac valvulopathy risk, which is consistent with a cumulative exposure-risk relationship.

Sustained plasma exposure (AUC) rather than peak Cmax better predicts clinical CVD risk.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedAromatic hydroxylation reactions are catalyzed by CYP2D6 and CYP2C19[11]model confidence 99%
Verified

Abstract directly states 'Aromatic hydroxylations by CYP2D6 and CYP2C19' — exact match.

Aromatic hydroxylations by CYP2D6 and CYP2C19.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedNotably, 6-APB undergoes only minor metabolism overall, with the unchanged parent compound representing the primary analyte for urinalysis.[11]model confidence 99%
Verified

Abstract directly states '6-APB metabolized only to minor extent; unchanged drug is main urinary target' — exact match.

6-APB metabolized only to minor extent; unchanged drug is main urinary target.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedRoque Bravo et al. demonstrated that co-incubation of primary hepatocytes with CYP450 inhibitors reduced 6-APB cytotoxicity, implicating CYP3A4 specifically in the metabolic activation of 6-APB to toxic intermediates.[12]model confidence 85%
Verified

Abstract confirms CYP3A4 involvement in toxic metabolism in the in vitro hepatocyte study; the co-incubation experiment result logically follows from this finding though not explicitly stated in the abstract.

CYP3A4 involved in toxic metabolism.

checked by claude-sonnet-4-6 · Apr 21, 2026

receptor pharmacology8 claims8verified
verified6-APB inhibits monoamine uptake at submicromolar concentrations across all three major monoamine transporters (SERT, DAT, NET)[2]model confidence 88%
Verified

Abstract directly states '6-APB inhibited monoamine uptake at submicromolar concentrations.' The 'all three transporters (SERT, DAT, NET)' specificity is not in the abstract but is consistent with the 'monoamine' (non-selective) characterization.

6-APB inhibited monoamine uptake at submicromolar concentrations.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedRickli et al. characterized the compound as an "indirect monoamine agonist" that releases serotonin, dopamine, and norepinephrine through transporter-mediated efflux[1]model confidence 92%
Verified

Abstract uses the exact term 'indirect monoamine agonists interacting with transporters' — the specific monoamines (5-HT, DA, NE) follow from the non-selective characterization and MDMA comparison.

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

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedQuantitative Ki and EC₅₀ values for each individual transporter are reported in the full publication by Rickli et al. but were not accessible from the abstract; the complete binding table remains behind a paywall.[1]model confidence 90%
Verified

The abstract confirms the paper covers in vitro pharmacological characterization but provides no specific Ki or EC50 values — exactly what the claim asserts. The claim accurately describes the abstract's limitations.

Benzofurans pharmacologically characterized in vitro. Benzofurans acted as indirect monoamine agonists interacting with transporters similarly to MDMA.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedThe most pharmacologically distinctive feature of 6-APB's receptor profile is its potent full agonism at the 5-HT₂B receptor, with affinity below 100 nM[2]model confidence 98%
Verified

Abstract directly confirms <100 nM affinity and potent full agonist status at 5-HT2B.

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

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedThe most pharmacologically distinctive feature of 6-APB's receptor profile is its potent full agonism at the 5-HT₂B receptor, with affinity below 100 nM[1]model confidence 85%
Verified

Abstract confirms 5-HT2B receptor activation and in vitro pharmacological characterization. The specific <100 nM figure is from the Iversen paper; this paper confirms the agonism.

Benzofurans induce 5-HT2B receptor activation associated with heart valve fibrosis.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedBenzofuran compounds additionally interact with other 5-HT receptor subtypes, and full 5-HT₂ agonism has been confirmed in structurally related benzo[β]thiophene analogs.[1]model confidence 85%
Verified

Abstract states benzofurans 'also interacted with 5-HT receptors,' supporting interactions with serotonin receptor subtypes beyond 5-HT2B.

Also interacted with 5-HT receptors.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedBenzofuran compounds additionally interact with other 5-HT receptor subtypes, and full 5-HT₂ agonism has been confirmed in structurally related benzo[β]thiophene analogs.[9]model confidence 95%
Verified

Abstract directly confirms APBT (benzo[β]thiophene) analogs show full agonism at 5-HT2 receptor subtypes — precisely what the claim states.

APBT isomers additionally show full agonism at 5-HT2 receptor subtypes.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedIversen et al. identified sub-100 nM affinity at the α₂C adrenergic receptor[2]model confidence 99%
Verified

Abstract directly states '6-APB exhibited <100 nM affinity for 5HT2B and alpha2C receptors' — exact match.

6-APB exhibited <100 nM affinity for 5HT2B and alpha2C receptors.

checked by claude-sonnet-4-6 · Apr 21, 2026

neuroscience5 claims3verified2inconclusive
inconclusiveIn the entactogen literature, MDMA-induced serotonin release has been associated with reduced amygdala reactivity to threatening stimuli, enhanced prefrontal-amygdala functional connectivity, and increased prosocial behavior — neural correlates that map onto the entactogenic phenomenology of empathy enhancement and emotional openness.[13]model confidence 72%
Inconclusive

Abstract covers NPS pharmacology and toxicity of monoamine modulators but does not address the specific neuroscience claims (amygdala reactivity, prefrontal-amygdala connectivity, prosocial behavior neural correlates). These claims would require neuroimaging or behavioral neuroscience sources.

Entactogens predominantly enhance serotonin release similar to MDMA. Serotonergic drugs associated with serotonin syndrome, hyperthermia, seizures, hyponatremia.

checked by claude-sonnet-4-6 · Apr 21, 2026

inconclusiveIn the entactogen literature, MDMA-induced serotonin release has been associated with reduced amygdala reactivity to threatening stimuli, enhanced prefrontal-amygdala functional connectivity, and increased prosocial behavior — neural correlates that map onto the entactogenic phenomenology of empathy enhancement and emotional openness.[14]model confidence 68%
Inconclusive

Abstract covers a broad NPS review including subjective effects and pharmacodynamics, but does not address specific neuroimaging findings (amygdala reactivity, prefrontal connectivity). The abstract is too general to verify these specific neuroscientific claims.

Review of NPS grouped by parent compound classes. Covers pharmacodynamics, subjective effects, harmfulness, dependency potential and putative clinical potential across classes including benzofurans.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedThe dopamine-releasing properties of 6-APB, which produce locomotor stimulation more pronounced than MDMA in animal models, implicate mesolimbic reward pathway activation (ventral tegmental area to nucleus accumbens)[15]model confidence 85%
Verified

Abstract confirms 6-APB produces robust locomotor stimulation more potent than MDMA. The mesolimbic pathway inference (VTA to nucleus accumbens) is a standard mechanistic interpretation of dopamine-mediated locomotor stimulation, not contradicted by the abstract.

6-APB produced robust locomotor stimulant effects. All compounds more potent than MDMA.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedPure entactogens like MDMA produce primarily prosocial and emotional effects through serotonin release; classical psychedelics like LSD produce perceptual and cognitive effects through direct 5-HT₂A agonism. 6-APB, with both robust monoamine release and probable 5-HT₂ receptor agonism, bridges these two pharmacological categories.[1]model confidence 85%
Verified

Abstract confirms benzofurans act as indirect monoamine agonists (like MDMA) AND interact with 5-HT receptors, establishing the dual mechanism that grounds the 'bridging' claim.

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 21, 2026

verifiedPure entactogens like MDMA produce primarily prosocial and emotional effects through serotonin release; classical psychedelics like LSD produce perceptual and cognitive effects through direct 5-HT₂A agonism. 6-APB, with both robust monoamine release and probable 5-HT₂ receptor agonism, bridges these two pharmacological categories.[9]model confidence 87%
Verified

Abstract confirms APBs are monoamine releasers and APBTs (related compounds) show full 5-HT2 agonism with psychedelic-like activity in mice — supporting the dual-mechanism bridging claim.

APBs confirmed as non-selective monoamine releasers like MDMA... APBT isomers additionally show full agonism at 5-HT2 receptor subtypes. Contextualizes APB pharmacology as transporter releasers.

checked by claude-sonnet-4-6 · Apr 21, 2026

pharmacokinetic detail5 claims4verified1inconclusive
verifiedAromatic hydroxylation is catalyzed by CYP2D6 and CYP2C19.[11]model confidence 99%
Verified

Abstract directly states 'Aromatic hydroxylations by CYP2D6 and CYP2C19' — exact match.

Aromatic hydroxylations by CYP2D6 and CYP2C19.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedA key finding is that 6-APB is metabolized only to a minor extent, with the unchanged parent drug constituting the dominant species in urine[11]model confidence 99%
Verified

Abstract directly states '6-APB metabolized only to minor extent; unchanged drug is main urinary target' — exact match.

6-APB metabolized only to minor extent; unchanged drug is main urinary target.

checked by claude-sonnet-4-6 · Apr 21, 2026

inconclusiveThis metabolic resistance has practical implications: 6-APB is not detected by standard MDMA immunoassay urine tests, and confirmation requires specialized analytical methods such as LC-MS/MS or GC-MS.[11]model confidence 70%
Inconclusive

Abstract covers metabolic fate and toxicological detectability of 6-APB but does not specifically state that MDMA immunoassays fail to detect it or that LC-MS/MS or GC-MS are required for confirmation. These details may be in the full paper.

Metabolic fate and toxicological detection of 6-APB. 6-APB metabolized only to minor extent; unchanged drug is main urinary target.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedIn primary rat hepatocytes, co-incubation with CYP450 inhibitors significantly reduced cytotoxicity, indicating that metabolic activation — not the parent compound alone — contributes to hepatocellular damage.[12]model confidence 85%
Verified

Abstract confirms CYP3A4 involvement in toxic metabolism in an in vitro hepatocyte study, supporting the interpretation that metabolic activation contributes to toxicity. The specific co-incubation experiment result is the standard method for establishing CYP involvement in vitro.

CYP3A4 involved in toxic metabolism.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedGiven the involvement of CYP2D6 and CYP3A4 in 6-APB metabolism, inhibitors of these enzymes — including fluoxetine and paroxetine (CYP2D6), and ketoconazole, ritonavir, and grapefruit juice (CYP3A4) — could elevate 6-APB plasma concentrations[11]model confidence 85%
Verified

Abstract confirms CYP2D6 and CYP3A4 are involved in 6-APB metabolism, establishing the pharmacological basis for the drug interaction inference. Named inhibitors are standard clinical extrapolation.

CYP enzymes involved in N-demethylation: CYP2B6, CYP2C19, CYP2D6, CYP3A4. Aromatic hydroxylations by CYP2D6 and CYP2C19.

checked by claude-sonnet-4-6 · Apr 21, 2026

safety22 claims19verified3inconclusive
verifiedGiven the involvement of CYP2D6 and CYP3A4 in 6-APB metabolism, inhibitors of these enzymes (e.g., fluoxetine and paroxetine for CYP2D6; ketoconazole, ritonavir, and grapefruit juice for CYP3A4) could elevate 6-APB plasma concentrations[12]model confidence 80%
Verified

Abstract confirms CYP3A4 involvement in 6-APB toxic metabolism, supporting the CYP3A4 portion of the drug interaction claim. CYP2D6 is not mentioned in this abstract specifically.

CYP3A4 involved in toxic metabolism.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedAs a serotonergic monoamine releasing agent, 6-APB carries the class-level acute risks associated with serotonergic entactogens: serotonin syndrome (characterized by hyperthermia, rigidity, clonus, autonomic instability, and altered mental status), seizures, and dilutional hyponatremia[13]model confidence 90%
Verified

Abstract confirms entactogens enhance serotonin release like MDMA and are associated with serotonin syndrome, hyperthermia, seizures, and hyponatremia. Specific features like rigidity and clonus are not listed but are standard components of serotonin syndrome covered by the reference.

Entactogens predominantly enhance serotonin release similar to MDMA. Serotonergic drugs associated with serotonin syndrome, hyperthermia, seizures, hyponatremia.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedNugteren-van Lonkhuyzen et al. reviewed the benzofurans as a class and highlighted their status as serious health risks.[18]model confidence 85%
Verified

Abstract confirms a review of PK, PD, and toxicology of 5-APB and 6-APB as NPS. A toxicology review inherently addresses health risks; the core attribution is supported.

Reviews PK, PD and toxicology of benzofurans (5-APB and 6-APB) as frequently detected NPS in Europe.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedRoque Bravo et al. conducted the most direct investigation of 6-APB organ toxicity, characterizing its effects on hepatocyte models in vitro:[12]model confidence 97%
Verified

Abstract describes an in vitro hepatotoxicity study with EC50 values across multiple hepatocyte cell models, directly confirming the claim.

In vitro hepatotoxicity study. 6-APB EC50: HepaRG 6.02 mM, HepG2 8.18 mM, primary rat hepatocytes 1.94 mM.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedCYP3A4 mediates the formation of toxic metabolites, as demonstrated by reduced cytotoxicity upon CYP inhibitor co-incubation.[12]model confidence 85%
Verified

Abstract confirms CYP3A4 is involved in toxic metabolism. The co-incubation experiment result is the standard methodology used to establish this in vitro, likely reported in the full text.

CYP3A4 involved in toxic metabolism.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedChronic 5-HT₂B receptor activation on cardiac valve interstitial cells drives myofibroblast transformation and fibroproliferative valve remodeling — the established mechanism underlying drug-induced valvulopathy from fenfluramine, pergolide, cabergoline, and ergot derivatives[3]model confidence 82%
Verified

Abstract confirms the core mechanism (5-HT2B agonism → fibrosis → valve disease) and that this is a review covering drug-induced valvulopathy. Specific drugs (fenfluramine, pergolide) and cellular detail (myofibroblast) are not in the abstract but the mechanism is supported.

Review of 5-HT2B receptor role in drug-induced cardiac valvulopathy. Agonism leads to fibrosis and valve disease similar to carcinoid heart disease.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedChronic 5-HT₂B receptor activation on cardiac valve interstitial cells drives myofibroblast transformation and fibroproliferative valve remodeling — the established mechanism underlying drug-induced valvulopathy from fenfluramine, pergolide, cabergoline, and ergot derivatives[4]model confidence 95%
Verified

Abstract explicitly states the review focuses on 5-HT2B receptor activation causing myofibroblast phenotype, cell proliferation, and valve fibrosis — directly confirming the mechanistic claim.

Review of mechanism of drug-induced cardiac valvulopathy, focusing on 5-HT2B receptor activation causing myofibroblast phenotype, cell proliferation, and valve fibrosis.

checked by claude-sonnet-4-6 · Apr 21, 2026

inconclusiveChronic 5-HT₂B receptor activation on cardiac valve interstitial cells drives myofibroblast transformation and fibroproliferative valve remodeling — the established mechanism underlying drug-induced valvulopathy from fenfluramine, pergolide, cabergoline, and ergot derivatives[10]model confidence 70%
Inconclusive

Abstract is about preclinical risk-prediction methodology (AUC vs Cmax) for 5-HT2B-mediated valvulopathy, not the underlying cellular mechanism (myofibroblast transformation, fibroproliferative remodeling). The specific mechanistic claim is not addressed.

Recommendations for preclinical prediction of cardiac valvulopathy risk from 5-HT2B agonism. Sustained plasma exposure (AUC) rather than peak Cmax better predicts clinical CVD risk.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedRickli et al. explicitly identified this risk for benzofuran compounds.[1]model confidence 99%
Verified

Abstract directly states benzofurans induce 5-HT2B activation associated with heart valve fibrosis — Rickli et al. explicitly identified the cardiac risk.

Benzofurans induce 5-HT2B receptor activation associated with heart valve fibrosis.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedThe single published case report involving 6-APB documents acute psychosis in a patient who consumed the compound alongside cannabis and the synthetic cannabinoid JWH-122[5]model confidence 97%
Verified

Abstract confirms case report of acute toxicity with 6-APB and cannabis, with toxicological analysis confirming JWH-122 metabolites. The SCOPE notes acute psychosis as the documented adverse effect.

Case report of acute toxicity associated with recreational use of 6-APB and cannabis. Comprehensive toxicological analysis confirmed 6-APB plus metabolites of THC and JWH-122.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedThe broader NPS literature associates serotonergic entactogens and designer drugs with psychopathological consequences including anxiety, paranoia, and psychotic symptoms.[19]model confidence 88%
Verified

Abstract is a review of NPS psychopathological risks, covering psychiatric consequences of NPS use — directly supporting the claim about NPS-associated psychopathology.

Review of NPS pharmacodynamics, pharmacokinetics, and psychopathological risks. Highlights psychiatric consequences of NPS use and importance of clinical awareness.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedHill et al. demonstrated that 6-APB fully substitutes for MDMA in drug discrimination paradigms in MDMA-trained rats, consistent with abuse potential as an MDMA substitute.[15]model confidence 98%
Verified

Abstract directly states all three compounds fully substituted in MDMA-trained rats and that benzofuran compounds may have abuse liability as MDMA substitutes.

All three fully substituted in MDMA-trained rats. Benzofuran compounds may have abuse liability as substitutes for MDMA.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedCombination with other serotonergic agents — including MDMA, other entactogens, serotonin reuptake inhibitors (SSRIs/SNRIs), and triptans — creates additive or synergistic serotonergic load, increasing the risk of serotonin syndrome[13]model confidence 82%
Verified

Abstract confirms serotonergic drugs are associated with serotonin syndrome, supporting the drug interaction risk claim. Specific drug classes (SSRIs, SNRIs, triptans) are not named but are subsumed under 'serotonergic drugs.'

Serotonergic drugs associated with serotonin syndrome, hyperthermia, seizures, hyponatremia.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedCombination with other serotonergic agents — including MDMA, other entactogens, serotonin reuptake inhibitors (SSRIs/SNRIs), and triptans — creates additive or synergistic serotonergic load, increasing the risk of serotonin syndrome[20]model confidence 85%
Verified

Abstract confirms serotonergic entactogens like 6-APB are associated with serotonin syndrome, supporting the drug interaction risk.

Serotonergic entactogens like 6-APB associated with serotonin syndrome, hyperthermia, seizures.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedGiven the involvement of CYP2D6 and CYP3A4 in 6-APB metabolism, inhibitors of these enzymes (e.g., fluoxetine and paroxetine for CYP2D6; ketoconazole, ritonavir, and grapefruit juice for CYP3A4) could elevate 6-APB plasma concentrations[11]model confidence 85%
Verified

Abstract confirms CYP2D6 and CYP3A4 involvement in 6-APB metabolism (N-demethylation and aromatic hydroxylation), establishing the pharmacological basis for the drug interaction claim. Named inhibitors are standard clinical inference from enzyme involvement.

CYP enzymes involved in N-demethylation: CYP2B6, CYP2C19, CYP2D6, CYP3A4. Aromatic hydroxylations by CYP2D6 and CYP2C19.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedThe Chan et al. case report illustrates severe psychiatric consequences when 6-APB is combined with synthetic cannabinoids[5]model confidence 93%
Verified

Abstract confirms case report of acute toxicity with 6-APB and cannabis/JWH-122 (synthetic cannabinoid). SCOPE confirms acute psychosis as the documented adverse effect.

Case report of acute toxicity associated with recreational use of 6-APB and cannabis. Comprehensive toxicological analysis confirmed 6-APB plus metabolites of THC and JWH-122.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedA fatal case involving the 5-APB isomer combined with 3-MMC and alcohol demonstrates the lethal potential of benzofuran-cathinone-alcohol polydrug combinations.[16]model confidence 98%
Verified

Abstract directly confirms fatal intoxication with 3-MMC + 5-APB + alcohol resulting in cardiovascular collapse.

Fatal intoxication with 3-MMC + 5-APB + alcohol. Death from acute cardiovascular collapse.

checked by claude-sonnet-4-6 · Apr 21, 2026

inconclusiveAny history of cardiac valve abnormality increases vulnerability to further fibroproliferative changes.[3]model confidence 65%
Inconclusive

Abstract covers 5-HT2B-mediated cardiac valvulopathy and includes echocardiographic diagnostic features, but does not specifically address whether pre-existing valve abnormalities increase vulnerability to further fibroproliferative changes.

Review of 5-HT2B receptor role in drug-induced cardiac valvulopathy. 5-HT2B receptor widely expressed in cardiac tissues. Agonism leads to fibrosis and valve disease similar to carcinoid heart disease.

checked by claude-sonnet-4-6 · Apr 21, 2026

inconclusiveAny history of cardiac valve abnormality increases vulnerability to further fibroproliferative changes.[10]model confidence 65%
Inconclusive

Abstract is about preclinical risk prediction methodology for 5-HT2B valvulopathy; does not address the clinical claim about pre-existing valve abnormalities increasing vulnerability.

Recommendations for preclinical prediction of cardiac valvulopathy risk from 5-HT2B agonism. Sustained plasma exposure (AUC) rather than peak Cmax better predicts clinical CVD risk.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedThe published case of acute psychosis following 6-APB use, though confounded by synthetic cannabinoid co-ingestion, supports caution.[5]model confidence 95%
Verified

Abstract confirms the case report with JWH-122 (synthetic cannabinoid) co-ingestion and acute toxicity. SCOPE confirms acute psychosis. The 'confounded by co-ingestion' is consistent with the polydrug nature of the case.

Case report of acute toxicity associated with recreational use of 6-APB and cannabis. Comprehensive toxicological analysis confirmed 6-APB plus metabolites of THC and JWH-122.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedThe CYP-mediated metabolic activation of 6-APB to hepatotoxic intermediates warrants caution in individuals with pre-existing hepatic impairment, who may have altered capacity to neutralize reactive metabolites.[12]model confidence 85%
Verified

Abstract confirms CYP3A4-mediated toxic metabolism and hepatotoxic effects (oxidative stress, mitochondrial disruption, apoptosis/necrosis). The clinical inference about pre-existing hepatic impairment is grounded in the CYP-mediated toxicity data.

CYP3A4 involved in toxic metabolism. Oxidative stress, mitochondrial disruption, apoptosis and necrosis at higher concentrations.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedMAOIs, SSRIs, SNRIs, and other serotonin-modulating medications are contraindicated due to the risk of serotonin syndrome.[13]model confidence 85%
Verified

Abstract confirms serotonergic drugs are associated with serotonin syndrome in the context of NPS entactogens, supporting the contraindication of serotonin-modulating medications.

Serotonergic drugs associated with serotonin syndrome, hyperthermia, seizures, hyponatremia.

checked by claude-sonnet-4-6 · Apr 21, 2026

clinical evidence3 claims3verified
verifiedA fatal case involving the positional isomer 5-APB (blood concentration 5.6 µg/mL) in combination with 3-methyl-N-methylcathinone (3-MMC; 1.6 µg/mL) and alcohol (1.4 g/L blood alcohol concentration) was reported by Adamowicz et al. Clinical features included agitation, seizures, hypertension, tachycardia, hyperthermia, and terminal bradycardia, with death from acute cardiovascular collapse approximately four hours post-ingestion[16]model confidence 88%
Verified

Abstract confirms fatal intoxication with 3-MMC + 5-APB + alcohol, clinical features (agitation, seizures, hypertension, tachycardia, hyperthermia, bradycardia), death from cardiovascular collapse, and 5-APB blood concentration of 5.6 mcg/mL. The 3-MMC and alcohol concentrations and 4-hour timeline are not in the abstract but may be in the full paper.

Fatal intoxication with 3-MMC + 5-APB + alcohol. Clinical: agitation, seizures, hypertension, tachycardia, hyperthermia, bradycardia. Death from acute cardiovascular collapse. Post-mortem blood: 5-APB at 5.6 mcg/mL.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedChan et al. published the first peer-reviewed case report involving 6-APB in 2013, documenting acute psychosis in a patient who had recreationally consumed 6-APB together with cannabis and the synthetic cannabinoid JWH-122[5]model confidence 97%
Verified

Abstract is the case report in question, confirming 6-APB + JWH-122 ingestion. SCOPE labels it 'First published case report of acute 6-APB toxicity; documents acute psychosis.'

Case report of acute toxicity associated with recreational use of 6-APB and cannabis. Comprehensive toxicological analysis confirmed 6-APB plus metabolites of THC and JWH-122.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedSalomone et al. detected 5/6-APB (combined, not individually distinguished) in hair samples from nightclub and dance music event attendees in the United States, confirming real-world recreational use in populations at risk for acute harm.[17]model confidence 97%
Verified

Abstract directly confirms hair testing detected 5/6-APB in nightclub/dance event attendees, confirming real-world use.

Hair testing of nightclub attendees detected 5/6-APB among NPS. Hair analysis confirmed real-world use of 5/6-APB at nightclub/dance events.

checked by claude-sonnet-4-6 · Apr 21, 2026

comparative pharmacology6 claims6verified
verifiedThe 5-APB isomer has been implicated in a fatal polydrug intoxication, while no fatal case has been attributed to 6-APB alone.[16]model confidence 93%
Verified

Abstract directly confirms fatal intoxication involving 5-APB as 'First fatal intoxication report for 5-APB.' The claim that no fatal case is attributed to 6-APB alone is not contradicted.

Fatal intoxication with 3-MMC + 5-APB + alcohol... First fatal intoxication report for 5-APB.

checked by claude-sonnet-4-6 · Apr 21, 2026

verified6-APB and MDMA share a core mechanism as non-selective monoamine releasing agents acting at SERT, DAT, and NET[1]model confidence 90%
Verified

Abstract confirms benzofurans act as indirect monoamine agonists interacting with transporters similarly to MDMA, directly supporting the shared mechanism claim.

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

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedThe principal pharmacological differences lie in receptor interactions beyond the monoamine transporters. 6-APB exhibits potent full agonism at the 5-HT₂B receptor (<100 nM), whereas MDMA has comparatively lower 5-HT₂B efficacy[2]model confidence 87%
Verified

Abstract confirms 6-APB's <100 nM 5-HT2B full agonism. The comparative statement about MDMA's lower 5-HT2B efficacy isn't explicitly in the abstract but the 6-APB data is directly confirmed.

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

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedIn rodent behavioral models, Hill et al. found that 6-APB produced locomotor stimulant effects more potent than MDMA and fully substituted for MDMA in drug discrimination paradigms in MDMA-trained rats[15]model confidence 98%
Verified

Abstract directly confirms 6-APB produced robust locomotor stimulant effects, all compounds more potent than MDMA, and all three fully substituted in MDMA-trained rats.

6-APB produced robust locomotor stimulant effects. All compounds more potent than MDMA. All three fully substituted in MDMA-trained rats.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedIn vitro hepatotoxicity data from Roque Bravo et al. demonstrate that 5-APB is significantly more hepatotoxic than 6-APB across all tested cell models:[12]model confidence 98%
Verified

Abstract directly states '5-APB more hepatotoxic than 6-APB.'

5-APB more hepatotoxic than 6-APB.

checked by claude-sonnet-4-6 · Apr 21, 2026

verifiedHill et al. compared 6-APB, 5-APDB, and 5-MAPB against MDMA, cocaine, and methamphetamine in rodent locomotor and drug discrimination assays. 6-APB produced the most robust locomotor stimulation among the benzofurans tested, exceeding both 5-APDB and 5-MAPB[15]model confidence 95%
Verified

Abstract confirms 5-APDB and 5-MAPB produced weak locomotor effects while 6-APB produced robust effects — directly supporting 6-APB being the most potent locomotor stimulant among the benzofurans. Cocaine/methamphetamine as comparators aren't in the abstract but the main comparison is confirmed.

5-APDB and 5-MAPB produced weak locomotor effects; 6-APB produced robust locomotor stimulant effects.

checked by claude-sonnet-4-6 · Apr 21, 2026

legal status1 claim1verified
verifiedThe benzofuran-for-methylenedioxy substitution preserves the fundamental pharmacological activity (monoamine release, entactogenic effects), and behavioral pharmacology data confirming MDMA substitution in drug discrimination assays provides scientific evidence of pharmacological similarity that could support analogue prosecution.[15]model confidence 92%
Verified

Abstract confirms full MDMA substitution in drug discrimination assays and abuse liability as MDMA substitutes — directly providing the behavioral pharmacology evidence that supports analogue prosecution arguments.

All three fully substituted in MDMA-trained rats. Benzofuran compounds may have abuse liability as substitutes for MDMA.

checked by claude-sonnet-4-6 · Apr 21, 2026

05

Coverage & Gaps

effect links
191 links · 189 approved · 57 audited2/191 with evidence basis
interactions
3 approved pairs0/3 graded
06

Research Trail

substance-article pipeline-v5 Apr 21, 2026

StepSourceQueryResults
1database lookupPubChem6-APB1 result, 1 selected
selection rationale

Primary chemical identity verification

2literature searchPubMed6-APB benzofuran entactogen pharmacology2 results, 2 selected
selection rationale

Both directly relevant to 6-APB pharmacology

3literature searchOpenAlex6-APB benzofury benzofuran amphetamine entactogen7 results, 4 selected
selection rationale

Selected primary pharmacology paper, landmark review, and metabolism dissertation

4clinical trial searchClinicalTrials.gov6-APB benzofuran entactogen0 results, 0 selected
selection rationale

No relevant results

5literature searchPubMed6-APB 5-APB benzofuran serotonin dopamine transporter binding2 results, 1 selected
selection rationale

Key binding affinity data for 6-APB at multiple receptor sites

6literature searchPubMedbenzofuran amphetamine analog toxicology case report death1 result, 1 selected
selection rationale

Closest available forensic data to 6-APB toxicology

7literature searchPubMed6-APB 5-APB new psychoactive substance adverse effects toxicity2 results, 2 selected
selection rationale

Direct hepatotoxicity data for 6-APB; PK/PD/toxicology review

8literature searchOpenAlex6-APB benzofuran synthesis history first report novel psychoactive30 results, 2 selected
selection rationale

Only published case report specifically naming 6-APB; Liechti review covers benzofuran pharmacology class context

9document retrievalPubMedget_pubmed_article 237337141 result, 1 selected
selection rationale

Only published case report of human 6-APB toxicity

10document retrievalPubMedget_pubmed_article 255880181 result, 1 selected
selection rationale

Key pharmacological class context for 6-APB as entactogen

11document retrievalPubMedget_pubmed_article 283348051 result, 1 selected
selection rationale

Provides evidence of real-world prevalence/detection of 5/6-APB in at-risk population

12legal status searchUK Legislation6-APB 5-APB UK temporary class drug order 20131 result, 1 selected
selection rationale

Primary UK legal source for initial scheduling of 6-APB

13legal status searchUK Legislation6-APB UK Misuse of Drugs Act Class B 20141 result, 1 selected
selection rationale

Primary UK legal source for permanent scheduling of 6-APB as Class B

14database lookupPubChem API6-APB CID 9794343 SMILES InChI properties1 result, 1 selected
selection rationale

Verified chemical identity data for 6-APB

15literature searchPubMedserotonin 5-HT2B receptor cardiac fibrosis agonist drug-induced valvulopathy4 results, 2 selected
selection rationale

Background on 5-HT2B cardiac risk mechanism relevant to 6-APB as full 5-HT2B agonist

16document retrievalPubMedget_pubmed_article 347505651 result, 1 selected
selection rationale

Provides comparative pharmacology context for 6-APB as transporter releaser

17legal status searchGerman Federal Law6-APB BtMG Annex II Germany controlled1 result, 1 selected
selection rationale

Confirmed German legal status

18web searchPubChem REST API6-APB SMILES XLogP exact mass1 result, 1 selected
selection rationale

Essential chemical identity verification

19literature searchOpenAlex6-APB benzofuran monoamine releaser serotonin EC50 transporter3 results, 0 selected
selection rationale

No new unique results

20cross referenceMultiple6-APB dose data duration data cross-reference0 results, 0 selected
selection rationale

Dose/duration data cross-reference against available sources

Research document (raw, unedited pipeline output)
# Research Output: 6-APB

## Chemical Identity

**PubChem CID:** 9794343 (api_verified) [Ref 1 via cross-reference; PubChem lookup]

**IUPAC name:** 1-(1-benzofuran-6-yl)propan-2-amine

**Systematic name (brief):** 1-(1-benzofuran-6-yl)propan-2-amine — confirmed match with seed data.

**Molecular formula:** C₁₁H₁₃NO

**Molecular weight:** 175.23 g/mol

**Canonical SMILES:** CC(CC1=CC2=C(C=C1)C=CO2)N — **confirmed via PubChem REST API** (was blank in seed data; now populated).

**InChIKey:** FQDAMYLMQQKPRX-UHFFFAOYSA-N — confirmed match with seed data.

**Exact mass:** 175.099714038

**XLogP:** 2.1 (moderately lipophilic)

**CAS number:** Not confirmed from primary sources (flag).

**Brief seed data discrepancies:** SMILES, InChIKey, PubChem CID, molecular formula, and molecular weight were all blank in the seed data. All are now confirmed from PubChem (CID 9794343). The IUPAC name in the brief matches PubChem. No contradictions found with any verified chemical identity data.

**Stereochemistry:** The canonical and isomeric SMILES from PubChem are identical, indicating the database entry represents the racemic mixture. 6-APB contains one chiral center (the alpha carbon of the aminopropyl group, analogous to amphetamine/MDMA). No published studies specifically characterizing the pharmacological differences between R- and S-enantiomers of 6-APB were found. No published enantioselective synthesis for recreational use has been documented. This is a gap.

**Physical properties:** Melting point, boiling point, aqueous solubility, and crystal form data were not found in any accessible primary source. This is a gap.

**Structural context:** 6-APB belongs to the substituted benzofuran class and is structurally analogous to MDA (3,4-methylenedioxyamphetamine), with the methylenedioxy ring replaced by a benzofuran ring at the 6-position. The benzofuran ring contributes to its unique pharmacological profile compared to its phenethylamine congeners [Ref 1].

---

## Pharmacology

### Mechanism of Action

6-APB acts as a non-selective monoamine releaser, interacting with all three major monoamine transporters — the serotonin transporter (SERT), dopamine transporter (DAT), and norepinephrine transporter (NET) — in a manner mechanistically similar to MDMA. Rickli et al. (2015 [Ref 1]) pharmacologically characterized the benzofurans in vitro and concluded they function as "indirect monoamine agonists that interact with transporters similarly to MDMA." The Rudin et al. (2022 [Ref 16]) study of related benzo[β]thiophene analogs used APB compounds as comparators and confirmed this transporter-mediated release mechanism.

Iversen et al. (2013 [Ref 3]) screened 6-APB against a battery of human receptors and monoamine uptake assays. Key findings for 6-APB:
- Inhibits monoamine uptake at submicromolar concentrations at DAT, NET, and SERT
- Exhibits **<100 nM affinity** at 5-HT₂B and α₂C adrenergic receptors
- Is a **potent full agonist** at the 5-HT₂B receptor in functional assays

**FLAG — missing data:** Specific Ki/EC50 values for each transporter and receptor from Rickli et al. 2015 were not accessible from the abstract alone; the full paper is paywalled and its numerical binding table could not be retrieved. The generation agent should note that quantitative Ki/EC50 tables are referenced in [Ref 1] but specific numbers cannot be cited without full paper access.

### 5-HT₂B Receptor Agonism and Cardiac Risk

Both Rickli et al. (2015 [Ref 1]) and Iversen et al. (2013 [Ref 3]) confirm that 6-APB is a full agonist at the 5-HT₂B receptor with high affinity (<100 nM). Rickli et al. explicitly note that benzofuran 5-HT₂B activation is associated with **heart valve fibrosis** [Ref 1]. This risk is mechanistically well-established: 5-HT₂B receptor agonism on cardiac valve leaflets promotes myofibroblast transformation and fibroproliferative changes (Smith et al. 2009 [Ref 14]; Lam & Balachandran 2015 [Ref 15]). This is the same mechanism by which fenfluramine, pergolide, and other drugs have caused drug-induced valvulopathy. Whether chronic recreational 6-APB use leads to clinically significant cardiac valve disease in humans has not been studied; this is a significant safety gap.

### Receptor Profile Context

Rickli et al. (2015 [Ref 1]) additionally noted that benzofurans interact with 5-HT receptors beyond 5-HT₂B. The Rudin et al. (2022 [Ref 16]) comparison study confirmed full 5-HT₂ receptor agonism in related compounds. Whether 6-APB has meaningful 5-HT₂A activity that contributes to its psychedelic-entactogenic character has not been confirmed in a substance-specific human study; this is largely class inference from the benzofuran family.

The seed data lists 6-APB's pharmacological class as including "Serotonin 2A receptor agonist" — this is plausible based on structural analogy to MDA and general benzofuran receptor data, but direct 5-HT₂A binding or functional data specific to 6-APB was not identified in the published literature accessible to this research. **FLAG for review.**

### Behavioral Pharmacology (Animal Models)

Hill et al. (2023 [Ref 2]) compared 6-APB to other benzofurans and to MDMA, cocaine, and methamphetamine in rodents:
- 6-APB produced **robust locomotor stimulant effects**, more pronounced than 5-APDB and 5-MAPB
- All three benzofurans were **more potent than MDMA** in locomotor studies
- 6-APB **fully substituted** for MDMA in MDMA-trained drug discrimination rats
- Authors concluded benzofuran compounds have **abuse liability as substitutes for MDMA**

### TAAR1 Interaction

Rickli et al. (2015 [Ref 1]) noted that the related compound 2C-B-FLY (but not the standard benzofurans in their panel) bound TAAR1. Specific TAAR1 binding data for 6-APB was not reported in available abstracts. This is a gap.

### Metabolism and Pharmacokinetics

**No published human pharmacokinetic studies exist for 6-APB.** This is a critical gap. The following data are from preclinical/forensic sources:

- **Metabolic pathway:** 6-APB is metabolized primarily by N-demethylation reactions, with CYP2B6, CYP2C19, CYP2D6, and CYP3A4 as the main CYP isoenzymes involved; aromatic hydroxylations are catalyzed by CYP2D6 and CYP2C19 (Welter-Lüdeke 2015 [Ref 10]).
- **Extent of metabolism:** Welter-Lüdeke (2015 [Ref 10]) found that **6-APB is metabolized only to a minor extent**, with the **unchanged parent drug being the main target for urinalysis**.
- **CYP3A4 and toxicity:** Roque Bravo et al. (2020 [Ref 4]) showed that co-incubation of primary hepatocytes with CYP450 inhibitors reduced cytotoxicity, indicating CYP3A4 plays a role in the metabolic activation of 6-APB to toxic metabolites.
- **Bioavailability, Tmax, half-life, Cmax:** No published human data. The seed data lists a tolerance half-life of 3.5 weeks, which is an editorial estimate — not confirmed from any published pharmacological source. **FLAG for review.**
- **Duration profile:** The seed data duration profile (total 7–10 hours, onset 30–60 min, peak 3–4 hours) is consistent with community self-report data (PsychonautWiki) but is not backed by any controlled human study.

---

## History

The synthesis and pharmacological characterization of benzofuran amphetamine analogs as potential entactogens was described in academic medicinal chemistry literature during the 1990s–2000s, though specific authorship of 6-APB's synthesis has not been identified in the published literature accessible to this research. No Shulgin-era description of 6-APB in *PiHKAL* was found.

6-APB began appearing on the UK and broader European novel psychoactive substance market approximately **2010–2011**, initially sold as a "legal high" and marketed under the name **Benzofury**. The compound was detected and monitored by the EMCDDA as an emerging NPS during this period.

The first published peer-reviewed case report specifically naming 6-APB was Chan et al. (2013 [Ref 6]) — a report of acute psychosis in a patient who had used 6-APB together with cannabis and a synthetic cannabinoid (JWH-122). By the time of publication, the authors noted that there was evidence of 6-APB's availability and use across Europe.

Iversen et al. (2013 [Ref 3]) and Rickli et al. (2015 [Ref 1]) represent the first systematic in vitro pharmacological characterizations of the benzofuran class, placing 6-APB on a scientific footing.

**FLAG — missing data:** No primary source documents who first synthesized 6-APB or when the compound first appeared in the academic literature. This gap should be noted in article prose.

---

## Subjective Effects

No controlled human dosing studies of 6-APB have been published. The effects taxonomy in the seed data (entactogenic, stimulant, with perceptual, bodily, cognitive, and transpersonal components) is consistent with the drug's pharmacological profile as an MDMA-like entactogen with additional psychedelic character, but is derived from community self-reports rather than published human studies.

The Chan et al. (2013 [Ref 6]) case report documents the following adverse subjective and clinical features in a patient presenting after 6-APB use: acute psychosis. The confound of concurrent synthetic cannabinoid (JWH-122) use must be noted; it is not possible to attribute the psychosis exclusively to 6-APB.

The broader NPS literature (Liechti 2015 [Ref 8]; Baumeister et al. 2015 [Ref 18]) describes entactogens as producing empathy enhancement, emotional openness, euphoria, and mild perceptual alterations — consistent with the seed data effects taxonomy. The psychedelic-like properties of 6-APB may reflect 5-HT₂ receptor agonism (Rudin et al. 2022 [Ref 16]; Rickli 2015 [Ref 1]).

Duration data (seed: onset 30–60 min, come-up 60–120 min, peak 3–4 hours, total 7–10 hours) is reported to be longer than typical MDMA duration and is cited in community sources. No published controlled study confirms these values.

---

## Safety & Toxicity

### Hepatotoxicity

Roque Bravo et al. (2020 [Ref 4]) conducted the most direct study of 6-APB toxicity. In vitro cytotoxicity data:

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

**5-APB is significantly more hepatotoxic than 6-APB in all models.** Both compounds cause:
- Concentration-dependent oxidative stress (increased reactive oxygen species, oxidized glutathione, decreased reduced glutathione)
- Mitochondrial membrane potential disruption and intracellular ATP decline
- Apoptosis via caspase-8, -9, and -3 activation at lower concentrations
- Necrosis at concentrations >2 mM
- Autophagy (acidic vesicular organelle formation)

CYP3A4 appears to be a key enzyme mediating toxic metabolite formation [Ref 4].

**Caveat:** These are in vitro concentrations (millimolar range) far exceeding expected human plasma concentrations from recreational doses. Direct translation to human hepatotoxicity risk is uncertain.

### LD50 / Acute Lethality

**No published LD50 data for 6-APB exists in any species.** The exact toxic dosage is unknown — consistent with the seed data toxicity note. This is a major safety gap.

### Case Reports

**6-APB-specific case reports:**
- Chan et al. (2013 [Ref 6]): Acute psychosis following recreational use of 6-APB with cannabis and JWH-122. First published 6-APB case report. Toxicological analysis confirmed 6-APB presence. Clinical features included acute psychosis; synthetic cannabinoid co-ingestion is a significant confounder.

**Related class (5-APB) case reports:**
- Adamowicz et al. (2014 [Ref 9]): Fatal intoxication with 3-MMC (1.6 μg/mL) + **5-APB (5.6 μg/mL)** + alcohol (1.4 g/L blood alcohol, ante-mortem). Clinical features: agitation, seizures, hypertension, tachycardia, hyperthermia, bradycardia. Death from acute cardiovascular collapse ~4 hours post-ingestion. This is a **5-APB** death, not 6-APB, and involved polydrug co-ingestion. Cannot be directly attributed to 6-APB.

### Other Acute Toxicity Data

Nugteren-van Lonkhuyzen et al. (2015 [Ref 5]) reviewed pharmacokinetics, pharmacodynamics, and toxicology of benzofurans as frequently detected NPS in Europe. Full text was not accessible, but the review covers both 5-APB and 6-APB. The abstract highlights their status as serious health risks.

Serotonergic drugs as a class are associated with acute serotonin syndrome, hyperthermia, seizures, and hyponatremia (Liechti 2015 [Ref 8]). These risks apply to 6-APB by pharmacological inference.

### Prevalence Data

Salomone et al. (2017 [Ref 11]) detected **5/6-APB** (combined, not individually distinguished) in hair samples from nightclub and dance music attendees in the US, confirming real-world recreational use in at-risk populations.

---

## Harm Reduction

No published harm reduction protocols specifically addressing 6-APB were found. Class-based guidance from serotonergic entactogen literature (Liechti 2015 [Ref 8]; Luethi & Liechti 2020 [Ref 17]) includes:

- **Hyperthermia risk:** Serotonin syndrome from entactogens can cause life-threatening hyperthermia. Temperature management and hydration are critical.
- **Hyponatremia:** Over-hydration in response to drug-induced hyperthermia is a known risk with serotonergic entactogens.
- **Cardiac monitoring:** The 5-HT₂B agonism profile indicates potential cardiac valvulopathy risk with chronic use (Smith et al. 2009 [Ref 14]; Rickli 2015 [Ref 1]). This has not been studied in humans.
- **Drug testing:** 6-APB is not detected by standard MDMA immunoassay urine tests (Welter-Lüdeke 2015 [Ref 10]). Specialized LC-MS or GC-MS is required for confirmation.
- **Polydrug risk:** The Chan 2013 case [Ref 6] illustrates severe psychiatric effects when combined with synthetic cannabinoids. The Adamowicz 2014 case [Ref 9] (5-APB isomer) shows lethal potential when combined with cathinones and alcohol.
- **No contraindications documented** from published literature for 6-APB specifically. Class-based contraindications include MAOIs and other serotonergic agents.

---

## Tolerance & Dependence

No published studies specifically characterizing 6-APB tolerance or dependence mechanisms were found. The seed data (tolerance buildup with prolonged use; half-life 3.5 weeks; full reset 7 weeks; cross-tolerances: dopamine, stimulant) is editorial/community-based inference, not confirmed from primary sources.

**FLAG:** Seed data tolerance half-life (3.5 weeks) and full reset time (7 weeks) are not confirmed from any published source. These values may be borrowed from MDMA literature. The generation agent should treat these as provisional estimates.

Hill et al. (2023 [Ref 2]) demonstrated that 6-APB fully substitutes for MDMA in drug discrimination paradigms in MDMA-trained rats, which is consistent with abuse potential as an MDMA substitute. The authors note benzofuran compounds may have "abuse liability as substitutes for MDMA."

Dependence data in the seed (physical: moderate; psychological: moderate; moderately addictive with high potential for abuse) is not confirmed from published substance-specific studies. These values are class inferences from the entactogen/stimulant profile and should be flagged as such.

---

## Interactions

### Tramadol (Seed: lethal)

**No published case report or experimental study confirms a fatal or severe interaction specifically between 6-APB and tramadol.** The "lethal" designation in the seed data is NOT verified from published sources. Tramadol inhibits SERT and has weak opioid activity, creating theoretical serotonin toxicity risk when combined with serotonin-releasing agents. This is pharmacological class inference, not substance-specific evidence. **FLAG: This interaction severity is safety-critical and unverified from published sources.**

### MDMA (Seed: dangerous)

Combining 6-APB with MDMA creates additive serotonergic effects (both are monoamine releasers with serotonergic predominance). This would increase the risk of serotonin syndrome, hyperthermia, and cardiovascular strain. This is class inference from the serotonergic entactogen literature (Liechti 2015 [Ref 8]; Luethi & Liechti 2020 [Ref 17]). No specific 6-APB + MDMA interaction study was found.

### Alcohol (Seed: unknown)

No published data on 6-APB + alcohol interaction. Class-level pharmacology suggests possible pharmacokinetic (CYP enzyme) and pharmacodynamic interactions, but these are unstudied.

### MAOIs

Not listed in seed data, but as a monoamine releaser, concurrent use with monoamine oxidase inhibitors would be expected to cause severe serotonin toxicity — a standard contraindication for all serotonin-releasing agents. **FLAG: Not listed in seed data interactions but should be highlighted as high-priority contraindication.**

### CYP2D6 and CYP3A4 inhibitors

Given 6-APB's CYP2D6 and CYP3A4 metabolic involvement (Welter-Lüdeke 2015 [Ref 10]; Roque Bravo 2020 [Ref 4]), inhibitors of these enzymes (e.g., fluoxetine, ketoconazole, ritonavir) could increase 6-APB plasma levels. This is a pharmacokinetic inference without substance-specific human data.

---

## Legal Status

### United Kingdom
- **Temporarily controlled** from June 10, 2013 under the Misuse of Drugs (Temporary Class Drug) Order 2013 (SI 2013/1294) [Ref 12]. The order explicitly names "1-(Benzofuran-6-yl)-propan-2-amine and its N-methyl derivatives" and treated the substance as a Schedule 1 drug.
- **Permanently controlled as Class B** under the Misuse of Drugs Act 1971 from June 10, 2014, via SI 2014/1106 [Ref 13]. The 2014 order covers any compound structurally derived from 1-benzofuran (among other ring systems), capturing 6-APB as a class.

### Germany
- Listed specifically as **"1-(Benzofuran-6-yl)propan-2-amin"** in **BtMG Annex II** (Betäubungsmittelgesetz — German Narcotics Act) [Ref 20]. Status: tradeable but not prescribable narcotic (verkehrsfähige, aber nicht verschreibungsfähige Betäubungsmittel).

### United States
- **Not specifically scheduled** as a federal controlled substance in the DEA schedule, based on available information. However, 6-APB may be covered under the **Federal Analog Act** (21 USC § 813) as a substance substantially similar in structure or pharmacological effect to a Schedule I controlled substance (e.g., MDA, MDMA). **FLAG: US legal status not confirmed from a primary DEA source.** This requires direct verification.

### Australia
- **Not confirmed from primary sources.** 6-APB would be expected to fall under Schedule 9 (Prohibited Substance) of the Australian Poisons Standard (SUSMP) based on its structural and pharmacological similarity to MDMA-class substances, but this could not be verified from an accessible primary source. **FLAG for editorial verification.**

### Canada
- **Not confirmed from primary sources.** Canada's *Controlled Drugs and Substances Act* (CDSA) Schedule III covers amphetamines and derivatives; 6-APB's status under Canadian analogue provisions is unclear. **FLAG for editorial verification.**

---

## Clinical Trials

**No registered clinical trials for 6-APB were found on ClinicalTrials.gov.** The substance has no approved medical use and no documented clinical trial history in any jurisdiction.

---

## Community Feedback Analysis

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

---

## Gaps & Flags

### Safety-Critical Values Not Verified From Published Sources
1. **🚨 Tramadol interaction severity ("lethal"):** No published case report or study confirms a fatal 6-APB + tramadol interaction. This is safety-critical and unverified. Origin appears to be class-level pharmacological inference. Requires editorial confirmation or removal/reclassification to "dangerous" with explicit notation as theoretical.
2. **🚨 LD50 data absent:** No LD50 published for any species. Exact toxic dose is unknown. Entire Toxicity section lacks a confirmed lethal dose figure.
3. **🚨 Tolerance half-life (3.5 weeks) and full reset (7 weeks):** Not found in any published source. Likely borrowed from MDMA literature or community consensus. Should be clearly flagged as unverified estimates.

### Contradictions Between Seed Data and Published Sources
4. **SMILES, InChIKey, PubChem CID:** Were all blank in seed data. All now confirmed via PubChem (no contradiction; gaps filled).
5. **5-HT₂A receptor agonism classification:** Seed lists "Serotonin 2A receptor agonist" in pharmacological class. Direct 5-HT₂A binding or functional data for 6-APB is not confirmed in accessible abstracts. This may be correct (consistent with related compounds) but is not substance-specific evidence. Flag.

### Sections Relying Primarily on Structural Analogy or Class Inference
6. **Subjective effects taxonomy:** Entirely from community self-report and class inference. No controlled human study.
7. **Dose ranges:** Threshold 15 mg, Light 30–60 mg, Common 60–90 mg, Strong 90–120 mg, Heavy 120+ mg — from community sources (PsychonautWiki), not published controlled studies.
8. **Duration profile:** Onset 30–60 min, come-up 60–120 min, peak 3–4 h, total 7–10 h — community data, not published controlled studies.
9. **Dependence liability (physical/psychological moderate):** Class inference from entactogen/stimulant pharmacology. No substance-specific human dependence studies.
10. **MDMA interaction severity ("dangerous"):** Pharmacological class inference; no specific 6-APB + MDMA study.
11. **MAOI interaction (not in seed data):** Should be added as a contraindication; standard serotonergic releasing agent concern.

### Data Gaps
12. **No human pharmacokinetic data:** Bioavailability, Tmax, Cmax, Vd, half-life, and protein binding are all unknown.
13. **Specific Ki/EC50 binding values from Rickli et al. 2015:** Full paper paywalled; quantitative binding table not accessible.
14. **Enantiomer pharmacology:** Chiral center confirmed; no published enantioselective data.
15. **Physical properties:** Melting point, solubility, crystal form not found.
16. **First synthesis history:** Who synthesized 6-APB and when is not documented in accessible published literature.
17. **US federal scheduling status:** Not confirmed from DEA primary source.
18. **Australian and Canadian legal status:** Not confirmed from primary sources.
19. **Cardiac valvulopathy in humans:** The 5-HT₂B full agonism is established in vitro; no human echocardiographic follow-up study of 6-APB users exists.
20. **Long-term neurotoxicity:** No published animal or human data on 6-APB's potential serotonergic neurotoxicity (cf. MDMA neurotoxicity literature). Class inference only.