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6-APB
Ball-and-stick model of the 6-APB molecule
Clinical data
Routes of
administration		By mouth, insufflation
Drug classSerotonin–norepinephrine–dopamine releasing agent; Serotonin 5-HT2 receptor agonist; Entactogen; Stimulant; Psychedelic
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
Onset of action30–60 minutes
Duration of action7–10 hours
Identifiers
  • 1-(1-benzofuran-6-yl)propan-2-amine
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC11H13NO
Molar mass175.231 g·mol−1
3D model (JSmol)
  • NC(C)CC1=CC(OC=C2)=C2C=C1
  • InChI=1S/C11H13NO/c1-8(12)6-9-2-3-10-4-5-13-11(10)7-9/h2-5,7-8H,6,12H2,1H3 checkY
  • Key:FQDAMYLMQQKPRX-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

6-APB (6-(2-aminopropyl)benzofuran) is an empathogenic psychoactive drug of the substituted benzofuran and substituted phenethylamine classes.[1] 6-APB and other compounds are sometimes informally called "Benzofury" in newspaper reports. It is similar in structure to MDA, but differs in that the 3,4-methylenedioxyphenyl ring system has been replaced with a benzofuran ring. 6-APB is also the unsaturated benzofuran derivative of 6-APDB. It may appear as a tan or brown grainy powder.[citation needed]

While the drug never became particularly popular, it briefly entered the rave and underground clubbing scene in the UK before its sale and import were banned. It falls under the category of research chemicals, sometimes called "legal highs” if uncontrolled. Because 6-APB and other substituted benzofurans have not been explicitly outlawed in some countries, they are often technically legal, contributing to its popularity.[citation needed]

Use

[edit]

6-APB can be found in freebase, hydrochloride, and succinate form. The freebase is purportedly 20% stronger than the hydrochloride salt and 65% stronger than the succinate. This means 100 mg of 6-APB HCl is equivalent to 83 mg of 6-APB freebase and 100 mg of 6-APB succinate is equivalent to 60 mg of 6-APB freebase. Different production batches may have impurities and should be treated with care.[citation needed]

Based on anecdotal reports, the dosages for 6-APB hydrochloride are the following:

Dosage
Oral
Threshold 15 mg
Light 15–60 mg
Common 60–90 mg
Strong 90–120 mg
Heavy 120 mg +
Duration
Oral
Onset 30–60 minutes (or more)
Come up 60–120 minutes
Peak 3–4 hours
Offset 2–3 hours
Total 7–10 hours
After effects 6–48 hours

The dosages for freebases or succinates have to be adjusted accordingly.

Effects

[edit]

6-APB is reported to produce entactogenic, stimulant, and mild psychedelic effects in humans.[2][3]

Adverse effects

[edit]

Acute psychosis has been associated with recreational use of 6-APB in combination with the synthetic cannabinoid JWH-122.[4]

Pharmacology

[edit]
Small clumps of 6-APB powder

Pharmacodynamics

[edit]

6-APB acts as a serotonin–norepinephrine–dopamine releasing agent (SNDRA), with EC50Tooltip half-maximal effective concentration values for monoamine release of 36 nM for serotonin, 14 nM for norepinephrine, and 10 nM for dopamine in rat brain synaptosomes.[5][6] Simultaneously, 6-APB is a serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI), with affinities (Ki) of 117 nM for the norepinephrine transporter (NET), 150 nM for the dopamine transporter (DAT), and 2,698 nM for the serotonin transporter (SERT)[1] as well as IC50Tooltip half-maximal effective concentration values for monoamine reuptake inhibition of 930 nM for serotonin, 190 nM for norepinephrine, and 3,300 nM for dopamine.[6]

In addition to actions at the monoamine transporters, 6-APB is a potent high-efficacy partial agonist or full agonist of the serotonin 5-HT2B receptor (Ki = 3.7 nM; EC50Tooltip half-maximal effective concentration = 140 nM; EmaxTooltip maximal efficacy = 70%).[1] It has higher affinity for this target than any other site.[7] Moreover, unlike MDMA, 6-APB shows 100-fold selectivity for the serotonin 5-HT2B receptor over the serotonin 5-HT2A and 5-HT2C receptors in terms of affinity.[7][8] It is notably both more potent and more selective as an agonist of the serotonin 5-HT2B receptor than the reference serotonin 5-HT2B receptor agonist, BW-723C86, which is commonly used for research into the serotonin 5-HT2B receptor.[citation needed] Although much more potent at the serotonin 5-HT2B receptor, 6-APB is also a partial agonist of the serotonin 5-HT2A receptor (EC50 = 5,900 nM; Emax = 43%) and shows affinity for the serotonin 5-HT2C receptor (Ki = 270 nM) and the serotonin 5-HT1A receptor (Ki = 1,500 nM).[6] It has been reported to act as an agonist of the serotonin 5-HT2C receptor similarly to the serotonin 5-HT2A and 5-HT2B receptors.[2][9]

Besides the serotonin 5-HT2 receptors, 6-APB has been found to bind with high affinity to the α2C-adrenergic receptor (Ki = 45 nM), although the significance of this action in humans is unknown.[1] 6-APB showed little other affinity at a wide selection of other sites, with some exceptions like the rodent trace amine-associated receptor 1 (TAAR1).[1][6]

The potent agonism of the serotonin 5-HT2B receptor makes it likely that 6-APB would be cardiotoxic with chronic or long-term use, as seen with other serotonin 5-HT2B receptor agonists such as the withdrawn serotonergic anorectic fenfluramine.[1][10]

Pharmacokinetics

[edit]

The pharmacokinetics of 6-APB have not been studied, however, some information can be extracted from user reports. These suggest a slow onset of 40–120 minutes. The drugs peak effects last 7 hours, followed by a comedown phase of approximately 2 hours, and after effects for up to 24 hours.[11]

Metabolism

[edit]

Although limited literature is available, there is some data on metabolism of 6-APB in rats. Its Phase I metabolism involves hydroxylation of the furan ring, then cleavage of the ring, followed by a reduction of the unsaturated aldehyde from the previous step. The resulting aldehyde may then take two paths. It is either oxidized to a carboxylic acid or reduced to an alcohol, and then hydroxylated. Phase II metabolism consists of glucuronidation. The most prevalent metabolites in rats were 3-carboxymethyl-4-hydroxyamphetamine and 4-carboxymethyl-3-hydroxyamphetamine.[12]

Chemistry

[edit]

Reagent results

[edit]

6-APB and its structural isomer 5-APB have been tested with a series of agents including: Marquis, Liebermann, Mecke, and Froehde reagents.[13] Exposing compounds to the reagents gives a colour change which is indicative of the compound under test.

Compound Marquis Mecke Mandelin Liebermann Froehde Gallic Ehrlich Hofmann Simon's Folin
6-APB Purple Purple to black Purple to black Black Purple Brown Orange Light orange No reaction Light orange
6-APB succinate Purple Purple to black Purple to black Black Purple Brown Faint orange No reaction No reaction Light orange

6-APB succinate is reported to be practically insoluble in CHCl3 as well as very minimally soluble in cold water. A batch seized by the DEA contained a 2:1 ratio of succinate to 6-APB.[14]

Synthesis

[edit]
Synthesis of 6-APB and its structural isomer 4-APB[14]

The synthesis by Briner et al.[8] entailed refluxing 3-bromophenol with bromoacetaldehyde diethylacetal and sodium hydride to give the diethyl acetal, which then was heated with polyphosphoric acid to give a mixture of bromobenzofuran structural isomers: 4-bromo-1-benzofuran and 6-bromo-1-benzofuran. The isomers were separated by silica gel column chromatography, then converted to their respective propanone derivatives, and then reductively aminated to give 6-APB and 4-APB, both of which were converted to their HCl ion pairs for further examination.

Society and culture

[edit]
[edit]

Canada

[edit]

In 1999, amphetamines were changed from Schedule III to Schedule I as a result of the Safe Streets Act. Some have speculated that 6-APB's structure qualifies it as a Schedule I drug as an analog of MDA.[15][unreliable source?]

In 2014, a study funded by the Canadian Institutes of Health Research noted that 6-APB "may or may not be legal in Canada depending on how one interprets the current Act"[16] and that it could be purchased for academic purposes without an exemption from Health Canada. The study also noted how, unlike the MDMA it often serves as a replacement for in countries like the US, 6-APB's benzofuran structure does not make it a direct analogue of amphetamine despite similarities in effects.

China

[edit]

6-APB has been a controlled substance in China since 1 July 2024[17]

Finland

[edit]

6-APB is scheduled in government decree on narcotic substances, preparations and plants and hence is illegal.[18]

France

[edit]

6-APB is illegal in France.[19]

Germany

[edit]

6-APB is illegal in Germany since the 17th of July, 2013, when it was added to Anlage II of the Betäubungsmittelgesetz.[citation needed]

Italy

[edit]

6-APB is illegal in Italy.[20]

Luxembourg

[edit]

In Luxembourg, 6-APB is not cited in the list of prohibited substances.[21] Therefore, it is still a legal substance.

Netherlands

[edit]

6-APB, as well as multiple substances based on the phenylethamine structure, like most cathinones and amphetamines, are banned under the Opium Law since July 1st, 2025,[22] following an amendment to deal with New Psychoactive Substances (NPS) in the Netherlands. Since this is a structural ban instead of a direct one, later substances that differ slightly but use the same skeleton will also be preemptively banned.

New Zealand and Australia

[edit]

Certain countries contain a "substantially similar" catch-all clause in their drug law, such as New Zealand and Australia. This includes 6-APB as it is similar in chemical structure to the class A drug MDA, meaning 6-APB may be viewed as a controlled substance analogue in these jurisdictions.[23]

Sweden

[edit]

In Sweden, as of 27 December 2009 6-APB is classified as "health hazard" under the act Lagen om förbud mot vissa hälsofarliga varor (translated Act on the Prohibition of Certain Goods Dangerous to Health).[24]

It is also classified as a narcotic substance since 2020.[25]

United Kingdom

[edit]

On June 10, 2013 6-APB and a number of analogues were classified as Temporary Class Drugs in the UK following an ACMD recommendation.[10] This means that sale and import of the named substances are criminal offences and are treated as for class B drugs.[26] On November 28, 2013 the ACMD recommended that 6-APB and related benzofurans should become Class B, Schedule 1 substances.[10] On March 5, 2014 the UK Home Office announced that 6-APB would be made a class B drug on 10 June 2014 alongside every other benzofuran entactogen and many structurally related drugs.[27]

United States

[edit]

6-APB is not scheduled at the federal level in the United States,[28][failed verification] but it may be considered an analog of amphetamine, in which case purchase, sale, or possession could be prosecuted under the Federal Analog Act.[29]

See also

[edit]

References

[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

6-APB

View on Grokipedia
from Grokipedia
6-(2-Aminopropyl) (6-APB) is a synthetic derivative classified as a novel psychoactive substance, recognized for its entactogenic and pharmacological profile. With the molecular formula C₁₁H₁₃NO and a molecular weight of 175.23 g/mol, it features a ring system attached to a 2-aminopropyl chain, structurally analogous to the derivative 3,4-methylenedioxy (MDA) but with the methylenedioxyphenyl moiety replaced by . First synthesized in the early 2010s as a , 6-APB gained notoriety in recreational circles for producing effects including euphoria, increased sociability, and mild visual distortions, often described as intermediate between and . Pharmacological studies indicate that 6-APB functions as a potent at serotonin 5-HT₂B and 5-HT₂C receptors, with additional activity at monoamine transporters, promoting the release of serotonin, , and norepinephrine in a manner mimicking MDA but with greater potency and sustained locomotor stimulation in animal models. Unlike traditional serotonergic psychedelics, its balanced monoamine modulation contributes to empathogenic rather than purely hallucinogenic outcomes, though human data remain limited to self-reports and case studies due to its status outside . Preclinical evidence highlights risks such as potential cardiovascular strain from sympathomimetic effects and at high doses, underscoring its unapproved status for therapeutic use. As a , 6-APB has been subject to scheduling under analogue laws in multiple countries, reflecting concerns over , including reports of and in recreational overdoses, though systematic long-term epidemiological data are scarce. Its emergence parallels the proliferation of benzofuran analogs like , driven by clandestine synthesis routes involving precursors, yet peer-reviewed metabolic profiling reveals extensive biotransformation via enzymes, complicating detection in forensic contexts.

History

Discovery and Initial Research

6-APB, chemically 6-(2-aminopropyl), was first synthesized in 1993 by Alexander P. Monte and colleagues in the laboratory of at as part of a program investigating analogs of (MDA). The synthesis involved preparing several such analogs to explore structure-activity relationships for serotonergic agents, with the goal of identifying compounds exhibiting MDA-like effects but potentially reduced neurotoxicity compared to traditional amphetamines like MDMA. Initial pharmacological research focused on preclinical evaluations, including discriminative stimulus effects in animal models, where the benzofuran derivatives generalized to the MDA cue, suggesting shared mechanisms of action involving serotonin release and receptor interactions. These studies established the compounds' potency as indirect monoamine agonists, particularly affecting serotonin and norepinephrine uptake over , though no immediate therapeutic development followed due to limited selectivity and safety data. Further binding assays in subsequent analyses confirmed affinity for serotonin receptors (e.g., 5-HT2A and 5-HT2B), aligning with the initial findings but highlighting potential cardiovascular risks from 5-HT2B agonism.

Emergence in Recreational Markets

6-APB entered recreational drug markets around 2010 as part of the wave of novel psychoactive substances (NPS) following regulatory crackdowns on synthetic cathinones like in the and elsewhere in . Marketed primarily under the "Benzo Fury," it was distributed online by vendors as an unregulated , often in capsule or powder form, positioned as a legal analogue with purportedly reduced . This timing aligned with users seeking alternatives after the April 2010 ban on , which created a market vacuum for stimulant-entactogen hybrids. Initial adoption occurred in club, , and scenes across the and , where 6-APB appealed for its reported empathogenic effects and extended duration compared to ecstasy. By late 2010, products labeled Benzo Fury—containing , 6-APB, or mixtures—were widely advertised on vendor websites, with sales peaking before analytical detection in seized materials confirmed its presence. User reports and early wastewater analyses indicated sporadic but growing recreational use, particularly among young adults in nightlife settings, though prevalence remained lower than established drugs like . Emergence was short-lived due to rapid regulatory responses; in the UK, 6-APB was linked to acute harms, including a reported in and subsequent fatalities involving polydrug use, prompting a temporary class drug order in June 2013 and permanent scheduling later that year. Similar bans followed in other jurisdictions, curtailing open market availability by 2014, though underground production persisted.

Chemistry

Molecular Structure and Properties

6-APB, systematically named 6-(2-aminopropyl), possesses the molecular formula and a molecular mass of 175.23 g/mol. The structure comprises a moiety, consisting of a benzene ring fused to a furan ring, with a propan-2-amine side chain attached at the 6-position. This configuration includes a chiral center at the beta-carbon of the side chain, yielding (R)- and (S)-enantiomers, though commercial and research samples are generally racemic. The freebase form is typically a colorless to pale yellow oil, while the hydrochloride salt appears as a white crystalline solid. Solubility data indicate moderate solubility in polar organic solvents such as dimethylformamide, dimethyl sulfoxide, and ethanol (approximately 20 mg/mL), with lower solubility in phosphate-buffered saline (1 mg/mL). Experimental melting and boiling points are not widely reported, reflecting limited standardized characterization due to its status as a research chemical. The hydrochloride salt exhibits a flash point of 9°C and is recommended for storage at -20°C to maintain stability.

Synthesis Routes

Benzofuran analogs of amphetamines, including 6-(2-aminopropyl) (6-APB), were originally synthesized in the early 1990s during pharmacological investigations into structure-activity relationships for compounds mimicking (MDA). One documented laboratory synthesis route, adapted for analytical characterization, begins with the reflux of 3-bromophenol and bromoacetaldehyde diethyl in the presence of to generate a diethyl intermediate. Subsequent heating of this intermediate with polyphosphoric acid promotes and intramolecular cyclization, producing a separable mixture of 5-bromobenzofuran and 6-bromobenzofuran isomers via . The isolated 6-bromobenzofuran undergoes catalytic transformation to the corresponding aryl methyl , 1-(benzofuran-6-yl)propan-2-one. of this with yields the primary 6-APB, which is commonly purified and stored as the hydrochloride salt for stability and handling. This multi-step process ensures at the 6-position of the scaffold, distinguishing 6-APB from its 5-isomer. Variations in synthesis may employ organometallic intermediates, such as Grignard reagents derived from the bromobenzofuran, followed by or reactions to install the propanone side chain, though detailed conditions in forensic literature are often omitted to deter illicit replication. These routes highlight the compound's derivation from substituted , leveraging the reactivity of the phenolic hydroxyl for furan ring formation.

Identification and Reagent Tests

6-APB can be presumptively identified using colorimetric reagent tests, which detect characteristic functional groups in its and aminopropyl structure but lack specificity and require confirmation via techniques like GC-MS or NMR. These tests are commonly employed in contexts to differentiate 6-APB from structurally similar entactogens such as or MDA. The yields a purple color reaction with 6-APB, contrasting with the black color observed for , aiding differentiation between benzofurans and methylenedioxyphenethylamines. This targets phenolic and indolic structures but reacts variably with amines, making it a secondary test after primary reagents like Marquis. Simon's reagent, which indicates secondary amines via a blue color change (as seen with ), produces no such reaction with 6-APB due to its primary amine moiety, similar to or MDA. Marquis reagent elicits a rapid color progression in s like 6-APB, often to orange-red or violet shades, though results overlap with amphetamines and necessitate multi-reagent confirmation. Mecke reagent provides supplementary data, typically showing green or blue-green shifts for related compounds, but specific documentation for 6-APB emphasizes its use alongside Froehde for verification.
ReagentExpected Reaction for 6-APBDistinguishing Note
FroehdePurpleVs. black for
Simon'sNo blue colorIndicates primary , unlike secondary in
MarquisRapid to violet/orange-redOverlaps with amphetamines; presumptive only
MeckeVariable green/blue-greenSupplementary; not diagnostic alone
These tests assume pure samples; adulterants can alter outcomes, underscoring the need for lab analysis, as seen in forensic identifications of APB isomers via chromatography.

Pharmacology

Pharmacodynamics

6-APB functions primarily as a substrate-type releaser of monoamine neurotransmitters, inducing non-exocytotic release via the dopamine transporter (DAT), norepinephrine transporter (NET), and serotonin transporter (SERT) in rat brain synaptosomes. In release assays, it exhibits EC50 values of 10 nM at DAT, 14 nM at NET, and 36 nM at SERT, demonstrating greater potency than 3,4-methylenedioxyamphetamine (MDA; EC50 values: 106 nM DAT, 47 nM NET, 162 nM SERT) and 3,4-methylenedioxymethamphetamine (MDMA; 120 nM DAT, 90 nM NET, 85 nM SERT). This non-selective profile (DAT/SERT ratio: 3.60; DAT/NET ratio: 1.40) leads to elevated extracellular levels of dopamine (peak 8.4-fold increase) and serotonin (peak 16-fold increase) in the rat nucleus accumbens following systemic administration of 1 mg/kg, surpassing MDA's effects at higher doses (3 mg/kg). In uptake inhibition assays using human transporters, 6-APB displays IC50 values of 3.3 μM at DAT, 0.19 μM at , and 0.93 μM at SERT, with a DAT:SERT selectivity ratio of 0.29, akin to (0.14). It also evokes release of norepinephrine, , and serotonin at concentrations of 100 μM in vitro, consistent with its substrate behavior at monoamine transporters. These actions contribute to stimulant-like locomotor effects in , with 6-APB producing robust increases in ambulation (up to 24-fold at 1 mg/kg), more sustained than those of MDA. Beyond transporter interactions, 6-APB acts as an at serotonin receptors, including partial at 5-HT2A (Ki = 0.97 μM; EC50 = 5.9 μM, 43% relative to 5-HT) and more potent at 5-HT2B (EC50 = 0.14 μM, 70% ). It binds trace amine-associated receptor 1 (TA1; Ki = 0.05–0.06 μM in rat and mouse) and shows moderate affinity for α-adrenoceptors (α1A Ki = 7.3 μM; α2A Ki = 0.38 μM), potentially modulating additional physiological responses. Overall, its pharmacodynamic profile resembles that of entactogens like , emphasizing serotonergic and noradrenergic release with secondary effects.

Pharmacokinetics

Limited pharmacokinetic exist for 6-APB, a novel derivative, owing to its emergence as a recreational substance without formal clinical trials; most insights derive from studies and liver microsome assays. Absorption details remain unquantified, though predominates recreationally, with inferred rapid uptake based on reported onset times of 30-120 minutes in user accounts cross-referenced with analogous entactogens like . No measurements are available, but structural similarity to amphetamines suggests high oral absorption potential via passive in the . Distribution pharmacokinetics are undocumented, but the compound's lipophilic profile (logP ≈ 2.0, inferred from molecular modeling of benzofurans) implies blood-brain barrier penetration, consistent with effects observed in preclinical models. Metabolism is hepatic, involving enzymes; in models, phase I transformations include ring , cleavage, and side-chain oxidation, yielding the principal 4-carboxymethyl-3-hydroxyamphetamine alongside minor N-acetyl and hydroxy derivatives. liver microsomes confirm CYP-mediated N-demethylation for the related 6-MAPB analog (via , , ), suggesting comparable pathways for 6-APB. Phase II conjugation likely follows, though uncharacterized. Excretion occurs primarily renally, with parent 6-APB and metabolites detectable in rat urine up to 48 hours post-dose via GC-MS and LC-HRMS after standard doses (e.g., 10 mg/kg), enabling forensic confirmation; human urine screening similarly identifies intake through these targets. No fecal or biliary elimination data exist. Plasma remains undetermined for 6-APB, though the congener exhibits first-order kinetics with t½ ≈ 6.5 hours in a reported intoxication case, akin to MDMA's 7-9 hours. Clearance likely mirrors amphetamine-like substances, emphasizing urinary dependence.

Metabolism and Elimination

The metabolism of 6-APB (6-(2-aminopropyl)) primarily occurs in the liver through phase I biotransformations, including alkyl chain followed by oxidation to ketones, direct dehydrogenation of the side chain, aromatic , N-acetylation, and ring opening of the benzofuran moiety leading to derivatives. In studies using hepatocytes and liver microsomes, the main phase I metabolite identified was 4-carboxymethyl-3-hydroxyamphetamine, alongside hydroxy, keto, and N-acetylated variants of the parent compound. Phase II conjugation, such as , sulfation, and O-methylation of hydroxy metabolites, further modifies these phase I products, facilitating excretion. Elimination of 6-APB occurs predominantly via renal of metabolites in urine, with the parent drug and its biotransformation products detectable using GC-MS and LC-HRMS techniques. In models administered typical recreational doses (approximately 15-20 mg/kg orally), urinary detection of 6-APB and key s, including the carboxymethyl-hydroxyamphetamine derivative, was possible up to 48 hours post-administration, confirming intake even at standard screening sensitivities. No human pharmacokinetic data on elimination are available, though structural analogs like exhibit first-order kinetics with a half-life of about 6.5 hours in preclinical assays, suggesting comparable renal clearance timelines. Fecal elimination appears minimal based on the profile observed in urinary-dominant patterns.

Effects

Desired Physiological and Psychological Effects

Users seek 6-APB primarily for its entactogenic properties, which mimic those of , including pronounced euphoria, empathy, and emotional openness. These psychological effects are described as fostering feelings of closeness, friendliness, and enhanced sociability, often leading to increased talkativeness and a sense of during social settings like parties or raves. Physiologically, desired outcomes include mild to moderate stimulation, elevated energy levels, and heightened sensory perception, such as enhanced appreciation of music and touch, without the intense jaw clenching or commonly associated with at equivalent doses. Some users report an increased and subtle , contributing to its appeal in recreational contexts seeking both emotional and physical enhancement. These effects are attributed to 6-APB's action as a serotonin, , and norepinephrine releaser, though human clinical data remain limited, with most evidence derived from self-reported experiences and preclinical studies.

Duration and Onset

The onset of subjective effects from 6-APB following typically begins within 30–90 minutes, with a gradual come-up phase extending to 1–2 hours as , , and entactogenic effects intensify. This delayed onset aligns with its pharmacokinetic profile, inferred from limited animal data showing rapid absorption but slower systemic distribution compared to intravenous routes, where locomotor peaks at 20–50 minutes post-injection in . User reports consistently describe variability influenced by dose (e.g., 100–150 mg common recreational range), stomach contents, and individual , with faster onset (20–40 minutes) occasionally noted when taken sublingually or on an empty . Peak effects, characterized by heightened , sensory enhancement, and mild hallucinations, persist for 3–5 hours, during which serotonin release sustains elevated mood and . The total duration of primary effects spans 6–10 hours, followed by a 2–4 hour offset phase involving residual stimulation and potential , with aftereffects like mild afterglow or lasting up to 48 hours. These estimates derive primarily from anecdotal self-reports on platforms, as human clinical trials are absent due to 6-APB's status as a novel psychoactive substance; animal microdialysis studies indicate prolonged serotonin efflux (up to 3 hours post-administration), supporting the extended duration but not directly translating to human timelines. Redosing after 3–5 hours is reported to extend effects but risks accumulation and intensified side effects like or .

Risks and Toxicity

Acute Adverse Effects

Acute adverse effects of 6-APB primarily manifest as sympathomimetic responses, including , , , and , alongside (jaw clenching) and potential reductions in level. These effects stem from its structural similarity to and amphetamines, promoting excessive release that overstimulates adrenergic and serotonergic systems. Neurological and psychological adverse reactions include acute anxiety, agitation, , , and , often exacerbated by polydrug use such as with or . A documented case involved a 21-year-old who, after ingesting 0.4 g of 6-APB over two days alongside , presented with paranoid delusions, agitation, (forearm lacerations), and , though without autonomic hyperactivity like sweating or seizures; symptoms resolved with treatment within days. Other reports note aggression and panic attacks during intoxication. In preclinical studies, high doses of 6-APB (e.g., 2.5 mg/kg in rats) induced decreased , excessive salivation, and convulsions, indicating potential for severe motor and autonomic disruption at supratherapeutic levels. case data remains limited, with effects frequently confounded by co-ingested substances, underscoring the challenges in isolating 6-APB-specific .

Overdose Potential and Case Reports

6-APB exhibits overdose potential akin to other entactogens like , primarily through excessive serotonergic and dopaminergic release, which can precipitate , , , , and seizures, though human lethal dose data are absent and toxicity appears dose-dependent in preclinical models. In hepatocyte assays, the 5-APB demonstrated greater than 6-APB, suggesting comparatively lower intrinsic for 6-APB, but both compounds elevate extracellular serotonin levels potently, mirroring 's profile and elevating risks of acute neurotoxicity at high doses. Anecdotal user reports from forums describe tolerance to doses exceeding 300 mg without fatality, but pharmacological similarity to implies a narrow in unsupervised use, exacerbated by impurities in unregulated products or concurrent vasopressin-mediated . Documented case reports of severe adverse events involving 6-APB are limited and predominantly feature polydrug intoxication, complicating attribution. A 2013 UK Advisory Council on the Misuse of Drugs report detailed four fatalities linked to 6-APB: one involving co-ingestion with and elevated body temperature; two with 5-IT and/or ; and one associated with "Benzofury" products containing 6-APB. In a separate postmortem analysis, 6-APB was detected at 0.2 mg/L in femoral blood alongside 5-IT (0.5 mg/L) in a 22-year-old male fatality, with as a , but causation remained unclear due to . Broader data from 2011 onward implicated 5- or 6-APB in approximately 10 deaths, all involving multiple substances postmortem, underscoring polysubstance confounding over isolated 6-APB lethality. Non-fatal presentations include a 2013 case of acute in a 21-year-old male after recreational 6-APB use with , manifesting as severe agitation, , and diaphoresis; urine confirmed 6-APB at 2000 ng/mL alongside its metabolite 6-MAPB (30 ng/mL) and , resolving with supportive care and antipsychotics. Seven hospitalizations followed a incident tied to "Benzofury" (containing 6-APB variants and adjuncts like ), featuring hyperpyrexia, , and , treated symptomatically. No verified reports exist of or solely from 6-APB, but its 5-HT release profile indicates plausible risk, particularly with re-dosing or environmental factors like dancing. Overall, empirical evidence points to moderate overdose resilience relative to analogs like , with harms amplified by adulteration and combinations rather than inherent potency.

Long-Term Health Implications and Dependence

Due to the novelty of 6-APB as a recreational substance, empirical on long-term effects in humans remain scarce, with most insights derived from pharmacological profiles and comparisons to structurally similar entactogens like . Chronic activation of the serotonin by 6-APB, observed at submicromolar concentrations (: 0.14 μM), raises concerns for , including potential heart fibrosis akin to that seen with other 5-HT2B agonists such as . government assessments have highlighted this risk, noting research indicating cardiac toxicity with prolonged 5- and 6-APB use, though no large-scale longitudinal studies confirm incidence rates or mechanisms in users. Neurotoxicity potential appears lower than for analogs, as preclinical models show 6-APB primarily promotes serotonin release (SERT:NET:DAT potency ratio favoring serotonin) without clear evidence of axonal damage or persistent depletion observed in studies; however, repeated use may disrupt serotonin , leading to protracted anxiety or mood dysregulation reported anecdotally post-acute phase. No verified cases link 6-APB to irreversible cognitive deficits or neurodegeneration, but from monoamine overflow could contribute to subtle long-term neuronal changes, as inferred from broader new psychoactive substance (NPS) . Dependence liability is considered low, mirroring MDMA's profile, due to 6-APB's skewed serotonin over release (DAT:SERT ratio of 0.29), which reduces reinforcing effects in self-administration paradigms despite inducing in rodents. Tolerance develops rapidly to subjective effects, potentially discouraging frequent use, with no documented severe withdrawal syndromes; mild symptoms like or may occur but lack the compulsive redosing seen in stimulants with higher activity. Human case reports do not indicate high rates, though polysubstance contexts complicate attribution.

Use and Prevalence

Patterns of Recreational Use

6-APB, marketed under names such as Benzo Fury, emerged on the illicit drug market around 2010–2011, with initial reports to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) from the (for ) and (for 6-APB). Recreational use is predominantly associated with environments, including nightclubs, music festivals, and parties, where it serves as an and mild akin to , promoting , sociability, and energy for extended durations. Users often consume it in social group settings, with 62.5% of surveyed Dutch users reporting ingestion alongside friends at clubs, pubs, or events. The primary is oral (88% of cases in analyzed user reports), typically via powder or pre-formed pellets of 120–125 mg, though nasal (24%) and rare occur. Common initial doses range from 100–140 mg, with redosing of approximately 50 mg after 3–5 hours to prolong effects, which last 6–8 hours; light doses are under 100 mg, while high doses exceed 175–200 mg. It is frequently combined with , , or , though users note intensified effects and risks when stacking with strong doses. Prevalence remains low and niche, with lifetime use of "benzofury" reported at 2.7% and past-year use at 2.3% among European nightlife visitors (primarily UK-based), and 3.2% lifetime/2.4% past-year in a UK survey. In the , fewer than 0.5% of respondents indicated past-12-month use. Use appears occasional rather than chronic, tied to event-based , with detections in samples from UK festivals and cities since 2010 but declining post-regulatory controls.

Research and Analytical Contexts

Preclinical pharmacological studies have characterized 6-APB as a nonselective monoamine releaser, with potent activity at serotonin (5-HT), , and norepinephrine (NE) transporters, inducing release via SERT, DAT, and in a dose-dependent manner similar to but more efficacious than in rat brain synaptosomes. In vivo rodent models demonstrate that 6-APB produces forward locomotion and stereotyped behaviors at doses of 1-10 mg/kg, with greater potency and extended duration relative to , alongside discriminative stimulus effects generalizing to and cues. These findings stem from controlled laboratory experiments, though human pharmacokinetic data remain sparse, limiting direct . Analytical chemistry research emphasizes chromatographic and spectrometric methods for 6-APB identification and quantification, particularly to distinguish it from positional isomers like 4-APB, , and 7-APB in forensic and toxicological samples. Gas chromatography- (GC-MS) protocols, often involving trimethylsilyl derivatization, enable detection in and at limits of 10-50 ng/mL, with characteristic fragments at m/z 174 and 188 confirming . Liquid chromatography-high-resolution (LC-HRMS/MS) provides superior sensitivity for metabolites, identifying phase I pathways such as O-demethylenation and in rat after 10-25 mg/kg dosing, with detectability up to 48 hours post-administration. High-performance liquid chromatography- (HPLC-MS/MS) assays validate simultaneous measurement of and 6-APB in , , and tissues, achieving linearity from 0.5-500 ng/mL with recovery rates exceeding 80%. Synthetic routes developed in peer-reviewed contexts facilitate reference standard preparation for analytical validation, typically involving core construction via condensation of 6-hydroxybenzofuran with nitropropene, followed by reduction, yielding racemic 6-APB with >95% purity confirmed by NMR and GC-MS. synthesis, such as hydroxylated derivatives from precursors, supports toxicity profiling by enabling spiked sample analysis. Toxicity research is constrained by ethical limits on human trials, relying on cytotoxicity assays showing 5-HT2B agonism-linked risks and isolated case reports of acute at recreational doses (100-200 mg), but no large-scale epidemiological data exist as of 2023. Overall, these contexts highlight 6-APB's structural analogy to but underscore gaps in long-term human safety data due to its emergence as a post-2010.

International and Analog Controls

6-APB, chemically known as 6-(2-aminopropyl)benzofuran, is not scheduled under the or any other international drug control treaty administered by the UNODC. The substance is classified as a new psychoactive substance (NPS) and has been monitored by the UNODC since its emergence around , with reports noting its detection in illicit markets primarily in and , but without triggering formal international scheduling recommendations. At the European level, the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) has tracked 6-APB through its since 2010, identifying it alongside related benzofurans like as entactogens with potential for abuse similar to . While no formal EMCDDA-led risk assessment specifically for 6-APB resulted in EU-wide scheduling, national controls proliferated; for instance, implemented controls on benzofurans including 6-APB in response to EMCDDA alerts, and the issued a temporary class drug order in 2013 citing risks of acute toxicity and cardiac effects before enacting permanent Class B status. Analog controls apply in jurisdictions with structural analogue laws, treating 6-APB as equivalent to scheduled substances due to its close similarity to phenethylamines like (MDA), where the methylenedioxy ring is replaced by a moiety. In the United States, under the (21 U.S.C. § 813), 6-APB is not explicitly scheduled federally but can be prosecuted as a Schedule I analogue if substantially similar in structure and effect to a like MDA and intended for human consumption, with enforcement documented in forensic analyses since at least 2011. Similarly, Canada's designates it a Schedule III analogue of MDA following amendments under the Safe Streets and Communities Act. Other nations, such as and , have incorporated benzofurans into analogue provisions or specific bans, reflecting a of national responses rather than unified international action.

Country-Specific Status and Recent Changes

In the United Kingdom, 6-APB is classified as a Class B controlled substance under the , following its addition via the (Amendment) Order 2013, effective June 10, 2013, after an initial temporary class drug order in May 2013. In the United States, 6-APB is not explicitly listed as a federally under the , but it may be treated as a positional or analog of Schedule I substances like under the (21 U.S.C. § 813) when intended for human consumption, enabling prosecution for distribution or possession with intent. Several states have independently scheduled it, including (effective March 18, 2014), , and .
Country/RegionLegal StatusKey Details and Date
Controlled (Narcotic)Listed as 1-(benzofuran-6-yl)propan-2-amine; requires import licenses and permits. No specific scheduling date identified in federal records, but subject to analogue provisions under the Criminal Code Act 1995.
Unscheduled federally; analogue risksNot explicitly controlled under the , but prosecutable under general provisions for substances substantially similar to Schedule I drugs like amphetamines if marketed for psychoactive use.
European Union (varies by member state)Mixed: Illegal in some (e.g., ); uncontrolled in others (e.g., )France prohibits it outright; reports no controls as of recent assessments; remains legal as of July 2025 but falls under a new psychoactive substances grouping law that could lead to future bans without specific implementation for 6-APB yet.
UncontrolledPreviously addressed under medicines law, but high court ruling excluded NPS like 6-APB, leaving it unregulated as of assessments.
No major regulatory changes specific to 6-APB have been enacted between 2023 and 2025 across surveyed jurisdictions, with statuses largely stable since mid-2010s bans in responsive countries; ongoing monitoring of new psychoactive substances has not targeted it anew.

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