:6-APB

{{Citations needed section|date=October 2024}}

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.{{cn|date=October 2024}}

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

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

6-APB is reported to produce entactogenic, stimulant, and mild psychedelic effects in humans.{{cite book | last=Greene | first=Shaun L | title=Novel Psychoactive Substances | chapter=Benzofurans and Benzodifurans | publisher=Elsevier | date=2013 | isbn=978-0-12-415816-0 | doi=10.1016/b978-0-12-415816-0.00016-x | url=https://linkinghub.elsevier.com/retrieve/pii/B978012415816000016X | access-date=15 April 2025 | page=383–392}}{{cite book | last=Canal | first=Clinton E. | title=New Psychoactive Substances | chapter=Serotonergic Psychedelics: Experimental Approaches for Assessing Mechanisms of Action | publisher=Springer International Publishing | publication-place=Cham | volume=252 | date=2018 | isbn=978-3-030-10560-0 | pmid=29532180 | pmc=6136989 | doi=10.1007/164_2018_107 | doi-access=free | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6136989 | access-date=15 April 2025 | page=227–260 | quote=Despite micromolar 5-HT1A affinities (Rickli et al. 2015b), Nbenzylphenethylamines retain potent psychedelic effects. Also, benzofurans, such as 5-APB and 6-APB, are potent and efficacious 5-HT2B agonists but have very low potency at 5-HT2A receptors. They also stimulate efflux of DA and 5-HT and have activity at TAAR1 receptors (Iversen et al. 2013; Rickli et al. 2015a), but anecdotal reports note that psychedelic effects are relatively minor compared to classic psychedelics. These observations provide further credence that the 5-HT2A receptor, but not 5-HT1A, 5-HT2B, TAAR1, or monoamine transporters, initiates psychedelic effects.}}

Acute psychosis has been associated with recreational use of 6-APB in combination with the synthetic cannabinoid JWH-122.{{cite journal | vauthors = Chan WL, Wood DM, Hudson S, Dargan PI | title = Acute psychosis associated with recreational use of benzofuran 6-(2-aminopropyl)benzofuran (6-APB) and cannabis | journal = Journal of Medical Toxicology | volume = 9 | issue = 3 | pages = 278–81 | date = September 2013 | pmid = 23733714 | pmc = 3770991 | doi = 10.1007/s13181-013-0306-y }}

File:6-APB.jpg

6-APB acts as a serotonin–norepinephrine–dopamine releasing agent (SNDRA), with {{Abbrlink|EC₅₀|half-maximal effective concentration}} values for monoamine release of 36{{nbsp}}nM for serotonin, 14{{nbsp}}nM for norepinephrine, and 10{{nbsp}}nM for dopamine in rat brain synaptosomes.{{cite journal | vauthors = Brandt SD, Walters HM, Partilla JS, Blough BE, Kavanagh PV, Baumann MH | title = The psychoactive aminoalkylbenzofuran derivatives, 5-APB and 6-APB, mimic the effects of 3,4-methylenedioxyamphetamine (MDA) on monoamine transmission in male rats | journal = Psychopharmacology (Berl) | volume = 237 | issue = 12 | pages = 3703–3714 | date = December 2020 | pmid = 32875347 | pmc = 7686291 | doi = 10.1007/s00213-020-05648-z | url = }}{{cite journal | vauthors = Rickli A, Kopf S, Hoener MC, Liechti ME | title = Pharmacological profile of novel psychoactive benzofurans | journal = British Journal of Pharmacology | volume = 172 | issue = 13 | pages = 3412–3425 | date = July 2015 | pmid = 25765500 | pmc = 4500375 | doi = 10.1111/bph.13128 | url = https://pmc.ncbi.nlm.nih.gov/articles/PMC4500375/pdf/bph0172-3412.pdf}} Simultaneously, 6-APB is a serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI), with affinities (K_i) of 117{{nbsp}}nM for the norepinephrine transporter (NET), 150{{nbsp}}nM for the dopamine transporter (DAT), and 2,698{{nbsp}}nM for the serotonin transporter (SERT){{cite journal | vauthors = Iversen L, Gibbons S, Treble R, Setola V, Huang XP, Roth BL|author6-link=Bryan Roth | title = Neurochemical profiles of some novel psychoactive substances | journal = European Journal of Pharmacology | volume = 700 | issue = 1–3 | pages = 147–151 | date = January 2013 | pmid = 23261499 | pmc = 3582025 | doi = 10.1016/j.ejphar.2012.12.006 }} as well as {{Abbrlink|IC₅₀|half-maximal effective concentration}} values for monoamine reuptake inhibition of 930{{nbsp}}nM for serotonin, 190{{nbsp}}nM for norepinephrine, and 3,300{{nbsp}}nM for dopamine.

In addition to actions at the monoamine transporters, 6-APB is a potent high-efficacy partial agonist or full agonist of the serotonin 5-HT_2B receptor (K_i = 3.7{{nbsp}}nM; {{Abbrlink|EC₅₀|half-maximal effective concentration}} = 140{{nbsp}}nM; {{Abbrlink|E_max|maximal efficacy}} = 70%). It has higher affinity for this target than any other site.{{cite journal | vauthors = Canal CE, Murnane KS | title = 2C receptor and the non-addictive nature of classic hallucinogens | journal = Journal of Psychopharmacology | volume = 31 | issue = 1 | pages = 127–143 | date = January 2017 | pmid = 27903793 | pmc = 5445387 | doi = 10.1177/0269881116677104 }} Moreover, unlike MDMA, 6-APB shows 100-fold selectivity for the serotonin 5-HT_2B receptor over the serotonin 5-HT_2A and 5-HT_2C receptors in terms of affinity.{{cite patent | country = US | number = 7045545 | status = patent | title = Aminoalkylbenzofurans as serotonin (5-HT(2c)) agonists | pubdate = 19 January 2000 | gdate = 16 May 2006 | inventor = Briner K, Burkhart JP, Burkholder TP, Fisher MJ, Gritton WH, Kohlman DT, Liang SX, Miller SC, Mullaney JT, Xu YC, Xu Y | assign1 = Eli Lilly Co. }} It is notably both more potent and more selective as an agonist of the serotonin 5-HT_2B receptor than the reference serotonin 5-HT_2B receptor agonist, BW-723C86, which is commonly used for research into the serotonin 5-HT_2B receptor.{{Citation needed|date=January 2016}} Although much more potent at the serotonin 5-HT_2B receptor, 6-APB is also a partial agonist of the serotonin 5-HT_2A receptor ({{Abbr|EC₅₀|half-maximal effective concentration}} = 5,900{{nbsp}}nM; {{Abbr|E_max|maximal efficacy}} = 43%) and shows affinity for the serotonin 5-HT_2C receptor (K_i = 270{{nbsp}}nM) and the serotonin]] 5-HT_1A receptor (K_i = 1,500{{nbsp}}nM). It has been reported to act as an agonist of the serotonin 5-HT_2C receptor similarly to the serotonin 5-HT_2A and 5-HT_2B receptors.{{ cite patent | country = US | number = 7045545 | status = patent | title = Aminoalkylbenzofurans as serotonin (5-HT(2c)) agonists | pubdate = 2000-01-19 | gdate = 2006-16-03 | inventor = Karin Briner et al | url = https://patents.google.com/patent/US7045545B1/}}

Besides the serotonin 5-HT₂ receptors, 6-APB has been found to bind with high affinity to the α_2C-adrenergic receptor (K_i = 45{{nbsp}}nM), although the significance of this action in humans is unknown. 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).

The potent agonism of the serotonin 5-HT_2B receptor makes it likely that 6-APB would be cardiotoxic with chronic or long-term use, as seen with other serotonin 5-HT_2B receptor agonists such as the withdrawn serotonergic anorectic fenfluramine.

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.{{cite book | title=Novel Psychoactive Substances: Classification, Pharmacology and Toxicology Chapter 16 – Benzofurans and Benzodifurans | publisher=Academic Press | author=Shaun L. Greene | date=2013 | location=Boston | pages=383–392 | isbn=978-0-12-415816-0 | doi=10.1016/B978-0-12-415816-0.00016-X}}

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.{{cite journal | vauthors = Nugteren-van Lonkhuyzen JJ, van Riel AJ, Brunt TM, Hondebrink L | title = Pharmacokinetics, pharmacodynamics and toxicology of new psychoactive substances (NPS): 2C-B, 4-fluoroamphetamine and benzofurans | journal = Drug and Alcohol Dependence | volume = 157 | pages = 18–27 | date = December 2015 | pmid = 26530501 | doi = 10.1016/j.drugalcdep.2015.10.011 }}

6-APB and its structural isomer 5-APB have been tested with a series of agents including: Marquis, Liebermann, Mecke, and Froehde reagents.{{Cite web|title=Results|url=https://www.protestkit.eu/results/|access-date=2021-06-01|website=PRO Test|language=en-US}} Exposing compounds to the reagents gives a colour change which is indicative of the compound under test.

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.{{cite journal | url=https://www.dea.gov/pr/microgram-journals/2012/mj9_61-74.pdf | title=The Characterization of 6-(2-Aminopropyl)benzofuran and Differentiation from its 4-, 5-, and 7-Positional Analogues | vauthors = Casale JF, Hays PA | journal=Microgram Journal | date=January 2012 | volume=9 | issue=2 | pages=61–74 | access-date=2016-06-08 | archive-date=2016-11-05 | archive-url=https://web.archive.org/web/20161105053635/https://www.dea.gov/pr/microgram-journals/2012/mj9_61-74.pdf | url-status=dead }}

File:Synthesis_of_6-APB_and_its_structural_isomer_4-APB.png

The synthesis by Briner et al. 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.

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.{{Cite web|url=https://isomerdesign.com/Cdsa/definitions.php?structure=C|title=Controlled Drugs and Substances Act : Definitions and Interpretations|website=isomerdesign.com|access-date=2019-11-11}}{{Unreliable source?|date=November 2019}}

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"{{Cite journal| vauthors = Hudson AL, Lalies MD, Baker GB, Wells K, Aitchison KJ |date=2014-04-16|title=Ecstasy, legal highs and designer drug use: A Canadian perspective|journal= Drug Science, Policy and Law |language=en|volume=1|pages=2050324513509190|doi=10.1177/2050324513509190|s2cid=159675835|issn=2050-3245|doi-access=free}} 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.

6-APB has been a controlled substance in China since 1 July 2024{{Cite web |last=National Medical Products Administration (NMPA) of China |date=July 22, 2024 |title=关于将溴啡等46种物质列入《非药用类麻醉药品和精神药品管制品种增补目录》的公告 |url=https://www.nmpa.gov.cn/xxgk/ggtg/ypggtg/ypqtggtg/20240619150650124.html}}

6-APB is scheduled in government decree on narcotic substances, preparations and plants and hence is illegal.{{Cite web |title=Ajantasa |url=https://finlex.fi/fi/lainsaadanto/2008/543 |website=finlex.fi}}

6-APB is illegal in France.{{cite web | url=https://www.legifrance.gouv.fr/loda/id/JORFTEXT000000533085/2023-06-23/ | title=Arrêté du 22 février 1990 fixant la liste des substances classées comme stupéfiants }}

6-APB is illegal in Germany since the 17th of July, 2013, when it was added to Anlage II of the Betäubungsmittelgesetz.{{cn|date=October 2024}}

6-APB is illegal in Italy.{{cite web | url=http://www.salute.gov.it/imgs/C_17_pagineAree_3729_listaFile_itemName_0_file.pdf | title=Nuove tabelle delle sostanze stupefacenti e psicotrope (DPR 309/90) | publisher=Ministero della Salute | language=it | access-date=2016-05-31 | archive-date=2016-02-06 | archive-url=https://web.archive.org/web/20160206033837/http://www.salute.gov.it/imgs/C_17_pagineAree_3729_listaFile_itemName_0_file.pdf | url-status=dead }}

In Luxembourg, 6-APB is not cited in the list of prohibited substances.{{Cite web|title=Loi du 19 février 1973 concernant la vente de substances médicamenteuses et la lutte contre la toxicomanie. - Legilux|url=http://legilux.public.lu/eli/etat/leg/loi/1973/02/19/n1/jo|access-date=2021-06-01|website=legilux.public.lu}} Therefore, it is still a legal substance.

6-APB is not listed under the Opium Law or the Medicine Act in the Netherlands, and thus currently legal.{{cn|date=October 2024}}

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.{{cite web | url=http://www.legislation.govt.nz/act/public/1975/0116/latest/DLM436101.html | title=Misuse of Drugs Act 1975 | date=7 November 2015 | publisher=New Zealand Legislation}}

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).{{cite web | url=http://www.notisum.se/rnp/sls/fakta/a9990058.HTM | title=Förordning (1999:58) om förbud mot vissa hälsofarliga varor | publisher=Lagbevakning med Notisum och Rättsnätet | date=24 November 2009 | language=sv | access-date=15 September 2013 | archive-date=4 October 2013 | archive-url=https://web.archive.org/web/20131004215233/http://www.notisum.se/rnp/sls/fakta/a9990058.HTM | url-status=dead }}

On June 10, 2013 6-APB and a number of analogues were classified as Temporary Class Drugs in the UK following an ACMD recommendation.{{cite web | url=https://www.gov.uk/government/publications/temporary-class-drug-order-report-on-benzofury-and-nbome-compounds | title=Temporary class drug order on benzofury and NBOMe compounds - letter from ACMD | publisher=GOV.UK | date=4 June 2013 | work = Advisory Council on the Misuse of Drugs | vauthors = Browne J }} This means that sale and import of the named substances are criminal offences and are treated as for class B drugs.{{cite news | url=https://www.gov.uk/government/news/nbome-and-benzofury-to-be-banned | title='NBOMe' and 'Benzofury' banned | date=4 June 2013 | agency=GOV.UK | work = Home Office | vauthors = Browne J }} On November 28, 2013 the ACMD recommended that 6-APB and related benzofurans should become Class B, Schedule 1 substances. 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.{{cite web | url=http://www.legislation.gov.uk/uksi/2014/1106/contents/made | title=The Misuse of Drugs Act 1971 (Ketamine etc.) (Amendment) Order 2014 | publisher=The National Archives | date=28 April 2014 | author=UK Home Office}}

6-APB is not scheduled at the federal level in the United States,{{Cite web |url=http://www.deadiversion.usdoj.gov/21cfr/cfr/1308/1308_11.htm |title=21 CFR — SCHEDULES OF CONTROLLED SUBSTANCES §1308.11 Schedule I. |access-date=2018-04-10 |archive-date=2009-08-27 |archive-url=https://web.archive.org/web/20090827043725/http://www.deadiversion.usdoj.gov/21cfr/cfr/1308/1308_11.htm |url-status=dead }}{{Failed verification|date=June 2019}} but it may be considered an analog of amphetamine, in which case purchase, sale, or possession could be prosecuted under the Federal Analog Act.{{cite journal | vauthors = Casale JF, Hays PA | title = The characterization of 5-and 6-(2-aminopropyl)-2, 3-dihydrobenzofuran. | journal = Microgram J. | date = January 2011 | volume = 8 | issue = 2 | pages = 62–74 | url = https://www.researchgate.net/publication/258111445 }}

• Borax combo
• 5-APB
• 6-APBT
• 6-API
• 6-APDB

{{Reflist}}

{{Entactogens}}

{{Psychedelics}}

{{Monoamine releasing agents}}

{{Serotonin receptor modulators}}

{{TAAR modulators}}

{{Phenethylamines}}

{{Chemical classes of psychoactive drugs}}

Category:5-HT2A agonists

Category:5-HT2B agonists

Category:5-HT2C agonists

Category:6-Benzofuranethanamines

Category:Designer drugs

Category:Entactogens

Category:Psychedelic phenethylamines

Category:Serotonin-norepinephrine-dopamine releasing agents

Category:Serotonin receptor agonists

Category:Substituted amphetamines

Category:TAAR1 agonists