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]
In addition to actions at the monoamine transporters, 6-APB is a potentfull agonist of the serotonin5-HT2B receptor (Ki = 3.7 nM),[1] with higher affinity for this target than any other site.[3] Moreover, unlike MDMA, 6-APB shows 100-fold selectivity for the 5-HT2B receptor over the 5-HT2A and 5-HT2C receptors.[3][4] It is notably both more potent and more selective as an agonist of the 5-HT2B receptor than the reference 5-HT2B receptor agonist, BW-723C86, which is commonly used for research into the 5-HT2B receptor.[citation needed] Aside from the 5-HT2B receptor, 6-APB has also been found to bind with high affinity to the α2C-adrenergic receptor subtype (Ki = 45 nM), although the clinical significance of this action is unknown.[1] 6-APB showed little other affinity at a wide selection of other sites.[1]
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.[6]
Acute psychosis has been associated with recreational use of 6-APB in combination with the synthetic cannabinoid JWH-122.[8]
Reagents results
6-APB and its structural isomer 5-APB have been tested with a series of agents including: Marquis, Liebermann, Mecke, and Froehde reagents.[9] 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.[10]
Synthesis
Synthesis of 6-APB and its structural isomer 4-APB[10]
The synthesis by Briner et al.[4] 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 gelcolumn 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 HClion pairs for further examination.
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.
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"[12] 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.
United States
6-APB is not scheduled at the federal level in the United States,[13][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.[14]
Finland
6-APB is scheduled in government decree on narcotic substances, preparations and plants and hence is illegal.[15]
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.[19]
On June 10, 2013 6-APB and a number of analogues were classified as Temporary Class Drugs in the UK following an ACMD recommendation.[5] This means that sale and import of the named substances are criminal offences and are treated as for class B drugs.[21] On November 28, 2013 the ACMD recommended that 6-APB and related benzofurans should become Class B, Schedule 1 substances.[5] 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.[22]
China
6-APB has been a controlled substance in China since 1 July 2024[23]
^Shaun L. Greene (2013). Novel Psychoactive Substances: Classification, Pharmacology and Toxicology Chapter 16 – Benzofurans and Benzodifurans. Boston: Academic Press. pp. 383–392. doi:10.1016/B978-0-12-415816-0.00016-X. ISBN978-0-12-415816-0.
^Nugteren-van Lonkhuyzen JJ, van Riel AJ, Brunt TM, Hondebrink L (December 2015). "Pharmacokinetics, pharmacodynamics and toxicology of new psychoactive substances (NPS): 2C-B, 4-fluoroamphetamine and benzofurans". Drug and Alcohol Dependence. 157: 18–27. doi:10.1016/j.drugalcdep.2015.10.011. PMID26530501.
