6-APB: Difference between revisions

'''6-(2-Aminopropyl)benzofuran''' (also known as '''6-APB''' and '''"Benzofury"''') is a novel [[psychoactive class::entactogen]] substance of the [[chemical class::benzofuran]] class. Its characteristic effects include [[anxiety suppression]], [[disinhibition]], [[muscle relaxation]], and [[euphoria]]. It is structurally related to entactogens like [[MDA]], [[MDMA]], [[5-APB]], and [[5-MAPB]].

6-APB was first synthesized in 1993 by [[David E. Nichols]] as a potential non-neurotoxic alternative to [[MDMA]].<ref name="Nichols">Monte, A. P., Marona-Lewicka, D., Cozzi, N. V., & Nichols, D. E. (1993). Synthesis and pharmacological examination of benzofuran, indan, and tetralin analogs of 3, 4-(methylenedioxy) amphetamine. Journal of Medicinal Chemistry, 36(23), 3700-3706. https://doi.org/10.1021/jm00075a027</ref> However, it did not come into popular recreational use until over a decade later, where it briefly entered the rave scene and global research chemicals market. It was sold along with other novel benzofuran entactogens under the name "Benzofury" before its sale and import were subsequently banned.{{citation needed}}

On June 10, 2013 6-APB and a number of analogues were classified as Temporary Class Drugs in the UK following an ACMD recommendation.<ref>Advisory Council on the Misuse of Drugs, Jeremy Browne (4 June 2013). "Temporary class drug order on benzofury and NBOMe compounds - letter from ACMD". GOV.UK.</ref> 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.<ref>UK Home Office (28 April 2014). "The Misuse of Drugs Act 1971 (Ketamine etc.) (Amendment) Order 2014". The National Archives.</ref>

6-APB is a [[serotonin]]–[[norepinephrine]]–[[dopamine]] [[reuptake inhibitor]] (SNDRI) with Ki values of 117, 150, and 2698 nM for the norepinephrine transporter (NET), dopamine transporter (DAT), and serotonin transporter (SERT), respectively.<ref name="6APBpharm1"> Iversen L, Gibbons S, Treble R, Setola V, Huang XP, Roth BL (2013). "Neurochemical profiles of some novel psychoactive substances". Eur. J. Pharmacol. 700 (1-3): 147–51. PMID 23261499. https://doi.org10.1016/j.ejphar.2012.12.006</ref> 6-APB also possesses additional activity as a [[releasing agent]] of these [[monoamine neurotransmitters]].<ref> Rickli A, Kopf S, Hoener MC, Liechti ME (2015). "Pharmacological profile of novel psychoactive benzofurans". Br. J. Pharmacol. 172 (13): 3412–25. PMID 25765500. https://doi.org/10.1111/bph.13128</ref>

6-APB is a potent [[Agonists#Types of agonist|full agonist]] of the serotonin 5-HT_2B receptor (Ki = 3.7 nM)<ref name="6APBpharm1" />, with higher affinity for this target than any other site.<ref name="5HT2C">Canal CE, Murnane KS (2017). "The serotonin 5-HT2C receptor and the non-addictive nature of classic hallucinogens". J. Psychopharmacol. (Oxford). 31 (1): 127–143. PMID 27903793. https://doi.org/10.1177/0269881116677104</ref> Moreover, unlike MDMA, 6-APB shows 100-fold selectivity for the 5-HT_2B receptor over the 5-HT_2A and 5-HT_2C receptors.<ref name="5HT2C"

/><ref>US patent 7045545, Karin Briner, Joseph Paul Burkhart, Timothy Paul Burkholder, Matthew Joseph Fisher, William Harlan Gritton, Daniel Timothy Kohlman, Sidney Xi Liang, Shawn Christopher Miller, Jeffrey Thomas Mullaney, Yao-Chang Xu, Yanping Xu, "Aminoalkylbenzofurans as serotonin (5-HT(2c)) agonists", published 19 January 2000, issued 16 May 2006</ref>

Aside from the 5-HT_2B receptor, 6-APB has also been found to bind with high affinity to the α_2C-adrenergic receptor subtype (Ki = 45 nM), although the clinical significance of this action is unknown.<ref name="6APBpharm1 />

The [[monoamine neurotransmitters]] known as [[serotonin]], [[dopamine]] and [[noradrenaline]] are the global [[neurotransmitters]] that modulate the brain's ability to feel pleasure, motivation, reward, planning, attention, and focus. When their reuptake is inhibited or their release is promoted, these neurotransmitters accumulate in the [[synaptic cleft]] (gaps between neurons) to non-ordinary levels, which makes them able to be reused. The result is neuronal activation at a multitude of brain regions which has the net result of producing a combination of stimulating, relaxing, disinhibiting and euphoric effects.<ref>New Insights into the Mechanism of Action of Amphetamines | http://www.annualreviews.org/doi/abs/10.1146/annurev.pharmtox.47.120505.105140</ref>

*'''[[Effect::External hallucinations]]''' (''[[effect::autonomous entities]]''; ''[[effect::settings, sceneries, and landscapes]]''; ''[[effect::perspective hallucinations]]'' and ''[[effect::scenarios and plots]]'') - This effect is very similar to the same experience found within [[deliriant]]s, but does not manifest itself consistently and usually happens only at high doses. It can be comprehensively described through its [[Visual_effects:_External_hallucinations#Variations|variations]] as delirious in believability, autonomous in controllability and solid in style. They usually follow themes of memory replays and semi-realistic or expected events. For example, people could be casually holding objects or performing actions which one would expect them to be in real life before disappearing and dissolving under further inspection. Common examples of this include seeing people wearing glasses or hats when they are not and mistaking faces of your friends for random people, and objects as human beings or animals.  

The cognitive effects of 6-APB can be broken down into several components which progressively intensify proportional to dosage. The general head space of 6-APB is described by many as one of moderate mental stimulation, feelings of love, openness or empathy, and a powerful sense of contentedness and euphoria. It displays a large number of typical [[psychedelic]], [[entactogenic]] and [[stimulant]] cognitive effects.  

*'''[[Effect::Focus enhancement]]''' - This component is most effective at low to moderate doses as anything higher will usually impair concentration.

*'''[[Effect::Wakefulness]]''' - This component is present, but to a noticeably lesser degree than [[MDMA]]. Users often report being heavily sedated or "floored" compared to typical stimulants.   

*'''[[Effect::Auditory hallucinations]]'''

*'''[[Effect::Unity and interconnectedness]]''' - While rare, experiences of unity, oneness and interconnectedness may occur on 6-APB. This component most reliably manifests itself at high doses within large crowds at raves and musical events in the form of "becoming one with the crowd."

* [https://erowid.org/experiences/subs/exp_6APB.shtml Erowid Experience Vaults: 6-APB]

Due to only having a short history of human use, the toxicity and harm potential is not exactly known. Due to its similarity to MDMA, it is likely that the administration of repeated or high dosages of 6-APB may be both neurotoxic and cardiotoxic<ref>Drug-induced Valvulopathy: An Update | tpx.sagepub.com/content/38/6/837.full</ref><ref>Possible association between 3,4-methylenedioxymethamphetamine abuse and valvular heart disease. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/17950805</ref> in some form.

Short-term physical health risks of 6-APB consumption include [[dehydration]], [[insomnia]], and hyperthermia (overheating).<ref>Drug-induced hyperthermia | http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2044.1993.tb07423.x/abstract;jsessionid=FC30A9B157A2BAFC81048D8595714565.f02t03</ref> Continuous activity without sufficient rest or rehydration may cause body temperature to rise to dangerous levels, and loss of fluid via excessive sweating puts the body at further risk as the stimulating and euphoric properties of the substance may render the user oblivious to their energy expenditure for quite some time. Diuretics such as alcohol may exacerbate these risks further.

Although it has not been formally studied, small changes in ambient temperature may cause large changes in 6-APB-induced serotonergic neurotoxicity as is the case with [[MDMA]].<ref>(PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/9634574</ref><ref>Vasopressin and oxytocin secretion in response to the consumption of ecstasy in a clubbing population | http://jop.sagepub.com/content/20/3/400</ref>

As with MDMA, the long-term, heavy usage of 6-APB (i.e. regular daily or weekly usage) is likely cardiotoxic and may lead to valvulopathy (heart valve issues) via its significant affinity for the 5-HT_2B receptor.<ref>Drug-induced Valvulopathy: An Update | tpx.sagepub.com/content/38/6/837.full</ref><ref>Possible association between 3,4-methylenedioxymethamphetamine abuse and valvular heart disease. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/17950805</ref>

There is an increased risk of serotonin syndrome when 6-APB is taken with many antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).{{citation needed}} Additionally, if 6-APB is taken with SSRIs and SNRIs, it is likely to be significantly less effective if it produces any discernible effects at all.

*'''Australia and New Zealand:''' 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.{{citation needed}}

*'''Canada:''' 6-APB is Schedule III in Canada as it is an analogue of MDA. The CDSA was updated as a result of the Safe Streets Act changing amphetamines from Schedule 3 to Schedule 1.{{citation needed}}

*'''Germany:''' 6-APB is illegal in Germany.<ref>{{cite web|url=http://archive.is/QEKft|accessdate=2018-01-12|title=Anlage II BtMG - Einzelnorm)}}</ref>

*'''Italy:''' 6-APB is illegal in Italy.<ref>http://www.salute.gov.it/imgs/C_17_pagineAree_3729_listaFile_itemName_0_file.pdf</ref>

*'''Sweden:''' 6-APB is prohibited in Sweden as a "health hazard" as of 2009.{{citation needed}}

*'''United Kingdom:''' On June 10, 2013, 6-APB and some analogues were classified as Temporary Class Drugs in the U.K. following an ACMD recommendation. On March 5, 2014, the U.K. 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.<ref>http://www.legislation.gov.uk/uksi/2014/1106/contents/made</ref>

*'''United States:''' 6-APB is unscheduled in the United States, but not currently approved by the Food and Drug Administration for human consumption.{{citation needed}}

*[[Designer drug]]

* Greene, S. L. (2013). Benzofurans and benzodifurans. In Novel Psychoactive Substances (pp. 383-392). https://doi.org/10.1016/B978-0-12-415816-0.00016-X