APICA: Difference between revisions

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'''2NE1''' (also known as '''APICA''') is a novel synthetic designer [[psychoactive class::cannabinoid]]~~. It has been shown to act~~ as a potent [[agonist]] for the CB1 and CB2 [[cannabinoid]] [[receptor]]s<ref>Samuel D. Banister, Jordyn Stuart, Richard C. Kevin, Amelia Edington, Mitchell Longworth, Shane M. Wilkinson, Corinne Beinat, Alexandra S. Buchanan, David E. Hibbs, Michelle Glass, Mark Connor, Iain S. McGregor, and Michael Kassiou. "Effects of Bioisosteric Fluorine in Synthetic Cannabinoid Designer Drugs JWH-018, AM-2201, UR-144, XLR-11, PB-22, 5F-PB-22, APICA, and STS-135" Chemical Neuroscience. 2015;6(8);1445-1458;doi:10.1021/acschemneuro.5b00107 (Pubmed / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/25921407</ref> ~~and~~ has been reported to produce subjective effects somewhat similar to ~~that~~ of [[cannabis]]~~, albeit with a short duration and an emphasis on intense physical sensations~~.

'''2NE1''' (also known as '''APICA''' and '''SDB-001''') is a novel synthetic designer [[psychoactive class::cannabinoid]] that acts as a potent [[agonist]] for the CB1 and CB2 [[cannabinoid]] [[receptor]]s.<ref>Samuel D. Banister, Jordyn Stuart, Richard C. Kevin, Amelia Edington, Mitchell Longworth, Shane M. Wilkinson, Corinne Beinat, Alexandra S. Buchanan, David E. Hibbs, Michelle Glass, Mark Connor, Iain S. McGregor, and Michael Kassiou. "Effects of Bioisosteric Fluorine in Synthetic Cannabinoid Designer Drugs JWH-018, AM-2201, UR-144, XLR-11, PB-22, 5F-PB-22, APICA, and STS-135" Chemical Neuroscience. 2015;6(8);1445-1458;doi:10.1021/acschemneuro.5b00107 (Pubmed / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/25921407</ref> It has been reported to produce subjective effects somewhat similar to those of [[cannabis]].

The name 2NE1 appears to be a reference to the South Korean all-girl K-Pop group.<ref>2NE1 (Wikipedia) | https://en.wikipedia.org/wiki/2NE1</ref> ~~It was~~ first identified in Japan as a ~~constituent of~~ a ~~brown powder~~ sold ~~in late 2011~~ under the name "Fragrance Powder" ~~as a mixture with its [[indazole]] analog [[AKB48]]~~<ref>Nahoko Uchiyama, Maiko Kawamura, Ruri Kikura-Hanajiri, Yukihiro Goda. "Identification of two new-type synthetic cannabinoids, N-(1-adamantyl)-1-pentyl-1H-indole-3-carboxamide (APICA) and N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide(APINACA), and detection of five synthetic cannabinoids, AM-1220, AM-2233, AM-1241, CB-13 (CRA-13), and AM-1248, as designer drugs in illegal products" Forensic Toxicol (2012) 30: 114-125;doi:10.1007/s11419-012-0136-7 (SpringerLink) | http://link.springer.com/article/10.1007/s11419-012-0136-7</ref> ~~and~~ has since been available for sale as a grey area [[research chemical]] through online vendors.

The name '2NE1' appears to be a reference to the South Korean all-girl K-Pop group<ref>2NE1 (Wikipedia) | https://en.wikipedia.org/wiki/2NE1</ref>, a naming convention shared by the closely related chemical [[AKB48]]. The two chemicals were first identified in Japan in 2011 as a mixture in a product sold under the name "Fragrance Powder".<ref>Nahoko Uchiyama, Maiko Kawamura, Ruri Kikura-Hanajiri, Yukihiro Goda. "Identification of two new-type synthetic cannabinoids, N-(1-adamantyl)-1-pentyl-1H-indole-3-carboxamide (APICA) and N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide(APINACA), and detection of five synthetic cannabinoids, AM-1220, AM-2233, AM-1241, CB-13 (CRA-13), and AM-1248, as designer drugs in illegal products" Forensic Toxicol (2012) 30: 114-125;doi:10.1007/s11419-012-0136-7 (SpringerLink) | http://link.springer.com/article/10.1007/s11419-012-0136-7</ref>. 2NE1 has since been available for sale as a grey-area [[research chemical]] through online vendors.

Cannabinoids are commonly [[smoked]] or [[vaporized]] to achieve a quick [[onset]] of effects and rapid [[offset]]. 2NE1 is [[~~oral~~]]ly active when dissolved in a lipid, which ~~can increase the~~ duration ~~significantly~~. ~~Like other [[cannabinoid]]s, it~~ is insoluble in water but dissolves in [[ethanol]] and lipids. Unlike many novel designer cannabinoids, its metabolism has been described in the scientific literature.<ref>Tim Sobolevsky, Ilya Prasolov and Grigory Rodchenkov. "Study on the phase I metabolism of novel synthetic cannabinoids, APICA and its fluorinated analogue". Drug Testing and Analysis. 2015;7(2);131-142;doi:10.1002/dta.1756 (Pubmed / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/25428705</ref>.

Cannabinoids are commonly [[smoked]] or [[vaporized]] to achieve a quick [[onset]] of effects and rapid [[offset]]. There is little information available about the use of 2NE1 via other [[routes of administration]], although in common with other synthetic cannabinoids 2NE1 could be expected to be [[orally]] active when dissolved in a lipid, which may significant extend its duration. It is insoluble in water, but dissolves in ethanol and lipids.

Unlike [[cannabis]], the chronic abuse of [[synthetic cannabinoids]] has been [[Synthetic_cannabinoid#Deaths|associated with multiple deaths]] and [[Synthetic cannabinoid#Harm potential|more dangerous side effects and toxicity]] in general. Therefore, it is strongly discouraged to take this substance for extended periods of time or in excessive doses.

==Chemistry==

2NE1, or N-(1-adamantyl)-1-pentyl-1H-indole-3-carboxamide, is a synthetic [[Chemical class::cannabinoid]] ~~which contains a substituted~~ indole group~~. This indole moeity~~ is substituted at R1 with a pentyl chain~~, a substitution shared with [[JWH-018]]. Additionally, the indole is substituted~~ at R3 with a carboxamide ~~group. This carboxamide group is N-substituted at its terminal amine group with~~ an ~~adamantane group. This group consists of four fused cyclohexane rings in a unique structure called a diamondoid~~. 2NE1 can be considered ~~the indole analog~~ of [[AKB48]] and ~~the pentyl analog of~~ [[STS-135]].

2NE1, or N-(1-adamantyl)-1-pentyl-1H-indole-3-carboxamide, is a synthetic [[Chemical class::indole cannabinoid]]. Like many synthetic cannabinoids, it can be considered to be composed of four linked structures: core, bridge, head and tail.<ref>Synthetic cannabinoids in Europe - Interactive: demystifying the chemistry (EMCDDA) | http://www.emcdda.europa.eu/topics/pods/synthetic-cannabinoids</ref>. In 2NE1, the core indole group is substituted at R1 with a pentyl chain tail and at R3 with a carboxamide bridge linking to an adamantyl head. 2NE1 can be considered an analogue of both [[AKB48]], which features an indazole group instead of 2NE1's indole, and [[STS-135]], in which the pentyl tail is further substituted with a terminal fluorine.

==Pharmacology==

2NE1 acts as a full agonist of the cannabinoid receptors, with similar potency at both [[CB1]] and [[CB2]]. In vivo experiments measuring the response of rats to 2NE1 and similar drugs found that 2NE1 had similar potency to Δ9-[[THC]] and around a third the potency of [[JWH-018]]. In comparison to these other cannabinoids, 2NE1 appeared to elicit a longer duration of effect. Caution should be exercised in interpreting studies using animals as effects may differ significantly in humans.<ref>Banister SD, Wilkinson SM, Longworth M, et al. The Synthesis and Pharmacological Evaluation of Adamantane-Derived Indoles: Cannabimimetic Drugs of Abuse. ACS Chemical Neuroscience. 2013;4(7):1081-1092. doi:10.1021/cn400035r. (PMC/NCBI) | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715837/</ref> Pharmacological studies have reported EC50 values of 6.89 ± 0.11nM at CB1 and 7.54 ± 0.11nM at CB2. <ref>Samuel D. Banister, Jordyn Stuart, Richard C. Kevin, Amelia Edington, Mitchell Longworth, Shane M. Wilkinson, Corinne Beinat, Alexandra S. Buchanan, David E. Hibbs, Michelle Glass, Mark Connor, Iain S. McGregor, and Michael Kassiou. "Effects of Bioisosteric Fluorine in Synthetic Cannabinoid Designer Drugs JWH-018, AM-2201, UR-144, XLR-11, PB-22, 5F-PB-22, APICA, and STS-135" Chemical Neuroscience (2015). 6(8). 1445-1458. doi:10.1021/acschemneuro.5b00107</ref> It is likely that 2NE1 shares many of the in vivo properties of [[Δ9-THC]]. However, the role of these interactions and how they result in the cannabinoid high has yet to be scientifically validated.

~~Pharmacological~~ studies of 2NE1 ~~report EC50 values~~ of 6.~~89 ± 0.11nM at CB1~~ and ~~7.54 ± 0.11nM at CB2. These values are fairly close to those found for Δ9-[[THC]], although 2NE1 is a full agonist at both receptors, while Δ9-THC is a partial agonist.~~<ref>Samuel D. Banister, Jordyn Stuart, Richard C. Kevin, Amelia Edington, Mitchell Longworth, Shane M. Wilkinson, Corinne Beinat, Alexandra S. Buchanan, David E. Hibbs, Michelle Glass, Mark Connor, Iain S. McGregor, and ~~Michael Kassiou~~. "~~Effects~~ of ~~Bioisosteric Fluorine in Synthetic Cannabinoid Designer Drugs JWH-018, AM-2201, UR-144, XLR-11, PB-22, 5F-PB-22~~, APICA, and ~~STS-135~~" ~~Chemical Neuroscience (~~2015~~). 6~~(8)~~. 1445~~-~~1458.~~ doi:10.~~1021~~/~~acschemneuro~~.~~5b00107~~</ref> ~~It is likely that 2NE1 shares many of the in vivo properties of [[Δ9-THC]]. However, the role of these interactions and how they result in the cannabinoid high has yet to be scientifically validated~~.

In vivo metabolic studies on 2NE1 have shown that the drug is fully metabolised with none of the original compound detectable in urine. The major metabolites were mono- or dihydroxylated on the adamantyl ring system and monohydroxylated on the pentyl chain<ref>Tim Sobolevsky, Ilya Prasolov and Grigory Rodchenkov. "Study on the phase I metabolism of novel synthetic cannabinoids, APICA and its fluorinated analogue". Drug Testing and Analysis. 2015;7(2);131-142;doi:10.1002/dta.1756 (Pubmed / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/25428705</ref>.

==Subjective effects==

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 {{SubstanceBox/2NE1}}
-'''2NE1''' (also known as '''APICA''') is a novel synthetic designer [[psychoactive class::cannabinoid]]. It has been shown to act as a potent [[agonist]] for the CB1 and CB2 [[cannabinoid]] [[receptor]]s<ref>Samuel D. Banister, Jordyn Stuart, Richard C. Kevin, Amelia Edington, Mitchell Longworth, Shane M. Wilkinson, Corinne Beinat, Alexandra S. Buchanan, David E. Hibbs, Michelle Glass, Mark Connor, Iain S. McGregor, and Michael Kassiou. "Effects of Bioisosteric Fluorine in Synthetic Cannabinoid Designer Drugs JWH-018, AM-2201, UR-144, XLR-11, PB-22, 5F-PB-22, APICA, and STS-135" Chemical Neuroscience. 2015;6(8);1445-1458;doi:10.1021/acschemneuro.5b00107 (Pubmed / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/25921407</ref> and has been reported to produce subjective effects somewhat similar to that of [[cannabis]], albeit with a short duration and an emphasis on intense physical sensations.
+'''2NE1''' (also known as '''APICA''' and '''SDB-001''') is a novel synthetic designer [[psychoactive class::cannabinoid]] that acts as a potent [[agonist]] for the CB1 and CB2 [[cannabinoid]] [[receptor]]s.<ref>Samuel D. Banister, Jordyn Stuart, Richard C. Kevin, Amelia Edington, Mitchell Longworth, Shane M. Wilkinson, Corinne Beinat, Alexandra S. Buchanan, David E. Hibbs, Michelle Glass, Mark Connor, Iain S. McGregor, and Michael Kassiou. "Effects of Bioisosteric Fluorine in Synthetic Cannabinoid Designer Drugs JWH-018, AM-2201, UR-144, XLR-11, PB-22, 5F-PB-22, APICA, and STS-135" Chemical Neuroscience. 2015;6(8);1445-1458;doi:10.1021/acschemneuro.5b00107 (Pubmed / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/25921407</ref> It has been reported to produce subjective effects somewhat similar to those of [[cannabis]].
-The name 2NE1 appears to be a reference to the South Korean all-girl K-Pop group.<ref>2NE1 (Wikipedia) | https://en.wikipedia.org/wiki/2NE1</ref> It was first identified in Japan as a constituent of a brown powder sold in late 2011 under the name "Fragrance Powder" as a mixture with its [[indazole]] analog [[AKB48]]<ref>Nahoko Uchiyama, Maiko Kawamura, Ruri Kikura-Hanajiri, Yukihiro Goda. "Identification of two new-type synthetic cannabinoids, N-(1-adamantyl)-1-pentyl-1H-indole-3-carboxamide (APICA) and N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide(APINACA), and detection of five synthetic cannabinoids, AM-1220, AM-2233, AM-1241, CB-13 (CRA-13), and AM-1248, as designer drugs in illegal products" Forensic Toxicol (2012) 30: 114-125;doi:10.1007/s11419-012-0136-7 (SpringerLink) | http://link.springer.com/article/10.1007/s11419-012-0136-7</ref> and has since been available for sale as a grey area [[research chemical]] through online vendors.
+The name '2NE1' appears to be a reference to the South Korean all-girl K-Pop group<ref>2NE1 (Wikipedia) | https://en.wikipedia.org/wiki/2NE1</ref>, a naming convention shared by the closely related chemical [[AKB48]]. The two chemicals were first identified in Japan in 2011 as a mixture in a product sold under the name "Fragrance Powder".<ref>Nahoko Uchiyama, Maiko Kawamura, Ruri Kikura-Hanajiri, Yukihiro Goda. "Identification of two new-type synthetic cannabinoids, N-(1-adamantyl)-1-pentyl-1H-indole-3-carboxamide (APICA) and N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide(APINACA), and detection of five synthetic cannabinoids, AM-1220, AM-2233, AM-1241, CB-13 (CRA-13), and AM-1248, as designer drugs in illegal products" Forensic Toxicol (2012) 30: 114-125;doi:10.1007/s11419-012-0136-7 (SpringerLink) | http://link.springer.com/article/10.1007/s11419-012-0136-7</ref>. 2NE1 has since been available for sale as a grey-area [[research chemical]] through online vendors.
-Cannabinoids are commonly [[smoked]] or [[vaporized]] to achieve a quick [[onset]] of effects and rapid [[offset]]. 2NE1 is [[oral]]ly active when dissolved in a lipid, which can increase the duration significantly. Like other [[cannabinoid]]s, it is insoluble in water but dissolves in [[ethanol]] and lipids. Unlike many novel designer cannabinoids, its metabolism has been described in the scientific literature.<ref>Tim Sobolevsky, Ilya Prasolov and Grigory Rodchenkov. "Study on the phase I metabolism of novel synthetic cannabinoids, APICA and its fluorinated analogue". Drug Testing and Analysis. 2015;7(2);131-142;doi:10.1002/dta.1756 (Pubmed / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/25428705</ref>.
+Cannabinoids are commonly [[smoked]] or [[vaporized]] to achieve a quick [[onset]] of effects and rapid [[offset]]. There is little information available about the use of 2NE1 via other [[routes of administration]], although in common with other synthetic cannabinoids 2NE1 could be expected to be [[orally]] active when dissolved in a lipid, which may significant extend its duration.  It is insoluble in water, but dissolves in ethanol and lipids.
 Unlike [[cannabis]], the chronic abuse of [[synthetic cannabinoids]] has been [[Synthetic_cannabinoid#Deaths|associated with multiple deaths]] and [[Synthetic cannabinoid#Harm potential|more dangerous side effects and toxicity]] in general. Therefore, it is strongly discouraged to take this substance for extended periods of time or in excessive doses.
 ==Chemistry==
-NE1, or N-(1-adamantyl)-1-pentyl-1H-indole-3-carboxamide, is a synthetic [[Chemical class::cannabinoid]] which contains a substituted indole group. This indole moeity is substituted at R<sub>1</sub> with a pentyl chain, a substitution shared with [[JWH-018]]. Additionally, the indole is substituted at R<sub>3</sub> with a carboxamide group.  This carboxamide group is N-substituted at its terminal amine group with an adamantane group. This group consists of four fused cyclohexane rings in a unique structure called a diamondoid. 2NE1 can be considered the indole analog of [[AKB48]] and the pentyl analog of [[STS-135]].
+NE1, or N-(1-adamantyl)-1-pentyl-1H-indole-3-carboxamide, is a synthetic [[Chemical class::indole cannabinoid]]. Like many synthetic cannabinoids, it can be considered to be composed of four linked structures: core, bridge, head and tail.<ref>Synthetic cannabinoids in Europe - Interactive: demystifying the chemistry (EMCDDA) | http://www.emcdda.europa.eu/topics/pods/synthetic-cannabinoids</ref>. In 2NE1, the core indole group is substituted at R<sub>1</sub> with a pentyl chain tail and at R<sub>3</sub> with a carboxamide bridge linking to an adamantyl head. 2NE1 can be considered an analogue of both [[AKB48]], which features an indazole group instead of 2NE1's indole, and [[STS-135]], in which the pentyl tail is further substituted with a terminal fluorine.
 ==Pharmacology==
+NE1 acts as a full agonist of the cannabinoid receptors, with similar potency at both [[CB1]] and [[CB2]]. In vivo experiments measuring the response of rats to 2NE1 and similar drugs found that 2NE1 had similar potency to Δ9-[[THC]] and around a third the potency of [[JWH-018]]. In comparison to these other cannabinoids, 2NE1 appeared to elicit a longer duration of effect. Caution should be exercised in interpreting studies using animals as effects may differ significantly in humans.<ref>Banister SD, Wilkinson SM, Longworth M, et al. The Synthesis and Pharmacological Evaluation of Adamantane-Derived Indoles: Cannabimimetic Drugs of Abuse. ACS Chemical Neuroscience. 2013;4(7):1081-1092. doi:10.1021/cn400035r. (PMC/NCBI) | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715837/</ref> Pharmacological studies have reported EC<sub>50</sub> values of 6.89 ± 0.11nM at CB1 and 7.54 ± 0.11nM at CB2. <ref>Samuel D. Banister, Jordyn Stuart, Richard C. Kevin, Amelia Edington, Mitchell Longworth, Shane M. Wilkinson, Corinne Beinat, Alexandra S. Buchanan, David E. Hibbs, Michelle Glass, Mark Connor, Iain S. McGregor, and Michael Kassiou. "Effects of Bioisosteric Fluorine in Synthetic Cannabinoid Designer Drugs JWH-018, AM-2201, UR-144, XLR-11, PB-22, 5F-PB-22, APICA, and STS-135" Chemical Neuroscience (2015). 6(8). 1445-1458. doi:10.1021/acschemneuro.5b00107</ref> It is likely that 2NE1 shares many of the in vivo properties of [[Δ9-THC]]. However, the role of these interactions and how they result in the cannabinoid high has yet to be scientifically validated.
-Pharmacological studies of 2NE1 report EC<sub>50</sub> values of 6.89 ± 0.11nM at CB1 and 7.54 ± 0.11nM at CB2. These values are fairly close to those found for Δ9-[[THC]], although 2NE1 is a full agonist at both receptors, while Δ9-THC is a partial agonist.<ref>Samuel D. Banister, Jordyn Stuart, Richard C. Kevin, Amelia Edington, Mitchell Longworth, Shane M. Wilkinson, Corinne Beinat, Alexandra S. Buchanan, David E. Hibbs, Michelle Glass, Mark Connor, Iain S. McGregor, and Michael Kassiou. "Effects of Bioisosteric Fluorine in Synthetic Cannabinoid Designer Drugs JWH-018, AM-2201, UR-144, XLR-11, PB-22, 5F-PB-22, APICA, and STS-135" Chemical Neuroscience (2015). 6(8). 1445-1458. doi:10.1021/acschemneuro.5b00107</ref> It is likely that 2NE1 shares many of the in vivo properties of [[Δ9-THC]]. However, the role of these interactions and how they result in the cannabinoid high has yet to be scientifically validated.
+In vivo metabolic studies on 2NE1 have shown that the drug is fully metabolised with none of the original compound detectable in urine. The major metabolites were mono- or dihydroxylated on the adamantyl ring system and monohydroxylated on the pentyl chain<ref>Tim Sobolevsky, Ilya Prasolov and Grigory Rodchenkov. "Study on the phase I metabolism of novel synthetic cannabinoids, APICA and its fluorinated analogue". Drug Testing and Analysis. 2015;7(2);131-142;doi:10.1002/dta.1756 (Pubmed / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/25428705</ref>.
 ==Subjective effects==