APICA: Difference between revisions

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==Chemistry==

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 analog of both [[AKB48]], which features an indazole in place of 2NE1's indole group, and [[STS-135]], in which the pentyl tail is further substituted with a terminal fluorine.

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 analog of both [[AKB48]], which features an indazole in place of 2NE1's indole group, and [[STS-135]], in which the pentyl tail is further substituted with a terminal fluorine.

==Pharmacology==

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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.

In vivo metabolic studies on 2NE1 have shown that the drug is fully metabolized 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>.

In vivo metabolic studies on 2NE1 have shown that the drug is fully metabolized 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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*'''[[Effect::Appetite enhancement]]''' - As with many other cannabinoids, 2NE1 causes an increase in appetite<ref>Mechoulam, R. (1984). Cannabinoids as therapeutic agents. Boca Raton, FL: CRC Press. ISBN 0-8493-5772-1.</ref>, known colloquially as "the munchies" in popular American and United Kingdom culture. Clinical studies and survey data have found that cannabis increases food enjoyment and interest in food.<ref>How Marijuana Works | http://science.howstuffworks.com/marijuana4.htm</ref> This is thought to be due to the way in which endocannabinoids in the hypothalamus activate cannabinoid receptors that are responsible for maintaining food intake.<ref>How Marijuana Works | http://science.howstuffworks.com/marijuana4.htm</ref>

*'''[[Effect::Pain relief]]''' - Cannabinoids have been clinically demonstrated to provide pain relief via agonism of cannabinoid receptors CB1 and CB2, which extends to [[synthetic cannabinoid]] receptor agonists.<ref>http://onlinelibrary.wiley.com/doi/10.1111/j.1526-4637.2009.00703.x/abstract</ref><ref>Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials | http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2125.2011.03970.x/abstract</ref>

*'''[[Effect::Perception of ~~increased weight~~]]''' ''or'' '''[[Perception of ~~decreased weight|Perception of decreased weight~~]]'''

*'''[[Effect::Perception of bodily heaviness]]''' or '''[[Perception of bodily lightness]]'''

*'''[[Effect::Changes in felt gravity]]'''

*'''[[Effect::Dehydration]]'''- This is known colloquially as "cotton mouth" in popular American and United Kingdom culture.

*'''[[Effect::Dehydration]]'''

*'''[[Effect::Dry mouth]]''' - This is known colloquially as "cotton mouth" in popular American and United Kingdom culture.

*'''[[Effect::Vasodilation]]'''{{citation needed}}

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*'''[[Effect::Information processing suppression]]'''

*'''[[Effect::Dream suppression]]'''

*'''[[Effect::Psychosis]]''' - The prolonged usage of synthetic [[cannabinoids]] may increase one's disposition to psychosis<ref>Causal association between cannabis and psychosis: examination of the evidence - The British Journal of Psychiatry Jan 2004, 184 (2) 110-117 | http://bjp.rcpsych.org/content/184/2/110.short</ref>, particularly in vulnerable individuals with risk factors for psychotic illnesses (like a past or family history of schizophrenia).<ref>Every-Palmer, S. [[Synthetic cannabinoid]] use and psychosis: an explorative study. Journal of Drug and Alcohol Dependence 2011.</ref><ref>“Spice” Girls: Synthetic Cannabinoid Intoxication - The Journal of Emergency Medicine Volume 40, Issue 3, March 2011, Pages 296–299 (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0736467910008802</ref><ref>A Teenager With Agitation: Higher Than She Should Have Climbed - Pediatric Emergency Care: June 2010 - Volume 26 - Issue 6 - pp 462-465 | http://journals.lww.com/pec-online/Abstract/2010/06000/A_Teenager_With_Agitation__Higher_Than_She_Should.16.aspx</ref>

*'''[[Effect::Psychosis]]''' - The prolonged usage of synthetic [[cannabinoids]] may increase one's disposition to psychosis,<ref>Causal association between cannabis and psychosis: examination of the evidence - The British Journal of Psychiatry Jan 2004, 184 (2) 110-117 | http://bjp.rcpsych.org/content/184/2/110.short</ref> particularly in vulnerable individuals with risk factors for psychotic illnesses (like a past or family history of schizophrenia).<ref>Every-Palmer, S. [[Synthetic cannabinoid]] use and psychosis: an explorative study. Journal of Drug and Alcohol Dependence 2011.</ref><ref>“Spice” Girls: Synthetic Cannabinoid Intoxication - The Journal of Emergency Medicine Volume 40, Issue 3, March 2011, Pages 296–299 (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0736467910008802</ref><ref>A Teenager With Agitation: Higher Than She Should Have Climbed - Pediatric Emergency Care: June 2010 - Volume 26 - Issue 6 - pp 462-465 | http://journals.lww.com/pec-online/Abstract/2010/06000/A_Teenager_With_Agitation__Higher_Than_She_Should.16.aspx</ref>

===Auditory effects===

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Anecdotal reports which describe the effects of this compound within our [[experience index]] include:

{{#ask: [[Category:2NE1]][[Category:Experience]]|format=ul|Columns=1}}

==Toxicity and harm potential==

{{further|Synthetic cannabinoid#Toxicity and harm potential|Research chemicals#Toxicity and harm potential}}

The toxicity and long-term health effects of recreational 2NE1 use do not seem to have been studied in any scientific context and the [[Toxicity::exact toxic dosage is unknown]]. This is because 2NE1 has very little history of human usage. Anecdotal evidence from people who have tried 2NE1 within the community suggests that there do not seem to be any negative health effects attributed to simply trying this substance at low to moderate doses by itself and using it sparingly (but nothing can be completely guaranteed). It has been reported that overdose on this substance will cause physical discomfort including heart palpitations, vertigo and sedation at much lower than dangerous doses, usually causing the user to suffer large amounts of [[anxiety]] or to fall asleep.

The toxicity and long-term health effects of recreational 2NE1 use do not seem to have been studied in any scientific context and the [[Toxicity::exact toxic dosage is unknown]]. This is because 2NE1 has very little history of human usage. Anecdotal evidence from people who have tried 2NE1 within the community suggests that there do not seem to be any negative health effects attributed to simply trying this substance at low to moderate doses by itself and using it sparingly (but nothing can be completely guaranteed).

It has often been recommended that those with severe pre-existing mental conditions should not ingest these substances due to the way they strongly amplify [[emotion enhancement|one's current state of mind and emotions]]. Also, as with [[THC]] and [[cannabis]], prolonged usage of synthetic [[cannabinoids]] including 2NE1 may increase one's disposition to mental illness and psychosis,<ref>Causal association between cannabis and psychosis: examination of the evidence - The British Journal of Psychiatry Jan 2004, 184 (2) 110-117 | http://bjp.rcpsych.org/content/184/2/110.short</ref> particularly in vulnerable individuals with risk factors for psychotic illnesses (like a past or family history of schizophrenia).<ref>Every-Palmer, S. [[Synthetic cannabinoid]] use and psychosis: an explorative study. Journal of Drug and Alcohol Dependence 2011.</ref><ref>“Spice” Girls: Synthetic Cannabinoid Intoxication - The Journal of Emergency Medicine Volume 40, Issue 3, March 2011, Pages 296–299 (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0736467910008802</ref><ref>A Teenager With Agitation: Higher Than She Should Have Climbed - Pediatric Emergency Care: June 2010 - Volume 26 - Issue 6 - pp 462-465 | http://journals.lww.com/pec-online/Abstract/2010/06000/A_Teenager_With_Agitation__Higher_Than_She_Should.16.aspx</ref>

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Tolerance to many of the effects of 2NE1 [[Time to full tolerance::develops with prolonged and repeated use]]. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about [[Time to half tolerance::3 - 7 days]] for the tolerance to be reduced to half and [[Time to zero tolerance::1 - 2 weeks]] to be back at baseline (in the absence of further consumption). 2NE1 presents cross-tolerance with [[Cross-tolerance::all [[cannabinoids]]]], meaning that after the consumption of 2NE all [[Psychoactive class::cannabinoid]]s will have a reduced effect.

===Overdose===

It has been reported that overdose on this substance will cause physical discomfort including [[abnormal heartbeat|heart palpitations]], vertigo and [[sedation]] at much lower than dangerous doses, usually causing the user to suffer large amounts of [[anxiety]] or to fall asleep.

==Legality==

@@ Line 13: / Line 13: @@
 ==Chemistry==
-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 analog of both [[AKB48]], which features an indazole in place of 2NE1's indole group, and [[STS-135]], in which the pentyl tail is further substituted with a terminal fluorine.
+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.
+NE1 can be considered an analog of both [[AKB48]], which features an indazole in place of 2NE1's indole group, and [[STS-135]], in which the pentyl tail is further substituted with a terminal fluorine.
 ==Pharmacology==
@@ Line 20: / Line 22: @@
 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.
-In vivo metabolic studies on 2NE1 have shown that the drug is fully metabolized 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>.
+In vivo metabolic studies on 2NE1 have shown that the drug is fully metabolized 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==
@@ Line 29: / Line 31: @@
 *'''[[Effect::Appetite enhancement]]''' - As with many other cannabinoids, 2NE1 causes an increase in appetite<ref>Mechoulam, R. (1984). Cannabinoids as therapeutic agents. Boca Raton, FL: CRC Press. ISBN 0-8493-5772-1.</ref>, known colloquially as "the munchies" in popular American and United Kingdom culture. Clinical studies and survey data have found that cannabis increases food enjoyment and interest in food.<ref>How Marijuana Works | http://science.howstuffworks.com/marijuana4.htm</ref> This is thought to be due to the way in which endocannabinoids in the hypothalamus activate cannabinoid receptors that are responsible for maintaining food intake.<ref>How Marijuana Works | http://science.howstuffworks.com/marijuana4.htm</ref>
 *'''[[Effect::Pain relief]]''' - Cannabinoids have been clinically demonstrated to provide pain relief via agonism of cannabinoid receptors CB<sub>1</sub> and CB<sub>2</sub>, which extends to [[synthetic cannabinoid]] receptor agonists.<ref>http://onlinelibrary.wiley.com/doi/10.1111/j.1526-4637.2009.00703.x/abstract</ref><ref>Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials | http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2125.2011.03970.x/abstract</ref>
-*'''[[Effect::Perception of increased weight]]''' ''or'' '''[[Perception of decreased weight|Perception of decreased weight]]'''
+*'''[[Effect::Perception of bodily heaviness]]''' or '''[[Perception of bodily lightness]]'''
 *'''[[Effect::Changes in felt gravity]]'''
-*'''[[Effect::Dehydration]]'''- This is known colloquially as "cotton mouth" in popular American and United Kingdom culture.
+*'''[[Effect::Dehydration]]'''
+*'''[[Effect::Dry mouth]]''' - This is known colloquially as "cotton mouth" in popular American and United Kingdom culture.
 *'''[[Effect::Vasodilation]]'''{{citation needed}}
@@ Line 44: / Line 47: @@
 *'''[[Effect::Information processing suppression]]'''
 *'''[[Effect::Dream suppression]]'''
-*'''[[Effect::Psychosis]]''' - The prolonged usage of synthetic [[cannabinoids]] may increase one's disposition to psychosis<ref>Causal association between cannabis and psychosis: examination of the evidence - The British Journal of Psychiatry Jan 2004, 184 (2) 110-117  | http://bjp.rcpsych.org/content/184/2/110.short</ref>, particularly in vulnerable individuals with risk factors for psychotic illnesses (like a past or family history of schizophrenia).<ref>Every-Palmer, S. [[Synthetic cannabinoid]] use and psychosis: an explorative study. Journal of Drug and Alcohol Dependence 2011.</ref><ref>“Spice” Girls: Synthetic Cannabinoid Intoxication - The Journal of Emergency Medicine  Volume 40, Issue 3, March 2011, Pages 296–299 (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0736467910008802</ref><ref>A Teenager With Agitation: Higher Than She Should Have Climbed - Pediatric Emergency Care: June 2010 - Volume 26 - Issue 6 - pp 462-465 | http://journals.lww.com/pec-online/Abstract/2010/06000/A_Teenager_With_Agitation__Higher_Than_She_Should.16.aspx</ref>
+*'''[[Effect::Psychosis]]''' - The prolonged usage of synthetic [[cannabinoids]] may increase one's disposition to psychosis,<ref>Causal association between cannabis and psychosis: examination of the evidence - The British Journal of Psychiatry Jan 2004, 184 (2) 110-117  | http://bjp.rcpsych.org/content/184/2/110.short</ref> particularly in vulnerable individuals with risk factors for psychotic illnesses (like a past or family history of schizophrenia).<ref>Every-Palmer, S. [[Synthetic cannabinoid]] use and psychosis: an explorative study. Journal of Drug and Alcohol Dependence 2011.</ref><ref>“Spice” Girls: Synthetic Cannabinoid Intoxication - The Journal of Emergency Medicine  Volume 40, Issue 3, March 2011, Pages 296–299 (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0736467910008802</ref><ref>A Teenager With Agitation: Higher Than She Should Have Climbed - Pediatric Emergency Care: June 2010 - Volume 26 - Issue 6 - pp 462-465 | http://journals.lww.com/pec-online/Abstract/2010/06000/A_Teenager_With_Agitation__Higher_Than_She_Should.16.aspx</ref>
 ===Auditory effects===
@@ Line 53: / Line 56: @@
 Anecdotal reports which describe the effects of this compound within our [[experience index]] include:
 {{#ask: [[Category:2NE1]][[Category:Experience]]|format=ul|Columns=1}}
 ==Toxicity and harm potential==
 {{further|Synthetic cannabinoid#Toxicity and harm potential|Research chemicals#Toxicity and harm potential}}
-The toxicity and long-term health effects of recreational 2NE1 use do not seem to have been studied in any scientific context and the [[Toxicity::exact toxic dosage is unknown]]. This is because 2NE1 has very little history of human usage. Anecdotal evidence from people who have tried 2NE1 within the community suggests that there do not seem to be any negative health effects attributed to simply trying this substance at low to moderate doses by itself and using it sparingly (but nothing can be completely guaranteed). It has been reported that overdose on this substance will cause physical discomfort including heart palpitations, vertigo and sedation at much lower than dangerous doses, usually causing the user to suffer large amounts of [[anxiety]] or to fall asleep.
+The toxicity and long-term health effects of recreational 2NE1 use do not seem to have been studied in any scientific context and the [[Toxicity::exact toxic dosage is unknown]]. This is because 2NE1 has very little history of human usage. Anecdotal evidence from people who have tried 2NE1 within the community suggests that there do not seem to be any negative health effects attributed to simply trying this substance at low to moderate doses by itself and using it sparingly (but nothing can be completely guaranteed).
 It has often been recommended that those with severe pre-existing mental conditions should not ingest these substances due to the way they strongly amplify [[emotion enhancement|one's current state of mind and emotions]]. Also, as with [[THC]] and [[cannabis]], prolonged usage of synthetic [[cannabinoids]] including 2NE1 may increase one's disposition to mental illness and psychosis,<ref>Causal association between cannabis and psychosis: examination of the evidence - The British Journal of Psychiatry Jan 2004, 184 (2) 110-117  | http://bjp.rcpsych.org/content/184/2/110.short</ref> particularly in vulnerable individuals with risk factors for psychotic illnesses (like a past or family history of schizophrenia).<ref>Every-Palmer, S. [[Synthetic cannabinoid]] use and psychosis: an explorative study. Journal of Drug and Alcohol Dependence 2011.</ref><ref>“Spice” Girls: Synthetic Cannabinoid Intoxication - The Journal of Emergency Medicine  Volume 40, Issue 3, March 2011, Pages 296–299 (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0736467910008802</ref><ref>A Teenager With Agitation: Higher Than She Should Have Climbed - Pediatric Emergency Care: June 2010 - Volume 26 - Issue 6 - pp 462-465 | http://journals.lww.com/pec-online/Abstract/2010/06000/A_Teenager_With_Agitation__Higher_Than_She_Should.16.aspx</ref>
@@ Line 68: / Line 72: @@
 Tolerance to many of the effects of 2NE1 [[Time to full tolerance::develops with prolonged and repeated use]]. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about [[Time to half tolerance::3 - 7 days]] for the tolerance to be reduced to half and [[Time to zero tolerance::1 - 2 weeks]] to be back at baseline (in the absence of further consumption). 2NE1 presents cross-tolerance with [[Cross-tolerance::all [[cannabinoids]]]], meaning that after the consumption of 2NE all [[Psychoactive class::cannabinoid]]s will have a reduced effect.
+===Overdose===
+It has been reported that overdose on this substance will cause physical discomfort including [[abnormal heartbeat|heart palpitations]], vertigo and [[sedation]] at much lower than dangerous doses, usually causing the user to suffer large amounts of [[anxiety]] or to fall asleep.
 ==Legality==