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'''STS-135''' (also called '''N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indole-3-carboxamide''' or '''5F-APICA''') is a drug that acts as a potent [[agonist]] for the [[psychoactive class::cannabinoid]] [[receptor]]s which produces subjective effects somewhat similar to that of [[cannabis]] with a short duration and an emphasis on intense physical sensations. There is very little information regarding the pharmacology of this compound within the scientific literature. Despite this, however, it is available for sale as a grey area [[research chemical]] through online vendors.
'''STS-135''' (also called '''N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indole-3-carboxamide''' or '''5F-APICA''') is a drug that acts as a potent [[agonist]] for the [[psychoactive class::cannabinoid]] [[receptor]]s which produces subjective effects somewhat similar to that of [[cannabis]] with a short duration and an emphasis on intense physical sensations. There is very little information regarding the pharmacology of this compound within the scientific literature. Despite this, however, it is available for sale as a grey area [[research chemical]] through online vendors.
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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.
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==
==Chemistry==
STS-135, or N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indole-3-carboxamide, is a synthetic [[chemical class::cannabinoid]] drug containing a substituted indole group. This indole moeity is substituted at R<sub>1</sub> with a fluoropentyl chain, a substitution shared with [[5F-PB-22]], [[THJ-2201]], and [[5F-AKB48]]. 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. STS-135 is an analog of [[5F-AKB48]] in which the core indazole structure is substituted with an indole base.
STS-135, or N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indole-3-carboxamide, is a synthetic [[cannabinoid]] drug containing a substituted indole group. This indole moeity is substituted at R<sub>1</sub> with a fluoropentyl chain, a substitution shared with [[5F-PB-22]], [[THJ-2201]], and [[5F-AKB48]]. 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. STS-135 is an analog of [[5F-AKB48]] in which the core indazole structure is substituted with an indole base.
==Pharmacology==
==Pharmacology==
Although this substance has not been formally studied, from analysis of the structure, it is presumed that STS-135 has a similar binding profile to that of other [[cannabinoids]] and matches many of the in vivo properties of [[Δ9-THC]].
Although this substance has not been formally studied, from analysis of the structure, it is presumed that STS-135 has a similar binding profile to that of other [[cannabinoids]] and matches many of the in vivo properties of [[Δ9-THC]].
Formal studies have demonstrated that STS-135 acts a potent cannabinoid receptor agonist in vitro with an EC50 of 51 nM for human CB2 receptors and 13 nM for human CB1 receptors.<ref>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 | http://pubs.acs.org/doi/abs/10.1021/acschemneuro.5b00107</ref> STS-135 produces bradycardia and hypothermia in rats at doses of 1-10 mg/kg, suggesting cannabinoid-like activity.<ref>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 | http://pubs.acs.org/doi/abs/10.1021/acschemneuro.5b00107</ref> However, the role of these interactions and how they result in the cannabinoid high experience continues to remain elusive.
Formal studies have demonstrated that STS-135 acts a potent cannabinoid receptor agonist in vitro with an EC50 of 51 nM for human CB2 receptors and 13 nM for human CB1 receptors.<ref name="Banister2015">{{cite journal | vauthors=((Banister, S. D.)), ((Stuart, J.)), ((Kevin, R. C.)), ((Edington, A.)), ((Longworth, M.)), ((Wilkinson, S. M.)), ((Beinat, C.)), ((Buchanan, A. S.)), ((Hibbs, D. E.)), ((Glass, M.)), ((Connor, M.)), ((McGregor, I. S.)), ((Kassiou, M.)) | journal=ACS Chemical Neuroscience | title=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 | volume=6 | issue=8 | pages=1445–1458 | date=19 August 2015 | url=https://pubs.acs.org/doi/10.1021/acschemneuro.5b00107 | issn=1948-7193 | doi=10.1021/acschemneuro.5b00107}}</ref> STS-135 produces bradycardia and hypothermia in rats at doses of 1-10 mg/kg, suggesting cannabinoid-like activity.<ref name="Banister2015"></ref> However, the role of these interactions and how they result in the cannabinoid high experience continues to remain elusive.
==Subjective effects==
==Subjective effects==
{{Preamble/SubjectiveEffects}}
{{Preamble/SubjectiveEffects}}
===Physical effects===
{{effects/base
|{{effects/physical|
*'''[[Effect::Spontaneous tactile sensations]]''' - The "body high" of STS-135 can be described as a sharp, uncomfortable, all-encompassing, electric tingling sensation that spreads over the body after initial ingestion. It maintains a consistent presence that quickly rises with the onset and hits its limit once the peak has been reached before immediately dissipating.
*'''[[Effect::Spontaneous tactile sensations]]''' - The "body high" of STS-135 can be described as a sharp, uncomfortable, all-encompassing, electric tingling sensation that spreads over the body after initial ingestion. It maintains a consistent presence that quickly rises with the onset and hits its limit once the peak has been reached before immediately dissipating.
*'''[[Effect::Motor control loss]]''' - This substance causes a partial to moderate suppression of motor control which intensifies proportional to dose, but rarely results in a complete inability to walk and perform basic movements.
*'''[[Effect::Motor control loss]]''' - This substance causes a partial to moderate suppression of motor control which intensifies proportional to dose, but rarely results in a complete inability to walk and perform basic movements.
*'''[[Effect::Appetite enhancement]]''' - As with many other cannabinoids, STS-135 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::Appetite enhancement]]''' - As with many other cannabinoids, STS-135 causes an increase in appetite<ref>{{cite book | veditors=((Mechoulam, R.)) | date= 1986 | title=Cannabinoids as therapeutic agents | publisher=CRC Press | isbn=9780849357725}}</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 name="HMW">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 name="HMW"></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::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>{{cite journal | vauthors=((Martín-Sánchez, E.)), ((Furukawa, T. A.)), ((Taylor, J.)), ((Martin, J. L. R.)) | journal=Pain Medicine | title=Systematic Review and Meta-analysis of Cannabis Treatment for Chronic Pain | volume=10 | issue=8 | pages=1353–1368 | date= November 2009 | url=https://academic.oup.com/painmedicine/article-lookup/doi/10.1111/j.1526-4637.2009.00703.x | issn=1526-2375 | doi=10.1111/j.1526-4637.2009.00703.x}}</ref><ref>{{cite journal | vauthors=((Lynch, M. E.)), ((Campbell, F.)) | journal=British Journal of Clinical Pharmacology | title=Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials: Cannabinoids for pain | volume=72 | issue=5 | pages=735–744 | date= November 2011 | url=https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2125.2011.03970.x | issn=03065251 | doi=10.1111/j.1365-2125.2011.03970.x}}</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 gravity]]'''
*'''[[Effect::Changes in gravity]]'''
*'''[[Effect::Dehydration]]'''- This is known colloquially as "cotton mouth" in popular American and United Kingdom culture.
*'''[[Effect::Dehydration]]'''- This is known colloquially as "cotton mouth" in popular American and United Kingdom culture.
*'''[[Effect::Vasodilation]]'''
*'''[[Effect::Vasodilation]]'''
===Cognitive effects===
}}
|{{effects/cognitive|
*'''[[Effect::Anxiety]]''' - In comparison to other cannabinoids, this compound is particularly prone to inducing feelings of anxiety and it should therefore be avoided by people who are particularly prone to this state of mind.
*'''[[Effect::Anxiety]]''' - In comparison to other cannabinoids, this compound is particularly prone to inducing feelings of anxiety and it should therefore be avoided by people who are particularly prone to this state of mind.
*'''[[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 name="Arseneault2004">{{cite journal | vauthors=((Arseneault, L.)), ((Cannon, M.)), ((Witton, J.)), ((Murray, R. M.)) | journal=The British Journal of Psychiatry | title=Causal association between cannabis and psychosis: examination of the evidence | volume=184 | issue=2 | pages=110–117 | date= February 2004 | url=https://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/causal-association-between-cannabis-and-psychosis-examination-of-the-evidence/71BA37D16485F186CE7B6B785E5B69A4 | issn=0007-1250 | doi=10.1192/bjp.184.2.110}}</ref>, particularly in vulnerable individuals with risk factors for psychotic illnesses (like a past or family history of schizophrenia).<ref name="Every-Palmer2011">{{cite journal | vauthors=((Every-Palmer, S.)) | journal=Drug and Alcohol Dependence | title=Synthetic cannabinoid JWH-018 and psychosis: An explorative study | volume=117 | issue=2–3 | pages=152–157 | date= September 2011 | url=https://linkinghub.elsevier.com/retrieve/pii/S0376871611000639 | issn=03768716 | doi=10.1016/j.drugalcdep.2011.01.012}}</ref><ref name="Schneir2011">{{cite journal | vauthors=((Schneir, A. B.)), ((Cullen, J.)), ((Ly, B. T.)) | journal=The Journal of Emergency Medicine | title=“Spice” Girls: Synthetic Cannabinoid Intoxication | volume=40 | issue=3 | pages=296–299 | date=1 March 2011 | url=https://www.sciencedirect.com/science/article/pii/S0736467910008802 | issn=0736-4679 | doi=10.1016/j.jemermed.2010.10.014}}</ref><ref name="Vearrier2010">{{cite journal | vauthors=((Vearrier, D.)), ((Osterhoudt, K. C.)) | journal=Pediatric Emergency Care | title=A Teenager With Agitation: Higher Than She Should Have Climbed | volume=26 | issue=6 | pages=462–465 | date= June 2010 | url=http://journals.lww.com/00006565-201006000-00016 | issn=0749-5161 | doi=10.1097/PEC.0b013e3181e4f416}}</ref>
The toxicity and long-term health effects of recreational STS-135 use do not seem to have been studied in any scientific context and the [[Toxicity::exact toxic dosage is unknown]]. This is because STS-135 has very little history of human usage. Anecdotal evidence from people who have tried STS-135 within the community suggest that there do not seem to be any negative health effects attributed to simply trying this drug at low to moderate doses by itself and using it sparingly (but nothing can be completely guaranteed). Informal experiments have shown that overdose 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 STS-135 use do not seem to have been studied in any scientific context and the [[Toxicity::exact toxic dosage is unknown]]. This is because STS-135 has very little history of human usage. Anecdotal evidence from people who have tried STS-135 within the community suggest that there do not seem to be any negative health effects attributed to simply trying this drug at low to moderate doses by itself and using it sparingly (but nothing can be completely guaranteed). Informal experiments have shown that overdose 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.
It has often been recommended that those with severe pre-existing mental conditions should not ingest these substances due to the way they strongly increase [[emotion enhancement|one's current state of mind and emotions]]. Also, like [[THC]], prolonged usage of synthetic [[cannabinoids]] 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>
It has often been recommended that those with severe pre-existing mental conditions should not ingest these substances due to the way they strongly increase [[emotion enhancement|one's current state of mind and emotions]]. Also, like [[THC]], prolonged usage of synthetic [[cannabinoids]] may increase one's disposition to mental illness and psychosis<ref name="Arseneault2004"></ref>, particularly in vulnerable individuals with risk factors for psychotic illnesses (like a past or family history of schizophrenia).<ref name="Every-Palmer2011"></ref><ref name="Schneir2011"></ref><ref name="Vearrier2010"></ref>
As synthetic cannabinoids are active in the milligram range (with below 5mg being a common dose), it is important to [[Dosage|use proper precautions when dosing]] to avoid a negative experience.
As synthetic cannabinoids are active in the milligram range (with below 5mg being a common dose), it is important to [[Dosage|use proper precautions when dosing]] to avoid a negative experience.
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Tolerance to many of the effects of STS-135 [[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). STS-135 presents cross-tolerance with [[Cross-tolerance::all [[cannabinoids]]]], meaning that after the consumption of STS-135 all cannabinoids will have a reduced effect.
Tolerance to many of the effects of STS-135 [[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). STS-135 presents cross-tolerance with [[Cross-tolerance::all [[cannabinoids]]]], meaning that after the consumption of STS-135 all cannabinoids will have a reduced effect.
==Legal issues==
===Dangerous interactions===
STS-135 was developed to bypass drug prohibition laws which have banned the possession and sale of many synthetic cannabinoids. As such, it remains legal in most of the world. This means that it is not known to be specifically illegal within any country, but people may still be charged for its possession under certain circumstances such as under analogue laws and with intent to sell or consume.
{{DangerousInteractions/Intro}}
*'''United Kingdom''' - STS-135 is a class B drug under the third-generation synthetic cannabinoids generic definition, which came into effect on the 14th December 2016 and is illegal to possess, produce, supply, or import. <ref>The Misuse of Drugs Act 1971 (Amendment) Order 2016 (Legislation.gov.uk) | http://www.legislation.gov.uk/uksi/2016/1109/made</ref>
{{DangerousInteractions/Cannabis}}
*'''China''' - As of October 2015, STS-135 is a controlled substance in China.<ref>关于印发《非药用类麻醉药品和精神药品列管办法》的通知 | http://www.sfda.gov.cn/WS01/CL0056/130753.html</ref>
*'''Germany''' - On December 13, 2014 STS-135 was added to the controlled substance act ("BtMG"), making it illegal to produce, sell or possess.<ref>Achtundzwanzigste Verordnung zur Änderung betäubungsmittelrechtlicher Vorschriften (28. BtMÄndV)| http://www.buzer.de/gesetz/11392/a189949.htm</ref>
==Legal status==
*'''Latvia''' - STS-135 is a Schedule I drug.<ref>Noteikumi par Latvijā kontrolējamajām narkotiskajām vielām, psihotropajām vielām un prekursoriem (Indola-3-karboksamīdi) | http://likumi.lv/doc.php?id=121086</ref>
STS-135 was developed to bypass drug prohibition laws which have banned the possession and sale of many synthetic cannabinoids. As such, it remains legal in many parts of the world. People may still be charged for its possession under certain circumstances such as under analogue laws and with intent to sell or consume.
*'''China''': As of October 2015, STS-135 is a controlled substance in China.<ref>关于印发《非药用类麻醉药品和精神药品列管办法》的通知 | http://www.sfda.gov.cn/WS01/CL0056/130753.html</ref>
*'''Germany''': STS-135 is controlled under Anlage II BtMG (''Narcotics Act, Schedule II'')<ref>{{cite web|url=https://www.gesetze-im-internet.de/btmg_1981/anlage_ii.html|title=Anlage II BtMG|publisher=Bundesministerium der Justiz und für Verbraucherschutz|access-date=December 30, 2019|language=de}}</ref> as of December 13, 2014.<ref>{{cite web|url=http://www.bgbl.de/xaver/bgbl/start.xav?startbk=Bundesanzeiger_BGBl&jumpTo=bgbl114s1999.pdf|title=Achtundzwanzigste Verordnung zur Änderung betäubungsmittelrechtlicher Vorschriften|publisher=Bundesanzeiger Verlag|work=Bundesgesetzblatt Jahrgang 2014 Teil I Nr. 57|publication-date=December 12, 2014|pages=1999-2002|access-date=December 19, 2019|language=de}}</ref> It is illegal to manufacture, possess, import, export, buy, sell, procure or dispense it without a license.<ref>{{cite web|url=https://www.gesetze-im-internet.de/btmg_1981/__29.html|title=§ 29 BtMG|publisher=Bundesministerium der Justiz und für Verbraucherschutz|access-date=December 19, 2019|language=de}}</ref>
*'''Latvia''': STS-135 is a Schedule I controlled substance.<ref>{{Citation | title=Zaudējis spēku - Noteikumi par Latvijā kontrolējamajām narkotiskajām vielām, psihotropajām vielām un prekursoriem | url=https://likumi.lv/doc.php?id=121086}}</ref>
*'''Switzerland''': STS-135 is a controlled substance specifically named under Verzeichnis E.<ref>{{cite web|url=https://www.admin.ch/opc/de/classified-compilation/20101220/index.html|title=Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien|publisher=Bundeskanzlei [Federal Chancellery of Switzerland]|access-date=January 1, 2020|language=de}}</ref>
*'''United Kingdom''': STS-135 is a Class B controlled substance under the third-generation synthetic cannabinoids generic definition, which came into effect on December 14, 2016 and is illegal to possess, produce, supply, or import.<ref>{{Citation | title=The Misuse of Drugs Act 1971 (Amendment) Order 2016 | url=https://www.legislation.gov.uk/uksi/2016/1109/made}}</ref>
WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.
DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.
STS-135 (also called N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indole-3-carboxamide or 5F-APICA) is a drug that acts as a potent agonist for the cannabinoidreceptors which produces subjective effects somewhat similar to that of cannabis with a short duration and an emphasis on intense physical sensations. There is very little information regarding the pharmacology of this compound within the scientific literature. Despite this, however, it is 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. STS-135 is orally active when dissolved in a lipid, which can increase the duration significantly. Like other cannabinoids, it is insoluble in water but dissolves in ethanol and lipids.
STS-135, or N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indole-3-carboxamide, is a synthetic cannabinoid drug containing a substituted indole group. This indole moeity is substituted at R1 with a fluoropentyl chain, a substitution shared with 5F-PB-22, THJ-2201, and 5F-AKB48. 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. STS-135 is an analog of 5F-AKB48 in which the core indazole structure is substituted with an indole base.
Pharmacology
Although this substance has not been formally studied, from analysis of the structure, it is presumed that STS-135 has a similar binding profile to that of other cannabinoids and matches many of the in vivo properties of Δ9-THC.
Formal studies have demonstrated that STS-135 acts a potent cannabinoid receptor agonist in vitro with an EC50 of 51 nM for human CB2 receptors and 13 nM for human CB1 receptors.[1] STS-135 produces bradycardia and hypothermia in rats at doses of 1-10 mg/kg, suggesting cannabinoid-like activity.[1] However, the role of these interactions and how they result in the cannabinoid high experience continues to remain elusive.
Subjective effects
Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWikicontributors. As a result, they should be viewed with a healthy degree of skepticism.
It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.
Physical effects
Spontaneous tactile sensations - The "body high" of STS-135 can be described as a sharp, uncomfortable, all-encompassing, electric tingling sensation that spreads over the body after initial ingestion. It maintains a consistent presence that quickly rises with the onset and hits its limit once the peak has been reached before immediately dissipating.
Motor control loss - This substance causes a partial to moderate suppression of motor control which intensifies proportional to dose, but rarely results in a complete inability to walk and perform basic movements.
Appetite enhancement - As with many other cannabinoids, STS-135 causes an increase in appetite[2], 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.[3] 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.[3]
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.[4][5]
Anxiety - In comparison to other cannabinoids, this compound is particularly prone to inducing feelings of anxiety and it should therefore be avoided by people who are particularly prone to this state of mind.
Psychosis - The prolonged usage of synthetic cannabinoids may increase one's disposition to psychosis[6], particularly in vulnerable individuals with risk factors for psychotic illnesses (like a past or family history of schizophrenia).[7][8][9]
The toxicity and long-term health effects of recreational STS-135 use do not seem to have been studied in any scientific context and the exact toxic dosage is unknown. This is because STS-135 has very little history of human usage. Anecdotal evidence from people who have tried STS-135 within the community suggest that there do not seem to be any negative health effects attributed to simply trying this drug at low to moderate doses by itself and using it sparingly (but nothing can be completely guaranteed). Informal experiments have shown that overdose 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.
It has often been recommended that those with severe pre-existing mental conditions should not ingest these substances due to the way they strongly increase one's current state of mind and emotions. Also, like THC, prolonged usage of synthetic cannabinoids may increase one's disposition to mental illness and psychosis[6], particularly in vulnerable individuals with risk factors for psychotic illnesses (like a past or family history of schizophrenia).[7][8][9]
As synthetic cannabinoids are active in the milligram range (with below 5mg being a common dose), it is important to use proper precautions when dosing to avoid a negative experience.
As with other synthetic cannibanoids, the chronic use of STS-135 can be considered moderately addictive with a high potential for abuse and is capable of causing psychological dependence among certain users. When addiction has developed, cravings and withdrawal effects may occur if a person suddenly stops their usage.
Tolerance to many of the effects of STS-135 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 3 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to be back at baseline (in the absence of further consumption). STS-135 presents cross-tolerance with [[Cross-tolerance::all cannabinoids]], meaning that after the consumption of STS-135 all cannabinoids will have a reduced effect.
Dangerous interactions
Warning:Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).
Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.
"[[UncertainInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]]
"[[UncertainInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]]
"[[UncertainInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]]
"[[UncertainInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Stimulants increase anxiety levels and the risk of thought loops which can increase Effect:Paranoia leading to negative experiences
"[[UncertainInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]]
"[[UncertainInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Stimulants increase anxiety levels and the risk of thought loops which can increase Effect:Paranoia leading to negative experiences
"[[UncertainInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]]
"[[UncertainInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]]
"[[DangerousInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Lithium is commonly prescribed in the treatment of bipolar disorder; however, there is a large body of anecdotal evidence that suggests taking it with cannabinoids can significantly increase the risk of psychosis and seizures. As a result, this combination should be strictly avoided.
"[[UncertainInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]]
"[[UncertainInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]]
"[[UncertainInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Cannabis can intensify the overall effects of psilocybin mushrooms, possibly leading to a bad trip.
"[[UncertainInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]]
Legal status
STS-135 was developed to bypass drug prohibition laws which have banned the possession and sale of many synthetic cannabinoids. As such, it remains legal in many parts of the world. People may still be charged for its possession under certain circumstances such as under analogue laws and with intent to sell or consume.
China: As of October 2015, STS-135 is a controlled substance in China.[10]
Germany: STS-135 is controlled under Anlage II BtMG (Narcotics Act, Schedule II)[11] as of December 13, 2014.[12] It is illegal to manufacture, possess, import, export, buy, sell, procure or dispense it without a license.[13]
Latvia: STS-135 is a Schedule I controlled substance.[14]
Switzerland: STS-135 is a controlled substance specifically named under Verzeichnis E.[15]
United Kingdom: STS-135 is a Class B controlled substance under the third-generation synthetic cannabinoids generic definition, which came into effect on December 14, 2016 and is illegal to possess, produce, supply, or import.[16]
