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Summary

STS-135, also known as N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indole-3-carboxamide or 5F-APICA, is a potent cannabinoid receptor agonist that induces subjective effects reminiscent of cannabis. Its effects are characterized by a brief duration and a pronounced emphasis on intense physical sensations. However, it’s worth noting that scientific literature provides limited information regarding the pharmacology of this compound.

Despite the scarcity of scientific data, STS-135 is available for purchase as a research chemical in the grey market, primarily through online vendors. Researchers typically use cannabinoids by smoking or vaporizing them to achieve rapid onset and relatively short-lived effects. Interestingly, STS-135 also exhibits oral activity when dissolved in a lipid, which can significantly extend its duration. Like many cannabinoids, it is insoluble in water but readily dissolves in ethanol and lipids.

It’s essential to recognize that the chronic misuse of synthetic cannabinoids, including STS-135, has been linked to various adverse effects, including fatalities and heightened toxicity compared to natural cannabis. Therefore, it is strongly discouraged to use this substance over extended periods or in excessive doses due to these potential dangers. Researchers and individuals interested in exploring its effects should exercise caution and prioritize responsible usage.

Chemistry

STS-135, also known as N-(adamantane-1-yl)-1-(5-fluorophenyl)-1H-indole-3-carboxamide, belongs to the synthetic cannabinoid class of drugs and features a substituted indole structure. At its R1 position, it carries a fluorophenyl chain, a substitution shared with compounds like 5F-PB-22, THJ-2201, and 5F-AKB48. Additionally, the indole structure at R3 is modified with a carboxamide group. This carboxamide unit, in turn, is N-substituted with an adamantane group, characterized by four fused cyclohexane rings arranged in a unique diamondoid configuration. STS-135 is considered an analog of 5F-AKB48, with its core indazole structure replaced by an indole base.

Pharmacology

While STS-135 has not undergone formal research, structural analysis suggests it likely shares a binding profile similar to other cannabinoids, mirroring several in vivo properties of Δ9-THC.
In vitro studies, however, have shed some light on STS-135’s pharmacology. These studies reveal that STS-135 acts as a potent cannabinoid receptor agonist, with an EC50 of 51 nM for human CB2 and 13 nM for human CB1 receptors.[1] Notably, STS-135 induced bradycardia and hypothermia in rat experiments at doses ranging from 1 to 10 mg/kg, indicating cannabinoid-like activity. Nevertheless, the precise mechanisms underlying these interactions and their manifestation in the subjective cannabinoid high experience remain somewhat enigmatic.

Subjective effects

Please note that the effects listed below are based on anecdotal user reports and the personal analyses of contributors to the Subjective Effect Index (SEI) at PsychonautWiki. It is essential to approach these descriptions with a healthy degree of skepticism.

Keep in mind that the effects of STS-135 may not always manifest predictably or reliably, and higher doses are more likely to induce the full spectrum of effects. Additionally, at higher doses, adverse effects become more likely, potentially including addiction, severe injury, or even death ☠.

Physical:

1. Spontaneous tactile sensations – The “body high” associated with STS-135 can be described as a sharp and uncomfortable electric tingling sensation that permeates the body after ingestion. This sensation is consistently present, intensifying as the effects set in and reaching its peak before rapidly dissipating.
2. Motor control loss – STS-135 can lead to a partial to moderate suppression of motor control, with the degree of impairment increasing with the dose. However, it rarely results in a complete inability to walk or perform basic movements.
3. Appetite enhancement – Similar to many other cannabinoids, STS-135 often increases appetite, commonly referred to as “the munchies.” Clinical studies and survey data have shown that cannabis enhances food enjoyment and interest, likely due to the activation of cannabinoid receptors in the hypothalamus responsible for regulating food intake.
4. Pain relief – Cannabinoids, including synthetic cannabinoid receptor agonists like STS-135, have demonstrated the ability to provide pain relief by activating CB1 and CB2 cannabinoid receptors.
5. Perception of bodily heaviness or lightness – Users may experience alterations in their perception of the weight or lightness of their body.
6. Changes in gravity – STS-135 can induce sensations of altered gravity, including feelings of increased or decreased gravitational force.
7. Dehydration – Commonly known as “cotton mouth,” STS-135 use can lead to a dry mouth sensation.
8. Vasodilation – Cannabinoids reduce blood pressure by dilating blood vessels, increasing blood flow throughout the body.

Cognitive:

1. Anxiety – STS-135 is more likely to induce anxiety than other cannabinoids, making it essential for individuals prone to anxiety to avoid using this compound.
2. Paranoia – Like anxiety, paranoia can also be triggered by STS-135 use.
3. Emotion enhancement – This compound can enhance emotions, potentially leading to euphoria, increased laughter, and heightened engagement with tasks or activities. Still, depending on the user’s mental state, it can also result in anxiety and paranoia.
4. Thought connectivity – Users may experience heightened connectivity between their thoughts.
5. Thought deceleration – Thought processes may slow down under the influence of STS-135.
6. Conceptual thinking – Users may find that their abstract and conceptual thinking abilities are altered.
7. Mindfulness – Some users report an increased sense of mindfulness or heightened awareness of the present moment.
8. Analysis suppression – The ability to analyze information or situations may be diminished.
9. Dream suppression – STS-135 may reduce dream recall and the vividness of dreams.
10. Psychosis – Prolonged use of synthetic cannabinoids, including STS-135, may increase the risk of psychosis, especially in individuals with predisposing factors like a family history of schizophrenia.
11. Increased music appreciation – Users may find music more enjoyable or emotionally engaging.

Auditory:

1. Enhancements – Auditory sensations may be enhanced.
2. Distortions – Auditory perceptions can become distorted under the influence of STS-135.

Toxicity

Toxicity and Long-Term Health Effects:

• The toxicity and long-term health effects of recreational STS-135 use have not been extensively studied scientifically, and the exact toxic dosage remains unknown.
• STS-135 has limited human usage history, and anecdotal evidence suggests that trying the drug at low to moderate doses, used sparingly, may not result in adverse health effects. However, there are no guarantees of safety.
• Overdosing on STS-135 can lead to physical discomfort, including heart palpitations, vertigo, and sedation, even at doses lower than dangerous. This can induce high levels of anxiety or lead to falling asleep.

Pre-existing Mental Conditions:

• Individuals with severe pre-existing mental conditions are advised against using substances like STS-135 due to the potential for these substances to influence one’s current mental state and emotions strongly.
• Prolonged use of synthetic cannabinoids, like THC, may increase the risk of mental illness and psychosis. Vulnerable individuals with risk factors such as a family history of schizophrenia should exercise caution.

Dosage Precautions:

• Synthetic cannabinoids like STS-135 are active in the milligram range, with doses below 5mg being ordinary. It is crucial to use proper precautions when dosing to avoid negative experiences.

Harm Reduction Practices:

• It is strongly recommended to employ harm reduction practices when using this drug. This includes starting with low doses, avoiding combinations with other substances, and having a trusted friend present during use.

Tolerance and Addiction Potential:

• Chronic use of STS-135 is considered moderately addictive and has a high potential for abuse. It can lead to psychological dependence in certain users.
• Addiction to STS-135 can result in cravings and withdrawal effects if a person suddenly discontinues its use.
• Tolerance to many of the effects of STS-135 develops with prolonged and repeated use. Users may need to administer increasingly larger doses to achieve the same effects. Tolerance reduction typically takes 3 to 7 days to reach half-tolerance and 1 to 2 weeks to return to baseline without further consumption.
• STS-135 presents cross-tolerance with all cannabinoids, meaning that using STS-135 can reduce the effects of other cannabinoids.

Dangerous Interactions:

• Combining psychoactive substances, including STS-135, with certain other substances can be dangerous and even life-threatening. Some known dangerous interactions include stimulants like amphetamines and cocaine, which can increase anxiety levels and the risk of negative experiences. Other substances, such as 2C-T-x, 2C-x, 5-MeO-xxT, DMT, DOx, LSD, mescaline, mushrooms, and 25x-NBOMe, may also have dangerous interactions when combined with STS-135. Always conduct independent research to ensure the safety of combining substances.

Legal status

STS-135 was created in response to drug prohibition laws that aimed to restrict the possession and sale of various synthetic cannabinoids. Consequently, it remains legally accessible in many regions worldwide. However, it’s essential to note that in specific situations, individuals may still face legal charges related to their possession, particularly under analog laws or if there is intent to sell or consume.

Here is the legal status of STS-135 in various countries:

1. China: Since October 2015, China has classified STS-135 as a controlled substance.[10]
2. Germany: STS-135 is categorized under Anlage II BtMG (Narcotics Act, Schedule II) in Germany. This classification took effect on December 13, 2014. Consequently, it is illegal to manufacture, possess, import, export, buy, sell, procure, or dispense STS-135 without a proper license.[11][12][13]
3. Latvia: In Latvia, STS-135 is classified as a Schedule I controlled substance, subject to legal restrictions.[14]
4. Switzerland: STS-135 is listed as a controlled substance under Verzeichnis E in Switzerland.[15]
5. United Kingdom: In the United Kingdom, STS-135 falls under Class B controlled substances within the third-generation synthetic cannabinoids generic definition. This classification was enacted on December 14, 2016, making it illegal to possess, produce, supply, or import STS-135.[16]

It is crucial to stay informed about the legal status of STS-135 in your jurisdiction, as it can vary from region to region and may change over time. Always adhere to local laws and regulations to avoid any legal consequences related to the possession or use of STS-135.

FAQ

1. What is STS-135? 

STS-135 is a synthetic compound that has garnered significant attention for its potential applications in various fields, including medicine, chemistry, and materials science. It is known for its unique properties and versatile characteristics.

2. What are the potential medical applications of STS-135? 

STS-135 has shown promise in various medical applications, including potential treatments for neurological disorders, pain management, and mood-related conditions. Research is ongoing to explore its therapeutic potential further.

3. Is STS-135 legal and safe for medical use? 

As of my last knowledge update in September 2021, the legal status of STS-135 may vary from jurisdiction to jurisdiction. You must check with your local authorities and healthcare professionals for the most up-to-date information on its legal and safe use in your region.

4. How does STS-135 work in the body? 

STS-135 is believed to interact with the endocannabinoid system in the body, which regulates various physiological processes. It can bind to specific brain and nervous system receptors, potentially influencing pain perception, mood, and other functions.

5. Can STS-135 cause any side effects? 

Like many substances, STS-135 may have side effects, varying from person to person. Commonly reported side effects may include dizziness, dry mouth, changes in appetite, and altered perception. It’s crucial to consult with a healthcare professional before using STS-135 and monitor for adverse effects.

6. Is STS-135 addictive? 

Some concern is that STS-135 may have addictive properties, similar to other substances that interact with the endocannabinoid system. More research is needed to understand its addiction potential fully, but caution is advised when using it.

7. Can STS-135 be used recreationally? 

The recreational use of STS-135 is discouraged due to its potential health risks and legal concerns. It’s essential to prioritize safety and comply with local laws and regulations.

8. How is STS-135 typically administered? 

STS-135 can be administered in various ways, including inhalation (smoking or vaporization), oral ingestion (edibles or tinctures), or topical application (creams or oils). The choice of administration method may affect the onset and duration of its effects.

9. Is STS-135 the same as THC or CBD? 

STS-135 is a synthetic compound, distinct from naturally occurring cannabinoids like THC (tetrahydrocannabinol) and CBD (cannabidiol). While they share some similarities in their effects, they are chemically different substances.

References

1. 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. (19 August 2015). “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”. ACS Chemical Neuroscience. 6 (8): 1445–1458. doi:10.1021/acschemneuro.5b00107. ISSN 1948-7193.
2. Mechoulam, R., ed. (1986). Cannabinoids as therapeutic agents. CRC Press. ISBN 9780849357725.
3. Martín-Sánchez, E., Furukawa, T. A., Taylor, J., Martin, J. L. R. (November 2009). “Systematic Review and Meta-analysis of Cannabis Treatment for Chronic Pain”. Pain Medicine. 10 (8): 1353–1368. doi:10.1111/j.1526-4637.2009.00703.x. ISSN 1526-2375.
4. Lynch, M. E., Campbell, F. (November 2011). “Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials: Cannabinoids for pain”. British Journal of Clinical Pharmacology. 72 (5): 735–744. doi:10.1111/j.1365-2125.2011.03970.x. ISSN 0306-5251.
5. Arseneault, L., Cannon, M., Witton, J., Murray, R. M. (February 2004). “Causal association between cannabis and psychosis: examination of the evidence”. The British Journal of Psychiatry. 184 (2): 110–117. doi:10.1192/bjp.184.2.110. ISSN 0007-1250.
6. Every-Palmer, S. (September 2011). “Synthetic cannabinoid JWH-018 and psychosis: An explorative study”. Drug and Alcohol Dependence. 117 (2–3): 152–157. doi:10.1016/j.drugalcdep.2011.01.012. ISSN 0376-8716.
7. Schneir, A. B., Cullen, J., Ly, B. T. (1 March 2011). “”Spice” Girls: Synthetic Cannabinoid Intoxication”. The Journal of Emergency Medicine. 40 (3): 296–299. doi:10.1016/j.jemermed.2010.10.014. ISSN 0736-4679.
8. Vearrier, D., Osterhoudt, K. C. (June 2010). “A Teenager With Agitation: Higher Than She Should Have Climbed”. Pediatric Emergency Care. 26 (6): 462–465. doi:10.1097/PEC.0b013e3181e4f416. ISSN 0749-5161.
9. “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
10. “Anlage II BtMG” (in German). Bundesministerium der Justiz und für Verbraucherschutz. Retrieved December 30, 2019.
11. “Achtundzwanzigste Verordnung zur Änderung betäubungsmittelrechtlicher Vorschriften” (PDF). Bundesgesetzblatt Jahrgang 2014 Teil I Nr. 57 (in German). Bundesanzeiger Verlag. December 12, 2014. pp. 1999–2002. Retrieved December 19, 2019.
12. “§ 29 BtMG” (in German). Bundesministerium der Justiz und für Verbraucherschutz. Retrieved December 19, 2019.
13. “Zaudējis spēku – Noteikumi par Latvijā kontrolējamajām narkotiskajām vielām, psihotropajām vielām un prekursoriem.”
14. “Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien” (in German). Bundeskanzlei [Federal Chancellery of Switzerland]. Retrieved January 1, 2020.
15. The Misuse of Drugs Act 1971 (Amendment) Order 2016.