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Summary

3-Methoxyphencyclidine (3-MeO-PCP) belongs to the arylcyclohexylamine class and is a dissociative hallucinogenic compound closely related to phencyclidine (PCP). It has gained notoriety for being available for purchase as a designer drug through online channels. This compound primarily functions as an antagonist for NMDA receptors, although it has also demonstrated interactions with the sigma σ1 receptor and the serotonin transporter. Notably, 3-MeO-PCP lacks any opioid-related activity and does not function as a dopamine reuptake inhibitor.

Pharmacology

3-MeO-PCP exhibits a Ki value of 20 nM at the dizocilpine (MK-801) binding site of the NMDA receptor, 216 nM for the serotonin transporter (SERT), and 42 nM for the sigma σ1 receptor. Notably, it does not display binding activity towards the norepinephrine or dopamine transporter or interact with the sigma σ2 receptor (Ki >10,000 nM).
Initially, due to its structural resemblance to 3-hydroxy-PCP (3-HO-PCP), which is unique among arylcyclohexylamines in its strong affinity for the μ-opioid receptor in addition to the NMDA receptor, it was anticipated that 3-MeO-PCP might possess opioid activity. However, thorough radioligand binding assays conducted with human proteins have convincingly debunked this belief, revealing that 3-MeO-PCP does not engage with the μ-, δ-, or κ-opioid receptors even at concentrations as high as 10,000 nM. Therefore, the notion that 3-MeO-PCP has any opioid activity has been conclusively debunked.
Furthermore, 3-MeO-PCP’s binding affinity to the NMDA receptor surpasses that of PCP itself, and it boasts the highest association among the three isomeric anisyl-substituted derivatives of PCP, with 2-MeO-PCP and 4-MeO-PCP following suit. These findings shed light on the compound’s specific receptor interactions, furthering our understanding of its pharmacological profile.

Chemistry

3-MeO-PCP hydrochloride presents as a white crystalline solid, characterized by a melting point within the range of 204 to 205°C.

History

3-Methoxyphencyclidine (3-MeO-PCP) was initially synthesized in 1979 to explore the structure-activity relationships of phencyclidine (PCP) derivatives. However, it wasn’t until 1999 that the effects of 3-MeO-PCP in humans were documented, with a chemist using the pseudonym John Q. Beagle reporting that 3-MeO-PCP exhibited qualitative similarities to PCP and possessed comparable potency.[6] Before the emergence of 3-MeO-PCP, the less potent dissociative compound 4-Methoxyphencyclidine (4-MeO-PCP) had been studied. It was only in 2011 that 3-MeO-PCP became available as a research chemical.

Legal status

United Kingdom:
On October 18, 2012, the Advisory Council on the Misuse of Drugs in the United Kingdom issued a report regarding methoxetamine, wherein it concluded that the “harmful effects of methoxetamine warrant its classification under Class B of the Misuse of Drugs Act (1971).” The report further recommended that all analogs of MXE, including 3-MeO-PCP, be categorized as Class B drugs, encompassing established and unexplored arylcyclohexylamines.
United States:
3-MeO-PCP is not classified as a controlled substance in the United States. However, it is essential to note that possessing or distributing 3-MeO-PCP for human consumption could potentially lead to prosecution under the Federal Analogue Act. This is due to its structural and pharmacological similarities to PCP.
Canada:
Under Canada’s Controlled Drugs and Substances Act, all analogs, derivatives, salts, and related compounds of PCP have long been categorized as Schedule 1 substances, alongside other highly prohibited psychoactive substances like opioids and cocaine. Consequently, 3-MeO-PCP is automatically considered banned, although it is not explicitly mentioned by name in the schedule. Only PCP and Ketamine are specifically listed.
Sweden:
On November 10, 2014, Sweden’s public health agency recommended classifying 3-MeO-PCP as hazardous.
Czech Republic:
3-MeO-PCP is explicitly banned in the Czech Republic.
Chile:
By Chile’s Ley de drogas, also known as Ley 20000, all esters and ethers of PCP are prohibited. Since 3-MeO-PCP is classified as an ether of PCP, it falls under this prohibition and is thus illegal.
Portugal:
3-MeO-PCP is not considered a salt or an isomer of PCP, which means it is not classified as illegal in Portugal.

FAQ

1. What is 3-MeO-PCP?

3-MeO-PCP, or 3-Methoxyphencyclidine, is a synthetic dissociative hallucinogen in the arylcyclohexylamine class. It shares structural similarities with phencyclidine (PCP) and is known for its psychoactive effects.

2. How is 3-MeO-PCP typically used?

3-MeO-PCP is often used recreationally, with users either ingesting it orally, snorting it in powder form, or vaporizing it for inhalation. It’s essential to note that 3-MeO-PCP is not approved for medical use.

3. What are the effects of 3-MeO-PCP?

The effects of 3-MeO-PCP can vary widely among individuals but may include dissociation from reality, altered perception of time and space, euphoria, and hallucinations. Users may also experience impaired motor skills and coordination.

4. Is 3-MeO-PCP legal?

The legal status of 3-MeO-PCP varies by country and region. It is considered a controlled substance in some places, while in others, it falls under analog laws or may not be explicitly regulated. Always check your local laws before acquiring or using it.

5. What are the potential risks and side effects of 3-MeO-PCP?

Using 3-MeO-PCP can lead to various adverse effects, including paranoia, anxiety, confusion, and even psychotic episodes. Physical side effects may include nausea, increased heart rate, and elevated blood pressure. It can be dangerous when used irresponsibly or in high doses.

6. Is 3-MeO-PCP addictive?

There is limited scientific research on the addictive potential of 3-MeO-PCP. However, like many dissociative drugs, it has the potential for psychological dependence when used regularly or in high quantities.

7. Can 3-MeO-PCP be used for medical purposes?

3-MeO-PCP is not approved for medical use and should not be used for self-medication. It has not undergone the rigorous testing required for pharmaceutical drugs and poses serious health risks.

8. Are there any interactions or contraindications with other substances?

Combining 3-MeO-PCP with other substances, especially depressants like alcohol or opioids, can be extremely dangerous and even life-threatening. Always consult with a healthcare professional and avoid mixing substances.

9. How can I reduce the risks associated with 3-MeO-PCP use?

The safest approach is not to use 3-MeO-PCP at all. If you choose to use it, research harm reduction strategies, use it in moderation and be cautious about its source and purity. Additionally, never use it while operating machinery or driving.

References

Morris H, Wallach J (2014). “From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs.” Drug Test Anal. 6 (7–8): 614–32. doi:10.1002/dta.1620. PMID 24678061.
Roth BL, Gibbons S, Arunotayanun W, Huang XP, Setola V, Treble R, Iversen L (2013). “The ketamine analog methoxetamine and 3- and 4-methoxy analogs of phencyclidine are high affinities and selective ligands for the glutamate NMDA receptor”. PLOS ONE. 8 (3): e59334. Bibcode:2013PLoSO…859334R. doi:10.1371/journal.pone.0059334. PMC 3602154. PMID 23527166.
“(ACMD) Methoxetamine Report (2012)” (PDF). UK Home Office. 2012-10-18. p. 14. Retrieved 2012-10-22.
Morris H (2011-02-11). “Interview with a ketamine chemist: or, to be more precise, an arylcyclohexylamine chemist.” Vice Magazine. Retrieved 2012-01-23.
Wallach J, De Paoli G, Adejare A, Brandt S (2013). “Preparation and analytical characterization of 1-(1-phenylcyclohexyl)piperidine (PCP) and 1-(1-phenylcyclohexyl)pyrrolidine (PCPy) analogs”. Drug Testing and Analysis. 6 (7–8): 633–650. doi:10.1002/dta.1468. PMID 23554350.
Morris H, Wallach J (2014). “From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs.” Drug Testing and Analysis. 6 (7–8): 614–632. doi:10.1002/dta.1620. PMID 24678061.
“Advisory Council on the Misuse of Drugs (ACMD) Methoxetamine report, 2012”. Advisory Council on the Misuse of Drugs. 18 October 2012.
“Controlled Drugs And Substances Act”. Government of Canada Justice Laws. 18 March 2021. Retrieved 25 April 2021.
“Cannabinoider föreslås bli klassade som hälsofarlig vara”. Retrieved 29 June 2015.
“Látky, o které byl doplněn seznam č. 4 psychotropních látek (příloha č. 4 k nařízení vlády č. 463/2013 Sb.)” (PDF) (in Czech). Ministerstvo zdravotnictví. Archived from the original (PDF) on 2016-03-09. Retrieved 2016-02-06.
“SUSTITUYE LA LEY Nº 19.366, QUE SANCIONA EL TRAFICO ILICITO DE ESTUPEFACIENTES Y SUSTANCIAS SICOTROPICAS” (in Spanish). Bibloteca Del Congreso Nacional. 22 October 2015. Retrieved 6 February 2018.
“Legislação de Combate à Droga, Tabela II-A.”