3-MeO-PCP

3-Methoxyphencyclidine (3-MeO-PCP) is a dissociative hallucinogen of the arylcyclohexylamine class related to phencyclidine (PCP) which has been sold online as a designer drug. It has been used across Europe and the United States. In some cases, consumption has been known to be fatal. It acts mainly as an NMDA receptor antagonist, though it has also been found to interact with the sigma σ$1$ receptor and the serotonin transporter. The drug does not possess any opioid activity nor does it act as a dopamine reuptake inhibitor.

Pharmacology
3-MeO-PCP has a K$i$ of 20 nM for the dizocilpine (MK-801) site of the NMDA receptor, 216 nM for the serotonin transporter (SERT), and 42 nM for the sigma σ$1$ receptor. It does not bind to the norepinephrine or dopamine transporter nor to the sigma σ$2$ receptor (Ki >10,000 nM). Based on its structural similarity to 3-hydroxy-PCP (3-HO-PCP), which uniquely among arylcyclohexylamines has high affinity for the μ-opioid receptor in addition to the NMDA receptor, it was initially expected that 3-MeO-PCP would have opioid activity. However, radioligand binding assays with human proteins have shown that, contrary to common belief, the drug also does not interact with the μ-, δ-, or κ-opioid receptors at concentrations of up to 10,000 nM. As such, the notion that 3-MeO-PCP has opioid activity has been described as a myth.

3-MeO-PCP binds to the NMDA receptor with higher affinity than PCP and has the highest affinity of the three isomeric anisyl-substitutions of PCP, followed by 2-MeO-PCP and 4-MeO-PCP.

As of 2018, controlled clinical studies have not been performed in humans but the elimination half-life is estimated to be between 10 and 11 hours.

Chemistry
3-MeO-PCP hydrochloride is a white crystalline solid with a melting point of 204–205 °C.

History
3-MeO-PCP was first synthesized in 1979 to investigate the structure–activity relationships of phencyclidine (PCP) derivatives. The effects of 3-MeO-PCP in humans were not described until 1999 when a chemist using the pseudonym John Q. Beagle wrote that 3-MeO-PCP was qualitatively similar to PCP with comparable potency. Interest in gray-market dissociates accelerated in 2008, when an online research chemical vendor began offering the less potent 4-MeO-PCP. In 2009, a Swiss chemist described the effects of taking the drug on the Bluelight forums. 3-MeO-PCP first became available as a research chemical in 2011. The drug was first reported to the European Monitoring Centre for Drugs and Drug Addiction by the UK on March 29, 2012.

Recreational Use
Based on the number of reported intoxications, 3-MeO-PCP is likely more popular than other similar grey market arylcyclohexylamines. 3-MeO-PCP has been available for purchase online as a research chemical. It has been found in drug samples in the United Kingdom and Italy. It is also known to be used in France, The Netherlands, Sweden, The United States, Spain, and the Czech Republic.

3-MeO-PCP is usually taken orally or nasally, but can also be injected or smoked. Duration and onset of effects varies depending on route of administration. When taken orally, onset takes 30-90 minutes and effects last 4-12 hours. It's effects are described as a dissociative hallucinogen, similar to PCP. Being slightly more potent than PCP, threshold activity is exhibited at 3-5mg, with dissociative effects starting at 5mg. Strong dissociative effects are seen at 10mg-20mg. The effects are generally reported as positive, with more euphoria and mental clarity than similar drugs. Negative effects include hypertension, tachycardia, confusion, and disorientation. In one case of an individual taking a very large oral dose (300-500mg), psychosis and aggressive behaviors, followed by amnesia were observed.

As of 2022, there has been two known deaths that can be attributed to 3-MeO-PCP alone; one in Sweden and one in the UK. There were 14 additional deaths where 3-MeO-PCP was detected in the blood post-mortem.

United Kingdom
On October 18, 2012, the Advisory Council on the Misuse of Drugs in the United Kingdom released a report about methoxetamine, saying that the "harms of methoxetamine are commensurate with Class B of the Misuse of Drugs Act (1971)". The report went on to suggest that all analogues of MXE should also become class B drugs and suggested a catch-all clause covering both existing and unresearched arylcyclohexylamines, including 3-MeO-PCP.

United States
3-MeO-PCP is not a controlled substance in the United States but possession or distribution of 3-MeO-PCP for human use could potentially be prosecuted under the Federal Analogue Act due to its structural and pharmacological similarities to PCP.

Canada
Canada's Controlled Drugs And Substances Act has for years placed all PCP analogues, derivatives, salts and further children thereof under a Schedule 1 prohibition, alongside opioids, cocaine and other top-ranked illegal psychoactives. As such, 3-MeO-PCP is automatically banned, although it is not mentioned by name in the schedule. Only PCP and Ketamine are specifically written in.

Sweden
Sweden's public health agency suggested classifying 3-MeO-PCP as hazardous substance on November 10, 2014.

Czech Republic
3-MeO-PCP is banned in the Czech Republic.

Chile
As per Chile's Ley de drogas, aka Ley 20000, all esters and ethers of PCP are illegal. As 3-MeO-PCP is an ether of PCP, it is thus illegal.

Portugal
3-MeO-PCP is neither a salt nor an isomer of PCP, not making it illegal.