From PCP to MXE: a comprehensive review of the non‐medical use of dissociative drugs

Abstract

PCP or phencyclidine was discovered in 1956 and soon became a popular street drug. Dissociatives including PCP, ketamine, and dextromethorphan have been used non-medically for their mind-altering effects for over 60 years. Many of these compounds have also been used clinically and in legitimate research. At least 14 derivatives of PCP were sold for non-medical and illict use from the late 1960s until the 1990s. With the advent of the Internet, the drug market underwent a dramatic evolution. While initially gray-market chemical vendors offering dextromethorphan and ketamine thrived, most recently the market has shifted to legal high and online-based research chemical vendors. Starting with the first dissociative research chemical, 4-MeO-PCP in 2008, the dissociative research chemical market has rapidly evolved and currently comprises at least 12 dissociatives, almost half of which were unknown in the scientific literature prior to their introduction. Several of these, including methoxetamine, have reached widespread use internationally. A historical account of non-medical use of over 30 dissociative compounds was compiled from a diverse collection of sources. The first complete portrait of this underground market is presented along with the relevant legal, technological, and scientific developments which have driven its evolution.

Acute toxicity associated with the recreational use of the novel dissociative psychoactive substance methoxphenidine

“…1 These recreational psychoactive substances with dissociative effects are highly addictive because of their ability to produce intense psychedelic effects. 1 Shortly after the 2013 UK ban on arylcyclohexylamines, methoxphenidine became available on the grey market. 1 It is advertised and sold through the internet as a research chemical in form of a white powder or crystals.…”

Preparation and characterization of the ‘research chemical’ diphenidine, its pyrrolidine analogue, and their 2,2‐diphenylethyl isomers

“…[4][5][6] While it appeared that PCP-type substances did not attract much attention for decades, renewed interest was sparked since the mid-2000s within the recreational substance community, which resulted in a re-emergence of a number of PCP-based substances predominantly encountered as research chemicals available from online vendors. [7] Methoxetamine (2-(ethylamino)-2-(3-methoxyphenyl)cyclohexan-1-one, MXE, Figure 1), which may be considered as an invention conceived and developed from within the recreational drug community, began to appear more widely in 2010 and attracted some F o r P e e r R e v i e w 3 form of popularity amongst users who showed interest in ketamine and arylcyclohexylamine-type substances. [7] In the UK, methoxetamine and a range of associated substances based on the 1-phenylcyclohexanamine and 2-amino-2-phenylcyclohexanone template became subject to legislative control in early 2013 using a set of generic definitions, thus, impacting on commercial availability of these substances.…”

“…[7] Methoxetamine (2-(ethylamino)-2-(3-methoxyphenyl)cyclohexan-1-one, MXE, Figure 1), which may be considered as an invention conceived and developed from within the recreational drug community, began to appear more widely in 2010 and attracted some F o r P e e r R e v i e w 3 form of popularity amongst users who showed interest in ketamine and arylcyclohexylamine-type substances. [7] In the UK, methoxetamine and a range of associated substances based on the 1-phenylcyclohexanamine and 2-amino-2-phenylcyclohexanone template became subject to legislative control in early 2013 using a set of generic definitions, thus, impacting on commercial availability of these substances. [8] A feature increasingly observed with a range of research chemicals and so-called new psychoactive substances is the expansion from the structurally-based search to the exploration of novel structures with equivalent pharmacological targets as banned substances.…”

“…Although these analogues have been introduced to the market, the availability of analytical data has been less abundant. [7,19] For this reason, it was decided to prepare the two corresponding pyrrolidine derivatives of these diphenylethylamines, i.e. 1-(1,2-diphenylethyl)pyrrolidine (1,2-DEPy) (3) and 1- (2,2-21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 F o r P e e r R e v i e w 4 diphenylethyl)pyrrolidine (2,2-DEPy) (4), respectively.…”

2-oxo-PCE: ketamine analogue on the streets

“…Historically, it was synthesised in 1962 in an attempt to develop a short-acting phencyclidine derivative, a project that culminated in the discovery of ketamine. 4 Drugs of this class are known to possess N-methyl-D-aspartate receptor antagonist activity with variable effects towards other receptors, 4 resulting in dissociative effects clinically. The use of this drug has been recently reported in Germany.…”