MXE is reported to have a similar effect to ketamine.[1] It was often believed to possess opioid properties due to its structural similarity to 3-HO-PCP,[4] but this assumption is not supported by data, which shows insignificant affinity for the μ-opioid receptor by the compound.[6] Recreational use of MXE has been associated with hospitalizations from high and/or combined consumption in the US and UK.[7][8][9] Acute reversible cerebellar toxicity has been documented in three cases of hospital admission due to MXE overdose, lasting for between one and four days after exposure.[8]
MXE was designed in part in an attempt to avoid the urotoxicity associated with ketamine abuse; it was thought the compound's increased potency and reduced dose would limit the accumulation of urotoxic metabolites in the bladder.[4][5] Like ketamine, MXE has been found to produce bladder inflammation and fibrosis after high dose, chronic administration in mice, although the dosages used were quite large.[10] Reports of urotoxicity in humans have yet to appear in the medical literature.[4]
MXE hydrochloride is soluble in ethanol up to 10 mg/ml at 25 °C.[17]
Detection in body fluids
A forensic standard of MXE is available, and the compound has been posted on the Forendex website of potential drugs of abuse.[18]
History
The qualitative effects of MXE were first described online in May 2010 and the compound became commercially available on a small scale in September 2010.[3][4] By November the use and sale of the MXE had increased enough for it to be formally identified by the European Monitoring Centre for Drugs and Drug Addiction. By July 2011, the EMCDDA had identified 58 websites selling the compound at a cost of 145–195 euros for 10 grams.[19]
Society and culture
Methoxetamine powder.
Media coverage
Mixmag reported in January 2012, that people in the dance music and clubbing community have given MXE the slang name 'roflcoptr'.[20]Vice commented that it was likely that the phrase will only be used by "the same politicians, parents and journalists" who called mephedrone 'meow meow'.[21] After being called mexxy in UK Home Office press releases, the media adopted the name.[9][22]
A literature review was published in March 2012 which looked at scientific literature and information on the web. It concluded that "the online availability of information on novel psychoactive drugs, such as MXE, may constitute a pressing public health challenge. Better international collaboration levels and novel forms of intervention are necessary to tackle this fast-growing phenomenon."[23]
Legal status
Brazil
MXE became classified as a narcotic in Brazil in February 2014.[24]
Canada
As of January 2010 MXE is a controlled substance in Canada.[25]
China
As of October 2015 MXE is a controlled substance in China.[26]
European Union
On 16 June 2014, the European Commission proposed that MXE be banned across the European Union, subjecting those in violation to criminal sanctions. This is following the procedure for risk-assessment and control of new psychoactive substances set up by the council: Decision 2005/387/JHA.[27]
Israel
MXE became classified as an illegal narcotic in Israel in May 2012.[28][29]
MXE became classified as a narcotic in Sweden in late February 2012.[34]
Switzerland
MXE has been illegal in Switzerland since December 2011.[35]
United Kingdom
Prior to March 2012, MXE was not controlled by the UK's Misuse of Drugs Act.[36] In March 2012, the Home Office referred MXE to the Advisory Council on the Misuse of Drugs for possible temporary controlling under the powers given in the Police Reform and Social Responsibility Act 2011.[37][38] The ACMD gave their advice on 23 March, with the chair commenting that "the evidence shows that the use of methoxetamine can cause harm to users and the ACMD advises that it should be subject to a temporary class drug order."[39] In April 2012, MXE was placed under temporary class drug control, which prohibited it's import and sale for 12 months.[40]
Theresa May commented in her reply to the ACMD that "the next step in this process is for the ACMD to undertake a full assessment of MXE for consideration for its permanent control under the 1971 Act." She goes on to say that she hopes the ACMD will do this as a part of the review of ketamine, "including its analogues" and that this review will be completed "within the 12 months from the making of the current order".[41]
On 18 October 2012 the ACMD released a report about MXE, saying that the "harms of methoxetamine are commensurate with Class B of the Misuse of Drugs Act (1971)", despite the fact that the act does not classify drugs based on harm. 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 arylcyclohexamines.
MXE ceased to be covered by the temporary prohibition on 26 February 2013, when it became classified as a Class B drug.[42]
United Nations
MXE was made a schedule II drug in November 2016.[43]
^ abcdefMorris 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. PMID24678061.
^Wood DM, Davies S, Puchnarewicz M, Johnston A, Dargan PI (May 2012). "Acute toxicity associated with the recreational use of the ketamine derivative methoxetamine". European Journal of Clinical Pharmacology. 68 (5): 853–856. doi:10.1007/s00228-011-1199-9. PMID22205276. S2CID4084801.
^ abShields JE, Dargan PI, Wood DM, Puchnarewicz M, Davies S, Waring WS (June 2012). "Methoxetamine associated reversible cerebellar toxicity: three cases with analytical confirmation". Clinical Toxicology. 50 (5): 438–440. doi:10.3109/15563650.2012.683437. PMID22578175. S2CID40114091.
^Dargan PI, Tang HC, Liang W, Wood DM, Yew DT (March 2014). "Three months of methoxetamine administration is associated with significant bladder and renal toxicity in mice". Clinical Toxicology. 52 (3): 176–180. doi:10.3109/15563650.2014.892605. PMID24580056. S2CID34284740.
^Roth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
^ abcdeZanda MT, Fadda P, Chiamulera C, Fratta W, Fattore L (September 2016). "Methoxetamine, a novel psychoactive substance with serious adverse pharmacological effects: a review of case reports and preclinical findings". Behavioural Pharmacology. 27 (6): 489–496. doi:10.1097/FBP.0000000000000241. PMID27128862. S2CID3657823.
^Hofer KE, Grager B, Müller DM, Rauber-Lüthy C, Kupferschmidt H, Rentsch KM, Ceschi A (July 2012). "Ketamine-like effects after recreational use of methoxetamine". Annals of Emergency Medicine. 60 (1): 97–99. doi:10.1016/j.annemergmed.2011.11.018. PMID22237166.
^Botanas CJ, Bryan de la Peña J, Custodio RJ, Joy Dela Peña I, Kim M, Woo T, et al. (November 2017). "Methoxetamine produces rapid and sustained antidepressant effects probably via glutamatergic and serotonergic mechanisms". Neuropharmacology. 126: 121–127. doi:10.1016/j.neuropharm.2017.08.038. PMID28867363. S2CID30870722.
^Horsley RR, Lhotkova E, Hajkova K, Jurasek B, Kuchar M, Palenicek T (September 2016). "Detailed pharmacological evaluation of methoxetamine (MXE), a novel psychoactive ketamine analogue-Behavioural, pharmacokinetic and metabolic studies in the Wistar rat". Brain Research Bulletin. 126 (Pt 1): 102–110. doi:10.1016/j.brainresbull.2016.05.002. PMID27155360. S2CID3955788.
^Beaumont-Thomas B (18 January 2012). "Methoxetamine is a new chemical analogue of ketamine. It's legal, it's cheap and it's trippy as hell - but is it safe?". Mixmag. No. 249. London, UK. p. 60.
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