|Summary sheet: Methoxetamine|
|Common names||Methoxetamine, MXE, Mexxy|
|Routes of Administration|
3-MeO-2'-Oxo-PCE (commonly known as Methoxetamine, MXE, Mexxy, among others) is a dissociative substance of the arylcyclohexylamine class that produces ketamine-like dissociative effects when administered. It is structurally related to ketamine, PCE, and 3-MeO-PCP.
MXE was originally developed through the use of intelligent drug design, as a potential treatment for Phantom Limb Syndrome among other ailments.
MXE had no documented history of human usage until it was first identified by the European Monitoring Centre for Drugs and Drug Addiction in November 2010. By July 2011, they had identified 58 websites selling the compound at the cost of 145–195 euros for 10 grams. Once highly popular, it is now thought to be extinct on the online research chemical market due to the global ban of the drug.
Limited data exists about the pharmacological properties, metabolism, and toxicity of MXE in humans, and it has a limited history of human use. It is highly advised to use harm reduction practices if using this substance.
Methoxetamine, or (RS)2-(3-methoxyphenyl)-2-(ethylamino)cyclohexanone, is classed as an arylcyclohexylamine. Arylcyclohexylamines are named for their structures which include a cyclohexane ring bound to an aromatic ring along with an amine group.
MXE contains a phenyl ring with a methoxy (CH3-O-) substituent at R3 bonded to a cyclohexane ring substituted at R2 with an oxo group (cyclohexanone). Bound to the same location (R1) of the cyclohexanone ring is an amino ethyl chain -N-CH2CH3.
MXE is a chiral molecule that is often produced as a racemate, although batches of its stereo-exclusive isomers have occasionally been produced and distributed.
MXE acts as a non-competitive NMDA receptor antagonist and serotonin-reuptake inhibitor.</ref> NMDA receptors allow for electrical signals to pass between neurons in the brain and spinal column; for the signals to pass, the receptor must be open. Dissociatives close the NMDA receptors by blocking them. This disconnection of neurons leads to loss of feeling, difficulty moving, and eventually an almost identical equivalent of the famous “k-hole.” MXE was reported to be similar to ketamine , despite being stronger and having a longer duration. 
Because of its structural similarity to 3-HO-PCP, it was falsely believed to carry opioid properties. This claim cannot be supported by actual data, instead showing only insignificant affinity for the µ-opioid receptor by the substance itself, although in-vivo metabolites could yield different effects.
Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.
It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.
- Spontaneous bodily sensations - The MXE "body high" can be described as a sharp, pleasurable tingling sensation which is location specific to the hands, feet, and head.
- Perception of bodily lightness - This creates the sensation that the body is floating and has become entirely weightless. This effect is strangely stimulating and encourages physical activities at low to moderate doses by making the body feel light and effortless to move.
- Motor control loss - A loss of gross and fine motor control alongside balance and coordination is prevalent within MXE and becomes especially strong at higher doses. This means that one should be sitting down before the onset (unless experienced) in the case of falling over and injuring oneself.
- Spatial disorientation
- Tactile suppression - This partially to entirely suppresses one's sense of touch, creating feelings of numbness within the extremities. It is responsible for the anesthetic properties of this substance.
- Pain relief
- Physical autonomy
- Dizziness - Although uncommon, some people report dizziness under the influence of MXE.
- Nausea - High dose MXE experience can sometimes result in nausea and vomiting at the peak of the trip. For most people, this is surprisingly not as unpleasant as they would initially expect due to the accompanying detachment from the physical senses.
- Optical sliding
- Orgasm suppression & Orgasm enhancement - Orgasm enhancement can sometimes also be present, even at higher doses, although this effect is not reliable.
- Tactile disconnection
- Visual disconnection - This eventually results in MXE's equivalent of the "k-hole" or more specifically, holes, spaces and voids alongside of structures.
- Consciousness disconnection
- Visual acuity suppression
- Double vision - This component is prevalent at moderate to heavy doses and makes reading impossible unless one closes an eye.
- Pattern recognition suppression - This effect generally occurs at higher doses and makes one unable to recognize and interpret perceivable visual data.
- Frame rate suppression
The visual geometry found within MXE can be described as very dark and bland when compared to that of ketamine or DXM and often consists of many tiny interlocking and woven lines. It does not extend beyond level 4 and can be comprehensively described through its variations as simplistic in complexity, algorithmic in style, synthetic in feel, unstructured in organization, dimly lit in lighting, multicolored in scheme, glossy in shading, soft in edges, small in size, slow in speed, smooth in motion, equal in rounded and angular corners, immersive in-depth and consistent in intensity.
High doses entering the "hole" can yield a white glow visual phenomena like ketamine.
At high doses, MXE can produce a full range of high level hallucinatory states in a fashion that is less consistent and reproducible than that of many other commonly used psychedelics. These effects include:
- Internal hallucination (autonomous entities; settings, sceneries, and landscapes; perspective hallucinations and scenarios and plots) - In comparison to other dissociatives, this effect can occur at heavy doses, but is considerably less common than the same effect found within psychedelics and deliriants. It can be comprehensively described through its variations as delirious in believability, fixed in style, equal in new experiences and memory replays in content, autonomous in controllability and solid in style.
- External hallucination (autonomous entities; settings, sceneries, and landscapes; perspective hallucinations and scenarios and plots) - In comparison to other dissociatives, this effect can occur at heavy doses, but is extremely infrequent in comparison to the same effect found within deliriants. It can be comprehensively described through its variations as delirious in believability, autonomous in controllability and solid in style. The most common theme for this effect to follow is one of experiencing and talking to friends when they are not actually present.
The general head space of MXE is often described as particularly euphoric and clear-headed in comparison to that of DXM and ketamine. The specific cognitive effects can be broken down into several separate subcomponents which are listed and described below:
- Anxiety suppression
- Cognitive euphoria
- Compulsive redosing
- Conceptual thinking
- Creativity enhancement
- Decreased libido - This is not experienced in all environments, as increased libido may also be experienced especially at lower dosage ranges.
- Déjà vu
- Dream potentiation
- Ego death
- Immersion enhancement
- Increased music appreciation
- analysis suppression
- Mania - This can potentially occur with users who are compulsively and regularly consuming large amounts of this compound. This effect occurs less often on MXE than it does on more stimulating dissociatives such as 3-MeO-PCP or 2-Oxo-PCE.
- Memory suppression
- Personal meaning enhancement
- Thought deceleration
- Time distortion
Anecdotal reports which describe the effects of this compound within our experience index include:
- Experience: 40mg 5-MeO-DMT (oral) + 40mg MXE (oral) - Untitled
- Experience:MXE: 37.5 mg - Calm and Cloudy Bliss
Additional experience reports can be found here:
Toxicity and harm potential
The toxicity and long-term health effects of recreational MXE use do not seem to have been studied in any scientific context and the exact toxic dosage is unknown.
This is because MXE is a research chemical with a very brief history of human usage.
Anecdotal reports from those who have tried MXE suggests that there do not seem to be any negative health effects attributed to simply trying this substance at low to moderate doses by itself and using it sparingly (but nothing can be completely guaranteed). Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.
It is strongly recommended that one use harm reduction practices when using this substance.
Dependence and abuse potential
As with other NMDA receptor antagonists, the chronic use of MXE can be considered moderately addictive with a high potential for abuse and is capable of producing psychological dependence among certain users. When addiction has developed, cravings and withdrawal effects may occur if a person suddenly stops their usage.
Tolerance to many of the effects of MXE develops with prolonged and repeated use. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about 3 - 7 days for the tolerance to be reduced to half and 1 - 2 weeks to be back at baseline (in the absence of further consumption).
MXE presents cross-tolerance with all dissociatives, meaning that after the consumption of MXE all dissociatives will have a reduced effect.
Urinary tract effects
In terms of its long-term health effects when used repeatedly and excessively for extended periods of time, MXE seems to exhibit almost identical bladder and urinary tract problems to those found within ketamine, but to a lesser extent. This is because MXE is four times as potent as ketamine, so significantly less of drug needs to be consumed. Symptoms of ketamine-induced cystitis can become extremely serious and can be described as:
- Urinary frequency - Urinary frequency is the need to empty the bladder every few minutes.
- Urinary urgency - This can be described as a sudden, compelling need to urinate.
- Urinary pressure - This is experienced as a constant sensation of fullness in the bladder that is unrelieved by urination.
- Pelvic and bladder pain - Pain can develop suddenly and severely, particularly as the bladder fills with urine.
- Hematuria - Hematuria is visible blood in the urine.
- Incontinence - This is the leakage of urine.
All of these, however, can easily be avoided by simply not using MXE on a daily or even weekly basis and manually limiting one's usage of the substance.
Warning: Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).
Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.
- DOx - As an NMDA antagonist MXE potentiates DOx which can be unpleasantly intense.
- 25x-NBOMe - As an NMDA antagonist MXE potentiates NBOMes which can be unpleasantly intense.
- PCP - There are no reports available about this combination.
- Amphetamines - Risk of tachycardia, hypertension, and manic states.
- MDMA - There have been reports of risky serotonergic interactions when the two are taken at the same time, but MXE taken to the end of an MDMA experience does not appear to cause the same issues.
- Cocaine - Stimulants taken with MXE can lead to hypermanic states much more easily, especially if sleep is avoided.
- Benzodiazepines - Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. Place affected patients in the recovery position to prevent vomit aspiration from excess.
- SSRIs - Depending on the SSRI this combination can be unpredictable.
- MAOIs - MAO-B inhibitors appear to increase the potency of MXE. MAO-A inhbitors have some negative reports associated with the combination but there isn't much information available.
- Alcohol - There is a high risk of memory loss, vomiting and severe ataxia from this combination.
- GHB - Both substances cause ataxia and bring a risk of vomiting and unconsciousness. If the patient falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position.
- GBL - Both substances cause ataxia and bring a risk of vomiting and unconsciousness. If the patient falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position.
- Opioids - This combination can potentiate the effects of the opioid.
In September 2014, the European Council decided that methoxetamine shall be subjected by the Member States to control measures and criminal penalties by October 2, 2015.
- Austria: Since June 26, 2019, MXE is illegal to possess, produce and sell under the SMG. (Suchtmittelgesetz Österreich)
- Brazil: Possession, production and sale is illegal as it is listed on Portaria SVS/MS nº 344 
- Canada: Health Canada declared MXE a controlled substance, citing it as "considered an analogue of ketamine." The possession, production, and sale are illegal.
- Cyprus: Methoxetamine was listed in the drug control law in 2012.
- Denmark: Methoxetamine is covered by the Executive Order on Euphoriant Substances.
- France: Methoxetamine was added to the list of illicit substances on August 5, 2013.
- Germany: MXE is controlled under BtMG Anlage I, making it illegal to manufacture, import, possess, sell, or transfer it without a license.
- Italy: According to the table of drugs, MXE has been illegal in Italy since 2016.
- Japan: MXE is a narcotic drug in Japan effective June 26th, 2016.
- Netherlands: It is illegal to possess, produce, trasnport, import, export, or sell MXE.
- Russia: It is illegal to possess, produce, or sell MXE.
- Slovenia: MXE is a controlled substance (Official Gazette of RS No. 62/2013).
- Sweden: Methoxetamine is controlled under the Narcotic Drugs Control Act (SFS 1992-860) and the Narcotic Drugs Control Ordinance (SFS 1994:1554).
- Switzerland: MXE is a controlled substance specifically named under Verzeichnis D.
- Turkey: Methoxetamine is regulated under the Law on Control of Narcotics no. 2313.
- United Kingdom: MXE is a Class B drug.
- United States: MXE is not illegal, however, if it is sold with the intention for human consumption (such as in capsules) it becomes illegal to possess under the Federal Analogue Act. This is avoided by placing the label "not for human consumption" on the container of the chemical.
- 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. https://doi.org/10.1002/dta.1620
- Halberstadt, A. L., Slepak, N., Hyun, J., Buell, M. R., & Powell, S. B. (2016). The novel ketamine analog methoxetamine produces dissociative-like behavioral effects in rodents. Psychopharmacology, 233(7), 1215-1225. https://doi.org/10.1007/s00213-016-4203-3
- ↑ 1.0 1.1 1.2 Advisory Council on the Misuse of Drugs (ACMD) Methoxetamine report, 2012
- ↑ Morris, H. (2011), Interview with a Ketamine Chemist
- ↑ Online sales of new psychoactive substances/‘legal highs’ | http://www.emcdda.europa.eu/attachements.cfm/att_143801_EN_SnapshotSummary.pdf
- ↑ Kjellgren, A., Jonsson, K. (1 July 2013). "Methoxetamine (MXE) – A Phenomenological Study of Experiences Induced by a "Legal High" from the Internet". Journal of Psychoactive Drugs. 45 (3): 276–286. doi:10.1080/02791072.2013.803647. ISSN 0279-1072.
- ↑ Coppola, M., Mondola, R. (October 2012). "Methoxetamine: From drug of abuse to rapid-acting antidepressant". Medical Hypotheses. 79 (4): 504–507. doi:10.1016/j.mehy.2012.07.002. ISSN 0306-9877.
- ↑ Morris, H., Wallach, J. (July 2014). "From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs: PCP to MXE". Drug Testing and Analysis. 6 (7–8): 614–632. doi:10.1002/dta.1620. ISSN 1942-7603.
- ↑ "Council Implementing Decision on subjecting 25I-NBOMe, AH-7921, MDPV and methoxetamine to control measures". Official Journal of the European Union. Office for Official Publications of the European Communites (published October 1, 2014). September 25, 2014. pp. 22–26. OCLC 52224955. L 287.
- ↑ https://www.ris.bka.gv.at/Dokumente/BgblAuth/BGBLA_2019_II_167/BGBLA_2019_II_167.pdfsig
- ↑ http://portal.anvisa.gov.br/documents/10181/3115436/%281%29RDC_130_2016_.pdf/fc7ea407-3ff5-4fc1-bcfe-2f37504d28b7
- ↑ "STATUS DECISION OF CONTROLLED AND NON-CONTROLLED SUBSTANCE(S)", https://web.archive.org/web/20160409135922/http://isomerdesign.com/Cdsa/HC/StatusDecisions/A-2013-00235%20-%20PDFs/C-Methoxetamine-2011-01-31.pdf. Retrieved January 24th, 2017.
- ↑ 11.0 11.1 11.2 11.3 11.4 11.5 "EMCDDA–Europol Joint Report on a new psychoactive substance: methoxetamine (2-(3-methoxyphenyl)-2-(ethylamino)cyclohexanone)" (PDF). European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), Europol. January 2014: 14–15. doi:10.2810/28543. ISBN 978-92-9168-686-5. ISSN 1977-7868. Retrieved April 19, 2020.
- ↑ Anlage I BtMG - Einzelnorm
- ↑ http://www.salute.gov.it/imgs/C_17_pagineAree_3729_listaFile_itemName_0_file.pdf
- ↑ 新たに指定薬物４物質を麻薬に指定します（注意喚起）｜厚生労働省, 厚生労働省 [Ministry of Health, Labour and Welfare (MHLW)]
- ↑ Koninkrijksrelaties, M. van B. Z. en, Opiumwet
- ↑ "Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien" (in German). Bundeskanzlei [Federal Chancellery of Switzerland]. Retrieved January 1, 2020.