Methoxetamine

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.^[1] 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 ^[4], despite being stronger and having a longer duration. ^[5]

Because of its structural similarity to 3-HO-PCP, it was falsely believed to carry opioid properties.^[6] 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.^[1]

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 ☠.

Experience reports

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:

• Erowid Experience Vaults: MXE

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.

Dangerous interactions

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.
• 2C-T-x
• 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.
• ΑMT
• 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.
• Tramadol

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.^[7]

• Austria: Since June 26, 2019, MXE is illegal to possess, produce and sell under the SMG. (Suchtmittelgesetz Österreich)^[8]
• Brazil: Possession, production and sale is illegal as it is listed on Portaria SVS/MS nº 344 ^[9]
• Canada: Health Canada declared MXE a controlled substance, citing it as "considered an analogue of ketamine."^[10] The possession, production, and sale are illegal.
• Cyprus: Methoxetamine was listed in the drug control law in 2012.^[11]
• Denmark: Methoxetamine is covered by the Executive Order on Euphoriant Substances.^[11]
• France: Methoxetamine was added to the list of illicit substances on August 5, 2013.^[11]
• Germany: MXE is controlled under BtMG Anlage I, making it illegal to manufacture, import, possess, sell, or transfer it without a license.^[12]
• Italy: According to the table of drugs, MXE has been illegal in Italy since 2016.^[13]
• Japan: MXE is a narcotic drug in Japan effective June 26th, 2016.^[14]
• Netherlands: It is illegal to possess, produce, trasnport, import, export, or sell MXE.^[15]
• Russia: It is illegal to possess, produce, or sell MXE.^{[citation needed]}
• Slovenia: MXE is a controlled substance (Official Gazette of RS No. 62/2013).^[11]
• Sweden: Methoxetamine is controlled under the Narcotic Drugs Control Act (SFS 1992-860) and the Narcotic Drugs Control Ordinance (SFS 1994:1554).^[11]
• Switzerland: MXE is a controlled substance specifically named under Verzeichnis D.^[16]
• Turkey: Methoxetamine is regulated under the Law on Control of Narcotics no. 2313.^[11]
• United Kingdom: MXE is a Class B drug.^{[citation needed]}
• United States: MXE is a schedule 1 controlled substance.^[17]

• Responsible use
• Research chemical
• Dissociatives
• Arylcyclohexylamines
• Ketamine
• 3-MeO-PCP

• MXE (Wikipedia)
• MXE (Erowid Vault)
• MXE (Isomer Design)

Discussion

• The Big & Dandy Methoxetamine Thread (Bluelight)

• 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