Methoxetamine
Methoxetamine is a dissociative substance of the arylcyclohexylamine class, structurally related to ketamine and PCP.12 It was intentionally designed as a possible therapy for phantom limb syndrome and first appeared on grey markets in late 2010. MXE was noted for its ketamine-like dissociative effects with a pronounced psychedelic character. Once widely available as a research chemical, it is now considered largely extinct due to global bans on its production.
Contents
Dosage & Duration
Dosage
High doses can cause nausea and vomiting near the peak. Compulsive redosing has been reported and may lead to overdose.
Duration
Subjective Effects
Effects vary widely by individual, dose, and context.
Physical
Cognitive
The general head space of MXE is often described as particularly euphoric and clear headed in comparison to that of DXM and Ketamine.
Visual
Distortions
MXE exhibits a full array of dissociative distortions and alterations in visual perception.
Geometry
The visual geometry found within MXE can be described as very psychedelic when compared to that of Ketamine but not as complex as that of DXM. It does not extend beyond level 5 and can be comprehensively described as simplistic in complexity, algorithmic in style, synthetic in feel, unstructured in organization, dimly lit in lighting, multicoloured in scheme, glossy in shading, soft in edges, large in size, fast in speed, smooth in motion, equal in rounded and angular corners, immersive in depth and consistent in intensity.
Hallucinatory States
At high dosages, 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.
Suppressions
This substance does not enhance visual stimuli; instead it tends to degrade and decrease visual aptitude in a variety of ways.
Auditory
The auditory effects of MXE are common in their occurrence and exhibit a range of effects.
Reagent Testing
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Pharmacology
Pharmacodynamics
MXE acts primarily as a high-affinity NMDA receptor antagonist at the dizocilpine (MK-801) binding site (Ki = 257 nM). It also functions as a serotonin reuptake inhibitor with moderate affinity (Ki = 479 nM), while showing negligible activity at the dopamine and norepinephrine transporters (Ki > 10,000 nM). Despite this lack of direct dopamine transporter activity, MXE has been found to activate dopaminergic neurotransmission in the mesolimbic reward pathway, a property shared with other NMDA receptor antagonists. The compound shows insignificant direct affinity for the μ-opioid receptor. The (S)- and (R)-enantiomers appear to contribute differently to the overall profile, with the (S)-enantiomer showing potent NMDA receptor activity and the (R)-enantiomer primarily associated with serotonin reuptake inhibition.
Pharmacokinetics
Limited pharmacokinetic data is available for MXE. O-demethylation of the methoxy group has been identified as a metabolic pathway3, producing a hydroxylated metabolite that may possess enhanced NMDA receptor activity. In-vivo metabolites may exhibit pharmacological properties distinct from the parent compound, including possible opioid receptor activity.
Dangerous
Highest riskThese combinations are considered extremely harmful and should always be avoided. Reactions to these drugs taken in combination are highly unpredictable and have a potential to cause death.
Unsafe
AvoidThere is considerable risk of physical harm when taking these combinations, they should be avoided where possible.
Caution
Use cautionThese combinations are not usually physically harmful, but may produce undesirable effects, such as physical discomfort or overstimulation. Extreme use may cause physical health issues. Synergistic effects may be unpredictable. Care should be taken when choosing to use this combination.
Tolerance
Dissociatives (ketamine, PCP, DXM, and related compounds)
Harm Potential
Addiction & Dependence
Psychological
ModerateMXE is considered moderately addictive with a high potential for abuse and is capable of producing psychological dependence among certain users.4 Multiple reports describe it as 'more-ish' with tendencies toward compulsive redosing, and cases of daily habitual use have been documented across online communities.4
Physical
LowMXE does not appear to be physically addictive. However, when psychological dependence has developed, some withdrawal effects may occur upon sudden cessation of use.
Toxicity
Repeated heavy use over extended periods may cause bladder and urinary tract problems similar to those seen with ketamine, including urinary frequency, urgency, pelvic pain, and hematuria; MXE's higher potency means smaller doses are required, potentially reducing but not eliminating this risk with chronic abuse patterns.5
Acute reversible cerebellar toxicity has been documented in overdose cases, with symptoms lasting one to four days after exposure; this appears to be associated with high-dose or combined consumption rather than typical recreational use.6
Animal research suggests potential harmful effects on the cardiovascular system; individuals with pre-existing cardiovascular conditions should exercise particular caution.7
History & Culture
Design and Synthesis
Methoxetamine represents a deliberate exercise in rational drug design rather than accidental discovery.8 The compound was conceived by an anonymous chemist who sought to create a ketamine analogue with improved therapeutic…
Trip Reports
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Legality
International
1961 Convention: not internationally scheduled.
1971 Convention: not internationally scheduled.
1988 Convention: not internationally scheduled.
By Country
References
Source Pages
Citations
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- (2014). Risk Assessment Report of a new psychoactive substance: methoxetamine (2-(3-methoxyphenyl)-2-(ethylamino)cyclohexanone). European Monitoring Centre for Drugs and Drug Addiction. https://www.euda.europa.eu/system/files/media/publications/documents/775/TDAK14004ENN_480922.pdf1
- Markus R. Meyer, Martina Bach, Jessica Welter, Michael Bovens, Alain Turcant, & Hans H. Maurer. (2013). Ketamine-derived designer drug methoxetamine: metabolism including isoenzyme kinetics and toxicological detectability using GC-MS and LC-(HR-)MSn. Analytical and Bioanalytical Chemistry, 405(19), 6307–6321. https://doi.org/10.1007/s00216-013-7051-61
- (2013). Methoxetamine (MXE)--a phenomenological study of experiences induced by a "legal high" from the internet. Journal of Psychoactive Drugs, 45(3), 276–286. https://doi.org/10.1080/02791072.2013.80364712
- (March 2014). Three months of methoxetamine administration is associated with significant bladder and renal toxicity in mice. Clinical Toxicology, 52(3), 176–180. https://doi.org/10.3109/15563650.2014.89260512
- (June 2012). Methoxetamine associated reversible cerebellar toxicity: three cases with analytical confirmation. Clinical Toxicology, 50(5), 438–440. https://doi.org/10.3109/15563650.2012.68343712
- (May 2012). Acute toxicity associated with the recreational use of the ketamine derivative methoxetamine. European Journal of Clinical Pharmacology, 68(5), 853–856. https://doi.org/10.1007/s00228-011-1199-91
- (2011-02-11). Interview with a ketamine chemist: or to be more precise, an arylcyclohexylamine chemist. Vice Magazine. https://www.vice.com/en/article/interview-with-ketamine-chemist-704-v18n2/12345
- (2014). EMCDDA–Europol Joint Report on a new psychoactive substance: methoxetamine (2-(3-methoxyphenyl)-2-(ethylamino)cyclohexanone). European Monitoring Centre for Drugs and Drug Addiction and Europol. https://www.drugsandalcohol.ie/21300/1/EMCDDA-Europol_Joint_Report_Methoxetamine.pdf123
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Further Reading
Alcohol and Drug Foundation - MXE Facts
Anodyne.wiki Entry on MXE
DrugFacts UK - MXE Duration and Harms
Halberstadt AL, et al. - Novel Ketamine Analog Methoxetamine Produces Dissociative-Like Behavioral Effects in Rodents
Hi-Ground Harm-Reduction Leaflet
Hofer KE, et al. - Ketamine-Like Effects After Recreational MXE Use
Ketamine-like effects after recreational MXE use
Meyer MR, et al. - MXE Metabolism Including Isoenzyme Kinetics and Toxicological Detectability
Morris H - Interview with a Ketamine Chemist
MXE NMDA IC50 data
Pain Medicine - Self-Medication Case Report
Pain Medicine – self-medication case
Phenomenological study of MXE experiences
Roth BL, et al. - Detailed Pharmacological Evaluation of MXE
ScienceDirect: Topics - Methoxetamine Duration by Route
Wood DM, et al. - Reversible Cerebellar Toxicity Case Report
Zanda MT, et al. - MXE Pharmacokinetics and Metabolites Review
Automated synthesisInformation aggregated and synthesized using an autonomous workflow built by Josie Kins.
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