Methoxetamine (MXE)

A ketamine-like dissociative designer drug (methoxetamine, MXE) used recreationally; not FDA-approved for medical use.

psilodex.org/m/methoxetamine · data v2026.10.05

Clinical contraindication: None listed; No label contraindication covering psilocybin was found. This is not a finding that the combination has been shown to be without risk.
Psilocybin evidence: No psilocybin data
Half-life: Not stated in label or references

Named in state rules?

Not namedColorado

Not namedOregon

PendingNew Mexico

Cite asPsilodex, “Methoxetamine (MXE)”, v2026.10.05. psilodex.org/m/methoxetamine

Clinical data and state rules are separate facts. Both are shown; neither is a decision.

What it is used for

FDA status

Not FDA-approved

Availability

Unregulated novel psychoactive substance; not FDA-approved

01 Interaction with psilocybin

Not studied with psilocybin; it is a ketamine-like drug, so added dissociation, confusion and blood pressure rise are possible.

Detail Methoxetamine is a ketamine analog that binds the NMDA receptor (a glutamate receptor). In lab binding studies, it also binds the serotonin transporter (Roth 2013). It has not been studied with psilocybin; combined use may add dissociation, confusion and blood pressure rise. Also, poisons-center reports describe stimulant, reduced-consciousness, dissociative and cerebellar (balance and coordination) presentations. They also describe frequent acute mental health disturbances (Hill 2013). Its use is associated with high blood pressure (Thornton 2017). Sources [1][2][3][4]

Human data with psilocybin: No psilocybin data; based on how it works and its label

Evidence types on this record

No psilocybin dataNo psilocybin data: no human data with psilocybin or another classic psychedelic; the text draws on the medication's own pharmacology and its label or reference facts

02 Pharmacology relevant to psilocybin

4 listed (1 possible) · counted on reports

Dissociative (NMDA antagonist): Blocks NMDA receptors and can cause dissociation: feeling detached from the body or surroundings. Effects can add to psilocybin’s. Sources [1]
Psychiatric reactions: The label or source warns of psychiatric effects such as psychosis, mania, hallucinations, suicidal thoughts or severe mood or behavior changes. Psilocybin can also bring up strong emotions, so these warnings are relevant to screening. Sources [2]
Raises blood pressure or heart rate: Raises blood pressure or heart rate. Psilocybin raises both for several hours, so the effects can add. Sources [3]
SerotonergicPossible: Increases serotonin activity, for example by blocking its reuptake or releasing it. Psilocybin acts on serotonin receptors, so effects can add together. With antidepressant use, the psilocybin response can be weaker.Possible: The source describes the effect as small, seen only in laboratory or animal studies, or theoretical. Sources [1]

03 State rules

Plain-language summary · official text governs

CO4 CCR 755-1

Not named

No provision names this medication or its class.

Colorado · checked 2026-10-04

OROAR 333-333

Not named

No provision names this medication or its class.

Oregon · checked 2026-10-04

NM7.35.3 NMAC (proposed)

Pending

New Mexico's clinical rules (proposed 7.35.3 NMAC) are not final. No provision naming this medication has been found.

New Mexico · checked 2026-10-04

04 Conditions to ask about

None linked

No condition named in state rules is linked to this medication.

05 Sources

Roth BL, Gibbons S, Arunotayanun W, et al. The ketamine analogue methoxetamine and 3- and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor. PLoS One 2013;8(3):e59334. — Dissociative (NMDA antagonist): Abstract "were all high affinity ligands for the PCP-site on the glutamate NMDA receptor" | Serotonergic: Abstract "In addition methoxetamine and PCP and its analogues displayed appreciable affinities for the serotonin transporter"
Hill SL, Harbon SCD, Coulson J, et al. Methoxetamine toxicity reported to the National Poisons Information Service: clinical characteristics and patterns of enquiries. Emerg Med J 2014;31(1):45–47. — Psychiatric reactions: Abstract "typical toxidromes were of stimulant (36%), reduced consciousness (17%), dissociative (11%) and cerebellar (6.4%) types, but also particularly featured acute disturbances in mental heath (43%)."
Thornton S, Lisbon D, Lin T, Gerona R. Beyond ketamine and phencyclidine: analytically confirmed use of multiple novel arylcyclohexylamines. J Psychoactive Drugs 2017;49(4):289–293. — Raises blood pressure or heart rate: Abstract (Conclusion) "Methoxetamine use is associated with altered mental status, ataxia, and hypertension."
Zanda MT, Fadda P, Chiamulera C, Fratta W, Fattore L. Methoxetamine, a novel psychoactive substance with serious adverse pharmacological effects: a review of case reports and preclinical findings. Behav Pharmacol 2016;27(6):489–496. — Abstract: "MXE is an arylcyclohexylamine with a chemical structure analogous to ketamine and phencyclidine, and similar noncompetitive glutamate N-methyl D-aspartate receptor antagonist properties."

Record history

v2026.10.02First published.
2026-10-04Last reviewed against its sources.

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