MXE

Methoxetamine, usually abbreviated MXE, is a synthetic dissociative drug of the arylcyclohexylamine class — the same chemical family as ketamine and PCP. It was designed as a ketamine analogue and first appeared for sale online around 2010, marketed as a "research chemical" and sometimes as a "legal" or bladder-friendly ketamine substitute (nicknames include Mexxy and M-ket). It is usually a white or off-white powder that people swallow or snort. Because it emerged from the unregulated designer-drug market rather than clinical development, far less is known about it than about ketamine.

MXE works mainly as an NMDA-receptor antagonist — it blocks the NMDA glutamate receptor at the same site targeted by ketamine, PCP, and the medicine memantine, interrupting the signalling that normally binds sensory experience together and producing the characteristic "dissociative" state. It is chemically very close to ketamine, differing by the addition of a methoxy group, and it also inhibits the reuptake of serotonin (a feature ketamine largely lacks) and increases dopamine activity in the brain's reward pathway. Its dissociative effects are reported to be more potent and longer-lasting than ketamine's, which contributes to its risks.

MXE produces ketamine-like dissociative effects: a sense of detachment from the body and surroundings, altered perception of time and space, dream-like or trance states, and at higher doses an intense immersive "hole" in which contact with the environment is lost. Users report the effects come on more slowly and last longer than ketamine. Stimulation, euphoria, and antidepressant-like mood lift are also described. Unwanted effects include confusion, loss of coordination, nausea, raised heart rate and blood pressure, and anxiety.

MXE has documented abuse potential and has been implicated in poisonings and deaths. Because it is more potent and longer-lasting than ketamine, and because powders vary in strength, it is easy to take too much; overdose can bring on severe dissociation, agitation, a dangerously raised heart rate and blood pressure, and loss of motor control that raises the risk of injury. Its stimulation of the brain's reward pathway gives it real potential for compulsive use and dependence, with tolerance building over time. Combining it with other depressants (alcohol, benzodiazepines, opioids) or with stimulants is especially dangerous. As an NMDA antagonist it shares cross-tolerance with other dissociatives such as ketamine and 2-FDCK.