I am very confused as to why it seems to be generally assumed that
methoxetamine acts on
serotonin receptors, and accordingly is contraindicated with other serotonergic
drugs.
I have not encountered any legitimate evidence that
MXE is serotonergic, and it does not make any sense to me based on its chemical structure. MXE is a NMDA antagonist that seems to have significant effect on
dopamine release in the brain, consistent with structurally similar compounds like
ketamine, PCE and
PCP. I've seen a lot of speculation that MXE also has some effect on u-
opioid receptors, although have not seen any solid evidence to back this up.
Ketamine, the closest chemical relative to MXE, to my knowledge has no effect on serotonin receptors, and combining ketamine with serotonin-releasing chemicals like
MDMA is common and (relatively) safe. The only
dissociatives that have a proven effect on serotonin in the brain are
DXM and maybe some of the related "-orphans". MXE differs significantly in chemical structure to these drugs, as does ketamine, PCP, etc. They are essentially a different class of dissociatives entirely.
It seems the assumption that MXE is serotonergic stems from the deadly
MDAI/MXE overdose combo that occurred in the UK, as well as a number of users reporting subjective effects from MXE combos that they claim to be
serotonin syndrome, but which seem much more likely to be instances of psychological freakouts over the side effects of the combo than actual serotonin syndrome.
With respect to the UK overdose:
-The dose of MDAI that the individual injected (400mg?) was probably high enough to cause serotonin syndrome on its own, particularly if the guy was sensitive to serotonergic drugs.
-From my research, it has not been confirmed that serotonin syndrome was the cause of death.
-We don't know what other drugs or medications the individual took in the days leading up to the overdose.
As MDMA and related serotonergic chemicals (MDA, 5/6-APB, etc.) are also
stimulants that affect dopamine, and MXE seems to have a strong dopaminergic effect, adverse side effects from the combos could be the result of excessive dopamine in the brain causing paranoia and panic attacks. Also the dissociation of mind and body makes hypochondria a common experience. This seems to me much more likely than any adverse serotonin-related reaction.
My bunny rabbit has extensive experience with MXE, MDxx, 6-APB, and a wealth of other
psychedelic chemicals. She is very familiar with what a serotonergic
drug experience feels like in the mind and body, and in her opinion the effects of MXE bear no similarity to the effects of serotonergics like MDxx, 6-APB, 2-CE, etc. The biggest indicator that MXE is not serotonergic, apart from its chemical makeup, is its lack of stomach/GI symptoms. Serotonergic drugs, whether releasers like MDxx, reuptake inhibitors like SSRIs, or even the serotonin precursor 5-HTP tend cause a wealth of GI symptoms (nausea, constipation, diarrhea, suppressed or increased appetite, etc.). The majority of serotonin receptors are in the digestive system, not in the brain, and the brain's serotonin system is also closely intertwined with the digestive system. What this means is you can't significantly alter serotonin in the brain without ramifications in the stomach and intestines, and the higher the dose of a serotonergic drug, the heavier this "body load" tends to be. However, in my bunny rabbit's experience, large doses of MXE cause no noticeable effects on her (very sensitive) stomach and GI tract. In fact, one of her favorite aspects of MXE is its lack of stomach and GI effects, as she frequently suffers from gastrointestinal pains that make
phenethylamines, DXM, and other serotonergics (particularly mushrooms) very difficult to handle. With MXE, she can take large doses even on a full stomach or while experiencing cramps, and the drug has a neutral impact or even improves the stomach pain via dissociation. She has also reported no comparable impact on body temperature and perspiration with MXE compared to serotonergics.
Is there ANY sound evidence to justify treating MXE as a serotonergic drug, apart from internet rumors and hearsay? My bunny rabbit and I are certainly not suggesting it is safe to mix MXE with other chemicals until more is known about its precise mechanism of action, but we are both frustrated by the overwhelming online consensus that MXE increases risk of serotonin syndrome when there seems to be no scientific grounds. In our opinion MXE's effects should be assumed to be strictly glutaminergic and dopaminergic until scientifically proven otherwise.
