Methoxetamine metabolism and effects

[selivu]

I recently acquired some 'MXE' from a vendor. I tried 50mg and felt essentially nothing. In fact, I didn't feel any significant dissociation until 200mg, which should be fatal for most people. Obviously, the vendor may be unreliable and I might have been taking creatine, but my previous experiences with DXM and tramadol suggest I'm deficient in CYP2D6 (tramadol does nothing, DXM effects linger for days), so it's possible MXE isn't the active NMDA antagonist we thought. Instead, it might be the demethylated molecule (oxetamine or hydroxetamine) that is responsible for NMDA antagonism. Maybe?

 

[serotonin2A]

MXE binds to and blocks NMDA receptors in vitro, so it doesn't need to be metabolized to produce an effect.

The initial metabolic step in humans is reportedly N-deethylation, but it is also demethylated and hydroxylated. I suspect none of those metabolites would be more active then MXE.

 

[sekio]

200mg of MXE is not fatal for someone without a tolerance, but it's a "black out and do retarded stuff" dosage.

 

[St3ve]

Another option is that what you received from this vendor is another misc. dissociative with a higher dose range than MXE...

 

[dopamimetic]

Yeah, would agree to that real MXE definitely has strong effects on its own, in users without dissociative tolerance the active dose usually starts way below 20mg, with 20-30mg already being moderate-strong dissociative (the border stage where an experienced user is still able to act normally).

But - while this has been discussed many times before, afaik there is no answer yet and no studies of in-vivo action and metabolism have been done (?) - and usually the conclusion was that there is only one "MXE" and the subjectively felt differences were placebo or due to acquired tolerance, other factors etc..

Now, while I have believed in this myself for long time (or tried to do so- as the experts out there usually aren't wrong) - I am sure there are different forms of MXE. Be it enantiomers like with ketamine, or something resulting of differing synth routes, no clue.

I think that somewhere they said that the usual synth routes would give racemic MXE and it would be unlikely to have S-/R-MXE on the market. But the differences in effects I experienced (and these were reliable to reproduce over and over) fit quite well to that scheme:

- One heavily dissociating isomer with few or lacking serotonergic / opioid / ? action, but with a pronounced weird psychedelic effect rising above a certain dose. There are some similarities to Methoxphenidine. It is difficult to dose, stronger than the other form(s) and with a narrow "therapeutic range". Heavily stimulating, increased heartbeat, unable to sleep up to 10h or more after dosing.

While I was / am a huge fan of MXE, I don't like this form at all. The same with Methox-/Diphenidine. And S-Ketamine.

- One empathogenic, uplifting, anxiolytic isomer with serotonergic, opioid, possibly dopaminergic action. Becomes active also at around 10mg but is easier to dose and has a wider "therapeutic range". This is what makes all the magic of Methoxetamine, and is very usable in everyday life.. I am not the only one who called it the "ultimate antidepressant". Also seems to have a wicked aphrodisiac effect to some woman (maybe just coming from that exceptionally socially opening effect). It literally erased all my social anxiety / phobia, after a time of daily dosing I even thought of having finally cut it....... Quite stimulating too, but much more on the mental side and no way the insomnia the other isomer gives me. Made a good combination with a low dose of a dopaminergic stimulant.

- And probably racemic MXE, which exerts combined effects.

I have used that good stuff daily for several months, it twisted me around, pushing into life and literally let me be like I wanted to be (and this is not just mania or delusion, as the reactions from other people who did not know about my drug use, reflected that too.. well, I was at least hypo-manic for sure, but.. it was the time of my life.. I wanna this back soo hard... 2-3x 10mg MXE, 5mg d-Amphetamine, 30mg Memantine made the ideal regimen and after initial settling tolerance did not increase)

And really, it was like night and day when taking another batch which I suspect to be the other isomer.
Of course other possibility is metabolic stuff ... say, some batches contain synth impurities / unreacted precursors / cutting agents which are either active on themselves or change the metabolism by competing for enzymes. Thinking of DXM, this is very well possible (DXM is only dissociative when metabolized to DXO. If 2D6 is inhibited and 3A4 not [could be wrong] it becomes more of a serotonergic psychedelic)..

Also 1) some effects of MXE build up when taking chronically, others change, some remain the same - sure, adaption / tolerance / downstream effects are responsible for a big part of that. But I'd bet that there is at least one active metabolite. And 2) there are some interactions with other drugs, which could also originate from changed metabolism -but this is really just guessing now.

So I am really, really interested in any data about MXE.

 

[adder]

There is no stereospecific synthesis route for arylcyclohexanamines with 2-carbonyl substituted cyclohexane ring that wouldn't use stereospecific catalysts, which take the synthesis effort to a different level (especially financially). So unless (S)- or (R)-methoxetamine was to be sold as a pure enantiomer at a higher price, nobody is going to make additional effort in synthesizing a pure enantiomer to sell it at a regular price for the joy of customers. This doesn't mean it's "unlikely", it means I'm 100% sure that no single enantiomer is sold as "methoxetamine".

 

[sekio]

cough tartaric acid cough

 

[adder]

Yeah, I kind of forgot about it, that definitely is not an expensive method, but it probably takes just as much time and effort as doing column chromatography if not more. Still there is some loss of the material, why would anyone decide to lose like 10% of a batch only to covert it to a single enantiomer? That's something you could do at an extra price and not to surprise and confuse customers, so my point still stands. I don't know what's up with different batches of MXE but I'm surprised not a single person managed to check them with a polarimeter.

BTW, I'd rather believe that different effects are due to an impurity from a side reaction. There was a topic on this matter and the structure of the impurity was confirmed with NMR if I remember correctly.

 

[sekio]

it probably takes just as much time and effort as doing column chromatography if not more.

If it's anything like resolving amphetamine, you could train monkeys (or grad students) to do it. Admittedly your total yield of one isomer is limited to 50% from the racemate then.

I somehow suspect placebo effect in the variations of MXE batches: I have seen batches claimed to be different and yet they're the same on MS. And from memory, every dissociative high is slightly unlike the previous.

 

[adder]

By the loss I mean the % loss of the enantiomer that one is interested in isolating. Resolution of amphetamine isomers using tartaric acid is pretty much straight-forward and basically anyone could do with instructions. In case of racemic ketamine it's much more of a fuss to isolate a satisfactorily pure enantiomer looking at the procedure, it certainly takes much more effort and experience in my opinion, thus it wouldn't make sense to perform this unless a single enantiomer were to be sold at a higher price.

If it's not an impurity present in some batches, then I'd be leaning towards placebo as well. I somehow don't buy all that talk about polymorphism or different energy transcending MXE molecules. As much as I'm a spiritual being (though certainly not religious!), my mind is always split between logic and feelings, so if I am to believe in any kind of "magic", I first need to understand or at least depict the mechanism behind it. We know only a fraction of the world around us and understand even less, and explaining the rest by simply calling it godly power or magic is the easiest way to explain something without really explaining it. I don't negate any "magic", but I like to think all the unknown is as comprehensible as everything that we now know for a fact.