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The Big & Dandy Methoxetamine Thread - The 3rd Dose

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What on earth is a schizo?

Sorry it just bothers me that such a term is bandied about, mental illness is an immensely complex subject and the whole concept of schizophrenia is probably wrong. Last time I looked psychiatry was by and large pseudo-science.
 
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knockando said:
What on earth is a schizo?

Sorry it just bothers me that such a term is bandied about, mental illness is an immensely complex subject and the whole concept of schizophrenia is probably wrong. Last time I looked psychiatry was by and large pseudo-science.
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Wow. It must be nice to be so confident in your analytical skills that you can dismiss hundreds of years of research by extremely intelligent people.

Hearing voices telling you to kill your mother is not a game. Schizophrenia a serious disease, and linked to physical abnormalities in the brain.
 
I would like to point out the obvious here and why it might not be such a great idea.
Light opiods with wethoxetamine may be fine, however o-desmethyltramadol is what i would call a pseudo-opiod, and is the principle active metabolite of tramadol, an NDMA receptor agonist.
Methoxetamine works by using those receptors.
Basically after tapering off of my prescribed tramadol for one day made taking a 3mg key bump kick my ass like no other dose of methoxetamine taken in the weeks after that. To make this more than an anecdote, I gave my friend who was on the tail end of a 100 mg dose of tramadol 2 separate 1-2mg bumps just so he could join in with some other buddies on a brownie who had each had ~15 mg lines. He went to hyperspace when we threw on some Skrillex.
I think we were fine in these instances because my allergy testing bit put me way too close to n20 or dxm headspace off a dose reputed to be paltry.
That said, take it with a grain of salt but be wary of mixing methoxetamine with any kind of NDMA agonist, and if you can't control the urge, for science's sake, tread carefully.
 
incognition said:
Wow. It must be nice to be so confident in your analytical skills that you can dismiss hundreds of years of research by extremely intelligent people.

Hearing voices telling you to kill your mother is not a game. Schizophrenia a serious disease, and linked to physical abnormalities in the brain.
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I apologise for being dismissive, however let me assure you I am not dismissive about the effect of mental illness on peoples' lives. I don't think it's a game and I don't think I said it was a game.

My attitude to mental illness is coloured by my relations with family members who have worked in psychiatric care. The impression I have built over the years is that psychiatric medicine is pseudo-science, and that the people who pass through the psychiatric treatment system are by and large treated as clusters of symptoms rather than people, and as a result they are treated badly. The problem being there is currently no objective test or proper neurological model for this thing we call schizophrenia and that the medicines used cause as many problems as they resolve, which would be expected from a practice based on unsound theory. So unless this picture is wrong, or unless things have drastically improved in the last, say, ten years, I tend to view statements about psychiatric conditions as being matters of controversy and not established fact.

I happily admit I know fuck all on this subject, I have just been in close proximity, for most of my life, to those who are involved in it.

I also do not like the use of the word "schizo" as it is pejorative and demeaning for those people who find themselves labelled with it.
 
Fixed5217 said:
tread carefully.
Click to expand...

Seems sensible.

I don't really understand this:
Basically after tapering off of my prescribed tramadol for one day made taking a 3mg key bump kick my ass like no other dose of methoxetamine taken in the weeks after that. To make this more than an anecdote, I gave my friend who was on the tail end of a 100 mg dose of tramadol 2 separate 1-2mg bumps just so he could join in with some other buddies on a brownie who had each had ~15 mg lines. He went to hyperspace when we threw on some Skrillex.
Click to expand...

You were on prescribed tramadol. You then tapered off your tramadol dose over a day then on that same day you took a 3mg bump of methoxetamine and the effects were, say, on a scale of 1 to 10, an 8, then in the following weeks, you were back on tramadol, and when you consumed methoxetamine the effects were more in the 4-5 region perhaps? Is that what you're saying? In which case you are suggesting that tramadol inhibits the effects of methoxetamine. Is that right? Sorry, I just want to understand what happened.

I read here that Tramadol and O-Desmethyltramadol inhibit NMDA receptors, is this antagonism? I think so, but I'm not sure. This would make Tramadol and O-Desmethyltramadol NMDA receptor antagonists, just like Methoxetamine. But that's the opposite of what I think you're saying.

Finally let's be clear, it's NMDA we're talking about, not NDMA like you wrote, which seems to be some kind of carcinogen!

I'm starting to think I might have been a bit silly with my dosing and I should take a step back. I don't think I fully understand the possible interactions. :| I also wish you were clearer, Fixed5217 ;)
 
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Fixed5217 said:
Basically after tapering off of my prescribed tramadol for one day made taking a 3mg key bump kick my ass like no other dose of methoxetamine taken in the weeks after that. To make this more than an anecdote, I gave my friend who was on the tail end of a 100 mg dose of tramadol 2 separate 1-2mg bumps just so he could join in with some other buddies on a brownie who had each had ~15 mg lines. He went to hyperspace when we threw on some Skrillex.
Click to expand...

As others have pointed out, tramadol is not an NMDA agonist.

The NMDA receptor is a ligand-gated ion channel whose function may be affected in multiple ways. The ion channel "opens" and allows for the passage of ions when it is bound to agonists at both the glutamate and glycine binding sites. Calling it a glutamate receptor is a bit misleading since it actually needs to bind to two endogenous ligands, gluatamate and glycine, in order for ions to flow through the channel.

There are several ways in which a drug may interact with this receptor, and only one is known to lead to recreational effects.

NMDA agonists bind to the main glutamate site on the NMDA receptor and cause it to open. These include N-methyl D-aspartate, aka "NMDA", hence the name, and all drugs which fall into this category are highly toxic and pro-convulsant.

Competitive NMDA antagonists bind to the main glutamate site on the NMDA receptor and do not cause it to fire. In doing so they prevent glutamate from binding to the receptor and lower its firing rate. These include aminophosphonic acids such as Selfotel, AP5, and AP7, and have no history of recreational use. Some have demonstrated anticonvulsant effects.

Uncompetitive NMDA channel blockers are what the majority of people refer to when they say "NMDA antagonist". These include ketamine, DXM, PCP, ethanol, diethyl ether, nitrous oxide, and most other classic dissociatives. They work by interfering with the opening of the ion channel without affecting the binding of either glutamate or glycine to the receptor sites. All of these display potent general anaesthetic effects and have a long history of recreational use.

Tramadol is an uncompetitive NMDA channel blocker. So is methoxetamine, or so we think, since no real binding studies have been conducted (but we'd be very surprised if it weren't).

Glycine site agonists and antagonists bind to the glycine site of the NMDA receptor, allowing the ion channel to open (in the case of agonists) or preventing it from opening (in the case of antagonists).

If you're taking methoxetamine with tramadol, you're combining the effects of not two but three active compounds.

Tramadol is a serotonin releaser, a norepinephrine reuptake inhibitor, an uncompetitive NMDA channel blocker, and a weak mu-opioid agonist.

O-desmethyltramadol is a mu-opioid agonist and a norepinephrine reuptake inhibitor (depending on chirality).

Methoxetamine is a dopamine reuptake inhibitor, a nicotinic acetylcholine receptor antagonist, an uncompetitive NMDA channel blocker, a dopamine D2 receptor agonist, and a mu-opioid agonist, according to the current SAR as well as subjective reports consistent with this effect profile.

Note the bolded words "serotonin releaser". Methoxetamine has in the past demonstrated the ability to cause serious problems in conjunction with serotonin releasers; the combination of methoxetamine and MDAI (which is a serotonin releaser with no other effects to speak of) lead to the death of one unfortunate Swede who had taken only a moderate dose of both compounds. Simply put: the combination of methoxetamine and a serotonin releaser appears to be extremely dangerous!

It is therefore highly inadvisable to combine methoxetamine with any serotonin releaser or suspected serotonin releaser, or with DXM (a very potent serotonin reuptake inhibitor, though not a releaser) -- this includes MDMA, 6-APB, AMT, MDAI to name a few.

The increasing number of these reports suggest that this interaction is indeed quite real; it is possible however unlikely that methoxetamine acts in some way to inhibit the breakdown of serotonin, via monoamine oxidase inhibition or otherwise. Methoxetamine and the other methoxylated arylcyclohexylamines (4-MeO-PCP, 3-MeO-PCP, 3-MeO-PCE) bear some structural similarity to the infamous PMA and the less-well-known MAOI para-methoxy-phenethylamine (PMPEA). The appearance of unexpected effects is always a possibility when testing a new compound especially testing in vivo with no pre-existing in vitro binding data. To combine these with other compound increases the risk of ingestion substantially.

Consider yourself lucky you got away with a more powerful than expected trip, and please everyone think twice before combining untested chemicals!
 
Wow, thanks Atara; I actually just learned quite a bit. Appreciated.
 
^^^ well put, succinct and thorough, thank you Atara. I agree caution is advised with methoxetamine and serotonin releasers (and any other combinations for that matter) as we don't know what is really going on. And admittedly, the purported death in conjunction with MDAI is a cause for serious concern. (and I dunno if 400mg of i.v. MDAI qualifies as a moderate dose. I wouldn't be surprised if this dose alone taken by this ROA could prove fatal via hyperthermia) But it seems to me that "serotonin syndrome" is something people are tossing about far too liberally nowadays. Sure, one can't be safe enough, but I've combined methoxetamine with a few releasers (MDA, MDMA, aMT, and tramadol) with no unexpected or worrying symptoms. YMMV.
 
i tried it with 250mg mephedrone and it was better than any mephedrone experience ive had before. They synergised splendidly. Caution should certainly be used but i think if done responsibly it can mix with other things.
I look forward to combining it with MDMA (ketamine and MDMA is one of my favorite drug combos). Id also like to combine it with ketamine. :)
 
wait, so mxe is a dopamine reuptake inhibitor.... like wellbutrin?

is that the reason why it has anti depressant effects?
 
knockando said:
Seems sensible.

I don't really understand this:

You were on prescribed tramadol. You then tapered off your tramadol dose over a day then on that same day you took a 3mg bump of methoxetamine and the effects were, say, on a scale of 1 to 10, an 8, then in the following weeks, you were back on tramadol, and when you consumed methoxetamine the effects were more in the 4-5 region perhaps? Is that what you're saying? In which case you are suggesting that tramadol inhibits the effects of methoxetamine. Is that right? Sorry, I just want to understand what happened.

I read here that Tramadol and O-Desmethyltramadol inhibit NMDA receptors, is this antagonism? I think so, but I'm not sure. This would make Tramadol and O-Desmethyltramadol NMDA receptor antagonists, just like Methoxetamine. But that's the opposite of what I think you're saying.

Finally let's be clear, it's NMDA we're talking about, not NDMA like you wrote, which seems to be some kind of carcinogen!

I'm starting to think I might have been a bit silly with my dosing and I should take a step back. I don't think I fully understand the possible interactions. :| I also wish you were clearer, Fixed5217 ;)
Click to expand...

I took the methoxetamine as an allergy test the day following my last tramadol dose(100mg). I'm used to conversational nuances, perdon. My friend took the even smaller dose of methoxetamine about 6 hours after dosing 100mg tramadol.
It's been my strongest subjective reaction to date. My friend was nearly incomprehensible after smoking cannabis too.
Effects that evening indeed I would classify an 8. to date I have only reached the 4-5 star range after consuming more(larger, more frequent bumps ~5-15mg each).

That said I would liken that feeling to an opiate consumed with some amp, each in low doses, and I like it just fine. It makes you feel good, but preserves mental clarity.

And certainly not NDMA...lol!

If I may have confused the receptor activity classifications, I did not, however misunderstand the potentiating effect of the interaction and will avoid like the plague for future use.
 
I'd like to pass along a thanks to Atara.
I certainly read up before consuming any substance, though in hours of wiki checking, trip reports and reading discussion on bluelight and elsewhere for both tramadol and MXE, you just concisely and correctly summarized both and enumerated potential reasons for my interaction.
Props!
 
Thanks Atara, I think you may have offered the real explanation for the horrific experience I had combining MXE with 5-APB.

Kinda reassuring to know I wasn't just spun out, and may be lucky to be alive....
 
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