Multi NMDA antagonist combination dangers?

[MyExcuse]

So recently I've been contemplating the combination of multiple NMDA antagonists (and possibly 4-substituted tryptamines). In particular I'm curious about experiencing the effects of memantine, 3-MeO-PCP/PCE and methoxetamine together or dosed spaced over the course of a short period of time.

My concern is if there could possibly be any physiological complications that would arise from such combination. I doubt there is any evidence to be found on this but I know other various combinations of NMDA antagonists have been attempted and I figured it wouldn't hurt to ask for some insight before embarking on a journey of such magnitude.

 

[reformer]

Beautiful post- Also Intrigued.

Thanks for bringing this up.

I'd like to hear the BL hierarchy reign down some wisdom on this un'.

At this stage I don't have much to offer, ecept to ask that we pay attention to the usual qualifiers: Half-life, ROA, affinity, hydrophobicity and overall impact (e.g. degree of antagonism; Ki for the receptor and magnitude of downstream effect on signalling pathways) that are elicited by each molecule under investigation.

Maybe a good starting point would be to list, in this thread, the known, defined properties of each of the substances that are on the table?

Will be checking in here in the hopes that a nice discussion develops...

r

 

[PsychedelicPeptide]

I'd have to think the most pertinent danger would be from a "near" shutdown of NMDA signaling. It is hard to say what level of antagonism you would achieve in combining compounds like PCP derivatives and MXE because there is no published work showing exactly how much antagonism they elicit (as far as I know, maybe there is something for PCP analogs?). For ketamine, we know it is about 50% signaling capacity- this has been published by numerous groups.

I have a hard time believing PCP analogs, MXE and K bind to different sites on the NMDA receptor, so odds are they would be at competition with each other for one site throughout the brain and body (Is NMDAR even expressed outside the CNS?). So you probably couldn't shut the NMDA system down entirely, which would probably be my biggest concern.

Other than that perhaps the biggest danger would be in overdosing, blacking out, and doing something really stupid?

 

[Darksidesam]

Ive combined Mxe and ketamine,

Felt a bit out of control tbh (I did it at a rave lol)

But the worst thing of all was this horrible comedown that lasted 6 days... On its own , ketamine acts an anti depressant for me, so does mxe... Combined Its a combo from hell afterwards

 

[bluedolphin]

I combined Ketamine and MXE.... drugs that I am well experienced with on their own, at a festival this summer. Ended up thinking I was going to have a heart attack, then completely dissociated into a mind trip that I thought I was going to the hospital. In reality I had just (somehow) found my way back to my tent and the next thing I knew a couple friends were looking a bit concerned for me.

So I basically blacked out and did what I needed to do... but in my mind I was somewhere else. Not fun, not at all recommended.

I should note that I do not believe I took very high doses of either chemical, but in conjunction it turned into another beast all together.

 

[PsychedelicPeptide]

Those stories are unfortunate, but interesting. It sounds like combining NMDA antagonists is a bad idea. I think I would be most concerned that in panic someone would do the worst thing they could possibly do and start drinking, or take a benzodiazepine, hoping to dull the effects of the MXE/K... this would probably be an instant ticket to the danger zone!

 

[wayab]

i dont know about mxe+ket but ket+dxm is a incredible combo for me one of my favorites

 

[Pjkt2501]

Those stories are unfortunate, but interesting. It sounds like combining NMDA antagonists is a bad idea. I think I would be most concerned that in panic someone would do the worst thing they could possibly do and start drinking, or take a benzodiazepine, hoping to dull the effects of the MXE/K... this would probably be an instant ticket to the danger zone!

I'm curious as to the statement with benzos; are you speaking in terms of chemical interaction or the dulling of the respiratory system that occurs? Asking because I take my prescribed clonazepam with just about every chem I ingest due to normal anxiety issues (and as a result never get a "scary" moment while tripping, just good to go).

To the OP: sorry, I only have personal experience with Ket as a dissociative (more than ought to have in the period of time), and one DXM trial.

 

[PsychedelicPeptide]

Well mostly the potential for unpredictable chemical interactions.

I would think in your case, if you are taking clonazepam daily it wouldn't be a big deal because you have some drug tolerance, but people that don't use the benzo very often might be a lot more susceptible to this sort of thing.

It's hard to say exactly though, there are always potential dangers when introducing combinations of chemicals to your body especially for the first time. I also just did a quick search and it looks like the NMDA receptor is expressed in cardiac tissue, so I certainly wouldn't discount the possibility that a high double dose of MXE and K plus some benzos could mess with the heart.

Personally I would avoid taking benzos with psychedelics altogether. I thought they (benzos) mostly just make you tired or dull the psychedelic high.

 

[Solipsis]

Benzo's are known for their relatively large therapeutic index which is an important reason why they are basically considered current generation sedatives (not next generation sedatives though). Even large doses typically do not cause dangerous depression of the autonomic nervous system, though I'm sure it is possible if you go high enough. Also it depends on the benzo. I believe something like midazolam can be quite dangerous - I would classify it as a very heavy and physical one. The least physical ones seem like the least dangerous ones.
Ketamine itself also has a fair therapeutic index which is why it is given to old people and children for medical operations. In reasonable doses it does not depress breathing, I think it even elevates breathing rate (or was it heart rate?). For medical operations it is often used together with benzo's to induce anterograde amnesia and consolidate the anaesthesia.

Oh for some reason I thought you posted that benzo's would be dangerous with ketamine.

Hmm MXE seems significantly different from ketamine in my opinion. The stimulant properties are pronounced enough that I would worry about them. It would take quite some MXE to kill you I think, but let's not forget the death with MDAI.

Isn't ketamine's large therapeutic index a sign that you would go into anaesthesia long before it would become a danger? I think that stimulant properties of compounds like 3-MeO-PCP and methoxetamine would pose a problem long before the dissociative anaesthesia though perhaps if you become manic and stimulated just as quickly as becoming dissociated and sedated the amount of stimulation might be seriously physically taxing. Still I would very much worry about your erratic behavior endangering you as well as psychological adverse effects and lasting personality associated pathology. But I know you asked about physical effects.

 

[PsychedelicPeptide]

For medical operations it is often used together with benzo's to induce anterograde amnesia and consolidate the anaesthesia.

Oh nice I didn't know that. I still think the biggest worry (aside from adverse psychological effects lol) would be blacking out and doing something stupid, either from MXE/K overdose or MXE/K + a depressant.

 

[Solipsis]

Of course you can find out for yourself by using search engines but to add some extra info apparently during surgery it is often used with midazolam for the most pronounced 'attenuation of the altered sensory perception and thought processes' in other words to prevent emergent states. Midazolam or diazepam are also used to prevent the tendency of ketamine to 'enhance rises in heart rate'.
Ketamine is also used with propofol (imagine that) because of a fair proportion of anaesthesia to respiratory depression (and also haemodynamic stability - I think that refers to blood pressure and the like).
Considering midazolam is one of the heaviest benzo's (great for sleep though lol) and propofol is quite a heavy drug as far as I'm aware... these things should be an indication of the relative safety of ketamine and as such of NMDA antagonism.
BUT let's not forget that during surgery there is an anesthesiologist standing by to keep an eye on you!!!!