Neurotoxicity of NMDA receptor antagonists w/ Serotonin Agonists

[sml-la]

Hello my fellow bluelighters,

After a weekend of slightly excessive use (at least in my realm of typical use), combining some sass I acquired (MDMA/MDA) with MXE and 6-APB, I have begun to wonder about the magnitude of neurotoxicity associated with combining an NMDA receptor antagonist with Serotonin agonists. I am a fairly hardened veteran of Ketamine, as well as a variety of other empathogenic, psychedelic, and dissociative drugs, and have frequently used and enjoyed the combination of MDMA and Ketamine. I know MDMA on its own can be a very neurotoxic substance, and am very curious as to what effect Ketamine, Methoxetamine, and other NMDA receptor antagonists could be. I know DXM and MDMA is a no-no, but Ketamine seems to lack the MAOI-inhibition of DXM, leading me to believe that MXE also avoids such contraindications (having combined copious amounts of these chems with Mdxx or other empathogens with no negative results). Any thoughts, speculations, or hardened evidence is greatly appreciated! Thanks!

 

[Bone14]

I would be very cautious with this combo. It is not the same as MDMA/MDA/6-APB + ketamine, methoxetamine is a DARI and a D2 partial agonist. (it most likely has a broad binding profile: NMDA antagonist, mu agonist, sigma agonist, K+ channel blocker, NACh antagonist,, what I'm saying it that it is not easy to predict if this is same to combine with MXE)

Something tells me that methoxetamine's dopaminergic pharmacology might be more similar to PCP than to ketamine. I don't have any data to back it up, because MXE is unstudied, but its just something my instinct tells me. I would honestly be pretty hesitant to combine any of above with MXE because some of the things involve a decent amount of dopamine.

When on MXE, I would stay away from stimulants and MDxx's it just does not seem safe.

I've seen people having insane motoric problems for as long as 20 hours when combining stimulants like methylphenidate and MXE - high doses though, but still, no reason to take the risk. Do not combine.

 

[greenmeanies]

4-FA or M1 even five hours after MXE has left me very lightheaded with a feeling of stimulant-toxicity type symptoms. So I would also caution against any kind of stimulant (MDMA, 6-APB) mixing with MXE. It intensifies the side effects.

 

[Ismene]

I know MDMA on its own can be a very neurotoxic substance

There's no evidence that Ecstasy causes brain damage at human sized oral doses.

4-FA or M1 even five hours after MXE has left me very lightheaded with a feeling of stimulant-toxicity type symptoms. So I would also caution against any kind of stimulant (MDMA, 6-APB) mixing with MXE. It intensifies the side effects.

I don't think neurotoxicity really works like that - you don't instantly "feel" neurotoxicity. You're simply feeling the hangover of a drug.

 

[Albion]

For the record, I've had multiple uncomfortable and sometimes downright physically scary experiences combining mxe with 5-apb, mdma and ethylphenidate.

I have also had good experiences combining mxe with these drugs, but only ever on the comedowns/after peak. The later, the better. MXE and ethylphenidate has done something of a number on my heart. I get chest pains much more readily ever since an mxe/eph health scare a couple of months ago...

 

[Isidor]

I had a very nasty experience combining MXE with 5-apb, with blackout and vomiting. Doses were not very high either, this was a while ago so don't quite remember the details but no more than 150mg 5-apb oral and then 40-50 mg mxe sublingual several hours later.

 

[Jesusgreen]

I think the key here is MXE, not NMDA antagonists, something a lot of people don't realise/forget is that Ketamine itself is a Serotonin Reuptake Inhibitor and a Dopamine Reuptake Inhibitor, albeit it is very weak when it comes to both. As you can see from MXE's effects, it's likely to be a much more potent DRI than Ketamine, and it's possible the same is true for its SRI action. Now compounding DRI/dopamine releasing effects can lead to some unpleasant side effects, difficulty sleeping, over-stimulation, high blood pressure etc - but when it comes to serotonin this can be far more dangerous, with Serotonin Syndrome a real possibility.

Now it's quite plausible that MXE has virtually no SRI action, but I definitely do not think it is a good idea to assume that combos between MXE and drugs that release/inhibit reuptake of serotonin are safe, until more about the actions of the drug are known.

Personally I think it's worth avoiding all of these sorts of combinations, a lot of people have reported nasty side-effects with them, so at the very best you're at some risk of ruining your experience - but more importantly, at worst, there could be real danger. The first reported MXE-related death was of a combination of MDAI + MXE, the doses were high, and the ROA was IV, but it still leaves me rather wary.

Stick to Ketamine when combining with SRA/SRIs imo, until we know more about MXE. Also, fyi, Serotonin Agonists would be a chemical that activates the Serotonin receptors, such as psychedelics, rather than a releasing agent/reuptake inhibitor (though some of them are also Serotonin Agonists).

 

[Survived Abortion]

I know DXM and MDMA is a no-no, but Ketamine seems to lack the MAOI-inhibition of DXM, leading me to believe that MXE also avoids such contraindications (having combined copious amounts of these chems with Mdxx or other empathogens with no negative results).

I just wanted to point out that DXM is not an MAOI. The reason it is dangerous is because of it's effects on serotonin - it is a serotonin reuptake inhibitor. As Jesusgreen points out, there may be similar effects with MXE, but we don't know enough about it's pharmacology. Until we do, I would assume that it does have effects on serotonin, just for safety's sake. I see bad experiences reported all the time involving combinations between MXE and serotonin drugs (such as the empathogens, and even 5-HTP). It would be safest to avoid such combos.