suspected serotonin syndrome from methoxetamine use

[Specified]

I wasn't sure to bump this ages old thread or start a new one, but for a long time I've been trying to understand this extremely distinct bad reaction involving methoxetamine (MXE) I've had on about a dozen or so occasions since I started using it in 2010.

I've probably used MXE close to 1000 times in various dosages so I'm very familiar with it's range of effects, but very rarely I've had this exact same terrifying reaction. The feeling comes on quite fast, often with no warning, but almost always after redosing multiple times, and having consumed other substances which affect serotonin prior (amphetamine, mephedrone, AMT etc.) seems to significantly increase the likelihood of this occurring.

Serotonin syndrome/toxicity was never something I suspected due to the misinformation that MXE doesn't affect serotonin (it does: Mion and Villevieille 2013, Hondebrink 2017 etc.), but the symptoms are a very close match.

When this delirium, confusion and panic comes on there's a very small window of time where I can react clearly and I've always taken benzos, ibuprofen, run my head under cold water or taken a cold shower and basically hoped for the best. As it turns out, this is fairly close to the the standard treatment for serotonin syndrome.

Having survived it so many times is some reassurance, but it's still always terrifying. 8(

The worst time was when I was briefly supplementing with lithium orotate, had taken amphetamine, then later in the night dosed MXE multiple times which lead to hospitalization (lithium and amphetamine are both listed as possible contributors to SS which supports the hypothesis). I was released after 6 hours in intensive care (cardiac monitoring etc.) To be honest I was in far too of a confused state to remember many specifics, but there was definitely a real concern for my vitals. (Thank god for universal health-care)

I'm sharing this partly as a cautionary harm-reduction tale, and also for those who've had this experience with MXE and will know exactly what I'm talking about.
MXE shouldn't be treated like ketamine when it comes to redosing, combinations, or a night-cap after a night of partying with other substances

I know serotonin syndrome is an often over used boogey-man for a lot adverse drug reactions where it's not applicable, and I'd be happy to be proven wrong.

The next time it happens I plan to test to serotonin syndrome hypothesis by taking Cyproheptadine which is the primary antiserotonergic drug used to treat SS.
To be safe I'll start with 4mg vs. the standard 8-12mg for treating moderate/severe SS and probably call 811 to speak with a nurse, but it should help settle this issue once and for all.

Luckily Cyproheptadine is OTC in Canada, and the cost is well worth it even if only to disprove the hypothesis.

I'll be sure to update with more information as I have it.

Your going to take cyproheptadine if you think serotonin syndrome is coming on? Stupid idea. I thought about doing that a few years ago after I suffered ss spent three nights intubated. I was lucky to survive. Don't take cyproheptadine instead of medical care. Your taking a risk by taking cyproheptadine instead of going to the ER. Believe me you don't want ss.

 

[socalrollin]

That's the scary thing about RC's it could be anything, yea you know the feelings mxe should produce so you assume yes this is mxe but in reality it could be a new batch with a slightly altered chemical structure or even mixed with another RC, who knows. I had a friend basically lose his mind and suffer kidney failure from mxe. Play safe my friend.

 

[e1evene1even]

Your going to take cyproheptadine if you think serotonin syndrome is coming on? Stupid idea. I thought about doing that a few years ago after I suffered ss spent three nights intubated. I was lucky to survive. Don't take cyproheptadine instead of medical care. Your taking a risk by taking cyproheptadine instead of going to the ER. Believe me you don't want ss.

If it was a severe case like the time I went to the ER I wouldn't fuck around.
Also, to socalrollin's point, this is the exact same MXE batch I've used for 5 years. It's been tested as 98+% pure.

Reading this new paper on MXE gave me some potential insights. (*I don't know if linking to the full paper breaks any rules so I'll stick to the abstract)

"Methoxetamine produces rapid and sustained antidepressant effects probably via
glutamatergic and serotonergic mechanisms"

What I think is likely happening is that tolerance to the NMDA effects builds much more rapidly than the serotonergic effects (which might be cumulative).

The habitual MXE user becomes tolerant to the NMDA effects, increasing dosage/frequency and when other serotonergic agents are used before or after, the likelihood of adverse interactions greatly increases. This matches my experience as every one of these adverse reactions occurred after cumulative dosing.

People with a high ketamine tolerance can keep re-dosing in higher amounts, and the drug mostly just becomes less effective as it lacks the additional mechanisms of action as MXE, and complications are less likely.


Recently I've been using a lot of ketamine (by my standards) to manage severe depression, so my NMDA tolerance is quite high. When I ran out I dipped into my rations of precious MXE but needed higher doses due to cross-tolerance. I didn't have a full-blown adverse reaction, and although the dissociative effects were minor, I could feel the "sketchiness" coming on.

After taking half of cyproheptadine pill (2mg), and the other half 10 minutes later, the negative side effects I was feeling went away entirely.

Compared to the hell of a full-blown adverse reaction, this was minor, and the dosage of cyproheptadine was about 1/3rd of what is typically used to treat serotonin syndrome.

One experience, by one person isn't much to go on, but we need to start somewhere.