Effects of parasympathomimetics combined with NMDA antagonists / dissociatives

[dopamimetic]

I just can't and can't leave these dissociatives behind. Only their psychotic nature is a hefty contrast to that spark of life that they manage to ignite each and every time again when I have been captivated by depression ...

Maybe it is completely wrong but somehow the thought concept of a certain part of their (now speaking mostly about the 2'-OxO-PCx ones) side effects being due to a dis-synchronization between the CNS and the PNS. How I come to think that has to do with some weirder effects I observed when (ab)using named chemicals over longer amounts of time chronically.. a strong influence to the skin (pale and very dry, antihyperhidrotic), pinpoint pupils, stomach and intestines in general (sure identificators for PNS agents, aren't they?) and the interference of NMDA antags with opioids- there are some other weird PNS links about morphine dependence ...

Then all the dissociatives appear to be anticholinergics too. Even memantine is an antagonist of some nAChR's. Nicotine has a reaally weird effects relationship with dissociatives, it's mentioned even in that good old DXM FAQ by White..
DXM is a very strange one. I would bet abusing it led to long-lasting changes in some cholinergic circuits ... and after buprenorphine finally messed it up (could barely urinate on <1mg of bupe) I did not tolerate even therapeutic dosages of DXM again.

It was like a sequence with several (maybe 7-10) steps, together with the sense of a spring that gets squeezed and at some point switches back with an enormous burden for - umm, whatever. Think this is hard enough for you to follow as I'm not a native English speaker but also unlikely that others will get the same imagination for such things.

And as these symptoms got worse together with psychotic ones, well I thought about the connection but it's easier to get your hands on anticholinergics than on pro-cholinergics. The only one I know of is galantamine, and some weird russian pharms (Tacrine, Ipidacrine). My doctors didn't give a shit on that theorism when I sat there and could barely speak a word while having a clear mind (weird residual effect of some batches or at least one that has been stronger with some. But even then I thought it might have that in common, e.g. synth leftover with similar structure but being x100 on some peripheric choline enzyme)

Is it complete bullshit or not?

 

[d1nach]

I dont completely understand. I believe dissociatives are nicotinic acetylcholine antagonists while lost common anticholinergics are muscarinic acetylcholine antagonists.

Are you asking if procholinergic drugs could reduce the side effects of dissociatives.

I used dxm in moderate doses like one or two 240 mg a day for like a few years. And, heavily used nicotine during that time and anticholinergics.

I am not sure why you would have trouble speaking when not intoxicated. If i used alot of dxm and anticholinergics id sometimes have trouble thinking what i wanted to say if that makes sense. But it always went away when the drugs stopped.

 

[dopamimetic]

Are you asking if procholinergic drugs could reduce the side effects of dissociatives.

Yes. This is the main point. But also how they would change the experience if, as it seems, all dissociative drugs are also anticholinergics ...

I am not sure why you would have trouble speaking when not intoxicated.

This was a really weird side effect that emerged when some potent batches of dissociatives went available. But I experienced it in a weaker form from heavy abuse of DXM alone. I will copy the links in later if I manage to find them. That I couldn't speak straight, at first it looked like stuttering (something I never really did) and also had some muscle jittery-/weakness ...

I think these things, fine motor skills and speech, are mediated by cholinergic circuits but I might be wrong. There might be some feedback loop or connection through irreversible-binding/long-lasting changes in enzymes..

Also I go as far as to rethink my experiences with bupropion & DXM - granted and okay, the former is an enzyme inhibitor. But this does not fully explain how completely different the trip was once with 400mg (afair) and 150mg Wellbutrin XR - like a full dissociative experience in 2D, it was really unique in that it wasn't a dissociation and no 5-HT trip either..might not more the bupropion have done some weird things over other routes?

 

[d1nach]

Have you tried practicing when i was using anticholinergics and dxm daily i would practice rapping to songs trying to copy it exactly so noone could notice any changes in my speach.

 

[dopamimetic]

I guess the effects I speculated about were indeed due to acetylcholine disruption (maybe specifically muscarinergic acetylcholine, but here I might be wrong. Just cause I smoke and nicotine changes them a bit but with a strong tendency to worsen).
Switching the methadone to morphine (currently maybe 120-160mg/d) greatly improved the situation. I do now have the problem to precisely dose the morphine as it lasts only for a few hours even with the XR formula and as usual with such, it's hard to grasp the duration and when to redose.

At least there has been a huge cumulation of choline blockade, I realized that my body almost lost its ability to sweat even with the (moderately) high temperatures here, 28-30 degrees Celsius .. this induced headaches and feelings of malaise, fever and weakness.. And apparently methadone is a medium strong anticholinergic, loperamide maybe being equipotent, buprenorphine felt worse (strange that there is little information about this but I'd bet they do inhibit cholinergic transmission) and dextromethorphan of course is a bad one about this.

But I am still curious about the relationship of dissociatives/dissociation and ACh blockade. Would administering parasympathomimetics alongside dissociatives improve the experience, simply change it or make it worse / induce bad side effects?

Also there is little information about how (too) high levels of ACh feels. I guess about the nicotinergic side one can take as an example how it feels to smoke more than usual in a short amount of time or stronger things (headache, dysphoria, tachycardia - weirdly anticholinergics also lead to abnormally fast heartbeat!? - rigid focus etc..) but about the muscarinergic side I just know that it makes one hyperhydrotic. Nicotine too but by far not as strong - or am I thinking in a wrong direction?

--

d1nach - a pronounced effect is that with the first trips on DXM, especially with med-high "Plateau 2" and above, I could hardly stand up not to speak about walking, typing on the keyboard or do handwriting (something probably everyone seems to experience?) ... this almost completely went away with continued use and did never come back. As I already hat a decent tolerance when I switched to the 2'-oxo substances I can't really tell but with them I never had that intensity of motor problems by far. Just what I described, this interference with speaking and fine motor skills, with a tendency of lasting a bit longer than the majority of effects and as said with certain batches and using them often with (too) few breaks it lasted for days. Had to completely stop the dissociatives then and gave my body time to heal.. well, I intended it. After a few weeks I relapsed and went then on opioid maintenance because I feared permanent damage and needed somthing that alteres my emotions and thoughts.........

The opioids do not fully substitute for me but they are apparently the only prescribable substance class that attenuates that drug seeking behavior..

But indeed one can learn how to handle the impaired motor control, at least to some extent. Just wonder if this is specific to that or whether the body regains its equilibrium by releasing / synthesizing the right chemicals.

If I get my hands on some proglumide I'll write a report about it