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Dissociative (PCP) Mania - Mechanism?

I don't know how much I would blame NAPDH oxidase... you can get into similar states with MXE or ketamine, it just takes a longer time of abuse.
 
I was mainly thinking of some recent publications, there were more but these are what I've remembered now:
Loss of phenotype of parvalbumin interneurons in rat prefrontal cortex is involved in antidepressant- and propsychotic-like behaviors following acute and repeated ketamine administration.
Interleukin-6 Mediates the Increase in NADPH-Oxidase in the Ketamine Model of Schizophrenia (and N-acetylcysteine is said to, among other effects, inhibit or alleviate the inflammation response particular to IL-6)
Understanding Brain Changes Caused by Ketamine or “Special K” Could Lead to New Therapies for Schizophrenia
 <-- good abstract of the topic

But of course we have to remind that it's mostly about rats and this can't be applied 1:1 to humans. I've been scared by these brain changes / damage seen in 'heavy' chronic ketamine users (at least 0.5g/d over the course of 185 days and more) and theorized that these will be the result of raised NADPH oxidase & IL-6 expression, more superoxide and ultimately cell death.

When you search for publications about DXM & brain damage, you'll only find some which suggest that it's actually neuroprotective by multiple mechanisms - DXM inhibiting the NADPHo, it and the metabolite 3-HM being anti-convulsive / calcium channel blockers and 3-HM also limiting glutamate trafficking. DXO hasn't been explored, and while I might be wrong, I attribute the negative / toxic things to DXO.

And things seem to be even more complicated, sex-dependent even in mice:
Ketamine alters cortical integration of GABAergic interneurons and induces long-term sex-dependent impairments in transgenic Gad67-GFP mice

Yeah, MXE especially with higher dosages can lead to psychosis too, and ketamine has also some rough sides - but overall I really feel that MXE in lower (sub-intoxicating, mood-lifting) dosages is the least toxic and most sustainable from all the dissociatives I know of. Could be because of it's overall effects though, that the mu agonism from the 3-HO metabolite as well as it's 5-HT2a agonism counter act the negatives from the pure NMDA antagonism. No clue, but weeks on good MXE felt easier than days on K or single usages of DXM / the diarylethylamines.

Or is it just that MXE doesn't activate sigma-1, or less strong than the PCP's and DXM?

With MXE psychosis seemed to be totally dosage-dependent and an acute phenomenon that's not the result of some chronic, hidden toxicity as DXM makes me feel..
 
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It's okay, I'm out there and positive ... but I'll have to face the fucking legal consequences probably, not because of this particular accident but I've been caught with some previously legal but now banned RCs like MXE. Thanks for asking! <3;) It's really nice for me to get responses, I'm such a hyper emotional person - this is why I've done drugs at first hand, to numb these damn feelings.. - I'll write you later maybe!

I can't put my finger on it, but I really think the dissociatives have changed my personality towards the positive. It was a hard learning, I've repeatedly thought or felt to be dying or to be already dead and caught in a never-ending loop where I am the only consciousness and everything around me was just imagined - this seems to be something quite a few people experience on 'bad trips' from dissociatives, but also from psychedelics. Think it has to do with neuronal network disruption and there's actually some loop running in the brain, and one feels that... crazy shit, but I know it's just drug induced. The real world things, e.g. war on drugs, society, criminalism, social isolation, aggression, do suck much more. And these things don't wean off when the substance metabolizes out :/

There appears to be a subgroup of suffering individuals, therapy-resistant depressed ones, but in particular probably those with borderline personality disorder / PTSD - split off feelings, memories and so on. Fatigued but restless. Tired but wired. Emotional hell. My theory is that for these the dissociatives offer an outstandingly unique therapeutic potential that has been overlooked because it doesn't apply to everyone.

I'm currently on sodium valproate of which I'm positively surprised (and mirtazapine 30mg/d at bedtime, I used to think that this substance doesn't do anything besides just locking one into bed, but maybe the dopamine disinhibition works now too, no clue. I'm happy to have it because even with this dose I only sleep some 6-7 hours per night currently). Just upped from 600mg/d to 900mg/d today. It's anxiolytic, disinhibiting, calming, but not limiting at all - really not comparable to these hellish neuroleptics. Think with some methylphenidate (I have adult inattentive ADD) on top of it, life could be flowing nice again :)
 
Dopa I hope you're doing alright over there! I missed you man.. I smiled big when I saw you had made a post, I had been worried about you <3

I think sodium valproate is a very interesting drug and it has actually been a recent area of research for me.. I would really love to try it and I have made an appointment with a psychiatrist in hopes of doing so. What do you think about it so far? I'm wondering how it will help with sleep.. It's neurotrophic effects are vast. Some people have claimed its acute effects are placebo-like however. Though I am sure the epileptics will disagree on that point.

I wish you all the best dopa. Break out the mindfulness meditation ;)
 
Quit the sodium valproate on leaving the hospital, the Invega injection is something else
Have they got takeaway night at the retreat dopa ?
 
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