• N&PD Moderators: Skorpio | thegreenhand

Chronic downregulation

No since it's a one-time experience, as opposed to something that's used regularily.

Glutamate excitotoxicity is real, and results form an INCREASE in NMDA activity, not less, again, antagonists don't cause tolerance.
I know but do recreational doses of dissos increase NMDA activity? If the receptors do not regulate, there shouldn't be any glutamatergic rebound ...? :unsure:

What would the signs and symptoms of glutamate excitotoxicity be?
Somewhen I thought of opioid withdrawal mimicking excitotoxicity but honestly it was just a thought..

I've done more dissos than anybody should and all I thought to be adverse reactions were due to concomitant opioid use. Took some time to recover from these month-long binges, yet would say meth does worse to people - and the subjects in this certain paper about holes on MRIs of long-term ket user (will search link if requested) almost all used that too, the other might well have lied about their use.

I don't want to say at all that dissociatives, especially K but also O-PCM/MXE (where interestingly the serotonergic agonism might actually mitigate some toxicity.. don't remember where I've read that unfortunately but it really feels to me that the serotonergic ones are less toxic. Might be coincidence) were harmless or not neurotoxic. But afaik we don't know for sure at least how much of the "damage" the brain is able to repair with abstinence..
And I'm very very interested in real evidence, for the good or the bad, but what I've saw up to now didn't satisfy me.
 
Last edited:
I know but do recreational doses of dissos increase NMDA activity? If the receptors do not regulate, there shouldn't be any glutamatergic rebound ...?
Generally all antagonists increase the action of said receptor afterwards, this is what Wikipedia says about it on the topic of 5-HT2A:
Thus, instead of tolerance, reverse-tolerance would be expected from 5-HT2A antagonists.
What would the signs and symptoms of glutamate excitotoxicity be?
Hard to say, increased risks for various diseases seem to be one.
Somewhen I thought of opioid withdrawal mimicking excitotoxicity but honestly it was just a thought..
Opioids are agonists, so opioid withdrawal is due to decreased mu-opioid receptor activity. Your body's endorphins have thus weakened influence over your physiology.
 
?Opioids are agonists, so opioid withdrawal is due to decreased mu-opioid receptor activity. Your body's endorphins have thus weakened influence over your physiology.
Always wondered why nalox/trexone are said to have little to no effects on opioid-naive individuals. Once I accidentally caught naloxone while just on memantine and it was among the most disturbing experiences. I just cried, felt like the most lonely person in the universe and such stuff. I wanted to say that withdrawal is primarily downstream effects but of course you have reason. Re-regulating mu fixes withdrawal.

How can antagonists increase action of a receptor when it does not regulate?

Yeah I thought too that antagonists should show reverse tolerance, antipsychotics for example increase dopamine receptor sensitivity, in some poor individuals enough to induce a state of psychosis from antipsychotics. Some time I actually believed dissociatives to have a complicated dose scheme, when using low doses of DXM I really became more sensitive to the point of 50-75mg causing confusion and dissociation. This lasted until I dosed higher, then regular tolerance occurs. Their tolerance isn't actually permanent but tachyphylaxis is very strong, guess even now 18 months after the last disso dose I won't be able to hole (but reach anesthesia before)..

Somehow this point worries me, I can't actually do anything about it but be more careful in future. I wanna these 50mg DXM effects back, was a good time.
Is psychosis among these various diseases?
 
Your brain doesn't have enough activity at a specific area of the brain, thus it increases receptor density to try to bring the activity of that brain region up.
Isn't exactly this up-regulation?
 
No probably not.
It's what I got from blowing through a three-figure number of arylcyclohexylamines (with MXE probably being the least harmful and - really! - K the most. Not including these crazy potent PCP analogues and the HO ones, which I didn't tolerate well, also assuming pure substances without impurities). Strange alternations in thought patterns, with similarity to yet qualitatively very different from "hearing voices" - something people outside of the psych ward don't speak about and these poor ones inside only get shot up with antipsychotics and more antipsychotics, and there isn't even a differential diagnosis for what I got: isolated, acoustic pseudo-hallucinations. On some occasion I also experienced true voices, calling down from the houses, paranoia etc. but this included an involuntary RC stim overdose together with sleepless nights and isn't that special but this incident offers a possible cause of course. If not of toxic origin then at least that the brain somehow learned how to "do" this feature. Yet, as said, it's very different, it never had actual volume even when it could become pretty "loud" but load as in screaming in thoughts vs. real, noisy screaming. Like it happens in a different dimension (probably the one of my own mind, for whatever this means, ask the psychedelic folks).
Other possible cause are toxic adulterants, which might boil down to similar than RC stims.

Or then it was the O-PCM itself. For which would speak that any dissociative, even memantine when dosed highly enough, can and will trigger the "feature" but after a year of healing it is even less random commentaries than it was before, sometimes it was like an entity of its own with which I could have conversation and sometimes still is but primarily it's like a mirror of myself, my own thinking. It can't provide any info I didn't know myself. The most annoying thing is an echo, when a "conversation" with it ends, the last word or the last few remain halling back and forth in my thoughts for maybe 30-45s (short time memory??).

I guess, but can't confirm it, that a mild 1cP-LSD trip at the end of my disso abuse career might have strongly contributed to things healing a bit, while antipsychotics - and opioids, but they felt reversible - had the tendency to cause worsening. I only said some little bit about "some acoustic hallucinations long ago while heavily intoxicated", big mistake, since then I couldn't get anymore Rx stims but rather antipsychs. Tried next to all of them and none worked or felt beneficial. Some, like risperidone or aripiprazole, caused acute worsening, a reoccurrence of whispering in noise and hearing conversations, screams, etc in running water. This alone is worrying enough but low-mid dose memantine, being a fucking D2 agonist, did not cause any worsening besides mentioned high dose inducing which happens at like 80mg.

The primary episode remained for longer time without any drug but faded pretty quickly after the 1cP-LSD. Now it comes and goes with dissociatives, which too is worrying because they were my favorite class of drugs & guess need to stay clear off them for longer, but it doesn't last any longer than the substance's effects. Notable exception seems to be dextromethorphan, when used together with a CYP2D6 inhibitor.

Strange, weird stuff. I heavily suspect my concomitant morphine/bupe use to have been a factor too, as I did abuse dissociatives before and got away with it. Or it was just toxicity of some batches, but then it shouldn't be so reliably triggerable by dissociatives, or the brain just learned to associate it with that state, or or or...
 
Last edited:
Top