Immune reactions responsible for tolerance, loss of magic, bad side effects

[dopamimetic]

In that the body begins to recognize a certain molecule as 'bad' and attacking it and/or its targets while it's attached to. Is this kind of reaction possible?

Theoretically, but also specifically with dissociatives. They apparently mess with some things that might be relevant, like NADPH-oxidase relative superoxide generation (or its inhibition, in the case of DXM, apparently).

DXM was the first one, in the beginnings it was wonderful (if I didn't take too much) but since some occasions I didn't tolerate it any more, it feels plainly toxic like downing 1g of caffeine or whatever. It's not just sensitization cause with a given (low) dose, maybe 200mg or even just 75mg, the effects are low or almost unnoticeable like they should be, but there's a strong aversive feeling and increase in symptoms that grew later into sort of psychotic/"schizo" positive/negative symptoms. Part might be pla/nocebo but I'd bet it's more than that cause once (years ago) I thought fuck it, it's just nocebo so I'll go straight for a real dose - took 440mg and ended up hearing true voices, something I've only ever experienced once when I had no sleep for maybe 3 days at least and was on O-PCM all the time. Even then, it was more benign in nature and just 'noise' but on DXM it was demonically. No dissociative / serotonergic symptoms to speak of. I packed myself into bed with earpods and thankfully I slept away soon, for pretty long and woke up as usual. Note that I wasn't sleep deprived or intoxicated at that time, I was "just" on buprenorphine maintenance, something between 2-4mg/d.

But it doesn't stop here. As you maybe can imagine, I've been in love with dissociation and O-PCM worked fine always that time. Sometimes when supply was short, I used ketamine instead and to K I've developed a similar, yet different condition. The K began to feel increasingly toxic over time, with much of the dosage apparently getting turned into some sort of static noise humming and buzzing in my hears, auditorially, visually and cognitively, something I haven't experienced before and feels very.. unhealthy. Needless to say that I stopped using K but much later I was for longer time off any disso, so tolerance should be down if anything, and decided to try low-dose K again. The first hours of the very first dose were fine, then the old symptoms began to set in and became so strong that I didn't do a third attempt.

So, while it's obvious to think of neurotoxicity, what really puzzled me was that now, while I don't tolerate tiny amounts of K or DXM, memantine is just fine, helps me so much and even remembers me much of my old days ... or what I've searched in these. So my hunch is that it's specific to a certain molecule regardless of its MOA (also I think to remember that I developed something not-so-different to 3-MMC). That taking MXE now might be fine, or if not then - let's say, diphenidine ... but if I used that instead of the K, then now I'd be allergic to that one..

I remember to have recognized red pustles from one of the very first DXM trips and probably slightly swollen face but didn't care cause I was too far off and it wasn't always there. Never got it again (but maybe some bad itching / pruritis from bad K batches). Also I had at least one, probably many, bad O-PCM batches with varying side effects. The one I remember well made me lose muscle tonus, I couldn't speak straight anymore or walk normally but thoughts were completely lucid.

 

[Bauhaus]

Immune reactions responsible for tolerance, loss of magic, bad side effects

In that the body begins to recognize a certain molecule as 'bad' and attacking it and/or its targets while it's attached to. Is this kind of reaction possible?

I dunno about dissociatives, but in case of sleep meds (benzos, z-drugs, pregabalin,...) there's definitely a correlation with immunity.
The more my immune system is compromised, especially in summertime when sunlight has a strong anti-inflammatory effect, the more sleep meds not only stop working but have the opposite effect: I feel nervous, hyperalert and usually have big hunger pangs. But when there's a rare day I actually feel really sleepy (like once or twice a year) and then take a benzo, pregabalin,... it DOES work. (And then the next day it has stopped working again).
It's like I first have to be completely exhausted before a sleep med elicits any hypnotic effect.

It's pretty odd, every time I try out a new sleep med the same pattern happens over and over again: the first time I take it I feel a little sleepy, the second time it has lost like 50% of it's effect and from the third time onwards it has completely lost it's hypnotic effect and I'm fully awake.
It's like you say, when you're body is exposed to a particular med, after a few times your body reacts opposite to it.
I just can't figure out the mechanism.

 

[sekio]

In that the body begins to recognize a certain molecule as 'bad' and attacking it and/or its targets while it's attached to.

Not unless you do some genetic engineering and start linking immunoglobins to them, as in the effort to produce a vaccine for cocaine. Generally speaking the immune system does not respond directly to "small" molecules, they need to be of a certain size to be recognized, which is why all antibodies and most allergens are protein-based. And as far as we know, people don't start producing antibodies for DXM upon exposure.

None of what you described sounds like an immune reaction or allergy either. It sounds to me like you simply overused dissociatives to the point where they were no longer considered novel and rewarding. And yeah, staying up for 3 days straight and taking DXM plus O-PCM... well, let's just say I'd be suprised if you didn't start tripping balls there. Sleep deprivation alone can cause serious cognitive problems up to and including full-blown hallucinations on all senses.

Also, I find it's normal to find that DXM is actually quite unpleasant once you've been exposed to other, better dissociatives like ketamine. After all, DXM is actually only a weak NMDA antagonist, it primarily functions as a serotonin-norepinephrine reuptake inhibitor with emphasis on the norepinephrine. So a dissociative dose is always underpinned with the effects of functionally OD'ing on antidepressants.

So, while it's obvious to think of neurotoxicity,

A lot of people jump to "neurotoxicity" as explanation for drugs having negative effects rather quickly, this doesn't seem like it. True neurotoxicity results in permanent cognitive deficits, personality changes, loss of bodily functions/sensation etc. but these effects persist even long after discontinuing the drugs in question. Also, acute neurotoxicity usually has some identifiably bad underlying incident that caused it beyond unpleasant drug trips - like an episode of serious overheating that goes uncontrolled or reckless behaviour resulting in injury.

My advice is to remember the old adage, "set and setting". Before you fixate on something being wrong with you, try to change as many variables about your experience as you can. If you normally do K in the same environment all the time your mind will no doubt begin to associate the emotionally powerful negative feelings with the setting you're in, so maybe switch it up and go outside to a park or something. Try it in a different room or different person's house. Plan some activities ahead of time that are new and enjoyable, if every time you do K you end up zonked looking at Netflix then of course the pleasure will fade away!

Switching drugs might help but in the long run if you have built negative associations (or rather, you've lost the positive associations) with the feeling of NMDA antagonism as presented by e.g. O-PCM, then MXE or diphenidine won't be that different aside from the timescale.

 

[dopamimetic]

="sekio"]Generally speaking the immune system does not respond directly to "small" molecules, they need to be of a certain size to be recognized, which is why all antibodies and most allergens are protein-based.

Thanks, didn't know this - but wait, what's about that take-an-allergy-test-dose-first (besides that to sort out whether whatever sub one's having is laced with another absurdly powerful one).

I should forget about that ugly toxic bastard DXM, you're absolutely right ... if just the other options weren't either so illegal (they managed to burn the RC scene here too with analogue laws now, and good luck finding a disso dealer on the streets) or, if remotely possible, fuck with your bladder and contain toxic impurities and/or metabolites [as like with K]. You might say, forget about the dissos - yeah if it just'd be so easy. They seemed like to be the answer I have been looking for and it's not yet ruled out, just law came in-between.

 

[Captain.Heroin]

the effort to produce a vaccine for cocaine.

ugh, please tell me that will never work...