Reversing opioid Tolerance through compounds

[Limpet_Chicken]

In the hundred mg range? at a few hundred mg...better pack a suitcase. And cold, clinical, thats how I'd describe it. Not so much as the reports of the like of MK-801/dizocilpine (now thats been on my to try list for WAY too long, or some competitive antagonists of NMDARs.) but its got an icy kinda feel to it.

Edit-isn't the rapid antidepressant effect independent at least of dissociative effects? last I heard some pharm companies had rapid acting glutamatergic antidepressants in testing, I see rapastinel and similar glycine site partial agonist or mixed glycine site agonist/NMDA antagonist drugs are in testing, and indeed in the case of rapastinel seemingly past phase II and getting fast-tracked in the US.

 

[Cotcha Yankinov]

Edit-isn't the rapid antidepressant effect independent at least of dissociative effects? last I heard some pharm companies had rapid acting glutamatergic antidepressants in testing

The NMDA antagonism may be leading simultaneously to both

1. Some dissociative effects via decreased communication between cortices (normally NMDAr seem to drive communication amongst cortices)
2. Some antidepressant effects via downstream transmitter release (as NMDAr seem to drive inhibitory neuron firing)

Maybe different NMDA antagonists have different ratios of those two effects. Ketamine, with HNK/metabolites especially seems to have rapid antidepressant effects. Makes me wonder what a low trapping NMDA antagonist adjuncted with HNK would do.

I think the dissociation may be helpful for some patients. It can be a nice break from constant rumination like many MDD patients suffer from, a bit of ego dissolution can go a long way The neurotrophic effects aside, the enhanced neuroplasticity/synaptic remodeling ability may combo well with concurrent ego dissolution, to help solidify that state if you will.

 

[freqsoft]

Is there any diagrams that show whats on a opioid postsynaptic cell, like the ones for dopamine and serotonin dopamine which are pictured below.
I'm asking because I would like to do intensive research into chemicals that interact via tolerance and take some compounds in research.
https://i.imgur.com/gonjJqc.png
https://i.imgur.com/YQVftJ6.png

I posted a video containing a 3D-rendered animation of the opioid receptor and ligand interaction. It's pretty cool. I got the DVD from a medical professional and then ripped it to YouTube.

Mechanism of Action: μ-Opioid Receptor Agonists and Antagonists (Vivitrol): https://www.youtube.com/watch?v=T5IbBX56OWw

 

[Limpet_Chicken]

Yeah I wasn't trying to argue that for some at least the dissociation is as bad of a thing as 'they' (I.e big pharma) make it out to be. Ability to dissociate was a key part of the self guided psychedelic-catalyzed therapy work I did on myself using AMT+lowish dose MXE to crack my PTSD open and start doing some rewiring of my own, of a more desirable kind.

(as to why PTSD, still rather not go into that. But I ended up going to a favourite woodland of mine, and after spending some time during the come up pondering things, whilst drifting from tree base to tree base, hunting down some tasty wild mushrooms to take home and fry up, roast and grill (depending on what I was cooking of course, some species are better one way or another, although can't beat frying for generic wild mushrooms. Although for Russula and Lactarius i rather like grilling or roasting, especially roasting Lactarius deliciosus..mmm..now thats what I call supper. Roasted with mozzarella and some black pepper and peppery boletus over the gills, whereas for say, parasols, fry 'em every time), and then settled down in a favourite particular spot, a little place I go to where I can to hunt for parasols in season, and curl up at the base of a tree and focus on the deeper rewiring work, re-soldering a few loose wetware connections if that makes sense)

IMO the dissociative effects were key to it succeeding, in that it let the AMT take me places that it'd otherwise have got my fight or flight response up against, feeling like my back is against the wall if that makes any sense. With the addition of lower dose MXE I could be my usual dispassionate, logical self and analyse things that all the same make some deep psychological impacts. But to stand aside when the faecal matter would otherwise fly.