palmanita
Bluelighter
Suggested opioid affinity of dissociatives / use f. mental disord. & psychosis risk
While this topic has been discussed often enough here and there, at least afaik there is no clear consens about it yet?
To the times when MXE came out, I too believed it to have opioid activity. It felt absolutely like one should, so it has to be one.
- Okay, I've changed my mind.
First I have to say that, because of whatever, opioids don't work for me or not as how I'd have expected them to do so. They are weird dysphoric sedatives with some physical antinociception thrown in, up to the dosage where I would nod hard and fear of respiratory depression. At this point I've experienced some euphoria and everything-is-pointless mood once with a 1:25 RC-fentanyl mixture.
This was being a reasonably experienced dissociative user. I could, and can't, believe why people are putting their health and lives into real danger every day by (ab)using potent opioids. (Why didn't I just stop? Because I'm severly mentally ill and dissociatives, feeling like opioids should, relieve just everything, and dissociatives tend to the unfortunate property of being not just prohibited but also prescriptionally unavailable. I know of other countries where ketamine scripts can be given to severly depressed people or those being in unbearable pain but not here... and... ketamine is short lived and dirty. I still have to experience pharmaceutically pure K straight out the ampoule though. Memantine isn't bad, especially in combination, but [WTF] it's easier to get a script for opioids than for that as off-label.)
Now we have things around like the diarylethylamines of which the levo half probably is an opioid, seeing MT-45 and lefetamine (while the latter's claims also, afaik, are solely based on that its analgesia is reversed by naloxone & anecdotary experiences). The diarylethylamines tend to feel dirty for part of the users, and appear to lack these particular low-dose effects I'm in need of.
Also we have the O-PCx'es. While I didn't believe it at first, probably because of impure shit being sold, pure O-PCM while on venlafaxine feels almost exactly like my beloved MXE just with a shorter duration and less impairing (which also could be attributed to impure MXE maybe).
Particularly I think now of the O-PCx psychosis cases - of which I too was one in the late 2015's - as following:
- Impurities. There is a shitload of them and I'd love to know what is in the remaining 2,5% or whatever purity vendors claim and that often unveils to be a comma-miss (25%).
- Compulsive redosing. The faster a dissociative hits, the more of a dopaminergic it becomes. Don't know how much it is about direct DAT antagonism, D2 agonism or just suddenly increased transmitter outflow including DA but ketamine and O-PCM have a short-lived fiendish dopamine hit and after the plateau has passed, feelings of (DA) comedown. With the PCMs for me it's at around one hour. This leads to redosing while the compound is still active, buildup and stronger NMDA blockade. A sneaky (but also very appreciable, if used right) property of NMDA antagonism is the subjective clarity.
- Mania. Or grandose thinking, behaviour, call it as you want but dissociatives are uplifting compounds and with the lack of show-stopping side effects that approved antidepressant agents usually have (or immobilization at least -> K, also something I weirdly don't get), one will eventually run into some sort of mania.
Okay, back to the topic. My theory is now, that not dissociatives are usually opioids, but rather with increasing real opioid activity, they begin to feel dirty and even dysphoric for some, probably those with little or no opioid tolerance.
Maybe dynorphins are part of the picture, why some people greatly enjoy opioids and other not or require tolerance to do so (I've read repeatedly now that the first or first few heroin doses weren't enjoyable, could be a matter of pre-existing conditions, genetics, or both). Buprenorphine is the only opioid I get somewhat positive effects out of and this too is now only because I'm in real mental pain now due to the shitty legal consequences of my drug use (say, prison hailing). It substitutes for this nice condition the docs home-made by stopping my memantine, cold-turkey, thrice. Probably DA agonist PAWS and/or exacrebation of what I think to be environmentally-induced or potentiated glutamate / NMDA disequilibrium (being overly sensible, chronically stressed, ADD-alike.. kinda mental hyperalgesia, my mother suffers from the same thing).
However, I'm on maintenance buprenorphine now, 4mg/d. For dissociative abuse, yeah. So there is very little chance of the O-PCM being able to hit my opioid receptors now in 1/5 or so the dose required to hole. Such strong affinity would be known and also lead to fatalities. Yet it feels the same as without the bupe. Very "opiated", much more so than any opioid ever did. Once I just wanted to know it and got two 10mg methadone pills. I've titrated up from 2.5mg and felt increasingly dysphoric at 10-15mg, so I threw the leftover away. This lasted for 36h maybe, in the meantime 0.4mg bupe intranasally- for potency and faster onset- relieved it partially, somewhat clearly inducing opioid receptor response with the additional bupe kicking the methadone off them(?). Other point I know now of course is that bupe/opioids, while keeping a background effect, require the usual steep dose escalation for being felt. Without direct opioid tolerance, every increase of the bupe dose had an acute effect for 2-3 days (at first I felt an increase of 0,4 - then 0,8 - you get it).
This is not the case with NMDA antagonists. Tolerance is very different with them and as I know from my relationship with MXE and later K, as long as I kept a healthy dosage regimen (not getting fooled by the DA -> or at least use a stimulant for re-dosing instead of the dissociative), the same dosage hits over and over again and I feel every dose, be it a tiny or a bigger one.
So after trying at least 7 different NMDA antagonists I think to know more or less what the effects of NMDA blockade are like, and what is due to other receptors. I know that one can't feel a particular receptors but yea. (Would make an interesting double-blind trial, e.g. quetiapine 25/50mg vs. hydroxyzine 10-20mg etc..)
Now the usual challenge to check (mu?)opioid activity, besides receptor ligand tests, afaik is to see whether analgesia or general effects are abolished by naloxone. Just that naloxone isn't exactly a silent agonist but an inverse one. And while strangely alcoholics usually tolerate naltrexone and it "should" not have effects in the naive, there are effects and I've read statements like "induces a frustrative state of non-reward". Also it diminishes the ability to tolerate stress and leads to hypersensitivity/-algesia in at least newborn chicks and guinea pigs. Doesn't this alone render naloxone challenges in this sense misleading? If we have an indirectly rewarding compound and one that is indirectly reward-abolishing - well
at least one would have to find a certain dose of an opioid with its naloxone counterpart which would neutralize each other, then administer this combination together with the to-be-checked drug and if there are differencies in the reactions to naloxone alone, then it wasn't because of increased opioid activity... or am I wrong here?
The point of dissociatives being analgesic w/o involving opioid receptors (directly), working side-by-side with and independent of opioids in the system- couldn't this mean that, regardless of NMDA-mu connections, one could block the mental effects of opioid reduction/WD together with associated conscious learning (what, in my laymans' speak, might be the cause of PAWS) and just let them re-adjust silently respectively leaving only the peripheral W/D that can be avoided with loperamide at first?
Question: I know of potential negative influences on learning and memory of continued NMDA antagonism, independent of the antagonists' kinetics. But seemingly the more severe consequences - psychosis, mania etc - only occur with those having a higher trapping than memantine, now leaving the secondary effects out of consideration for a moment. Will a strict, low-dosed but continuous, regimen of a pure but high trapping antagonist like O-PCM (should it prove to be non-antibiotic) inevitably lead to psychosis or is moderation the key? Pain patients using K don't run into psychosis if I'm correctly informed.
Or, other question, what is wrong with me having a weird state of mental illness that -out of the drugs available today- only responds to NMDA antagonists in a relatively narrow dose window? Nothing else helps as good by far, and also continued so it's not just an addiction. Many other agents only work as expected with a bit of a NMDA antag in my system, like stimulants / methylphenidate, antidepressants / SSRIs, opioids / painkillers, even caffeine! I very probably do have PTSD (could be the cause and/or result of a faulted stress-regulating or responding glutamatergic circuit??), hyper-sensibility and easy distraction (again, might be the result of the previous), hyperalgesia mentally as well as to some extent physically (dito, and together building a solid base for social phobia, mood swings, depression) ... as I wrote, my mother suffers from the same things and (also, but more than myself) becomes delusional when she's alone for too long periods of time ... so genetics might well be to blame.
Might this fall into the spectrum of ailments like Huntington's etc. (I know you can't diagnose over the net %) just asking) and maybe a related specialist could help me more? I'm also putting some hope into riluzole, being another scarcerly used glutamate modulating agent- if this isn't wrong and it acts only on soium channels but even then it mighr help.
Sodium valproate did help too, for a very high price. Among the countless, partially barely researched drugs I've done in my life this was the first one that had real, bad physical side effects and if what I've read here is true, then that price would raise even higher if I'd have continued it or would start it again. I'm literally aged 3-4 years outwardly in the 6 months on and after valproate, confirmed by independent individuals.
Will the use of NMDA antagonists over extended amounts of time, even if it's just memantine, induce a vicious circle of more glutamate / NMDA receptors and exacrebation of the symptoms that is worse than just tolerance to the agent?
Thank you.
While this topic has been discussed often enough here and there, at least afaik there is no clear consens about it yet?
To the times when MXE came out, I too believed it to have opioid activity. It felt absolutely like one should, so it has to be one.
- Okay, I've changed my mind.
First I have to say that, because of whatever, opioids don't work for me or not as how I'd have expected them to do so. They are weird dysphoric sedatives with some physical antinociception thrown in, up to the dosage where I would nod hard and fear of respiratory depression. At this point I've experienced some euphoria and everything-is-pointless mood once with a 1:25 RC-fentanyl mixture.
This was being a reasonably experienced dissociative user. I could, and can't, believe why people are putting their health and lives into real danger every day by (ab)using potent opioids. (Why didn't I just stop? Because I'm severly mentally ill and dissociatives, feeling like opioids should, relieve just everything, and dissociatives tend to the unfortunate property of being not just prohibited but also prescriptionally unavailable. I know of other countries where ketamine scripts can be given to severly depressed people or those being in unbearable pain but not here... and... ketamine is short lived and dirty. I still have to experience pharmaceutically pure K straight out the ampoule though. Memantine isn't bad, especially in combination, but [WTF] it's easier to get a script for opioids than for that as off-label.)
Now we have things around like the diarylethylamines of which the levo half probably is an opioid, seeing MT-45 and lefetamine (while the latter's claims also, afaik, are solely based on that its analgesia is reversed by naloxone & anecdotary experiences). The diarylethylamines tend to feel dirty for part of the users, and appear to lack these particular low-dose effects I'm in need of.
Also we have the O-PCx'es. While I didn't believe it at first, probably because of impure shit being sold, pure O-PCM while on venlafaxine feels almost exactly like my beloved MXE just with a shorter duration and less impairing (which also could be attributed to impure MXE maybe).
Particularly I think now of the O-PCx psychosis cases - of which I too was one in the late 2015's - as following:
- Impurities. There is a shitload of them and I'd love to know what is in the remaining 2,5% or whatever purity vendors claim and that often unveils to be a comma-miss (25%).
- Compulsive redosing. The faster a dissociative hits, the more of a dopaminergic it becomes. Don't know how much it is about direct DAT antagonism, D2 agonism or just suddenly increased transmitter outflow including DA but ketamine and O-PCM have a short-lived fiendish dopamine hit and after the plateau has passed, feelings of (DA) comedown. With the PCMs for me it's at around one hour. This leads to redosing while the compound is still active, buildup and stronger NMDA blockade. A sneaky (but also very appreciable, if used right) property of NMDA antagonism is the subjective clarity.
- Mania. Or grandose thinking, behaviour, call it as you want but dissociatives are uplifting compounds and with the lack of show-stopping side effects that approved antidepressant agents usually have (or immobilization at least -> K, also something I weirdly don't get), one will eventually run into some sort of mania.
Okay, back to the topic. My theory is now, that not dissociatives are usually opioids, but rather with increasing real opioid activity, they begin to feel dirty and even dysphoric for some, probably those with little or no opioid tolerance.
Maybe dynorphins are part of the picture, why some people greatly enjoy opioids and other not or require tolerance to do so (I've read repeatedly now that the first or first few heroin doses weren't enjoyable, could be a matter of pre-existing conditions, genetics, or both). Buprenorphine is the only opioid I get somewhat positive effects out of and this too is now only because I'm in real mental pain now due to the shitty legal consequences of my drug use (say, prison hailing). It substitutes for this nice condition the docs home-made by stopping my memantine, cold-turkey, thrice. Probably DA agonist PAWS and/or exacrebation of what I think to be environmentally-induced or potentiated glutamate / NMDA disequilibrium (being overly sensible, chronically stressed, ADD-alike.. kinda mental hyperalgesia, my mother suffers from the same thing).
However, I'm on maintenance buprenorphine now, 4mg/d. For dissociative abuse, yeah. So there is very little chance of the O-PCM being able to hit my opioid receptors now in 1/5 or so the dose required to hole. Such strong affinity would be known and also lead to fatalities. Yet it feels the same as without the bupe. Very "opiated", much more so than any opioid ever did. Once I just wanted to know it and got two 10mg methadone pills. I've titrated up from 2.5mg and felt increasingly dysphoric at 10-15mg, so I threw the leftover away. This lasted for 36h maybe, in the meantime 0.4mg bupe intranasally- for potency and faster onset- relieved it partially, somewhat clearly inducing opioid receptor response with the additional bupe kicking the methadone off them(?). Other point I know now of course is that bupe/opioids, while keeping a background effect, require the usual steep dose escalation for being felt. Without direct opioid tolerance, every increase of the bupe dose had an acute effect for 2-3 days (at first I felt an increase of 0,4 - then 0,8 - you get it).
This is not the case with NMDA antagonists. Tolerance is very different with them and as I know from my relationship with MXE and later K, as long as I kept a healthy dosage regimen (not getting fooled by the DA -> or at least use a stimulant for re-dosing instead of the dissociative), the same dosage hits over and over again and I feel every dose, be it a tiny or a bigger one.
So after trying at least 7 different NMDA antagonists I think to know more or less what the effects of NMDA blockade are like, and what is due to other receptors. I know that one can't feel a particular receptors but yea. (Would make an interesting double-blind trial, e.g. quetiapine 25/50mg vs. hydroxyzine 10-20mg etc..)
Now the usual challenge to check (mu?)opioid activity, besides receptor ligand tests, afaik is to see whether analgesia or general effects are abolished by naloxone. Just that naloxone isn't exactly a silent agonist but an inverse one. And while strangely alcoholics usually tolerate naltrexone and it "should" not have effects in the naive, there are effects and I've read statements like "induces a frustrative state of non-reward". Also it diminishes the ability to tolerate stress and leads to hypersensitivity/-algesia in at least newborn chicks and guinea pigs. Doesn't this alone render naloxone challenges in this sense misleading? If we have an indirectly rewarding compound and one that is indirectly reward-abolishing - well
at least one would have to find a certain dose of an opioid with its naloxone counterpart which would neutralize each other, then administer this combination together with the to-be-checked drug and if there are differencies in the reactions to naloxone alone, then it wasn't because of increased opioid activity... or am I wrong here?The point of dissociatives being analgesic w/o involving opioid receptors (directly), working side-by-side with and independent of opioids in the system- couldn't this mean that, regardless of NMDA-mu connections, one could block the mental effects of opioid reduction/WD together with associated conscious learning (what, in my laymans' speak, might be the cause of PAWS) and just let them re-adjust silently respectively leaving only the peripheral W/D that can be avoided with loperamide at first?
Question: I know of potential negative influences on learning and memory of continued NMDA antagonism, independent of the antagonists' kinetics. But seemingly the more severe consequences - psychosis, mania etc - only occur with those having a higher trapping than memantine, now leaving the secondary effects out of consideration for a moment. Will a strict, low-dosed but continuous, regimen of a pure but high trapping antagonist like O-PCM (should it prove to be non-antibiotic) inevitably lead to psychosis or is moderation the key? Pain patients using K don't run into psychosis if I'm correctly informed.
Or, other question, what is wrong with me having a weird state of mental illness that -out of the drugs available today- only responds to NMDA antagonists in a relatively narrow dose window? Nothing else helps as good by far, and also continued so it's not just an addiction. Many other agents only work as expected with a bit of a NMDA antag in my system, like stimulants / methylphenidate, antidepressants / SSRIs, opioids / painkillers, even caffeine! I very probably do have PTSD (could be the cause and/or result of a faulted stress-regulating or responding glutamatergic circuit??), hyper-sensibility and easy distraction (again, might be the result of the previous), hyperalgesia mentally as well as to some extent physically (dito, and together building a solid base for social phobia, mood swings, depression) ... as I wrote, my mother suffers from the same things and (also, but more than myself) becomes delusional when she's alone for too long periods of time ... so genetics might well be to blame.
Might this fall into the spectrum of ailments like Huntington's etc. (I know you can't diagnose over the net %) just asking) and maybe a related specialist could help me more? I'm also putting some hope into riluzole, being another scarcerly used glutamate modulating agent- if this isn't wrong and it acts only on soium channels but even then it mighr help.
Sodium valproate did help too, for a very high price. Among the countless, partially barely researched drugs I've done in my life this was the first one that had real, bad physical side effects and if what I've read here is true, then that price would raise even higher if I'd have continued it or would start it again. I'm literally aged 3-4 years outwardly in the 6 months on and after valproate, confirmed by independent individuals.
Will the use of NMDA antagonists over extended amounts of time, even if it's just memantine, induce a vicious circle of more glutamate / NMDA receptors and exacrebation of the symptoms that is worse than just tolerance to the agent?
Thank you.
