Identifying opioidergic dysfunction and sustainably remedying it

[achey node]

Given that mental illness is characterised by a disorder in one or more brain systems it is quite contradictory that the endogenous opioid system and in particular the mu opioid recpetor and its native agonists are ignored. Prolific serotonin reuptake and monoamine oxidation both result in the presentationof depressive symptoms but there is no scientific model that I know of describing the same situation at the mu opioid receptor site.

I vaguely remember that Effexor or some similar SNRI has been identified as binding to receptor sites but overall medical orthodoxy seems to lack the courage to remedy disorders of the opioid system.

What is the current state of affairs regarding this and are there any long term non neurotoxic/sustainable opioid derivatives which can prevent attenuating factors in endorphin production and longevity.

 

[Hammilton]

Opioids were used for this purpose, they haven't been ignored, they've been discarded in favor of drugs with fewer side effects. Patients on a live long course of opioid therapy generally take higher and higher doses, especially when they're being used for their mood altering properties, which requires higher doses than the analgesic properties do.

There is some use of Buprenorphine patches and even Suboxone for this purpose, but it's real limited, and tramadol has been prescribed as an antidepressant.

 

[Lightning-Nl]

Yeah there is antidepressive actions from the opioids. However, the side-effects of exerting antidepression through the opioid system is way too high, especially when compared to other medications. This has been studied since the discovery of Opium. However, it was deemed unacceptable for that use because of the very high likelihood of addiction and the indirect side-effects that addiction brings upon someone (depression, loss of job, loss of money, anxiety).

Use of opioids as a means of antidepression would be paradoxical because; in the long-run, opioids will just cause pain and missery.

 

[Lightning-Nl]

This is why opioids aren't an option. There is literally no better explanation that can ever be said. This, right here, is why opiates aren't an option. I'm dead serious.

 

[ebola?]

We haven't yet developed the tools to reliably identify such a deficiency or sustainably treat it. The current best bet is partial agonists like bupe', but even this line of treatment doesn't appear indefinitely sustainable.

ebola

 

[endotropic]

Yeah there is antidepressive actions from the opioids. However, the side-effects of exerting antidepression through the opioid system is way too high, especially when compared to other medications. This has been studied since the discovery of Opium. However, it was deemed unacceptable for that use because of the very high likelihood of addiction and the indirect side-effects that addiction brings upon someone (depression, loss of job, loss of money, anxiety).

Use of opioids as a means of antidepression would be paradoxical because; in the long-run, opioids will just cause pain and missery.

Well said, that pretty much sums up why traditional opiates aren't used for major depressive disorder these days.

On the other hand, there could be mood disorders that are caused by deficiencies in the endogenous opiate system, and we might be able to treat them through the delta and kappa receptors. You might find this interesting OP:


Opioid receptors: distinct roles in mood disorders.

Abstract
The roles of opioid receptors in pain and addiction have been extensively studied, but their function in mood disorders has received less attention. Accumulating evidence from animal research reveals that mu, delta and kappa opioid receptors (MORs, DORs and KORs, respectively) exert highly distinct controls over mood-related processes. DOR agonists and KOR antagonists have promising antidepressant potential, whereas the risk-benefit ratio of currently available MOR agonists as antidepressants remains difficult to evaluate, in addition to their inherent abuse liability. To date, both human and animal studies have mainly examined MORs in the etiology of depressive disorders, and future studies will address DOR and KOR function in established and emerging neurobiological aspects of depression, including neurogenesis, neurodevelopment, and social behaviors.

 

[Lightning-Nl]

Good information. Thanks for read.

I remember reading something about the role that the opioid system plays in the phenomena we know as derealization/depersonalization. They found this out because Naloxone seems to be an effective treatment for dissociation. That's quite fascinating to be honest. I'd theorize that what ever is causing you to dissociate is so traumatic that the brain has no idea how to deal with that emotional trauma - so it manifests itself as physical pain. How does the body deal with physical pain? Endogenous opioids...

 

[Hammilton]

I would think that Kratom would be a decently sustainable opioid for long term use.

 

[ebola?]

mmm...7-ho-mitragynine is a fairly straightforward full mu-agonist with affinity several times that of morphine. It seems to be primarily because of auxiliary adrenergic activity that people don't take their kratom habits too far.

ebola

 

[Hammilton]

Sure, but what about mitragynine? There are a number of compounds with affinity for opioid receptors, and I don't think it's the adrenergic activity. I think it's got a huge range of activities. While it may be blocking withdrawal for me very effectively and not taking it will result in withdrawal symptoms, it feels absolutely nothing like an opiate. There's zero warmth, no nodding, no fleeting images when I fall asleep.

It's an extremely complicated plant, probably up there with marijuana.

Some strains are certainly very stimulating, I can't stand maeng da's because they are all adrenergic stimulation. However, a red vein Bali feels nice- but it doesn't feel anything like an opioid. It's sedating, kind of messes with my vision, like a benzo- you may not notice it when you're sitting down, but you get up and walk around and you really notice it. You're not dizzy, so much, but your vision isn't right. I don't know if it's due to delta affinity, I've never tried a strong delta agonist. Perhaps the oxindoles are gaba agonists- it feels like a depressant to me, not a euphoric one, though, it's a pretty neutral thing.

I don't think this extends to the extracts, though. 9, 10g 's of RVB keeps me out of withdrawal, and makes me a little wobbly. A gram or a gram and a half of gold reserve or a full spectrum red extract have some warmth and euphoria that just isn't present in the whole plant, regardless of dose.

 

[ebola?]

While it may be blocking withdrawal for me very effectively and not taking it will result in withdrawal symptoms, it feels absolutely nothing like an opiate. There's zero warmth, no nodding, no fleeting images when I fall asleep.

YMMV...feels like an opiod to me, particularly Bali strains. Yes, I get warmth and can nod from it. This is without significant acquired tolerance to any opioid though. However, you're probably right about extractions being a different story, particularly if partially selective for 7-ho-mitragynine, I hypothesize.

I don't know if it's due to delta affinity, I've never tried a strong delta agonist.

Y'know, my memory may be malfunctioning here, but I think I read a study demonstrating strong selectivity for mu by 7-ho-m...but this doesn't really extend to the other alkaloids.

ebola

 

[sekio]

Mitragynine substitutes for morphine in rats, I don't think anyone is debating its opioidergic nature, seeing as humans use it in opioid w/d too. Whether or not it subjectively feels the same to morphine seems irrelevant, expectation effects and all.

At most higher doses the adrenergic effects of even the "narcotic" strains do become apparent, though. I guess this is the buproprion of opioids.

 

[ebola?]

Right, but each with distinct mechanisms for their 'ceiling effects'. I mean, maybe kratom is a demonstration of what someone should combine with yohimbine to make the experience tolerable.

ebola

 

[Hammilton]

I dunno, I've had an ounce of Bali and never had any sort of stimulation, and the whole classic description is that kratom is a dual level experience, a stimulant at low doses, depressant opioid at higher doses. Just feels like a depressant, and a weird long acting one that doesn't actually last very long. A bag of dope would have me nodding, so my tolerance isn't high. A gram of extract feels a bit like a roxy. There just seems to be so much going on with kratom, and while it'll block withdrawal, it doesn't feel like an opioid at all, perhaps because of my tolerance.

 

[sekio]

it doesn't feel like an opioid at all, perhaps because of my tolerance.

I think this is probably a large factor. Most opioid-naive/low-tolerance people I know who have tried kratom at higher doses get their socks knocked off, puking, passing out, shit like that.

You're right though: the experience is not 100% representative of opioids... very likely the yohimbine-type adrenergic antagonism plays a role.

One day when I have some free time I will (instead of just eating it) try to crunch numbers on the alkaloid content of the various strains that are sold near me... would be neat.

 

[ebola?]

Please keep me posted, as one of the more minor constituents (Rhynchophylline) has been found to antagonize NMDA, but I have no idea whether the concentrations are high enough for this to prove relevant.

ebola

 

[yaesutom]

I would think that Kratom would be a decently sustainable opioid for long term use.

I was addicted to kratom for a couple years, i really enjoyed it... just decided to take it daily. Near the end, i started to get a "withdrawal" even when I was taking it like normal. When I went to sleep, right as i'm dozing off I would get a jolt that would wake me up.. but if i tried to take a little kratom then i'd get stimulated and couldn't sleep. Even when i was REALLY tired... nothing I could do to sleep because the jolts would zap me awake. So I just had to quit totally.

Then months later (after successfully quitting and getting back to normal) I thought I could do some here and there but even after just a couple days I started to get the body/brain zaps preventing me from sleeping... The zaps would be like strong chills all over my body like I was hot and cold at the same time, and would only happen right when I fell asleep (waking me back up over and over... awful!)