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  1. #1
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    ^



    I know opioids work by agonizing mu-opioid receptors, but why does that cause such an effect? It feels remarkably different from every other drug I have experienced. How could activating a receptor cause perfect contentment, instant alleviating of depression, anxiety, emotional and physical pain?



    I guess what I mean is, we all say this drug works by activating this receptor. Well, duh, but what happens next? I guess I need some kind of primer on neuroscience. Any suggestions?

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    Senior Member habit's Avatar
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    Quote Originally Posted by DeGenisis View Post
    ^



    I know opioids work by agonizing mu-opioid receptors, but why does that cause such an effect? It feels remarkably different from every other drug I have experienced. How could activating a receptor cause perfect contentment, instant alleviating of depression, anxiety, emotional and physical pain?



    I guess what I mean is, we all say this drug works by activating this receptor. Well, duh, but what happens next? I guess I need some kind of primer on neuroscience. Any suggestions?


    I know enough to know I don't know. They certainly must affect dopamine, even with their anti sexual properties (IE, most dopamine agonists make you feel good and sexual, but you can't get it up, case in point coke or speed dick) whilst opiates, with SOME people, are pro sexual but you CAN get it up but You WILL NEVER bust a nut unless the stars align or you bust your back out while curling your toes.



    ...and then their is the whole "natural endorphin" aspect to them. Someone smarter than I can explain it better.



    What I can tell you, from personal experience is opiates might make you feel good at first BUT THEY WILL RUIN YOU. I've been clean from them for alllllllloooooong time now, I still don't shit solid and without a doubt my brain is permanently changed, for the worse.



    Everyone has to learn the hard way, but I wish I never saw an OC or a bag of dope in my life. It's systematically destroyed mind, body, soul and all relationships.



    I chemically respect everyone's right here to do as they see fit, but IMHO I'd just forget opiates all together. Toughest drug in the world. It WILL beat you.



    /warning off



    /knowledge about why opiates feel so good?



    /learning mode on just for nostalgia

  3. #3
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    I dont know all of the science behind it, but like Habit said, sex on them sucks. No doubt a percocet and a few beers will have you feeling nice, but if you can keep your dick up, good luck nutting.



    I dabled with them off and on for a few years. I never had a severe problem, as I would never take more than 15 mg or so at a time, and the most I ever took in a day was around 45 mgs, split over the course of a day. I guess everyone is different, but if you lose control of them (which can happen really quick), its not a good thing in the end.



    The only thing I felt when stopping, was like I had a bad cold for a few days, and after that I was fine...but then again, I didnt increase doses, and kept it somewhat under control.

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    Senior Member Ex Dubio's Avatar
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    Quote Originally Posted by DeGenisis View Post
    ^



    I know opioids work by agonizing mu-opioid receptors, but why does that cause such an effect? It feels remarkably different from every other drug I have experienced. How could activating a receptor cause perfect contentment, instant alleviating of depression, anxiety, emotional and physical pain?



    I guess what I mean is, we all say this drug works by activating this receptor. Well, duh, but what happens next? I guess I need some kind of primer on neuroscience. Any suggestions?


    It's not particularly different from any other drug of abuse; it all comes back to the mesolimbic DA system.



    I don't recall offhand whether mu opioid receptors are situated pre- or post-synaptically in the nucleus accumbens (NAc), but the upshot is that mu-opioid binding results in a fairly dramatic increase in DA release that is not (at least not immediately) responsive to the consequent D2 autoreceptor binding. In essence, you have instantly increased hedonic tone.



    Now, [meth]amphetamine, MDMA, ketamine, cocaine, etc. all have similar effects in the mesolimbic system, but one of the primary differences between opiates and amphetamine/cocaine-like stimulants is that opiates are highly selective for activating the DA system. The result is that, in individuals with high baseline anxiety or who are otherwise sensitive to enhanced stimulation, opiates are euphoric without being anxiogenic, whrereas cocaine and amphetamine-like stimulants tend to do both.



    The details of the differences are fairly sophisticated, but that's the basic idea.

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    Senior Member Azx's Avatar
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    I've gotten panic attacks twice from taking oxycodone, could be coincidence but I would guess that maybe it does indeed have some kappa opioid agonist properties? It's probably something else. So for me they are not truly 'anxiolytic' but they make talking to other people feel so good and rewarding that it abolishes my social anxiety. And unfortunately they kinda suck for neuropathic pain but I bet fentanyl would take care of anything.

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    Senior Member Ex Dubio's Avatar
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    Quote Originally Posted by Azx View Post
    I've gotten panic attacks twice from taking oxycodone, could be coincidence but I would guess that maybe it does indeed have some kappa opioid agonist properties? It's probably something else. So for me they are not truly 'anxiolytic' but they make talking to other people feel so good and rewarding that it abolishes my social anxiety. And unfortunately they kinda suck for neuropathic pain but I bet fentanyl would take care of anything.


    Don't know much about oxycodone, but from the Wikipedia article:




    A group of Australian researchers has proposed (based on a 1997 study in rats) that oxycodone, unlike morphine (the effect of which is mediated by μ-opioid receptors), acts on κ-opioid receptors.[52] Further research by this group indicates the drug appears to be a κ2b-opioid agonist.[53] However, this has been disputed, primarily on the basis that oxycodone produces effects typical of μ-opioid agonists.[54]



    Research by a Japanese group suggests that the effect of oxycodone is mediated by different receptors in different situations. Specifically, in diabetic mice the κ-opioid receptor appears to be involved in the antinociceptive effects of oxycodone,[55] while in non-diabetic mice the μ1-opioid receptor seems to be primarily responsible for these effects.[56]


    Given how little the kappa opioid receptor is understood, I'd bet it's both a mu- and kappa-agonist, but the mu-agonistic effects "win" out for most.

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    Senior Member Azx's Avatar
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    Quote Originally Posted by Ex Dubio View Post
    Don't know much about oxycodone, but from the Wikipedia article:







    Given how little the kappa opioid receptor is understood, I'd bet it's both a mu- and kappa-agonist, but the mu-agonistic effects "win" out for most.


    Damn you're fast

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    Quote Originally Posted by DeGenisis View Post
    ^

    I guess what I mean is, we all say this drug works by activating this receptor. Well, duh, but what happens next? I guess I need some kind of primer on neuroscience. Any suggestions?


    This is exactly the kind of question I love pondering.



    Here's my take, super-simplistically:



    Opioids block pain signals. Normally, the nervous system is very effective at transmitting sensory information and both signals of pain and the signalling that perceives pain in the CNS. This system is powerfully antagonised by nerves and other cells that express certain opioid receptors.



    Dopamine, on the other hand, stimulates reward pathways, or rather primes them, which we experience as an awareness of rewarding opportunities. It simultaneously, in other parts of the brain, also increases pain transmission via anxiety mechanisms - anxiety is stimulated ultimately by painful stimuli, which we anticipate. Hence because it activates both systems via dopamine sensitive nerves, it manifests as a focus and motivational effect which is distinct to classic opioid action (ignoring the vagaries of receptor subtypes).



    Its a really basal, ancient pathway. A good example is in wounds. Opiates are released from white blood cells that accumulate at the site of injury, and they then release

    opioides that reduce pain.



    The opiate system is also transplantable: in animal studies, immune cells could transfer reward to certain stimuli from one animal to another (adoptive transfer), which was manifested through opiate signalling betwen these cells and nerves that they migrate to.
    ------



    These ideas are released under a Creative Commons Share and Share alike license

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    Quote Originally Posted by Section 8 View Post
    In theory, tramadol would be close to ideal for a situation like this, given its serotonergic and noradrenergic properties, in addition to the opiod activities. One of the main functions of the opiod system is to manage the axis of existential contentment. Main problem is that the initial hopes / manufacturer's claims that tramadol wouldn't elicit tolerance in users (which is the only reason it wasn't scheduled) haven't panned out in practice; every doc I've talked to about it has expressed disappointment with the drug, paired with concern about the seizure thresshold issue (which I suspect is probably doubly troublesome in the application of treatment for a condition like OCD).



    Some of my behaviors have been described by others as compulsive, but I wouldn't describe myself as obsessive. For some reason, tramadol turns me into a bit of an asshole, which is highly unusual for me.


    That's the line that got me intruiged.

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    Senior Member John Barleycorn's Avatar
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    You don't hear about too many folks with runaway buprenorphine habits. That's possibly because access is so tightly controlled, but it could also be because of its unique pharmacology. Not that the medical establishment seems to understand this too well. I proposed low-dose bupe as an anti-depressant to a psych with an addicition specialisation a while ago, and even he couldn't see where I was coming from.

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    Senior Member MeDieViL's Avatar
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    They induce dopamine release, however thats only part of the story, dopamine release on its own doesnt cause euphoria, activation of several other receptors is needed too.



    I forgot the details but someone gave the damn rats some cookie's and the rats still loved the stuff, dopamine isnt the only player around.
    Prophet currently looking for a new job

    Getting rich or dying trying, or might as well let others enjoy my posts made on the limitless pill. But as you know, they are the best.

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    Junior Member shawn5's Avatar
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    Hi,..

    I am not quite sute how to explain it, I do not remember all of the technical terms, but I am sure you could find out if you just do a search and look for the info, google usually provides great results.



    They do react on Dopamine, which is something in the brain's pleasure centers, and opiates trigger the release of it.



    thanks,.

  13. #13
    Senior Member FunkOdyssey's Avatar
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    Quote Originally Posted by shawn View Post
    Hi,..

    I am not quite sute how to explain it, I do not remember all of the technical terms, but I am sure you could find out if you just do a search and look for the info, google usually provides great results.



    They do react on Dopamine, which is something in the brain's pleasure centers, and opiates trigger the release of it.



    thanks,.


    Don't post shit like this on M&M, it's an insult to everyone here. WTF
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    Senior Member D-termine's Avatar
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    Quote Originally Posted by FunkOdyssey View Post
    Don't post shit like this on M&M, it's an insult to everyone here. WTF


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