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Morphine drives cells to suicide (and this could be inhibited)

dopamimetic

dopamimetic

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Joined
Mar 21, 2013
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Just found this, which I thought might be very interesting to the one or other around here.

Opium-related compounds, or 'opioids', have been used as painkillers for centuries. However, as well as being highly addictive, opioids, doctors have observed, can somehow affect the functioning of the immune system.
Now Yufang Shi and colleagues of the American Red Cross, Rockville, Maryland may have discovered how. Shi's group report in Nature that morphine can stimulate some cells to kill themselves. It does this by encouraging them to manufacture, or 'express', a protein, 'Fas', which they display on their surfaces. But Fas is no harmless artefact. Quite the contrary, Fas is the cellular version of the white flag of surrender. For, once Fas appears on the outside of a cell, another protein, 'Fas Ligand' (FasL) locks onto it, triggering the death of that cell.
Morphine can induce cell suicide (so-called 'apoptosis') only in cells to which it can actually affix - cells, that is, with opioid receptors. The two best-characterised groups of such cells are brain cells (neurons) and certain white blood cells (lymphocytes - a key part of the immune system.) Indeed Shi's team found that morphine induced a dramatic increase in the expression of Fas in fresh human lymphocytes - a phenomenon that could be prevented by blocking the opioid receptors.
In addition the researchers proved that the protein Fas is an essential piece of the cell-suicide jigsaw by showing that morphine did not promote apoptosis in white cells taken from Fas-deficient mice. They also proved that it is the interaction of Fas with its complementary protein, FasL, that induces cell death, by administering another Fas-binding substance, 'FasIg' to normal mice at the same time as the morphine. As predicted, FasIg prevented cell suicide by hooking onto Fas, thereby stopping FasL from doing likewise. Morphine sulphate alone, on the other hand, reduced the number of splenocytes (spleen white cells) in normal mice by 30% in 24 hours.
Under normal circumstances Shi's group explain "only a small portion of cells undergo opioid-induced apoptosis because Fas-mediated apoptosis requires FasL, which is expressed in only a limited number of cells." But during illness or injury, they suggest, "the amount of FasL may increase [and thus] opioid-induced apoptosis could also increase."
So, given that opioid-receptors are found mainly in brain and the immune cells, this is a discovery which not only bears on the consequences of taking morphine but that, as the researchers conclude, "should also help our understanding of the interaction between the nervous and the immune systems."
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Source

What are the implications of that, I thought of morphine etc. being some of the few substances you could theoretically do for life without causing physical harm. At least addiction experts tell that.
 
At first glance it would appear that morphine would be less effective at its intentions as not only is the bioavailablity a travesty but if it fights itself we def need a new drug. :)
 
Something very interesting is the fact that when you have a dope/opiate habit, you don't get sick even though your immune system is supressed. I swear last year i was banging 100mg morphine daily i didn't get sick once until recently that i quit, i finally catched a cold in years.
 
Interesting, is it saying this predominately targets brain cells in this flagging for death? You'd think if this causes any substantial deficit in neurons this would've been shown before what this study is inferring of this mechanism.
 
nznity said:
Something very interesting is the fact that when you have a dope/opiate habit, you don't get sick even though your immune system is supressed. I swear last year i was banging 100mg morphine daily i didn't get sick once until recently that i quit, i finally catched a cold in years.
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I'd second that, while on opiates for about 2 years I was never really sick, yet not really healthy either ... over time I felt the hormone/immune suppression as sort of physical exhaustion / chronic fatigue which led me to using stimulants and the worst point is that it's a kind of chemical imbalance which lasts way beyond acute withdrawal/tolerance. But yeah, never sick as in cold. (Edit: Oh wait, isn't the cold syndrom actually the immune response??)

@Nagelfar: I've barely read anything about how clean long-term addicts cope with life and in terms of cognitions/emotions? Just cause sth isn't as easy visible as in alcoholics, it doesn't have to be absent :) even when it's something particularly to morphine then the heroin folks should get it too ... in clinics, the methadone people tend to look worse physically but to me morphine felt definitely more taxing than metha/other synthetics.
 
dopamimetic said:
I'd second that, while on opiates for about 2 years I was never really sick, yet not really healthy either ... over time I felt the hormone/immune suppression as sort of physical exhaustion / chronic fatigue which led me to using stimulants and the worst point is that it's a kind of chemical imbalance which lasts way beyond acute withdrawal/tolerance. But yeah, never sick as in cold.

@Nagelfar: I've barely read anything about how clean long-term addicts cope with life and in terms of cognitions/emotions? Just cause sth isn't as easy visible as in alcoholics, it doesn't have to be absent :) even when it's something particularly to morphine then the heroin folks should get it too ... in clinics, the methadone people tend to look worse physically but to me morphine felt definitely more taxing than metha/other synthetics.
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i haven't had a cold in 2 years, been clean for 3 weeks of morphine. Let's see how ilong i can last without getting sick.
 
nznity said:
Something very interesting is the fact that when you have a dope/opiate habit, you don't get sick even though your immune system is supressed. I swear last year i was banging 100mg morphine daily i didn't get sick once until recently that i quit, i finally catched a cold in years.
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So true. Opiates seem to do the same with illness as they do with problems - I.e. screw them up and brush them under the carpet.

But when you stop, they come back with a vengeance...
 
F.U.B.A.R. said:
So true. Opiates seem to do the same with illness as they do with problems - I.e. screw them up and brush them under the carpet.

But when you stop, they come back with a vengeance...
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u can be using rain water to prepare ur shots, spend all night on rainy/snowy days begging for money high on dope and not get fucking sick but u quit and catch a cold immediately.
 
F.U.B.A.R. said:
I stopped banging smack in 2010, came off methadone a few years later. The good thing is that I can't say for definite when I got 'clean', because I've stopped counting. Afaic, if you're still counting the days, you're still an addict...
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it's like preparing for the next relapse.......yeah been there too many times, my brain is so fucked up atm. I'm using a lot of crack these days to not think about Morphine, shit's got a grip so hard on me. But I'm getting there one step at a time....
 
nznity said:
it's like preparing for the next relapse.......yeah been there too many times, my brain is so fucked up atm. I'm using a lot of crack these days to not think about Morphine, shit's got a grip so hard on me. But I'm getting there one step at a time....
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One step at a time is all you can do. The worst thing is to try and run before you can walk. Slow and easy wins the race, as the tortoise said to the hare.

All the best mate... 👍
 
F.U.B.A.R. said:
Opiates are the perfect antidote to life...
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Somehow I continue to think that this is only part of the picture.. Maybe these agents are too strong or they have additional activities like this one here but I like opioids and think they can be used in a non-destructive way.. All drugs can be..
 
dopamimetic said:
Somehow I continue to think that this is only part of the picture.. Maybe these agents are too strong or they have additional activities like this one here but I like opioids and think they can be used in a non-destructive way.. All drugs can be..
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For me the main reason I could never use them in a non-destructive way was lack of access. I think if a doctor would have prescribed me opioids on a dosing schedule I wouldn't have pushed it as far as I did. Since my access was always limited I went elsewhere to seek them out. By seeking them out like that I always bought more than I needed and did more than required during sessions.

If a doctor would have given me 30mg of oxycodone daily 10 years ago I would have probably maintained using it that way orally for a long time. Maybe there would have been a bump in dosage here or there but I would have remained stable. Since they wouldn't do this I went to the street where I would usually obtain 50-100mg at a time. Having the extra supply I pushed the dose and explored other ROAs. In time I even explored other opioids due to oxycodone getting harder to find. Eventually this led to full blown addiction to opioids and taking risks I wouldn't have done otherwise.

I've always been of the opinion that if some opioids were OTC or available OTC in their natural forms (say smoking opium) we would have less of a problem with them. You make them OTC and you make them boring. People are less inclined to try things that they see as boring. Those that would become addicts anyway would be able to obtain their drugs for cheaper, it would be taxed, and it would be safer than buying them where they buy them now. Another thing to consider is the fact it's easy to maintain an addict on a drug like heroin than it is methadone. Studies suggest that it's more effective and easier to ween an addict off a drug like heroin than it is methadone or subs.

I think most opioids addicts are like functional alcoholics. If obtaining their drugs were easier they could hold down a job and function in society. Since their drugs are so expensive, seeking help is looked down upon, and it's nearly impossible to work while in w/d we've ended up with a lot of folks that don't cause many problems causing lots of problems for society. I know when I was using heavy I had no problems holding a job as long as I had enough drugs to starve off w/d during my shifts. I lost my jobs back then because my supply would suddenly be cut off for a few days and I'd have to lay out of work with "the flu" multiple times a year. When I was using at work no one could tell and I was often told by my bosses that I was a great employee.
 
That's so true 😐

Access to NMDA antagonists (or psychedelics??) might be crucial too. I guess you could use opioids every, don't know, pretty often with no consequences if you do it right.
 
dopamimetic said:
I guess you could use opioids every, don't know, pretty often with no consequences if you do it right.
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Having used a lot of drugs daily over the years I'd say opioids allow you to remain more functional than most. It isn't a free ride, you have to deal with things like constipation, but for the most part they could be used near daily for most without creating many problems. They certainly create less problems than common drugs used daily that can't even get one high. The main problem with opioids has always been running out of them.
 
HeadphonesandLSD said:
Having used a lot of drugs daily over the years I'd say opioids allow you to remain more functional than most. It isn't a free ride, you have to deal with things like constipation, but for the most part they could be used near daily for most without creating many problems. They certainly create less problems than common drugs used daily that can't even get one high. The main problem with opioids has always been running out of them.
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Some doctors say that daily opioid use makes a person more selfish, because their source of pleasure is then a chemical one instead of doing work and socializing with others. And that even when there's no problem in obtaining your drug supply. There doesn't necessarily exist any proof of this claim, though.

In the political climate of many nations, even the fact how easy it is to use opiates as an intentional suicide method would alone be enough to keep them off the free market.
 
Programmed cell death is a rampant adaptive mechanism throughout childhood. Children end up losing 33% of the neurons naturally on the way to adulthood.

Opioids can depress breathing so that your cells don't get enough nutrition, mostly with higher ("nod") doses and while sleeping. That probably isn't healthy.
 
Yeah I know that "cell death" isn't always what it seems to be, it is absolutely necessary to stay alive and healthy, to sort out e.g. cancer cells etc. but in moderation ... so I would love if somebody more educated than me could shed some light on whether this is something we have to worry about and whether it is special to morphine or not. These papers are confusing snapshots sometimes.
 
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