Author Topic: The NO-ONOO theory of oxidative stress as the cause of disease (ML Pall)  (Read 4796 times)

[Buddie]

Re: The NO-ONOO theory of oxidative stress as the cause of disease (ML Pall)
« Reply #70 on: November 03, 2021, 05:49:11 pm »
interesting thread and theory - has anyone had any success in healing their Benzo Withdrawal with this method???
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[Buddie]

Re: The NO-ONOO theory of oxidative stress as the cause of disease (ML Pall)
« Reply #71 on: November 18, 2021, 08:16:41 pm »
Really - did this conversation just die out?
Has there been any new insights?  Seems like a real possibility of what is going on, but taking 15 supplements seems impossible for most of us.  Just wondering if ANYONE saw ANY sign that this is the right direction...
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[Buddie]

Re: The NO-ONOO theory of oxidative stress as the cause of disease (ML Pall)
« Reply #72 on: November 23, 2021, 12:00:53 am »
I tried following the recommendations Pall has made assuming that the NO/ONOO cycle he describes is the root cause for protracted benzo withdrawal issues.

Sort of his silver bullet for reducing NO levels is injected hydroxocobalamin (a form of B12).  I started at injecting 2mg/day and eventually went up to 10mg/day. No joy.

There was a period where it seemed like it was working, but if it was it wasn't sustainable.



« Last Edit: November 23, 2021, 12:07:39 am by [Buddie] »
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[Buddie]

Re: The NO-ONOO theory of oxidative stress as the cause of disease (ML Pall)
« Reply #73 on: November 26, 2021, 05:47:07 pm »
Thanks [...] for responding...Sorry to hear that but certainly not surprised.  I figured if this had a real shot at unraveling the  mystery we would see more ppl with positive result about it. 

Seems like no matter what we do that might help the body compensates to throw us back into the protracted withdrawal state.  Like neuroplasty gone very very wrong   :-\
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[Buddie]

Re: The NO-ONOO theory of oxidative stress as the cause of disease (ML Pall)
« Reply #74 on: November 26, 2021, 07:28:41 pm »

Seems like no matter what we do that might help the body compensates to throw us back into the protracted withdrawal state.  Like neuroplasty gone very very wrong   :-\


What you said there is the most consistent thing I've seen in this whole ordeal.

There have been a handful of things that I have tried out of a list of dozens of different trials that really seemed to work ..... for awhile.  Some of them have worked so well and for long enough that I really don't think it's placebo.  But, ultimately the body seems to compensate and return itself to this pathological state.

Of the things that I have tried, here's my short list of things that really seemed to have worked but were not sustainable:

Agmatine   - Worked very well for about 6 weeks, then ultimately become ineffective and I suffered significant rebound effects once I discontinued. When I say this one worked well, I mean that I was near normal while it was effective, at least for my mental symptoms.

Bacopa - Very similar to agmatine. Maybe worked not quite as long, closer to 1 month. Became ineffective then suffered significant rebound effects upon discontinuation.

Hydroxocobalamin (Injected) - Seemed to help but not quite as much as the first two. Did not suffer much rebound effect upon discontinuation.

These were the standouts from trying literally dozens of different supplements. By far, most supplements simply did nothing. No positive or negative effects. I don't think it was placebo for these three. After all, why should these three work when so many others did nothing and frankly my expectation was they would as well?  Also, the results were so consistent for so long. 4-6 weeks is a long time for me. I can sometimes kind of psych myself up for something and get a little placebo effect that might last days to maybe a week, but not to this extent and not for so long. It really felt like I was taking an effective agent that eventually my body simply compensated for which caused them to become useless in the long term.

I really wish I knew what was going on here, maybe it would be a clue to what our underlying issue is.



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[Buddie]

Re: The NO-ONOO theory of oxidative stress as the cause of disease (ML Pall)
« Reply #75 on: November 26, 2021, 08:43:52 pm »
I agree with you [...], it seems like it should be a clue to the riddle that something might work and then become ineffective.  And then of course there's the rebound which suggests that the body got used to the "something" we were trying and it is yet another "stress" for the body to be without it again.

I'm no neuroscientist or biochemist, but I'm both fascinated and demoralized by this condition.  I was starting to feel better the month of September, thought I was really improving, and now I'm doing badly again.  I can't help  but think it is the change of seasons, lack  of sunlight, etc.  If I exert myself in any way whatsoever I get thrown into a wave of fibromyalgia and/or chronic fatigue.  I am scared to death that this is my life from now on.  I've practiced acceptance which helps, but dear lord this can't be it from here on out, can it??

My best theory at this point is that the drug changed our gene expression profile, and it may be possible to change it back, but HOW??? My autonomic nervous system feels like it has been fried, and I'm trying to do everything I can think of to enhance neuroplastic changes to become healthy again.  And I am so frustrated that NO ONE is working on this!!!
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[Buddie]

Re: The NO-ONOO theory of oxidative stress as the cause of disease (ML Pall)
« Reply #76 on: November 26, 2021, 09:13:28 pm »
My best theory at this point is that the drug changed our gene expression profile, and it may be possible to change it back, but HOW??? My autonomic nervous system feels like it has been fried, and I'm trying to do everything I can think of to enhance neuroplastic changes to become healthy again.  And I am so frustrated that NO ONE is working on this!!!

My two personal theories as to what is going on with us are:

1.) It's some sort of positive feedback loop where various neurotransmitters/receptors have entered a pathological state where the output state feeds back to the input and drives it further into a pathological situation. That's essentially what Pall's theory is for NO/ONOO, though there are probably dozens of different physiological mechanisms that might operate in a similar fashion.

2.) Long term exposure to benzos/z-drugs have instituted epigenetic changes where some gene expression has been either down regulated or enhanced. For instance, the genes that control the production of something like GAD65 might become down regulated such that we are producing less glutamic acid decarboxylase, thus converting less glutamate to GABA. There might be dozens of different genes that might have their expression altered as a response to a constant exposure to something like a GABA PAM.

For the first one, if you could ever interrupt the loop you would think that the system would return to a non-pathological state.  For the second one, time may ultimately restore normal gene expression. Reversing epigenetic changes is also a large area of study since some epigenetic changes are thought to lead to some cancers (though most do not). The ability to wipe the epigenetic slate clean is something that is one of the holy grails of medicine at the moment.

It would be nice if someone in the medical community gave enough of a damn to look into this.



 
Suggestions, opinions and/or advice provided by the author of this post should not be regarded as medical advice; nor should it substitute for professional medical care. Consult your doctor before making any changes to your medication. Please read our Community Policy Documents board for further information.

[Buddie]

Re: The NO-ONOO theory of oxidative stress as the cause of disease (ML Pall)
« Reply #77 on: November 27, 2021, 12:19:29 pm »
My best theory at this point is that the drug changed our gene expression profile, and it may be possible to change it back, but HOW??? My autonomic nervous system feels like it has been fried, and I'm trying to do everything I can think of to enhance neuroplastic changes to become healthy again.  And I am so frustrated that NO ONE is working on this!!!

My two personal theories as to what is going on with us are:

1.) It's some sort of positive feedback loop where various neurotransmitters/receptors have entered a pathological state where the output state feeds back to the input and drives it further into a pathological situation. That's essentially what Pall's theory is for NO/ONOO, though there are probably dozens of different physiological mechanisms that might operate in a similar fashion.

2.) Long term exposure to benzos/z-drugs have instituted epigenetic changes where some gene expression has been either down regulated or enhanced. For instance, the genes that control the production of something like GAD65 might become down regulated such that we are producing less glutamic acid decarboxylase, thus converting less glutamate to GABA. There might be dozens of different genes that might have their expression altered as a response to a constant exposure to something like a GABA PAM.

For the first one, if you could ever interrupt the loop you would think that the system would return to a non-pathological state.  For the second one, time may ultimately restore normal gene expression. Reversing epigenetic changes is also a large area of study since some epigenetic changes are thought to lead to some cancers (though most do not). The ability to wipe the epigenetic slate clean is something that is one of the holy grails of medicine at the moment.

It would be nice if someone in the medical community gave enough of a damn to look into this.

[...], Totally agree with your theories, and heck BOTH could be true.  If I were a PhD candidate I would jump on this as a thesis project!
Suggestions, opinions and/or advice provided by the author of this post should not be regarded as medical advice; nor should it substitute for professional medical care. Consult your doctor before making any changes to your medication. Please read our Community Policy Documents board for further information.