How chronic administration of benzodiazepines leads to unexplained chronic illne

Published by Stephen, a co-director of BIC.  Available online for about 50 days.  https://www.sciencedirect.com/science/article/pii/S0306987718303645

Hi MsAtomicBomb,

Thanks for sharing this info. I have so many questions!

 

Is it possible to know more about Stephen? What is his background? How did he come up with this hypothesis, and is it based on other literature or studies that you or he can share? Does this hypothesis tell us what we should or should not be doing in order to make things better? Has he tested this hypothesis, or is he planning to do so?

 

 

 

 

Hi MsAtomicBomb,

Thanks for sharing this info. I have so many questions!

 

Is it possible to know more about Stephen? What is his background? How did he come up with this hypothesis, and is it based on other literature or studies that you or he can share? Does this hypothesis tell us what we should or should not be doing in order to make things better? Has he tested this hypothesis, or is he planning to do so?

 

Hi Lap,

 

Stephen's the codirector as BIC - I'll DM you his email.  He is going to present this.  It's a hypothesis so if we can get funding/grant for this/convince a research institute to take an interest we will do it.

Thanks so much, Ms.A.

Thanks for this article.

 

The mthfr Genetic mutation affects the Nitric Oxide levels for many

 

 

I notice that the "vicious" cycle referred to in the article is called the "NO....O NOO!" cycle. How fitting! On bad days, I certainly yell "No! Oh nooooooo!" 

It would be nice to see these ideas tested and progress beyond a hypothesis.  "It is thought...it may...etc."  So much speculative, tentative language in the abstract.

Published by Stephen, a co-director of BIC.  Available online for about 50 days.  https://www.sciencedirect.com/science/article/pii/S0306987718303645

 

Do you have a full document of this, or is there any way you can get it, MAB? I sent it over to dm123 in Chewing the Fat so that he could better adapt it for laypeople as I, for one, do not understand it. Thank you!!

In the UK we firmly believe there is a connection with M.E.  -  many similar symptoms.  I hope as research into M.E.  expands it might help shed some light also. 

I wouldn't be at all surprised if such illnesses as ME (and others too, such as MS, Lupus, Parkinsons, ALS, etc.) are as a result of various medications, not necessarily benzo withdrawal of course.  Would love to see comprehensive research focused solely on med histories etc.

 

I know this NO/ONOO hypothesis has been floating around for a few years and catching more and more steam for conditions such as fibromyalgia and CFS but, if I remember correctly (haven't checked recently), it seemed as usual that the studies were being conducted with a view to new drug development. 

 

There are a lot of layman explanations on Youtube, it depends how deeply one wants to delve into it.  Here's just one that gives an easy-peasy understanding.

https://youtu.be/b1-M4aJCz84

I wouldn't be at all surprised if such illnesses as ME (and others too, such as MS, Lupus, Parkinsons, ALS, etc.) are as a result of various medications, not necessarily benzo withdrawal of course.  Would love to see comprehensive research focused solely on med histories etc.

 

I know this NO/ONOO hypothesis has been floating around for a few years and catching more and more steam for conditions such as fibromyalgia and CFS but, if I remember correctly (haven't checked recently), it seemed as usual that the studies were being conducted with a view to new drug development. 

 

There are a lot of layman explanations on Youtube, it depends how deeply one wants to delve into it.  Here's just one that gives an easy-peasy understanding.

https://youtu.be/b1-M4aJCz84

 

thanks abcd  easy explanation

 

This ties into so many areas and shows how different we all are as well.

and that we  need vastly different approaches to healing as well

 

Time works for some, for others it is not the answer  :'(

 

also how drugs, histamines, genetics, life styles, toxins and bugs  affect us all very differently too

and  also supplements, along with all the many and varied opinions here on BB

and how they work differently for everyone. 

 

and how we heal and detox properly after the toxins rise.

Published by Stephen, a co-director of BIC.  Available online for about 50 days.  https://www.sciencedirect.com/science/article/pii/S0306987718303645

 

Do you have a full document of this, or is there any way you can get it, MAB? I sent it over to dm123 in Chewing the Fat so that he could better adapt it for laypeople as I, for one, do not understand it. Thank you!!

 

Hi Terry

 

I will make the first post today.  It’s a simplified version of what I’m working on.  For you, I was more interested in the applicability of this hypothesis to link Benzodiazaphine post withdrawal to persistent HBP issues.

 

There’s a very detailed video on the NO/ONOO- in the first post. 

 

It boils down to other forms of negative stress called oxidative stress and mitochondrial dysfunction. 

 

I don’t want to make the full post without reading the full source document.  I don’t have access to it.

Thank you very much, dm123!!

 

 

Seems fairly straightforward to me. I had parents who smoked and drank a ton everyday. And both came from Ireland.

 

I inherited a rare disease called idiopathic subglottic stenosis. I participated in a huge study by all the research universities in the US to find out the cause of it. General always occurs in women, just barely pre/postmenopausal, Caucasian, and of European ancestry. Idiopathic means "of unknown cause," but mine was specifically identified as being inherited. Took my DNA from tissue, blood, inside cheek.

 

Then I was asked to be part of substudy to identify specific gene.

 

Upshot I guess is that I already had that inherited gene from one or both of my parents, and all those toxins they kept putting into their bodies (and I don't even know if it was before I was born or not, but definitely after,) combined with 4 super stressful events in my life all coinciding at once caused that "spillover" effect that video talks about.  Got 2 younger brothers who also went through child hood like mine, but both men, and not same traumas as me.

 

Anything here align with your thoughts, dm123?

Hi intendtobeoff

 

1. Just so that i answer you correctly, can you tell me if you are in PWS, or if you are  currently tapering?

 

2. Also relative to the cluster of those 4 major stressors, were you on benzodiazaphines at the time, or did you start after the cluster stress event?

 

The very short answer to your question is that the stress system is the critical link between the layman’s benzodiazaphine model and the NO/ONOO- model proposed in that link above.  Both models have benzodiazaphines as the initial inciting force that causes destabilization.

 

The NO/ONOO- dysfunction ultimately results in “ cellular stress” ( persistent oxidative stress and mitochondrial dysfunction) which serve as more negative inputs into the “stress system” of the laymans benzodiazaphine model.

 

In the laymans thread there are many “other systems” that directly influence benzodiazaphine tolerance, wd , and PWS.  I have only mentioned them briefly in that thread so far.

 

Some addtional pillars are:

 

1. NO and NOS system (ie, the NO/ONOO- cycle above)

2. GPCRs (5-ht, DA, ACh, etc)

3. Neurotrophic factors

4. Kindling

5. And some others.

 

So far Ive only covered the glutamatergic , GABAergic, and stress hormone pillars in the laymans thread.  All the pillars interact with one another, and destabilizing one has the potential to destabilize some of the others.  Once the pillars are destabilized stress resiliency deteriorates and this perpetuates symptoms (PWS).

 

The NO and NOS system would be added as a 4th pillar alongside the 3 that I have covered.

 

The important thing for you is to minimize negative stressors during your recovery.  There are a lot of CFS supplements that can help restore the NO/ONOO- cycle back to normalcy, but PWS, like CFS, is a syndrome, ie a constellation of symptoms with a complex etiology.    Benzodiazaphine PWS is also  due to additional adverse neuroplastic and neurogenic ( adult neurogenesis) changes that can take a long time to resolve.

 

I haven’t read the complete hypothesis document cited above, but the author does state that the ailments that occur in benzdiazaphine PWS may at least in part be due to NO/NOS cycle dysfunction.  I believe it’s part of the much larger model, as described above.

 

 

 

I wouldn't be at all surprised if such illnesses as ME (and others too, such as MS, Lupus, Parkinsons, ALS, etc.) are as a result of various medications, not necessarily benzo withdrawal of course.  Would love to see comprehensive research focused solely on med histories etc.

 

I know this NO/ONOO hypothesis has been floating around for a few years and catching more and more steam for conditions such as fibromyalgia and CFS but, if I remember correctly (haven't checked recently), it seemed as usual that the studies were being conducted with a view to new drug development. 

 

There are a lot of layman explanations on Youtube, it depends how deeply one wants to delve into it.  Here's just one that gives an easy-peasy understanding.

https://youtu.be/b1-M4aJCz84

 

thanks abcd  easy explanation

 

This ties into so many areas and shows how different we all are as well.

and that we  need vastly different approaches to healing as well

 

Time works for some, for others it is not the answer  :'(

 

also how drugs, histamines, genetics, life styles, toxins and bugs  affect us all very differently too

and  also supplements, along with all the many and varied opinions here on BB

and how they work differently for everyone. 

 

and how we heal and detox properly after the toxins rise.

 

This is confusing to me.  Not so long ago on another thread, I was attempting to offer some practical strategies to a member with a 3+ year history of depression, and your contribution was that there was no solution for him except this thing called "time".  Remember?  And now you post this, I don't get it?

dm123,

 

If by PWS you mean protracted withdrawal syndrome, the answer is no. I'm still tapering.

 

And the second question requires an explanation to properly answer as they all occurred concurrently.

 

My husband fell off a moving train and suffered a TBI. I had just started back to school and had to attend my first class the morning after the injury. He had been taken to a hospital 40 miles away from where we lived. They had no facilities to treat a TBI, yet were determined to keep him there. I had to drive to this hospital through heavy freeway traffic up and back for 3 days as my kids were teenagers. The only specialist there was an eighty year old neurologist who took an X-ray and said it looked fine. But I started to spot differences in him, and just wanted to get him home to see his doctor. But another young primary care doctor was taking charge by then. He just would not let him leave, and I had to demand his release. That doctor said I'd be taking him out against medical advice, becoming threatening. The social worker there got involved finally, and had him transferred by ambulance to a hospital in our home location. His own doctor was at that hospital and was seriously concerned. He diagnosed numerous complications and wanted him transferred again to the huge hospital that housed the Quincey Rehabilitation Institute. So it happened. And he spent over two years there, had several operations, and was treated by 17 different specialists. All this time, I was continuing to finish my education and we were also in a massive litigation suit with the railroad he worked for. I took him home at night (not right after surgery, but over the course of all this. So I think the traumas here are the accident, me going back to school at an Ivy League school, the horrendous litigation, and a surprise announcement by my youngest daughter that she was pregnant by a 22 year old man. And all this was concurrent over the two years I navigated all this. He was finally dxed permantly disabled and on numerous medications. It would seem it was time to relax a bit, but the litigation became intense and ended up in federal court. And then the baby was born. So all this was on my plate. His treatment continued however outpatient. Finally the case was settled, 4 years after the accident, and we were taking care of a tiny child, and a teenage mother. Can't remember the laws at the time, but the age of our daughter and the guy involved were too close together for him to be formally charged. Those laws have definitely changed since then. But the whole situation was so intense, that I'm still surprised I handled it so well.

 

Things did finally settle down, and I continued my education and finally got my masters. And then the breathing problems started slowly. I would rush to post graduate classes, having to run up 3 flights of stairs for a class. And that problem advanced rapidly from that point. Gasped for air and couldn't get across a room w/o stopping to gasp for air. Went to doctor myself, and immediately sent for tests. Nothing in my lungs or bronchial tubes, very well oxygenated, but saw ENT within a day. Took one look down my throat?and saw a 97 % closure of my trachea. Was at university of Utah hospital next day as emergency case. In operating room next morning for the first of 14 surgeries. And the dx was idiopathic subglottic stenosis. Worst case they'd ever seen at the time. Tennacious problem that wouldn't stop. Kept closing. Finally had to have cricotracheal resection soon after multiple microlaryngoscopies and a laryngeoplasty. Had what I call my Frankenstein stitches across my slit throats twice. Quite the adventure. Lots of info here. You most likely get the picture.

Following.

Forgot to say that hubbys psychiatrist thought I was under too much stress and pressure. Had stressful job by then. She wanted me to take xanax. I didn't think I needed it and didn't even know what it was. But took it anyway. So the benzo taking was towards the "middle of the end" of these traumas. Sounds to me like I had more traumas than I thought I had.

 

abcd, this all has to do with that NO/OONO theory and your YouTube video. I thought I am a good example of that theory. Not really sure.

Forgot to say that hubbys psychiatrist thought I was under too much stress and pressure. Had stressful job by then. She wanted me to take xanax. I didn't think I needed it and didn't even know what it was. But took it anyway. So the benzo taking was towards the "middle of the end" of these traumas. Sounds to me like I had more traumas than I thought I had.

 

abcd, this all has to do with that NO/OONO theory and your YouTube video. I thought I am a good example of that theory. Not really sure.

 

Intend, that was a riveting but very harrowing read.  I'm so sorry for everything you went through, and yet it's such a testimony of your strength and determination.  I assume you're referring to your idiopathic subglottic stenosis as being an example?  I'd imagine it's certainly a possibility, who knows, right.  Let's keep fingers crossed it won't be the case for you with regard to your benzo use, I hope your taper's going well thus far.  Stress, sigh.  I think we'd all agree that stress in any/all of its forms can be an absolute killer.  Literally.  Even how our thoughts alone trigger a cascade of physiological reactions; for example, a spontaneous heart attack upon hearing bad news.

 

Just a side note about this particular video, folks.  Let's keep in mind that it's by a chiropractor, lol, hence the reference to high concentrations of NMDA receptors at the base of the skull which chiropractic adjustments can help to downregulate 

 

Some general layman ramblings on hypotheses/theories.  The human body (well, actually the bodies of all living creatures) are such extraordinarily complex and mysterious ecosystems (I saw Mutuuraia use that term and I think it's perfect).  So, considering that what the drug does to the body is only half the story, the other half being the matter of what the body does to the drug.  Then let's consider how both of these phenomena can vary so greatly between people.  Then, add to that, how it can be so inconsistent even within the same person.  Such is the beauty of our ever-changing body ecosystems.  THEN, if we top it off by throwing in the position taken by Prof. John Ioannidis that most published research findings are false - here, for anyone interested:  http://www.benzobuddies.org/forum/index.php?topic=203424.0 ...

 

Well, I guess everyone needs to decide for themselves how much stock they want to put into all these theories and research studies.  I'm keeping my money in the bank. 

 

thanks abcd  easy explanation

 

This ties into so many areas and shows how different we all are as well.

and that we  need vastly different approaches to healing as well

 

Time works for some, for others it is not the answer  :'(

 

also how drugs, histamines, genetics, life styles, toxins and bugs  affect us all very differently too

and  also supplements, along with all the many and varied opinions here on BB

and how they work differently for everyone. 

 

and how we heal and detox properly after the toxins rise.

 

This is confusing to me.  Not so long ago on another thread, I was attempting to offer some practical strategies to a member with a 3+ year history of depression, and your contribution was that there was no solution for him except this thing called "time".  Remember?  And now you post this, I don't get it?

 

:'( :'( :'(

I have never ever  been a proponent of  "Time"  being the only way to heal.

 

Maybe I didnt express myself well there on that post, or was misunderstood perhaps

so  my apologies if you read it that way.

we all express ourselves differently,

especially in waves,when in pain or in cognitive black spot even,

or  perhaps when something triggers us, etc etc. 

even posts on here.

 

I had kept it short on that post  short didnt elaborate, and said listen to your own body also.

 

I take many supplements, and trial many many  things often.

 

So no "Time" is not the only way to heal,

 

however we must be patient in some areas, as we heal too

 

I certainly dont believe the  " Time" mantra solution only.

 

We must help ourselves and listen to our own bodies and needs

 

Well, I guess everyone needs to decide for themselves how much stock they want to put into all these theories and research studies.  I'm keeping my money in the bank. 

 

Agree     

 

time for some  :sleepy:    

 

Well,

 

I didn't realize that this NO/OONO video involved a chiropractor. I do think time is a huge factor in at least getting off this horrible stuff. I shudder to think what my mind will be like IF I ever get off.

 

And I don't like to take supplements of any kind. I just figure too much has happened to my poor CNS to try any supplements. I'm not on xanax now-had difficult cross to clonazepam by the know nothing doctor, and now 4 generic switches of clonazepam.

 

If someone that knows more than I do thinks I fit into this NO/OONO theory, I was just interested in finding out. Wish I could say I was off, but with all these forced switches and holds for adjustment I'm still about halfway there. And I'm getting older, so times a'wasting for me.

 

thanks abcd  easy explanation

 

This ties into so many areas and shows how different we all are as well.

and that we  need vastly different approaches to healing as well

 

Time works for some, for others it is not the answer  :'(

 

also how drugs, histamines, genetics, life styles, toxins and bugs  affect us all very differently too

and  also supplements, along with all the many and varied opinions here on BB

and how they work differently for everyone. 

 

and how we heal and detox properly after the toxins rise.

 

This is confusing to me.  Not so long ago on another thread, I was attempting to offer some practical strategies to a member with a 3+ year history of depression, and your contribution was that there was no solution for him except this thing called "time".  Remember?  And now you post this, I don't get it?

 

:'( :'( :'(

I have never ever  been a proponent of  "Time"  being the only way to heal.

 

Maybe I didnt express myself well there on that post, or was misunderstood perhaps

so  my apologies if you read it that way.

we all express ourselves differently,

especially in waves,when in pain or in cognitive black spot even,

or  perhaps when something triggers us, etc etc. 

even posts on here.

 

I had kept it short on that post  short didnt elaborate, and said listen to your own body also.

 

I take many supplements, and trial many many  things often.

 

So no "Time" is not the only way to heal,

 

however we must be patient in some areas, as we heal too

 

I certainly dont believe the  " Time" mantra solution only.

 

We must help ourselves and listen to our own bodies and needs

 

Well, I guess everyone needs to decide for themselves how much stock they want to put into all these theories and research studies.  I'm keeping my money in the bank. 

 

Agree     

 

time for some  :sleepy:    

 

 

 

 

 

Hi, yes I did read it that way, it was this post.  Sorry you were in a wave, hope you're feeling better.

 

 

I dont honestly think there is anything that helps if the source of the depression is benzo withdraw... I have had a clinical depressions before my benzo withraw and that was a very different experience. In the "normal" depresseion there was a logic... There is no logic in anything that is benzo related. And no solution. Besides time or more benzos. So only time then. 

 

agree.    Time patience and listening to your own body I guess. 

dm123,

 

If by PWS you mean protracted withdrawal syndrome, the answer is no. I'm still tapering.

 

And the second question requires an explanation to properly answer as they all occurred concurrently.

 

My husband fell off a moving train and suffered a TBI. I had just started back to school and had to attend my first class the morning after the injury. He had been taken to a hospital 40 miles away from where we lived. They had no facilities to treat a TBI, yet were determined to keep him there. I had to drive to this hospital through heavy freeway traffic up and back for 3 days as my kids were teenagers. The only specialist there was an eighty year old neurologist who took an X-ray and said it looked fine. But I started to spot differences in him, and just wanted to get him home to see his doctor. But another young primary care doctor was taking charge by then. He just would not let him leave, and I had to demand his release. That doctor said I'd be taking him out against medical advice, becoming threatening. The social worker there got involved finally, and had him transferred by ambulance to a hospital in our home location. His own doctor was at that hospital and was seriously concerned. He diagnosed numerous complications and wanted him transferred again to the huge hospital that housed the Quincey Rehabilitation Institute. So it happened. And he spent over two years there, had several operations, and was treated by 17 different specialists. All this time, I was continuing to finish my education and we were also in a massive litigation suit with the railroad he worked for. I took him home at night (not right after surgery, but over the course of all this. So I think the traumas here are the accident, me going back to school at an Ivy League school, the horrendous litigation, and a surprise announcement by my youngest daughter that she was pregnant by a 22 year old man. And all this was concurrent over the two years I navigated all this. He was finally dxed permantly disabled and on numerous medications. It would seem it was time to relax a bit, but the litigation became intense and ended up in federal court. And then the baby was born. So all this was on my plate. His treatment continued however outpatient. Finally the case was settled, 4 years after the accident, and we were taking care of a tiny child, and a teenage mother. Can't remember the laws at the time, but the age of our daughter and the guy involved were too close together for him to be formally charged. Those laws have definitely changed since then. But the whole situation was so intense, that I'm still surprised I handled it so well.

 

Things did finally settle down, and I continued my education and finally got my masters. And then the breathing problems started slowly. I would rush to post graduate classes, having to run up 3 flights of stairs for a class. And that problem advanced rapidly from that point. Gasped for air and couldn't get across a room w/o stopping to gasp for air. Went to doctor myself, and immediately sent for tests. Nothing in my lungs or bronchial tubes, very well oxygenated, but saw ENT within a day. Took one look down my throat?and saw a 97 % closure of my trachea. Was at university of Utah hospital next day as emergency case. In operating room next morning for the first of 14 surgeries. And the dx was idiopathic subglottic stenosis. Worst case they'd ever seen at the time. Tennacious problem that wouldn't stop. Kept closing. Finally had to have cricotracheal resection soon after multiple microlaryngoscopies and a laryngeoplasty. Had what I call my Frankenstein stitches across my slit throats twice. Quite the adventure. Lots of info here. You most likely get the picture.

 

Hi intendtobeOff

 

Yes, I get the picture.    The 14 surgeries alone were a tremendous psychological and physical stress, let alone all the other issues.  These are all negative stressors.  You had no control, they were completely unpredictable and they were relentless.   

 

Do you mind me asking when The benzdiazaphines entered the picture relative to the above, initial starting dosage, how you take them (dose them) , and took them (in the past) each day, what benzdiazaphine you are on, if you did a crossover at any point?

 

I had a stress cluster occur five years back as well.  Many different negative stressors came together all at once.

 

The tragedy in our cases is that the very pharmaceutical that was given To help with the chaos and negative stressors, ends up being one of the worst insults of all.(in my case the benzdiazaphine was the thing that did the most damage by far)

 

I hope you are in a bit of a better place relative to negative stressors at this time.  I’m very glad to hear you are not in PWS.  I’m going to research the subglottic stenosis.  The fact that you made it through says a lot about your innate stress resiliency.  Very very strong.

Well,

 

I didn't realize that this NO/OONO video involved a chiropractor. I do think time is a huge factor in at least getting off this horrible stuff. I shudder to think what my mind will be like IF I ever get off.

 

And I don't like to take supplements of any kind. I just figure too much has happened to my poor CNS to try any supplements. I'm not on xanax now-had difficult cross to clonazepam by the know nothing doctor, and now 4 generic switches of clonazepam.

 

If someone that knows more than I do thinks I fit into this NO/OONO theory, I was just interested in finding out. Wish I could say I was off, but with all these forced switches and holds for adjustment I'm still about halfway there. And I'm getting older, so times a'wasting for me.

 

I just posted above.  I see you’ve crossed over to clonazepam.  There are some blood tests to test for the Peroxynitrate levels in your blood, that could help you determine if That’s what’s going on.  I forgot to ask you what you present symtoms are.