Can anyone make sense of this to explain to a layperson?

[[...]]

SS .... Yes easier said than done . I think once these 'tracks' happen , it's quite hard to undo them .... And during benzo WD I think we develop many , it's like a deep hole of chronic reactions. And we can get so easily triggering into new 'tracks '.

Like today I had a friend over and I was feeling really fragile in my nervous system ..... Her energy and lack of understanding triggered me big time , I identified the track as feeling out of control , but the effect it had on me was awful.... I had what I call my seizures , I'm not sure if that's what they are , but they are stress induced . My hands curl up tight and a I feel like I can't breath, my whole body tenses up from stress. Now she's gone and I feel so shaky , and having pins stuck all over me . It was a horrible experience . I know she cares about me but she has no idea .

 

So , a track that triggered a stress response , and our already fragile nervous systems that can't handle normal things at all .

 

I sure hope this awful feeling passes soon .....

( hope this isn't too off topic here )

MiYu

[[Su...]]

SS .... Yes easier said than done . I think once these 'tracks' happen , it's quite hard to undo them .... And during benzo WD I think we develop many , it's like a deep hole of chronic reactions. And we can get so easily triggering into new 'tracks '.

Like today I had a friend over and I was feeling really fragile in my nervous system ..... Her energy and lack of understanding triggered me big time , I identified the track as feeling out of control , but the effect it had on me was awful.... I had what I call my seizures , I'm not sure if that's what they are , but they are stress induced . My hands curl up tight and a I feel like I can't breath, my whole body tenses up from stress. Now she's gone and I feel so shaky , and having pins stuck all over me . It was a horrible experience . I know she cares about me but she has no idea .

 

So , a track that triggered a stress response , and our already fragile nervous systems that can't handle normal things at all .

 

I sure hope this awful feeling passes soon .....

( hope this isn't too off topic here )

MiYu

 

Yes Miyu,

Much easier said than done.  Just after I wrote that - and thought I had some control -- I went into the biggest panic attack of my life....

I take back those words when it comes to BenZos..... And I hope you are feeling better.... yes such seemingly small things can trigger....

Sorry if this is off topic but I needed to apologize for my breezy comment......

 

[[...]]

SS .... Yes easier said than done . I think once these 'tracks' happen , it's quite hard to undo them .... And during benzo WD I think we develop many , it's like a deep hole of chronic reactions. And we can get so easily triggering into new 'tracks '.

Like today I had a friend over and I was feeling really fragile in my nervous system ..... Her energy and lack of understanding triggered me big time , I identified the track as feeling out of control , but the effect it had on me was awful.... I had what I call my seizures , I'm not sure if that's what they are , but they are stress induced . My hands curl up tight and a I feel like I can't breath, my whole body tenses up from stress. Now she's gone and I feel so shaky , and having pins stuck all over me . It was a horrible experience . I know she cares about me but she has no idea .

 

So , a track that triggered a stress response , and our already fragile nervous systems that can't handle normal things at all .

 

I sure hope this awful feeling passes soon .....

( hope this isn't too off topic here )

MiYu

 

Yes Miyu,

Much easier said than done.  Just after I wrote that - and thought I had some control -- I went into the biggest panic attack of my life....

I take back those words when it comes to BenZos..... And I hope you are feeling better.... yes such seemingly small things can trigger....

Sorry if this is off topic but I needed to apologize for my breezy comment......

 

It's ok SS , I didn't feel it was 'breezy'...... I'm so sorry about your panic attack , how awful . what I have is terrible stressin intolerance .... It feels like my whole body is tensed up . I don't know why I'm so bad right now , I haven't cut back on dose . Just more WDs or more brain , nervous system trying to get back in balance . I was so much better three months ago .....

Anyway , I hope you feel better too . Let's continue any conversations around this via Pm shall we , if we need to , so as not to hijack this thread !

Love, MiYu 

[[cs...]]

Thank you dm123 for all your research .......

I can't absorb all of it , but ! A laymans question ..... Where is the hope in all of this ? I tend to feel more hopeless in reading all the research .....

 

I was on high dose hydrocortisone fro 9 months and had to cold turkey when it 'turned ' on me , which I now think was a bad idea , though they were making me so sick I felt I had no choice .

 

Now I am coming up against the same type of reaction to Valium ... Which is very frightening . As I know ct is not an option .

 

Now that I knwo that steroids are PAMS , it makes sense why , after my ct and then starting klonopin , I began to feel a lot better ! I then corssed to Valium when I had a difficult time trying to taper klonopin . The crossover was brutal and I don't think I ever stabilized on Valium . I am also I now find a fast metabolizer of at least the parent drug Diazepam .

 

What does all this mean fro me ? My taper seems impossible with extreme WDs at the slightest reduction . I'm stuck and feel quite trapped now with the benzo.

 

I hope your research leads to some answers for those of us struggling so much .

 

Interestingly ,valium has become extremely sedating fro me this last month , way more than it ever has been before ,to the point where I can only take 1/2 mg in the am and 1/2 at lunch , and the rest at night . The sedative effects are supposed to become quickly tolerant.  I have found the opposite , the anxiolytic effects are pretty much zero , and the sedation over the top !

Complicated is an understatement isnt it!

MiYu

Hi MiYu,

 

I hope the research helps as well.  We are in the same boat.  The waves are horrible.

 

Although I do feel hydrocortisone is a PAM, it's officially not a neurosteroid and is not in the official listings. https://en.m.wikipedia.org/wiki/Category:GABAA_receptor_positive_allosteric_modulators

My Benzo doc did say it does influence the Cl- influx, and I know Pers indicated it was a modulator as well, so these two resources are reliable.

 

I know where you are at.  I was on HC for 2.5 years.  It is really is tough on the body.  I tapered it very slowly over a 6 month period.  I was just finishing off the taper when I crossed over to Librium.  So I definitely know the feeling.  When you crossed over did the doc titrate you up on the Valium until your wd symptoms faded or did he not do this?

It sounds like you were never stabilized to start.

 

What are these wd symptoms that you are feeling?  It does not sound like hyperexcitability, because you mentioned you feel overly sedated.  That might not be such a bad thing. I've tapered the morning and after noon doses, and am just on nightly.  You should ask your doc if you can just take all 8 mgs at night. (See also Ashton manual taper schedules)However, phsiologically, the .5 mgs should not make a difference due to the long half life. 

  Don't make any changes without consulting your doctor.   

 

Also how long ago did you drop the HC?  It takes a while for the pituitary and hypothalamus to pick up the drop and normalize the ACTH.  Especially that you cold turkeyed it.

 

You should be going by symptoms, and if you feel ill, don't make the cut, and tell your doc.  I know you are on gabapentin.  I unfortunately could not tolerate it, (too stoned and spaced out)and can't use it as an adjunctive med.

 

can you ask your doc if that's what is making you so sedated.?  Perhaps your excitatory system does not need as much of the gabapentin to blunt the neuron potential at this point. 

 

You would need to ask your doc about the current dose

 

So you are sedated at the same time anxious?.  Horrible feeling. I've felt that.  Are you able to sleep well?

 

Yes my next ADDENDUM will go deep into the different physiological aspects of tolerance for benzos and how that correlates to the subunit configuration of the receptor.  Yes, the sedation and hypnotic is supposed to wear off week (tolerance builds fast) and anxiolytic effect wears off slow, so you are just the opposite.  I found my tolerance to Librium sedation to wear off fast. 

 

I think you need to talk to your doc about the gabapentin. Are you taking any other adjunctive meds?

 

Glad you and I are off the HC.

 

How did you find out you are a fast metabolizer of Valium?

 

So ....thanks  for answering Dm .... My story is a bit complex but I'll try and keep it as simple as possible .

I was on HC fro adrenals....which I think was actually just hormonal in the end ...the HC didn't help me at all , I never improved on it , in fact I got worse , so doctors kept raising my dose as they thought I want absorbing it or something.

I ended up on 60-80 mgs , a lot ! I tried to taper it a few times and couldn't . I tried prednisone too , that was a bit better and not so "sudden" in onset , but I still ended up having a bad reaction to it , so I went back to HC , and finally was able to taper down to 20 mgs . Fairly rapidly . At that point I ended up on ER one day , just crazy reaction , perhaps it was WDs , I don't know . Anyway , I pretty much dropped to zero in a month. I was super sick . I actually thought I was going to die . I could barely move , totally opposite response to what steroids should do .

During that time I couldn't sleep , so I was prescribed ambien and Xanax as needed . I started having panic attacks after the steroids , and my stress tolerance was zero as you can imagine .

I took 5 mgs ambien to sleep most nights during the nine months , and the Xanax initially only .125 a couple of times a week .

The gabapentin , I've been on for some years befor all this , for restless legs , always only between 100-3oo mgs . But the steroids made my RLS so bad I had to go up to 900 !

 

So then , a life trauma , right after the steroid cT , and I couldn't cope without the benzo or the ambien . So now 5 mgs ambien , and either .125-.25 Xanax , or 1/2 mg of Ativan which I also had been prescribed as needed.

 

I had no idea during all this about the addictive nature of benzos .

 

On to dec 2016 ( this all started in November 2014) , I was so sick my friend took me to a naturopath ,who prescribed me klonopin! I dropped the ambien , still on 900 sometimes more gabapentin .

I took .25 mgs klonopin and .125 mgs Xanax for two months at that point . Then decided I wanted off the klonopin and Xanax.

Dropped the Xanax and discovered benzo WD hell!

Bad ......

Upped the K To .375 in Feb 2016 to cover the Xanax .

 

March began cross to Valium .... Really hard , I had terrible WDs from K for three months , like I had CTd it , even with crossing to 10 mgs Valium .

 

So I guess I was never really stable , and my body had been through so much with the steroids and the ups and downs of meds .

 

I'm on 360 mgs gabapentin now , I tapered that this last year . Seemed a lot easier than the Valium in terms of WDs .,

As for the Valium , I can't get below where I'm at . Each cut i try to  make makes me very sick .

 

Bottom line now -

360 mgs gabapentin

7.93 Valium ( that's 8 mgs minus the 1/8 th I microtapered in June , still having horrible WDs from that cut)

 

Just holding and hoping things even out . I haven't cut back the gabapentin since March this year .

 

Well that wasn't exactly short! Writing it makes me realize what my body has been through these last 2-1/2 years . I really was only on benzos daily fro six months before I started trying to taper . But I had the steroid ct 8 months before that.

 

Not sure if any of this means anything except a good old mess!

 

MiYu 

Hi MiYu,

I agree the HC is nasty.  That a gigantic dose. It's no wonder you could not sleep.... I was on 30 mgs for 2.5 years. I have no clue why they would put you on such a high dose unless they thought you had an autoimmune inflammatory condition.

 

Regarding naturopaths. They can prescribe class IV drugs which is ridiculous.  One of my main motivations is to get the shorter and more potent benzos rescheduled to class II.  Very few docs can and will prescribe class IIs liberally.  Benzos are under, and opioids are flagged. One reason for this is the class designation.  I do realize that benzos have very low overdose toxicy, unlike opioids, but that should not be the sole determinant.

 

I guess looking at your story I started out  higher than you and used much longer.  I'm thankful to be as far as I am, but this last part is horrendous.  I wish I could make sense of the social aspects of benzodiazaphines.  It's much more difficult to sort that out than the clinical aspects.

[[cs...]]

Side note: I've tried to find that 'medical wiki' but for some reason it's nigh impossible unless I know the URL. It's a medical wiki, isn't it ?

 

As in https://en.m.wikipedia.org/wiki                                /Category:GABAA_receptor_positive_allosteric_modulators#/search

 

I couldn't find it with google. Unless it's related to a language or country ...

 

It must be.  This link works for me.  I would publish it here but it's far too long

Try a google on this part

 

Category:GABAA_receptor_positive_allosteric_modulators#/search

[[cs...]]

About hyperexcitability. For those who are not familiar with teh concept, this seems like a very nice introduction : https://www.ncbi.nlm.nih.gov/books/NBK2510/

Many things referenced to in this thread are mentioned. Even a hint about sodium channels, perhaps related to glutamate ?

Thank liberty.  Sodium channels no doubt have a profound effect on APs.  The VG sodium channels are responsible for the hyperpolarization overshoot.  They recover during the repolarization phase. Benzos interfere with the recovery rate, slowing it down, so that there is less chance of seizure activity.  Their recovery rate is one thing that determines how soon you can fire off the next AP, and how much of an input stimulus is required to get that next AP to fire off,

 

 

Here is a section on kindling from the above

 

Quote

An important experimental model of epileptogenesis is kindling, discovered by Goddard and coworkers in the 1960s. Daily, subconvulsive stimulation (electrical or chemical) of certain brain regions such as the hippocampus or amygdala result in electrical afterdischarges, eventually leading to stimulation-induced clinical seizures, and in some instances, spontaneous seizures. This change in excitability is permanent and presumably involves long-lasting biochemical and/or structural changes in the CNS. A variety of changes have been measured in kindling models, including alterations in glutamate channel properties, selective loss of neurons, and axonal reorganization. However, the exact mechanisms underlying kindling, and its applicability to human epileptogenesis, remain unknown. (Slide 26)

End quote

 

Note the article is a bit dated, but very good.

 

Glutamate and Glutamate ionotropic channels play a big part in many areas.  We will see they play a large role in addiction physiology as well and affect dopamine neurons in the VTA profoundly.

[[Su...]]

About hyperexcitability. For those who are not familiar with teh concept, this seems like a very nice introduction : https://www.ncbi.nlm.nih.gov/books/NBK2510/

Many things referenced to in this thread are mentioned. Even a hint about sodium channels, perhaps related to glutamate ?

Thank liberty.  Sodium channels no doubt have a profound effect on APis.  The VG sodium channels are responsible for the hyperpolarization overshoot.  They recover during the repolarization phase. Benzos interfere with the recovery rate, slowing it down, so that there is less chance of seizure activity.  Their recovery rate is one thing that determines how soon you can fire off the next AP, and how much of an input stimulus is required to get that next AP to fire off,

 

 

Here is a section on kindling from the above

 

Quote

An important experimental model of epileptogenesis is kindling, discovered by Goddard and coworkers in the 1960s. Daily, subconvulsive stimulation (electrical or chemical) of certain brain regions such as the hippocampus or amygdala result in electrical afterdischarges, eventually leading to stimulation-induced clinical seizures, and in some instances, spontaneous seizures. This change in excitability is permanent and presumably involves long-lasting biochemical and/or structural changes in the CNS. A variety of changes have been measured in kindling models, including alterations in glutamate channel properties, selective loss of neurons, and axonal reorganization. However, the exact mechanisms underlying kindling, and its applicability to human epileptogenesis, remain unknown. (Slide 26)

End quote

 

Note the article is a bit dated, but very good.

 

Glutamate and Glutamate ionotropic channels play a big part in many areas.  We will see they play a large role in addiction physiology as well and affect dopamine neurons in the VTA profoundly.

Hi Terry and all,

(Sorry for getting us a bit off track for a bit)  Is this bolded quote accurate --  that it is permanent?  Or has more research shown that the CNS heals more slowly with kindling.

[[Te...]]

Well, I'm not going to believe it. A person heals after kindling. There have certainly been a lot of success stories about kindling and healing. Things have changed since the '60s. I'm sorry, but I'm going to keep my focus firmly on healing. I think the brain is much more flexible and the CNS can withstand a lot. I have certainly been very sick, but I'm healing. At a snail's pace, but healing.

 

I don't know about the research, though. We've come a long, long way in scientific studies since the '60s.

[[Su...]]

Well, I'm not going to believe it. A person heals after kindling. There have certainly been a lot of success stories about kindling and healing. Things have changed since the '60s. I'm sorry, but I'm going to keep my focus firmly on healing. I think the brain is much more flexible and the CNS can withstand a lot. I have certainly been very sick, but I'm healing. At a snail's pace, but healing.

 

I don't know about the research, though. We've come a long, long way in scientific studies since the '60s.

 

Yes there is so much research about neuroplasticity etc. since the time of this research..... and of course the many buddies who have healed... I wrote in an anxious moment....

 

[[Te...]]

I don't blame you. This can be anxiety-provoking. But we'll make it through!! Step by step. No matter what!! Personally, I think a belief system that's strong helps. I know a woman on here who said her dad, when she was young, was very sick. He didn't want to hear the prognosis. So his family went in and heard from the doctor. The prognosis was bad. But since the father didn't hear it and no one told him, pretending that everything was okay, his immune system didn't go down and he remained positive. Well, he's still alive today! So it just goes to show that our attitudes have a lot to say about this, too. That's why I hate going to the doctor. I've heard way too much negativity, and of course I'm down, and my immune system isn't doing too well, afterwards and for a long time. Unfortunately, I have to have frequent visits. I don't know how to get around this.  :'(

[[cs...]]

a

Thanks for this thread .... I've no idea if this is at all of interest or relevant ,

but I'd like to add a little something that I've thought about relative to the brain and healing. I feel there's possibly a trauma factor in cold turkeys and rapid withdrawals that maybe causes brain lesions and ongoing symptoms.

 

There's a German man called dr . Hamer ( passed away recently) who spent a lot of his life researching cancer and trauma , and how shock effects the brain , he was able to image parts of the brain and make connections to other parts of the body where specifically,  cancers would manifest.

In his work ( he was an oncologist) , he found that he had over 90% cure  success rate with cancer patients simply by dealing with the traumas / shocks.

He had his license taken away in Germany for this research ! And lived abroad to continue his research .

Anyway , relative to benzos , it's not the whole picture , but I wonder how , if the brain is shocked, perhaps it causes lesions that then cause symptoms ongoing ....in the case of abrupt discontinuation this would  not neccesarily be a conscious shock, ( also can very much be) but  then not are shocks in those that develop cancers always... They are repressed in the subconscious.

I also wonder if this plays some roll in kindling ? Repeated feelings / symptoms of WD that the brain then patterns subconsciously,and physically in both the brain and thus the body ..... I'm not a scientist so I don't if any of this makes sense .

 

If you want to check out his work you can google Dr. Hamer ,German  new medicine .

He was against antianxiety meds , antidepressants , also steroids , as he felt they also suppressed the emotional roots of disease . Remarkable man ....he did go on to explore all kinds of other body illnesses related to trauma and shock . He found always that if the original shock was brought to consciousness , and a different meaning found in present time , the body would start to "reverse" the imbalance / illness.

 

MiYu

( both he and his wife developed cancer after their son died in a tragic accident , this initiated his research . He survived his cancer, his wife did not. He had access to many patients as he was an oncologist . So began his work )

 

Hi, thanks for this very interesting post.  I'm going to look into his work.  Speaking of trauma, the field of long term potentiation is huge, and very interesting.  This might interest you in the context of repeated traumas and fear processing,,,,,

 

 

 

LTP in fear processing

Quote

 

 

While the long-term potentiation of synapses in cell culture seems to provide an elegant substrate for learning and memory, the contribution of LTP to behavioral learning — that is, learning at the level of the whole organism — cannot simply be extrapolated from in vitro studies. For this reason, considerable effort has been dedicated to establishing whether LTP is a requirement for learning and memory in living animals. Because of this, LTP also plays a crucial role in fear processing.

 

End quote

 

 

 

Quote

 

In 2006, Jonathan Whitlock and colleagues reported on a series of experiments that provided perhaps the strongest evidence of LTP's role in behavioral memory, arguing that to conclude that LTP underlies behavioral learning, the two processes must both mimic and occlude one another.[50] Employing an inhibitory avoidance learning paradigm, researchers trained rats in a two-chambered apparatus with light and dark chambers, the latter being fitted with a device that delivered a foot shock to the rat upon entry. An analysis of CA1 hippocampal synapses revealed that inhibitory avoidance training induced in vivo AMPA receptor phosphorylation of the same type as that seen in LTP in vitro; that is, inhibitory avoidance training mimicked LTP. In addition, synapses potentiated during training could not be further potentiated by experimental manipulations that would have otherwise induced LTP; that is, inhibitory avoidance training occluded LTP. In a response to the article, Timothy Bliss and colleagues remarked that these and related experiments "substantially advance the case for LTP as a neural mechanism for memory."[51]

End quote

 

 

LTP in contextual cues to instigate anxiety(fear)

 

From Pers’ paper on LTP

 

In this study, rats were administered diazepam (DZ) for 18 days then abruptly taken off the drug.  The rats exhibited symptoms of withdrawal anxiety for 4 days after the drug was withdrawn.  On the 15th day the rats were re-exposed to the same environment (a plus maze, or PM) where they had originally experienced the withdrawal symptoms.  The contextual cues in the environment of the PM triggered a recurrence of the withdrawal symptoms. If the contextual cues were changed in the environment of the PM, the rats did not experience a recurrence of the withdrawal symptoms on re-exposure. 

 

“In the present investigation we demonstrated that changes in the environmental cues associated with DZ withdrawal prevented the expression of the anxiety-like behavior observed during PM test re-exposure.” (19)

 

 

The researchers attributed the recurrence of symptoms in conjunction with contextual cues to a lowered threshold to generate LTP.  Next they repeated the experiment, but this time they administered the PKMζ inhibitor ZIP two hours prior to re-exposure and observed the following:

 

“In the present study we found that inhibition of PKMζ prior to re-exposure to the withdrawal environment with preserved contextual cues not only prevented the anxiety expression but also reversed the facilitated LTP in all DZ-dependent animals, suggesting that plasticity in the hippocampus has a crucial role in maintenance of these memories that were vulnerable to the amnesic effects of ZIP.” (19)

 

It was interesting that this study showed environmental cues could trigger withdrawal symptoms in conjunction with LTPs, which may demonstrate an overlap in functional characteristics between memory LTPs and BZ withdrawal LTPs.  This poses a question as to whether LTPs which occur during withdrawal could share other commonalities with memories.  Other LTPs, such as LTPs involved in chronic pain conditions, have been shown to share characteristics with memory LTPs:

 

 

“…these findings point to a spinally encoded mechanism for the persistence of nociceptive sensitization with molecular underpinnings that closely resemble those involved in L-LTP and the maintenance of long-term memory traces.” (24)

 

 

Functional similarities between withdrawal LTPs and memory LTPs might include such things as distraction and time, which are two concepts discussed frequently with regards to benzo withdrawal.  Distraction appears help reduce withdrawal symptoms, and ironically is also a factor in both avoidance and fading of memories.  Time has been suggested to be the only known cure for withdrawal, similarly it is also the cure for painful memories as ‘time heals all wounds.’  Just as withdrawal symptoms can seemingly pop up again out of the blue, so can memories.  As demonstrated in the previous study, this may be due to contextual cues in the environment, either consciously or subconsciously, triggering the ‘biological memory’ stored in the Central Nervous system (CNS).  Contextual cues may be varied and might result from single or multiple environmental perceptions involving visual, tactile, olfactory, or gustatory senses.  Formation of LTPs may be the reason why withdrawal symptoms can persist for such a long time.

 

 

End quote

Thanks DM ..... This confirms my feelings that trauma triggers can indeed bring on WD symptoms....

And I believe this is why for some who experience protracted WD after CTs are actually being subconsciously triggered by things they ar not aware of .

 

In German new medicine they call them 'tracks '. Becoming conscious of the tracks or triggers are essential to healing the brain .

Dr Hamer was actually able to observe circular patterns in areas of the brain , that , on trauma resolve would just disappear . These circles would correspond to certain areas of the body , and also specifically to how the individual responded emotionally to the trauma , and also the meaning they made out of it . Changing the meaning was also key to healing .

 

What is LTP , sorry , I've missed that somewhere !

 

Time and distraction , yes , for sure .

I think fro some of us healing is much harder once we have an associated trauma 'sensation '. I speak fro myself .

 

I am working with someone who cured herself of epilepsy by identifying all tracks that stimulated her seizures. I hope she can help me .

I believe I now have a trauma 'track ' from my CT of steroids , as I have many similar symptoms during this attempt to withdraw from Valium .

It's also interesting to me how some people can try several times to withdraw and sometimes on their final try have very few symptoms .....

 

 

All very interesting , thank you for your research DM ,

MiYu 

 

Hi MiYu,

 

I included a very high level overview of LTP in ADDENDUM 8.  I hope you can find it in this thread.  It's in bold.  In layman's terms LTP is long term potentiation, usually referring to potentiation of Glutamate receptors, and in many cases a Glutamate receptor called the  AMPA.  You will see this pop up a lot in the next ADDENDUM, where I get into addiction physiology.    In this ADDENDUM 8 the LTP refers to a sensitization and/or upregulation of glutamate receptors, like the AMPAR.  It's long term in that the upregulation and/or sensitization can be very very persistent and long lasting.  This is important , because as we have seen glutamate ionic channels let in positive ions in the post synaptic membrane, and depolarize it.  Thus one can end up with persistently hyperexcitable neurons.  From your description of your encounter with a friend, hyperexcitability came to my mind.  It's a very uncomfortable feeling beyond anxiety, and in it's severe forms you feel an aura almost like a seizure like feeling.  Cues can trigger these LTPs,  pers also wrote two excellent papers on this entitled the Glutamate Hypotheses, and another on Nuclear Mechanisms of PWS.    LTPs are thought to contribute to extended post withdrawal symptoms long after the cessation of the benzodiazaphine.  It's a field where they are learning new things every day and ties in neurophysiological and neuropsychological aspects of the human brain.

 

Learning and memory is tied very closely to Glutamate receptors, especially NMDARs and AMPARs.....and LTP can also be viewed as a strengthening between synapses that form the basis of learning and memory.

 

Speaking of contextual cues, i will get into what is called behavioral tolerance.  There are a few types, one of which is called context-specific tolerance.  This is tolerance that builds up due to either external cues, or internal cues. 

 

Cues , as you've found, are very critical to triggering off chain reactions in the brain neurophysiology .  In this light, I can understand why they refer to them as tracks or triggers...

[[Be...]]

Too much external stress on a person who already has LTP keeps one from healing, IMO.  Keeps those glutamate receptors firing and causes more to come online.  I've got the environmental cue problem, too.  Lived in this place when I got off the pills and still here.  That's my problem. 

[[cs...]]

I don't blame you. This can be anxiety-provoking. But we'll make it through!! Step by step. No matter what!! Personally, I think a belief system that's strong helps. I know a woman on here who said her dad, when she was young, was very sick. He didn't want to hear the prognosis. So his family went in and heard from the doctor. The prognosis was bad. But since the father didn't hear it and no one told him, pretending that everything was okay, his immune system didn't go down and he remained positive. Well, he's still alive today! So it just goes to show that our attitudes have a lot to say about this, too. That's why I hate going to the doctor. I've heard way too much negativity, and of course I'm down, and my immune system isn't doing too well, afterwards and for a long time. Unfortunately, I have to have frequent visits. I don't know how to get around this.  :'(

 

Hi Terry, I feel much worse the more doctor appts I have.  They know that neuropsychology is tied very closely to the immune system,as you pointed out....

[[Te...]]

Thanks, dm123!! At least you feel the same.

[[Su...]]

I don't blame you. This can be anxiety-provoking. But we'll make it through!! Step by step. No matter what!! Personally, I think a belief system that's strong helps. I know a woman on here who said her dad, when she was young, was very sick. He didn't want to hear the prognosis. So his family went in and heard from the doctor. The prognosis was bad. But since the father didn't hear it and no one told him, pretending that everything was okay, his immune system didn't go down and he remained positive. Well, he's still alive today! So it just goes to show that our attitudes have a lot to say about this, too. That's why I hate going to the doctor. I've heard way too much negativity, and of course I'm down, and my immune system isn't doing too well, afterwards and for a long time. Unfortunately, I have to have frequent visits. I don't know how to get around this.  :'(

 

Hi Terry, I feel much worse the more doctor appts I have.  They know that neuropsychology is tied very closely to the immune system,as you pointed out....

 

Yes the staying strong part is definitely trying -- and as much as possible -- to mange thinking, to know the triggers and recognize the tracks..  As MiYu said much easier said than done.  However it seems to be an essential part of this healing -- and possibly the thinking that got so derailed by using benZos all those years -- even if I thought I was just asking them for sleep.  The cuts from my short acting Xanax hit me day 3-5 so in essence I was always medicated, to an extent I didn't realize.

 

Knowing the physiological challenges behind the experience is so helpful to me dm123..  It's not such a mystery but a recognizable and detailed response that the body does and can heal from....

SS

[[li...]]

You misunderstood. It's about the en.M.wikipedia . With the emphasis on M. Some sort of medical wiki that doesn't show up when you're googling for it ? Does it have a name ? An entry ? Who started it ?

Usually I just get to en.wikipedia ... I need to remember that M ...

 

Side note: I've tried to find that 'medical wiki' but for some reason it's nigh impossible unless I know the URL. It's a medical wiki, isn't it ?

 

As in https://en.m.wikipedia.org/wiki                                /Category:GABAA_receptor_positive_allosteric_modulators#/search

 

I couldn't find it with google. Unless it's related to a language or country ...

 

It must be.  This link works for me.  I would publish it here but it's far too long

Try a google on this part

 

Category:GABAA_receptor_positive_allosteric_modulators#/search

[[cs...]]

Hi all,

 

I wanted to post 2 things today.  The first in this post one of the best and shortest descriptions of classical LTP that I've read in a long time. See below.

 

The second post will be ADDENDUM 9 , and it will be posted via a Dropbox link to a word doc.  The doc can also be downloaded for offline reading. The LTP discussed in the ADDENDUM 9 is referred to as LTP-like in the scientific literature, because the mechanism of AMPAR receptor sensitization is different from the classical LTP.  Furthermore the LTP-like potentiation in ADDENDUM 9 is relative to a specific area of the brain called the VTA and is a potentiation of the AMPARs on the VTA DA(dopamine) neurons.  It's explained in the context of benzodiazaphine addiction Physiology , and makes up the last half of the paper.

 

It's a very long paper, and the last section on addiction Physiology gets a bit complex.  I've used a variety of bolding, highlighting, colors, etc to try to get the point across, and realize it's content might not be suitable for everyone.

 

Let me know if the Dropbox link does NOT work.

 

Here is the quote on classical NMDAR LTP

 

 

https://en.m.wikipedia.org/wiki/AMPA_receptor

Quote

The simplest explanation for LTP is as follows (see the long-term potentiation article for a much more detailed account). Glutamate binds to postsynaptic AMPARs and another glutamate receptor, the NMDA receptor (NMDAR). Ligand binding causes the AMPARs to open, and Na+ flows into the postsynaptic cell, resulting in a depolarization. NMDARs, on the other hand, do not open directly because their pores are occluded at resting membrane potential by Mg2+ ions. NMDARs can open only when a depolarization from the AMPAR activation leads to repulsion of the Mg2+ cation out into the extracellular space, allowing the pore to pass current. Unlike AMPARs, however, NMDARs are permeable to both Na+ and Ca2+. The Ca2+that enters the cell triggers the upregulation of AMPARs to the membrane, which results in a long-lasting increase in EPSP size underlying LTP. The calcium entry also phosphorylates CaMKII, which phosphorylates AMPARs, increasing their single-channel conductance.

End quote

 

 

[[cs...]]

Here is the ADDENDUM 9 and a dropox link to the word document.

 

Please see the post above for a brief introduction to this link

Title

ADDENDUM 9:

GABAa subunit configuration tolerance characteristics.

Tolerance, abuse liability (potential for addiction),  drug reinforcement (drug seeking),

Tolerance: more than just GABAaRs…..

Addiction Physiology and Benzodiazaphines

By dm123

 

Here is the opening quote.  I'm posting it here because this is honestly how I feel given the 100s of clinical studies, and thousands of pages  that I've read through in the last several months.

 

~”Well, in regards to prescribing long term benzodiazaphines, it looks like many doctors have completely thrown out all of the damning scientific evidence and clinical studies that preclude their long term use.  They have decided to indiscriminately prescribe benzodiazaphines  to suit their business and clinical practice needs and objectives. In doing so, they have blatantly and arrogantly disregarded the long term consequences and repercussions that their actions have had on their patients’ health and well being.” – dm123

 

 

Here is the Dropbox link

 

 

 

 

 

 

[[li...]]

My compliments. I briefly read or skimmed through the material. It´s a lot.

 

Two comments. The connection between dopamine and ´addiction´. As far as I know, dopamine is associated with motivation, not reward. Second, that´s the bias of ´addiction medicine´, I think. Addiction is an incurable brain disease blahblahblah

 

Short half life vs. long half life ! We are never going to agree on that one, are we ? Then there is ´duration of action´ ...

One point I´d like to make: with a drug that has a long half life (assuming it ´does´ something past its duration of action) in the case of daily consumption the CNS is constantly exposed to the drug. Solely on the basis of that, I would expect faster neuroadaptation. (I know other factors play a role) I think you underestimate how awful long half life benzos can be.

[[cs...]]

My compliments. I briefly read or skimmed through the material. It´s a lot.

 

Two comments. The connection between dopamine and ´addiction´. As far as I know, dopamine is associated with motivation, not reward. Second, that´s the bias of ´addiction medicine´, I think. Addiction is an incurable brain disease blahblahblah

 

Short half life vs. long half life ! We are never going to agree on that one, are we ? Then there is ´duration of action´ ...

One point I´d like to make: with a drug that has a long half life (assuming it ´does´ something past its duration of action) in the case of daily consumption the CNS is constantly exposed to the drug. Solely on the basis of that, I would expect faster neuroadaptation. (I know other factors play a role) I think you underestimate how awful long half life benzos can be.

 

 

My compliments. I briefly read or skimmed through the material. It´s a lot.

 

Two comments. The connection between dopamine and ´addiction´. As far as I know, dopamine is associated with motivation, not reward. Second, that´s the bias of ´addiction medicine´, I think. Addiction is an incurable brain disease blahblahblah

 

Short half life vs. long half life ! We are never going to agree on that one, are we ? Then there is ´duration of action´ ...

One point I´d like to make: with a drug that has a long half life (assuming it ´does´ something past its duration of action) in the case of daily consumption the CNS is constantly exposed to the drug. Solely on the basis of that, I would expect faster neuroadaptation. (I know other factors play a role) I think you underestimate how awful long half life benzos can be.

Hi liberty,

Yes but the motivation and reward are both intimately tied together....as you know there's lots of references on this, especially relative to the brain location, and DA plays an integral part in the reward system in those areas of the brain.

I'm hoping the takeaway is that DA homeostasis is messed up with benzodiazaphines in these parts of the brain,  including the NAc and possibly other areas, as the references state, and that's not a good thing.  It's part of addiction Physiology, if not addiction medicine.  I think addiction medicine is tratement for addiction.

As I mentioned, once we are off the drug it appears that things are physiologically in place to correct the imbalances.

https://www.ncbi.nlm.nih.gov/pubmed/2648975

 

Long vs. short

I think they are both very bad, but if I had to chose, I wish I had been put on Valium initially.  I agree with some of what you state, but paradoxically constant exposure has benefits as well as drawbacks and same for shorter life benzodiazaphines.  I would get rid of all of them

 

Kindling is a big factor with shorter acting benzodiazaphines. Even though we don't have a clear picture on how it occurs exactly on the excitatory side, it does occur.  I realize that's not the only factor, but it's significant for one who has gone through it. 

 

 

[[Su...]]

Here is the ADDENDUM 9 and a dropox link to the word document.

 

Please see the post above for a brief introduction to this link

Title

ADDENDUM 9:

GABAa subunit configuration tolerance characteristics.

Tolerance, abuse liability (potential for addiction),  drug reinforcement (drug seeking),

Tolerance: more than just GABAaRs…..

Addiction Physiology and Benzodiazaphines

By dm123

 

Here is the opening quote.  I'm posting it here because this is honestly how I feel given the 100s of clinical studies, and thousands of pages  that I've read through in the last several months.

 

~”Well, in regards to prescribing long term, short-acting benzodiazaphines, it looks like many doctors have completely thrown out all of the damning scientific evidence and clinical studies that preclude their long term use.  They have decided to indiscriminately prescribe benzodiazaphines  to suit their business and clinical practice needs and objectives. In doing so, they have blatantly and arrogantly disregarded the long term consequences and repercussions that their actions have had on their patients’ health and well being.” – dm123

 

 

Here is the Dropbox link

 

I don't seem to have the dropbox link on the page.  Could you repost it?  I'd like to read this paper.

Many thanks for all of this as always.

SS

[[Te...]]

Well done, dm123!!! This is exactly how I feel, and to have scientific studies to back that up is wonderful!

 

"Here is the opening quote.  I'm posting it here because this is honestly how I feel given the 100s of clinical studies, and thousands of pages  that I've read through in the last several months."

~”Well, in regards to prescribing long term, short-acting benzodiazaphines, it looks like many doctors have completely thrown out all of the damning scientific evidence and clinical studies that preclude their long term use.  They have decided to indiscriminately prescribe benzodiazaphines  to suit their business and clinical practice needs and objectives. In doing so, they have blatantly and arrogantly disregarded the long term consequences and repercussions that their actions have had on their patients’ health and well being.” – dm123

[[Su...]]

Well done, dm123!!! This is exactly how I feel, and to have scientific studies to back that up is wonderful!

 

"Here is the opening quote.  I'm posting it here because this is honestly how I feel given the 100s of clinical studies, and thousands of pages  that I've read through in the last several months."

~”Well, in regards to prescribing long term, short-acting benzodiazaphines, it looks like many doctors have completely thrown out all of the damning scientific evidence and clinical studies that preclude their long term use.  They have decided to indiscriminately prescribe benzodiazaphines  to suit their business and clinical practice needs and objectives. In doing so, they have blatantly and arrogantly disregarded the long term consequences and repercussions that their actions have had on their patients’ health and well being.” – dm123

 

Yes yes Yes!

SS

[[cs...]]

Here is the ADDENDUM 9 and a dropox link to the word document.

 

Please see the post above for a brief introduction to this link

Title

ADDENDUM 9:

GABAa subunit configuration tolerance characteristics.

Tolerance, abuse liability (potential for addiction),  drug reinforcement (drug seeking),

Tolerance: more than just GABAaRs…..

Addiction Physiology and Benzodiazaphines

By dm123

 

Here is the opening quote.  I'm posting it here because this is honestly how I feel given the 100s of clinical studies, and thousands of pages  that I've read through in the last several months.

 

~”Well, in regards to prescribing long term, short-acting benzodiazaphines, it looks like many doctors have completely thrown out all of the damning scientific evidence and clinical studies that preclude their long term use.  They have decided to indiscriminately prescribe benzodiazaphines  to suit their business and clinical practice needs and objectives. In doing so, they have blatantly and arrogantly disregarded the long term consequences and repercussions that their actions have had on their patients’ health and well being.” – dm123

 

 

Here is the Dropbox link

 

I don't seem to have the dropbox link on the page.  Could you repost it?  I'd like to read this paper.

Many thanks for all of this as always.

SS

Hi SS, there are issues with the Dropbox account and I've taken it down..  I don't know how I'm going to post it, but if anyone has a public Dropbox that blocks editing of the source doc, let me know and I will drop it there.  It's a long doc, and can't be pasted here.  It's hard enough to understand as it is 

[[cs...]]

Hi all,

 

I'm going to continue to do research.  I will cover the following areas in the future, but won't post the papers.  (They are too long and overwhelming).  I will leverage the knowledge to help in any way possible if there are any questions in the areas above or below. 

 

I'm going through the taper myself, and so I can really feel the clinical aspects of the research in my own physiology. 

 

I will post ADDENDUM 10 on the value of exercise during a taper.  This can be used as a supplement to Bart's excellent post pinned above.

Exercise has been,  and is,  an incredibly valuable tool that all of us have to help foster  resilency and healing during and after a taper

 

Here are the topics I will or am researching following ADDENDUM 10

 

These will be researched in the context of ADDENDUM 8 Scope areas 3,4, and 5

-area 3 Chronic use with tolerance

-area 4 interdose withdrawal without tolerance (tolerance has started with changes in GABAa endocytosis and receptor trafficking)

- area 5 interdose wd with tolerance

 

Topics after ADDENDUM 10:

11. Phosphorylation and kinases,  in general . 

-Then GABAa  β1-3 and γ2 subunit phosphorylation, then GABAa α and δ subunit phosphorylation

 

12. Benzodiazaphines and GPCRs for ACh, serotonin, and dopamine

-GPCR coupling to potassium (GIRKS), sodium, Calcium and chloride ionotropic channels

-GPCR coupling to GABAa receptors

-benzodiazaphine effects on extracellular neurotransmitter levels and physiological effects on GPCRs

-GPCRs and presynaptic modulation

 

13. Glutamate ionotropic channels and benzodiazaphines

-NMDAR and AMPAR antagonist studies and benzodiazaphines

 

14. Glycine: an excitatory and inhibitory neurotransmitter, and benzodiazaphines

 

15.  Classic neuro-kindling and epileptogenesis (seizure development), and Glutamate and GABAa ionotropic channels

-hyperexcitability and seizure threshold

-what can we learn from the studies of epileptogenesis

-molecular basis of kindling

-dysregulation of GABAa receptor trafficking in kindled seizure development

 

16. Kindling and alcohol studies (binge and chronic) and extrapolating to chronic benzodiazaphine use:

-the physiological effects on GABAa receptors

-why alcohol effects on Glutamate receptors are unique and different from benzodiazaphine use

-dysregulation of GABAa receptor trafficking in alcoholism

-alcohol withdrawal and kindling seizure development

 

17.  Putting it all together: Action Potential (AP) dynamics and Benzodiazaphines

-Voltage gated sodium and voltage gated potassium channels and the effects that benzodiazaphines have on them

-A review of APs

-presynaptic quantal analysis

-benzodiazaphines and the AP dynamics of a hyperexcitable neuron: why we feel so sick

 

18. Other areas that affect benzodiazaphine tolerance development

-Transcriptional and Neurotrophic factors and benzodiazaphine tolerance development

-Neurosteroids and Benzodiazaphine tolerance development

-Nitric oxide (NO) and benzodiazaphine tolerence: alcohol studies

 

19.  Presynaptic activity and extracellular Glutamate and GABA homeostasis during  benzodiazaphine use, and withdrawal.

-revisiting presynaptic quantal analysis

-brain specific region variance of extracellular GABA and Glutamate

-neurotransmitter extracellular clearance transporters (EAATs), GAT, GAD ( glutamate decarboxylase ) and benzodoazaphines

-synaptotagmins and synaptic vesicles

-retrograde messengers

 

20. Tolerance adaptation as a heterogeneous process: a different viewpoint of tolerance relative to brain region

-development of tolerance on different time scales

-GABAa receptor subtypes, brain region, and half life as determinants