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

[[cs...]]

dm123,

 

That these 'steroids' affect the brain through the glucocorticoid and mineralocorticoid receptors seems very sensible. As Perseverance stated, low amounts affect MRs, high amonts GRs (or something like that)

 

I know  (?) that the theory says that in humans the only active glucocorticoid is cortisol, but I've doubted that myself.

 

What I recall from exercise, and running is a good example, is that there are long lasting effects from one session. Also the 'acute' (post acute?) effect after the exercise can last a long time. It feels like a high amount of an active glucocorticoid has has been released, one that also has a long half life. And I'm writing this as I remember, the reported half lives for cortisol seem to differ. Aside from any other issues, I would describe the effect as a dampening effect, typically improving mental lucidity and dampening metabolic rate ('body temperature') This may mostly be a clonazepam thing.

 

Ok great to know Pers and I are on the same general direction.  I agree with you on all the above.  Please see this reference.  I'm still working though it myself, but it explains what you've been trying to figure out regarding stress, GABAaRs, extracellular GABA, CRH, steroids and Neurosteroids, etc.  it ties up the loose ends .  I'm going to study it for the next several days.  Knowledge is power

 

 

The section on CRH and the feedback mechanism with GABAaRs is particle interesting and amazing.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3268361/

 

The reciprocal regulation of stress hormones and GABAA receptors

Istvan Mody and Jamie Maguire

 

 

[[fr...]]

  I sleep fair.  I get about 4 to 5 hrs. of sleep and then can sometimes get another hr or so in.  So sleep isn't really great but I think its the nerve pain which keeps me awake.  I think I will just refuse the shots.  I will deal with that pain.  I don't know what they inject.  I know he did two shots in spine back two years ago.  He likes to do one and then a booster.  They didn't help that time.  I had gotten some for years on and off that helped so much but that was pre benzos.  I was only taking the soma and pain med then.  Have had some in knees.  I need knee replacements but am putting them off also.  Pain is a terrible issue for me.  Anyway, thanks for all your help. 

[[...]]

dm123,

 

That these 'steroids' affect the brain through the glucocorticoid and mineralocorticoid receptors seems very sensible. As Perseverance stated, low amounts affect MRs, high amonts GRs (or something like that)

 

I know  (?) that the theory says that in humans the only active glucocorticoid is cortisol, but I've doubted that myself.

 

What I recall from exercise, and running is a good example, is that there are long lasting effects from one session. Also the 'acute' (post acute?) effect after the exercise can last a long time. It feels like a high amount of an active glucocorticoid has has been released, one that also has a long half life. And I'm writing this as I remember, the reported half lives for cortisol seem to differ. Aside from any other issues, I would describe the effect as a dampening effect, typically improving mental lucidity and dampening metabolic rate ('body temperature') This may mostly be a clonazepam thing.

 

Ok great to know Pers and I are on the same general direction.  I agree with you on all the above.  Please see this reference.  I'm still working though it myself, but it explains what you've been trying to figure out regarding stress, GABAaRs, extracellular GABA, CRH, steroids and Neurosteroids, etc.  it ties up the loose ends .  I'm going to study it for the next several days.  Knowledge is power

 

 

The section on CRH and the feedback mechanism with GABAaRs is particle interesting and amazing.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3268361/

 

The reciprocal regulation of stress hormones and GABAA receptors

Istvan Mody and Jamie Maguire

 

DM , do you think the HPA axis recovers from disregulation from steroids once the steroids are stopped?    And the fact that my cortisol levels were normal after stopping ,mellow that would indicate at least that the adrenals and presumably pituitary were working ok .

 

I feel that my HPA axis is now disregulated from the benzos , I do find now that I am on klonopin again that it actually seems to effect CRH more . I get more early morning cortisol surges than I did with the Valium .

I actually brought up with my doctor about the previous steroid use effecting my WD from benzos , and he was clueless , he just said , they are completely different drugs ....

 

I'm glad you're  doing this research . I hope perhaps you'll be able to provide some kind of educational paper on your findings that might help educate some of the medical community , that would be really great .

 

Free , there's a book I don't know if you'd be interested , written by a doctor who had a lot of success helping people deal with back pain , the book is called "The Mindbody prescription " Healing the Body , healing the pain. By John E. Sarno. I don't knwo your situation, but I wanted to mention it.

 

Miyu

 

 

[[...]]

dm123,

 

That these 'steroids' affect the brain through the glucocorticoid and mineralocorticoid receptors seems very sensible. As Perseverance stated, low amounts affect MRs, high amonts GRs (or something like that)

 

I know  (?) that the theory says that in humans the only active glucocorticoid is cortisol, but I've doubted that myself.

 

What I recall from exercise, and running is a good example, is that there are long lasting effects from one session. Also the 'acute' (post acute?) effect after the exercise can last a long time. It feels like a high amount of an active glucocorticoid has has been released, one that also has a long half life. And I'm writing this as I remember, the reported half lives for cortisol seem to differ. Aside from any other issues, I would describe the effect as a dampening effect, typically improving mental lucidity and dampening metabolic rate ('body temperature') This may mostly be a clonazepam thing.

 

So Liberty , are you concluding that excercise is helpful for your healing ?

Also As I wrote to DM , I am finding klonopin to have a different effect relative to CRH , it's more intense , definitely a different drug from Valium ,I find it kind of stimulating actually overall.

 

(DM, I am able to walk around a little bit in my house , and I can do some gentle stretches . Also I haven't touched alcohol in many years, I think I had a glass of wine some years back and was sick for 48 hrs , pre steroids and pre benzos ....so seems like my GABA system was already sensitive . )

 

MiYu

[[fr...]]

  Thanks MiYu for the info on book.  Hope you start to feel better soon.  I am so sick, just very discouraged at the moment.  You know how it is.  Thanks again., 

[[...]]

  Thanks MiYu for the info on book.  Hope you start to feel better soon.  I am so sick, just very discouraged at the moment.  You know how it is.  Thanks again., 

 

Yes Free , I do know , I feel the same way , it's hard to see any end to it, without thinking all th 'what if'thoughts too.

I am having so much cortisol surges in the mornings I get anxious about my adrenals giving up on me . I shake all the time .....and just feel so fragile .

 

Keep holding on !

MiYu 

[[fr...]]

  My hands shake in the morning too now.  Never used to.  Also am bruising easily but I thik it was from taking the Advil for so long.  I haven't taken it in over a week now.  Very hard to keep hanging in there.  I hope your cross starts to give you some relief. 

[[cs...]]

dm123,

 

That these 'steroids' affect the brain through the glucocorticoid and mineralocorticoid receptors seems very sensible. As Perseverance stated, low amounts affect MRs, high amonts GRs (or something like that)

 

I know  (?) that the theory says that in humans the only active glucocorticoid is cortisol, but I've doubted that myself.

 

What I recall from exercise, and running is a good example, is that there are long lasting effects from one session. Also the 'acute' (post acute?) effect after the exercise can last a long time. It feels like a high amount of an active glucocorticoid has has been released, one that also has a long half life. And I'm writing this as I remember, the reported half lives for cortisol seem to differ. Aside from any other issues, I would describe the effect as a dampening effect, typically improving mental lucidity and dampening metabolic rate ('body temperature') This may mostly be a clonazepam thing.

 

Ok great to know Pers and I are on the same general direction.  I agree with you on all the above.  Please see this reference.  I'm still working though it myself, but it explains what you've been trying to figure out regarding stress, GABAaRs, extracellular GABA, CRH, steroids and Neurosteroids, etc.  it ties up the loose ends .  I'm going to study it for the next several days.  Knowledge is power

 

 

The section on CRH and the feedback mechanism with GABAaRs is particle interesting and amazing.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3268361/

 

The reciprocal regulation of stress hormones and GABAA receptors

Istvan Mody and Jamie Maguire

 

DM , do you think the HPA axis recovers from disregulation from steroids once the steroids are stopped?    And the fact that my cortisol levels were normal after stopping ,mellow that would indicate at least that the adrenals and presumably pituitary were working ok .

 

I feel that my HPA axis is now disregulated from the benzos , I do find now that I am on klonopin again that it actually seems to effect CRH more . I get more early morning cortisol surges than I did with the Valium .

I actually brought up with my doctor about the previous steroid use effecting my WD from benzos , and he was clueless , he just said , they are completely different drugs ....

 

I'm glad you're  doing this research . I hope perhaps you'll be able to provide some kind of educational paper on your findings that might help educate some of the medical community , that would be really great .

 

Free , there's a book I don't know if you'd be interested , written by a doctor who had a lot of success helping people deal with back pain , the book is called "The Mindbody prescription " Healing the Body , healing the pain. By John E. Sarno. I don't knwo your situation, but I wanted to mention it.

 

Miyu

 

Hi MiYu, my first thought I had when you mentioned you were on 60mg HC a day was amazement when you said your serum (.? Or was it saliva?) cortisol levels were normal once you were off it.  It took me several months to get off of the 30 I was on.  If your morning cortisol was normal, you did indeed recover.  It's amazing and you have a very resilient HPA.  How long did it take you to taper the HC?   

 

So the HPA does recover from steroid use, but I have heard anecdotal evidence of people having a much harder time getting off of it due to ACTH suppression, at doses as low as 30 mg, which is a tragedy.  I have not bothered to do the clinical research on this, but I know of one endocrinologist who wanted me off the stuff 3 months after I started.  He was probably right, but I was too cautious about crashing again , and ended up on it for 2.5 years.  After all that my morning ACTH is normal now. Depending on how I sleep, the cortisol levels are still unstable, but resilient. So some of us are very fortunate and we recover.  We are indeed lucky.  Steroid use can cause damage to the beta insulin producing cells in the pancreas and can cause adult diabetes.  As you know, there are many other negative side effects, mostly dose dependent.

 

I know that you are aware of steroid effects on bone turnover. It disrupts both osteoblastogenesis and osteoclastogenisis, i.e. Bone buliding and bone terardown.  So remodeling is disrupted while on the steroid.  Once you get off, these things return to normal.  I assume you have had a DEXA bone scan to establish a baseline bone density in your femur and lower spine, especially given you are small framed, as you mentioned in a precious post.  I assume you are on Ca, vit D, magnesium, and boron and have a good intake of dairy.

 

I also want to post another recent 2012 study on the effects of chronic and acute CRH elevations on he hippocampus.  The hippocampus is an area I researched in the context of an exercise module.  It's affected by benzodiazaphines, but exercise can be therapeutic, because it's highly plastic.

 

 

If you are interested, here the paper on CRH and it's relationship to stress and hippocampal neurogenesis

 

https://www.frontiersin.org/articles/10.3389/fncel.2012.00013/full

 

Regarding the research, I hope to collect all the modules (ADDENDUMs)when it's done.  They are  quite long, and I do post small portions to this thread as I move through the research.  I'm currently investigating alcohol and Neurosteroids, the link I just posted yesterday on the reciprocal stress GABAaR relstionship, and also tonic inhibition and  extrasynaptic GABAaRs and brain neurocircuitry, which is a huge area.

[[cs...]]

  Thanks MiYu for the info on book.  Hope you start to feel better soon.  I am so sick, just very discouraged at the moment.  You know how it is.  Thanks again., 

 

Yes Free , I do know , I feel the same way , it's hard to see any end to it, without thinking all th 'what if'thoughts too.

I am having so much cortisol surges in the mornings I get anxious about my adrenals giving up on me . I shake all the time .....and just feel so fragile .

 

Keep holding on !

MiYu 

 

Hi MiYu, if you are sleeping fairly ok, at least 4-5 hours, you will be surprised of how resilient you HPA can be.  Sleep is the most important thing for adrenal HPA recovery and stability.  The more sleep the better, and once you are up, avoid napping.  For those of us with HPA issues it will just mess with the circadian rhythm.

[[cs...]]

  I sleep fair.  I get about 4 to 5 hrs. of sleep and then can sometimes get another hr or so in.  So sleep isn't really great but I think its the nerve pain which keeps me awake.  I think I will just refuse the shots.  I will deal with that pain.  I don't know what they inject.  I know he did two shots in spine back two years ago.  He likes to do one and then a booster.  They didn't help that time.  I had gotten some for years on and off that helped so much but that was pre benzos.  I was only taking the soma and pain med then.  Have had some in knees.  I need knee replacements but am putting them off also.  Pain is a terrible issue for me.  Anyway, thanks for all your help.

That's great.  You are getting enough sleep.

[[cs...]]

  My hands shake in the morning too now.  Never used to.  Also am bruising easily but I thik it was from taking the Advil for so long.  I haven't taken it in over a week now.  Very hard to keep hanging in there.  I hope your cross starts to give you some relief.

Can you increase your vitamin C intake.  It well help prevent the little capillaries from breaking.  You don't need to megadose.  I take 1000 mg a day.

[[fr...]]

  Yes I can try it.  Thanks again. 

[[li...]]

dm123,

 

That these 'steroids' affect the brain through the glucocorticoid and mineralocorticoid receptors seems very sensible. As Perseverance stated, low amounts affect MRs, high amonts GRs (or something like that)

 

I know  (?) that the theory says that in humans the only active glucocorticoid is cortisol, but I've doubted that myself.

 

What I recall from exercise, and running is a good example, is that there are long lasting effects from one session. Also the 'acute' (post acute?) effect after the exercise can last a long time. It feels like a high amount of an active glucocorticoid has has been released, one that also has a long half life. And I'm writing this as I remember, the reported half lives for cortisol seem to differ. Aside from any other issues, I would describe the effect as a dampening effect, typically improving mental lucidity and dampening metabolic rate ('body temperature') This may mostly be a clonazepam thing.

 

So Liberty , are you concluding that excercise is helpful for your healing ?

Also As I wrote to DM , I am finding klonopin to have a different effect relative to CRH , it's more intense , definitely a different drug from Valium ,I find it kind of stimulating actually overall.

(DM, I am able to walk around a little bit in my house , and I can do some gentle stretches . Also I haven't touched alcohol in many years, I think I had a glass of wine some years back and was sick for 48 hrs , pre steroids and pre benzos ....so seems like my GABA system was already sensitive . )

 

MiYu

 

Response to bold.

 

1) No. But no exercise poses its own problems ...

 

2) Stimulating, that sounds so familiar.

[[cs...]]

  I sleep fair.  I get about 4 to 5 hrs. of sleep and then can sometimes get another hr or so in.  So sleep isn't really great but I think its the nerve pain which keeps me awake.  I think I will just refuse the shots.  I will deal with that pain.  I don't know what they inject.  I know he did two shots in spine back two years ago.  He likes to do one and then a booster.  They didn't help that time.  I had gotten some for years on and off that helped so much but that was pre benzos.  I was only taking the soma and pain med then.  Have had some in knees.  I need knee replacements but am putting them off also.  Pain is a terrible issue for me.  Anyway, thanks for all your help.

 

Hi freeme, I am glad you are passing on the injections.  Just for reference on this thread here are some papers on HPA suppression and steroid injections. 

 

Google "HPA suppression and steroid injections"

 

 

 

I like this paper on the same because it has all the clinical details , lab values, and time references clearly indicated.  Most people experience some suppression, but probably don't really crash because they are relatively systemically healthy and are not under long term stress that would predispose one to a crash.

 

https://www.hindawi.com/journals/crie/2013/617042/

[[Le...]]

  I sleep fair.  I get about 4 to 5 hrs. of sleep and then can sometimes get another hr or so in.  So sleep isn't really great but I think its the nerve pain which keeps me awake.  I think I will just refuse the shots.  I will deal with that pain.  I don't know what they inject.  I know he did two shots in spine back two years ago.  He likes to do one and then a booster.  They didn't help that time.  I had gotten some for years on and off that helped so much but that was pre benzos.  I was only taking the soma and pain med then.  Have had some in knees.  I need knee replacements but am putting them off also.  Pain is a terrible issue for me.  Anyway, thanks for all your help.

 

Hi freeme, I am glad you are passing on the injections.  Just for reference on this thread here are some papers on HPA suppression and steroid injections. 

 

Google "HPA suppression and steroid injections"

 

 

 

I like this paper on the same because it has all the clinical details , lab values, and time references clearly indicated.  Most people experience some suppression, but probably don't really crash because they are relatively systemically healthy and are not under long term stress that would predispose one to a crash.

 

https://www.hindawi.com/journals/crie/2013/617042/

Very interesting dm123. Thank you for this. I had a bad reaction to steroid injections in both knees in 2014, have refused them ever since.

[[...]]

dm123,

 

That these 'steroids' affect the brain through the glucocorticoid and mineralocorticoid receptors seems very sensible. As Perseverance stated, low amounts affect MRs, high amonts GRs (or something like that)

 

I know  (?) that the theory says that in humans the only active glucocorticoid is cortisol, but I've doubted that myself.

 

What I recall from exercise, and running is a good example, is that there are long lasting effects from one session. Also the 'acute' (post acute?) effect after the exercise can last a long time. It feels like a high amount of an active glucocorticoid has has been released, one that also has a long half life. And I'm writing this as I remember, the reported half lives for cortisol seem to differ. Aside from any other issues, I would describe the effect as a dampening effect, typically improving mental lucidity and dampening metabolic rate ('body temperature') This may mostly be a clonazepam thing.

 

Ok great to know Pers and I are on the same general direction.  I agree with you on all the above.  Please see this reference.  I'm still working though it myself, but it explains what you've been trying to figure out regarding stress, GABAaRs, extracellular GABA, CRH, steroids and Neurosteroids, etc.  it ties up the loose ends .  I'm going to study it for the next several days.  Knowledge is power

 

 

The section on CRH and the feedback mechanism with GABAaRs is particle interesting and amazing.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3268361/

 

The reciprocal regulation of stress hormones and GABAA receptors

Istvan Mody and Jamie Maguire

 

DM , do you think the HPA axis recovers from disregulation from steroids once the steroids are stopped?    And the fact that my cortisol levels were normal after stopping ,mellow that would indicate at least that the adrenals and presumably pituitary were working ok .

 

I feel that my HPA axis is now disregulated from the benzos , I do find now that I am on klonopin again that it actually seems to effect CRH more . I get more early morning cortisol surges than I did with the Valium .

I actually brought up with my doctor about the previous steroid use effecting my WD from benzos , and he was clueless , he just said , they are completely different drugs ....

 

I'm glad you're  doing this research . I hope perhaps you'll be able to provide some kind of educational paper on your findings that might help educate some of the medical community , that would be really great .

 

Free , there's a book I don't know if you'd be interested , written by a doctor who had a lot of success helping people deal with back pain , the book is called "The Mindbody prescription " Healing the Body , healing the pain. By John E. Sarno. I don't knwo your situation, but I wanted to mention it.

 

Miyu

 

Hi MiYu, my first thought I had when you mentioned you were on 60mg HC a day was amazement when you said your serum (.? Or was it saliva?) cortisol levels were normal once you were off it.  It took me several months to get off of the 30 I was on.  If your morning cortisol was normal, you did indeed recover.  It's amazing and you have a very resilient HPA.  How long did it take you to taper the HC?   

 

So the HPA does recover from steroid use, but I have heard anecdotal evidence of people having a much harder time getting off of it due to ACTH suppression, at doses as low as 30 mg, which is a tragedy.  I have not bothered to do the clinical research on this, but I know of one endocrinologist who wanted me off the stuff 3 months after I started.  He was probably right, but I was too cautious about crashing again , and ended up on it for 2.5 years.  After all that my morning ACTH is normal now. Depending on how I sleep, the cortisol levels are still unstable, but resilient. So some of us are very fortunate and we recover.  We are indeed lucky.  Steroid use can cause damage to the beta insulin producing cells in the pancreas and can cause adult diabetes.  As you know, there are many other negative side effects, mostly dose dependent.

 

I know that you are aware of steroid effects on bone turnover. It disrupts both osteoblastogenesis and osteoclastogenisis, i.e. Bone buliding and bone terardown.  So remodeling is disrupted while on the steroid.  Once you get off, these things return to normal.  I assume you have had a DEXA bone scan to establish a baseline bone density in your femur and lower spine, especially given you are small framed, as you mentioned in a precious post.  I assume you are on Ca, vit D, magnesium, and boron and have a good intake of dairy.

 

I also want to post another recent 2012 study on the effects of chronic and acute CRH elevations on he hippocampus.  The hippocampus is an area I researched in the context of an exercise module.  It's affected by benzodiazaphines, but exercise can be therapeutic, because it's highly plastic.

 

 

If you are interested, here the paper on CRH and it's relationship to stress and hippocampal neurogenesis

 

https://www.frontiersin.org/articles/10.3389/fncel.2012.00013/full

 

Regarding the research, I hope to collect all the modules (ADDENDUMs)when it's done.  They are  quite long, and I do post small portions to this thread as I move through the research.  I'm currently investigating alcohol and Neurosteroids, the link I just posted yesterday on the reciprocal stress GABAaR relstionship, and also tonic inhibition and  extrasynaptic GABAaRs and brain neurocircuitry, which is a huge area.

 

Sorry DM , I missed your response .....

Let's see, I was on the steroids 9 months . I think I was on 40-60 for 5 months , Dan a couple of times I took like, 120 Mgs! This was twice when I went to ER . Who knows what was really happening , I don't know. I could NEVER get the dosing right . I was given methylprednesolone .... To see if it work "better". Two weeks on that at equivalent of 80 mgs HC . Started getting cushings , not surprise there ....went back to hC , I just couldn't cut lower than 60 mgs fro a couple of months , then I could , and  I started reducing rapidly . I got down to 20 mgs in about a month probably , another trip to the ER, after really bad reaction to a dose. Switched over to prednisone ....and I think I was down to 1/18th mg of that in a month.... I had bad WDs . I couldn't get off that last tiny bit . Kept trying until one day I was able to . I felt like I was dying during that last part , and I would feel so much worse after taking that tiny amount . Eventually I stopped that though.

I was pretty sick and my nervous system was very unstable .

Then had a life crisis and my body couldn't handle the stress , enter daily benzos .

 

I don't think there was ever anything wrong with my adrenals or pituitary . I was just stressed and going through perimenopause .

 

Now benzos are a nightmare for me to withdraw from so I'm sure it has something to with the steroid trauma .,

I haven't had a bone density test . I can't manage any appointments at the moment . Thoigh I did have some bloodwork done in June , most things normal except low white blood cell . It was a fasting test and my glucose level was good .

 

I'm cautious with supplements , but I do drink nut milk that is fortified .

 

One if my most disturbing symptoms with benzos is this stress intolerance . It may have to do with the steroids and HPA suppression as I can't handle any stress . Maybe my adrenals/HPA axis are not yet responsive enough to stressors having been suppressed so much .

It was puzzling how normal my cortsol was after all these steroids .....I should probably do another Saliva test.

 

Thanks for all your research DM ,

MiYu

 

[[cs...]]

dm123,

 

That these 'steroids' affect the brain through the glucocorticoid and mineralocorticoid receptors seems very sensible. As Perseverance stated, low amounts affect MRs, high amonts GRs (or something like that)

 

I know  (?) that the theory says that in humans the only active glucocorticoid is cortisol, but I've doubted that myself.

 

What I recall from exercise, and running is a good example, is that there are long lasting effects from one session. Also the 'acute' (post acute?) effect after the exercise can last a long time. It feels like a high amount of an active glucocorticoid has has been released, one that also has a long half life. And I'm writing this as I remember, the reported half lives for cortisol seem to differ. Aside from any other issues, I would describe the effect as a dampening effect, typically improving mental lucidity and dampening metabolic rate ('body temperature') This may mostly be a clonazepam thing.

 

Ok great to know Pers and I are on the same general direction.  I agree with you on all the above.  Please see this reference.  I'm still working though it myself, but it explains what you've been trying to figure out regarding stress, GABAaRs, extracellular GABA, CRH, steroids and Neurosteroids, etc.  it ties up the loose ends .  I'm going to study it for the next several days.  Knowledge is power

 

 

The section on CRH and the feedback mechanism with GABAaRs is particle interesting and amazing.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3268361/

 

The reciprocal regulation of stress hormones and GABAA receptors

Istvan Mody and Jamie Maguire

 

DM , do you think the HPA axis recovers from disregulation from steroids once the steroids are stopped?    And the fact that my cortisol levels were normal after stopping ,mellow that would indicate at least that the adrenals and presumably pituitary were working ok .

 

I feel that my HPA axis is now disregulated from the benzos , I do find now that I am on klonopin again that it actually seems to effect CRH more . I get more early morning cortisol surges than I did with the Valium .

I actually brought up with my doctor about the previous steroid use effecting my WD from benzos , and he was clueless , he just said , they are completely different drugs ....

 

I'm glad you're  doing this research . I hope perhaps you'll be able to provide some kind of educational paper on your findings that might help educate some of the medical community , that would be really great .

 

Free , there's a book I don't know if you'd be interested , written by a doctor who had a lot of success helping people deal with back pain , the book is called "The Mindbody prescription " Healing the Body , healing the pain. By John E. Sarno. I don't knwo your situation, but I wanted to mention it.

 

Miyu

 

Hi MiYu, my first thought I had when you mentioned you were on 60mg HC a day was amazement when you said your serum (.? Or was it saliva?) cortisol levels were normal once you were off it.  It took me several months to get off of the 30 I was on.  If your morning cortisol was normal, you did indeed recover.  It's amazing and you have a very resilient HPA.  How long did it take you to taper the HC?   

 

So the HPA does recover from steroid use, but I have heard anecdotal evidence of people having a much harder time getting off of it due to ACTH suppression, at doses as low as 30 mg, which is a tragedy.  I have not bothered to do the clinical research on this, but I know of one endocrinologist who wanted me off the stuff 3 months after I started.  He was probably right, but I was too cautious about crashing again , and ended up on it for 2.5 years.  After all that my morning ACTH is normal now. Depending on how I sleep, the cortisol levels are still unstable, but resilient. So some of us are very fortunate and we recover.  We are indeed lucky.  Steroid use can cause damage to the beta insulin producing cells in the pancreas and can cause adult diabetes.  As you know, there are many other negative side effects, mostly dose dependent.

 

I know that you are aware of steroid effects on bone turnover. It disrupts both osteoblastogenesis and osteoclastogenisis, i.e. Bone buliding and bone terardown.  So remodeling is disrupted while on the steroid.  Once you get off, these things return to normal.  I assume you have had a DEXA bone scan to establish a baseline bone density in your femur and lower spine, especially given you are small framed, as you mentioned in a precious post.  I assume you are on Ca, vit D, magnesium, and boron and have a good intake of dairy.

 

I also want to post another recent 2012 study on the effects of chronic and acute CRH elevations on he hippocampus.  The hippocampus is an area I researched in the context of an exercise module.  It's affected by benzodiazaphines, but exercise can be therapeutic, because it's highly plastic.

 

 

If you are interested, here the paper on CRH and it's relationship to stress and hippocampal neurogenesis

 

https://www.frontiersin.org/articles/10.3389/fncel.2012.00013/full

 

Regarding the research, I hope to collect all the modules (ADDENDUMs)when it's done.  They are  quite long, and I do post small portions to this thread as I move through the research.  I'm currently investigating alcohol and Neurosteroids, the link I just posted yesterday on the reciprocal stress GABAaR relstionship, and also tonic inhibition and  extrasynaptic GABAaRs and brain neurocircuitry, which is a huge area.

 

Sorry DM , I missed your response .....

Let's see, I was on the steroids 9 months . I think I was on 40-60 for 5 months , Dan a couple of times I took like, 120 Mgs! This was twice when I went to ER . Who knows what was really happening , I don't know. I could NEVER get the dosing right . I was given methylprednesolone .... To see if it work "better". Two weeks on that at equivalent of 80 mgs HC . Started getting cushings , not surprise there ....went back to hC , I just couldn't cut lower than 60 mgs fro a couple of months , then I could , and  I started reducing rapidly . I got down to 20 mgs in about a month probably , another trip to the ER, after really bad reaction to a dose. Switched over to prednisone ....and I think I was down to 1/18th mg of that in a month.... I had bad WDs . I couldn't get off that last tiny bit . Kept trying until one day I was able to . I felt like I was dying during that last part , and I would feel so much worse after taking that tiny amount . Eventually I stopped that though.

I was pretty sick and my nervous system was very unstable .

Then had a life crisis and my body couldn't handle the stress , enter daily benzos .

 

I don't think there was ever anything wrong with my adrenals or pituitary . I was just stressed and going through perimenopause .

 

Now benzos are a nightmare for me to withdraw from so I'm sure it has something to with the steroid trauma .,

I haven't had a bone density test . I can't manage any appointments at the moment . Thoigh I did have some bloodwork done in June , most things normal except low white blood cell . It was a fasting test and my glucose level was good .

 

I'm cautious with supplements , but I do drink nut milk that is fortified .

 

One if my most disturbing symptoms with benzos is this stress intolerance . It may have to do with the steroids and HPA suppression as I can't handle any stress . Maybe my adrenals/HPA axis are not yet responsive enough to stressors having been suppressed so much .

It was puzzling how normal my cortsol was after all these steroids .....I should probably do another Saliva test.

 

Thanks for all your research DM ,

MiYu

 

Hi MiYu, I understand.  I agree with your statements.  I also know that feeling of stress intolerance.  It's such a strange feeling, almost impossible to articulate.  I started getting them several months after starting low dose benzos for sleep.  I had no clue that they were causing the problem at the time, nor that they suppress the HPA, and that they would ultimately contribute to my HPA suppression.   

[[cs...]]

Hi all, I just wanted to post an introduction to part II of corticosterone and cortisteroid effects on GABAaRs and inhibitory signaling.

 

 

 

I will post further on this topic once I'm through some of the remaining research. 

 

------------

The relationship of corticosterones and corticosteroids to GABAARs and inhibitory signaling: At first glance the research is confusing and appears conflicting.  However, as i researched further, it became clear that the clinical results were not conflicting, but the understanding of the underlying physiology was lacking at the time of the earlier citations.

 

I will get into the details in a subsequent post, but suffice it to say, the original clinical results from say 10 years ago, are only now able to be explained by a model that has recently been proposed.  The original studies were not wrong or incorrect information , but they were not controlled properly because other factors were and are involved.  Had these issues been accounted for when testing for the clinical effects of corticosteriods on neurons, the results would have been more consistent.  For example, Corticosteroids have one effect on inhibitory signaling in the ventral hippocampus, and an entirely different effect in the dorsal hippocampus......and this is due, in part, to the difference in the distribution of mebrane based GRs and MRs as opposed to intracellular nuclear receptor MR and GRs in these distinct areas of the brain.  There was also a significant challenge in the earlier studies, in that these so called membrane GRs and MRs were not really known to have existed, and this made it very difficult to account for the fast acting Nongenomic aspects of steroids on LTP and LTD in the brain.  The mMRs were the first to be proposed, followed by mGRs.    The mechanism of action is not entirely clear, but they work through Nongenomic pathways, unlike their nuclear receptor counterparts (genomic).

 

This physiological difference of the distribution of these receptors in the VH and DH , for example, has a purpose.  It allows us to acknowledge  a stressor first, consolidate it in memory(DH), and then emotionally process((VH) the event.  This is how we properly cope with stressors.  When things go wrong in these areas of the brain we run into stress coping issues, anxiety, etc....

 

The membrane receptors appear to work through changing the frequency or amplitude of inhibitory post synaptic currents, which then affect LTP or LTD through NMDARs, VGCCs(voltage gated Calcium channels) and Metabotropic group 1 glutamate receptors , and these in turn affect Synaptic LTP and LTD in a neuroplastic fashion to adapt to the stressor.  This is all done for the purpose outlined above in mind(literally in "mind" ).... to effectively acknowledge and emotionally cope with stress. 

 

When stress becomes chronic, unpredictable, repeated, and uncontrollable, things start to fall apart in this process as aberrant neuroplastic changes occur in the brain, and especially in the very plastic region of the brain called the hippocampus.

[[...]]

Thanks DM , makes me feel a bit hopeless with my benzo taper after all the steroids mess I was in and hadn't really recovered from before I got in the benzo situation .

 

Solutions ? 

 

Neuroplasticity still possible I assume , but  maybe more challenging ...

 

MiYu

[[Re...]]

Outstanding thread.  I am following this one.

 

Here's a question:  I ended up on gabapentin after my short benzo nightmare and have been taking 2 doses per day.  I have tapered down to 50mg at night and 50mg in the morning (12 hours apart).  I am now really struggling to deal with the painful physical sensations that seem to be withdrawal.  So, would dosing 3 times per day be better for me given that gabapentin's half life is only 5 to 7 hours?   

 

I didn't want to go to doses 3 times per day but that may have actually been a mistake, from what I have gleaned on this thread.  As many of you know, gabapentin's half life is 5 to 7 hours.  So, my plasma levels are spiky and my body is probably going for homeostasis when the spikes are lowest (6 hours after each dose). 

 

I never had interdose withdrawal before like this, this is the first time, really although I've had withdrawal from tapering where I've held many times but it resolved.  This last hold is just not stabilizing and seems to be getting worse incrementally every day.  If I could divide my dose into 3 doses per day, would that be better or not?  It would be smoother, no doubt and I hope give some limit to the body trying to go for homeostasis during the lowest moments of the plasma concentration.  Any thoughts?

 

-RST

[[cs...]]

Thanks DM , makes me feel a bit hopeless with my benzo taper after all the steroids mess I was in and hadn't really recovered from before I got in the benzo situation .

 

Solutions ? 

 

Neuroplasticity still possible I assume , but  maybe more challenging ...

 

MiYu

Hi MiYu, no fear and hopelessness.    I'm in the same mess, but I think the suggestions below can help based on the model I am developing.

 

 

 

First, those neuroplastic changes above are completely normal, and only become aberrant when the inputs to hippocampus neurogenesis become dysfunctional.  There are a lot of inputs into hippocampal neurogenesis, but let's focus on three of he big ones.  The first is the stress system.  This includes neuropeptides like CRH, catecholamines like noradrenaline, DA, serotonin and epinephrine , and finally corticosteroids (glucocorticoids like corticosterone and cortisol; mineralocorticoids like aldosterone) and Neurosteroids.

 

The second is the GABAergic system and GABAaRs

 

The third system is the glutamatergic system.

 

The stress system affects the GABAergic system and he GABAergic system affects the HPA stress system.

 

The stress system directly affects the GABAErgic system through several mechanisms (including direct modulation of the GABAA receptor via Neurosteroids) and the stress system directly affects the  glutamatergic system (both NMDARs and AMPARs)

 

Now all three of these systems directly affect hippocampal neurogenesis, and you can see from the above that destabilizing any one of these systems will affect the other systems and ultimately hippocampal neurogenesis , and this can cause a vicious feedback loop of worsening stress response, which feeds back into the system....etc

 

 

There are lots of other pieces to the model, some that have been touched upon earlier, and these primarily affect the action potiential dynamics, but let's focus on the neurogenesis part since we know that hydrocortisone directly affects it.

 

So what can we do with all of this information above?

First, by tapering the Benzo, believe me, you are restoring one of THE main pillars to the withdrawal and tolerance mess of dysfunctional action potential dynamics, and you are helping restore stress resiliency.

 

 

Let's focus on another area that we can change or affect.  It's the stress system, of course.  I know I've brought up moderate exercise before, and I know several people have challenges in that area, but any kind of movement and standing is helpful in the beginning.

 

The clinical studies clearly differentiate between "good" stress and "bad" stress.  Stress that produces aberrant neurogenesis in he hippocampus is

 

Chronic

Repeated over and over

Unpredictable

Uncontrollable

 

That sounds like life 

 

These are the stresses that you have to minimize.

 

In the literature, an "enriched environment " is one that fosters healthy neuroplastic changes in the hippocampus (increased dendritic length, spine density, etc)

This includes

 

-expanded learning opportunities

-increased social interaction

-more physical activity (exercising)

-larger housing

-exploring new locations (spatial “stress”)

 

 

In practical terms, we can't get a larger house, but getting out of a room and getting outside is where it's at.  For those of you with agoraphobia, the spatial expanse might be overwhelming at first, so move around the house, then gradually step outside of the house.  The hippocampus is highly plastic and will slowly adapt.

 

Learning opportunities.  I'm writing a lot.  Word searching is used extensively in all types of writing, even in a post like this.  It uses particular areas of the hippocampus that are highly plastic

 

I'm not a big group social person.  Don't isolate yourself.  This is a very negative stress.  If you have someone around who you are not self conscious around , that's ideal.  Talk to them.

 

For those that can get out of the house, navigate to a new location using GPS.  If you can hike, navigate a trail.

 

Finally, keep moving in one way or the other.  Exercise is the foundation. It's nonchronic, predictable, controllable and most certainly can be stopped at any time.

 

The objective is to increase stress resiliency through positive stress, increase learning and memory retention, and ultimately to decrease the anxiety that is present due to deficits in these areas....

 

 

To answer your question, aberrant neurogenesis in the hippocampus is reversible.  It's not damage, its adaptive change, and the hippocampus  can readily readapt to an enriched environment in a positive manner, even after being subjected to adverse chronic stress or excessive steroids.    I want to close with a wonderful clinical quote to reinforce this reversibility in an intentionally chronically stressed animal study.  These adaptive studies of recovery are numerous.  It's not damage , it's an adaptive change that's reversible.

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248634/

 

Quote

 

Indeed, after repeated stress, dendritic remodeling is reversible (Conrad et al 1999), and in species of mammals that hibernate, dendritic remodeling is a reversible process and occurs within hours of the onset of hibernation in European hamsters and ground squirrels, and it is also reversible within hours of wakening of the animals from torpor (Arendt et al 2003; Magarinos et al 2006; Popov & Bocharova 1992). Along with data on post-translational modification of cytoskeletal proteins, this implies that reorganization of the cytoskeleton is taking place rapidly and reversibly (Arendt et al 2003) and that changes in dendrite length and branching are not “damage” but a form of structural plasticity.

 

End quote

 

 

[[...]]

Let's focus on another area that we can change or affect.  It's the stress system, of course.  I know I've brought up moderate exercise before, and I know several people have challenges in that area, but any kind of movement and standing is helpful in the beginning.

 

The clinical studies clearly differentiate between "good" stress and "bad" stress.  Stress that produces aberrant neurogenesis in he hippocampus is

 

Chronic

Repeated over and over

Unpredictable

Uncontrollable

 

That sounds like life 

 

These are the stresses that you have to minimize.

 

In the literature, an "enriched environment " is one that fosters healthy neuroplastic changes in the hippocampus (increased dendritic length, spine density, etc)

This includes

 

-expanded learning opportunities

-increased social interaction

-more physical activity (exercising)

-larger housing

-exploring new locations (spatial “stress”)

 

 

In practical terms, we can't get a larger house, but getting out of a room and getting outside is where it's at.  For those of you with agoraphobia, the spatial expanse might be overwhelming at first, so move around the house, then gradually step outside of the house.  The hippocampus is highly plastic and will slowly adapt.

 

Learning opportunities.  I'm writing a lot.  Word searching is used extensively in all types of writing, even in a post like this.  It uses particular areas of the hippocampus that are highly plastic

 

I'm not a big group social person.  Don't isolate yourself.  This is a very negative stress.  If you have someone around who you are not self conscious around , that's ideal.  Talk to them.

 

For those that can get out of the house, navigate to a new location using GPS.  If you can hike, navigate a trail.

 

Finally, keep moving in one way or the other.  Exercise is the foundation. It's nonchronic, predictable, controllable and most certainly can be stopped at any time.

 

The objective is to increase stress resiliency through positive stress, increase learning and memory retention, and ultimately to decrease the anxiety that is present due to deficits in these areas....

 

*GREAT* post, dm! 

 

Larger housing?  That's an interesting one. 

 

From personal experience, I'd add regular mindfulness meditation practice to the list.

[[cs...]]

Outstanding thread.  I am following this one.

 

Here's a question:  I ended up on gabapentin after my short benzo nightmare and have been taking 2 doses per day.  I have tapered down to 50mg at night and 50mg in the morning (12 hours apart).  I am now really struggling to deal with the painful physical sensations that seem to be withdrawal.  So, would dosing 3 times per day be better for me given that gabapentin's half life is only 5 to 7 hours?   

 

I didn't want to go to doses 3 times per day but that may have actually been a mistake, from what I have gleaned on this thread.  As many of you know, gabapentin's half life is 5 to 7 hours.  So, my plasma levels are spiky and my body is probably going for homeostasis when the spikes are lowest (6 hours after each dose). 

 

I never had interdose withdrawal before like this, this is the first time, really although I've had withdrawal from tapering where I've held many times but it resolved.  This last hold is just not stabilizing and seems to be getting worse incrementally every day.  If I could divide my dose into 3 doses per day, would that be better or not?  It would be smoother, no doubt and I hope give some limit to the body trying to go for homeostasis during the lowest moments of the plasma concentration.  Any thoughts?

 

-RST

 

Hi RST,

Congrats on being benzodiazaphine free.

 

are the physical symptoms nerve pain, i.e. Burning or tingling , and if so where?

 

I just want to determine if it is indeed hyperexcitability of the glutamatergic system.

 

 

I've received a lot of questions on gabapentin, and I have not had the time to really research it in depth like benzodiazaphines.

I don't know much about its pharmacokinetics either.

 

My main concern is that if you spread out the 100 in 3 doses you might not be hitting a serum level that has much efficacy for your particular symptoms, tolerance,  and withdrawals from the drug (i.e., you might feel uncomfortable for most of the day)

 

I don't know if gabapentin can cause the same type of neuro kindling that we see with the short acting benzodiazaphines because as you know, gabapentin is primarily acting on the voltage gated channels.

 

Assuming no neuro kindling, I can still certainly see how it could destabilize the action potential dynamics to a point where the body overcorrects and hyperexcites to counteract the dampening that it's been under while on the drug, as you withdraw...... but voltage gated channels are physiologically so much different than the ionotropics. 

 

 

[[cs...]]

Let's focus on another area that we can change or affect.  It's the stress system, of course.  I know I've brought up moderate exercise before, and I know several people have challenges in that area, but any kind of movement and standing is helpful in the beginning.

 

The clinical studies clearly differentiate between "good" stress and "bad" stress.  Stress that produces aberrant neurogenesis in he hippocampus is

 

Chronic

Repeated over and over

Unpredictable

Uncontrollable

 

That sounds like life 

 

These are the stresses that you have to minimize.

 

In the literature, an "enriched environment " is one that fosters healthy neuroplastic changes in the hippocampus (increased dendritic length, spine density, etc)

This includes

 

-expanded learning opportunities

-increased social interaction

-more physical activity (exercising)

-larger housing

-exploring new locations (spatial “stress”)

 

 

In practical terms, we can't get a larger house, but getting out of a room and getting outside is where it's at.  For those of you with agoraphobia, the spatial expanse might be overwhelming at first, so move around the house, then gradually step outside of the house.  The hippocampus is highly plastic and will slowly adapt.

 

Learning opportunities.  I'm writing a lot.  Word searching is used extensively in all types of writing, even in a post like this.  It uses particular areas of the hippocampus that are highly plastic

 

I'm not a big group social person.  Don't isolate yourself.  This is a very negative stress.  If you have someone around who you are not self conscious around , that's ideal.  Talk to them.

 

For those that can get out of the house, navigate to a new location using GPS.  If you can hike, navigate a trail.

 

Finally, keep moving in one way or the other.  Exercise is the foundation. It's nonchronic, predictable, controllable and most certainly can be stopped at any time.

 

The objective is to increase stress resiliency through positive stress, increase learning and memory retention, and ultimately to decrease the anxiety that is present due to deficits in these areas....

 

*GREAT* post, dm! 

 

Larger housing?  That's an interesting one. 

 

From personal experience, I'd add regular mindfulness meditation practice to the list.

 

on the meditation.  Spirituality is so important.,,,,,

[[Re...]]

Outstanding thread.  I am following this one.

 

Here's a question:  I ended up on gabapentin after my short benzo nightmare and have been taking 2 doses per day.  I have tapered down to 50mg at night and 50mg in the morning (12 hours apart).  I am now really struggling to deal with the painful physical sensations that seem to be withdrawal.  So, would dosing 3 times per day be better for me given that gabapentin's half life is only 5 to 7 hours?   

 

I didn't want to go to doses 3 times per day but that may have actually been a mistake, from what I have gleaned on this thread.  As many of you know, gabapentin's half life is 5 to 7 hours.  So, my plasma levels are spiky and my body is probably going for homeostasis when the spikes are lowest (6 hours after each dose). 

 

I never had interdose withdrawal before like this, this is the first time, really although I've had withdrawal from tapering where I've held many times but it resolved.  This last hold is just not stabilizing and seems to be getting worse incrementally every day.  If I could divide my dose into 3 doses per day, would that be better or not?  It would be smoother, no doubt and I hope give some limit to the body trying to go for homeostasis during the lowest moments of the plasma concentration.  Any thoughts?

 

-RST

 

Hi RST,

Congrats on being benzodiazaphine free.

 

are the physical symptoms nerve pain, i.e. Burning or tingling , and if so where?

 

I just want to determine if it is indeed hyperexcitability of the glutamatergic system.

 

 

I've received a lot of questions on gabapentin, and I have not had the time to really research it in depth like benzodiazaphines.

I don't know much about its pharmacokinetics either.

 

My main concern is that if you spread out the 100 in 3 doses you might not be hitting a serum level that has much efficacy for your particular symptoms, tolerance,  and withdrawals from the drug (i.e., you might feel uncomfortable for most of the day)

 

I don't know if gabapentin can cause the same type of neuro kindling that we see with the short acting benzodiazaphines because as you know, gabapentin is primarily acting on the voltage gated channels.

 

Assuming no neuro kindling, I can still certainly see how it could destabilize the action potential dynamics to a point where the body overcorrects and hyperexcites to counteract the dampening that it's been under while on the drug, as you withdraw...... but voltage gated channels are physiologically so much different than the ionotropics.

 

The physical sensations are primarily nerve pain, although I have muscle spasming, muscle clenching and other symptoms.  But the most uncomfortable physical sensation by far is the burning.  It manifests primarily on my chest, legs and arms.  On my arms, it is most noticeable  half-way down the bicep to the mid length of my forearm.  On my legs it is primarily my lower leg area and my feet on both the top and the bottom.  Many times I've used a cold gell pack just to try to send a different 'message' to my CNS about what is really happening; i.e.  I'm not actually on fire.

 

I don't want to updose, but if I need to updose and go to three doses per day I would consider that in an effort to smooth out my plasma levels.  As a test, I did take an additional 10 mg halfway between each of my regular doses today and it gave me some limited relief from the burning.  So, today I've taken 120mg, whereas I normally take 100mg as 50mg BID. 

 

Like many, I have no medical help where I live and as many doctors as I've tried to see, few understand the complexities of these drugs for those of us who are so sensitive to their effects.  Honestly, I thought once I got down to 50mg BID I was getting close to being able to drop it alltogether...... go figure.