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

[[Re...]]

 

 

Yikes !!!, that is some heavy stuff. I will need to read it over.

 

Initially i thought you were referring to TRPs or transient receptor potential channels, which interestingly enough are heavily associated with neuropathic pain (and i mentioned them a bit during the NO/ONOO- discussion0.  However, TARPs are a totally different thing.

Here’s a bit on TRPs which are not TARPs.  The research in this area shows some promise for neuropathic pain, and there are lots of articles on it (full citations)

 

 

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

 

Yes Trp's vs TARP's.  Gaaaaakkkkkk.  No that's not a gene sequence, merely the sound I make these days due to brain pain thinking about all this.

 

I remember the great links and your work recently on the NO/ONOO- cycle.  Very helpful,.  I'm reading now about the role inflammation can have in all this.

 

-RST

 

-

[[li...]]

A bit of a repetiton of an earlier post ...

 

I get the feeling that the solution would have to be to get the poison out of the body ...

 

Clonazepam acts on the hypothalamus ... also thalamus, spinal cord, motor circuits etc. GCPRs, circuits/connectivity etc.

I'm really not fine ! I've seen the results of that bloodwork, and I know about the changes of/in my body.

 

Aside from the the CNS, my hormones and general state of my body including morphology is really messed up. Just focusing on the hypothalamus for a moment, since it's crucial for all those hormones ... why, for god's sake, why, why would that be 'fine' again after I got the drug out of the body ?

 

And again, in my case it's not 'you're fine, it's just the benzo'. Tapering in time while I'm still fine, gradually, getting proper medical treatment in time would have avoided problems ... I just get the feeling I have to tear the drug of the receptors .. sorry to be so blunt.

 

It´s important to ´see´ things ...just like a GP ´sees´ things ... Now I´m seeing some things I didn´t see a couple of years ago. Young men ... I certainly didn´t forsee the effects of aging.You don´t die easily while on this drug, quite possibly not even off this drug  (not so sure actually). While on this drug (continuing the course) my health would be even more devastated. I´d only wish it would kill me. Unfortunately not (likely), but there are things much worse. Someone made a comment about my resilient physiology ... I have the opposite. I just don´t tend to get in acute life threatening situations easily. But those homeostatic principles can keep you alive in most of the worst circumstances. A bit like you survive, but your body doesn´t. Sorry to be blunt. It´s a bit as if I had been forced to stay on K as part of forced treatment by a psychiatrist ... except that a psychiatrist would never have been so cruel.

 

And aside from anything else, it seems that the K is carrying the burden of the general physiological strain. It gives me ´energy´ to get throught he day. But enough about that.

[[Re...]]

A bit of a repetiton of an earlier post ...

 

I get the feeling that the solution would have to be to get the poison out of the body ...

 

Clonazepam acts on the hypothalamus ... also thalamus, spinal cord, motor circuits etc. GCPRs, circuits/connectivity etc.

I'm really not fine ! I've seen the results of that bloodwork, and I know about the changes of/in my body.

 

Aside from the the CNS, my hormones and general state of my body including morphology is really messed up. Just focusing on the hypothalamus for a moment, since it's crucial for all those hormones ... why, for god's sake, why, why would that be 'fine' again after I got the drug out of the body ?

 

And again, in my case it's not 'you're fine, it's just the benzo'. Tapering in time while I'm still fine, gradually, getting proper medical treatment in time would have avoided problems ... I just get the feeling I have to tear the drug of the receptors .. sorry to be so blunt.

 

You've been getting beat down in withdrawal for a long time.  I agree with you that the affect is to have negative  affects on our overall health.  After 18 months of this, I'm starting to see my liver panel creep up.  Everything else looks very good on my blood work.  But is it any surprise the liver is beginning to show signs of stress???  I don't think so.

 

What to do.  We know that 'normally', when a person stops benzodiazepines there is a concurrent increase in AMPA current amplitude.  In some of the studies, the increase in Glu1 receptors at the receptor membrane and decline in Glu2 therein coincides with a chronic increase in the amplitude of up to 50%.  In people who experience little or no withdrawal, there appears to be a compensatory decline in NMDA receptor current amplitude that offsets the increase in AMPA receptor sensitivity.  People like us aren't getting part two of this process, regardless of what else is happening in the rest of the neural circuits.

 

Pulling off the Klonopin - I don't know if that is going to be manageable.  Is it not going to result in further increases in AMPA current that will not be offset by NMDA downregulation?  Your dilema, and my dilema, and all of us who aren't 'healing' are in this boat, I think.  I honestly feel this is the key.  Forgetting all the complicated interactions and pieces, basically  I postulate that those who have been on benzos for years but have no withdrawal after ceasing have GABA receptors that may be just as downregulated as us.  I think for them, however, it is the compensatory NMDA downregulation that buffers post-benzo AMPA upregulation; homeostasis in glutamatergic system that retains the E/I balance.  Why our NMDA receptors won't downregulate to compensate is a phenomenon that is most interesting to me now.

 

When I look at my life and the emotional and physical trauma I have experienced, coupled with exposure to many other different things that can negatively influence the CNS, I'm not at all surprised that I am in this situation now.

 

You are obviously tremendously strong, Liberty.  All the best to you. 

 

-RST

 

 

[[cs...]]

DM123

You seem to have a good understanding about all this stuff which I appreciate. I am so happy the lysine helped. I have read not to take anything that works on gaba receptors because this prevents your own GABA receptors to heal or something like that. I don’t really understand all if it. I don’t want to do anything that prevents healing but my thought has always been to try stuff and see how my body reacts. Many things I have not reacted well to but lysine seems to be a good one. I found this article and am not sure what it is trying to say. Would it means lysine is not a good idea in withdrawal?

 

https://www.ncbi.nlm.nih.gov/m/pubmed/8587651/

 

Yes, if one were to go by that article above alone, it would not be a good idea.  It would appear that lysine is modulating the GABAaR.  However, i have found many of these “petri” dish style neuron studies to be outdated in terms of explaining PWS, tolerance, etc. because they do not consider the circuit level, nor the homeostatic plasticity responses that occur in real life biological entities.

 

I’m sure there a tons of other lysine articles like this. 2 were directly linked on pubmed

 

https://www.ncbi.nlm.nih.gov/m/pubmed/2560434/?i=2&from=/8587651/related

 

https://www.ncbi.nlm.nih.gov/m/pubmed/1904823/?i=3&from=/8587651/related

 

These studies are very old and i was unable to pull up the full citation to read what were the methods implored in the lab to arrive at these conclusions.  If they were done with live rats or something, there might be some merit to the findings.  If they were done with cultured isolated brain slices, its less reliable.

 

It does appear to affect the Benzodiazaphine binding site on the GABAaR, so it might be potentiating the receptor.

Here is the quote:

“The above results suggest that L-lysine and pentobarbital acted at the same site of the GABA/benzodiazepine receptor complex which was different from the GABA binding site.”

 

Thank you for your input. It seem anything that May help is  a no go.

 

Hi Jen, there are some adjunctive medications that do not affect the GABAaR, but as discussed earlier, these do have their own side effects and risks despite not afffecting the GABAaR.

It would be best to talk to your doctor if you are thinking of using one of these meds and then post to the appropriate thread topic if you need more information on whether or not to use one of these meds.

 

I would only resort to these meds if the withdrawal symptoms during the taper wind out of control and the symptoms are unbearable.  That is just my opinion.

 

[[cs...]]

I suppose there is no specific theory about getting the circuits 'back in order' ? I feel like it's  a dumb qustion.

 

I don’t think it is a bad question

 

1.Try to always maintain steady state

2.Try to use a slow onset Benzodiazaphine to taper.  That heterosynaptic plasticity will be less strained with a slow onset benzo, and this means less GPCR dysregulation.

3.Play defensive when necessary, ie do a symptom based taper.  Do not be on the offensive (tapering and cutting) when you are sick from withdrawal or tolerance. The benzo is stronger but not smarter.

4.Time is your greatest ally for healing.  It’s a marathon and not a sprint and circuits heal when given the right envionroment and enough time.

5.Keep moving as much as you can. (Thinking, creating, and walking are the best recovery tools for neural circuits)

[[li...]]

Well, in one way the circuits are in order:

 

Exercise causes a strong reaction by the HPA axis. It appears to be somewhat intact as a principle, although the actual hormone levels are not ´all right´. From a long, long time ago I recall a weaker HPA axis reaction to exercise at a lower dose, but possibly accompanied by a higher treshold for falling asleep and a subjective slowing down of time.

 

As an interpretation, adding a bit of diazepam can disrupt the circuits or so it would appear.

 

But prior to the lorazepam, the effects of exercise depended on the dose.

[[Fr...]]

dm 123 I try to limit my questions to you , but as I recall you did taper on Librium? I just read another post that seemed to indicate Librium worked really well for them. Do you think it is an underrated option

 

Hi Matt,

 

I am in the last portions of the taper. Yes, i crossed over from assorted z drugs (ambien,lunesta) and lorazepam.  I could not have tapered from them directly.

 

I do think it is a very underrated option, as i was just going to post a piece on this thread about the very same, but could not get to it due to lack of time.

 

My thoughts on the issue are this:

There are many people on BB who get ill from valium itself.  By “many” we should take it into the proper context.  Most people on BB are in pain and not doing well. So the population here is biased to the negative. So if we see 50% of the people here that get sick from valium, it is not representative of the real population in the outside world.

 

If we look at Ashton’s clinical studies that’s more representative of the effectiveness of valium as a crossover benzo for tapering. Here stats are very good (positive). I don’t have the time now to pull the stats but i am guessing around 90% success rate tapering off. Now that’s not to say that there are no relapses post taper. She might not have followed up.  But the point is, there’s probably perhaps 10% of the people who crossover to Valium that get sick from valium itself. 

 

So this is a very real lissue and from what I’ve read on this forum it can be very very disabiling.

 

They typically get sick when they take the drug, and sometimes moving to three doses a day does not help at all. So it’s more than just steady state.

 

I thought about it, and perhaps it’s due to valiums fast onset of action.  It has a very fast onset of action. I’ve only taken it a few times, but it seems much more “powerful” than Librium in this respect. It’s like a sledghammer, to the librium’s hammer, if i were to describe it. 

 

So librium has a very slow onset of action, and i would be curious to find out what would happen if some of the valium 3 times a day suffererers were to move to librium with 3 dosing a day.

 

So i do think it is an underrated option in this respect.

 

I hope this helps.

 

Best wishes.

Just wanted to add, that the taper has not been easy.  Anything but.    I don’t know if there is any easy way out of this, but perhaps librium might be an option for some who are doing worse on valium.

 

 

P.S. Sorry for typos if any, as i typed it very quick and did not have a chance to spellcheck.

 

I am doing my crossover to Valium now and I am finding the more V I take the more stimulated I become. It has made my sleep worse it makes me feel like stimulated. Is this what you mean it making some sick? I wonder if I will get used to this feeling. I don’t want to have this stimulation everyday as I try to taper.

[[li...]]

Jlavogt,

 

Perhaps this is due tio an interaction with the K ? I recall a similar thing while being on both for a short while.

 

dm123,

 

Possibly I did overlook an earlier post. Woudl Librium have a longer 'duartion of action' than diazepam, or would it be similar ?

My recollection of diazepam is that the onset is not that fast. I'm not sure, 30-60 minutes ?

[[Fr...]]

Jlavogt,

 

Perhaps this is due tio an interaction with the K ? I recall a similar thing while being on both for a short while.

 

dm123,

 

Possibly I did overlook an earleir post. Woudl Librium have a longer 'duartion of action' than diazepam, or would it be similar ?

My recollection of diazepam is that the onset is not that fast. I'm not sure, 30-60 minutes ?

 

Thank you. I am hoping I get used to it. That 1mg was a test to see how I would feel. I am onto my full nighttime dose of v in the crossover and still taking k for morning and afternoon. V seems to hit me very hard and fast almost like euphoric within 20 mins but then another twenty mins later I have obsessive thoughts and seem agitated almost stimulated but drugged at the same time. It is not a good feeling. Also I can not fall asleep until about 5 hours after taking it at night until the v wears off.

 

DM123 wondering your opinion on these symptoms. Rapid onset hitting me hard? Not sure if I should hold out and try and get used to it. I feel rather sick, poisoned. But the side effects are still better than tolerance on K.

[[...]]

Dm123- why can we dose less often as the dose gets lower? It seems the med would wear off sooner with a lower dose and more frequent dosing might be needed instead of less frequent. Yet I do see many buddies dosing less frequently as they go lower. Does anyone dose MORE frequently as they go lower? Maybe with shorter acting stuff? And what dose of Librium do you think once a day dosing is enough- I know it varies by person, but ballpark? Thanks!

[[cs...]]

dm 123 I try to limit my questions to you , but as I recall you did taper on Librium? I just read another post that seemed to indicate Librium worked really well for them. Do you think it is an underrated option

 

Hi Matt,

 

I am in the last portions of the taper. Yes, i crossed over from assorted z drugs (ambien,lunesta) and lorazepam.  I could not have tapered from them directly.

 

I do think it is a very underrated option, as i was just going to post a piece on this thread about the very same, but could not get to it due to lack of time.

 

My thoughts on the issue are this:

There are many people on BB who get ill from valium itself.  By “many” we should take it into the proper context.  Most people on BB are in pain and not doing well. So the population here is biased to the negative. So if we see 50% of the people here that get sick from valium, it is not representative of the real population in the outside world.

 

If we look at Ashton’s clinical studies that’s more representative of the effectiveness of valium as a crossover benzo for tapering. Here stats are very good (positive). I don’t have the time now to pull the stats but i am guessing around 90% success rate tapering off. Now that’s not to say that there are no relapses post taper. She might not have followed up.  But the point is, there’s probably perhaps 10% of the people who crossover to Valium that get sick from valium itself. 

 

So this is a very real lissue and from what I’ve read on this forum it can be very very disabiling.

 

They typically get sick when they take the drug, and sometimes moving to three doses a day does not help at all. So it’s more than just steady state.

 

I thought about it, and perhaps it’s due to valiums fast onset of action.  It has a very fast onset of action. I’ve only taken it a few times, but it seems much more “powerful” than Librium in this respect. It’s like a sledghammer, to the librium’s hammer, if i were to describe it. 

 

So librium has a very slow onset of action, and i would be curious to find out what would happen if some of the valium 3 times a day suffererers were to move to librium with 3 dosing a day.

 

So i do think it is an underrated option in this respect.

 

I hope this helps.

 

Best wishes.

Just wanted to add, that the taper has not been easy.  Anything but.    I don’t know if there is any easy way out of this, but perhaps librium might be an option for some who are doing worse on valium.

 

 

P.S. Sorry for typos if any, as i typed it very quick and did not have a chance to spellcheck.

 

I am doing my crossover to Valium now and I am finding the more V I take the more stimulated I become. It has made my sleep worse it makes me feel like stimulated. Is this what you mean it making some sick? I wonder if I will get used to this feeling. I don’t want to have this stimulation everyday as I try to taper.

 

Hi Jen,

 

I am not sure but there was a great thread started by Maryxxxxx (not sure her full username on BB) about 2-3 months ago on this issue. THere are a few people here on BB that do not react very well to valium.  I have never had the issue but have only used valium twice and that was a long time back before the taper.  I have never had this experience on librium.  At higher doses of librium i felt tired but i think that is normal as the nervous system acclimates.    I do not feel any librium at the low dose that i am on now, and haven’t felt it for quite some time.

 

The only difference that i can think of is the fast onset of action of valium.  It requires more immediate accomodation from the nervous system and more adjustment of those neurotransmitters that i mentioned in a post above (heterosynaptic plasticity).  In terms of long term adaptation, its probably very similar to librium, whereby there is homeostatic plasticity that does occur over days and weeks.  This happens with all benzos.  I think one of the reasons at least for me, that it takes so long to recover from each cut (approx 30-35 days) is because the homeostatic plasticity is a very slow adaptive response and the unwind of these changes is also quite slow. So even though the majority of the drug (excluding secondary metabolites for a moment here) is washed out after 10 days, the nervous system has to reacclimate to this new steady state, and that takes some time.

 

In part 3 i will present more detail in my own words of these various forms of plasticity, which account in part for why slow symptom based tapers, in general, work better than fast tapers.  There’s also the neurogeneisis aspect , but that’s a different topic altogether, and that’s part of the model as well. That aspect most likely comes into play to a much greater degree with PWS.

 

 

[[cs...]]

Jlavogt,

 

Perhaps this is due tio an interaction with the K ? I recall a similar thing while being on both for a short while.

 

dm123,

 

Possibly I did overlook an earlier post. Woudl Librium have a longer 'duartion of action' than diazepam, or would it be similar ?

My recollection of diazepam is that the onset is not that fast. I'm not sure, 30-60 minutes ?

 

Hi liberty, i am not sure on this one, but i think i posted a link earlier on the onset of action and duration of action.  The pharmacokinetics seem to be different across different tables, and i have trouble finding consistency. One thing we are sure of is that the onset of action is much slower with librium than with valium and i can attest to that first hand.  I really don’t know about the duration of action, which as you know, is not necessarily directly correlated to half lives (ie, even though half lives are similar, does not mean duration of action is necessarily the same).

 

So onset is faster with valium, but i don’t know about duration of action differences between the two. I think the fast onset of valium might be one of many things that could be causing issues with poor valium experiences.(probably many other things involved as well).

[[cs...]]

Jlavogt,

 

Perhaps this is due tio an interaction with the K ? I recall a similar thing while being on both for a short while.

 

dm123,

 

Possibly I did overlook an earleir post. Woudl Librium have a longer 'duartion of action' than diazepam, or would it be similar ?

My recollection of diazepam is that the onset is not that fast. I'm not sure, 30-60 minutes ?

 

Thank you. I am hoping I get used to it. That 1mg was a test to see how I would feel. I am onto my full nighttime dose of v in the crossover and still taking k for morning and afternoon. V seems to hit me very hard and fast almost like euphoric within 20 mins but then another twenty mins later I have obsessive thoughts and seem agitated almost stimulated but drugged at the same time. It is not a good feeling. Also I can not fall asleep until about 5 hours after taking it at night until the v wears off.

 

DM123 wondering your opinion on these symptoms. Rapid onset hitting me hard? Not sure if I should hold out and try and get used to it. I feel rather sick, poisoned. But the side effects are still better than tolerance on K.

 

Hi Jen, sorry you are experiencing this. Yes valium hits hard. I know from the few times i have used it. That is why i thought librium might have been better. I will send you a PM. 

 

Also, i did not know you were still on clonazepam.  As liberty mentioned we don’t know how these various benzos interact precisely and there might be some sort of crosstalk on the receptor between the two benzos going on there. The subunit bindings are unique for each benzo.

 

I will get to my PMs in a few hours.

 

 

[[cs...]]

Dm123- why can we dose less often as the dose gets lower? It seems the med would wear off sooner with a lower dose and more frequent dosing might be needed instead of less frequent. Yet I do see many buddies dosing less frequently as they go lower. Does anyone dose MORE frequently as they go lower? Maybe with shorter acting stuff? And what dose of Librium do you think once a day dosing is enough- I know it varies by person, but ballpark? Thanks!

 

Hi libr

 

According to the model, if one does a symptom based taper the nervous system does recover slowly as one continues through the taper.  The resiliency and stability of the nervous system improves with time.  That is the first reason.

 

The second reason is that at lower doses, there’s less accomodation needed and there’s a natural tendency for the homeostatic processes to be less “stretched” , ie there’s less accomodation needed at the lower dosages.  It is also true that as the dose goes down, that heterosynaptic response (GPCRs) is no longer required to such a great extent.  Slow onset of action plus lower doses are much more easy on the neuroadaptive processes.  We slowly move towards baseline homeostasis where lower accomodation is needed with each successive cut.

 

As resiliency of the nervous system improves, it is much more capable in handling small fluctuations in the serum levels of the Benzodiazaphine. 

 

In kindling that is the worst scenario and requires the greatest degree of  steady state, then in tolerance , that’s the next level up, and finally once out of tolerance as you taper there’s less of a need to maintain perfect steady state as the nervous system becomes more resilient.

 

Also keep in mind that with valium and librium, 24 hours is not huge relative to the average half life.

 

(A bit off topic:

Another reason why people might have issues when crossing over to valium is that they might be fast metabolizers of the this particular benzo, and i know of a few on BB that are. In this case, it is difficult to maintain steady state of the drug.)

 

I went to one time dosing at around 20 mg of librium , but i had started much higher at around 70.

 

I am much lower than 20 right now, and have been single dosing since i hit 20.

 

I tapered the afternoon and morning doses first, then phased out afternoon dose, then morning dose, then was left with night dose.

 

 

please note EDITED typos.

 

[[Su...]]

dm 123 I try to limit my questions to you , but as I recall you did taper on Librium? I just read another post that seemed to indicate Librium worked really well for them. Do you think it is an underrated option

 

Hi Matt,

 

I am in the last portions of the taper. Yes, i crossed over from assorted z drugs (ambien,lunesta) and lorazepam.  I could not have tapered from them directly.

 

I do think it is a very underrated option, as i was just going to post a piece on this thread about the very same, but could not get to it due to lack of time.

 

My thoughts on the issue are this:

There are many people on BB who get ill from valium itself.  By “many” we should take it into the proper context.  Most people on BB are in pain and not doing well. So the population here is biased to the negative. So if we see 50% of the people here that get sick from valium, it is not representative of the real population in the outside world.

 

If we look at Ashton’s clinical studies that’s more representative of the effectiveness of valium as a crossover benzo for tapering. Here stats are very good (positive). I don’t have the time now to pull the stats but i am guessing around 90% success rate tapering off. Now that’s not to say that there are no relapses post taper. She might not have followed up.  But the point is, there’s probably perhaps 10% of the people who crossover to Valium that get sick from valium itself. 

 

So this is a very real lissue and from what I’ve read on this forum it can be very very disabiling.

 

They typically get sick when they take the drug, and sometimes moving to three doses a day does not help at all. So it’s more than just steady state.

 

I thought about it, and perhaps it’s due to valiums fast onset of action.  It has a very fast onset of action. I’ve only taken it a few times, but it seems much more “powerful” than Librium in this respect. It’s like a sledghammer, to the librium’s hammer, if i were to describe it. 

 

So librium has a very slow onset of action, and i would be curious to find out what would happen if some of the valium 3 times a day suffererers were to move to librium with 3 dosing a day.

 

So i do think it is an underrated option in this respect.

 

I hope this helps.

 

Best wishes.

Just wanted to add, that the taper has not been easy.  Anything but.    I don’t know if there is any easy way out of this, but perhaps librium might be an option for some who are doing worse on valium.

 

 

P.S. Sorry for typos if any, as i typed it very quick and did not have a chance to spellcheck.

 

I am doing my crossover to Valium now and I am finding the more V I take the more stimulated I become. It has made my sleep worse it makes me feel like stimulated. Is this what you mean it making some sick? I wonder if I will get used to this feeling. I don’t want to have this stimulation everyday as I try to taper.

 

Hi Jen,

 

I am not sure but there was a great thread started by Maryxxxxx (not sure her full username on BB) about 2-3 months ago on this issue. THere are a few people here on BB that do not react very well to valium.  I have never had the issue but have only used valium twice and that was a long time back before the taper.  I have never had this experience on librium.  At higher doses of librium i felt tired but i think that is normal as the nervous system acclimates.    I do not feel any librium at the low dose that i am on now, and haven’t felt it for quite some time.

 

The only difference that i can think of is the fast onset of action of valium.  It requires more immediate accomodation from the nervous system and more adjustment of those neurotransmitters that i mentioned in a post above (heterosynaptic plasticity).  In terms of long term adaptation, its probably very similar to librium, whereby there is homeostatic plasticity that does occur over days and weeks.  This happens with all benzos.  I think one of the reasons at least for me, that it takes so long to recover from each cut (approx 30-35 days) is because the homeostatic plasticity is a very slow adaptive response and the unwind of these changes is also quite slow. So even though the majority of the drug (excluding secondary metabolites for a moment here) is washed out after 10 days, the nervous system has to reacclimate to this new steady state, and that takes some time.

 

In part 3 i will present more detail in my own words of these various forms of plasticity, which account in part for why slow symptom based tapers, in general, work better than fast tapers.  There’s also the neurogeneisis aspect , but that’s a different topic altogether, and that’s part of the model as well. That aspect most likely comes into play to a much greater degree with PWS.

Hi Jen,

It's Mary5588 that started the thread on valium... she's having a tough time on it as well.

SS

[[Fr...]]

Thank you DM123

 

So it seems between me being an ultra rapid metabolizer of v with the fast onset of v plus me still being on partial clonazepam and being kindled with z drugs along with single dosing in the past I am a disaster. I feel much like the short acting roller coaster of xanex that I used to be on. Trying to find the safest way through this with my nervous system. I am grateful for your information and will look forward to your PM.

[[Fr...]]

dm 123 I try to limit my questions to you , but as I recall you did taper on Librium? I just read another post that seemed to indicate Librium worked really well for them. Do you think it is an underrated option

 

Hi Matt,

 

I am in the last portions of the taper. Yes, i crossed over from assorted z drugs (ambien,lunesta) and lorazepam.  I could not have tapered from them directly.

 

I do think it is a very underrated option, as i was just going to post a piece on this thread about the very same, but could not get to it due to lack of time.

 

My thoughts on the issue are this:

There are many people on BB who get ill from valium itself.  By “many” we should take it into the proper context.  Most people on BB are in pain and not doing well. So the population here is biased to the negative. So if we see 50% of the people here that get sick from valium, it is not representative of the real population in the outside world.

 

If we look at Ashton’s clinical studies that’s more representative of the effectiveness of valium as a crossover benzo for tapering. Here stats are very good (positive). I don’t have the time now to pull the stats but i am guessing around 90% success rate tapering off. Now that’s not to say that there are no relapses post taper. She might not have followed up.  But the point is, there’s probably perhaps 10% of the people who crossover to Valium that get sick from valium itself. 

 

So this is a very real lissue and from what I’ve read on this forum it can be very very disabiling.

 

They typically get sick when they take the drug, and sometimes moving to three doses a day does not help at all. So it’s more than just steady state.

 

I thought about it, and perhaps it’s due to valiums fast onset of action.  It has a very fast onset of action. I’ve only taken it a few times, but it seems much more “powerful” than Librium in this respect. It’s like a sledghammer, to the librium’s hammer, if i were to describe it. 

 

So librium has a very slow onset of action, and i would be curious to find out what would happen if some of the valium 3 times a day suffererers were to move to librium with 3 dosing a day.

 

So i do think it is an underrated option in this respect.

 

I hope this helps.

 

Best wishes.

Just wanted to add, that the taper has not been easy.  Anything but.    I don’t know if there is any easy way out of this, but perhaps librium might be an option for some who are doing worse on valium.

 

 

P.S. Sorry for typos if any, as i typed it very quick and did not have a chance to spellcheck.

 

I am doing my crossover to Valium now and I am finding the more V I take the more stimulated I become. It has made my sleep worse it makes me feel like stimulated. Is this what you mean it making some sick? I wonder if I will get used to this feeling. I don’t want to have this stimulation everyday as I try to taper.

 

Hi Jen,

 

I am not sure but there was a great thread started by Maryxxxxx (not sure her full username on BB) about 2-3 months ago on this issue. THere are a few people here on BB that do not react very well to valium.  I have never had the issue but have only used valium twice and that was a long time back before the taper.  I have never had this experience on librium.  At higher doses of librium i felt tired but i think that is normal as the nervous system acclimates.    I do not feel any librium at the low dose that i am on now, and haven’t felt it for quite some time.

 

The only difference that i can think of is the fast onset of action of valium.  It requires more immediate accomodation from the nervous system and more adjustment of those neurotransmitters that i mentioned in a post above (heterosynaptic plasticity).  In terms of long term adaptation, its probably very similar to librium, whereby there is homeostatic plasticity that does occur over days and weeks.  This happens with all benzos.  I think one of the reasons at least for me, that it takes so long to recover from each cut (approx 30-35 days) is because the homeostatic plasticity is a very slow adaptive response and the unwind of these changes is also quite slow. So even though the majority of the drug (excluding secondary metabolites for a moment here) is washed out after 10 days, the nervous system has to reacclimate to this new steady state, and that takes some time.

 

In part 3 i will present more detail in my own words of these various forms of plasticity, which account in part for why slow symptom based tapers, in general, work better than fast tapers.  There’s also the neurogeneisis aspect , but that’s a different topic altogether, and that’s part of the model as well. That aspect most likely comes into play to a much greater degree with PWS.

Hi Jen,

It's Mary5588 that started the thread on valium... she's having a tough time on it as well.

SS

 

Thank you I will see if I can find it.

[[cs...]]

Thank you DM123

 

So it seems between me being an ultra rapid metabolizer of v with the fast onset of v plus me still being on partial clonazepam and being kindled with z drugs along with single dosing in the past I am a disaster. I feel much like the short acting roller coaster of xanex that I used to be on. Trying to find the safest way through this with my nervous system. I am grateful for your information and will look forward to your PM.

 

Hi Jen,

I. have heard of people getting tested for the fast metabolizer aspect, but i am not sure what that test is. Perhaps someone can chime in on if there is a test and what that test is.

I know that we discussed librium and i am really interested in seeing if librium would be any different. I don’t know what Mary is or has been doing, but we can most likely find out from here directly here on BB.

 

I did not have that excitability response when i crossed over to librium and i was still on some z drugs at the initial crossover time.  But we are all so different, and one size does not fit all......

[[Fr...]]

Thank you DM123

 

So it seems between me being an ultra rapid metabolizer of v with the fast onset of v plus me still being on partial clonazepam and being kindled with z drugs along with single dosing in the past I am a disaster. I feel much like the short acting roller coaster of xanex that I used to be on. Trying to find the safest way through this with my nervous system. I am grateful for your information and will look forward to your PM.

 

 

 

Hi Jen,

I. have heard of people getting tested for the fast metabolizer aspect, but i am not sure what that test is. Perhaps someone can chime in on if there is a test and what that test is.

I know that we discussed librium and i am really interested in seeing if librium would be any different. I don’t know what Mary is or has been doing, but we can most likely find out from here directly here on BB.

 

I did not have that excitability response when i crossed over to librium and i was still on some z drugs at the initial crossover time.  But we are all so different, and one size does not fit all......

 

I did have a test. It’s called Genomind. Ultra rapid metabolizer of V.

[[cs...]]

Dm123- why can we dose less often as the dose gets lower? It seems the med would wear off sooner with a lower dose and more frequent dosing might be needed instead of less frequent. Yet I do see many buddies dosing less frequently as they go lower. Does anyone dose MORE frequently as they go lower? Maybe with shorter acting stuff? And what dose of Librium do you think once a day dosing is enough- I know it varies by person, but ballpark? Thanks!

 

Hi libr

 

According to the model, if one does a symptom based taper the nervous system does recover slowly as one continues through the taper.  The resiliency and stability of the nervous system improves with time.  That is the first reason.

 

The second reason is that at lower doses, there’s less accomodation needed and there’s a natural tendency for the homeostatic processes to be less “stretched” , ie there’s less accomodation needed at the lower dosages.  It is also true that as the dose goes down, that heterosynaptic response (GPCRs) is no longer required to such a great extent.  Slow onset of action plus lower doses are much more easy on the neuroadaptive processes.  We slowly move towards baseline homeostasis where lower accomodation is needed with each successive cut.

 

As resiliency of the nervous system improves, it is much more capable in handling small fluctuations in the serum levels of the Benzodiazaphine. 

 

In kindling that is the worst scenario and requires the greatest degree of  steady state, then in tolerance , that’s the next level up, and finally once out of tolerance as you taper there’s less of a need to maintain perfect steady state as the nervous system becomes more resilient.

 

Also keep in mind that with valium and librium, 24 hours is not huge relative to the average half life.

 

(A bit off topic:

Another reason why people might have issues when crossing over to valium is that they might be fast metabolizers of the this particular benzo, and i know of a few on BB that are. In this case, it is difficult to maintain steady state of the drug.)

 

I went to one time dosing at around 20 mg of librium , but i had started much higher at around 70.

 

I am much lower than 20 right now, and have been single dosing since i hit 20.

 

I tapered the afternoon and morning doses first, then phased out afternoon dose, then morning dose, then was left with night dose.

 

 

please note EDITED typos.

 

Hi libr,

 

I forgot to convert librium to valium for you. 20 librium is equivalent to about 8 of valium.

 

I also forgot to answer your second question. I personally don’t think a short acting Benzodiazaphine would be wise at any point, because then you are in fact going to very very low serum levels (even though you are at presumably low doses at this point) after around 12 hours.  There would be wide swings in serum levels with single dosing the short acting benzo.  Now, each of us is different and your nervous system might be at a point to tolerate a short acting Benzodiazaphine ,but it does not serve any constructive process.  Switching back and forth from different benzos is not a good idea

 

I don’t think i will ever be able to tolerate short acting benzos or z drugs again.  I don’t think i will ever recover to that extent.  It does not mean i won’t be resilient and able to handle stress, it just means that i will not be able to tolerate such a direct form of insult and stress on my nervous system.

 

I hope this helps.

[[...]]

Dm123- why can we dose less often as the dose gets lower? It seems the med would wear off sooner with a lower dose and more frequent dosing might be needed instead of less frequent. Yet I do see many buddies dosing less frequently as they go lower. Does anyone dose MORE frequently as they go lower? Maybe with shorter acting stuff? And what dose of Librium do you think once a day dosing is enough- I know it varies by person, but ballpark? Thanks!

 

Hi libr

 

According to the model, if one does a symptom based taper the nervous system does recover slowly as one continues through the taper.  The resiliency and stability of the nervous system improves with time.  That is the first reason.

 

The second reason is that at lower doses, there’s less accomodation needed and there’s a natural tendency for the homeostatic processes to be less “stretched” , ie there’s less accomodation needed at the lower dosages.  It is also true that as the dose goes down, that heterosynaptic response (GPCRs) is no longer required to such a great extent.  Slow onset of action plus lower doses are much more easy on the neuroadaptive processes.  We slowly move towards baseline homeostasis where lower accomodation is needed with each successive cut.

 

As resiliency of the nervous system improves, it is much more capable in handling small fluctuations in the serum levels of the Benzodiazaphine. 

 

In kindling that is the worst scenario and requires the greatest degree of  steady state, then in tolerance , that’s the next level up, and finally once out of tolerance as you taper there’s less of a need to maintain perfect steady state as the nervous system becomes more resilient.

 

Also keep in mind that with valium and librium, 24 hours is not huge relative to the average half life.

 

(A bit off topic:

Another reason why people might have issues when crossing over to valium is that they might be fast metabolizers of the this particular benzo, and i know of a few on BB that are. In this case, it is difficult to maintain steady state of the drug.)

 

I went to one time dosing at around 20 mg of librium , but i had started much higher at around 70.

 

I am much lower than 20 right now, and have been single dosing since i hit 20.

 

I tapered the afternoon and morning doses first, then phased out afternoon dose, then morning dose, then was left with night dose.

 

 

please note EDITED typos.

Thank you dm123. It kinda makes sense. I don't exactly know what heterosynapyic response is but I can guess- multiple types of receptors having to fix themselves?

 

How did you decide that 20mg was the right time for you to go to once daily dosing?

Are you still experiencing sxs at your current dose? You don't have to list them- just wondering if you still have them? Is it "better" overall... or hard to tell? 

 

Yes, 24 hrs is much less than the reported half life. Some buddies are big on dosing twice a day bc of duration of action being 6-12 hrs as they say, but they are all on V.  Do you think duration of action is longer for L esp since onset is later? My doc chose L for that gentler onset too. I've never taken V.

 

And out of curiousity, what model are you referring to with your posts and how did you come up w/ it? I have a science background but can't follow all your detailed info. Does any of your modeling help figure out a good taper rate? I'm struggling with how to figure out if/when I need to slow my daily taper rate...as my sxs go in waves and windows and external stress is often what sparks my waves. Almost feel like I need to get off so external stress doesn't cause waves, but don't want to tax my system too much either.

 

I know this post is all over the place- thanks for any input! Glad to have met you here!

[[cs...]]

Thank you DM123

 

So it seems between me being an ultra rapid metabolizer of v with the fast onset of v plus me still being on partial clonazepam and being kindled with z drugs along with single dosing in the past I am a disaster. I feel much like the short acting roller coaster of xanex that I used to be on. Trying to find the safest way through this with my nervous system. I am grateful for your information and will look forward to your PM.

 

 

 

Hi Jen,

I. have heard of people getting tested for the fast metabolizer aspect, but i am not sure what that test is. Perhaps someone can chime in on if there is a test and what that test is.

I know that we discussed librium and i am really interested in seeing if librium would be any different. I don’t know what Mary is or has been doing, but we can most likely find out from here directly here on BB.

 

I did not have that excitability response when i crossed over to librium and i was still on some z drugs at the initial crossover time.  But we are all so different, and one size does not fit all......

 

I did have a test. It’s called Genomind. Ultra rapid metabolizer of V.

 

Thanks, i have never heard of it but will take a look at it. Is it similar to the 23andMe genetic profiling testing?

[[cs...]]

Thank you DM123

 

So it seems between me being an ultra rapid metabolizer of v with the fast onset of v plus me still being on partial clonazepam and being kindled with z drugs along with single dosing in the past I am a disaster. I feel much like the short acting roller coaster of xanex that I used to be on. Trying to find the safest way through this with my nervous system. I am grateful for your information and will look forward to your PM.

 

Hi Jen, yes most likely a combination of those things.  I think the z drugs are the biggest instigator of issues, and i am glad that you are no longer on them. It takes a while to acclimate once you get off of those types of drugs.

[[cs...]]

Dm123- why can we dose less often as the dose gets lower? It seems the med would wear off sooner with a lower dose and more frequent dosing might be needed instead of less frequent. Yet I do see many buddies dosing less frequently as they go lower. Does anyone dose MORE frequently as they go lower? Maybe with shorter acting stuff? And what dose of Librium do you think once a day dosing is enough- I know it varies by person, but ballpark? Thanks!

 

Hi libr

 

According to the model, if one does a symptom based taper the nervous system does recover slowly as one continues through the taper.  The resiliency and stability of the nervous system improves with time.  That is the first reason.

 

The second reason is that at lower doses, there’s less accomodation needed and there’s a natural tendency for the homeostatic processes to be less “stretched” , ie there’s less accomodation needed at the lower dosages.  It is also true that as the dose goes down, that heterosynaptic response (GPCRs) is no longer required to such a great extent.  Slow onset of action plus lower doses are much more easy on the neuroadaptive processes.  We slowly move towards baseline homeostasis where lower accomodation is needed with each successive cut.

 

As resiliency of the nervous system improves, it is much more capable in handling small fluctuations in the serum levels of the Benzodiazaphine. 

 

In kindling that is the worst scenario and requires the greatest degree of  steady state, then in tolerance , that’s the next level up, and finally once out of tolerance as you taper there’s less of a need to maintain perfect steady state as the nervous system becomes more resilient.

 

Also keep in mind that with valium and librium, 24 hours is not huge relative to the average half life.

 

(A bit off topic:

Another reason why people might have issues when crossing over to valium is that they might be fast metabolizers of the this particular benzo, and i know of a few on BB that are. In this case, it is difficult to maintain steady state of the drug.)

 

I went to one time dosing at around 20 mg of librium , but i had started much higher at around 70.

 

I am much lower than 20 right now, and have been single dosing since i hit 20.

 

I tapered the afternoon and morning doses first, then phased out afternoon dose, then morning dose, then was left with night dose.

 

 

please note EDITED typos.

Thank you dm123. It kinda makes sense. I don't exactly know what heterosynapyic response is but I can guess- multiple types of receptors having to fix themselves?

 

How did you decide that 20mg was the right time for you to go to once daily dosing?

Are you still experiencing sxs at your current dose? You don't have to list them- just wondering if you still have them? Is it "better" overall... or hard to tell? 

 

Yes, 24 hrs is much less than the reported half life. Some buddies are big on dosing twice a day bc of duration of action being 6-12 hrs as they say, but they are all on V.  Do you think duration of action is longer for L esp since onset is later? My doc chose L for that gentler onset too. I've never taken V.

 

And out of curiousity, what model are you referring to with your posts and how did you come up w/ it? I have a science background but can't follow all your detailed info. Does any of your modeling help figure out a good taper rate? I'm struggling with how to figure out if/when I need to slow my daily taper rate...as my sxs go in waves and windows and external stress is often what sparks my waves. Almost feel like I need to get off so external stress doesn't cause waves, but don't want to tax my system too much either.

 

I know this post is all over the place- thanks for any input! Glad to have met you here!

 

Hi Libr,

 

Heterosynaptic response is just a fancy term for neighboring neurons that modulate other neurons presynaptically and postsynaptically

 

I have been trying to keep the quotes to a minimum here, because they can get overwhelming, but from wikipedia

 

“Heterosynaptic Plasticity (or also heterotropic modulation) is a change in synaptic strength that results from the activity of other neurons. Again, the plasticity can alter the number of vesicles or their replenishment rate or the relationship between calcium and vesicle release. Additionally, it could directly affect calcium influx. Heterosynaptic plasticity can also be postsynaptic in nature, affecting receptor sensitivity.

One example is again neurons of the sympathetic nervous system, which release noradrenaline, which, in addition, generates an inhibitory effect on presynaptic terminals of neurons of the parasympathetic nervous system.[16]”

 

What’s interesting about this type of plasticity is that it can involve what are called GPCRs, ie the neuromodulation can be done via dopamine (DA), and serotonin release from interneurons to the synapse of an adjacent neuron synapse.  I imagine other GPCRs are involved like AChRs. GPCRs are an important pillar in the model.

 

The adjacent neuron synapse is the one that is getting presumably hit by the benzos and the immediate homeostatic response would be done through this heterosynaptic plasticity (and other forms of plasticity).  A longer term plasticity called homeostatic plasticity takes place over hours, days and even weeks. Both forms of plasticity are at work trying to maintain balance inside the neuron. There are other forms of plasticity involved in homeostasis as well.

 

——-

Regarding the 20 mg it just turned out that way. And the doctor indicated i could phase out the other two (AM and afternoon) after some point of stability was achieved.  This assessment was correct.

The 20 mg was down from 25mg and was just what was left after phasing out the AM and afternoon.

 

Let’s say you start with

AM 10

Afternoon 10

Evening 10

 

You might taper down the afternoon to 7.5

Then work on the morning 7.5

Then afternoon 5

Then morning 5

Then afternoon 2.5

Then morning 2.5

Then evening 7.5

Then drop the afternoon dose

Then drop the morning dose

So now you are left with 7.5 evening and you would whittle that down with the continued slow symptom based taper.

 

Regarding symptoms, i still get hit after a cut.  It is no walk in the park.  It can be very tough.  The nausea can get bad as well.

However over time there is an improvement in all aspects of symptoms.  It is kind of like the bull stock market.  One step back, two steps forward, one step back , three forward, two backward.  Etc....  The overall trend is up. That is what you want to look at. Overall monthly trends.  You should keep a symptom diary and rate your symptoms each day or every few days so you can see the trends.  Also monitor BP and pulse each morning.  Don’t focus on the day , but the longer term trends.

 

 

——-

Regarding the duration of action, i don’t see consistency in the charts that i have seen so i gave up. I do not know if the duration of action is longer with librium than valium.  This has to do with the pharmacokinetics and how the benzo locks in and then releases from the binding site.  It can be very complex.    I am sure i can research it and get an answer for you , but charts are not always predictable relative to our unique way that we react to these drugs.  Regarding the every 12 hours or every 24 hours, either way is fine. One has to do what is best for them. If there are issues with sleep one might be more comfortable leaving the night dose for last and taper it at a lower rate than the others, like the example above.  I believe Ashton’s examples do something similar.  THe key is that you must be resilient enough to handle slight changes in serum levels with single dosing per day.    Most will not be able to do this initially when getting out of tolerance and most definitely not if recovering from kindling.  Over time it becomes an option.  You will know if you can handle it based on symptoms.  If you are not ready you will most likely get anxious and nauseated during the 18-20 hour mark. I did not encounter this but you will know when and if you are ready.

 

————

 

Regarding the model, i developed it based on research. If you take a look at the earlier posts it is heavily referenced. I starting doing away with the references in the last two posts (Part 1 and Part 2 of neural circuit dynamics) so that people could understand it in some way.  It is still based on research and clinical citations but its written in my own words to simplify it.    The signature that i have has a table of contents, but i will have to assemble all the information at some point.  It’s a model based on a system wide approach to PWS and tolerance and wd.  There are 6 pillars and 4 component systems and it is extensible meaning components and pillars can be added as the model develops and we gain more knowledge. It’s a way in which we can understand how and why PWS occurs and how and why tolerance develops and how the body deals with the onslaught of the Benzodiazaphine.

 

It does help one understand and design a proper taper program. It stresses the importance of maintaining steady state with benzos from a physiological perspective.  It explains why fast onset benzos are “harder” on the neural circuitry than slower onset benzos.  It also explains how critical negative stressors are to preventing healing and how negative stressors are involved in PWS and the perpetuation of symptoms after benzo washout.  It also explains how the pillars interact with one another and how the pillars affect each of the component systems.  It explains how destabilization in one pillar like the GABAergic pillar by benzos can create system wide chaos.  It also makes it very clear that benzo PWS is much much more than just GABA and the GABAaR.

 

 

——————-

I understand about wanting to fast taper the rest of the benzo detox.  I don’t know if it is wise. Some people can do this , and others cannot. It depends on how resilient your recovery mechanisms are, what your life situation is (ie, negative stressors), and from a genetic perspective how quicky your neural circuits can neuroadapt in the absence of the benzo.    For some of us, this neuroadaptiation process is slow and in that case its best to listen to your symptoms.  I personally do not think a fast washout will always work at the tail end of a taper because if your physiology is pushed beyond what it can accomodate, it can be very difficult to get out of that hole. You might have a weak area that is susceptible to this type of rapid washout.

 

 

—————-

 

The Benzodiazaphine is stronger than we are but not smarter.  We have time on our side, we can throttle back the taper based on symptoms(defensive mode),  we can maintain steady state, and we can try to avoid negative stressors as much as possible and try to stay moving (in mind and body) in some way or another.  Walking is a great therapy for recovery.

 

I hope this helps.

 

Best wishes,

Dm123

[[...]]

Thanks dm123 for that last explanation!

It all makes sense.

I'm not planning to speed up my taper- mostly trying to figure out when/if to go slower.

I never plan to take any benzo again after this taper. Or alcohol. Or z drug. Or Magnesium supp.

 

Can we talk a little more about negative stressors? Do you mean external life stress? How do you all handle this?? It does make sense to keep stress down even after completing taper esp in the beginning (and always of course). But you also mentioned stress resiliency increasing. Can you talk a little more about these things? And how it relates to PAWS. Like do we get resilient enough at some point that there is no PAWS- is that when ppl say they are healed?