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

[[li...]]

Jlavogt,

 

'I am wondering about crossing over. I know Clonazepam is a nasty drug but v is not an option for me as I am a fast metabolizer of the drug due to my genomind test. I have tried it before and it drops out very quick for me after hitting for hard for about an hour then I feel nothing. I have thought about Librium but don’t know how you taper the capsules. Is it a problem to taper clonazepam directly?'

 

I did read a bit about that genomind test, and I'm not so sure it has a solid foundation.

 

'after hitting for hard for about an hour then I feel nothing' V ? Not surprising. It has a relatively short duration of action, (moderate to long half life). Clonazepam has a long duration of action.

IMO you always need to be cautious when switching to a different drug. It's very individual !

[[Fr...]]

Thanks Liberty

 

It seems contradictory to what they tell you to do in Ashton Manuel. Get on V because of long half life but it has the short onset duration. Clonazepam seems so potent that any tapering feels like torture.

 

How is the onset of action for Librium? I am not sure about changing meds I just know what I am doing isn’t working and I can not taper this way.

[[li...]]

I don´t know much about L, that´s dm123´s area of expertise ; )

 

On the positive side, 0.5 mg isn´t that much. In diazepam equivalent, it´s 10 mg. How long have you been taking it ? There are many reasons why tapering can be more difficult, such as how long you´ve been on the drug.

 

It´s potent and it can be harsh. There is no one true answer for everyone. Sometimes it helps to split doses, and sometimes to take it once a day. That depends a lot on your relationship with the drug. Sometimes you just need to ´break through it´, sometimes you need to go slow. I know that´s very generic.

 

Generally I would prefer not to switch to a different drug.

 

 

 

 

[[Fr...]]

I don´t know much about L, that´s dm123´s area of expertise ; )

 

On the positive side, 0.5 mg isn´t that much. In diazepam equivalent, it´s 10 mg. How long have you been taking it ? There are many reasons why tapering can be more difficult, such as how long you´ve been on the drug.

 

It´s potent and it can be harsh. There is no one true answer for everyone. Sometimes it helps to split doses, and sometimes to take it once a day. That depends a lot on your relationship with the drug. Sometimes you just need to ´break through it´, sometimes you need to go slow. I know that´s very generic.

 

Generally I would prefer not to switch to a different drug.

 

I started in Nov 2016 and splitting to three doses made a big difference for me in the beginning but so many bumps in the road and can’t get back to that stable place. Clonazepam seems to sedate and agitate also it’s horrible.

[[cs...]]

I don´t know much about L, that´s dm123´s area of expertise ; )

 

On the positive side, 0.5 mg isn´t that much. In diazepam equivalent, it´s 10 mg. How long have you been taking it ? There are many reasons why tapering can be more difficult, such as how long you´ve been on the drug.

 

It´s potent and it can be harsh. There is no one true answer for everyone. Sometimes it helps to split doses, and sometimes to take it once a day. That depends a lot on your relationship with the drug. Sometimes you just need to ´break through it´, sometimes you need to go slow. I know that´s very generic.

 

Generally I would prefer not to switch to a different drug.

 

I started in Nov 2016 and splitting to three doses made a big difference for me in the beginning but so many bumps in the road and can’t get back to that stable place. Clonazepam seems to sedate and agitate also it’s horrible.

 

Hi Jlav

The numbers in the tables are not always consistent.  I do know the onset of action of Librium is quite a bit slower than valium.  That is why some clinicians prefer librium to valium.  In theory with a much slower onset of action you are less likely to further disrupt dopamine homeostasis, and it’s also more gentle to the nervous system from an adaptive perspective, ie the compensatory mechanisms of the nervous system have a bit of an easier time dealing with the slower onset of action.

 

I’m sure you’ve seen charts like this one.  Valium has much faster onset of action

 

http://www.vhpharmsci.com/vhformulary/tools/benzodiazepines-comparison.htm

 

Hope this helps,

 

 

[[cs...]]

There are some questions regarding onset of action, duration of action , half life, etc.  I’m not going to get into the details, but am posting some starter references below for those who want to understand pharmacodynamics and pharmacokinetics more deeply.

 

I think the main takeaway is how one feels when taking the various drugs. 

 

=======

 

Librium has a slower onset of action than valium and lorazepam.  Peak onset is further out on the timescale

 

Duration of action is not the same thing as onset of action.

 

Duration of action is much more complex.

 

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

Quote

 

The duration of action of a drug is the length of time that particular drug is effective.[3] Duration of action is a function of several parameters including plasma half-life, the time to equilibrate between plasma and target compartments, and the off rate of the drug from its biological target.[4]

 

End quote

 

 

Off rate is below.  It’s an important part of duration of action.  Note it’s not necessarily directly related to potency.

http://blogs.sciencemag.org/pipeline/archives/2013/10/29/unraveling_an_offrate

 

Quote

Medicinal chemists talk a lot more about residence time and off rate than they used to. It’s become clear that (at least in some cases) a key part of a drug’s action is its kinetic behavior, specifically how quickly it leaves its binding site. You’d think that this would correlate well with its potency, but that’s not necessarily so. Binding constants are a mix of on- and off-rates, and you can get to the same number by a variety of different means. Only if you’re looking at very similar compounds with the same binding modes can you expect the correlation your intuition is telling you about, and even then you don’t always get it.

 

End quote.

 

 

And this.  It’s very complex.

http://csmres.co.uk/cs.public.upd/article-downloads/Pan.pdf

 

==========

 

I know it’s complex but for the discussion of Librium and valium focus on the difference between onset of action for now.  Librium’s onset is much longer (slower) than valium.

 

 

The bottom line for me:

Librium does not have the same seesaw effect for me as the high potency lorazepam did.  Each of us is unique in how we metabolize drugs and how they affect us.  In general, Librium is not considered a high potency drug.  You will not feel a sudden intense effect when taking it.  It’s onset is slow.  It’s effects occurs over a matter of several hours, and even then it’s potency seems much weaker than the “table equivalent” of lorazepam.  But each person is different and unique in how they react to these drugs and one does not truly find out how they react until they attempt the crossover.

 

In this respect, a slow partial crossover similar to Ashton might be helpful.

 

For 0.5 mg clonazepam you can try a 15 mg Librium and 0.25 clonazepam mix (note there’s a slight updose here according to the charts) initially.

[[Fr...]]

DM

All Your info is so helpful Thank you for taking the time to explain. 🙏

[[li...]]

I don´t know much about L, that´s dm123´s area of expertise ; )

 

On the positive side, 0.5 mg isn´t that much. In diazepam equivalent, it´s 10 mg. How long have you been taking it ? There are many reasons why tapering can be more difficult, such as how long you´ve been on the drug.

 

It´s potent and it can be harsh. There is no one true answer for everyone. Sometimes it helps to split doses, and sometimes to take it once a day. That depends a lot on your relationship with the drug. Sometimes you just need to ´break through it´, sometimes you need to go slow. I know that´s very generic.

 

Generally I would prefer not to switch to a different drug.

 

I started in Nov 2016 and splitting to three doses made a big difference for me in the beginning but so many bumps in the road and can’t get back to that stable place. Clonazepam seems to sedate and agitate also it’s horrible.

 

(bold)

 

Oh, I do know that ! Just a property of the drug I guess. The drug should be illegal.

 

And that reminds me. If I ever get back to that place of about 7 years ago ... I'd still have to deal with that ...

 

Dutch doctors tend to be expectative, but that won't stop them from going into 'attack mode' like American doctors if they really 'see' something getting out of hand. Obviously, you don't want to get into that situation when your CNS is seriously compromised and they want to 'attack' you with neurotoxic drugs.

[[li...]]

dm123,

 

While I was not planning to taper Librium, would you happen to know how long it takes to get Librium and all the metabolites out of the body ? Not every source says the same about the metabolites.

 

For diazepam it's obvious, diazepam (1-2 days) > desmethyldiazepam (50-100 hours ? ? ?)>oxazepam. Temazepam is a metabolite of diazepam, so ultimately it's that diazepam plus (50-100? ?) hours. I'm not sure if cumulative dosing makes a difference.

[[Su...]]

dm123,

thank you again for more information that helps explain some of my experience 

 

The personal nature of how we metabolize meds and the duration of action has been a tricky thing of me for a long time.

 

I have been told over and over on the boards that I "shouldn't need to dose Valium more than once a day" and yet if I do that I am in interdose w/d all day.  I have been told "that is impossible" -- but i'm living it.  I can even feel changes in dosing times in 3-4 hours....  duration of action!

 

I think the half-life will come into play when I start to taper the Valium, very nervous about that.

 

I also had a genetics test and was told I am NOT a fast metabolizer of Valium....

 

It may be that that is simply how damaged my CNS is from the Xanax /ambien combo -- but I do know that being in interdose w/d is not a way to heal.

And the Xanax that I take at night continues to hold me for at least 12-14 hours, which is within the half-life measures.  weird but that's my body's experience...

 

All that to say that even though i don't really understand these scientific article, I can glean much that helps me make decisions about how I should proceed with this body.  Which is continuing to dose many times a day to maintain a "rock steady blood serum level" as much as I can.  And at Day 60 of this hold I can see how many things are better -- and many things continue to be very fragile...

 

Thanks all for reading my morning diatribe and story....

SS

[[cs...]]

dm123,

 

While I was not planning to taper Librium, would you happen to know how long it takes to get Librium and all the metabolites out of the body ? Not every source says the same about the metabolites.

 

For diazepam it's obvious, diazepam (1-2 days) > desmethyldiazepam (50-100 hours ? ? ?)>oxazepam. Temazepam is a metabolite of diazepam, so ultimately it's that diazepam plus (50-100? ?) hours. I'm not sure if cumulative dosing makes a difference.

 

Hi liberty there was a great thread on the same about 4 weeks ago.  You should be able to find it. The commenter ran through the calculations.  The metabolites can stick around for 30-60 days, the range being dependent on the differences between individuals.  ( this would be in alignment to a 100 hour half life)

 

If we throw out all the scientific charts, pharmacodynamics, etc, ( which is unusual for me    ) I can tell you from personal experience that it takes me 26-34 days to completely stabilize, so that 30-60 day range is probably correct.

 

We both know that valium and librium get deposited in the fatty tissue as well, and I’ve heard that this takes around 6 months to purge , but do not have references for this.  It would not surprise me.

 

I’ve never agreed with a fixed 2 week cutting schedule for valium and librium, but rather a symtom based defensive strategy for dealing with the benzo beast.

 

Multiple dosing per day of Valium and librium seems to not make scientific sense (ie, why not just single dose) , but early on in the taper the nervous system is usually so sensitized (especially if one was at tolerance or kindled), that “rock solid” steady state is absolutely required.  If one does things right, and is recovering while in taper, one can discard afternoon dose, then morning dose, as nervous system resiliency builds up. (Ashton even does this)  I’m only doing the last final bit at night now, but early on, I was doing 3 times a day.  It’s what sustained me and gave my nervous system a chance to recover and unwind the imbalances.

 

One really has to listen to one’s own body (symtoms) in this respect.

[[Fr...]]

Suffering

How often are you dosing?

 

My Teva brand of clonazepam was discontinued. It had an active ingredient in it called providone that was like a time release. There are no other generics or brand that had this ingredient and I am having a hard time becoming stable. I did an increase of 20% yesterday and  I feel like it sedated me more but then the drop off four hours later is worse. I am moving to dosing 4x a day today and lowered my updose to just 10% to see if the sedation and drop off swing with be less extreme with a lower updose amount. I guess I need to take this slow. My first dose this morning with an 10% increase and split in four amount sedated me and then four hours later horrible drop off. Waited until the five hour mark to take the second dose and it’s been two hours with no relief. Trying to make sense of all this so I can find something that works to get stable enough to taper again.

 

My plan is to keep with the 10% updose over the next 3-5 days and dose 4x a day to see how that feels. If still not stable considering dosing 5 times a day and increase the updose 20%. I am starting to wonder if K is just to hard for me to taper and should cross to Librium( I am a fast metabolizer of valium according to my gene test so that is not an option) I am just scared for the crossover withdrawal off k.

 

[[li...]]

I get the feeling that I have to reconfigure my entire CNS to get out of this ...

 

Dutch medicine, the worst. Anyone ever heard of 'waiting till it is over' by a doc when you say problems are caused by the benzodiazepine ?

[[Su...]]

Suffering

How often are you dosing?

I dose 4X a day.  that may seem excessive, but i am really listening to my body.  tried an experiment of dosing less frequently and it was hell.  I was in extreme tolerance when i started down and tapered a ridiculous amount in the beginning (that's why I don't even include it in my sig any longer) so my CNS is super duper messed up.

 

As I mentioned before the Xanax holds me for 12-14 hours which is weird, but I have found something that my body is tolerating.

I am going to continue to hold for another month even though I am fairly stable at this point.  i put my CNS through hell with my quick taper.

 

So sorry about the change in Clonazepam that you are dealing with...  I know many folks who have had trouble with the change in generics.

 

But I think that using dm123's guide of getting really stable, however we do it is critical.  Wish I could offer more, but for me it was trial and error until I got to this formula for my body.  Now it's letting my body heal more before I taper again.

 

And the scientific papers on this thread, although over my head, give me an indication of how many systems are involved in the healing process once we are in tolerance or kindled.  it all takes time....

SS

 

 

 

 

[[li...]]

dm123,

 

While I was not planning to taper Librium, would you happen to know how long it takes to get Librium and all the metabolites out of the body ? Not every source says the same about the metabolites.

 

For diazepam it's obvious, diazepam (1-2 days) > desmethyldiazepam (50-100 hours ? ? ?)>oxazepam. Temazepam is a metabolite of diazepam, so ultimately it's that diazepam plus (50-100? ?) hours. I'm not sure if cumulative dosing makes a difference.

 

Hi liberty there was a great thread on the same about 4 weeks ago.  You should be able to find it. The commenter ran through the calculations.  The metabolites can stick around for 30-60 days, the range being dependent on the differences between individuals.  ( this would be in alignment to a 100 hour half life)

 

If we throw out all the scientific charts, pharmacodynamics, etc, ( which is unusual for me    ) I can tell you from personal experience that it takes me 26-34 days to completely stabilize, so that 30-60 day range is probably correct.

 

We both know that valium and librium get deposited in the fatty tissue as well, and I’ve heard that this takes around 6 months to purge , but do not have references for this.  It would not surprise me.

 

I’ve never agreed with a fixed 2 week cutting schedule for valium and librium, but rather a symtom based defensive strategy for dealing with the benzo beast.

 

Multiple dosing per day of Valium and Librium seems to not make scientific sense (ie, why not just single dose) , but early on in the taper the nervous system is usually so sensitized (especially if one was at tolerance or kindled), that “rock solid” steady state is absolutely required.  If one does things right, and is recovering while in taper, one can discard afternoon dose, then morning dose, as nervous system resiliency builds up. (Ashton even does this)  I’m only doing the last final bit at night now, but early on, I was doing 3 times a day.  It’s what sustained me and gave my nervous system a chance to recover and unwind the imbalances.

 

One really has to listen to one’s own body (symtoms) in this respect.

 

I can't readily find that thread.

 

Anyway, the way you describe it the cumulative half life is longer than diazepam's. 30-60 days seems very long. Especially when one is one a high dose, that seems slow.

 

One thing we disagree on is short half life vs. long half life. True, short half life can cause kindling more easily. But on the other hand, you're more likely to achieve full adaptation of the GABAA receptor if you're 'on' a benzo 24 hours a day (admittedly, lorazepam is particulary harsh). And usually you are able to get off a short acting one faster, although it may be harsher. It's my guess that tolerance to the alpha 1 subunit occurs faster, but once tolerance to the alpha 2 and 3 subunit has developed it will take much longer to reverse.

 

'Multiple dosing per day of Valium and librium seems to not make scientific sense (ie, why not just single dose) , but early on in the taper the nervous system is usually so sensitized (especially if one was at tolerance or kindled), that “rock solid” steady state is absolutely required.  If one does things right, and is recovering while in taper, one can discard afternoon dose, then morning dose, as nervous system resiliency builds up. (Ashton even does this)  I’m only doing the last final bit at night now, but early on, I was doing 3 times a day.  It’s what sustained me and gave my nervous system a chance to recover and unwind the imbalances.'

 

What about duration of action ? If the dependence is very strong it often matters. Half life is about elimination. But true, if you're on a benzo with a relatively short duration of action (lorazepam) that may offer a different experience than the clonazepam. I never consciously experienced interdose withdrawal prior to the lorazepam. And also, the (unbound fraction?) clonazepam's blood level should be more steady during the 'duration of action' compared to lorazepam, which peaks quickly.

 

Mostly unrelated, I'm just stuck in the worst healthcare system in the world. I don't think I can get a physical problem fixed, caused by a doctor (NICE guidelines UK: consider treating problems that cause physical distress or that impair functoning). My clonazepam has a bit the function of that in palliative care.  I got his letter in which he is cheering I'm leaving his practice but I'm not gonna see another 'village idiot' (which he expects). They don't have the expertise, they got it all wrong. The mentality is all wrong too (waiting for it to pass!) That awful GP brotherhood/sisterhood, corrupt as hell. I'd much prefer abuse by the system in the USA. <sorry about the rant>

[[cs...]]

dm123,

thank you again for more information that helps explain some of my experience 

 

The personal nature of how we metabolize meds and the duration of action has been a tricky thing of me for a long time.

 

I have been told over and over on the boards that I "shouldn't need to dose Valium more than once a day" and yet if I do that I am in interdose w/d all day.  I have been told "that is impossible" -- but i'm living it.  I can even feel changes in dosing times in 3-4 hours....  duration of action!

 

I think the half-life will come into play when I start to taper the Valium, very nervous about that.

 

I also had a genetics test and was told I am NOT a fast metabolizer of Valium....

 

It may be that that is simply how damaged my CNS is from the Xanax /ambien combo -- but I do know that being in interdose w/d is not a way to heal.

And the Xanax that I take at night continues to hold me for at least 12-14 hours, which is within the half-life measures.  weird but that's my body's experience...

 

All that to say that even though i don't really understand these scientific article, I can glean much that helps me make decisions about how I should proceed with this body.  Which is continuing to dose many times a day to maintain a "rock steady blood serum level" as much as I can.  And at Day 60 of this hold I can see how many things are better -- and many things continue to be very fragile...

 

Thanks all for reading my morning diatribe and story....

SS

 

Hi SS,

 

As usual you bring up some very very important points that are occurring in real life. It’s not just theory.  The scientific theory is great to know, but you are proof of how these drugs and the recovery from these drugs really work.

 

I’m going to tie together all the loose ends on why things are happening to you the way they are.  Why it is that you feel better with three times a day dosing at this stage than single dosing? And why is it taking so long to feel “right”..

 

In theory the long half life of valium should be sufficient in a nervous system that has not been assaulted. 

 

In our cases, we are talking about a nervous system that has been compensating from an assault for a long time..  Both you and i, and many of the people here coming off of short acting single dosing  Benzodiazaphines and/or short acting Benzodiazaphines + z drugs have nervous systems that have plastically tried to adapt to the assault. 

 

When the compensatory (plastic) mechansims that fight the assault are stretched to the limit (as they are in our cases), the neurons in a neural circuit tend towards hyperexcitability.  There’s no reserve in the adaptability mechanism. This occurs slowly over time as tolerance builds up or as one is kindled.  The homeostatic mechansims that try to maintain stability in the face of the assault are no longer as capable as they are in a normal person or as they once were. 

 

This is not permanent damage, but the mechanisms need stability and time to recover. There are feedback loops that take time to settle down.  Prior to that recovery, the nervous system is Hyperexcitable meaning small inputs generate erratic bursting responses in the neuronsm and this produces horrendous symptoms.  In this precarious state, the nervous system can indeed detect very small variances in serum levels.

 

So in a normal person, or a person that has not come out of tolerance or kindling, they can and do taper with single dosing valium just fine.  For you and I this was not an option, because of the stage that had been set.

 

There is good news here.  The nervous system and the adaptive response system does heal with time and does become more resilient with time.  Adaptive plasticity does return to its former state.  So as you continue stabilizing you will be able to go to 2 doses a day of valium because your nervous system can handle those small variances in serum levels. But you cannot do that right now.  Finally towards the last 20% of the taper you can go to single dosing the valium.  The variances in serum levels are tolerable because your nervous system is regaining compensatory ability and control, and resiliency to circuit stress

 

Steady state 3 times dosing is what is helping you recover right now.

 

But you will know based on your symtoms when you are getting better and when you can drop that afternoon dose and not feel the interdose withdrawal. ....

 

I hope this helps shed the light on things even further.......

 

 

[[Su...]]

dm123.

Thank you, thank you, thank you.

Your post explains so much, and also helps with some of the things that I have been told on the boards:

"it is impossible to feel a change in Valium for 3-5 days."

No trying to call anyone out here but my experience was so different i was beginning to doubt my sanity, although as my body continues to feel better I knew that the multiple doses per day were what I needed to do for this body.

It also provides hope and the idea that I too can help others on the boards who are suffering through a once a day regimen when I multiple dosing idea may be more helpful.

All the pieces finally fit together in a way that I can understand and use for my recovery.  Now to continue to have patience and to listen to my body.

I am so sorry that we are both in this same position, but know that all will be well in the end -- whenever that may be!

 

Now atm I am trying to find some scientific papers -- of which there seem to be quite a few!-- to suggest that Lion's Mane mushroom as a supplement may help with NGF.....  I am wary of supplements so research them a lot before I ever ingest anything.

The nervous system is very tenuous atm, although I can absolutely see that it is healing -- quite thrilling.

 

Again thank you for your patience with us less scientifically minded folks who try, and continue to get so much from your posts and the papers provided.

:smitten:

SS

[[cs...]]

dm123,

 

While I was not planning to taper Librium, would you happen to know how long it takes to get Librium and all the metabolites out of the body ? Not every source says the same about the metabolites.

 

For diazepam it's obvious, diazepam (1-2 days) > desmethyldiazepam (50-100 hours ? ? ?)>oxazepam. Temazepam is a metabolite of diazepam, so ultimately it's that diazepam plus (50-100? ?) hours. I'm not sure if cumulative dosing makes a difference.

 

Hi liberty there was a great thread on the same about 4 weeks ago.  You should be able to find it. The commenter ran through the calculations.  The metabolites can stick around for 30-60 days, the range being dependent on the differences between individuals.  ( this would be in alignment to a 100 hour half life)

 

If we throw out all the scientific charts, pharmacodynamics, etc, ( which is unusual for me    ) I can tell you from personal experience that it takes me 26-34 days to completely stabilize, so that 30-60 day range is probably correct.

 

We both know that valium and librium get deposited in the fatty tissue as well, and I’ve heard that this takes around 6 months to purge , but do not have references for this.  It would not surprise me.

 

I’ve never agreed with a fixed 2 week cutting schedule for valium and librium, but rather a symtom based defensive strategy for dealing with the benzo beast.

 

Multiple dosing per day of Valium and librium seems to not make scientific sense (ie, why not just single dose) , but early on in the taper the nervous system is usually so sensitized (especially if one was at tolerance or kindled), that “rock solid” steady state is absolutely required.  If one does things right, and is recovering while in taper, one can discard afternoon dose, then morning dose, as nervous system resiliency builds up. (Ashton even does this)  I’m only doing the last final bit at night now, but early on, I was doing 3 times a day.  It’s what sustained me and gave my nervous system a chance to recover and unwind the imbalances.

 

One really has to listen to one’s own body (symtoms) in this respect.

 

I can't readily find that thread.

 

Anyway, the way you describe it the cumulative half life is longer than diazepam's. 30-60 days seems very long. Especially when one is one a high dose, that seems slow.

 

One thing we disagree on is short half life vs. long half life. True, short half life can cause kindling more easily. But on the other hand, you're more likely to achieve full adaptation of the GABAA receptor if you're 'on' a benzo 24 hours a day. And usually you are able to get off a short acting one faster, although it may be harsher. It's my guess that tolerance to the alpha 1 subunit occurs faster, but once tolerance to the alpha 2 and 3 subunit has developed it will take much longer to reverse.

 

Hi Liberty,

 

Yes 30-60 days is long. 

 

Yes, we disagree on the short vs. long half life Benzodiazaphines.  Please see my response to SS above.  If you are entering a taper from tolerance and/or a kindled state, a short acting Benzodiazaphine taper will be excruciatingly difficult.  It can no doubt be done by some individuals, but it will make things very very hard to do in terms of a taper.  I could have never done it.

 

I used to think that flushing out was a good thing for the receptor and for the nervous system. But the nervous system simply doesn’t work that way when it comes to Benzodiazaphines.  This is the big myth of Benzodiazaphines and many fall into this trap.  Receptor adaptation is different between the two classes of drugs, but we do not know if the conformational changes are any more worse with one benzo vs. another..  It’s just different.  As we both know there’s not enough scientific literature to say which one is more “profound”.

 

However, one area is clear in the literature.......

 

There’s a completely different level of neuro adaptation at the circuit level that goes far beyond the receptor itself.  This type of circuit level adaptation is terribly assaulted by short acting single dose Benzodiazaphines.  It’s this neuroadaptation that is so dangeraous, not the receptor level adaptation.  It is this neuroadaptation that causes so many issues long after the Benzodiazaphine is stopped and long after the receptor should have “healed”.  Focusing at the neuron receptor level is not where it is at. It’s only part of a larger picture. This focus on the receptor and subunits, etc.....has created a lot of confusion realtive to PWS, tapering, withdrawal and tolerance.

 

Wellbeing is based on homeostasis.  All biological systems have homeostasis as the cornerstone of their physiology.  When serum levels are erratic one is doing the exact opposite of what the body prefers.

 

WIth a short life Benzodiazaphine you are adding a massive layer of additional circuit level neuroadatation that is required to maintain physiological function.  It’s a huge accommodation for the plastic mechanisms to adapt to a serum level that goes up and down each day versus a constant saturation of steady state. 

 

The adaptations at the circuit level that occur with the long half life Benzodiazaphine are a smaller subset of a much much larger set of accommodations that are required when one doses a short acting Benzodiazaphine once a day.  It’s much easier for the body to heal from a smaller set of neuro adaptions than from a set of much larger neuro adaptations.

 

Regarding getting off a short acting Benzodiazaphine taking a shorter time, it all depends on if you have hit tolerance and/or are kindled.  In theory if you are neither kindled or in tolerance getting off a short acting Benzodiazaphine should not be difficult.  But the mainstream theory does not account for circuit level neuroadaptations that take time to revert, and we know in reality it can be very difficult getting off these drugs.  As we know, Valium and librium don’t work for everyone. Some get ill from the drugs themselves

 

I wish i had been given valium or Librium from the onset, rather than the short acting Benzodiazaphine.

 

 

[[cs...]]

dm123.

Thank you, thank you, thank you.

Your post explains so much, and also helps with some of the things that I have been told on the boards:

"it is impossible to feel a change in Valium for 3-5 days."

No trying to call anyone out here but my experience was so different i was beginning to doubt my sanity, although as my body continues to feel better I knew that the multiple doses per day were what I needed to do for this body.

It also provides hope and the idea that I too can help others on the boards who are suffering through a once a day regimen when I multiple dosing idea may be more helpful.

All the pieces finally fit together in a way that I can understand and use for my recovery.  Now to continue to have patience and to listen to my body.

I am so sorry that we are both in this same position, but know that all will be well in the end -- whenever that may be!

 

Now atm I am trying to find some scientific papers -- of which there seem to be quite a few!-- to suggest that Lion's Mane mushroom as a supplement may help with NGF.....  I am wary of supplements so research them a lot before I ever ingest anything.

The nervous system is very tenuous atm, although I can absolutely see that it is healing -- quite thrilling.

 

Again thank you for your patience with us less scientifically minded folks who try, and continue to get so much from your posts and the papers provided.

:smitten:

SS

 

Hi SS

 

I am very glad that you have stabililzed and are actually reversing the course.  Yes, please spread the message. The more people we help, the better place the world becomes.

 

Yes, just be careful with supplements. I take all the usual vitamins and probiotics but for now, i don’t take any other supplements, etc.  Your body will tell you if the supplement is no good pretty quickly 

 

EDIT: fixed typos.  The auto spell is sticking in all sorts of words.

[[cs...]]

Suffering

How often are you dosing?

 

My Teva brand of clonazepam was discontinued. It had an active ingredient in it called providone that was like a time release. There are no other generics or brand that had this ingredient and I am having a hard time becoming stable. I did an increase of 20% yesterday and  I feel like it sedated me more but then the drop off four hours later is worse. I am moving to dosing 4x a day today and lowered my updose to just 10% to see if the sedation and drop off swing with be less extreme with a lower updose amount. I guess I need to take this slow. My first dose this morning with an 10% increase and split in four amount sedated me and then four hours later horrible drop off. Waited until the five hour mark to take the second dose and it’s been two hours with no relief. Trying to make sense of all this so I can find something that works to get stable enough to taper again.

 

My plan is to keep with the 10% updose over the next 3-5 days and dose 4x a day to see how that feels. If still not stable considering dosing 5 times a day and increase the updose 20%. I am starting to wonder if K is just to hard for me to taper and should cross to Librium( I am a fast metabolizer of valium according to my gene test so that is not an option) I am just scared for the crossover withdrawal off k.

 

Hi Jlav,

 

I think it is a good idea to wait those 3-5 days.  If you keep changing to many times (like every day) it will be hard to separate out what is working and what is not. There will be a bit of a lag effect for the full effect of the change to occur.

 

 

[[cs...]]

dm123,

 

While I was not planning to taper Librium, would you happen to know how long it takes to get Librium and all the metabolites out of the body ? Not every source says the same about the metabolites.

 

For diazepam it's obvious, diazepam (1-2 days) > desmethyldiazepam (50-100 hours ? ? ?)>oxazepam. Temazepam is a metabolite of diazepam, so ultimately it's that diazepam plus (50-100? ?) hours. I'm not sure if cumulative dosing makes a difference.

 

Hi liberty there was a great thread on the same about 4 weeks ago.  You should be able to find it. The commenter ran through the calculations.  The metabolites can stick around for 30-60 days, the range being dependent on the differences between individuals.  ( this would be in alignment to a 100 hour half life)

 

If we throw out all the scientific charts, pharmacodynamics, etc, ( which is unusual for me    ) I can tell you from personal experience that it takes me 26-34 days to completely stabilize, so that 30-60 day range is probably correct.

 

We both know that valium and librium get deposited in the fatty tissue as well, and I’ve heard that this takes around 6 months to purge , but do not have references for this.  It would not surprise me.

 

I’ve never agreed with a fixed 2 week cutting schedule for valium and librium, but rather a symtom based defensive strategy for dealing with the benzo beast.

 

Multiple dosing per day of Valium and Librium seems to not make scientific sense (ie, why not just single dose) , but early on in the taper the nervous system is usually so sensitized (especially if one was at tolerance or kindled), that “rock solid” steady state is absolutely required.  If one does things right, and is recovering while in taper, one can discard afternoon dose, then morning dose, as nervous system resiliency builds up. (Ashton even does this)  I’m only doing the last final bit at night now, but early on, I was doing 3 times a day.  It’s what sustained me and gave my nervous system a chance to recover and unwind the imbalances.

 

One really has to listen to one’s own body (symtoms) in this respect.

 

I can't readily find that thread.

 

Anyway, the way you describe it the cumulative half life is longer than diazepam's. 30-60 days seems very long. Especially when one is one a high dose, that seems slow.

 

One thing we disagree on is short half life vs. long half life. True, short half life can cause kindling more easily. But on the other hand, you're more likely to achieve full adaptation of the GABAA receptor if you're 'on' a benzo 24 hours a day (admittedly, lorazepam is particulary harsh). And usually you are able to get off a short acting one faster, although it may be harsher. It's my guess that tolerance to the alpha 1 subunit occurs faster, but once tolerance to the alpha 2 and 3 subunit has developed it will take much longer to reverse.

 

'Multiple dosing per day of Valium and librium seems to not make scientific sense (ie, why not just single dose) , but early on in the taper the nervous system is usually so sensitized (especially if one was at tolerance or kindled), that “rock solid” steady state is absolutely required.  If one does things right, and is recovering while in taper, one can discard afternoon dose, then morning dose, as nervous system resiliency builds up. (Ashton even does this)  I’m only doing the last final bit at night now, but early on, I was doing 3 times a day.  It’s what sustained me and gave my nervous system a chance to recover and unwind the imbalances.'

 

What about duration of action ? If the dependence is very strong it often matters. Half life is about elimination. But true, if you're on a benzo with a relatively short duration of action (lorazepam) that may offer a different experience than the clonazepam. I never consciously experienced interdose withdrawal prior to the lorazepam. And also, the (unbound fraction?) clonazepam's blood level should be more steady during the 'duration of action' compared to lorazepam, which peaks quickly.

 

Mostly unrelated, I'm just stuck in the worst healthcare system in the world. I don't think I can get a physical problem fixed, caused by a doctor (NICE guidelines UK: consider treating problems that cause physical distress or that impair functoning). My clonazepam has a bit the function of that in palliative care.  I got his letter in which he is cheering I'm leaving his practice but I'm not gonna see another 'village idiot' (which he expects). They don't have the expertise, they got it all wrong. The mentality is all wrong too (waiting for it to pass!) That awful GP brotherhood/sisterhood, corrupt as hell. I'd much prefer abuse by the system in the USA. <sorry about the rant>

 

Hi Liberty

Quote

“I never consciously experienced interdose withdrawal prior to the lorazepam. ”

 

 

 

I think the lorazepam’s shorter half life did indeed have something to do with what happened.  I don’t think it was/is the conformational changes in the receptor itself, per my last positing to you.

 

Can i ask why they switched you from clonazepam to lorazepam for a taper?  It seems counterintuitive.  It would produce more of a strain on the accomodative processes to maintain homeostasis.

 

 

Were you already experiencing tolerance @ the 2-4 mg clonazepam dose when they switched you?

 

Were you single dosing the lorazepam during the 3 month taper period? Or was it broken up into 2-3 doses a day?

 

 

Similar to you, i never experienced interdose wd on lorazepam until the ambien and lunesta were added to the mix.  As the z drugs increased, the interdose wd and kindling became worse.  It all goes back to adding that additional massive layer of instability in the form of inconsistent serum levels.  That, in an of itself, can induce tolerance and eventually kindling. 

 

I wish we could help more.

 

Best

Dm123

 

 

 

 

[[li...]]

'Can i ask why they switched you from clonazepam to lorazepam for a taper?  It seems counterintuitive.  It would produce more of a strain on the accomodative processes to maintain homeostasis.

 

 

Were you already experiencing tolerance @ the 2-4 mg clonazepam dose when they switched you?

 

Were you single dosing the lorazepam during the 3 month taper period? Or was it broken up into 2-3 doses a day?'

 

I had difficulties tapering clonazepam.  Keep in mind, I had that idiot GP. He actually managed to increase my difficulties by making and breaking promises, prescribing the wrong medications, not taking my physical health seriously .. Thus increasing the problems ! And he sort of phoned with various specialists for opinions ... Ultimately, from a hodgepodge of advice and suggestions, and his desire to see what was 'underneath everything' (since it was all mental !!!) he chose lorazepam. At the time I had already come up with alternatives like clobazam (probably wouldn't have worked, but it wouldn't have caused this disaster) or an anticonvulsant assisted CT, but I was pretty much at the end of a rope and accepted the lorazepam. He didn't have experience tapering people, he did have experience with lorazepam for therapeutic purposes. In short, it couldn't have gone worse. I think it's fair to say there was something mentally wrong with that man.

 

'Were you already experiencing tolerance @ the 2-4 mg clonazepam dose when they switched you?' Physical dependence, yes. Tolerance also, but no or minor tolerance withdrawal.

 

'Were you single dosing the lorazepam during the 3 month taper period? Or was it broken up into 2-3 doses a day?''

From a single dose of 2 mg clonazepam a day to two doses of 2 mg lorazepam a day. For two weeks, then 2 weeks at 3 mg lorazepam a day etc. <short version> At first the hypnotic and amnestic properties of the drug wore off. When the sedative properties of the lorazepam has dissappeared (took some time) I was relying on a crude and short acting drug to keep away to withdrawal from the clonazepam. Pretty much end of taper.

 

 

dm123,

 

While I was not planning to taper Librium, would you happen to know how long it takes to get Librium and all the metabolites out of the body ? Not every source says the same about the metabolites.

 

For diazepam it's obvious, diazepam (1-2 days) > desmethyldiazepam (50-100 hours ? ? ?)>oxazepam. Temazepam is a metabolite of diazepam, so ultimately it's that diazepam plus (50-100? ?) hours. I'm not sure if cumulative dosing makes a difference.

 

Hi liberty there was a great thread on the same about 4 weeks ago.  You should be able to find it. The commenter ran through the calculations.  The metabolites can stick around for 30-60 days, the range being dependent on the differences between individuals.  ( this would be in alignment to a 100 hour half life)

 

If we throw out all the scientific charts, pharmacodynamics, etc, ( which is unusual for me    ) I can tell you from personal experience that it takes me 26-34 days to completely stabilize, so that 30-60 day range is probably correct.

 

We both know that valium and librium get deposited in the fatty tissue as well, and I’ve heard that this takes around 6 months to purge , but do not have references for this.  It would not surprise me.

 

I’ve never agreed with a fixed 2 week cutting schedule for valium and librium, but rather a symtom based defensive strategy for dealing with the benzo beast.

 

Multiple dosing per day of Valium and Librium seems to not make scientific sense (ie, why not just single dose) , but early on in the taper the nervous system is usually so sensitized (especially if one was at tolerance or kindled), that “rock solid” steady state is absolutely required.  If one does things right, and is recovering while in taper, one can discard afternoon dose, then morning dose, as nervous system resiliency builds up. (Ashton even does this)  I’m only doing the last final bit at night now, but early on, I was doing 3 times a day.  It’s what sustained me and gave my nervous system a chance to recover and unwind the imbalances.

 

One really has to listen to one’s own body (symtoms) in this respect.

 

I can't readily find that thread.

 

Anyway, the way you describe it the cumulative half life is longer than diazepam's. 30-60 days seems very long. Especially when one is one a high dose, that seems slow.

 

One thing we disagree on is short half life vs. long half life. True, short half life can cause kindling more easily. But on the other hand, you're more likely to achieve full adaptation of the GABAA receptor if you're 'on' a benzo 24 hours a day (admittedly, lorazepam is particulary harsh). And usually you are able to get off a short acting one faster, although it may be harsher. It's my guess that tolerance to the alpha 1 subunit occurs faster, but once tolerance to the alpha 2 and 3 subunit has developed it will take much longer to reverse.

 

'Multiple dosing per day of Valium and librium seems to not make scientific sense (ie, why not just single dose) , but early on in the taper the nervous system is usually so sensitized (especially if one was at tolerance or kindled), that “rock solid” steady state is absolutely required.  If one does things right, and is recovering while in taper, one can discard afternoon dose, then morning dose, as nervous system resiliency builds up. (Ashton even does this)  I’m only doing the last final bit at night now, but early on, I was doing 3 times a day.  It’s what sustained me and gave my nervous system a chance to recover and unwind the imbalances.'

 

What about duration of action ? If the dependence is very strong it often matters. Half life is about elimination. But true, if you're on a benzo with a relatively short duration of action (lorazepam) that may offer a different experience than the clonazepam. I never consciously experienced interdose withdrawal prior to the lorazepam. And also, the (unbound fraction?) clonazepam's blood level should be more steady during the 'duration of action' compared to lorazepam, which peaks quickly.

 

Mostly unrelated, I'm just stuck in the worst healthcare system in the world. I don't think I can get a physical problem fixed, caused by a doctor (NICE guidelines UK: consider treating problems that cause physical distress or that impair functoning). My clonazepam has a bit the function of that in palliative care.  I got his letter in which he is cheering I'm leaving his practice but I'm not gonna see another 'village idiot' (which he expects). They don't have the expertise, they got it all wrong. The mentality is all wrong too (waiting for it to pass!) That awful GP brotherhood/sisterhood, corrupt as hell. I'd much prefer abuse by the system in the USA. <sorry about the rant>

 

Hi Liberty

Quote

“I never consciously experienced interdose withdrawal prior to the lorazepam. ”

 

 

 

I think the lorazepam’s shorter half life did indeed have something to do with what happened.  I don’t think it was/is the conformational changes in the receptor itself, per my last positing to you.

 

Can i ask why they switched you from clonazepam to lorazepam for a taper?  It seems counterintuitive.  It would produce more of a strain on the accomodative processes to maintain homeostasis.

 

 

Were you already experiencing tolerance @ the 2-4 mg clonazepam dose when they switched you?

 

Were you single dosing the lorazepam during the 3 month taper period? Or was it broken up into 2-3 doses a day?

 

 

Similar to you, i never experienced interdose wd on lorazepam until the ambien and lunesta were added to the mix.  As the z drugs increased, the interdose wd and kindling became worse.  It all goes back to adding that additional massive layer of instability in the form of inconsistent serum levels.  That, in an of itself, can induce tolerance and eventually kindling. 

 

I wish we could help more.

 

Best

Dm123

[[li...]]

I took a look at the circuit level, briefly.

 

I can see that interdose withdrawal can cause problems (example). Do short acting benzos cause more problems in that regard ? I can see why they would. On the other hand, the neuroadaptations can become more 'complete'. It's obvious that clonazepam causes some of those circuit problems too, taking it once a day. Since I was on lorazepam, anyway. And yet splitting is an issue at best.

 

In a nutshell: clonazepam is not a 'calming tablet', and it doesn't feel 'GABAergic'. Many things, that thalamic reticular nucleus thingy and consequences, very high potency benzo binding to areas other benzos do not bind to, alterations in the serotonergic/cholinergic systems/GCPRs, hormones ?

It looks like it rewired the circuits after long term use, and that it's to be important to function well physically to get off well !

[[cs...]]

'Can i ask why they switched you from clonazepam to lorazepam for a taper?  It seems counterintuitive.  It would produce more of a strain on the accomodative processes to maintain homeostasis.

 

 

Were you already experiencing tolerance @ the 2-4 mg clonazepam dose when they switched you?

 

Were you single dosing the lorazepam during the 3 month taper period? Or was it broken up into 2-3 doses a day?'

 

I had difficulties tapering clonazepam.  Keep in mind, I had that idiot GP. He actually managed to increase my difficulties by making and breaking promises, prescribing the wrong medications, not taking my physical health seriously .. Thus increasing the problems ! And he sort of phoned with various specialists for opinions ... Ultimately, from a hodgepodge of advice and suggestions, and his desire to see what was 'underneath everything' (since it was all mental !!!) he chose lorazepam. At the time I had already come up with alternatives like clobazam (probably wouldn't have worked, but it wouldn't have caused this disaster) or an anticonvulsant assisted CT, but I was pretty much at the end of a rope and accepted the lorazepam. He didn't have experience tapering people, he did have experience with lorazepam for therapeutic purposes. In short, it couldn't have gone worse. I think it's fair to say there was something mentally wrong with that man.

 

'Were you already experiencing tolerance @ the 2-4 mg clonazepam dose when they switched you?' Physical dependence, yes. Tolerance also, but no or minor tolerance withdrawal.

 

'Were you single dosing the lorazepam during the 3 month taper period? Or was it broken up into 2-3 doses a day?''

From a single dose of 2 mg clonazepam a day to two doses of 2 mg lorazepam a day. For two weeks, then 2 weeks at 3 mg lorazepam a day etc. <short version> At first the hypnotic and amnestic properties of the drug wore off. When the sedative properties of the lorazepam has dissappeared (took some time) I was relying on a crude and short acting drug to keep away to withdrawal from the clonazepam. Pretty much end of taper.

 

 

dm123,

 

While I was not planning to taper Librium, would you happen to know how long it takes to get Librium and all the metabolites out of the body ? Not every source says the same about the metabolites.

 

For diazepam it's obvious, diazepam (1-2 days) > desmethyldiazepam (50-100 hours ? ? ?)>oxazepam. Temazepam is a metabolite of diazepam, so ultimately it's that diazepam plus (50-100? ?) hours. I'm not sure if cumulative dosing makes a difference.

 

Hi liberty there was a great thread on the same about 4 weeks ago.  You should be able to find it. The commenter ran through the calculations.  The metabolites can stick around for 30-60 days, the range being dependent on the differences between individuals.  ( this would be in alignment to a 100 hour half life)

 

If we throw out all the scientific charts, pharmacodynamics, etc, ( which is unusual for me    ) I can tell you from personal experience that it takes me 26-34 days to completely stabilize, so that 30-60 day range is probably correct.

 

We both know that valium and librium get deposited in the fatty tissue as well, and I’ve heard that this takes around 6 months to purge , but do not have references for this.  It would not surprise me.

 

I’ve never agreed with a fixed 2 week cutting schedule for valium and librium, but rather a symtom based defensive strategy for dealing with the benzo beast.

 

Multiple dosing per day of Valium and Librium seems to not make scientific sense (ie, why not just single dose) , but early on in the taper the nervous system is usually so sensitized (especially if one was at tolerance or kindled), that “rock solid” steady state is absolutely required.  If one does things right, and is recovering while in taper, one can discard afternoon dose, then morning dose, as nervous system resiliency builds up. (Ashton even does this)  I’m only doing the last final bit at night now, but early on, I was doing 3 times a day.  It’s what sustained me and gave my nervous system a chance to recover and unwind the imbalances.

 

One really has to listen to one’s own body (symtoms) in this respect.

 

I can't readily find that thread.

 

Anyway, the way you describe it the cumulative half life is longer than diazepam's. 30-60 days seems very long. Especially when one is one a high dose, that seems slow.

 

One thing we disagree on is short half life vs. long half life. True, short half life can cause kindling more easily. But on the other hand, you're more likely to achieve full adaptation of the GABAA receptor if you're 'on' a benzo 24 hours a day (admittedly, lorazepam is particulary harsh). And usually you are able to get off a short acting one faster, although it may be harsher. It's my guess that tolerance to the alpha 1 subunit occurs faster, but once tolerance to the alpha 2 and 3 subunit has developed it will take much longer to reverse.

 

'Multiple dosing per day of Valium and librium seems to not make scientific sense (ie, why not just single dose) , but early on in the taper the nervous system is usually so sensitized (especially if one was at tolerance or kindled), that “rock solid” steady state is absolutely required.  If one does things right, and is recovering while in taper, one can discard afternoon dose, then morning dose, as nervous system resiliency builds up. (Ashton even does this)  I’m only doing the last final bit at night now, but early on, I was doing 3 times a day.  It’s what sustained me and gave my nervous system a chance to recover and unwind the imbalances.'

 

What about duration of action ? If the dependence is very strong it often matters. Half life is about elimination. But true, if you're on a benzo with a relatively short duration of action (lorazepam) that may offer a different experience than the clonazepam. I never consciously experienced interdose withdrawal prior to the lorazepam. And also, the (unbound fraction?) clonazepam's blood level should be more steady during the 'duration of action' compared to lorazepam, which peaks quickly.

 

Mostly unrelated, I'm just stuck in the worst healthcare system in the world. I don't think I can get a physical problem fixed, caused by a doctor (NICE guidelines UK: consider treating problems that cause physical distress or that impair functoning). My clonazepam has a bit the function of that in palliative care.  I got his letter in which he is cheering I'm leaving his practice but I'm not gonna see another 'village idiot' (which he expects). They don't have the expertise, they got it all wrong. The mentality is all wrong too (waiting for it to pass!) That awful GP brotherhood/sisterhood, corrupt as hell. I'd much prefer abuse by the system in the USA. <sorry about the rant>

 

Hi Liberty

Quote

“I never consciously experienced interdose withdrawal prior to the lorazepam. ”

 

 

 

I think the lorazepam’s shorter half life did indeed have something to do with what happened.  I don’t think it was/is the conformational changes in the receptor itself, per my last positing to you.

 

Can i ask why they switched you from clonazepam to lorazepam for a taper?  It seems counterintuitive.  It would produce more of a strain on the accomodative processes to maintain homeostasis.

 

 

Were you already experiencing tolerance @ the 2-4 mg clonazepam dose when they switched you?

 

Were you single dosing the lorazepam during the 3 month taper period? Or was it broken up into 2-3 doses a day?

 

 

Similar to you, i never experienced interdose wd on lorazepam until the ambien and lunesta were added to the mix.  As the z drugs increased, the interdose wd and kindling became worse.  It all goes back to adding that additional massive layer of instability in the form of inconsistent serum levels.  That, in an of itself, can induce tolerance and eventually kindling. 

 

I wish we could help more.

 

Best

Dm123

 

Liberty,

 

So at one point you were up to 2 X 3mg of lorazepam a day during this so called taper plan?

 

I can tell you from experience that after i broke up the doses of lorazepam to get relief, it did help somewhat but i was already on my way to developing increasing levels of tolerance to my TDD and i would have had to increase TDD at some point. And this tolerance developed quickly.  Lorazepam was a real #@@#**$.    Too much for me to handle.  It does not suprise me that even escalating your dose did not help at that point.

 

Looking back i developed tolerance to the lorazepam after a few weeks.  It did not do much for the rest of the few years i was on it.    Interdose wd did not come into play until after the lunesta and ambien were added.  Interdose wd occurs as the neural circuit homeostatic mechansims start to fall apart.

 

The model tells us two things:  the Action potiential dynamics, so there’s no doubt that there were adverse conformational changes in the receptor from the lorazepam.  However, the Neural circuit dynamics component tells us of a much larger higher level of homeostasis that was strained by the drug.  I’m gong to post more on this very subject, but the next post won’t have this information. It will come as a later part.  I hope it will at least help you understand what happened to you in the context of the higher level neural circuit homeostatic mechanisms that take a beating on short acting Benzodiazaphines.

 

My first hand experience with lorazepam tells me that it has to be dosed at least 3 times a day to insure individual variances in metabolizing the drug don’t cause issues.  Fast metabolizers of the drug are on the short end of its 8 hour half life.  2 times a day was not enough for me.  Initially it was ok but it did not last long.  Once the neural circuit level mechansims start to go off course  it is very difficult to get them to stabilize.

 

“When the sedative properties of the lorazepam has dissappeared (took some time) I was relying on a crude and short acting drug to keep away to withdrawal from the clonazepam. ”

 

Was this another short acting drug in addition to the lorazepam?  Was it GABAergic?  This would have exasperated the issue at the neural circuit level.

 

In a nutshell, we need to consider things at both the neuron level (receptor level) and the neural circuit level to fully understand things like Benzodiazaphine tolerance development, PWS, and withdrawal symptom manifestations over time.

[[cs...]]

I took a look at the circuit level, briefly.

 

I can see that interdose withdrawal can cause problems (example). Do short acting benzos cause more problems in that regard ? I can see why they would. On the other hand, the neuroadaptations can become more 'complete'. It's obvious that clonazepam causes some of those circuit problems too, taking it once a day. Since I was on lorazepam, anyway. And yet splitting is an issue at best.

 

In a nutshell: clonazepam is not a 'calming tablet', and it doesn't feel 'GABAergic'. Many things, that thalamic reticular nucleus thingy and consequences, very high potency benzo binding to areas other benzos do not bind to, alterations in the serotonergic/cholinergic systems/GCPRs, hormones ?

It looks like it rewired the circuits after long term use, and that it's to be important to function well physically to get off well !

 

Hi Liberty,

I rapidly developed further tolerance even after i started splitting.  I was about to increase TDD (total daily dose) but then found help.  I agree with the doctor’s assessment of my case.  I was at a requirement level of 50% more of lorazepam than i was taking,  which manifested itself as tolerance.  As you know that is basically what i converted to in librium.

 

I will try to close the loops on the understanding in this area in a later section.  In addition i will include more useable information on how to effectively taper according to the model dynamics.  The next section will  not have this circuit level description of what happens with short acting Benzodiazaphines. 

 

I do think that the lorazepam’s effects on your GABAaRs itself has long since reverted.  We can never be sure.  It’s just what the model is telling me. The lorazepam destabilized and severely stressed your circuit level neuroadaptive mechansims and when this happens, as you said above, neurotransmiiter and neuromodulator levels, all those knobs and switches, and the mechansims of homeostatic plasticity adjust to try to keep the circuits physiologically functioning.  And they adjust radically.    Just because the lorazepam is out of your body does not mean that these adaptive plastic disturbances automatically revert.  They do not.  They are plastic and if there are reinforcing loops like negative stress, these plastic changes have a very difficult time returning to “normal”.    This is precisely why even after complete Benzodiazaphine washout , PWS can remain for quite a long time.  Adaptive mechansims need the right environment to settle down and regain resiliency.

 

Obviously you know that the clonazepam is not helping.  The good news is plastic changes can and do revert. There is no permanent damage. 

 

Regarding closing the loop on this topic, just a preview: Intracellular proceses are driven in part by feedback from extracellular inputs.  If you pound a receptor it is those many many complex intracellular processes and signaling proteins that regulate the receptor trafficking, exocytosis, endocytosis, dephosphorylation, phosphorylation , etc at the molecular and gene regulatory level. 

 

If you pound the receptor sporadically once a day, then washout, there is the same type of instability at this micro (cell) level, as there is a the higher circuit level (macro).  The body does not like instability of any sort and adaptive mechanisms will be stretched thin to try to accomodate.  I don’t know this for sure, but i would think that the micro cellular adaptation mechanisms have a hard time adapting to this on-off-on-off, much moreso than a constant “on”.  What i do know for sure, is that at the circuit level adaptive mechanisms are far more strained with the on-off-on-off non steadystate condition than they are with the steady state.  Homeostasis seems to be the once constant driving force from the biological micro all the way to the macro.

 

Perhaps at some point the research will be there for differences in intracelluar adaptive receptor level mechansims of chronic steady state vs. chronic nonsteady state benzos.    But keep in mind, the body always seeks homeostasis, and the further you are away from that, the more the adaptive mechanisms have to accomodate, and the more they have to accomodate, the more susceptible they are to failing at that accommodation, and when they fail the body tends towards hyperexcitability, which i will get into at a later time.

 

I hope this helps.

 

Dm123