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

[[li...]]

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

 

No, (now without all the quotes):

 

First two weeks 2 times 2 mg lorazepam a day.

The two weeks after than 1.5 mg twice a day.

Then slowing down, and when the sedative properties disappeared it was just a crude, weak and short acting drug, barely holding the withdrawl of clonazepam at bay. At some point I tried taking it three times a day but it was a mess and there was no sense in going on, obviously.

 

(and yes, circuit level: if you think in terms of neural pathways that was obviously messed up, receptors too)

 

'“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.'

No, I was referring to the lorazepam itself. Lorazepam minus hypnotic, amnestic, sedative properties. (In short: what 'we' did , was nuts)

 

'I do think that the lorazepam’s effects on your GABAaRs itself has long since reverted' I'd be very surprised. I did take lorazepam once a couple of months after the 'experiment' and it was crude. I may have taken it once in 2016 or 2017 and it was less crude, but not what it once was and much shorter acting.

 

There is neuroplasticity, but that's not always good !

 

The circuit level, does that include a reasonably smooth working body rather than being a dysfunctional wreck ? (putting it bluntly)

[[li...]]

Okay ...

 

Since I had some persistant and very unpleasant side effects of that exercise session on Sunday ...

Today I took a fraction of one dose/tablet of solifenacin, what had been prescribed for a supposed ´bladder problem´ by that idiot GP. The acute effects are rather powerful. These effects shouldn´t happen.

 

For one thing, there is acute and moderate to strong relaxation in the skeletal muscles ! As a reminder, lorazepam has ´normal´ but strong muscle relaxing effects. For as far as I know the muscle relaxing effects of clonazepam depend on its antimyoclonic properties, which are not blocked by GABA antagonists but are blocked by serotonin antagonists (https://www.ncbi.nlm.nih.gov/pubmed/520416). That seems like a puzzle.

 

Note solifenacin: Ki values of solifenacin for human muscarinic M1, M2, M3, M4 and M5 receptors were 26, 170, 12, 110 and 31 nM, respectively (https://www.ncbi.nlm.nih.gov/pubmed/17202659)

´M1, M2, M3, M4 and M5 receptors were 26, 170, 12, 110 and 31 nM, respectively. ´(https://www.ncbi.nlm.nih.gov/pubmed/17202659)

I know I shouldn´t mess with this, just one dose.

 

[[cs...]]

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

 

No, (now without all the quotes):

 

First two weeks 2 times 2 mg lorazepam a day.

The two weeks after than 1.5 mg twice a day.

Then slowing down, and when the sedative properties disappeared it was just a crude, weak and short acting drug, barely holding the withdrawl of clonazepam at bay. At some point I tried taking it three times a day but it was a mess and there was no sense in going on, obviously.

 

(and yes, circuit level: if you think in terms of neural pathways that was obviously messed up, receptors too)

 

'“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.'

No, I was referring to the lorazepam itself. Lorazepam minus hypnotic, amnestic, sedative properties. (In short: what 'we' did , was nuts)

 

'I do think that the lorazepam’s effects on your GABAaRs itself has long since reverted' I'd be very surprised. I did take lorazepam once a couple of months after the 'experiment' and it was crude. I may have taken it once in 2016 or 2017 and it was less crude, but not what it once was and much shorter acting.

 

There is neuroplasticity, but that's not always good !

 

The circuit level, does that include a reasonably smooth working body rather than being a dysfunctional wreck ? (putting it bluntly)

 

No, not all Neuroplasticity is good.  Hebbian plasticity must constantly be reigned in by homeostatic plasticity.  Something i will get into later.

 

Regarding circuit level and physiological function (working body vs. dysfunctional wreck) the next positing below begins to unravel how the two are connected in a scientific way.  Neural circuits and homeostasis is where a large part of “it” is at when talking about Benzodiazaphine tolerance, wd and PWS.

[[cs...]]

Neural circuits Dynamics in the context of the Benzodiazaphine model:  PART 2

 

Who cares about how neural circuits are supposed to function anyways. What does this have to do with withdrawal, tolerance, and PWS??!

 

((((A surrogate for Neural Circuits Modules 5-9)))))

 

Picking up from where we left off in part 1 (page 64)

 

 

 

 

 

 

 

8.Pick your poison: What about other drugs beyond Benzodiazaphines ?  What’s so special about benzos?

 

 

Nothing really.  They are deplorable drugs. However, they do have a penchant for causing more mischief than many of the other drug classes..  I guess one could call that “special”.  What a notable distinction this is! And there is a reason why benzodiazaphines are so mischievous.

 

 

So all of this discussion thus far goes way beyond Benzodiazaphines.  A fifth pillar called the GPCRs (G protein coupled receptors) has a profound effect on excitatory and inhibitory signaling in neurons.(Ie, the “Action potential” component system of the Benzdiazaphine model).  This GPCR pillar  includes serotonin, dopamine and acetylcholine, and more.  It’s not just about GABA and glutamate and Benzodiazaphines when we enter the realm of pharmaceutically induced post withdrawal syndromes.  It’s a matter of what disrupts postsynaptic inhibitory and/or excitatory signaling. Any drug that acts on the CNS in this manner has the propensity to knock out a pillar.  And this is precisely what induces feedback loops and other pillars to destabilize.  And once one pillar is down we now know that there is an  ‘overstretched” compensation or accommodating effort required to maintain neural circuit physiological function.  And once multiple pillars start to destabilize, those knobs and switches are no longer very effective at maintaining homeostasis in circuit function.. And we can feel very ill at even normal levels of physiological stress, as a result of this.

 

 

Any drug that can knock out pillars and start the destabilization process has the potential to cause issues post withdrawal in susceptible individuals.  Remember, we are all created differently when it comes to when we crash.  We accommodate to maintain similar neural circuit functionality during times of “normal” stress, but our circuits all will crash in a different manner and at a different point given the same type of stress (Benzodiazaphines, for example)

 

 

Now here is the kicker: GABAaRs are a very temperamental receptor, meaning that they downregulate readily (think in terms of extrasynaptic and synaptic subunit compositions, not necessarily populations) when allosterically modulated (think PAMs). And they recover very slowly on drug washout.  This is especially true if there are conformational changes in the receptor, ie the subunit configurations and distributions (synaptic vs extra synaptic) are altered.    The neural circuit now has to work with broken down dysfunctional GABAaRs.  A broken knob that’s really important.  And it is a very pervasive common and important knob that the neural circuit needs to rely on in the face of stress. And, furthermore,  the slow speed of recovery of the GABAa receptor is the thing that makes Benzodiazaphines so much more dangerous in the context of getting “stuck” in these feedback loops of the model.  Remember, the longer a pillar is down the more likely other pillars are to destabilize and the more pillars destabilized, the more profoundly the component systems are affected and the more  difficult it is to “unwind” out of the mess.  Also the more disrupted the component systems are, and the longer a pillar is down,  the more likely feedback loops ensue.  The model tells us this dynamic. 

 

 

So the receptor that makes us calm is, itself,  a very very “emotionally liable” and temperamental receptor that shouldn’t be messed around with.  Such irony.

 

 

  So there can be people who take antidepressants that most assuredly fall into PWS, but Benzodiazaphine post withdrawal is much more susceptible to  PWS because the receptor is terribly slow to recover, and because GABAaRs are so widely distributed in the CNS, and because GABAaRs profoundly affect adult neurogenesis, and because GABAaRs adversely affect intracellular Ca levels when discontinued and because GABAaRs form the most powerful and common element of the  backbone that makes neural circuits oscillate (ie, phased shifted inhibitory based firing off of neurons. Think of the simple neural circuit of neuron A and B presented earlier).  I will get a withdrawal from an antihistamine, but histamine receptors are relatively quick to reacclimate after drug washout, and protracted and deeply entrenched feedback loops are very unlikely.

 

 

Like I said, the GABAaR is a very temperamental receptor, and it should have never been messed around with in the outpatient setting.  So much for Benzodiazaphines as effective therapeutics.

 

 

 

 

 

 

 

 

 

9.Extensibility of the model, and the importance of phasic relationships and oscillators, and more questions that need to be answered…..

 

 

The model is extensible.  Pillars and components will be added.  The model is accurate, but NOT complete!!  We all know this.

 

 

  For example, with vestibular PWS dysfunction we know that the glutamatergic, GABAERGIC and GPCR pillars are involved. We also know that the stress system is involved in impeding vestibular compensation (recovery) to vestibular insults or deficits.  And we know that stress hormones affect excitatory and inhibitory postsynaptic potentials in the vestibular areas of the brain.  We know that all 4 of these 5 pillars directly act on the  neural circuit components involved in the vestibular system.  From the clinical research we know that the vestibular neural circuits can become “entrained” and we know that this is very detrimental to the normal function of neural circuits.  They are not supposed to be entrained and synchronized!!.  They are supposed to be firing out of sequence relative to one another.  Why exactly this is true is beyond the scope of this document.

 

 

    Once one understands how neural circuits are supposed to function, one can also readily understand how “entrainment” of neural circuits (synchronization) can be very detrimental to normal physiological function, and this doesn’t just pertain to vestibular neural circuits.  Many neural circuits regardless of their location and regardless of their neural, function depend on a phasic (shifted) relationship between the firing off of the neurons in the circuit..once again this is beyond the scope of this document, but, for example a basic knee reflex or basic motor movements like walking involve extensive use of inhibitory signaling in a very precise ( phasic )manner to coordinate the muscles involved in these types of activities.

We understand that Benzodiazaphines can break down the phasic firing relationship between neurons in a neural circuit by creating dysfunction in post synaptic inhibitory signaling. That’s enough to explain tolerance and withdrawal symtomatology.  But there are still many unanswered questions…..

 

 

The greater question is can Benzodiazaphines cause neural circuits be entrained to one another in certain regions of the brain (in the same way that continuous extended background motion like being on a ship can entrain vestibular neural circuits)??  And if so, why and how does this particular problem persist?  Is it the same feedback loops alluded to above?  Or is it something entirely different?  That’s where more research is required.

 

 

And these questions not only pertain to entrainment. 

 

Let’s bring this up to a whole different level.  Are other types of neural circuit “dislocations or distortions” or dysfunctions  involved in the myriad of other post withdrawal symptoms?  Are certain regions of the brain more susceptible to these “distortions” ? 

 

And if certain regions of the brain are more susceptible to these Benzodiazaphine induced circuit “distortions” does this help explain why certain PWS symptoms are much more prevalent than others (for example, persistent cognitive dysfunction as it pertains to the Hippocampal circuits , vestibular dysfunction as it pertains to the entorhinal cortex and amygdala complex, and persistent neuropathy as it pertains to the sensory circuits).

 

 

The research is certainly pointing towards metabolic and connectivity changes between neural circuits that affect oscillations between particular parts of the brain.  More Neuroplasticity!!

 

  We’ve still got a long way to go in terms of understanding the very organ that permits us to understand and think in the first place.  More irony…..

 

 

 

 

 

 

 

 

 

10.What’s so important about neural oscillations in the brain?

 

 

And you might be asking what’s so important about the phasic relationship between how neurons and circuits fire off from one another (ie, oscillators).  It gets a bit abstract here but take a look at the introduction to this research study below, which explains it very very well.  We haven’t explored this much in the way of neural circuit examples, but once one does this, it’s clear just how important oscillation is to the physiology of brain function.  The article  brings up a very valid question.  Are brain rhythms causally implicated in brain function itself?  We know at the simple single circuit level they are.  This article addresses this at a higher macroscopic level and at a level dealing with how neural circuits express themselves in terms of physiological function (this is called “emergent properties” of the neural circuit, a bit more on this later). 

 

 

We know that vestibular dysfunction clearly has entrainment (synchronization) of various brain specific regions as part of its pathophysiology. But we don’t know if Benzodiazaphine induced vestibular dysfunction in PWS has this characteristic as part of its pathology.  There is something profound going on in this area of neuroscience.  I believe that neural circuits, which depend in large part on inhibitory signaling, are susceptible to this type of  dysfunction in PWS.  Whether its entrainment, or some other “dislocation” is the bigger question. We don’t know.  We do know that brain rhythms are implicated in brain function itself.

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142861/pdf/fpsyg-02-00170.pdf

 

 

 

 

Quote

 

Physiological rhythms are ubiquitous in living organisms (e.g., Glass, 2001). In the brain, oscillations are supported by distinct neuronal elements across different spatial (dm123: ie brain region) scales (e.g., Buzsáki and Draguhn, 2004). These elements range from the single neu- ron (Hutcheon and Yarom, 2000) over neuronal circuits (e.g., Whittington et al., 1997) to thalamo-cortical and cortico-cortical networks at the macroscopic level (e.g., Lorincz et al., 2009).

 

Furthermore, brain oscillations occur in distinct frequency bands as a function of micro- and macro-network architecture (Buzsáki and Draguhn, 2004). Some aspects of brain activity can therefore be described in a simplified model as a system of hierarchically stacked neuronal oscillators, that cycle and interact at different frequencies (Buzsáki and Draguhn, 2004). But are these brain rhythms causally implicated in brain function, or do they merely reflect by-products of other, underlying mechanisms?

 

One of the computational processes that oscillations likely enable is the dynamic routing/gating of information through the synchronization of neuronal elements (Salinas and Sejnowski, 2001; Fries, 2005; Jensen and Mazaheri, 2010).

…..

 

Perception also relies on processes that enable effective selection and integration of relevant information from the vast amount of sensory inputs that is constantly bombarding our brain.

System characteristics therefore endow neuronal elements or networks to oscillate at specific frequencies, and these oscillations may implement specific processes.

 

End quote

 

 

 

 

 

 

 

 

 

 

11.So speaking of neural circuit “distortions”, what is entrainment exactly (one such possible distortion)?

 

 

Why the obsession with entrainment?  Well, it’s basically the antithesis of what oscillators do in our brain, ie the creation of  a phase shifted firing off between neurons .  And the antithesis is not good.  That means brain function is compromised and that means symptoms.  And the symptoms seem to be correlated to the areas of the brain that get entrained.  From the above citation

 

 

Quote

 

One property of oscillating elements commonly found in nature is that they are self-sustained and dynamic (e.g., Glass, 2001; Pikovsky et al., 2003). Such oscillators can be perturbed by an external force. If this force is periodic, the natural oscillation may then become syn- chronized to the periodic event. Synchronization here means that the oscillating element starts to cycle with the same period as the external force. Or in other terms, the oscillator becomes entrained or locked to the external event. In this context, synchronization, entrainment, and locking are synonymous1 (Pikovsky et al., 2003). We will use the term entrainment to denote synchronization to a rhythmic stream (or train) of external events.

 

End quote

 

 

Refer to box 1 of the same article link above,  for a lesson on entrainment.  Look at part B, and the figure where 3 initially independent oscillator “elements” (for now think of this as 3 neurons firing out of phase from one another)  slowly get synchronized to an external force.  Look at the start of the diagram all the way on the left side.  Note how the oscillator elements are all out of phase, peaking and dipping at different times relative to one another.  At the end of the diagram, all 3 oscillator elements are “in phase”,ie they have been entrained by the external force.    (Note in this simple example, all 3 oscillator elements have the same frequency, but are out of phase.  This gives rise to a population synchronized oscillator that has this same frequency.  In real life different oscillating elements have different frequencies and are out of phase, and so the population synchronized oscillator would have a frequency that is a combination of the constituents.)

 

 

This synchronization isn’t normal brain function.  In this simple example, in their original state,  2 of the 3 oscillators are out of phase with the external force, and you can see the other two slowly get pulled into synchronization with the external force.

 

 

And of what benefit is this research? 

 

We already know that entrainment in specific regions of the brain can cause certain types of vestibular function, but we don’t know if the etiology of Benzodiazaphine induced vestibular dysfunction (PWS) is based on this same distortion.  Similar symptoms can very often have different etiologies.  However, we do know that entrainment does have behavioral consequences, ie it does affect physiological function.  We don’t know exactly in what manner, except that in some areas of the brain it can cause very overt symptoms (like vestibular dysfunction).  There needs to be further research in this area.

 

Quote

 

Controlled entrainment of brain rhythms may therefore prove highly beneficial for the study of human brain oscillation. First, by generating oscillatory signatures through entrainment, we would be able to study in detail the behavioral consequences of these modulations, thereby increasing our understanding of the role of oscillations for behavior. Second, EEG-recording during controlled experimental induction of oscillations would enable the detailed study of the system’s behavior under various scenarios. Third, further research in this area may well lead to applications in rehabilita- tion or treatment of disease.

 

End quote

 

 

And here is a very important point.  The external event that’s synchronizing things must be imperceptible.  Otherwise different regions of the brain get involved (with the awareness) and these other regions of the brain can compensate for the attempted entrainment that is occurring. (Another example of adaptive compensation by the brain).    In other words, the test subject cannot be aware of the entrainment external force itself.  Anything that bypasses direct sensory input will do the job.  Biologically this has been found to be true. This is why persistent background motion (on a ship, for example) has the potential to cause entrainment in various regions of the brain.  Initially it might be quite noticeable, but after a period of time, it becomes unnoticeable, and that’s when entrainment is able to take hold.

 

 

Quote

 

Unless the external force is imperceptible, the periodicity of the external event will likely engage attentional mechanisms, such as reflexive orienting or anticipation of the next, predicable event in the event sequence (Nobre, 2001).

 

End quote

 

 

 

Thinking of neural circuit “distortions” at a higher level: emergent properties

 

And now’s a great time to discuss these neural circuit “distortions” at a higher level.  A neural circuit distortion is most easily thought of in terms of the normal phasic firing off of neurons in a neural circuit and across neural circuits.  We know a little more about entrainment, to discern what this exactly means, because entrainment is pretty much the extreme of a neatly organized phasic firing relationship.  In a sense entrainment is no phase shift at all,  so that everything is firing off together in phase.  Too perfect.  This is not good. 

 

 

There’s another side to this coin as well, and it’s something that we are going to discuss quite a bit in the next section on hebbian plasticity and homeostatic plasticity.  For now, I just want to discuss these forms of plasticity in the context of hyperexcitability. 

 

If entrainment is the boring perfect cousin of a healthy circuit, hyperexcitability would be the manic, chaotic friend who’s out of control and cannot sit still.    As we will see, homeostatic plasticity is like the brakes on a car.  It’s a set of accommodative neuroadaptive mechanisms that “absorb” perturbations to the circuit.  But it even goes further than that.  Homeostatic plasticity is basically always at work.

 

 

And here’s why:

 

  The natural inclination of a bunch of neurons connected to each other in a circuit is to strengthen their synaptic connections between them over time, providing there is input into the circuit (which is the case).  This is a very important concept.  A very simplistic way of looking at this is that “neurons wired together fire together.” But in reality, as is often the case, it’s much more involved than that.  LTP is a form of hebbian plasticity, and these types of mechanisms are driven by presynaptic and postsynaptic neuron firings.  Without homeostatic plasticity to temper or “calm down” these LTP mechanisms, they will continually unregulate synaptic strengths.  The connections between the neurons would become increasingly sensitized to inputs.  The end result would be a circuit and neurons that would fire chaotically in the form of “bursts” at the slightest input. 

 

Like entrainment, the delicate and precise phasic relationship is broken down in this case as well, but in a different manner.  And in many cases these bursts of erratic firing can be all at once (synchronous). So this is like a very sensitized manic and sporadic version of entrainment that is set off with the slightest input.  Very bad. You cannot drive a car without any brakes.  Sooner or later it will crash.

 

 

It’s no great mystery that both entrainment and hyperexcitability can result in dysfunctional physiological function that manifests itself as bad symptoms.    These symptoms can take the form of anxiety, panic attacks, vestibular issues, cognitive dysfunction, digestive issues, stress intolerance, exercise intolerance, and neuropathic pain, amongst many others.  So it should be clear now why proper function at the neural circuit level is very important to our well being.  And what about the implications of other neural circuit distortions?  This is a topic that will be discussed in the context of more useful and relevant Benzodiazaphine research in a later section.

 

 

I’m also going to discuss more on this topic about how circuits manifest themselves in physiological function ( called “emergent properties” or the emergent level of a neural circuit) a bit later as well.  This emergent level of expression that is generated by the functional interactions of large populations of neurons in many neural circuits is best understood by a simple analogy. 

 

Can one understand the function of a house(macro) by analyzing the molecular structure (micro) of the bricks used to build it?  No.  In the same way, would one expect to understand the function of collections of neural circuits (macro) in the brain, by measuring activities in individual neurons (micro)?  No. 

 

 

And if we take this up a notch and think of this in terms of the benzodiazaphine model, we have the Action Potential Dynamics component system (the micro, dealing with receptors, subunit expression , downregulation, membrane potentials, etc), and we have the Neural Circuit Dynamics component system of the  model.  Both are required to fully understand what happens to our physiological function during tolerance, withdrawal and PWS. 

 

 

I realize that this is some pretty heavy stuff…….And so we will stop for now.

 

 

 

 

 

Next up: some pretty technical stuff on homeostatic plasticity and  hebbian plasticity, and the story of The Door and a Brightly Lit Room?!!

 

[[li...]]

Very good ! It's going to take me some time to assimilate this.

 

And as a side note, I get the feeling that my brain must rewire from the past 8 years ...

[[li...]]

Of course, another way of looking at some of my issues:

 

Clonazepam dampens electrical activity in the motor cortex. ´interdose withdrawal´ (the official doa varies from to 18-12-24 hours) causes some hyperexcitability.

Add all other kinds of issues.

 

And yes, it does bind to ´unique receptors´ (put simply), quite unlike diazepam.

[[cs...]]

Very good ! It's going to take me some time to assimilate this.

 

And as a side note, I get the feeling that my brain must rewire from the past 8 years ...

 

Yes that’s a good way of putting it.  We also need to rewire the way we think about Benzodiazaphine tolerance and PWS.  We need to look beyond that GABAaR and broaden our understanding of how the brain works.  It’s a collection of neurons, not just single neurons with receptors. Emergent level is the key and homeostasis is always the goal......

 

 

I know the folks at google and many other companies are working on neural networks.  AI or Artificial Intelligence.  The human brain is so much more even at the most basic fundamental level.  Hopefully they are taking a closer look at the Design of the human brain as they try to develop ever more complex and capable neural networks.

[[Ba...]]

Wow I am feeling terrible so not clear on all this.

 

Am on ambien for sleep... dr. said to up it a bit.  Am on valium for the taper (crossed from clonopin).  I was only on a bit of clon wish had not switched.

 

Anyhow I am a wreck now-- very bad-- terror, depression, light/sound sensitivity/  losing weight/ sweaty / hopeless.

 

I take everything at night to sleep--  my main prob, tho yes, there was some anxiety and also anxiety about sleeping.

 

Is the recommendation to lower the ambien first?  I'm sorry just not absorbing anything complex at all.  But I think am the worst I have been.

 

Used to be occasionally would up ambien for sleep but then i got afraid to change anything at all so take it and get a few hours on it that is all.  Until somewhat recently I got better than that... it seems to not work the same now.

 

Lunesta would be the same prob?

 

And does the 25 lyrica do anything? So afraid to change anything, dr. said up ambien.... I don't know and would appreciate simplification for addled brain here... or pm... anything.  Thank you!

 

 

[[cs...]]

Wow I am feeling terrible so not clear on all this.

 

Am on ambien for sleep... dr. said to up it a bit.  Am on valium for the taper (crossed from clonopin).  I was only on a bit of clon wish had not switched.

 

Anyhow I am a wreck now-- very bad-- terror, depression, light/sound sensitivity/  losing weight/ sweaty / hopeless.

 

I take everything at night to sleep--  my main prob, tho yes, there was some anxiety and also anxiety about sleeping.

 

Is the recommendation to lower the ambien first?  I'm sorry just not absorbing anything complex at all.  But I think am the worst I have been.

 

Used to be occasionally would up ambien for sleep but then i got afraid to change anything at all so take it and get a few hours on it that is all.  Until somewhat recently I got better than that... it seems to not work the same now.

 

Lunesta would be the same prob?

 

And does the 25 lyrica do anything? So afraid to change anything, dr. said up ambien.... I don't know and would appreciate simplification for addled brain here... or pm... anything.  Thank you!

 

Hi Barbara, always feel free to PM me.  I know how bad it is.  I’m very sorry.

 

I am not a medical doctor but i can tell you what i had to do to get off this stuff.

You needn’t understand all the theory and clinical data in this thread at this time.  Perhaps for some other time, once you start recovering.

There’s no permanent damage.

I will be posting a TAPERING protocol at some point based on all the clinical stuff and the theory, but a summary is below.

 

Please note, once again i am not a medical doctor.

 

I was on ambien, lunesta, lorazepam and some other assorted hormones.

 

First step was to crossover to long half life benzo for the lorazepam. You have already done a crossover and are on a fairly low dose of valium. I used librium , but at this stage valium will have to do, since that is what you are on.

 

I know it is difficult but you have to get rid of the ambien.  The lunesta will not help. It’s in the same class, as you know. I found lunesta much more powerful than ambien. It will give you short term relief, and very short term blocks of rest, but nothing more and you build up tolerance to the z drugs very quickly (we all do). So you have to find a way to get off the ambien first. Don’t bother tapering the valium yet.

 

Can you talk to your doctor about increasing the valium total daily dose, spreading it over the entire day, every 8 hours on the hour to the minute, until you are stable, keep ambien steady, and then slowly getting off the ambien once you start feeling better?

 

You will most likely have to updose the valium during this process. I know its is difficult but you must think of it as a trade off for the ambien.  It would be far better being on more of the valium and doing it every 8 hours, then single dosing smaller valium and ambien all at night.  That is what is causing the problem.

 

I tapered the lunesta and ambien very quickly once stabilized. It took about a month to get stable.  The taper off the z drugs took about 3 weeks. 

 

The lyrica (or gabapentin) is fine. I am not on it, but it does not directly bind to the GABAaR. You want to avoid any and all drugs that bind directly to the GABAaR.  The lyrica should help with the hyperexcitability that you are experiencing. 

 

Right now your receptors need to heal, but at a higher level, your neural circuits are being see sawed back and forth because the serum level of the benzos is not being held constant.

 

Yoiu can help the second part (see sawing) by making the changes above and taper off the ambien first.  The steady state valium will help calm down the second part (see sawing)

 

The taper off the valium will be a much longer and slower process.

 

I do understand that you have a sleep disorder, but there are other pharmaceuticals like lyrica and gabapentin that may be able to help. I do understand that Remeron did not work out for you. I know you already know about trazadone as well.

 

It does not sound like you have a benzo wise doctor.  Is there any way that yoiu can find a doctor that is more open to Ashton style tapering with symptom based tapering included. That is the way to go on this.

 

I hope this helps.

 

Best

Dm123

[[Ba...]]

I'm sorry, not concentrating well now.  I will pm you.

But the ambien does not seem to help anything at all-- in fact when I took  it felt awful... sudden shaking/sweating/shortness of breath.

 

A little more ambien and I sleep-- that is the difference.  And then I am somewhat ok.

 

Or so it seems...  I will pm you if only so can write more later.

 

I can get more valium-- but it makes me sick it seems.  SIGH.

[[...]]

 

The lyrica (or gabapentin) is fine. I am not on it, but it does not directly bind to the GABAaR. You want to avoid any and all drugs that bind directly to the GABAaR.  The lyrica should help with the hyperexcitability that you are experiencing. 

 

Right now your receptors need to heal, but at a higher level, your neural circuits are being see sawed back and forth because the serum level of the benzos is not being held constant.

 

Yoiu can help the second part (see sawing) by making the changes above and taper off the ambien first.  The steady state valium will help calm down the second part (see sawing)

 

The taper off the valium will be a much longer and slower process.

 

I do understand that you have a sleep disorder, but there are other pharmaceuticals like lyrica and gabapentin that may be able to help. I do understand that Remeron did not work out for you. I know you already know about trazadone as well.

 

 

 

I don't know that I'd be recommending Lyrica and/or Gabapentin, and stating they're "fine".  Not everything's about avoiding GABAa receptors only, and this class of drugs comes with its own very severe side effects, including having as much dependency potential as benzos ... they can be extremely difficult to withdraw from! 

 

I'd personally caution you, Barbara, especially as you're already so symptomatic.  I hope you'll be able to find something a little more benign to help with your sleep.

[[Ba...]]

What do you think is benign?

 

I am finding the valium causes probs.  I take it and feel sweaty, trembly, etc, right after taking.

 

I can see spreading it out not just at night, tho.

 

Ambien sure helps me feel better -- a lot. 

 

Really feel the valium is bad stuff for me.

 

;(

[[...]]

Barbara, I'm sure you've tried a myriad of different things over the years to assist with your sleep problems and, obviously, the only truly benign remedies are things like guided meditations, self hypnosis and all the usual sleep hygiene tricks.  I've also read of some members having success with tart cherry concentrate, I don't know if you've tried that.  At least twice a week I'm awake the whole night and then I'll finally catch a couple hours in the early morning (such as today, I slept from 7am-9am).  Sometimes I'll put on 1/2 hour of tunes and it helps, sometimes listening to a podcast or interview will put me to sleep, sometimes I need pure quiet, and sometimes doing sudoku puzzles can also do the trick.  And sometimes, nothing works and I've learned to just accept it and let it be.  Btw, it's my physical sxs that prevent me from sleeping, it's not insomnia per se, I don't know if that's the case with you too?

 

Anyhow, not to derail this thread but please be very careful, you don't want to be messing with the big guns when your system is obviously so very fragile now.  I just fear it could bring you another whole world of problems and you won't know what's doing what.  Particularly, as you say, you previously had a bad experience using Remeron.

 

I really don't know what to say about the Valium and Ambien, I'm sorry you're having such a rough time and really hope you can find a way to make it more bearable. 

[[cs...]]

 

The lyrica (or gabapentin) is fine. I am not on it, but it does not directly bind to the GABAaR. You want to avoid any and all drugs that bind directly to the GABAaR.  The lyrica should help with the hyperexcitability that you are experiencing. 

 

Right now your receptors need to heal, but at a higher level, your neural circuits are being see sawed back and forth because the serum level of the benzos is not being held constant.

 

Yoiu can help the second part (see sawing) by making the changes above and taper off the ambien first.  The steady state valium will help calm down the second part (see sawing)

 

The taper off the valium will be a much longer and slower process.

 

I do understand that you have a sleep disorder, but there are other pharmaceuticals like lyrica and gabapentin that may be able to help. I do understand that Remeron did not work out for you. I know you already know about trazadone as well.

 

 

 

I don't know that I'd be recommending Lyrica and/or Gabapentin, and stating they're "fine".  Not everything's about avoiding GABAa receptors only, and this class of drugs comes with its own very severe side effects, including having as much dependency potential as benzos ... they can be extremely difficult to withdraw from! 

 

I'd personally caution you, Barbara, especially as you're already so symptomatic.  I hope you'll be able to find something a little more benign to help with your sleep.

 

I agree.  Gabapentin is a powerful drug, and many have run into issues on it. 

All pharmaceuticals have dangers.  I can say that she does not necessarily have to add pharmaceuticals.    She can try steady state dosing as a first step.    I also see that valium is making her ill as well, so this may not work out with valium either.  There is no easy solution, as is often the case.

 

 

 

 

 

[[li...]]

Clonazepam to diazepam is often a problem.

 

As for my condition, I get the impression that healing would have to consist of 'getting the poison out of the body'. CT or a variation. Basically, K is not a calming tablet, you need to be functioning reasonably well and gradually lowering the dose, stabilizing as you go, taking a beating during the taper process ... the last part should be absolute hell. That's not my situation, only the recollection of years ago.

 

Oh, my most recent sugegstion might suggestion I could go on diazepam while adding some solifenacin to cover for the motor pathways of clonazepam ...but that seems nuts. But up to some extent solifenacin could acutely cover for some of my physical issues ... it certainly negated some of the effects of exercise (sedation). FUBAR.

 

I'm just wondering if I should try that ... can't go on ... but I rely on sleep to be a bit functional. Full body experience. I have an idea what could be done, but getting a doc to do that ...

 

'Yes that’s a good way of putting it.  We also need to rewire the way we think about Benzodiazaphine tolerance and PWS.  We need to look beyond that GABAaR and broaden our understanding of how the brain works.  It’s a collection of neurons, not just single neurons with receptors. Emergent level is the key and homeostasis is always the goal.....' In that sense I'm so ****** up, if only I could go back a few years ago.

 

Patients right in the NL ? Bluntly: doctors pick their patients, and sometimes they pick on us. Patients' rights and NL, something like an oxymoron.

[[Ba...]]

Could another benzo be substituted forvalium?

back to clonopin ?  or ativan or restoril?  If val makes me sick can one switch to restoril?

 

Am lying here after 2 hrs sleep tremliing/sweaty in teh dark.

 

Also would addiction dr. help if mine is not so good?  (heis not a member of americ society of addiction medicine I noticed).

 

thx

[[Fr...]]

Barbara

I can’t tell by your signature but it seems as if you tapered k to quickly and then tried to cross to V you may be in pretty severe withdrawal and needed more V to stabilize before continuing your taper. I know when I was dosing once or twice a day I would get sick when taking the med. I found for me if I did not take a steady state of the med every 8 hours once I finally did take it would hit me hard and make me sick. Our CNS is so sensitive right now that anything dramatic up or down affects us horribly. To only dose once a day until you are fairly recovered can be very hard and you make things worse. I split my dose to three times a day and got of the Ambien and things got better. My guess is you may need a considerable amount more Valium than you are on and dosing 3 x a day to get stable or you could possibly try Librium.

[[Ba...]]

Barbara

I can’t tell by your signature but it seems as if you tapered k to quickly and then tried to cross to V you may be in pretty severe withdrawal and needed more V to stabilize before continuing your taper. I know when I was dosing once or twice a day I would get sick when taking the med. I found for me if I did not take a steady state of the med every 8 hours once I finally did take it would hit me hard and make me sick. Our CNS is so sensitive right now that anything dramatic up or down affects us horribly. To only dose once a day until you are fairly recovered can be very hard and you make things worse. I split my dose to three times a day and got of the Ambien and things got better. My guess is you may need a considerable amount more Valium than you are on and dosing 3 x a day to get stable or you could possibly try Librium.

 

Wow, I thought my taper was super slow.  In fact, adding the ambien and valium total I'm above what I was on clonopin ;(  So 1 3/4 years later and feeling worse.  I am off the mirtazapine, which I CT which upset everything.  I did not know it would do that, obviously.

 

I can split up the valium dose, no problem, esp as it seems to make me feel sick.  But ambien seems to help a little.  If I were to increase a little as dr. said, I would feel human the next day as would get some sleep.

 

I kind of feel the valium is toxic to me. 

[[Fr...]]

Go with your gut with what  you feel is best. Everyone has a different experience but I believe we know what is best for us deep down. I am just sharing what worked for me. I have a very long way to go but am better than I was a year ago. Progress is so slow.

[[Ba...]]

Barbara, I'm sure you've tried a myriad of different things over the years to assist with your sleep problems and, obviously, the only truly benign remedies are things like guided meditations, self hypnosis and all the usual sleep hygiene tricks.  I've also read of some members having success with tart cherry concentrate, I don't know if you've tried that.  At least twice a week I'm awake the whole night and then I'll finally catch a couple hours in the early morning (such as today, I slept from 7am-9am).  Sometimes I'll put on 1/2 hour of tunes and it helps, sometimes listening to a podcast or interview will put me to sleep, sometimes I need pure quiet, and sometimes doing sudoku puzzles can also do the trick.  And sometimes, nothing works and I've learned to just accept it and let it be.  Btw, it's my physical sxs that prevent me from sleeping, it's not insomnia per se, I don't know if that's the case with you too?

 

Anyhow, not to derail this thread but please be very careful, you don't want to be messing with the big guns when your system is obviously so very fragile now.  I just fear it could bring you another whole world of problems and you won't know what's doing what.  Particularly, as you say, you previously had a bad experience using Remeron.

 

I really don't know what to say about the Valium and Ambien, I'm sorry you're having such a rough time and really hope you can find a way to make it more bearable. 

 

Yes I've never been able to tolerate ADs, really.  I was feeling so down I tried the mirtazapine which, well, obliterated my CNS.

 

I do not think I can get off this stuff without something as:  no sleep.  I don't heal with no sleep.  It is not physical pain keeping me up it is my brain is fried. ;(

 

Did try tart cherry in the past, did nothing.  I have tried some supplements but at this point nothing is going to help I don't think. 

 

I guess an addiction dr. would not shed any light on this? I have an old psychiatrist who would rx anything and everything (got me into this), then local family dr. who rxed mirtazapine.  Then he left some really lame woman dr. knows nothing but continues the valium........ long story.

 

I really could use a good dr. to work with.  Someone suggested this other dr. was benzowise-- went to him.  He is the one said up the ambien after asking me could I take flexoril (I can try again, but it upset stomach)... rozarem (tried long ago gave nightmares)... Saphris  (put me to sleep once or twice then caused intense back pain)...... etc.  So there is not a lot I can take.

 

He also suggested gabapentin or lyrica.  Think it may help a bit but in doses to put me to sleep I become a zombie.

 

I don't see a way to do this!  Would I feel better just staying on?? omg...

 

So you have to find a way to get off the ambien first. Don’t bother tapering the valium yet.

 

Edit: Fixed quote box

[[cs...]]

Barbara

I can’t tell by your signature but it seems as if you tapered k to quickly and then tried to cross to V you may be in pretty severe withdrawal and needed more V to stabilize before continuing your taper. I know when I was dosing once or twice a day I would get sick when taking the med. I found for me if I did not take a steady state of the med every 8 hours once I finally did take it would hit me hard and make me sick. Our CNS is so sensitive right now that anything dramatic up or down affects us horribly. To only dose once a day until you are fairly recovered can be very hard and you make things worse. I split my dose to three times a day and got of the Ambien and things got better. My guess is you may need a considerable amount more Valium than you are on and dosing 3 x a day to get stable or you could possibly try Librium.

 

Very well said Jlav.  Jolting the system causes those adaptive responses that i mentioned in the Parts 1 and 2 above.  Those make us feel very very ill because neuroadaptation always involves adjusting the knobs and switches or neurotransmitters and neuromodulators.

WHen ACh, DA and serotonin levels adjust to accomodate, they adjust to insure the circuits continue to fire off as they were designed. The changes in neurotransmitter levels affect other areas and regions of the brain and this makes us feel “not right”

 

Also at some point the neuroadaptive mechanisms start to fail and this makes the circuit activity become unwieldy. This also makes us ill.

 

EDIT ADD: I just wanted to add that its the uneven dosing that causes stress on the circuits and causes them to become entrained, hyperexcitable, etc (i call these neural circuit distortions, which are any neural circuit function that is no longer “normal” or phasic).  Neural circuit distortions account for a large part of our symptoms. I wrote a piece on this a while back and will integrate it into the thread blog.

[[cs...]]

Barbara, I'm sure you've tried a myriad of different things over the years to assist with your sleep problems and, obviously, the only truly benign remedies are things like guided meditations, self hypnosis and all the usual sleep hygiene tricks.  I've also read of some members having success with tart cherry concentrate, I don't know if you've tried that.  At least twice a week I'm awake the whole night and then I'll finally catch a couple hours in the early morning (such as today, I slept from 7am-9am).  Sometimes I'll put on 1/2 hour of tunes and it helps, sometimes listening to a podcast or interview will put me to sleep, sometimes I need pure quiet, and sometimes doing sudoku puzzles can also do the trick.  And sometimes, nothing works and I've learned to just accept it and let it be.  Btw, it's my physical sxs that prevent me from sleeping, it's not insomnia per se, I don't know if that's the case with you too?

 

Anyhow, not to derail this thread but please be very careful, you don't want to be messing with the big guns when your system is obviously so very fragile now.  I just fear it could bring you another whole world of problems and you won't know what's doing what.  Particularly, as you say, you previously had a bad experience using Remeron.

 

I really don't know what to say about the Valium and Ambien, I'm sorry you're having such a rough time and really hope you can find a way to make it more bearable. 

 

Yes I've never been able to tolerate ADs, really.  I was feeling so down I tried the mirtazapine which, well, obliterated my CNS.

 

I do not think I can get off this stuff without something as:  no sleep.  I don't heal with no sleep.  It is not physical pain keeping me up it is my brain is fried. ;(

 

Did try tart cherry in the past, did nothing.  I have tried some supplements but at this point nothing is going to help I don't think. 

 

I guess an addiction dr. would not shed any light on this? I have an old psychiatrist who would rx anything and everything (got me into this), then local family dr. who rxed mirtazapine.  Then he left some really lame woman dr. knows nothing but continues the valium........ long story.

 

I really could use a good dr. to work with.  Someone suggested this other dr. was benzowise-- went to him.  He is the one said up the ambien after asking me could I take flexoril (I can try again, but it upset stomach)... rozarem (tried long ago gave nightmares)... Saphris  (put me to sleep once or twice then caused intense back pain)...... etc.  So there is not a lot I can take.

 

He also suggested gabapentin or lyrica.  Think it may help a bit but in doses to put me to sleep I become a zombie.

 

I don't see a way to do this!  Would I feel better just staying on?? omg...

 

So you have to find a way to get off the ambien first. Don’t bother tapering the valium yet.

 

Edit: Fixed quote box

 

Hi Barbara,

 

I responded to your PM.  The only thing that helped me was to even out the serum levels.  A benzo wise doctor would have to titrate up (go up) on the valium or Librium dose until you start getting some rest. This might take quite a bit more. For me it was 50% over the table conversion level.

 

Once you are stable and getting some rest, you would taper off the ambien, which i believe is causing a lot of the problems and making things worse.

 

It won’t be easy sailing all the way, but the first step is to get you stable and resting. 

 

Calming the nervous system 24/7 will lower your stress hormone levels, which are escalating right now during the day.

 

This will help with the night in addition to the steady state calming the circuit behavior down.

 

You will most likely have to titrate up during the first week to 10 days.  And then stay stable with ambien for a month. Then try cutting the ambien first over the next month.  Then once stable you can start the slow symptom based taper off the valium.  This will be slow.

 

You will need to work with your doctor on this because it involves a lot of trial and error and dosage modification.

 

There’s not permanent damage that has occurred.  You just need the right setting and environment in which to give your body time to heal.

 

Also, please see Jlav’s post above as well.  I don’t know if you are intrinsically getting sick from the valium or if it is from the single dosing, but the only way you can find out is to try the procedure above.

 

Best

Dm123

[[li...]]

First a comment to what dm123 wrote:

 

''EDIT ADD: I just wanted to add that its the uneven dosing that causes stress on the circuits and causes them to become entrained, hyperexcitable, etc (i call these neural circuit distortions, which are any neural circuit function that is no longer “normal” or phasic).  Neural circuit distortions account for a large part of our symptoms. I wrote a piece on this a while back and will integrate it into the thread blog.

 

That can happen, in my view that doesn't always happen. Clonazepam has a long half life and a long duration of action. It's complicated !

 

Barbara, I'm not sure about the timeline of your K taper.

 

35 years is a long time. But anyway, you had gotten to a very low dose. I suspect it was a mistake to switch to diazepam. And mixing V and K ? many people who went from K to V got into trouble.

My guess is, about half. I'm not sure what's best. Usually one should take one benzo at a time. And as a general rule, as few drugs as possible.

I know that K can be incredibly rough at very low doses. Maybe it had been better if you had continued tapering or had forced yourself off.

 

[[cs...]]

First a comment to what dm123 wrote:

 

''EDIT ADD: I just wanted to add that its the uneven dosing that causes stress on the circuits and causes them to become entrained, hyperexcitable, etc (i call these neural circuit distortions, which are any neural circuit function that is no longer “normal” or phasic).  Neural circuit distortions account for a large part of our symptoms. I wrote a piece on this a while back and will integrate it into the thread blog.

 

That can happen, in my view that doesn't always happen. Clonazepam has a long half life and a long duration of action. It's complicated !

 

Barbara, I'm not sure about the timeline of your K taper.

 

35 years is a long time. But anyway, you had gotten to a very low dose. I suspect it was a mistake to switch to diazepam. And mixing V and K ? many people who went from K to V got into trouble.

My guess is, about half. I'm not sure what's best. Usually one should take one benzo at a time. And as a general rule, as few drugs as possible.

I know that K can be incredibly rough at very low doses. Maybe it had been better if you had continued tapering or had forced yourself off.

 

Yup. 

 

There are many causes for hyperexcitability.  I wasn’t being exclusive to the nature of short acting benzos.

 

The circuit will try to accommodate on any Benzodiazaphine.  Any benzo.  It will need to accomodate much further with nonsteady state serum levels.  All Benzodiazaphines require the circuit accommodates even when they are “working  fine.”  The accommodation increases as tolerance is reached, and the accommodation increases further with short half life single dosed benzos.  This is how we are designed.  Accommodation is also greater with fast onset of action.  There are a lot of other factors.  My point was simply that nonsteady state dosing is increasing the amount of neuroadaptation required for the circuit to maintain homeostatic function.

 

Those other neurotransmitters have to adjust to compensate for the tolerance and this occurs with all benzos, even valium and librium and clonazepam. Hyperexcitability is not exclusive to short acting benzos.  And one can become tolerant to valium and librium as well!

 

The main question you need to ask at the end of the day is “Is my protocol and drug adding to the requirements placed on the neuroadaptive response system ?”

 

That’s it.

 

And if it is adding to the requirements what can I do to alleviate this?

 

[[li...]]

dm123,

 

Do you have a definition of 'circuit' in this context ?

 

And I get the feeling that getting off this drug would increase my allostatic load ...