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

[[cs...]]

Module 4(PART 3) of the Neural Circuits paper is presented below.  The presentation  of  neural circuits will help us understand the homeostatic plasticity component of the benzodiazaphine model.

 

Module 4 on brain neuroanatomy, lays the foundation for understanding how basic neural circuits work.

 

A summary of all of the model’s components and pillars is on page 40 of this blog thread.

 

 

=======================================================

 

4. Module 4(PART 3): Introduction to brain architecture and brain neuroanatomy, microcircuits, and a brief introduction to some neural brain circuits   

 

 

 

 

(4.6)Basic brain architecture: the thalamus

 

 

 

 

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

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

 

The next to the last stop on the brain circuit for motor control and reward lies in the thalamus, which is a very complex area of the brain.  The output nuclei of the basal ganglia pass the data to the thalamus.  Not surprisingly, the thalamus has several functions such as relaying of sensory signals, including motor signals, to the cerebral cortex,and the regulation of consciousness, sleep, and alertness.

 

The relaying of sensory and motor signals to the cerebral cortex will be examined in a later module relative to a complete motor neural circuit example involving a simple knee reflex action.

We know that the thalamus receives data from the output nuclei of the basal ganglia , i.e. From the GPi, from the preceding discussion.  Some other connections are listed below. It’s a very complex hub region of the brain.

 

 

 

 

Quote

The thalamus is manifoldly connected to the hippocampus via the mammillo-thalamic tract, this tract comprises the mammillary bodies and fornix.[11]

 

The thalamus is connected to the cerebral cortex via the thalamocortical radiations.[12]

 

The spinothalamic tract is a sensory pathway originating in the spinal cord. It transmits information to the thalamus about pain, temperature, itch and crude touch. There are two main parts: the lateral spinothalamic tract, which transmits pain and temperature, and the anterior (or ventral) spinothalamic tract, which transmits crude touch and pressure.

End quote

 

 

 

 

We will focus on the connections to the cerebral cortex (frontal lobe), as this is the final stop along the brain circuit for the motor neural circuit and the risk reward circuit.  The spinothalamic  tract is important as part of the thalamus connections,  in that it is the sensory pathway from the skin to the thalamus.

 

The thalamus is a very very complex region of the brain.  Below are 3 subregions of the thalamus, 2 of which are primarily involved in movement control and the third involved in many different functions including interactions with the limbic system, and inhibition of the dorsal striatal movements via feedback.  This is described in the next module.

 

 

 

 

 

 

(4.6.1)Basic brain architecture(thalamus): the ventrolateral thalamus (VTh or VL) (motor control)

 

 

 

This is a subregion of the thalamus, and is the next to last stop on the motor circuit on the way to the cerebral cortex.  Walking provides excellent stimulation of this motor circuit that passes through the VTh.  There is a subregion of the VTh called the thalamic reticular nucleus, but it’s main function is to modulate information from other nuclei in the thalamus.  It does not project out to the cortex, and thus we won’t be focusing on this region in our neural circuit analyses.  Recent research indicates that it might have nuclei that lie in the dorsal region of the thalamus (i.e., the medial dorsal thalamus).

 

 

 

 

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

 

As we have already seen:

 

 

Quote

It receives neuronal inputs from the basal nuclei which includes the substantia nigra and the globus pallidus (via the thalamic fasciculus). It also has inputs from the cerebellum (via the dentatothalamic tract).

It sends neuronal output to the primary motor cortex and premotor cortex.

The ventral lateral nucleus in the thalamus forms the motor functional division in the thalamic nuclei along with the ventral anterior nucleus. The ventral lateral nucleus receives motor information from the cerebellum and the globus pallidus. Output from the ventral lateral nucleus then goes to the primary motor cortex.[1]

 

The function of the ventral lateral nucleus (ventrolateral thalamus) is to target efferents including the motor cortex, premotor cortex, and supplementary motor cortex. Therefore, its function helps the coordination and planning of movement. It also plays a role in the learning of movement.[2]

 

A lesion of the VL has been associated with synesthesia.[3]

 

End quote

 

“This study on the activity of the ventrolateral thalamus (VL) in the walking cat was prompted by the fact that during locomotion the activity of the target of VL projection—the motor cortex—changes periodically in the rhythm of locomotor movements”:

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349693/

 

Signals from the ventrolateral thalamus to the motor cortex during locomotion

Vladimir Marlinski, Wijitha U. Nilaweera, [...], and Irina N. Beloozerova

 

 

 

 

 

(4.6.2)Basic brain architecture(thalamus): the ventral anterior nucleus (VA) of the thalamus (motor control)

 

 

 

The VA acts with the VTh in motor control.  It projects to the premotor cortex, which is involved with the planning of movement, and provides necessary feedback to the basal ganglia for motor control.

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

 

 

 

 

Quote

The ventral anterior nucleus (VA) is a nucleus of the thalamus. It acts with the anterior part of the ventral lateral nucleus to modify signals from the basal ganglia.[1]

 

The ventral anterior nucleus receives neuronal inputs from the basal ganglia. Its main afferent fibres are from the globus pallidus. The efferent fibres from this nucleus pass into the premotor cortex for initiation and planning of movement.[2]

 

It helps to function in movement by providing feedback for the outputs of the basal ganglia.[3]

End quote

 

 

 

 

 

 

(4.6.3)Basic brain architecture(thalamus):  dorsomedial nucleus of the dorsal thalamus (medial dorsal thalamus) (limbic interaction, memory, planning and inhibition of dorsal striatal movement; interacts with PFC)

 

 

 

This brain region interacts with the limbic system and also is involved with the planning (PFC)  and inhibition of movements from the dorsal striatum complex that was discussed earlier

 

This region will be explored in a later module in combination with the ventral striatum circuitry.

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

 

 

Quote

 

It is believed to play a role in memory.[1]

It relays inputs from the amygdala and olfactory cortex and projects to the prefrontal cortex and the limbic system and in turn relays them to the Pre-Frontal Association Cortex. As a result, it plays a crucial role in attention, planning, organization, abstract thinking, multi-tasking, and active memory.

 

While both the ventral and medial dorsal nuclei process pain, the medial dorsal nucleus bypasses primary cortices, sending their axons directly to secondary and association cortices. The cells also send axons directly to many parts of the brain, including nuclei of the limbic system such as the lateral nucleus of the amygdala, the anterior cingulate, and the hippocampus. This part of the sensory system, known as the non-classical or extralemniscal system is less accurate, and less detailed in regards to sensory signal analysis. This processing is known colloquially as "fast and dirty" rather than the "slow and accurate" system of classical or lemniscal system. This pathway activates parts of the brain that evoke emotional responses.

End quote

 

 

To get an idea of what damage to this area can cause see this link

 

https://en.m.wikipedia.org/wiki/Korsakoff%27s_syndrome

 

[[Re...]]

That is great, dm123.  However, the link on Korsakoff syndrome is quite depressing.... boooo to Korsakoff!!!

 

-RST

[[li...]]

QUOTING

 

'The benzodiazaphine withdrawal model thus far has 3 major components to it:

 

1.  The action potential dynamics at the individual neuron level.  This is directly affected by the stress system (via LTP and LTD), the glutamatergic system, the GABAergic system, as well as a number of “other systems” that have not been presented yet.

 

2.  The neurogenesis component, which accounts, in part, for benzodiazaphine PWS.  Neurogenesis  initially can be destabilized by dysfunction in the GABAergic system (alcohol or benzodiazaphines; see the alcohol study referred to in an earlier post, one of many references in this area) and perpetuated through the negative stress system.Neurogenesis is directly affected by the glutamatergic, GABAergic and stress systems, as well as many other different neurogenic modulators (including serotonin) that were briefly discussed in the Neurogenesis (PART 1) post above.

 

3.    The neuroplasticity overlay, which includes neural circuit dynamics, and homeostatic plasticity, as well as hebbian plasticity (LTP and LTD; note this is not the same as non-hebbian glutamatergic LTP which can be associated with PWS under abrupt withdrawal).  Neuroplasticity is also affected by the stress system, the GABAergic system, and the glutamatergic system, as well as many many (the list is huge!)different neuromodulators.

 

 

 

The 3 major components above are affected by benzodiazaphines through the 3 major mechanistic systems or “pillars” alluded to above (reduced to 3 for simplicity):

 

1.    The glutamatergic system,

 

2.  the GABAergic system, and of course

 

3.  the stress system. 

 

 

What’s interesting, and what makes the model dynamics so complex,  is that each of these three pillars affect one another.

 

Destabilizing a pillar (for example, chronic  benzodiazaphine use directly destabilizes the GABAergic system) has the potential to throw the entire system off, and the stress system can perpetuate the dysfunction not only through further aberrant neurogenesis, but through its direct effects on the other two systems.'

 

I'm screwed.

 

I was never good with pills. I never had an anxiety disorder, but to put it simple: the balance between GABA and glutamate was never in my favor. Elevated treshold for falling asleep, slower healing rate, depending on sleep for recovery etc.  I don't see the sedating antipsychotics and antidepressants working for me. Let's call it 'genes'.

 

Whacked by lorazepam, clonazepam, a little diazepam, chronic stress. Real damage to my health by doctor's actions. I just don't see me getting things fixed with librium and sedating antidepressants, especially while I have all these untreated health problems (iatrogenic, so I don't think I can get it fixed, and some problems are just ridiculous).

 

Everybody heals. Really ?? I've been thinking about CT but that would be most gruesome. My relationship with clonazepam is not so positive, oversimplifying I could say that higher doses work differently than lower doses ('not a sleeping or calming tablet'). Lowering that dose is not healing, it requires stamina.

[[cs...]]

That is great, dm123.  However, the link on Korsakoff syndrome is quite depressing.... boooo to Korsakoff!!!

 

-RST

Hi RST,,

I agree.  I should have edited it out.

 

Hope things are ok

[[cs...]]

QUOTING

 

'The benzodiazaphine withdrawal model thus far has 3 major components to it:

 

1.  The action potential dynamics at the individual neuron level.  This is directly affected by the stress system (via LTP and LTD), the glutamatergic system, the GABAergic system, as well as a number of “other systems” that have not been presented yet.

 

2.  The neurogenesis component, which accounts, in part, for benzodiazaphine PWS.  Neurogenesis  initially can be destabilized by dysfunction in the GABAergic system (alcohol or benzodiazaphines; see the alcohol study referred to in an earlier post, one of many references in this area) and perpetuated through the negative stress system.Neurogenesis is directly affected by the glutamatergic, GABAergic and stress systems, as well as many other different neurogenic modulators (including serotonin) that were briefly discussed in the Neurogenesis (PART 1) post above.

 

3.    The neuroplasticity overlay, which includes neural circuit dynamics, and homeostatic plasticity, as well as hebbian plasticity (LTP and LTD; note this is not the same as non-hebbian glutamatergic LTP which can be associated with PWS under abrupt withdrawal).  Neuroplasticity is also affected by the stress system, the GABAergic system, and the glutamatergic system, as well as many many (the list is huge!)different neuromodulators.

 

 

 

The 3 major components above are affected by benzodiazaphines through the 3 major mechanistic systems or “pillars” alluded to above (reduced to 3 for simplicity):

 

1.    The glutamatergic system,

 

2.  the GABAergic system, and of course

 

3.  the stress system. 

 

 

What’s interesting, and what makes the model dynamics so complex,  is that each of these three pillars affect one another.

 

Destabilizing a pillar (for example, chronic  benzodiazaphine use directly destabilizes the GABAergic system) has the potential to throw the entire system off, and the stress system can perpetuate the dysfunction not only through further aberrant neurogenesis, but through its direct effects on the other two systems.'

 

I'm screwed.

 

I was never good with pills. I never had an anxiety disorder, but to put it simple: the balance between GABA and glutamate was never in my favor. Elevated treshold for falling asleep, slower healing rate, depending on sleep for recovery etc.  I don't see the sedating antipsychotics and antidepressants working for me. Let's call it 'genes'.

 

Whacked by lorazepam, clonazepam, a little diazepam, chronic stress. Real damage to my health by doctor's actions. I just don't see me getting things fixed with librium and sedating antidepressants, especially while I have all these untreated health problems (iatrogenic, so I don't think I can get it fixed, and some problems are just ridiculous).

 

Everybody heals. Really ?? I've been thinking about CT but that would be most gruesome. My relationship with clonazepam is not so positive, oversimplifying I could say that higher doses work differently than lower doses ('not a sleeping or calming tablet'). Lowering that dose is not healing, it requires stamina.

 

Hi liberty.

 

I’m very sorry.  I don’t think anyone is screwed, even after all that I’ve read on ithis.

Time may not heal all wounds, but it’s the most powerful ally that we have going for us.

 

We don’t end up coming out of this the same (I know that I haven’t), but as I’ve always said, “different” doesn’t always mean worse.  It’s just different. 

 

    I will have some permanent scars and damage from this ordeal most likely for the rest of my life, nonetheless these things are slowly improving with time.  Nerves don’t always heal the way that we want them to, and that’s ok.  Being thankful for each new small little improvement helps us along the way.....

[[Pl...]]

QUOTING

 

'The benzodiazaphine withdrawal model thus far has 3 major components to it:

 

1.  The action potential dynamics at the individual neuron level.  This is directly affected by the stress system (via LTP and LTD), the glutamatergic system, the GABAergic system, as well as a number of “other systems” that have not been presented yet.

 

2.  The neurogenesis component, which accounts, in part, for benzodiazaphine PWS.  Neurogenesis  initially can be destabilized by dysfunction in the GABAergic system (alcohol or benzodiazaphines; see the alcohol study referred to in an earlier post, one of many references in this area) and perpetuated through the negative stress system.Neurogenesis is directly affected by the glutamatergic, GABAergic and stress systems, as well as many other different neurogenic modulators (including serotonin) that were briefly discussed in the Neurogenesis (PART 1) post above.

 

3.    The neuroplasticity overlay, which includes neural circuit dynamics, and homeostatic plasticity, as well as hebbian plasticity (LTP and LTD; note this is not the same as non-hebbian glutamatergic LTP which can be associated with PWS under abrupt withdrawal).  Neuroplasticity is also affected by the stress system, the GABAergic system, and the glutamatergic system, as well as many many (the list is huge!)different neuromodulators.

 

 

 

The 3 major components above are affected by benzodiazaphines through the 3 major mechanistic systems or “pillars” alluded to above (reduced to 3 for simplicity):

 

1.    The glutamatergic system,

 

2.  the GABAergic system, and of course

 

3.  the stress system. 

 

 

What’s interesting, and what makes the model dynamics so complex,  is that each of these three pillars affect one another.

 

Destabilizing a pillar (for example, chronic  benzodiazaphine use directly destabilizes the GABAergic system) has the potential to throw the entire system off, and the stress system can perpetuate the dysfunction not only through further aberrant neurogenesis, but through its direct effects on the other two systems.'

 

I'm screwed.

 

I was never good with pills. I never had an anxiety disorder, but to put it simple: the balance between GABA and glutamate was never in my favor. Elevated treshold for falling asleep, slower healing rate, depending on sleep for recovery etc.  I don't see the sedating antipsychotics and antidepressants working for me. Let's call it 'genes'.

 

Whacked by lorazepam, clonazepam, a little diazepam, chronic stress. Real damage to my health by doctor's actions. I just don't see me getting things fixed with librium and sedating antidepressants, especially while I have all these untreated health problems (iatrogenic, so I don't think I can get it fixed, and some problems are just ridiculous).

 

Everybody heals. Really ?? I've been thinking about CT but that would be most gruesome. My relationship with clonazepam is not so positive, oversimplifying I could say that higher doses work differently than lower doses ('not a sleeping or calming tablet'). Lowering that dose is not healing, it requires stamina.

 

Hi liberty.

 

I’m very sorry.  I don’t think anyone is screwed, even after all that I’ve read on ithis.

Time may not heal all wounds, but it’s the most powerful ally that we have going for us.

 

We don’t end up coming out of this the same (I know that I haven’t), but as I’ve always said, “different” doesn’t always mean worse.  It’s just different. 

 

    I will have some permanent scars and damage from this ordeal most likely for the rest of my life, nonetheless these things are slowly improving with time.  Nerves don’t always heal the way that we want them to, and that’s ok.  Being thankful for each new small little improvement helps us along the way.....

 

Could u elaborate on permanent scars and damage u feel from this?

Emotionally and physically?

I hope I’m not being too forward;

I’ve been asking people lately to relate what they r feeling -

as I feel I have been inundated with too many sxs at one time

I feel would be too much for any one person

too bear as they are too intense and all at one time ; as u

Already know from my prior posts

 

Thank u kindly

[[li...]]

I've been processing various scenarios over the past two days. Every single one of them has likely gruesome outcomes.

 

Pills don't fix everything. My case is not 'just the benzo'.  I was never good with pills. I already mentioned my elevated treshold for falling asleep, something I've always had. I suspect that every way I try to mess with pills will end up in a CT like situation, mild or not.

 

Has there every been a case of somewho is somewhat older, seriously kindled/sensitized, on clonazepam, under non-drug related physical distress, in poor health, who got out of that with a CT like situation and who still recovered within a few years ? Tiring myself out is the last thing I should do while tapering/getting off, I wouldn't get tired but wired.

 

Getting off while under chronic high physiological stress levels ... even if it worked, it seems the scenario's I've processed would likely result in a very different person, not in the good sense. I'm just trying to be realistic.

 

And dm123, I think you don't mind me saying this (I'm not sure whether you said it in a post or PM) about needing a benzo wise doctor: other people in this country who have looked much harder than me have not been able to find a single one who knows a bit more than the average doc. This in a country of 17 million inhabitants.

[[cs...]]

QUOTING

 

'The benzodiazaphine withdrawal model thus far has 3 major components to it:

 

1.  The action potential dynamics at the individual neuron level.  This is directly affected by the stress system (via LTP and LTD), the glutamatergic system, the GABAergic system, as well as a number of “other systems” that have not been presented yet.

 

2.  The neurogenesis component, which accounts, in part, for benzodiazaphine PWS.  Neurogenesis  initially can be destabilized by dysfunction in the GABAergic system (alcohol or benzodiazaphines; see the alcohol study referred to in an earlier post, one of many references in this area) and perpetuated through the negative stress system.Neurogenesis is directly affected by the glutamatergic, GABAergic and stress systems, as well as many other different neurogenic modulators (including serotonin) that were briefly discussed in the Neurogenesis (PART 1) post above.

 

3.    The neuroplasticity overlay, which includes neural circuit dynamics, and homeostatic plasticity, as well as hebbian plasticity (LTP and LTD; note this is not the same as non-hebbian glutamatergic LTP which can be associated with PWS under abrupt withdrawal).  Neuroplasticity is also affected by the stress system, the GABAergic system, and the glutamatergic system, as well as many many (the list is huge!)different neuromodulators.

 

 

 

The 3 major components above are affected by benzodiazaphines through the 3 major mechanistic systems or “pillars” alluded to above (reduced to 3 for simplicity):

 

1.    The glutamatergic system,

 

2.  the GABAergic system, and of course

 

3.  the stress system. 

 

 

What’s interesting, and what makes the model dynamics so complex,  is that each of these three pillars affect one another.

 

Destabilizing a pillar (for example, chronic  benzodiazaphine use directly destabilizes the GABAergic system) has the potential to throw the entire system off, and the stress system can perpetuate the dysfunction not only through further aberrant neurogenesis, but through its direct effects on the other two systems.'

 

I'm screwed.

 

I was never good with pills. I never had an anxiety disorder, but to put it simple: the balance between GABA and glutamate was never in my favor. Elevated treshold for falling asleep, slower healing rate, depending on sleep for recovery etc.  I don't see the sedating antipsychotics and antidepressants working for me. Let's call it 'genes'.

 

Whacked by lorazepam, clonazepam, a little diazepam, chronic stress. Real damage to my health by doctor's actions. I just don't see me getting things fixed with librium and sedating antidepressants, especially while I have all these untreated health problems (iatrogenic, so I don't think I can get it fixed, and some problems are just ridiculous).

 

Everybody heals. Really ?? I've been thinking about CT but that would be most gruesome. My relationship with clonazepam is not so positive, oversimplifying I could say that higher doses work differently than lower doses ('not a sleeping or calming tablet'). Lowering that dose is not healing, it requires stamina.

 

Hi liberty.

 

I’m very sorry.  I don’t think anyone is screwed, even after all that I’ve read on ithis.

Time may not heal all wounds, but it’s the most powerful ally that we have going for us.

 

We don’t end up coming out of this the same (I know that I haven’t), but as I’ve always said, “different” doesn’t always mean worse.  It’s just different. 

 

    I will have some permanent scars and damage from this ordeal most likely for the rest of my life, nonetheless these things are slowly improving with time.  Nerves don’t always heal the way that we want them to, and that’s ok.  Being thankful for each new small little improvement helps us along the way.....

 

Could u elaborate on permanent scars and damage u feel from this?

Emotionally and physically?

I hope I’m not being too forward;

I’ve been asking people lately to relate what they r feeling -

as I feel I have been inundated with too many sxs at one time

I feel would be too much for any one person

too bear as they are too intense and all at one time ; as u

Already know from my prior posts

 

Thank u kindly

 

Hi PbH

 

Yes, I’m very familiar with all that you’ve gone through.  My encouragement to you remains the same.  You were born normal as far as I know, and the issues began with the prescription drugs, and the drugs that you used were not dopamine antagonists.  Given my personal experiences with the Benzodiazaphine type drugs,  I don’t doubt that it is/was the drugs that got you into the situation, and as such I personally don’t think you have permanent damage.  But I’m not a medical doctor and I’ve never examined you first hand, so I always have to defer to the medical doctors that are directly interacting with you.  Especially in regards to medication and the details on how they want you to taper.

 

Regarding my long lasting damage, it’s the nerve pain down the legs.  RST (another BB on this forum)  and I share neuropathic pain as part of our residual symtoms, and I’ve discussed this with him quite often.    I’ve found a partial solution in standing most of the day, and walking a lot.  This desensitizes the nerves via “overuse”, and it has also helped me in recovering stamina.  It’s not a direct solution.  After a Benzodiazaphine cut,  the nerve pain increases, but then subsides back to a steady state after around 14 days post cut.  The steady state pain is slowly dissipating but nerves unfortunately take years to heal, and sometimes don’t fully heal.  I’m ok with that because, I’m thankful for the progress so far. 

 

The other slow healing item is for stress resiliency, which I’ve written about quite a bit in several of the papers in this thread.  My tolerance for stress (in particular negative stress,which I’ve discussed in detail) is not anywhere where it used to be.  I used to have a very high physiological and psychological capacity to handle enormous amounts of stress.  Not so anymore.....but it’s slowly improving as time goes on.    How we handle stress forms one of the cornerstones (pillars) of the model.  This is from both the psychological perspective (our perception of stressors) and the physiological perspective.  The model was created from my own experiences and from the knowledge I have in cellular neurophysiology and biology, and from thousands of abstracts and clinical studies.  Not surprisingly, the leg nerve pain worsens with more negative stress.  This tells us that the nervous system isn’t quite fully capable to adapting to negative stressors, and that neuropathic pain is just another manifestation of the imbalance in inhibitory and excitatory signaling.  This has been known for a long time in the cellular neurophysiology literature.

 

I don’t think the damage is “permanent”, but rather it’s going to heal to a different state from that which I started from.  That different state will not be ideal, but will be acceptable.

 

I hope this helps.

[[cs...]]

I've been processing various scenarios over the past two days. Every single one of them has likely gruesome outcomes.

 

Pills don't fix everything. My case is not 'just the benzo'.  I was never good with pills. I already mentioned my elevated treshold for falling asleep, something I've always had. I suspect that every way I try to mess with pills will end up in a CT like situation, mild or not.

 

Has there every been a case of somewho is somewhat older, seriously kindled/sensitized, on clonazepam, under non-drug related physical distress, in poor health, who got out of that with a CT like situation and who still recovered within a few years ? Tiring myself out is the last thing I should do while tapering/getting off, I wouldn't get tired but wired.

 

Getting off while under chronic high physiological stress levels ... even if it worked, it seems the scenario's I've processed would likely result in a very different person, not in the good sense. I'm just trying to be realistic.

 

And dm123, I think you don't mind me saying this (I'm not sure whether you said it in a post or PM) about needing a benzo wise doctor: other people in this country who have looked much harder than me have not been able to find a single one who knows a bit more than the average doc. This in a country of 17 million inhabitants.

 

I agree liberty, a Benzodiazaphine wise doctor is very very helpful.  I know a lot of Ashton is posted online, but it’s simply not the same.  Many of the ideas for the model began with some of the basic knowledge that I learned from the Benzo wise doctor.  With those fundamentals in place , the model developed.  For example, maintaining steady state is based on our basic cellular neurophysiology and how the body seeks homeostasis at all costs, even if it’s to the detriment of the host.(ie, worsening symptoms).  If steady state is not maintained , the body will physiologically compensate to try to restore homeostasis.  That’s why a symptom based taper is the safest approach.  If your body is hurting, it’s telling you to back off on the taper, because it’s in the process of adjusting.

 

There’s also the concept of “falling behind the curve “.  What I mean by this is that sometimes, after a cut there can be a substantial delay in symtoms worsening and then alleviating.  If one tries to cut before the symtoms hit, the serum level continues to drop and the body falls further and further behind, as the body tries to heal.  This feedback loop can cause problems because if symptoms do not adequately stabilize prior to the next cut, the physiological stress itself makes it more difficult for the body to heal from the previous cut.    This is highly dependent on the half life of the taper drug.

 

For Librium (similar to Valium half life) symptoms first erupt at around days 4-7,and serum levels mostly stabilize by day 10. Withdrawal  Symptoms persist as the body tries to acclimate to the lower serum level.  This takes around another 7 days.  So it takes generally around 17 days to fully stabilize after a small 5-10% cut.  However not all cuts are created equally.  A long stretch (bad cut) can extend out to around 26 days.  This of course varies a bit from person to person . A 26 day schedule I’ve found prevents an  “accumulating “  backlog of symptoms.  This means one can be pretty sure that he or she is not endeavoring on another cut while the body’s still healing.  This is based on symptom clearance..  If one continues to “accumulate “ a backlog of “unresolved healing”  with too frequent cuts,  it can hit a person 3 or 4 cuts down the line and result in a very very bad prolonged cut. At this point things get very confusing because it’s not the most recent cut that directly caused the problem, but rather the accumulation of a bunch of “bad” (too frequent) cuts that came to a head several weeks later.

 

The above generally aligns with the standard protocols of 5-10% every 2-4 weeks.

 

 

I agree, it is a catch 22. We are broken down by the Benzodiazaphine, yet to get off of the poison, we have to endure great physiological stress, which in and of itself can make the symtoms temporarily worse and the taper extremely difficult.  Benzodiazaphines are “paradoxical” in every sense of the word.

[[Su...]]

Thank you dm123 for the description of how you deal with long half-life benzo tapering.

I have been tapering from Xanax and have been wondering how to go about doing a taper on Valium with the half-life.  The half-life is a good news bad news kind of thing.  But at least one month between cuts seems to be what you are suggesting.  And I'm guessing that a DLMT that doesn't exceed that amount could work as well.

I understand that we are all very different in these realms and yet the experience of others' is very helpful.

And your posts are very informative for me.

Thanks again!

SS

[[Te...]]

Excellent explanation, dm123!!

[[li...]]

dm123,

 

Did your doc say anything about switching from a high dose of clonazepam to either Librium or diazepam ? Unfortunately, ´stable´ is in the past.

I´m not aware of alternate drug except for anticonvulsants, but ...

[[cs...]]

Thank you dm123 for the description of how you deal with long half-life benzo tapering.

I have been tapering from Xanax and have been wondering how to go about doing a taper on Valium with the half-life.  The half-life is a good news bad news kind of thing.  But at least one month between cuts seems to be what you are suggesting.  And I'm guessing that a DLMT that doesn't exceed that amount could work as well.

I understand that we are all very different in these realms and yet the experience of others' is very helpful.

And your posts are very informative for me.

Thanks again!

SS

 

Hi SS,

 

I’m glad it helped a bit.  A DLMT should work fine.  I’m not using one myself, but as long as you bound it by 5-10%, you should be fine.  What I have found at the very low amounts (ie, below 5mg Valium) that sensitivity does increase and moving towards the lower bound (5%) might be helpful if you encounter any difficulties.    Once you are off that last bit of Xanax your serum levels will be very nice and steady and that will help you stabilize further and you will feel better.

 

I’m glad you’ve hit a nice window.  Benzodiazaphines are insidious, And once one starts hitting windows, thisi insidious nature becomes much more apparent.  We begin to see what they’ve done to our physiology in a much much clearer fashion.  I call this the Realization phase

[[cs...]]

Excellent explanation, dm123!!

 

Thanks Terry.

 

I hope the HBP is moderating a bit.

[[cs...]]

dm123,

 

Did your doc say anything about switching from a high dose of clonazepam to either Librium or diazepam ? Unfortunately, ´stable´ is in the past.

I´m not aware of alternate drug except for anticonvulsants, but ...

 

Hi liberty,

 

He’s treated patients on very very high levels of high potency Benzodiazaphines, but since I was on lorazepam and z drugs, we discussed those the most,

 

I did a crossover in one day and the Librium was titrated up to a point where I was no longer kindling and in interdose tolerance wd.  The conversion charts are general approximations.    If you are in tolerance or kindled the actual starting dose can be quite a bit different from the conversion chart.  In my case I converted to approximately 40%  over the conversion chart.  (It’s not unheard of for patients having to go up to several 100 mugs of Librium, depending on their specific circumstances.)

 

    In general, you then stabilize for around a month at that starting total daily dose.  It’s usually broken up to dosing every 8 hours .  This is very important, especially during the first month of adjustment.    The 8 hour dosing persists until you get to levels where you can start dropping them.  For example, you might taper all equally at first , then focus on the afternoon and morning doses, finish off the afternoon dose, the morning dose, then finally work on the evening dose.  If you are doing a liquid microtaper you will have much more flexibility with this.

 

Another crossover approach, as you know, is Ashton’s piecemeal approach, slowly “trading” off some of the high potency for the Librium or Valium.  The Ashton manual has more information on how that’s done, but I think you are familiar with it.

 

For 2 mg clonazepam, the table conversion is 100 mg Librium.  If you are kindled or in tolerance you might have to add another 40%, which would work out to 140 mg Librium or more.    After stable for a month you would cut 5% and wait at least 10-14 days to assess how it goes.  After a stable 5% cut you can increase cuts up to 10% per your comfortable cutting period that I outline above.  For me it works out to 17-26 days,and at lower doses I’m doing 26 day cuts as it is a bit more challenging.

 

One last note: in my experience, the 40% overshoot was quite easy to cut after the stable 4 week initializing period I mentioned above.  After that things become more challenging, but are manageable.

 

Please note that I am not a medical doctor, and a tapering program should be performed in conjunction with working with your medical doctor.

[[Te...]]

Excellent explanation, dm123!!

 

Thanks Terry.

 

I hope the HBP is moderating a bit.

 

Thanks, dm123!!

 

I went to the nephrologist the other day, and he thinks my hbp/kidney problems are the result of excess anxiety. He prescribed Losartan, 25 mg. to start with. I was really hesitant because I'm taking a lot of other pills. But I decided to take it. I thought it would take awhile to work, but I was surprised that right away I was getting lower numbers when ALL THE TIME I'd been taking my other drugs, they didn't do a THING when anxiety hit. Looks like I've been on the wrong pills all this time. I read your info about it and also some other info that I found.

 

So thank you very much for taking the time to write the piece on Losartan. I just figured bp pills couldn't help me, and it was getting terrible. I never went anywhere for fear of an anxiety attack/high bp occurring. I think next time I will up the dose to 50 mg. But they say it takes a few weeks to get the full effect.

[[li...]]

dm123,

 

Aside from the GABA system, the GPCRs are affected in a very pronounced way with clonazepam. For me, anyway. That doc's approach is to just leave that alone ? My cholinergic, serotonergic, glutamate (?) systems are profoundly altered. And there's that motor cortex thingy.

 

'Please note that I am not a medical doctor, and a tapering program should be performed in conjunction with working with your medical doctor.' I'm glad you're not, and mine could be called Dr Mengele.

 

[[cs...]]

Excellent explanation, dm123!!

 

Thanks Terry.

 

I hope the HBP is moderating a bit.

 

Thanks, dm123!!

 

I went to the nephrologist the other day, and he thinks my hbp/kidney problems are the result of excess anxiety. He prescribed Losartan, 25 mg. to start with. I was really hesitant because I'm taking a lot of other pills. But I decided to take it. I thought it would take awhile to work, but I was surprised that right away I was getting lower numbers when ALL THE TIME I'd been taking my other drugs, they didn't do a THING when anxiety hit. Looks like I've been on the wrong pills all this time. I read your info about it and also some other info that I found.

 

So thank you very much for taking the time to write the piece on Losartan. I just figured bp pills couldn't help me, and it was getting terrible. I never went anywhere for fear of an anxiety attack/high bp occurring. I think next time I will up the dose to 50 mg. But they say it takes a few weeks to get the full effect.

 

Hi Terry that’s great.  Hopefully you can get rid of the medications that aren’t helping. 

[[cs...]]

dm123,

 

Aside from the GABA system, the GPCRs are affected in a very pronounced way with clonazepam. For me, anyway. That doc's approach is to just leave that alone ? My cholinergic, serotonergic, glutamate (?) systems are profoundly altered. And there's that motor cortex thingy.

 

'Please note that I am not a medical doctor, and a tapering program should be performed in conjunction with working with your medical doctor.' I'm glad you're not, and mine could be called Dr Mengele.

 

Hi liberty,

 

I agree.  There’s no additional adjunctive meds beyond those what we already know about.  Unfortunately no breakthroughs. Those neurotransmitters and neuropeptides do become “destabilized” during wd.  As you know, they also go off kilter during tolerance development.  I think adjunctive meds can be very helpful, especially if one does not have the time or patience for a slow taper.

 

The only adjunctive med that looks interesting to me is ketamine.  I’ve never used it , but in theory it might be able to quiet down those out of control action potentials and it does affect the neuroplastic morphology of dendrites and spines.  It’s usually administered in a hospital setting or under direct medical supervision, and is administered as a periodic therapeutic regimen. 

 

[[li...]]

I forgot to ask about the affinity of Librium for the various GABAA subunits, and that goes for the metabolites as well. I know of only one source that claim affinity for alpha 3, but I haven´t seen proper documentation.

 

I recall that the various properties of clonazepam (including GABAB) cause different effects (postsynaptic, presynaptic, etc) on the action potential, but that that approach basically states it´s something you´ll have to live (?) with ?

 

I´m dealing with other physical issues as well, but I already mentioned that so I´ll leave it at that.

[[li...]]

As a note: early 2016 I lasted 7-9 days on diazepam, early 2017 2.5 days till it became quite apparent that it wasn't going to work.

 

Issue: CNS and the rest of the body.

 

In 2016 and 2017 I crashed. I knew my health was deteriorating, but I did find out how badly way too late. One of the properties of K, it can reduce one's suffering ...

They really ****** me up. So that leaves some questions about Librium.

 

GP (medical errors): I know a little bit of everything, and such a person is supposed to handled almost all health issues ... and then the lying and witholding of information ... a 2010 projection estimated that it would take 25 years to fix the issue of doctors way of dealing with medical errors. Could take more.

[[cs...]]

I forgot to ask about the affinity of Librium for the various GABAA subunits, and that goes for the metabolites as well. I know of only one source that claim affinity for alpha 3, but I haven´t seen proper documentation.

 

I recall that the various properties of clonazepam (including GABAB) cause different effects (postsynaptic, presynaptic, etc) on the action potential, but that that approach basically states it´s something you´ll have to live (?) with ?

 

I´m dealing with other physical issues as well, but I already mentioned that so I´ll leave it at that.

 

No, I don’t have affinities for the subunits for various Benzodiazaphines.  No reliable resources that I’ve found.  Just that one that we know about already::

 

Moderate A3 affinity: Alprazolam, Adinazolam, Estazolam, Chlordiazepoxide, Clorazepate, and Flurazepam.

 

 

Unfortunately there’s no perfect  replacement for clonazepam during crossover. So they would have to raise the starting Librium dose ( perhaps double it to 200 mg) to cover for its relative weakness for A3, if that’s what it took to get crossover  symtom relief.    As you know, clonazepam has a very very high affinity for A3 and most of the other alphas, and in general is a very potent drug.

[[Re...]]

Interesting about the A3 affinity and the difficulty of crossing over to something with a longer half-life.  No wonder clonazepam can be so hard for some people.  I feel for you, Liberty, in particular with having had Ativan and Diazepam thrown into the mix and still having to return to clonazepam. 

 

I spoke to an MD who is also a PhD in pharmacology practicing here in Canada.  He said that soon no one will be able to prescribe benzodiazepines and possibly antidepressants without having signed a full-disclosure form.  I know that won't be a panacea but I think it represents a good step toward informed consent.  I think it will save a lot of people from going down a path of misery unnecessarily.

 

Thanks for this ongoing and excellent dialogue you fantastic people.

 

-RST

[[li...]]

RST, good for the Canadians. Although I suspect that warning will be an understatement. In The Netherlands, it can get real abusive. GPs are more cautious prescribing benzos to new patients, but for those already on the drug ... you have almost no legal rights, except a continuation of the prescription ... My GP would say about certain things I have to deal with 'that is not possible'. But I heard those words only in 2017 ... I was the victim of several non-drug related medical errors.

 

dm123, I´m not quite sure if that Tocris number for clonazepam´s supposed affinity for the subunits is correct. But even if it is ..

 

A phrase like ´there are few benzodiazepine receptors in the brainstem´ would explain why clonazepam as a high potency benzodiazepine does have certain effects there that other benzos do not have. As I recall, that Tocris numer for alpha 3 wasn´t that much higher than alpha 1. But if it takes a very high potency benzo to do anything at that location ... The raphe nuclei is in the brainstem (serotonin!). I don´t think dousing the body with Librium will do much at that location, and that´s just an example. Time, sensitization, how you react to a drug as a person also plays a role.

 

So I don´t think it´s that simple, and I´ve read reports about people having a much harder time crossing over from clonazepam to Librium than to diazepam.

 

Tocris numbers clonazepam alpha 1,2,3    1.3 1.7 2

diazepam alpha 1,2,3,5                            16.1  16.9 17.0 14.9 (and a negligible number for alpha4)

                                             

A phrase comes to mind ´you have to destroy the CNS to save it´.

 

And that still leaves my situation with physical problems (iatrogenic) that impair normal physical functioning and cause physical distress, especially if I try to taper. Doctors here think about benzodiazepines 'it calms' and that's basically it.  Anyway, the basic foundation of the healthcare system is rationing and it looks like I can't get any recognition of the medical errors. The medical records are written in a very ugly way, like when the GP proposed drug X or procedure X it would show as 'patient asks for X' etc.  When you fall on the wrong side of this system it can get very ugly, with doctors playing games, 'I do not know', 'it's mental' attitudes and agression. Not what you'd expect in a 1st world nation in the 21th century. In situations like those, the 'God complex' can thrive. And from a medical perspective, maybe some things can be fixed. But there is generally no hope if the medical errors are being denied. Why did that GP act the way he did ? Basically: arrogance, ignorance, a certain mental laziness, being way too comfortable in his own practice and network, and something with his personality/something is off. A streak of narcissism possibly. And check my signature ... anyway, enough blogging.

[[cs...]]

Liberty,

 

Is that Tocris Bioscience, the biotech company?

 

You did get a data sheet for relative subunit binding affinities for various Benzodiazaphines?  If so, that’s  good.

Are there units specified in the data sheet.?  I assume Ki in nM?

 

Looking at the relative affinities, the ratios of diazepam  to clonazepam from that data you have below are

 

 

A1  A2  A3  12.38.  9.94.  8.5. (Ie, relative binding affinity weakness)

 

I agree that brain region specific binding properties are unfortunately very different across the drugs.  We also each have unique receptor densities in these various regions of the brain, partly explaining why 2 different people can react to the same drug quite differently.

 

 

I’m not a proponent of either Valium or Librium.  I think each person should use whatever is best for them.  Unfortunately,  there’s no perfect match for clonazepam. Ultimately it  comes down to trial and error, sometimes.

 

 

 

 

 

RST, good for the Canadians. Although I suspect that warning will be an understatement. In The Netherlands, it can get real abusive. GPs are more cautious prescribing benzos to new patients, but for those already on the drug ... you have almost no legal rights, except a continuation of the prescription ... My GP would say about certain things I have to deal with 'that is not possible'. But I heard those words only in 2017 ... I was the victim of several non-drug related medical errors.

 

dm123, I´m not quite sure if that Tocris number for clonazepam´s supposed affinity for the subunits is correct. But even if it is ..

 

A phrase like ´there are few benzodiazepine receptors in the brainstem´ would explain why clonazepam as a high potency benzodiazepine does have certain effects there that other benzos do not have. As I recall, that Tocris numer for alpha 3 wasn´t that much higher than alpha 1. But if it takes a very high potency benzo to do anything at that location ... The raphe nuclei is in the brainstem (serotonin!). I don´t think dousing the body with Librium will do much at that location, and that´s just an example. Time, sensitization, how you react to a drug as a person also plays a role.

 

So I don´t think it´s that simple, and I´ve read reports about people having a much harder time crossing over from clonazepam to Librium than to diazepam.

 

Tocris numbers clonazepam alpha 1,2,3    1.3 1.7 2

diazepam alpha 1,2,3,5                            16.1  16.9 17.0 14.9 (and a negligible number for alpha4)

                                             

A phrase comes to mind ´you have to destroy the CNS to save it´.

 

And that still leaves my situation with physical problems (iatrogenic) that impair normal physical functioning and cause physical distress, especially if I try to taper. Doctors here think about benzodiazepines 'it calms' and that's basically it.  Anyway, the basic foundation of the healthcare system is rationing and it looks like I can't get any recognition of the medical errors. The medical records are written in a very ugly way, like when the GP proposed drug X or procedure X it would show as 'patient asks for X' etc.  When you fall on the wrong side of this system it can get very ugly, with doctors playing games, 'I do not know', 'it's mental' attitudes and agression. Not what you'd expect in a 1st world nation in the 21th century. In situations like those, the 'God complex' can thrive. And from a medical perspective, maybe some things can be fixed. But there is generally no hope if the medical errors are being denied. Why did that GP act the way he did ? Basically: arrogance, ignorance, a certain mental laziness, being way too comfortable in his own practice and network, and something with his personality/something is off. A streak of narcissism possibly. And check my signature ... anyway, enough blogging.