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

[[cs...]]

dm123,

Thank you for this!  it all makes sense -- Oh Not that I Understand it all  -- but I do get the gist of what we are dealing with, and with how my body adjusted over the years.  And there are lots of terms and systems to google and get a more accurate understanding of.

 

It also validates -- I believe- the idea of long holds to try to get the body to some kind of stability before tapering again. I tapered from a very unstable place and had all the things one would expect. Out of sheer terror and resignation I decided on a long hold (I'm very lucky to have a doc who simply follows my lead)  Now that i am down this far, and feeling pretty well on day 43 I intend to hold until I feel really well to allow things to adjust, understanding that I will again stress all the systems when I begin to taper again.  I just think it is from a less stressed place to begin with, which sounds positive if I'm understanding you thesis here.

 

I took these years with NO, yup no, problems -- and now i realize that I also had come off various benzos 5X in my life over the last 40 years.  All that  being said to remind myself,  and anyone else who is struggling that I/we have had a strong physiology, that our body fights for homeostasis, and that with that in mind I can taper.

 

Sorry for the long post!  It's just that this post spoke to me so strongly!  Is so hope filled.

Again I thank you for all the great work that you do here!  Yes I too hope you publish some day in the area that we are all struggling so hard to deal with.

 

All the best to everyone!

SS

 

Hi SS,

 

Yes i understand what you are saying and you have understood the major takeaway from the post.  That’s what matters.    If people understand how things happen, it doesn’t necessarily give us one size fit all therapeutics, but it does tell us how to live, what to avoid and how to taper successfully.

 

Symptom based taper is the safest way to approach any Benzodiazaphine taper.  Symptoms are the body’s way of telling us that things have not settled down yet, things are not yet balanced, things are not in homeostasis (to use the scientific term).  For whatever reason: drug serum levels have not stabilized yet, emotional stress, etc.  It doesn’t matter.  It’s all stress that the body has to acclimate to prior to the next cut.

 

I have learned quite a bit from my own taper, and like you, its getting low. I won’t feel safe until I’m completely off.  My body’s response for the most part is deterministic and predictable, but every now a cut can throw me for a loop. 

 

As RST mentioned above, its far more than just the taper that’s involved when it comes to stress and withdrawal and ultimate recovery.  There are lifestyle challenges, there are mortgages to be paid, there are families that need to be supported. It’s all piling on more emotional (and sometimes physical ) stress.  And the main point is that we have to factor in all of these things because they do affect our ultimate recovery.

 

I am glad you are doing better.  THere was another thread on half lives and valium and valium metabolites.  I’m tapering with librium, which is is similar to valium in many ways, and i have found a 26-30 day cut recovery period (for me) is sufficient. It varies a bit, from cut to cut, but it is around that ballpark.  The metabolite takes around 30-60 days to clear out , depending on ones physiology, etc.  So these numbers make sense from a clinical standpoint.  But we still have to factor in how generic stress affects our taper.  And that’s the point i wanted to make with part 1 above.

 

Stupid question and one you're likely not able to answer ...

 

In my case: symptoms of what ? Not just 'the benzo'. The entire body has been affected, there are a few major components. Maybe something could be done, medically. Even though I pretty much fired that GP, the local healthcare system is restrictive. What if some of my physical issues cause distress or impairment of function ? Clonazepam can dampen certain forms of physical distress (and cause that too) in ways no other benzo can. Yeah, I get the feeling 'stupid question'. Most docs everywhere would say something like 'taper the clonazepam first'. And in an unhealthy way, it can promote sleep. Tapering while in physical distress and lacking sleep is not ideal ... primary cause: multiple medical errors, iatrogenic damage.

 

I agree. It is very difficult to get off.  This is why these drugs are so dangerous.  I understand.

 

Sorry, forgot to answer the question.

 

Symptoms of what?  It is The symtoms of the wd itself, but the theory is that once you stabilize serum levels, many of the tolerance symtoms improve.  That is the approach i used.  Nerve pain will not disappear but will improve slowly.  That is the point of titrating up until you are out of tolerance, and getting the serum levels to be constant.  You then wait a month or two to stabilize, then start a slow taper.  If one does it in this order, then there is a better chance of being able to cut.

[[fr...]]

Yes I take 1/2 tab every 4 hrs.  Can’t believe dr told me years ago these were safe drugs and to take them all together.  My nerve pain is worsening.  Am stuck at 12 mg of Valium also. Drs just keep wanting to add more drugs and I’m scared they will force me into rehab, which would kill me.  Family is over it al and don’t understand the depth of my pain and despair.  Thanks for always trying to help.

[[li...]]

'Symptoms of what?  ' Actually I was referring to the concept of underlying physical problems, that either impair functioning or cause physical distress.

 

Up to a point, clonazepam covers that up. The way an opiate would cover up pain.

[[cs...]]

Yes I take 1/2 tab every 4 hrs.  Can’t believe dr told me years ago these were safe drugs and to take them all together.  My nerve pain is worsening.  Am stuck at 12 mg of Valium also. Drs just keep wanting to add more drugs and I’m scared they will force me into rehab, which would kill me.  Family is over it al and don’t understand the depth of my pain and despair.  Thanks for always trying to help.

 

Hi freeme, i am glad i looked up soma.  I wish I knew more about the drug.  Is it possible for you to talk to your docs and ask them if you can hold on the valium and taper the soma first?

 

The soma is potentiating the GABAaR, at least from the little that i just read on it.  I hadn’t realized it has such a short half like.  Every 4 hours is good but the half life is so short that it’s difficult to keep your serum levels rock solid, especially if you are a fast metabolizer of soma. 

 

Another approach would be to go up on the valium, with your doctors permission, while decreasing the soma.

 

Are you on a high dose of soma?  What is considered a high dose of soma?

 

Hopefully we can get input from your doctors on the approach above.  For me personally, i would rather convert to valium and get rid of the soma first, then start going down on the valium.  But i cannot give direct medical advice. Please ask your docs about the above approach and if they will sign on.

 

Best

Dm123

[[cs...]]

'Symptoms of what?  ' Actually I was referring to the concept of underlying physical problems, that either impair functioning or cause physical distress.

 

Up to a point, clonazepam covers that up. The way an opiate would cover up pain.

 

Yes, that is what adjunctive medication would be for. I don’t know what the underlying physical problems are exactly, and i don’t know if the clonazepam is the only therapy available for it.

[[cs...]]

I have seen the smartest guys in the room thread here, but most of it is way over my head  I am however interested in this quote from dm123

 

Tolerance is exasperated by interdose withdrawals, in particular with the high potency short half life Benzodiazaphines (i include clonazepam in this group).  Persistent interdose withdrawals day to day can lead to a slowly evolving neuro kindling effect.

 

I ave only been tapering a few weeks and still waiting for appointments for a prescribing physicam for tapering In the meantime my dosing is something like this  four doses per day of slightl under .25 mg X Those time have been

 

3 AM  9-11 AM  3-5 PM  9 PM 

 

I have been playing with moving 9 PM to 8 and 3 AM to  2 Mostly due to the fact that #AM just seems too late for more good sleep

 

 

My question is however about the other two late morning late afternoon doses I try to stretch these out to an 8 hour interdose window and often suffer some symptoms in doing so in the hope that my evening doses will be more effective for sleep But it sounds like what you are saying is that could be causing me problems

 

Hi Matt, yes.  You have the correct idea.  You can have some people who can do ok with every 8 hours on Xanax and suffer no interdose symptoms at all, and others that metabolize the drug faster, and have issues like you do.  As you know xanax is a short half life high potency drug.  I’m glad you are dosing every 6 hours. I do see from your chart that worst case scenario is you take it at 9am and dont take the next dose until 5pm which is that 8 hour high water mark that you are hitting.

 

Yes, if you can avoid symtoms it means you’ve achieved a good steady state for your physiology and metabolism and you will be better off. 

 

“Saving” up doses for more Benzodiazaphine close to sleep in the long run is not helping things.  I fell into that trap early on prior to crossover.  It is one of the biggest traps of the Benzodiazaphine.  It leads to faster tolerance development and more dependence on the drug. 

 

Your nervous system will calm down more quickly the more level you keep the dose.  Initially keeping with the every 6 hour dose might be more difficult, but over time things should get better.  It may take 2-4 weeks for your nervous system to adapt to the strict dosing regimen.(in a good way)

 

Don’t cut until you stabilize your dosing regimen.  That’s where things can go wrong.

 

Best

Dm123

[[Ma...]]

Thanks dme 123 I think I am still trying to absorb all your information I was worried that my strategy was poorly thought out, maybe a bit a\of machismo thinking if you can tough it out a bit, stretching interdose windows, then you can tame the drug in some way My first symptom a couple of weeks ago is parathesia in toes and front pad of the foot. not terrible but significant Does not really effect walking I hit tolerance obviously. It seems like you advised slowly updosing until tolerance symptoms resolve ,and then start a slow taper? I am not sure if I can get a doc to go for that and a little anxiety producing but if it meant a better chance of not having those parathesia symptoms for life it might be good I have pretty bad LPR and a tight throat is just barely within tolerable limits I assume it is possible that the throat symptoms may become more under control as well?

[[cs...]]

Thanks dme 123 I think I am still trying to absorb all your information I was worried that my strategy was poorly thought out, maybe a bit a\of machismo thinking if you can tough it out a bit, stretching interdose windows, then you can tame the drug in some way My first symptom a couple of weeks ago is parathesia in toes and front pad of the foot. not terrible but significant Does not really effect walking I hit tolerance obviously. It seems like you advised slowly updosing until tolerance symptoms resolve ,and then start a slow taper? I am not sure if I can get a doc to go for that and a little anxiety producing but if it meant a better chance of not having those parathesia symptoms for life it might be good I have pretty bad LPR and a tight throat is just barely within tolerable limits I assume it is possible that the throat symptoms may become more under control as well?

 

Hi Matt, i think it is well thought out.  I had the same attitude a long time back.  For me, the Benzodiazaphine tolerance and kindling was by far the stronger force.  Like you , i am pretty resilient, but it was nothing in the face of the Benzodiazaphine.  I respect the drug, but i also detest the drug.

 

How long have you been holding at .9mg?

 

If it is not too long (ie over 2-3 months) perhaps it is best to wait it out and stick to the 6 hour regiment very tightly to see if you can stabilize at .9 mg. 

 

Also are you dry cutting or doing a liquid microtaper. ?  I would think dry cutting would be difficult with such a potent drug@ .9mg

 

I don’t recommend updosing frequently.  What i meant by titrating it up. was in the context for those who are initially starting a taper. (Which may or may not involve a crossover as well).  Some of us had to crossover to a higher Ashton “table” equivalent dose to stabilize because we were in severe tolerance even before starting the taper.I had been such a person.  Some of us do not need the initial updose.  Same goes with noncrossover starting of taper.  Some have to stabilize on a higher dose of the drug, split up dosing (like you are doing), to stabilize.  One cannot cut until one is at least partially stable.

 

If you are talking about updosing during a taper, it can be helpful sometimes, but as you have read, sometimes it does not work.  This is sort of a last resort, if adjunctive meds are not availbable or not working to help out.

 

Looking at your signature your highest total daily dose was  around 1 mg correct? So you are still early in the taper.

 

I have leg neuropathy, so i know what you are going through.

 

I have a good friend with GERD, and i know that LPR is horrendous.  I don’t know if the Benzodiazaphine wd is causing that, but it can certainly cause nausea.

 

Best,

Dm123

 

 

[[Ma...]]

Thanks dme123 At about .9 for a month maybe only 3 weeks My dry cutting is fairly primitive and I just try to shave enough of each pill each day to approximate.1 mgs I came off a period of using slightly more than 1 mg for a couple of months during the kidney stone and opiates through about May through June So .9 is definitely a cut in my opinion I am fairly OK but I think, as you suggest, trying to get stable 6 hour dosing could make things better Also microdosing is something I hope to be able to do soon

 

I have read a lot of posts on whether to direct taper Xanax or crossover to Valium My present though is to trey to get down to .5 on Xanax an then try a crossover Though once I find a prescribing doc it may not be under my control I am aware that the crossover could include both drugs for a period of time, and now understand that it is during this period that you advise titrating up if an individual is struggling

 

I have appointments with two different Psychiatrists who are supposedly familiar with Benzo withdrawal, and hopefully Ashton, but it is of course near impossible to clear information on their approach before driving an hour or more one way to find out One is about 3 weeks out I probably will not cut below.9 before then It could be worse since many never get past their original prescribing GP I did get at least two in case I hit a roadblock wit the first  I though Northern California might be a bit better than other areas for this, but BW seems to have a universal roadblock for quality medical experts

 

Best as well

                      Matt

[[fr...]]

Thanks DM I will ask drs.  Don’t know what he will say. Thanks again.

[[li...]]

Unfortunately there is not a 'symptom' pill for every problem.

 

There is one major non-CNS issue (does have a rather major indirect effect on the CNS) that's most likely untreatable. In this country, anyway. Or you'd need the help from a GP, but in my case 'good luck with that'. Main cause: medical errors, problems treated too late/not at all/incorrectly. The GPs are like a layer above the general population, determining your ration of healthcare. I wish I had been more 'street smart', bypassed the GPs and payed out of pocket many years ago.

 

Yes I know you can't help with that, this excuse for a healthcare system ****. And only the USA is more expensive.

 

Dutch GPs often won't kill you, but sometimes you 'd wish they had.

 

American GPs don't have time for the stupid games some Dutch ones play.

 

'Symptoms of what?  ' Actually I was referring to the concept of underlying physical problems, that either impair functioning or cause physical distress.

 

Up to a point, clonazepam covers that up. The way an opiate would cover up pain.

 

Yes, that is what adjunctive medication would be for. I don’t know what the underlying physical problems are exactly, and i don’t know if the clonazepam is the only therapy available for it.

[[li...]]

Yes I take 1/2 tab every 4 hrs.  Can’t believe dr told me years ago these were safe drugs and to take them all together.  My nerve pain is worsening.  Am stuck at 12 mg of Valium also. Drs just keep wanting to add more drugs and I’m scared they will force me into rehab, which would kill me.  Family is over it al and don’t understand the depth of my pain and despair.  Thanks for always trying to help.

 

If you don't mind, I did look into the pharmacological part of your situation.

 

That's a tab of 350 mg ? I know tabs of 500 mg exist. Assuming the former, that's about 1 gr of carisoprodol a day.

 

In some ways it's quite complicated, I did try looking into what it actually does. One very large file : https://pdfs.semanticscholar.org/3891/59df637f558b16b05035a7855d66f5c11029.pdf

As a brief and likely partly incorrect summary, it appears it has barbiturate like properties. Up to a point, maybe acting as a GABA agonist.

References (web) to carisoprodol acting on the spinal cord, the descending reticular formation and the brain stem.

It seems it also has an effect on serotonin, although that is more likely on higher doses IMO.

I know that meprobamate (metabolite) is also a strong adenosine reuptake inhibitor.

 

As for your practical situation, it would seem an interaction exists although I do not know up to what point it is significant. I've read references about acute carisoprodol withdrawal being very physical and sometimes intense, but brief.

 

If you 'wanted' to get off both drugs, the most rational approach would seem to taper off the carisoprodol (soma) first.

 

Completely unrelated, a very long time ago I did take carisoprodol briefly and recall that coffee blocked or somehow messed up its effects.

 

Added note: you're also on hydrocodone, I don't know the dose. A tool for checking drug interactions suggests major interactions with both diazepam and carisoprodol, but IMO I suspect that carisoprodol interacts more strongly with opiates than diazepam. (brain stem, spinal cord)

[[fr...]]

Thanks for caring.  I don’t think I can do this anymore.  I have so much pain and neuropathy I am out of my mind with worry and sadness. I just see no way forward, too old and on the meds for too long. They were all prescribed together so I guess I won’t od on them at this point.  Hope you feel better.

[[cs...]]

Thanks for caring.  I don’t think I can do this anymore.  I have so much pain and neuropathy I am out of my mind with worry and sadness. I just see no way forward, too old and on the meds for too long. They were all prescribed together so I guess I won’t od on them at this point.  Hope you feel better.

 

Hi freeme,

 

At least we identified a potential source of what’s been aggravating your nervous system.  I had no idea that soma had such a short half life.  I don’t know how they expect people to maintain steady state with a drug that has a half life of 2 hours.

 

Even the active metabolite has a half life of 10 hours

 

Please see this article. It does act on the GABAaR. The exact mechanism is unknown, but that does not matter.

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858432/pdf/nihms183444.pdf

 

Please keep us posted on what the doctor says.

I would hold the valium right where it is and work on the soma.  Neuropathic pain is aggravated by these short half life GABAERGIC drugs.

I am very hopeful for your case.

Best

 

Dm123

[[cs...]]

Thanks dme123 At about .9 for a month maybe only 3 weeks My dry cutting is fairly primitive and I just try to shave enough of each pill each day to approximate.1 mgs I came off a period of using slightly more than 1 mg for a couple of months during the kidney stone and opiates through about May through June So .9 is definitely a cut in my opinion I am fairly OK but I think, as you suggest, trying to get stable 6 hour dosing could make things better Also microdosing is something I hope to be able to do soon

 

I have read a lot of posts on whether to direct taper Xanax or crossover to Valium My present though is to trey to get down to .5 on Xanax an then try a crossover Though once I find a prescribing doc it may not be under my control I am aware that the crossover could include both drugs for a period of time, and now understand that it is during this period that you advise titrating up if an individual is struggling

 

I have appointments with two different Psychiatrists who are supposedly familiar with Benzo withdrawal, and hopefully Ashton, but it is of course near impossible to clear information on their approach before driving an hour or more one way to find out One is about 3 weeks out I probably will not cut below.9 before then It could be worse since many never get past their original prescribing GP I did get at least two in case I hit a roadblock wit the first  I though Northern California might be a bit better than other areas for this, but BW seems to have a universal roadblock for quality medical experts

 

Best as well

                      Matt

 

Hi Matt, there are lots of people here on BB that are good with liquid microtapering.  You might eventually need it given the potency of xanax.

 

My doctor crossed me over one day.  It was very frightening  to be sure, but it went relatively well.  It took about a week to settle into the crossover and another 4 weeks to stabilize the tolerance and symtoms.  It was during this time that the dose was titrated up for symtom relief. It was the best decision i made in my life.

 

Some do piecemeal crossovers and others do not.  THere’s no way to predict how any one individual will react, because we are all so different in that respect.

 

.5 xanax would be 10 mg valium and you could dry cut the valium to a very slow taper rate.

 

Benzo experts are notoriously hard to find. 

 

I hope the 6 hour schedule gives you some relief over the next several weeks.

 

Best

 

Dm123

[[fr...]]

Thanks DM for finding this but I can’t get past the terror of how badly I feel now.  I just see no way forward, what a sad mess.  I’m too sick to even try just pathetic.  If things change I will certainly let you know.  Maybe ask to go on a longer acting muscle relaxer like flexeril and try to taper that.  Don’t know if it acts the same way and dr probably doesn’t either.  Thanks again and God bless you for all the wonderful work you do for all. 

[[li...]]

Pheno doesn´t seem to be my thing. Really nasty stuff. Second day, all sorts of interaction with the clonazepam. Hormones, acetylcholine, glutamate-dopamine etc.

 

GPCRs being neuromodulators, I get that. After these medical experiments, messed up. New GP ? They pride themselves on keeping people away from the hospital, not prescribing drugs (what aboutt hat clonazepam?? rationalizations), blocking access to care in general. In charge of rationing. And oh so loyal to their collegues. I doubt I could find one anywhere in Europe willing to ´break ranks´. 5 years is a long time.

 

Maybe a stupid question. Well, likely. A drug that reduces the release of acetylcholine ? I took a quick glance, I had my doubts about atropine ... In the end, those doctors will kill you ?

[[li...]]

Been reading a bit about acetylcholine.

 

I wouldn´t be surprised if I felt more clear minded after my evening dose (one a day) because it boosts acetylcholine, possibly in the nucleus accumbens.

 

https://www.ncbi.nlm.nih.gov/pubmed/23040810

 

Maybe that´s why beign active is required for tapering ? I used to be more active during my first real tapers.

 

https://en.wikipedia.org/wiki/Neuromodulation#Cholinergic_system

 

´Cholinergic system

 

The cholinergic system consists of projection neurons from the pedunculopontine nucleus, laterodorsal tegmental nucleus, and basal forebrain and interneurons from the striatum and nucleus accumbens. It is not yet clear whether acetylcholine as a neuromodulator acts through volume transmission or classical synaptic transmission, as there is evidence to support both theories. Acetylcholine binds to both metabotropic muscarinic receptors (mAChR) and the ionotropic nicotinic receptors (nAChR). The cholinergic system has been found to be involved in responding to cues related to the reward pathway, enhancing signal detection and sensory attention, regulating homeostasis, mediating the stress response, and encoding the formation of memories.[19][20]

GABA

 

Gamma-aminobutyric acid (GABA) has an inhibitory effect on brain and spinal cord activity.[13] ´

The last sentence: yes, and there is no benzo that does that as much as clonazepam.

 

Given the fact that a certain opiate has muscle relaxing proterties, which would bring back clonazepam´s muscle relaxing properties to what it used to be and the general state of my muscle fibers, I wouldn´t be surprised if acute withdrawal meant extreme physical pain.

 

Not expecting any true answers here. I´m at the end of a medical  experiment that has been running for 5 years. With, for situations like these, the worst healthcare system in the world.

 

[[Re...]]

Been reading a bit about acetylcholine.

 

I wouldn´t be surprised if I felt more clear minded after my evening dose (one a day) because it boosts acetylcholine, possibly in the nucleus accumbens.

 

https://www.ncbi.nlm.nih.gov/pubmed/23040810

 

Maybe that´s why beign active is required for tapering ? I used to be more active during my first real tapers.

 

https://en.wikipedia.org/wiki/Neuromodulation#Cholinergic_system

 

´Cholinergic system

 

The cholinergic system consists of projection neurons from the pedunculopontine nucleus, laterodorsal tegmental nucleus, and basal forebrain and interneurons from the striatum and nucleus accumbens. It is not yet clear whether acetylcholine as a neuromodulator acts through volume transmission or classical synaptic transmission, as there is evidence to support both theories. Acetylcholine binds to both metabotropic muscarinic receptors (mAChR) and the ionotropic nicotinic receptors (nAChR). The cholinergic system has been found to be involved in responding to cues related to the reward pathway, enhancing signal detection and sensory attention, regulating homeostasis, mediating the stress response, and encoding the formation of memories.[19][20]

GABA

 

Gamma-aminobutyric acid (GABA) has an inhibitory effect on brain and spinal cord activity.[13] ´

The last sentence: yes, and there is no benzo that does that as much as clonazepam.

 

Given the fact that a certain opiate has muscle relaxing proterties, which would bring back clonazepam´s muscle relaxing properties to what it used to be and the general state of my muscle fibers, I wouldn´t be surprised if acute withdrawal meant extreme physical pain.

 

Not expecting any true answers here. I´m at the end of a medical  experiment that has been running for 5 years. With, for situations like these, the worst healthcare system in the world.

 

Interesting, especially about the pain.  I am in a bucketload of pain.  It's my most significant issue (followed closely by a wheelbarrow of others).  The burning body is not pleasant.  It started with the lorazepam, was mitigated (as was all my withdrawal originally) by the gabapentin.  But now, the piper needs to get paid, I guess.  I was so darned close to getting off the gabapentin last fall........  Aaaaggghhh. 

 

I was thinking that acetylcholine might be an answer too.  Unfortunately short-term dosing of citicholine didn't go well.  It boosted all my pain somewhat but REALLY messed with my thinking.  I had a very hard time for about a 2 week period after citicholine.

 

-Maybe I'll just give cannabis a go..........

 

:thumbsup:

 

On another matter of pain.  I have some corydalis yanhuoso.  It's mechanism of action is varied but one of the things it does is influence Dopamine receptors.  I took a little a few nights ago and a few hours later my pain was intense, intense, intense but particularly located where I have my predictable restless leg syndrome discomfort.  I find this particularly telling given the purported role of dopamine / dopamineR's in RLS. 

 

I know among everything else, you and I both wish we'd avoided the Lorazepam disaster!

 

-RST

[[li...]]

Exercised today in the gym. Partly  because I felt that hangover form that one dose of phenobarbital. Half life of more than 48 hours !

 

There sure is an acetylcholine issue. Muscles, CNS. Very clear headed afterwards. And a massive hormonal reponse. Even (or especially) when resting on the bed. Not quite sure what the body was doing ! Pheno hangover gone for the moment.

After the evening dose I feel colder than normal. So there is definitely a HPA axis thingy.

 

Healthcare here ****. especially after medical errors. Obviously clonazepam strongly acts on the motor neurons, spinal cord, brain stem, likely more. Rather different than diazepam, and I´m not ´fine´. I had expected to be off 2014 latest ! Currently multiple health components interacting. That lorazepam was rather sedating and it must have messed with many gabaa receptors.

 

Not sure if I have question here ! Can I skip the whole tapering process and move to the part where I´m normal again and work on the other issues ? (partly sarcastic)

Primary care restrictive, backwards, benzo user ´satisfied user´/´mental or psychiatric´/´it´s an addiction´ That´s how they learned their job. They are supposed to follow the law, which didn´t happen.

[[cs...]]

Pheno doesn´t seem to be my thing. Really nasty stuff. Second day, all sorts of interaction with the clonazepam. Hormones, acetylcholine, glutamate-dopamine etc.

 

GPCRs being neuromodulators, I get that. After these medical experiments, messed up. New GP ? They pride themselves on keeping people away from the hospital, not prescribing drugs (what aboutt hat clonazepam?? rationalizations), blocking access to care in general. In charge of rationing. And oh so loyal to their collegues. I doubt I could find one anywhere in Europe willing to ´break ranks´. 5 years is a long time.

 

Maybe a stupid question. Well, likely. A drug that reduces the release of acetylcholine ? I took a quick glance, I had my doubts about atropine ... In the end, those doctors will kill you ?

 

Hi Liberty,

 

I don’t know much about the atropine, but i have heard of it.. It has been around for a while.  Regarding drugs that reduce ACh, as you know there are always many different drugs for these things, but i don’t have the expertise in this area to recommend something clinically.  It might have side effects that i am not aware of, particularly when used with a Benzodiazaphine.

 

I agree with your last sentence

 

[[cs...]]

Been reading a bit about acetylcholine.

 

I wouldn´t be surprised if I felt more clear minded after my evening dose (one a day) because it boosts acetylcholine, possibly in the nucleus accumbens.

 

https://www.ncbi.nlm.nih.gov/pubmed/23040810

 

Maybe that´s why beign active is required for tapering ? I used to be more active during my first real tapers.

 

https://en.wikipedia.org/wiki/Neuromodulation#Cholinergic_system

 

´Cholinergic system

 

The cholinergic system consists of projection neurons from the pedunculopontine nucleus, laterodorsal tegmental nucleus, and basal forebrain and interneurons from the striatum and nucleus accumbens. It is not yet clear whether acetylcholine as a neuromodulator acts through volume transmission or classical synaptic transmission, as there is evidence to support both theories. Acetylcholine binds to both metabotropic muscarinic receptors (mAChR) and the ionotropic nicotinic receptors (nAChR). The cholinergic system has been found to be involved in responding to cues related to the reward pathway, enhancing signal detection and sensory attention, regulating homeostasis, mediating the stress response, and encoding the formation of memories.[19][20]

GABA

 

Gamma-aminobutyric acid (GABA) has an inhibitory effect on brain and spinal cord activity.[13] ´

The last sentence: yes, and there is no benzo that does that as much as clonazepam.

 

Given the fact that a certain opiate has muscle relaxing proterties, which would bring back clonazepam´s muscle relaxing properties to what it used to be and the general state of my muscle fibers, I wouldn´t be surprised if acute withdrawal meant extreme physical pain.

 

Not expecting any true answers here. I´m at the end of a medical  experiment that has been running for 5 years. With, for situations like these, the worst healthcare system in the world.

 

Thanks for posting the pubmed link.  GPCRs are a vast area, and I’m glad you are researching them in the context of neuromodulation.    That’s precisely how they fit into the model.  They also affect almost all of the other pillars as well, including the stress system.  This is why disrupting one pillar leads to a cascade of feedback loops that can manifest themselves as a protracted withdrawal.

[[cs...]]

Been reading a bit about acetylcholine.

 

I wouldn´t be surprised if I felt more clear minded after my evening dose (one a day) because it boosts acetylcholine, possibly in the nucleus accumbens.

 

https://www.ncbi.nlm.nih.gov/pubmed/23040810

 

Maybe that´s why beign active is required for tapering ? I used to be more active during my first real tapers.

 

https://en.wikipedia.org/wiki/Neuromodulation#Cholinergic_system

 

´Cholinergic system

 

The cholinergic system consists of projection neurons from the pedunculopontine nucleus, laterodorsal tegmental nucleus, and basal forebrain and interneurons from the striatum and nucleus accumbens. It is not yet clear whether acetylcholine as a neuromodulator acts through volume transmission or classical synaptic transmission, as there is evidence to support both theories. Acetylcholine binds to both metabotropic muscarinic receptors (mAChR) and the ionotropic nicotinic receptors (nAChR). The cholinergic system has been found to be involved in responding to cues related to the reward pathway, enhancing signal detection and sensory attention, regulating homeostasis, mediating the stress response, and encoding the formation of memories.[19][20]

GABA

 

Gamma-aminobutyric acid (GABA) has an inhibitory effect on brain and spinal cord activity.[13] ´

The last sentence: yes, and there is no benzo that does that as much as clonazepam.

 

Given the fact that a certain opiate has muscle relaxing proterties, which would bring back clonazepam´s muscle relaxing properties to what it used to be and the general state of my muscle fibers, I wouldn´t be surprised if acute withdrawal meant extreme physical pain.

 

Not expecting any true answers here. I´m at the end of a medical  experiment that has been running for 5 years. With, for situations like these, the worst healthcare system in the world.

 

Interesting, especially about the pain.  I am in a bucketload of pain.  It's my most significant issue (followed closely by a wheelbarrow of others).  The burning body is not pleasant.  It started with the lorazepam, was mitigated (as was all my withdrawal originally) by the gabapentin.  But now, the piper needs to get paid, I guess.  I was so darned close to getting off the gabapentin last fall........  Aaaaggghhh. 

 

I was thinking that acetylcholine might be an answer too.  Unfortunately short-term dosing of citicholine didn't go well.  It boosted all my pain somewhat but REALLY messed with my thinking.  I had a very hard time for about a 2 week period after citicholine.

 

-Maybe I'll just give cannabis a go..........

 

:thumbsup:

 

On another matter of pain.  I have some corydalis yanhuoso.  It's mechanism of action is varied but one of the things it does is influence Dopamine receptors.  I took a little a few nights ago and a few hours later my pain was intense, intense, intense but particularly located where I have my predictable restless leg syndrome discomfort.  I find this particularly telling given the purported role of dopamine / dopamineR's in RLS. 

 

I know among everything else, you and I both wish we'd avoided the Lorazepam disaster!

 

-RST

 

Hi RST, add me to that list. Also affected by lorazepam.  Nowadays its bigger everything, and supersized everything, and turbo charged everything from our food to our cars, to the medications.  They decided to supercharge the Benzodiazaphine several decades ago, when they should have just left the valium and librium as it was.  More potent is not necessarily better

 

Your experiences with various GPCR modulators is consistent with the model.  They are very potent neuromodulators and they are what allow us to function, somewhat, even well into tolerance.  THey are more of those “knobs and switches”.  But the circuits can only take so much for some of us........

 

The cannabis is interesting. They have some very knowledgeable people on BB for this.  You probably already know about the thread on here.  They might help you prepare for it.

 

 

 

 

[[Re...]]

Been reading a bit about acetylcholine.

 

I wouldn´t be surprised if I felt more clear minded after my evening dose (one a day) because it boosts acetylcholine, possibly in the nucleus accumbens.

 

https://www.ncbi.nlm.nih.gov/pubmed/23040810

 

Maybe that´s why beign active is required for tapering ? I used to be more active during my first real tapers.

 

https://en.wikipedia.org/wiki/Neuromodulation#Cholinergic_system

 

´Cholinergic system

 

The cholinergic system consists of projection neurons from the pedunculopontine nucleus, laterodorsal tegmental nucleus, and basal forebrain and interneurons from the striatum and nucleus accumbens. It is not yet clear whether acetylcholine as a neuromodulator acts through volume transmission or classical synaptic transmission, as there is evidence to support both theories. Acetylcholine binds to both metabotropic muscarinic receptors (mAChR) and the ionotropic nicotinic receptors (nAChR). The cholinergic system has been found to be involved in responding to cues related to the reward pathway, enhancing signal detection and sensory attention, regulating homeostasis, mediating the stress response, and encoding the formation of memories.[19][20]

GABA

 

Gamma-aminobutyric acid (GABA) has an inhibitory effect on brain and spinal cord activity.[13] ´

The last sentence: yes, and there is no benzo that does that as much as clonazepam.

 

Given the fact that a certain opiate has muscle relaxing proterties, which would bring back clonazepam´s muscle relaxing properties to what it used to be and the general state of my muscle fibers, I wouldn´t be surprised if acute withdrawal meant extreme physical pain.

 

Not expecting any true answers here. I´m at the end of a medical  experiment that has been running for 5 years. With, for situations like these, the worst healthcare system in the world.

 

Interesting, especially about the pain.  I am in a bucketload of pain.  It's my most significant issue (followed closely by a wheelbarrow of others).  The burning body is not pleasant.  It started with the lorazepam, was mitigated (as was all my withdrawal originally) by the gabapentin.  But now, the piper needs to get paid, I guess.  I was so darned close to getting off the gabapentin last fall........  Aaaaggghhh. 

 

I was thinking that acetylcholine might be an answer too.  Unfortunately short-term dosing of citicholine didn't go well.  It boosted all my pain somewhat but REALLY messed with my thinking.  I had a very hard time for about a 2 week period after citicholine.

 

-Maybe I'll just give cannabis a go..........

 

:thumbsup:

 

On another matter of pain.  I have some corydalis yanhuoso.  It's mechanism of action is varied but one of the things it does is influence Dopamine receptors.  I took a little a few nights ago and a few hours later my pain was intense, intense, intense but particularly located where I have my predictable restless leg syndrome discomfort.  I find this particularly telling given the purported role of dopamine / dopamineR's in RLS. 

 

I know among everything else, you and I both wish we'd avoided the Lorazepam disaster!

 

-RST

 

Hi RST, add me to that list. Also affected by lorazepam.  Nowadays its bigger everything, and supersized everything, and turbo charged everything from our food to our cars, to the medications.  They decided to supercharge the Benzodiazaphine several decades ago, when they should have just left the valium and librium as it was.  More potent is not necessarily better

 

Your experiences with various GPCR modulators is consistent with the model.  They are very potent neuromodulators and they are what allow us to function, somewhat, even well into tolerance.  THey are more of those “knobs and switches”.  But the circuits can only take so much for some of us........

 

The cannabis is interesting. They have some very knowledgeable people on BB for this.  You probably already know about the thread on here.  They might help you prepare for it.

 

DM, you are so correct.  I don't do a lot of fiddling around with direct action supplements/drugs that often.  The citicholine was 4 months ago.  The Corydalis was a week ago and one dose.  You may know it is primarily defined as a pain medicine but, as we've discussed about so many of these supplements, multiple other mechanisms of action that are unpredictable can co-occur.

 

As a side note, I came across a very interesting recent study on α2δ-1 subunits and VACC's. 

 

https://reader.elsevier.com/reader/sd/84CE83480C24C1F28C6CBBA35D45CE22B83BF25DB6E95BCB68CFAA3C9236C0FEF9C47ABC608CB6B904FAD5244F5686DE 

 

This study makes some groundbreaking claims about gabapentin's main mechanism of action in nerve pain. 

 

"Gabapentin and pregabalin bind to both a2d-1 and a2d-2(Marais et al., 2001). Unlike a2d-1, which is mainly expressed in excitatory neurons, a2d-2 is predominantly expressed in inhibitory neurons (Cole et al., 2005; Taylor and Garrido, 2008) and may mediate some of the adverse effects of gabapentinoids, such as dizziness and sedation. We showed that the designed peptide targeting the C-terminal domain of a2d-1 effectively disrupted the a2d-1-NMDAR association and normalized the synaptic NMDAR activity and pain hypersensitivity induced by nerve injury. Because this sequence is unique to a2d-1, it is conceivable that drugs that target this domain may have fewer adverse effects than gabapentinoids. Both a2d-1 and NMDARs are coexpressed in many important brain regions. Because we demonstrated that a2d-1 can physically interact with NMDARs and increase their activity even in a cell line, such interaction is unlikely to be limited to the spinal cord. Thus, targeting a2d-1-bound NMDARs may be a promising strategy for treating neuropathic pain and other NMDAR-dependent neurological and psychiatric disorders such as epilepsy, neurodegenerative disease, anxiety, and alcohol and drug dependence."

 

So, chronic gabapentin use may very well influence gabbaAR's akin to long term low dose benzodiazepines modulation???  Looks like this could be the case and that all the focus on VACC's as the primary mechanism of action could be misleading.  There has been some vague sense of NMDA receptor influence on behalf of gabapentin for a while but it hasn't beren clearly elucidated.  However, this study seems to show some pretty powerful evidence of direct modulation of NMDAR's.  Good Grief!!!!!

 

In the authors' words.......

 

" Here we present our striking findings that α2δ-1, through its C-terminal domain, forms a heteromeric complex with NMDARs to potentiate their synaptic trafficking and excitatory synaptic transmission and that interrupting the α2δ-1-NMDAR interaction reverses the synaptic NMDAR hyperactivity associated with neuropathic pain. This new information redefines our understanding of the α2δ-1 function and the role of α2δ-1 in neuropathic pain development. Our findings also challenge the conventional perception about the molecular action of gabapentinoids, showing that α2δ-1-bound NMDARs, rather than VACCs, are the relevant target of gabapentinoids."

 

OK, so let's turn all the thinking upside down again....... 

 

-RST

 

 

 

[[li...]]

Knowing the theory and being able to use that to fix myself are two very different things. I now know what I shouldn´t have done ... of course, the lorazepam was not my idea and normally I´d never have taken it.

 

As far as the ´motor cortex´ theory is concerned, the binding profile of both clonazepam and lorazepam are relatively close. Diazepam is very different.

Diazepam, lorazepam, phenobarbital, beer are clearly GABAergic. Clonazepam isn´t. Not to me. As some docs say ´it´s an anticonvulsant´.

 

I read somewhere https://www.ncbi.nlm.nih.gov/pubmed/11830761 (or elsewhere) that activating GABAB causes dopamine release. Knowing that clonazepam acts on the thalamic reticular nucleus and GABAB in that part of the brain, it should cause the release of dopamine. I´m not sure what that´d do.

 

And part (only part) of my problem is the extreme muscle damage to put it that way, using the analogy of the 'motor cortex' it gives a very different physiological effect. If I were to say that I'm in a constant state of CNS overtraining that's maybe not correct, but it's an analogy. It may not kill me quickly, but that doesn't mean I'm fine. And I have the 'genes' for rapid loss of muscle mass and being a hardgainer. Moving a little will at best do very little ... I don't see how an antidepressant or antipsychotic would help ... 'Interdose withdrawal' (very imperfect description, I neverconsciously experienced interdose withdrawal before the lorazepam) is not something I can just fix by splitting the dose and I'm very skeptical about Librium or diazepam. I did last only 2.5 days on diazepam early 2017.

 

´Humpty Dumpty´·