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

[[Re...]]

RKO- I wonder if the multivitamin plays a role here. I know for me, I was dependent on even small doses of Magnesium. And it is a short acting benzo basically. I had to slowly taper mag and it was very difficult. Actually it's sxs from mag w/d that led to the benzo Rx.... before I knew what was going on. Also ppl report setbacks from other vits including Bs, D, Calcium, Mag of course, and probably more. I even avoid coconut water bc of the high concentration of mag. Anyway, just some thoughts- idk your whole story or if this vitamin plays a role for you but just sharing some other experiences. You will turn around again!

 

Thanks libr. Should I resume the Centrum? I have to get a flu shot too and am scared of the consequences. None of this makes any sense.

 

Hey, RKO.  I'm glad you found this thread.

 

The first thing is to take a moment and breathe.  Like dm123 said here and I said in PM's you are going to be OK.  You just need to take it easy and maybe take it easy for longer than you would like.  Also, as has been noted, you are off the benzo so your body will adapt back to a better place.  That is huge. 

 

Also, in respect of vitamins and supplements, you really have to be careful about what you are doing.  It is not so simple as starting and stopping these substances as they can have profound effects in those of us recovering from benzo damage.  For example, depending on the oral dosage, vitamin C can be a powerful antioxidant.  That is generally a good thing.  However, what most people do not know is that the body's natural ability to manage free radicals (where vitamin C plays a significant role), can be  downregulated when we consume antioxidants chronically.  Therefore, when we stop taking vitamin C, the compensatory response of the body lags and you may end up with a significant increase in free radical concentration leading to problems such as the promotion of peroxynitrite and all of the issues that can come with that.

 

I am not a medical doctor or research scientist so please understand I am not giving medical advice.  All I am saying is  to be aware of the effects of what you are taking.  Moreover, any substance be it 'natural' or 'synthethic' can have a multiplicity of actions in our bodies and we need to think about all of the potential actions and interactions before we choose to add or remove supplements.  Just a little FYI.

 

Again, I am pretty confident you're going to be fine.  Just take it easy and try to refrain from causing perturbations in your CNS by adding and removing supplements.

 

-RST

[[...]]

Great advice realslimtaper! I agree completely.

[[...]]

Thanks RST. I’m being REALLY hard on myself. Especially because another buddy told me repeatedly to avoid exercise after my initial attack and I didn’t listen and I proved that person right as I wasn’t prioritizing my healing actions.

 

Then again I didn’t know I would have a setback after going several times with no reaction. This last workout just put me over the edge. But I’ve come to learn that it definitely ties to the food sensitivities and foggy reactions in my brain to exercise as those are now heightened.

 

We made a Blue Apron meal that used bone broth last night which is naturally high in glutamate so maybe that’s why I had issues feeling anxious and wired with zero hour sleep last night. I don’t know. I just feel there’s even more glutamate floating around my brain than prior to this gym visit hence the exacerbated symptoms. I had a gluten free protein bar (pea and rice protein) after the workout and have been using that the last few times, avoiding whey protein as that’s high in glutamate.

 

None of this makes any sense but this has been the worst wave yet between the depression and severe insomnia along with the newly introduced body tremors.

 

This just totally sucks since I was asymptomatic just two weeks ago. I long for that sleep and just want a redo in the worst way possible.

[[Su...]]

Thanks RST. I’m being REALLY hard on myself. Especially because another buddy told me repeatedly to avoid exercise after my initial attack and I didn’t listen and I proved that person right as I wasn’t prioritizing my healing actions.

 

Then again I didn’t know I would have a setback after going several times with no reaction. This last workout just put me over the edge. But I’ve come to learn that it definitely ties to the food sensitivities and foggy reactions in my brain to exercise as those are now heightened.

 

We made a Blue Apron meal that used bone broth last night which is naturally high in glutamate so maybe that’s why I had issues feeling anxious and wired with zero hour sleep last night. I don’t know. I just feel there’s even more glutamate floating around my brain than prior to this gym visit hence the exacerbated symptoms. I had a gluten free protein bar (pea and rice protein) after the workout and have been using that the last few times, avoiding whey protein as that’s high in glutamate.

 

None of this makes any sense but this has been the worst wave yet between the depression and severe insomnia along with the newly introduced body tremors.

 

This just totally sucks since I was asymptomatic just two weeks ago. I long for that sleep and just want a redo in the worst way possible.

Hi RKO,

FWIW I was advised by a clinic to use pea protein powder which caused and immediate increase in anxiety.  When I checked the label it has glutamic acid in it. Glutamic acid = glutamate...

So there may be a few things contributing to your uptick in sxs.

SS

[[Te...]]

dm123, can you explain this in plain English?  THANK YOU FOR ALL YOU DO!!!  :thumbsup:

 

https://www.ncbi.nlm.nih.gov/pubmed/30287828

 

Lapis posted this in Benzos in the News. You might want to answer there. Thanks again!!!

[[li...]]

dm123,

 

I've been reading a bit about Librium. Although some data are hard to come by, it seems it's lipophilicity is relatively low compared to drugs like diazepam. Which is not suprising, considering its slow onset.

 

You have written some things about benzos with a slow onset versus a quick onset. I don't know the theory as well as you do, but I suspect that part of your analysis about onset of action (heterogenic plasticity?, don't recall the exact phrases) is incorrect. After all, 30-60 minutes for diazepam's onset (my experience) is not that fast.

 

Lipid solubility may be more relevant. I know you don't have proper data about Librium's doa, but if it takes 4 hours to peak (one source) will it not suggest a lower lipid solubility and a longer duration of action ? It's a bit hard to imagine otherwise, for me anyway. I could imagine it would also affect distribution, for me that's complicated. Possibly, lipid solubility will also affect where/how the drug binds to ?

 

[[Fr...]]

Liberty

I have been on both now and I can tell you how I experienced them but I know everyone is different. Valium hit me quick in 20 mins and peaked within an hour. Librium hit me 1-1.5 hours and peaks 1-2 hour after that. As far as duraction of action for me Valium was 3-4 hours and Librium seems to be about six hours.

[[Su...]]

Liberty

I have been on both now and I can tell you how I experienced them but I know everyone is different. Valium hit me quick in 20 mins and peaked within an hour. Librium hit me 1-1.5 hours and peaks 1-2 hour after that. As far as duraction of action for me Valium was 3-4 hours and Librium seems to be about six hours.

Good to know.... it's so hard to come up with some information about duration of action, and I think it's a crucial part of the decision s to what to cross to and how to dose.

Many thanks 

SS

[[Fr...]]

Ss

Keep in mind these are new meds to me and I still feel the effects. K used to last me six hours too but now I feel nothing when taking it.

[[li...]]

I just learned a new thing. By accident.

 

https://www.khanacademy.org/science/biology/human-biology/neuron-nervous-system/a/neurotransmitters-their-receptors

 

The acetylcholine receptors in skeletal muscle cells are called nicotinic acetylcholine receptors. They are ion channels that open in response to acetylcholine binding, causing depolarization of the target cell. [More info]

When a nicotinic acetylcholine receptor opens, it lets sodium (Na+\text {Na}^+Na+N, a, start superscript, plus, end superscript) ions flow into the cell down their concentration gradient. The channel is also permeable to K+\text {K}^+K+K, start superscript, plus, end superscript ions, which flow out of the cell down their own concentration gradient. Although the two types of ions move in opposite direction, the net effect is depolarizing, because there are more Na+\text {Na}^+Na+N, a, start superscript, plus, end superscript ions that flow in than K+\text K^+K+K, start superscript, plus, end superscript ions that flow out.

 

NEXT The acetylcholine receptors in heart muscle cells are called muscarinic acetylcholine receptors. They are not ion channels, but trigger signaling pathways in the target cell that inhibit firing of an action potential

 

Interesting, that exercise definitely does something with Ach in the skeletal  muscles. That's nicotinic, it seems.

It does have an effect on Ach in smooth muscle, exercise tends to relax smooth muscle afterwards for many days. Apparently, decreasing release.

 

I have been abusing exercise for some time (at least since this year), to relieve abdominal distress. Not healthy on the long run.Seems to be some kind of overexhaustion.

 

 

 

 

[[Su...]]

Ss

Keep in mind these are new meds to me and I still feel the effects. K used to last me six hours too but now I feel nothing when taking it.

ahh very good point.  I'll await an update when it feels right to do so.

[[cs...]]

dm123,

 

I've been reading a bit about Librium. Although some data are hard to come by, it seems it's lipophilicity is relatively low compared to drugs like diazepam. Which is not suprising, considering its slow onset.

 

You have written some things about benzos with a slow onset versus a quick onset. I don't know the theory as well as you do, but I suspect that part of your analysis about onset of action (heterogenic plasticity?, don't recall the exact phrases) is incorrect. After all, 30-60 minutes for diazepam's onset (my experience) is not that fast.

 

Lipid solubility may be more relevant. I know you don't have proper data about Librium's doa, but if it takes 4 hours to peak (one source) will it not suggest a lower lipid solubility and a longer duration of action ? It's a bit hard to imagine otherwise, for me anyway. I could imagine it would also affect distribution, for me that's complicated. Possibly, lipid solubility will also affect where/how the drug binds to ?

 

Hi liberty,

 

I’m not sure about the lipid solubility, and would have to read up on that.    As Jen stated, I just know that valium hit me very quickly (minutes)relative to librium (an hour or so).  Given that, the heterosynaptic plasticity , in theory, would have to adapt more quickly. Adaptability has a few parameters, two of which are “by how much”, and how quickly (rate of adaptation).    Adaptation is “greater” the more “how much” there is and the faster the “how much” occurs.  If we assume the same “how much”  , it becomes an issue of differences in how fast.  Homosynaptic plasticity takes place over longer timeframes like 4 hours to days and weeks.  Heterosynaptic plasticity is the fast responder on the order of minutes and an hour or two.  I agree, data is not consistent between the two.

[[cs...]]

dm123, can you explain this in plain English?  THANK YOU FOR ALL YOU DO!!!  :thumbsup:

 

https://www.ncbi.nlm.nih.gov/pubmed/30287828

 

Lapis posted this in Benzos in the News. You might want to answer there. Thanks again!!!

 

Hi Terry,

 

I just had time to read the abstract.  It looks like in PTSD (note it is important that they were not exposed to drugs) there are adaptive changes at the benzo receptor sites in certain regions of the brain, that make the receptor sites more sensitive.  This is a good thing and tells us that these changes  are sensitizing the areas of the brain and the binding sites of receptors at these sites, so that they are better able to inhibit neurons, which is good for an overly excitable disorder like PTSD.

 

The areas of the brain affected include areas that are responsible for interception, which itself is important for maintaining homeostasis (see below).

 

From wiki

 

Quote

Interoception is contemporarily defined as the sense of the internal state of the body.[1] It encompasses the brain’s process of integrating signals relayed from the body into specific subregions—like the brainstem, thalamus, insula, somatosensory, and anterior cingulate cortex—allowing for a nuanced representation of the physiological state of the body.[2][3] This is important for maintaining homeostatic conditions[4] in the body and, potentially, aiding in self-awareness.[5]

End quote

 

 

[[...]]

Librium is less lipophilic than V  - that is why on the MT thread, it was concluded that L could be make into a liquid for tapering with just using water - something that cannot be done for the other benzos, esp not V or K.  Onset and duration of action are both more complicated than going just by how lipophilic something is although it may play a role. Anyway, L is specifically used b/c it doesn't give that sudden rush like V and therefore is not abused.  I have never taken V, but I can say I do not feel the onset of L at all and I do not feel it wearing off at all. I dose once a day.  Onset of action can be measured in studies...duration is more variable by person.

[[li...]]

I wouldn't be able to get away with once a day dosing.

 

Your dose of K was low, and as I understand once a day. K has certain dose dependent effects.

[[...]]

I wouldn't be able to get away with once a day dosing.

 

Your dose of K was low, and as I understand once a day. K has certain dose dependent effects.

Interesting-  What are the dose dependent effects?

Also, what's "low" for one person may not be low for the next. Certain ppl get the same effect from lower doses as other ppl get from higher doses. Typically higher doses are studied and published bc there is more likely to be an "effect" but many ppl can get the same effect from lower doses- lower doses just aren't studied much. Costs too much and once you've proven efficacy, why spend more to figure out the right range of doses...

 

Anyway, in general, those who get the same effect from lower doses are women, lower weight, Asians, elderly, children.

[[...]]

Just saw my doctor and he agrees duration of action is really what matters, not half life. He said Librium definitely has a longer duration of action than Valium. With V, he generally has ppl dosing twice a day but with L, once a day can be enough. Also, he said drugs get absorbed by tissue, fatty tissue in particular, I think, and that pulls it out of the blood so the duration of action is shorter when that happens. He said someone who has less body fat (and these are my words- maybe less body tissue in general- like overall lower weight) will experience a longer duration of action bc the drug stays in the blood longer. This all makes sense to me!

 

He did not say anything about whether L vs V getting more absorbed by tissue but I would think they both do get absorbed but idk if one does so more or not.

 

He also advised me to never drink alcohol again for the rest of my life.

[[li...]]

'Interesting-  What are the dose dependent effects? ' Binding to receptors, affecting GPCRs (https://en.wikipedia.org/wiki/G_protein-coupled_receptor) probably serotonergic and cholinergic systems in particular.

 

I wouldn't be able to get away with once a day dosing.

 

Your dose of K was low, and as I understand once a day. K has certain dose dependent effects.

Interesting-  What are the dose dependent effects?

Also, what's "low" for one person may not be low for the next. Certain ppl get the same effect from lower doses as other ppl get from higher doses. Typically higher doses are studied and published bc there is more likely to be an "effect" but many ppl can get the same effect from lower doses- lower doses just aren't studied much. Costs too much and once you've proven efficacy, why spend more to figure out the right range of doses...

 

Anyway, in general, those who get the same effect from lower doses are women, lower weight, Asians, elderly, children.

[[li...]]

Did you get a doc who was particulary benzo wise ? GP, addiction doc ? Here, they are all idiots.

 

Just saw my doctor and he agrees duration of action is really what matters, not half life. He said Librium definitely has a longer duration of action than Valium. With V, he generally has ppl dosing twice a day but with L, once a day can be enough. Also, he said drugs get absorbed by tissue, fatty tissue in particular, I think, and that pulls it out of the blood so the duration of action is shorter when that happens. He said someone who has less body fat (and these are my words- maybe less body tissue in general- like overall lower weight) will experience a longer duration of action bc the drug stays in the blood longer. This all makes sense to me!

 

He did not say anything about whether L vs V getting more absorbed by tissue but I would think they both do get absorbed but idk if one does so more or not.

 

He also advised me to never drink alcohol again for the rest of my life.

[[li...]]

Note, observation:

 

I can see one common denominator bewteen lorazepam and the antimuscarinic drugs mebeverine and solifenacin. Acetylcholine. A certain effect on color perception.

 

It's is possible that lorazepam had a significant effect on the GPCRs. If I compare the effects of one particular dose of solifenacin en lorazepam, one could wonder if benzodiazepines (lorazepam) do not exert their effect in a significant degree by reducing acetylcholine.

[[Su...]]

Just saw my doctor and he agrees duration of action is really what matters, not half life. He said Librium definitely has a longer duration of action than Valium. With V, he generally has ppl dosing twice a day but with L, once a day can be enough. Also, he said drugs get absorbed by tissue, fatty tissue in particular, I think, and that pulls it out of the blood so the duration of action is shorter when that happens. He said someone who has less body fat (and these are my words- maybe less body tissue in general- like overall lower weight) will experience a longer duration of action bc the drug stays in the blood longer. This all makes sense to me!

 

He did not say anything about whether L vs V getting more absorbed by tissue but I would think they both do get absorbed but idk if one does so more or not.

 

He also advised me to never drink alcohol again for the rest of my life.

This is so validating!!!

I wish I had known of

Librium when I added a longer acting benzo, very reluctant to make a switch atm. But that could change. Also have some extra weight on me.... Benzoland blahhs don’t make for much exercise.

No alcohol ever, now that I need to get my head around. Sure have enjoyed the occasional glass of wine.

Thanks for this update and information it’s all so important.

👍🏻🙏🏻💕

[[li...]]

A few thoughts, most of those already mentioned in some form.

 

I think that clonazepam affects GPCRs more that almost (?) all other benzodiazepines. Possibly also those network/circuit effects. I think I sent a PM in which I mentioned an effect on GPCRs with ADs and which would be why ADs are ´slower´. I´m not sure about the source.

 

My thinking is that if I were to switch to diazepam or Librium, I would need extra time (probably a lot of time) for the GPCRs to catch up. So, much longer stabilization or tapering phase. Those GPCRs would need to catch up. Librium is weak, and diazepam ... didn´t work out well early 2017 (2.5 days !, I know approx. why) acts on alpha 1 and 5 which is not good to stay on at high doses.

 

I know, interpretations ... would you agree ? (I´m aware that you can take drugs that act fairly directly on GPCRs like ADs and APs, but if it helps .. not selective/different)

)

 

 

 

 

[[Fr...]]

Liberty

I would say if you are not making progress with what you are doing it maybe time to try something different. I have not had a problem with Librium at all except I may have to updose it because it does feel weaker. K withdrawal is brutal but I am certain once the Librium builds up to a good level of stabilization things will be better and I can get on with a slow taper and get off this stuff.

[[cs...]]

Just saw my doctor and he agrees duration of action is really what matters, not half life. He said Librium definitely has a longer duration of action than Valium. With V, he generally has ppl dosing twice a day but with L, once a day can be enough. Also, he said drugs get absorbed by tissue, fatty tissue in particular, I think, and that pulls it out of the blood so the duration of action is shorter when that happens. He said someone who has less body fat (and these are my words- maybe less body tissue in general- like overall lower weight) will experience a longer duration of action bc the drug stays in the blood longer. This all makes sense to me!

 

He did not say anything about whether L vs V getting more absorbed by tissue but I would think they both do get absorbed but idk if one does so more or not.

 

He also advised me to never drink alcohol again for the rest of my life.

 

Thanks Libr.  Very interesting information.

[[Re...]]

Note, observation:

 

I can see one common denominator bewteen lorazepam and the antimuscarinic drugs mebeverine and solifenacin. Acetylcholine. A certain effect on color perception.

 

It's is possible that lorazepam had a significant effect on the GPCRs. If I compare the effects of one particular dose of solifenacin en lorazepam, one could wonder if benzodiazepines (lorazepam) do not exert their effect in a significant degree by reducing acetylcholine.

 

Liberty:

 

I think there is some validity in your observation.  Moreover, cholinergic receptors are known to upregulate very quickly in response to antagonism.  My own observation (strictly subjective) is that the majority of sufferers in the short-term exposure group list lorazepam in their signatures.  That's the one that drop-kicked me!!!

 

-RST