Benzo stored in fat causing waves??

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Braban

I've wondered about the 200 hour half life thing too. Maybe most of us fall closer to 36 rather than 200 hours and it is just the rare individual who is at 200 hours. The median and mode of this would be interesting information.  My own duration of action of Valium seemed to fall nicely in the 6-12 hour range, maybe closer to 6. But when I tested my urine via home test strips when I was close to threshold and up-dosed I tested positive quite easily even before I thought I should have and tested negative again rather quickly. Now the elimination half life of Valium is biphasic, but my "eyeballed" results are consistent with a pretty short elimination half life at least for me.

Bart

[[Co...]]

Hi One.

I think you're right about that. I used the average half life. Interesting, all the people who say the half life of Valium is 200 hours. Actually it varies a whole lot among individuals and ranges from 36-200 hours. Your chances that Valium's half life for you being 36 hours is the same as it being 200 hours. The average of this is (36+200)/2=118 hours or about 5 days. It takes slightly less than 3 1/2 half lives to reduce a drug by 90% or 1 power of 10. I rounded things off to simplify the math. There was a survey of people who had completed their tapers which found that the most difficult time for the most people was at the end and right after the end of their tapers. I suspect the reason for this is that you are not exactly "jumping" from your last dose. You are going to 0 from the total amount of benzo in your body which is a whole lot more than your last dose. This amount is determined by 2 factors. One is the very long half life of Valium which will lead to accumulation by its own right. The other factor is related and is due to tissue distribution and accumulation of the drug which in the case of Valium is around 8 times your daily dose. So when you think you are jumping from a very low dose, in reality you are not. IMO this is the real reason the end of the taper is so "difficult" and helps symptoms go on and on. If you look at my sig line you will see how slow I went at the very end which is why I ended the taper with essentially no symptoms unless I do something "bad" to bring them out like have too much sugar, alcohol, too much stress, not enough rest, etc. Hope this helps.

Bart

 

Hi Bart,

 

I'm not sure about your explanation for the end part of a Valium taper being more difficult for some people. Maybe I'm missing something. Whilst it is certainly true that there is a great deal of accumulation with longer half-life benzodiazepines (like Valium), when the last dose is taken, the long half-life also means that what's left in the body will be metabolised relatively slowly, over a week or two or more. So, the last dose does not result in sudden drop in blood levels. In addition to this, with Valium, we have to take large doses not just because it is a relatively weak benzo, but because the long half-life probably means that it is less than fully effective while blood level build up and (near) steady state is achieved. What I'm trying to get at is that it doesn't matter that it builds up to something like eight times the initial peak (after the first dose) if eight times that blood level is what is required for therapeutic effect.

[[Co...]]

Hey Braban

Thanks for the info. There seems to be a lot of variation among individuals, huh? My overall point was Valium takes a long time to all be eliminated from your body but it does come out of fat cells at a steady rate. It does not come out in irregular quantities causing variation in symptoms.

Bart

 

Hi Bart,

 

I'm sure you are right about this. Even if you are wrong, if the benzodiazepine is stored in fat cell, I suggest that it can have no effect upon GABA receptors. If it is instead released from the fat cells, it will be metabolised. There is a finite supply of benzodiazepine within fat cells, so no matter how we look at this, it is not an issue.

[[Pi...]]

Well... Talk about a wet blanket..... Lol Colin u just squashed that conversation....lol

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Hi Pinkee

Like Colin said, the effect is negligible. There is storage of benzos in fat cells but it will come out at a steady rate as the benzo will remain in equilibrium with our plasma and be metabolized and excreted also at a fairly constant rate.

Bart

[[Pi...]]

So what do u mean Bart when u say when u jump at what u think is a low dose, it's actually a high dose due to ginormous half life ? Or was it Braban who said that?

                  Anyway I am nearly ready for that jump, and I'm just wondering.... Am I going to get smashed with w/ds??? I HOPE not !

[[ih...]]

I jumped at 0.5mg valium & did get some sx after about 2 weeks by which time my blood was probably completely free of the drug. It was nowhere near a smash though & the main sx, insomnia was only really bad for another couple of weeks.

[[Pi...]]

Good to know Ihope ! I am so happy to be so close but at the same time a bit nervous. Still , I have to do it. Hopefully it won't get too bad.

[[On...]]

So what do u mean Bart when u say when u jump at what u think is a low dose, it's actually a high dose due to ginormous half life ? Or was it Braban who said that?

                  Anyway I am nearly ready for that jump, and I'm just wondering.... Am I going to get smashed with w/ds??? I HOPE not !

 

Hi Pink! Congratulations on your amazing taper and fortitude in sticking with it. I know how very hard it has been for you as you have shared many details with me in our conversations.

 

In very simple terms, what Bart is saying is that, because the metabolites of Valium are stored in the body, they build up to 8 times what your daily dose is. So if you are taking .5 mg, you can think of it as 4.0 mg, which is .5 x 8. This stored Valium is released slowly over time back into your system and then eventually eliminated. The "half lives" Bart refers to is the rate at which this stored Valium is released back into your system and eliminated.

 

So, again, in the most basic and simple terms, if you jump from .5, you are essentially jumping from a dose of 4.0 mgs due to the Valium stored in your system.

 

This is why many people, though not all, have some pretty extreme and extended withdrawal effects after jumping from this high a dose. It's not "really" just .5 mg.

 

You are so close to being free and you have suffered so much. I hope you consider, since it is already such a low dose anyway, staying with it and going much lower for longer before jumping.  If you look at Bart's signature history and consider that he is now basically done and is having NO withdrawal symptoms, I think it could be well worth it. I hate to see you suffer anymore than you already have and you have invested so much in getting back your life again. I'd really be sad to see you set back due to jumping too soon and too high.

 

Much love and high hopes for your total recovery,  ~OneLove  :smitten:

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Hi Colin

I was looking for an explanation of why the end and just beyond the end of a taper tends to be difficult for a lot of people. Regardless of how we cut, the percentage of our cuts  have to go up at the end of a taper. The last cut to 0 will be 100%. From here the amount of Valium in our serum falls by 50% every 36-200 hours including the amount of drug coming out of our fat cells. Thus, the highest percentage drops in serum levels occur at the end and shortly after the taper's completion and is a whole lot more on a percentage basis than at any other time in our tapers. The shorter half lived benzos will show a more rapid percentage drop. Perhaps the body perceives these higher percentage drops as more of a shock even though the absolute amount of the cut is small as we near the end and complete the taper. For some of us who need to taper very slowly, really slowing things down at the very end may be beneficial for those reasons.

Bart

[[Co...]]

So what do u mean Bart when u say when u jump at what u think is a low dose, it's actually a high dose due to ginormous half life ? Or was it Braban who said that?

                  Anyway I am nearly ready for that jump, and I'm just wondering.... Am I going to get smashed with w/ds??? I HOPE not !

 

Hi Pink! Congratulations on your amazing taper and fortitude in sticking with it. I know how very hard it has been for you as you have shared many details with me in our conversations.

 

In very simple terms, what Bart is saying is that, because the metabolites of Valium are stored in the body, they build up to 8 times what your daily dose is. So if you are taking .5 mg, you can think of it as 4.0 mg, which is .5 x 8. This stored Valium is released slowly over time back into your system and then eventually eliminated. The "half lives" Bart refers to is the rate at which this stored Valium is released back into your system and eliminated.

 

So, again, in the most basic and smile terms, if you jump from .5, you are essentially jumping from a dose of 4.0 mgs due to the Valium stored in your system.

 

This is why many people, though not all, have some petty extreme and extended withdrawal effects after jumping from this high a dose. It's not "really" just .5 mg.

 

You are so close to being free and you have suffered so much. I hope you consider, since it is already such a low dose anyway, staying with it and going much lower for longer before jumping. F you look at Bart's signature history and consider that he is now basically done and is having NO withdrawal symptoms, I think it could be well worth it. I hate to see you suffer anymore than you already have and you have invests so much in getting back your life again. I'd really be sad to see you set back due to jumping too soon and too high.

 

Much love and high hopes for your total recovery,  ~OneLove  :smitten:

 

I think this false logic.

 

I posted about this yesterday, but no one responded: http://www.benzobuddies.org/forum/index.php?topic=91838.msg1181969#msg1181969

 

The build up in blood levels (because of Valium's long half-life value) is required for therapeutic effect. If Valium instead had a short half-life (and this was the only difference), we would need to take much higher doses of Valium for a similar effect. Valium is a very weak benzodiazepine, even weaker than the 'equivalent dose' might indicate on the surface. So, even if you wish to think of a single 0.5mg dose equating to about 4mg (in some people) after extended use (after it has built up in their system), it is still only a 0.5mg dose. What I am saying is that if Valium builds up by, say, a factor of eight after extended use, Valium is actually eight times weaker than the 0.5mg dose might indicate. So, quitting at 0.5mg is still quitting at 0.5mg; it is not quitting at a 4mg dose equivalent.

[[Co...]]

Hi Colin

I was looking for an explanation of why the end and just beyond the end of a taper tends to be difficult for a lot of people. Regardless of how we cut, the percentage of our cuts  have to go up at the end of a taper. The last cut to 0 will be 100%. From here the amount of Valium in our serum falls by 50% every 36-200 hours including the amount of drug coming out of our fat cells. Thus, the highest percentage drops in serum levels occur at the end and shortly after the taper's completion and is a whole lot more on a percentage basis than at any other time in our tapers. The shorter half lived benzos will show a more rapid percentage drop. Perhaps the body perceives these higher percentage drops as more of a shock even though the absolute amount of the cut is small as we near the end and complete the taper. For some of us who need to taper very slowly, really slowing things down at the very end may be beneficial for those reasons.

Bart

 

Hi Bart,

 

I think this is the wrong way of thinking about it.

 

When at high doses, where GABA functioning is almost totally regulated by benzodiazepine, looking at the dose cut in terms of percentages makes sense. However, at lower doses (particularly after following a sensible taper plan), much of our normal GABA functioning has returned to us. So, any cut to our dose of benzodiazepine has a proportionately smaller effect. So, absolute cuts (milligrams) rather than proportional cuts (percentages) makes more sense at lower doses (and keeps the taper plan to a reasonable length). If this were not how it works, quitting our last molecule of benzodiazepine would have the same withdrawal effect as quitting cold turkey from a dose of 20mg.

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Hi Colin

What you're saying certainly sounds logical. Unfortunately it does not fit with our experience. If as you say the absolute cuts have a smaller proportional effect  our tapers should get easier as we go down and should be the easiest at the very end of the taper. This is not what most people experience. Certainly the absolute amount of our cuts at the end have importance, but I believe the percentage of our cuts near the end may carry more significance  than is generally believed. It certainly fits better with the aforementioned study and the experience of many of us. Another interesting thing about Valium and GABA receptors is that if I do a back of the envelope calculation it appears that even at small doses we are ingesting more than enough drug to cover every GABA receptor in our bodies. Now Valium is known to bind to other tissues such as skeletal muscle and to be taken up and stored by other tissues such as fat but there still seems to be an awful lot of molecules of the stuff sitting around in our bodies. Perhaps it just takes a lot of Valium to overwhelm some other modulating factors in GABA receptor physiology. Naturally, all my arm chair speculation  could be completely wrong, but there are a lot of curious things about benzos which are fun to think about. It seems the more you learn about something like this the more you realize how little is actually known.

Bart

[[Br...]]

Hey Braban

Thanks for the info. There seems to be a lot of variation among individuals, huh? My overall point was Valium takes a long time to all be eliminated from your body but it does come out of fat cells at a steady rate. It does not come out in irregular quantities causing variation in symptoms.

Bart

 

Hi Bart,

 

I'm sure you are right about this. Even if you are wrong, if the benzodiazepine is stored in fat cell, I suggest that it can have no effect upon GABA receptors. If it is instead released from the fat cells, it will be metabolised. There is a finite supply of benzodiazepine within fat cells, so no matter how we look at this, it is not an issue.

 

Hello Colin.  I have heard it said before (perhaps it was by Barry Haslam) that the benzo stored for a long time in parts of the body is eliminated without any active effect.  This is also what I think you have written.  However I am not sure this has been proven to be true. 

 

As I understand it, normally a drug that moves into another compartment will, to a greater or lesser extent, leak back to the active compartment.  I believe diazepam is no exception. 

 

In other words, with repeated dosing the stores of diazepam will affect the level of active diazepam.  (Of course I'm simplifying the terminology because diazepam decomposes into several metabolites which in turn are converted to yet another metabolite.  I have called all these "diazepam" but I don't think the name makes any difference.)

 

 

 

 

 

[[...]]

There's no reason for a drug leaching back into the serum from a tissue ( or compartment as we say) it has been stored in to behave any differently than the drug already there.

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Hi Pinkie,

Congrats on being so close to the end of your taper.  OneLove and Bart have a point regarding the jumping off point.  We see so many members who have jumped off of .5 or higher end up suffering for months after the last dose.  I have not yet planned out how low I will go or how long I end up holding the last dose because it is yet months away, but I believe I will drop the last three or four cuts over weeks instead of days just to be sure that I remain functional since I have to work.

 

I hope which ever way you choose it works out well for you and please keep coming back to post your progress.  Those of us nearing the end will want to know how you are doing!  :smitten:

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/quote]

 

. So, quitting at 0.5mg is still quitting at 0.5mg; it is not quitting at a 4mg dose equivalent.

 

It certainly seems to me that if you taper down to .5mg and then quit, you are not quitting just from .5mg but rather with all the Valium in your body at the time. It does help that Valium has a long elimination half life.

Bart

[[Co...]]

So, quitting at 0.5mg is still quitting at 0.5mg; it is not quitting at a 4mg dose equivalent.

 

It certainly seems to me that if you taper down to .5mg and then quit, you are not quitting just from .5mg but rather with all the Valium in your body at the time. It does help that Valium has a long elimination half life.

Bart

 

Hi Bart,

 

Yes, the long half-life certainly helps, but accumulation of about eight times the dose (in your example*) only serves to demonstrate the extreme relative weakness of Valium. Eight times steady state blood levels compared to blood levels after a single dose just means that Valium is eight times weaker than we might suppose, and that accumulation is required for the expected therapeutic effect for a given dose. So, quitting at 0.5mg is still quitting at 0.5mg, not an equivalent of 4mg, even after extended use.

 

How long a half-life and how many doses per day did you use for your x8 accumulation?

[[pr...]]

Suppose you take .5mg for long enough that your blood concentration reaches a steady state level. If you stop abruptly then the blood level can only decrease, not increase.

 

It makes no sense to me that taking .5mg can be the same as taking 4mg.

[[On...]]

Suppose you take .5mg for long enough that your blood concentration reaches a steady state level. If you stop abruptly then the blood level can only decrease, not increase.

 

It makes no sense to me that taking .5mg can be the same as taking 4mg.

 

And you are right! Taking .5 mg. is simply taking .5 mg.

 

Jumping from .5 has been discussed as having something akin to the equivalent of 40 mg of the metabolites still in the body tissues from previous continuous doses of .5 mg.

 

 

 

[[...]]

So, quitting at 0.5mg is still quitting at 0.5mg; it is not quitting at a 4mg dose equivalent.

 

It certainly seems to me that if you taper down to .5mg and then quit, you are not quitting just from .5mg but rather with all the Valium in your body at the time. It does help that Valium has a long elimination half life.

Bart

 

Hi Bart,

 

Yes, the long half-life certainly helps, but accumulation of about eight times the dose (in your example*) only serves to demonstrate the extreme relative weakness of Valium. Eight times steady state blood levels compared to blood levels after a single dose just means that Valium is eight times weaker than we might suppose, and that accumulation is required for the expected therapeutic effect for a given dose. So, quitting at 0.5mg is still quitting at 0.5mg, not an equivalent of 4mg, even after extended use.

 

How long a half-life and how many doses per day did you use for your x8 accumulation?

 

Hi Colin

Interesting topic

 

Here's a piece from Reg Peart where says Valium accumulates to 8x its daily dose in 4 weeks. I've seen the more conservative statement that Valium accumulates up to 8x in about 8 weeks somewhere else, so I just went with the more conservative number.

 

Accumulation could be related to but is not  dependent on half life which renders it immaterial for  accumulation levels.

http://www.benzo.org.uk/vot4.htm

 

 

This gets a bit muddy here (doesn't it always?). Certainly, if you take 5mg of V every day you will not be experiencing the same effect after 4-8 weeks as taking a single dose 8x this or 40mg. We have to take into consideration the duration of action of Valium which is commonly 6-12 hours and may be up to 24 hours. Ashton mentions duration of action but talked more about the long elimination half life. If I remember correctly, she did say the long half life would account for some subtle effects after the immediate effect or duration of action is over. IMO, once we get below the minimum dose for a therapeutic effect, say around 2mg or so, these other "subtle" effects become more significant. If this were not the case and if the accumulation effect were unimportant then jumping from a steady state at any level below 2mg should not cause  problems to any greater extent than we are already experiencing from the accrued benzo withdrawal damage. In other words, symptoms should not worsen if you jumped at .5mg, 1mg or 1.5mg. This clearly is not the case for most people.

 

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Hi One

I know one person who regrets he tapered so slowly. I'm sure there are others. My taper will end up taking around 22 months. I'll bet the majority of people are able to do it faster than me. I would say just keep tapering at whatever rate gives you symptoms you can reasonably tolerate. I would advise against jumping at a level higher than your cut rate. There are some theoretical reasons for going super slow at the very end but nobody really knows if this better or not. It's entirely possible I could still take a very long time to heal even after doing it this way. There are downsides to staying on benzos for a long time, even if the dose is very small.

Bart

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Hi Bart,

Your last statement about downsides for being on benzos so long even at small doses does haunt me when I think about it.  Have I made my long term recovery longer because of a slow taper after such short term use, or have I made it easier to live a normal life by doing it this way....only time will tell I guess.  Since this is the decision I made and I am here now, this is the way it will be.

 

If only you and I had professional help we may have taken different paths but we both had to find out what to do on our own and so now here we are.

 

Thanks for all your information - it is really helpful to know what to expect from someone who has already been there.

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Hi eliz

Your taper doesn't look at all long to me. I always thought that if I developed problems such as toxicity, paradoxicity or some other adverse issue with Valium I would just speed up my taper and get off the drug in short order. It seems I never developed any of these problems and have now arrived at the end of a long taper feeling pretty well. I would think most people could have done this a lot faster than me, but it is what it is and has now ended when it ends for me.

Bart

[[Pi...]]

I don't know why this is so confusing to me! I find decimals are not my forte.. I am eyeballing my cuts and have just found I am now down to what looks like 1/8 of mg. I get stuck the decimal point.

  However  tonight is my drop night. I have all day to figure whether I drop or jump. I will decide with my gut. I have never updosed  or rescue dosed. So when I do jump I will have no rescue. I will not have any safety net. 

                    Thank you to all of you who have posted on this topic. I am off today to see a specialist about my dodgy throat. So won't see any BBs for the day.

                    If there are any ideas I can look at when I get home please , please put them down on cyber paper for me??? I will check back in when I get back to see. Then I will make my decision!

          To jump ..........or to drop!          Have a good night....or day.  Big hugs to all of u my special buddies!      Pinkee