HOW GABAA RECEPTORS ARE CREATED AND BENZO INDUCED CHANGES

[[Br...]]

Hello Perseverance.  Bravo for a wonderful piece! 

 

I will need to set aside some time to digest it properly when I get a genuinely lucid interval.

 

Glancing through your article, I am intrigued and disheartened by the possibility of neuroadaptations failing to ever fully restore the former status quo.

 

Hi Braban,

 

I have not seen anything that makes me think this that this is true...I think that there are some changes that happen in the signal transduction pathways- which I am looking into now.  But there is no change to our DNA, just how it is being copied and how things are phosphorylated--so while these changes may have been set into motion, I don't see why they would not eventually come back to status quo as the cell moves back towards homeostasis.  I think that because there are so many ligands that were thrown off kilter, this may take a long time to come back around...but again, these are all functional changes that were initiated to counteract the effects of the drug--and now that the drug is out of the picture, it would not make sense for the receptors to eventually revert back to their original states.

 

 

Hi Pers.  From a paper you posted which systematically went thru the permutations, I seem to recall there are something like 19 variants of GABA(A) receptors depending on which components constitute the pentameric structures. 

 

I have the impression that under certain circumstances (such as a very rapid taper) the newly expressed GABA receptors may not necessarily be exactly the same as the ones which were down-regulated.  In other words, we sometimes may not get exact replacements.  I think it is Ashton who suggests that it may be a mechanism similar to that which underlies PAWS.

 

 

[[Be...]]

What I was concerned about early on when I got off these benzo's was whether these drugs cause "structural" damage to our DNA, the double helix, and therefore would alter our natural transcription process for healing repair.  Was Dr. Ashton referring to DNA damage when she said there is no permanent damage?  It does make clear that there are functional alterations in gene expression.  Why can one person take these long-term and come off with no problem and another be stuck in benzo w/d s/x's?  Our genetics.  But, how can the same person take the same drug decades earlier long term and get off them with no problem, like I did, then have benzo w/d s/x's at a later time with long-term usage?  Should I truly be looking at my psychological state and what has contributed to my GABA receptors not fixing themselves in a timely manner like they should have?  People take these drugs for a reason:  stress.     

 

Hi Becksblue,

 

I saw in your signature that you were also prescribed Ambien?  Were you taking both Ambien and a benzo the first time around?  That may have tipped the scales and made a difference.  The other thing is I have noticed some people do seem to skate by the first time around but get hit the second time they try the drug...so there may be some sort of sensitization happening.

 

Looking at your signature it looks like you are around 18 months off?  You may be getting close, I have seen many people recover around the 22 month mark, although each persons recovery is unique.  I know it is hard, believe me.  Try to hang in there, because really you never know, it could be just around the corner for you.  You have a lot of time under your belt.

Perserverance, I'm only 6 months off now.  I didn't take ambien back in 1989, only the Xanax.  It always agreed with me and I always felt good taking it, except for this last time I was in tolerance w/d early on and the shrink attributed it to my nerves, etc.  Years ago, I remember not being in tolerance w/d when I quit taking it, and I can't remember how long I was on it.  I know it was more than a couple weeks.  I'm interested in knowing more about the active phase, because I've noticed that some of my s/x's have gotten worse, while others have improved.  I was interested in knowing about any DNA damage, because my understanding is that if there is damage or a nick to the backbone or breakage of both strands of the DNA in certain areas, then our bodies would not be able to repair itself.  I read somewhere that certain drugs can do this and I was wondering if benzo's have been tested for this.  I believe that as long as we have the good DNA strand to copy out our repair products for our GABA receptors, then we will heal, and can create more natural GABA receptors and prune out the ones that aren't funtioning properly, eventually.  My natural GABA receptors always worked fine and I was never an anxious, depressed, or antisocial person like I am right now.  I always felt good in my own skin' that's why this is so devastating to me.  I just spoke to my neighbor a few weeks ago, and she was on Klonopin for one year, went to detox, and said she couldn't remember much for three days, but felt fine afterward.  I thought, what the heck, why me, now? 

[[Pe...]]

 

Hi P,

 

Wow, you are just amazing! Can't wait to share this with my husband who IS a molecular biologist and has watched all my suffering while doctors didn't know what to do with me. I will be curious too to hear his thoughts about prospects for potential testing for people susceptible to benzo issues as he is working on related technology for diagnostics in general. (I'll share anything I learn.)

 

I hope you do, we would all be very interested in that.

 

I also appreciate the info on the problems with reinstatement after the silent phase. I did reinstate successfully once long ago after 30 days off due to unbearable migraines and iatrogenic depression. Having tried it every other way, I am finding that a slow daily microtaper works much better for me.

 

I'm interested in your thoughts in terms of a few practical applications for what you have shared here:

 

Any theories why some people seem to be able to tolerate alcohol post-benzo and others not? Is there a consensus that it should definitely be always avoided due to more sensitized/altered gaba receptors? (Having a hard time coming to terms with the fact that I may never be able to have a glass of wine again.) And IF I did the wine experiment at some point after feeling totally healed and fell apart, then it would seem that reinstatement and re-tapering would not be a good idea at all.

 

Benzodiazepines and alcohol bind to different GABAA receptors, however, both are allosteric modulators and therefore allosterically enhance the action of GABA causing more chloride to enter neurons.  Benzodiazepines like to attach to GABAA receptors that contain either an a1, a2, a3, or a5 sub unit plus a y sub unit.  Alcohol and neurosteroids like to attach to GABAA receptors that contain an a4 or a6 subunit.

 

However, since the inner workings of the brain are so intertwined, it has the potential to upset the recovery process.  After recovery we may still be vulnerable to sx recurrence and alcohol could throws things off and cause this.

 

I think that the body will strive over the years to set things back, so some people may find that they can tolerate alcohol down the road after they have recovered.  If you experienced a reoccurrence of sx, reinstating benzos would not be the way to go.  The best thing to do IMO would be to wait for the sxs to subside on their own.

 

Also along practical lines, I recently read this article on how meditation promotes genes for good health which was new to me. Perhaps that is one thing we can do in w/d that helps in ways more profoundly than just stopping obsessive worrying (which is also important):

http://www.newscientist.com/article/dn23480-meditation-boosts-genes-that-promote-good-health.html

 

I apologize for not having time to read this now, in fact, I may be leaving the forum for a while again to allow me to catch up on some work.  Perhaps you could share this with the members here by starting a thread on the topic.

 

And last, in reading your goals here for why you are sharing your research (i.e. education), I'm wondering what you think about supplements post-benzo to support return to function. It would seem that doctors who specialize in functional medicine (an example: www.drhyman.com) would be a good fit for those post-withdrawal as it would seem we have a functional vs. structural disorder as you pointed out. I have seen several but they have not been helpful DURING withdrawal. But what about, say, adrenal support supplements AFTER withdrawal to speed things along? Or do you think we should just let our bodies recover on their own?

 

The answer to most of the things you have asked me here I answered in this thread:

 

http://www.benzobuddies.org/forum/index.php?topic=77803.0

 

We really got into some deep discussions regarding supplements which I think you may find interesting.

 

As far as adrenal support- your adrenals are most likely working fine.  If the outputs are off due to benzos that would have happened higher up on the HPA Axis (e.g hypothalamus or pituitary gland).  Benzos affect the organs that give your adrenals instructions on what to do.  So as far as benzos go, if your adrenal glands do not have any other problems, I don’t see the need for adrenal support.

 

However, avoiding caffeine and excessive sugar could help take the load off the adrenals, which is always a good idea in any situation.

 

[[Pe...]]

 

Hi Pers.  From a paper you posted which systematically went thru the permutations, I seem to recall there are something like 19 variants of GABA(A) receptors depending on which components constitute the pentameric structures. 

 

I have the impression that under certain circumstances (such as a very rapid taper) the newly expressed GABA receptors may not necessarily be exactly the same as the ones which were down-regulated.  In other words, we sometimes may not get exact replacements.  I think it is Ashton who suggests that it may be a mechanism similar to that which underlies PAWS.

 

Hi Braban,

 

If you go back a few posts you will see that Bart threw out that same theory and we discussed possible 'short cuts' that may have happened post transcriptionally.  I also included in my original post research that supported this type of change, although in this research it was observed during long term benzo administration, I copied and pasted it here for you--

 

Researchers observed a change in subunit configuration after chronic benzodiazepine use that appeared to originate in the expression of new receptors.  In this study the neuron apparently swaps out receptors with subunit configurations sensitive to benzodiazepine binding with ones that are not:

 

“In rats given benzodiazepines chronically, the common α 1 γ2 sub-units are down-regulated, while rarer sub-units are elevated proportionately (Holt et al, 1999). It is suggested that transcription of the Gene cluster on Chromosome 5 (which encodes for α1 β2 γ2 sub-units) is inhibited on chronic benzodiazepine administration, while the transcription of the Gene cluster on Chromosome 15 is upregulated (Holt et al, 1999). In certain brain regions, the Chromosome-5-encoded receptor sub-unit proteins are replaced by those encoded in Chromosome 15, which show less sensitivity.” (7)

 

In this situation, the neurons apparently switched out receptors that had high sensitivity to benzodiazepines for ones with low sensitivity to counteract the effect of the drug.

 

 

--in any case, I should think that over time, after benzo discontinuation, this would eventually revert back to status quo as the neuron attempts to restore homeostasis.

[[Pe...]]

 

Perserverance, I'm only 6 months off now.  I didn't take ambien back in 1989, only the Xanax.  It always agreed with me and I always felt good taking it, except for this last time I was in tolerance w/d early on and the shrink attributed it to my nerves, etc.  Years ago, I remember not being in tolerance w/d when I quit taking it, and I can't remember how long I was on it.  I know it was more than a couple weeks.

 

You may not have been on it long enough back then for dependence to set in- plus the second time around you took Ambien, which would have definitely contributed to the situation.

 

I'm interested in knowing more about the active phase, because I've noticed that some of my s/x's have gotten worse, while others have improved.

 

This is a common trend and may have to do with phosphorylation- which I will get into more if I can get the Glutamate Hypothesis paper done- which will be a while.  The active phase appears to be when the wd sxs begin--but you have been in recovery for a long time now and many things have been happening since then.  No one has offered a concrete explanation as to why sxs wax and wane, disappear/reappear, windows & waves, etc... but it may have something to do with phosphorylation--- however I think that everyone is still trying to figure it all out...at least I know I am, lol.

 

 

I was interested in knowing about any DNA damage, because my understanding is that if there is damage or a nick to the backbone or breakage of both strands of the DNA in certain areas, then our bodies would not be able to repair itself.  I read somewhere that certain drugs can do this and I was wondering if benzo's have been tested for this.  I believe that as long as we have the good DNA strand to copy out our repair products for our GABA receptors, then we will heal, and can create more natural GABA receptors and prune out the ones that aren't funtioning properly, eventually.  My natural GABA receptors always worked fine and I was never an anxious, depressed, or antisocial person like I am right now.  I always felt good in my own skin' that's why this is so devastating to me.  I just spoke to my neighbor a few weeks ago, and she was on Klonopin for one year, went to detox, and said she couldn't remember much for three days, but felt fine afterward.  I thought, what the heck, why me, now?

 

I have not seen any research indicating that there were changes to the DNA molecules.  The only things I have seen are changes in the expression, or copies, of the DNA-- which are functional or plastic changes.  Based on that, functional changes should do just what you suggested and turn around over time.

 

There are so many factors involved that it is really no surprise that people have different experiences.  Everything form your own genetic make up, to benzo dosage and duration, to environmental factors, to other medications, etc... can produce a plethora of combinations making an endless array of situaions--which is why you should never compare your recovery to someone elses.

[[Pe...]]

Hi everyone,

 

Just letting you all know that I may be absent for a while as I need time to catch up on some of my other projects and personal stuff.  In the mean time, I hope that you all keep this thread alive- discussing related research and contributing anything you find.

[[Be...]]

Perserverance, you mentioned in a different post:  After recovery we may still be vulnerable to sx recurrence.  I was wondering if there is some genetic research done about why this may be the case?  This makes me think that I do have permanent damage and may never be able to fully heal and function normally if I'm always going to have flare-ups.  I want to work again, but if stress puts me into a wave again, then what?  It's disheartening to read this.

[[Kr...]]

Are there any indications of epigenetic changes to the DNA that may be effecting the gene expression of the GABAARs?  Have any researchers looked at this?

 

Thanks so much for the info!  I'm really looking forward to reading about glutamate as I found an article recently that linked high levels of glutamate in the brain to restless legs syndrome.  I've been suffering from this horribly in the last several months after I came off Klonopin.

 

Kris

[[...]]

Perserverance, you mentioned in a different post:  After recovery we may still be vulnerable to sx recurrence.  I was wondering if there is some genetic research done about why this may be the case?  This makes me think that I do have permanent damage and may never be able to fully heal and function normally if I'm always going to have flare-ups.  I want to work again, but if stress puts me into a wave again, then what?  It's disheartening to read this.

 

Hi Blue

I think this may be due to GABA receptors coming back in slightly altered form less responsive to GABA. Presumably, the body slowly corrects this over some variable time frame.

Bart

[[Be...]]

Are there any indications of epigenetic changes to the DNA that may be effecting the gene expression of the GABAARs?  Have any researchers looked at this?

 

Thanks so much for the info!  I'm really looking forward to reading about glutamate as I found an article recently that linked high levels of glutamate in the brain to restless legs syndrome.  I've been suffering from this horribly in the last several months after I came off Klonopin.

 

Kris

Kris, this was what I was also curious about also, whether the benzo's cause damage to the DNA which woud affect the transcription process for healing.  I know some drugs do damage the DNA double strand through breakages and nicks, which I understand, is bad news.  Of course, it depends on ones own genetic makeup, whether this damage will occur, if it does at all.  I don't think there has been any research done on this issue or it's not made available for public consumption by the makers of Xanax, Klonopin. . .Big Pharma keeping it under wraps.  I guess just like drinking alcohol, it can eventually do some real damage depending on the person.  I'd rather remain hopeful that this problem can all be healed fully in time and that there is no permanent symptoms.  I keep thinking if millions of people can come off long-term use with no lingering s/x's, then I can too. 

Also, I had a Rheumatologist do some blood tests while I was in tolerance w/d with leg cramps in my calves, restless leg s/x's, and the only positive finding was an an antiphospholipid antibody called Anti Beta 2 Glycoprotein 1 (IGM).  This causes blood-clotting issues in the circulatory system, causing the cramping in my legs and elsewhere.  My Sed rate was also quite low at about a 2, which indicated that I had some clotting issues going on at the time, an antibody-platelet complex dropping out quickly in the plasma.  I noticed that if I don't go for a walk almost everyday, I get the leg cramping, so I need to keep moving so my blood keeps from clotting in my system.  When I'm in a wave, I feel my whole body sort of cramp up and my veins feel like their rolling.  Well, this is off the topic, but not really, because it's all related to the benzo use and genetics, but thought I'd mention it. 

[[In...]]

I've just read through this thread sort of fast, and thus obviously not getting all the scientific info digested.

 

But I wanted to add what i learned in college some years back in abnormal psychology, and that is cognitive mapping. This is essentially that our brains are born with many pathways to develop skills and abilities, and as time goes by, certain pathways become dominant as "our way of doing things."

 

But developing the dominant pathways did not preclude that others could not also develop also as subsets or become dominant later on.

 

And of course, I have only to see my husband who has suffered a TBI years ago come back to a good portion of his function when he could not even sit still, sleep at all, remember anything, read anything, understand what he heard (auditory nerve damage), and somehow learned to read lips as a result without realizing how his brain has done some major rewiring.

 

And during a TBI, nerves in the brain are shaken back and forth within the skull, and thousands severed. So, this would seem to give some hope to the neuroplasticity of the brain and it's ability to recover. I hope I haven't repeated something here that was already said.

 

And by the way, his personality is pretty much the same as before other than he is older now, and so am I.

 

Intend

[[Ma...]]

Thank you intend.  That's very reassuring.

[[Kr...]]

Are there any indications of epigenetic changes to the DNA that may be effecting the gene expression of the GABAARs?  Have any researchers looked at this?

 

Thanks so much for the info!  I'm really looking forward to reading about glutamate as I found an article recently that linked high levels of glutamate in the brain to restless legs syndrome.  I've been suffering from this horribly in the last several months after I came off Klonopin.

 

Kris

Kris, this was what I was also curious about also, whether the benzo's cause damage to the DNA which woud affect the transcription process for healing.  I know some drugs do damage the DNA double strand through breakages and nicks, which I understand, is bad news.  Of course, it depends on ones own genetic makeup, whether this damage will occur, if it does at all.  I don't think there has been any research done on this issue or it's not made available for public consumption by the makers of Xanax, Klonopin. . .Big Pharma keeping it under wraps.  I guess just like drinking alcohol, it can eventually do some real damage depending on the person.  I'd rather remain hopeful that this problem can all be healed fully in time and that there is no permanent symptoms.  I keep thinking if millions of people can come off long-term use with no lingering s/x's, then I can too. 

Also, I had a Rheumatologist do some blood tests while I was in tolerance w/d with leg cramps in my calves, restless leg s/x's, and the only positive finding was an an antiphospholipid antibody called Anti Beta 2 Glycoprotein 1 (IGM).  This causes blood-clotting issues in the circulatory system, causing the cramping in my legs and elsewhere.  My Sed rate was also quite low at about a 2, which indicated that I had some clotting issues going on at the time, an antibody-platelet complex dropping out quickly in the plasma.  I noticed that if I don't go for a walk almost everyday, I get the leg cramping, so I need to keep moving so my blood keeps from clotting in my system.  When I'm in a wave, I feel my whole body sort of cramp up and my veins feel like their rolling.  Well, this is off the topic, but not really, because it's all related to the benzo use and genetics, but thought I'd mention it.

 

Hi Becksblue,

 

Well, epigenetic modifications aren't DNA damage.  But they do effect transcription.  They are potentially reversible, which is good.

 

I agree, it's best to keep hopeful and keep as healthy as possible so as not to hinder recovery.

 

Regards,

Kris

[[li...]]

bump

 

[[Pe...]]

Are there any indications of epigenetic changes to the DNA that may be effecting the gene expression of the GABAARs?  Have any researchers looked at this?

 

Thanks so much for the info!  I'm really looking forward to reading about glutamate as I found an article recently that linked high levels of glutamate in the brain to restless legs syndrome.  I've been suffering from this horribly in the last several months after I came off Klonopin.

 

Kris

Kris, this was what I was also curious about also, whether the benzo's cause damage to the DNA which woud affect the transcription process for healing.  I know some drugs do damage the DNA double strand through breakages and nicks, which I understand, is bad news.  Of course, it depends on ones own genetic makeup, whether this damage will occur, if it does at all.  I don't think there has been any research done on this issue or it's not made available for public consumption by the makers of Xanax, Klonopin. . .Big Pharma keeping it under wraps.  I guess just like drinking alcohol, it can eventually do some real damage depending on the person.  I'd rather remain hopeful that this problem can all be healed fully in time and that there is no permanent symptoms.  I keep thinking if millions of people can come off long-term use with no lingering s/x's, then I can too. 

 

 

My understanding of epigenetics is that a tag, such as a Methyl molecule, affixes near a gene on the DNA, or can tighten or loosen the histone backbone of the DNA, which then effectively silences the expression of that gene.  I have not seen any connection to benzodiazepines in anything that I have read.

[[Pe...]]

I recently read an article which contained information I wanted to contribute to this thread.  In this study they demonstrated that the neurotransmitter GABA can influence GABAAR Cell Surface Expression (CSE) by acting as a ligand chaperone in the Endoplasmic Reticulum (ER).  This could be a factor in benzo recovery.  Here are some highlights from the article:

 

“Here, using recombinant GABAA receptors, we provide the first demonstration, to our knowledge, that a neurotransmitter can act as a ligand chaperone in the endoplasmic reticulum to promote the cell surface expression of its receptor.

 

In this study GABA treatment of HEK 293 cells expressing GABAA receptors resulted in an increase in receptor surface expression. Several lines of evidence indicate that this effect is due to GABA acting as a ligand chaperone. First, the GABA effect is blocked by brefeldin A, a compound that inhibits trafficking in the early secretory pathway. Second, the GABA effect is facilitated by expression of the GABA transporter GAT-1 and is blocked by the GAT inhibitor NO-711 showing that GABA uptake into the cell is important for the GABA effect. Third, coexpression of the receptor with the GABA synthetic enzyme GAD67 results in an increase in receptor surface expression experiments. Lastly, we show that GABA can rescue the surface expression of a receptor construct that is retained in the secretory pathway. The chaperoning action of GABA is specific for GABAA receptors and not a general effect on secretory pathway proteins since GABA does not chaperone 5-HT3a receptors. Furthermore, GABA fails to promote the surface expression of GABAA receptors in which a key GABA binding residue is mutated.

 

Our data in rGAT-1HEK 293 cells indicate that active transport of GABA into the cell can mediate the chaperone effect."

 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2941995/

 

[[...]]

 

Hi Pers

I replied to your pm but your message receptions are blocked

 

Yes, that's interesting. The phenomenon of ligand chaperones and other kinds of auto-inducement occurs by various mechanism for a number of molecular species. I don't know that this information has a practical benefit for the BB crowd, and I try and keep my comments as simple as possible. If you're interested in a great primer on molecular biology, I would recommend the book Rcombinant DNA by James Watson, et al to anyone looking for a good source on basic molecular biology. It is available in paperback on Amazon. Research articles are much easier to evaluate and put in perspective when you have a good overview of the subject such as is in this book. Thanks again for your great work.

Bart

[[Pe...]]

Are there any indications of epigenetic changes to the DNA that may be effecting the gene expression of the GABAARs?  Have any researchers looked at this?

 

Thanks so much for the info!  I'm really looking forward to reading about glutamate as I found an article recently that linked high levels of glutamate in the brain to restless legs syndrome.  I've been suffering from this horribly in the last several months after I came off Klonopin.

 

Kris

Kris, this was what I was also curious about also, whether the benzo's cause damage to the DNA which woud affect the transcription process for healing.  I know some drugs do damage the DNA double strand through breakages and nicks, which I understand, is bad news.  Of course, it depends on ones own genetic makeup, whether this damage will occur, if it does at all.  I don't think there has been any research done on this issue or it's not made available for public consumption by the makers of Xanax, Klonopin. . .Big Pharma keeping it under wraps.  I guess just like drinking alcohol, it can eventually do some real damage depending on the person.  I'd rather remain hopeful that this problem can all be healed fully in time and that there is no permanent symptoms.  I keep thinking if millions of people can come off long-term use with no lingering s/x's, then I can too. 

 

 

My understanding of epigenetics is that a tag, such as a Methyl molecule, affixes near a gene on the DNA, or can tighten or loosen the histone backbone of the DNA, which then effectively silences the expression of that gene.  I have not seen any connection to benzodiazepines in anything that I have read.

 

 

 

---I posted this earlier but also wanted to add that the tag puts up a physical barrier which blocks transcription factors and polymerase from attaching to the DNA strand preventing transcription (copying the gene).  This is how the gene is 'silenced.'  Just wanted to say that to give people a better understanding of how it works.

 

 

[[Pe...]]

 

Hi Pers

I replied to your pm but your message receptions are blocked

 

Yes, that's interesting. The phenomenon of ligand chaperones and other kinds of auto-inducement occurs by various mechanism for a number of molecular species. I don't know that this information has a practical benefit for the BB crowd, and I try and keep my comments as simple as possible. If you're interested in a great primer on molecular biology, I would recommend the book Rcombinant DNA by James Watson, et al to anyone looking for a good source on basic molecular biology. It is available in paperback on Amazon. Research articles are much easier to evaluate and put in perspective when you have a good overview of the subject such as is in this book. Thanks again for your great work.

Bart

 

Agreed.  I try to first learn about the topic or else the research doesn't really make any sense.  Sometimes I think I am well versed, then run into something during the course of reading a piece of research I don't know---in which case I have to pause- learn what it is, then continue, lol.

 

The article did mention this potentially applying to other neurotransmitters:

 

"Evidence that receptor ligands can act in the ER to facilitate receptor biogenesis comes from studies of membrane permeant drugs called “pharmacological chaperones”, “pharmacochaperones” or “pharmacoperones” [3,4,13,29,75] which can facilitate the biogenesis and surface expression of a variety of receptors and ion channels including δ opioid [52], β1-adrenergic [33], dopamine D4 [73], and nicotinic acetylcholine (nACh) receptors [35,59]). In the latter case, drugs that chaperone nACh receptors have been termed SePhaChARNS for “selective pharmacological chaperoning of acetylcholine receptor number and stoichiometry” [40]. In the future, it will be important to examine whether the neurotransmitters which activate these receptors can also act as ligand chaperones, as this may represent a physiological mechanism to post-translationally regulate receptor number."

 

The reason I thought this might be a factor is because multiple neurotransmitter levels are effected from benzo usage.

 

I appreciate you giving me titles to books- I will look at them if I get time (and if that happens before my recovery is finished).  I am trying to get through the Glutamate hypothesis now- but keep running into things like this that side track me.  I do not plan to make a career out of this- just sharing things I find out.

 

I always appreciate your input.

[[Pe...]]

Hi Perseverance.

 

Good to see you are around and still working on this material. Many thanks.

 

One of my providers is interested in the informations you've put together here. I assume it's ok to share the paper you've written?  Also, I wonder if its possible to put a link to a PDF of it so it would be easier to print. Of course it would need to still have no identifying info. I don't know if this interests you, but I for one would print a copy for myself. 

 

 

Thanks again.

 

Perseus

[[...]]

I think that benzodiazepines bind to a lot more places then than the benzo binding site on GABA receptors. This is in part responsible for the huge variety of symptoms people get when withdrawing. From a strictly molecular biology viewpoint it makes sense to withdraw at whatever rate gives you minimal symptoms unless your are in tolerance or having some direct adverse effect from the drug.

[[Kr...]]

 

Hi Pers

I replied to your pm but your message receptions are blocked

 

Yes, that's interesting. The phenomenon of ligand chaperones and other kinds of auto-inducement occurs by various mechanism for a number of molecular species. I don't know that this information has a practical benefit for the BB crowd, and I try and keep my comments as simple as possible. If you're interested in a great primer on molecular biology, I would recommend the book Rcombinant DNA by James Watson, et al to anyone looking for a good source on basic molecular biology. It is available in paperback on Amazon. Research articles are much easier to evaluate and put in perspective when you have a good overview of the subject such as is in this book. Thanks again for your great work.

Bart

 

I'm currently taking a free class on Coursera called "Useful Genetics".  It's certainly challenging but you learn a lot and the instructor and 2 TAs are readily available to answer questions.  It's a great way to learn molecular biology which is really important in keeping abreast of all the advances in the health care field.  The instructor has one module all on personal genomics. This class is already half way through but my understanding is it will begin again in September.

[[ih...]]

Hi Pers, lots to consider here.

 

You may interested in the following:-

"Epigenetic mechanisms in stress and adaptation". PDF available at:-

 

http://www.aipro.info/drive/File/Epigenetic%20mechanisms%20in%20stress%20and%20adaptation%20-%20K.R.%20Mifsud%20et%20al..pdf

[[Pe...]]

I think that benzodiazepines bind to a lot more places then than the benzo binding site on GABA receptors. This is in part responsible for the huge variety of symptoms people get when withdrawing. From a strictly molecular biology viewpoint it makes sense to withdraw at whatever rate gives you minimal symptoms unless your are in tolerance or having some direct adverse effect from the drug.

 

I think you are right Bart, I run into odd articles like this one every so often that discuss things that fall outside of the 'GABAAR' or 'GluR' box:

 

http://www.ncbi.nlm.nih.gov/pubmed/12717139

 

 

[[Pe...]]

 

I'm currently taking a free class on Coursera called "Useful Genetics".  It's certainly challenging but you learn a lot and the instructor and 2 TAs are readily available to answer questions.  It's a great way to learn molecular biology which is really important in keeping abreast of all the advances in the health care field.  The instructor has one module all on personal genomics. This class is already half way through but my understanding is it will begin again in September.

 

Awesome...this is what I am talking about.

 

I am so happy to see people getting motivated like this.  As people recover (myself included) they leave the forum and unless others are willing to learn and carry the baton I fear that the research we have collectively acquired will become buried in the posting history of this forum.

 

This is one of the reasons why I have been trying to educate people here so that BBs will always be able to present the latest science to people who are just joining.  I will not be here forever- I can't speak for others, but I hope that everyone here understands the importance of passing down this information.

 

When I joined the molecular aspects were vague and largely misunderstood which generated a lot of misconceptions about the recovery process causing unnecessary fear among other things...

 

It is my hope that everyone will start educating themselves to the best of their abilities so as members leave the information will not get lost in the shuffle.