If there is a specific thread already on this topic I apologize. In my internet research regarding my own situation, I find a lot of conflicting information on whether downregulation of GABA receptors from benzodiazepine use can be "permanent," with the implication that there may be people who will never completely recover even after a sensible taper. There clearly are some people here who are very knowledgeable about benzos and I wonder what your opinion is and what evidence supports it. Thank you in advance.
GABA receptor down-regulation from benzos -- does it reverse?
#1
Posted 08 October 2012 - 04:49 PM
If there is a specific thread already on this topic I apologize. In my internet research regarding my own situation, I find a lot of conflicting information on whether downregulation of GABA receptors from benzodiazepine use can be "permanent," with the implication that there may be people who will never completely recover even after a sensible taper. There clearly are some people here who are very knowledgeable about benzos and I wonder what your opinion is and what evidence supports it. Thank you in advance.
#2
Posted 08 October 2012 - 05:18 PM
This is the explanation to why some have a lot of difficulties to recover and why people on benzo withdrawal feel happy and recovered one day and crash 1 week after.
The solution to that is make a lot of exercise so that cells can excrete toxins and lose weight.
You may also use detoxifiers such as MSM, chlorella to clean up all the benzo rubbish. And of course water supplementation is needed.
Edited by renfr, 08 October 2012 - 05:18 PM.
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#3
Posted 08 October 2012 - 08:43 PM
#4
Posted 09 October 2012 - 02:49 PM
#5
Posted 09 October 2012 - 08:49 PM
#6
Posted 14 October 2012 - 09:30 AM
Overall doing nothing is a good remedy for the post-acute withdrawal - many substances only end up causing more confusion.
#7
Posted 30 October 2012 - 06:01 AM
Benzo PAWS can in fact be permanent. Some symptoms seem to clear up completely while others can potentially stick around for the long haul. Kompota is right in that most people recover fully after a handful of years. This is assuming of course, that the individual does not touch Benzos ever again and tries to limit the usage of other GABA agonists (i.e. Ethanol, Phenibut, Gotu Kola, etc.). I'm sure you'll be fine though!
Also, Benzos are not stored in our fat cells. That theory was disproven a little while back. It seems that the problem mainly stems from down-regulation of certain GABAa subtypes and the up-regulation of others. Also, an uncoupling effect is observed between the Benzodiazepine site and the GABA orthosteric site.
If you want some additional resources to help you or have any questions, please don't hesitate to ask.
#8
Posted 30 October 2012 - 01:14 PM
#9
Posted 30 October 2012 - 01:55 PM
#10
Posted 30 October 2012 - 02:58 PM
Patience is unfortunately the key here. It can take 10 years to feel appreciably better. Maybe longer even! Terrible drugs, eh?
Below is a quote from one of Ashton's entries. By the way, Ashton is sort of a mentor of mine. We have been in contact for some time now and I've learned a great deal from her. I'll have to share some of the insight I've gained from her one of these days!
"Poor memory and cognition. Although it is well known that benzodiazepines impair memory and some cognitive functions, particularly the ability to sustain attention, some long-term users complain of continued loss of intellectual abilities persisting after withdrawal. There have been several studies on this question which indicate that improvement may be very slow. The longest studies in therapeutic dose long-term users extend for only 10 months after withdrawal. Cognitive impairment, though slowly improving, persisted for at least this time and was not related to anxiety levels (Tata et al. Psychological Medicine 1994, 24, 203-213). Some Swedish studies have found that intellectual impairment, although improved, was still present 4-6 years after cessation of benzodiazepine use, but it was not clear whether high dosage and/or alcohol use were added factors."
#11
Posted 30 October 2012 - 03:37 PM
#12
Posted 30 October 2012 - 03:54 PM
Muira Puama is a natural GABA-A receptor antagonist. It should help upregulate those receptors (like pharmaceutical GABA-antagonists) but will probably initially increase anxiety symptoms. Careful approach is required with these substances. I'm gonna try Muira Puama soon as I get my order altough biggest damage for me is probably in the GABA-B receptors (Phenibut). Bacopa may be safer way to go because it also upregulates GABA receptors through different mechanism but I didn't respond well to it.
Overall doing nothing is a good remedy for the post-acute withdrawal - many substances only end up causing more confusion.
Nice info, never heard of Multra Puama before, good find. But same, gotta find something safe for the B receptor, I'm also in the phenibut gaba-b receptor downregulated crowd.
edit: wait hang on where did you see info that it was a gaba antagonist? also as discussed in earlier threads we are not yet sure if bacopa does upregulate gaba receptors.
Edited by protoject, 30 October 2012 - 03:55 PM.
#13
Posted 30 October 2012 - 05:33 PM
http://onlinelibrary...tr.825/abstract
I've experimented with it several times and I find it definitely anxiogenic and "anti-sedative", in high doses symptoms being similar to rebounds from GABAergics.
Altough it does have other qualities such as AChE-inhibition:
http://www.sciencedi...091305703001138
and may have unique anti-stress effects of its own despite being anxiogen:
http://www.sciencedi...944711309001792
It is actually classically used as an aphrodisiac.
There is some evidence that certain MAOIs (and some antidepressants) could upregulate or "lead to increased expression of" GABA-B receptors (check the page 269):
http://link.springer...?LI=true#page-1
Phenylethylamines may also work:
http://molpharm.aspe...67/4/1283.short
But of course we know oral pure phenylethylamine needs MAOI and it's VERY unpredictable.
"Somatic treatments for depression and mania upregulate the GABAB receptor"
http://www.sciencedi...16503279500025I
Let me know if you find something that works.
Edited by Galaxyshock, 30 October 2012 - 05:52 PM.
#14
Posted 06 December 2012 - 12:46 AM
http://en.wikipedia....wiki/Viloxazine
#15
Posted 06 December 2012 - 05:47 AM
#16
Posted 06 December 2012 - 10:11 AM
just in case anyone is interested, the following compound has been noted as a GABAb up-regulator in the frontal cortex.
http://en.wikipedia....wiki/Viloxazine
Good find. This could have some therapeutic potential if withdrawal symptoms from phenibut or baclofen tend to persist long time. Reversing tolerance should also be possible. Doesn't alcohol also affect GABAb?
#17
Posted 06 December 2012 - 01:15 PM
There is some debate in this area but Alcohol is thought to bind to some of the gamma subunits of GABAa receptors.
#18
Posted 18 January 2013 - 01:23 AM
I know a member on here felt back to normal around month 13 but then had some alcohol and it set them back into withdrawal for a few weeks. I think the intensity of withdrawal was nothing like the beginning. I also saw a lot of examples of pepole that when healed, they can drink with no issue just as they did prior to benzo use.
I tried bacop, l-theanine, 5-htp, and some others a few months ago but I couldn't tell a difference, seemed like it revved up the anxiety.
#19
Posted 19 January 2013 - 02:36 AM
My 2 Week Trial:
~5,000 MG of Holvis Dolvis fruit (NOT AN EXTRACT).
2,400 MG Kudzu root (not extract)
75% of the time I take this combo I get such anxiety I convince my self I have overdosed and much more. The times I took it with food, my anxiety was lowered so this suggests a delayed release is better. But 2 weeks of trying this and my results are good. I plan on trying this for 1 month in the hopes of curing GABA A down regulation. It was hell during taking it, but it will be worth it!
This is the safest way to upregulate your gaba receptors. But remember these receptors are delicate so ask a doctor if you are sensitive to seizures.
Edited by kevinseven11, 19 January 2013 - 02:41 AM.
#20
Posted 19 January 2013 - 03:16 AM
#21
Posted 19 January 2013 - 07:57 AM
I have used dihydromyricetin and kudzu root to relieve stress. That combination is very effective because kudzu root is an agonist at a serotonin ANTI SEIZURE receptor site (5ht2c) so you can take doses of antagonists with confidence of safety. This receptor is why bacopa upregulates gaba, it prevents 5ht2c downregulation. Kudzu actually upregulates it!
My 2 Week Trial:
~5,000 MG of Holvis Dolvis fruit (NOT AN EXTRACT).
2,400 MG Kudzu root (not extract)
75% of the time I take this combo I get such anxiety I convince my self I have overdosed and much more. The times I took it with food, my anxiety was lowered so this suggests a delayed release is better. But 2 weeks of trying this and my results are good. I plan on trying this for 1 month in the hopes of curing GABA A down regulation. It was hell during taking it, but it will be worth it!
This is the safest way to upregulate your gaba receptors. But remember these receptors are delicate so ask a doctor if you are sensitive to seizures.
No, puerarin from kudzu is 5HT2c-ANTAGONIST and also GABAa-antagonist
http://www.sciencedi...09130570300114X
Edited by Galaxyshock, 19 January 2013 - 07:57 AM.
#22
Posted 19 January 2013 - 05:46 PM
I mismatched it.
STILL beneficial to long term anxiety relief.
#23
Posted 21 January 2013 - 03:48 PM
#24
Posted 21 January 2013 - 08:07 PM
#25
Posted 21 January 2013 - 09:21 PM
I actually used a drug that strips the brain of gaba receptors, along with moderate alcohol use. The last time I used a benzo was sometime in 2011 I can't really remember , which was Xanax at 1mg a day. I was so tired of the xanax that I decided to c/t off it. In all honesty I believe I'm 80-90% my normal self at this point. I have occasional waves where I feel basically 100% every few months. In terms of functional, I'm fine and can do normal activites and school work etc with no problem. It's a really tough journey tho so make sure you lay off alcohol and benzos, also prescription gabaergics. Let your body reset, it sucks so bad and feels like it will never go away, but wait it out and you'll be fine. The first 7 months I remember were tourture, I literally thought I was going crazy, couldn't leave the house etc. So if my body can fix itself up you should be alright soon enough.Brendan - How long were you on benzos and at what dose? How functional are you now at 20 months out? Good luck and thanks for the tips
I also disagree with people that say Gaba receptor damage is permanent. If you lay off the alcohol, benzos and other gaba effecting drugs your body eventually will get better. People lose hope , and I have read that it can take up to 36 months to fully heal, which is very long but it's better than permanent.
#26
Posted 21 January 2013 - 11:45 PM
Edited by inw, 21 January 2013 - 11:46 PM.
#27
Posted 22 January 2013 - 01:26 AM
I totally understand you. Honestly you need to realize you will be alright and just fight to get out of the house. Repetition is what you need, just get out shortly each day, get used to the feeling, and work from there. That is what I did.Ok cool, yea I'm still having a very tough time at 8.5 months out from a slow taper of 3mg xanax. I've had windows the past 4 months and I was able to go to the gym for 1.5 hrs last week but then I was shot for another week where I couldn't go anywhere etc...
#28
Posted 22 January 2013 - 03:27 AM
#29
Posted 22 January 2013 - 07:02 AM
no it is permanent, when you downregulate short term it's okay because you just "inactivate" receptors.I actually used a drug that strips the brain of gaba receptors, along with moderate alcohol use. The last time I used a benzo was sometime in 2011 I can't really remember , which was Xanax at 1mg a day. I was so tired of the xanax that I decided to c/t off it. In all honesty I believe I'm 80-90% my normal self at this point. I have occasional waves where I feel basically 100% every few months. In terms of functional, I'm fine and can do normal activites and school work etc with no problem. It's a really tough journey tho so make sure you lay off alcohol and benzos, also prescription gabaergics. Let your body reset, it sucks so bad and feels like it will never go away, but wait it out and you'll be fine. The first 7 months I remember were tourture, I literally thought I was going crazy, couldn't leave the house etc. So if my body can fix itself up you should be alright soon enough.Brendan - How long were you on benzos and at what dose? How functional are you now at 20 months out? Good luck and thanks for the tips
I also disagree with people that say Gaba receptor damage is permanent. If you lay off the alcohol, benzos and other gaba effecting drugs your body eventually will get better. People lose hope , and I have read that it can take up to 36 months to fully heal, which is very long but it's better than permanent.
when you downregulate long term inactivated receptors die and you can't rebuild them.
why do you think people still have benzo withdrawal symptoms even 10-15 years after stopping?
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#30
Posted 22 January 2013 - 07:24 AM
no it is permanent, when you downregulate short term it's okay because you just "inactivate" receptors.I actually used a drug that strips the brain of gaba receptors, along with moderate alcohol use. The last time I used a benzo was sometime in 2011 I can't really remember , which was Xanax at 1mg a day. I was so tired of the xanax that I decided to c/t off it. In all honesty I believe I'm 80-90% my normal self at this point. I have occasional waves where I feel basically 100% every few months. In terms of functional, I'm fine and can do normal activites and school work etc with no problem. It's a really tough journey tho so make sure you lay off alcohol and benzos, also prescription gabaergics. Let your body reset, it sucks so bad and feels like it will never go away, but wait it out and you'll be fine. The first 7 months I remember were tourture, I literally thought I was going crazy, couldn't leave the house etc. So if my body can fix itself up you should be alright soon enough.Brendan - How long were you on benzos and at what dose? How functional are you now at 20 months out? Good luck and thanks for the tips
I also disagree with people that say Gaba receptor damage is permanent. If you lay off the alcohol, benzos and other gaba effecting drugs your body eventually will get better. People lose hope , and I have read that it can take up to 36 months to fully heal, which is very long but it's better than permanent.
when you downregulate long term inactivated receptors die and you can't rebuild them.
why do you think people still have benzo withdrawal symptoms even 10-15 years after stopping?
There is absolutely no scientific evidence that this is the case. Existing studies do not tell us at what point in time, down regulation occurs & some people report withdrawal sx lasting months after only weeks of bz use. As for human studies, Ashton's are the best evidence there is & that is still not very scientific as the population used was a self selecting group of those having prolonged withdrawal sx & in many cases polydrugged.
Still the vast majority of people are able to discontinue benzos with minimal withdrawals so this is also not consistent with permanent damage. It also appears from anecdotal accounts on the main benzo forums that the majority of those who have problems are significantly healed within 18 months. An unfortunate group of outliers seem to require up to 3 years but it is virtually unheard of to hear accounts of withdrawals beyond that point & you can't discount confounding factors such as other substance use & illnesses.
Also tagged with one or more of these keywords: anxiety, gaba, benzos, downregulation
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