42 replies to this topic

[pspa123]

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.

[renfr]

Downregulation of GABA through benzos is not permanent. Why some people never recover is because benzos are fat-soluble molecules therefore they are stored in body fat and are sporadically used by our body from time to time.
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.

[stablemind]

Sorry slightly off topic, but how do you feel when you take MJ or Booze? Do you feel depressed the next day or cognitively impaired?

[Kompota]

Yes, it does reverse, and no, it is not permanent. The process can take a quite a while though and the pace of healing could be discouraging for many. In sources I have researched, it seems most people make it within 18-24 months, some need less, and only very few need more than 2 years.

[protoject]

iwish i could get oral flumazenil

[Galaxyshock]

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.

[thegron]

I have Benzo Post Acute Withdrawal Syndrome (PAWS) and I consider myself a pseudo expert of anything Benzo related.

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.

[pspa123]

What evidence is there that down-regulation of receptors can be permanent; all I have seen are a couple of theoretical snippets from Ashton that contradict other things she has said, and a few anecdotal claims by individuals where causation seemed unclear to me? Also are there particular types of symptoms that in your opinion are more suggestive than others of being due to this permanent down-regulation? Or is it just any symptom that persists, of whatever nature?

[Kompota]

From what I remember, there was an explanation that during benzodiazepine use GABA receptor subunits not only become downregulated (decrease of receptor density, the mentioned above uncoupling from main receptor site, conformational changes), but they eventually may undergo changes in gene expression (scary thing). We know that gene mutation happens as a result of environmental factors. The presence of benzodiazepines might be one of those, and GABA receptor gene expression changes may be part of some long-term adaptations in strife for homeostasis. Of course that would require a person to be on benzos for very long time, a few years at least. Gene expression changes may be reversible though, I am not sure.

[thegron]

I will admit that some of what Ashton said was based on Anecdotal evidence. However, after my own personal research it seems as if for example, symptoms such as anxiety and depression tend to disappear with time while others (like cognitive dysfunction) have the potential to be semi-permanent. So some symptoms are more likely to be permanent than others. Of course, most of the studies I have read capped at some point under 2 years. It may be that the individuals used in the study recovered but only after many many years. I didn't mean to say that all of the symptoms are permanent or even that they will likely be permanent. I'm just saying that it can happen. And even when it does, it is always semi-permanent, meaning that there is always improvement to some degree.

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."

[pspa123]

In my own case, I don't have any intellectual/cognitive issues at all as far as I know, the only one I was wondering about was muscle pain in a particular area that seems to have started during my taper which was many years ago now (although arguably it just moved locations rather than starting) and never went away -- in fact, if anything, it's worse and worse over time, which seems somewhat inconsistent with it being a protracted withdrawal symptom as according to what you posted and most of what I read even persistent symptoms do slowly improve. Most likely, it's an anxiety symptom, which I have had my whole life, pre, during, and post benzo. Thanks for your insight.

[protoject]

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.

[Galaxyshock]

I may have made too early conclusions but everything seems to indicate Muira Puama may act as a GABA-A antagonist:
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 GABA_B receptor"
http://www.sciencedi...16503279500025I


Let me know if you find something that works.

Edited by Galaxyshock, 30 October 2012 - 05:52 PM.

[thegron]

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

[Kompota]

I believe the issue with benzos is more related to the downregulation of the GABA-A complex.

[Galaxyshock]

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?

[thegron]

Yeah Kompota, it doesn't really help you or I but i was thinking of those who have used phenibut/baclofen long-term.

There is some debate in this area but Alcohol is thought to bind to some of the gamma subunits of GABAa receptors.

[inw]

I'm ~8 months 2 weeks out from the last dose of a 3+ year long xanax use prescribed by a dr. I've seen improvement in being able to go to a store and stay in there longer, I can hang out places, big difference from even 4 months ago. But I still have a crazy amount of fatigue and dp/dr. Mood is also not back to normal,most of the time I can't drive far b/c my vision gets this virtigo/dizziness that turns into claustraphobia/anxiety symptoms. Still not close to 100% but I can see VERY SLOW progress. From what I've seen, most people are healing and making big strides in the 12-14 month range.

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.

[kevinseven11]

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.

Edited by kevinseven11, 19 January 2013 - 02:41 AM.

[inw]

Interesting, I might look into Kudzu. It does seem that the GABA Antagonists may cause more anxiety BUT they could be speeding up the recovery time.

[Galaxyshock]

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.

[kevinseven11]

Yeah sorry.It is an antagoinst but like an agonist would, Puerarin downregulates the 5ht2c receptor. 5ht2c activation is related to anxiety.
I mismatched it.
STILL beneficial to long term anxiety relief.

[Bman56]

To the OP, it will get better over time as long as you lay off benzos, alcohol, and other prescription gaba effecting drugs. Personally I try to take natural supplements and it hasn't impeded my healing. I'm about 20 months into my own gaba healing and I can tell marked differences from last year at this time to now. Your brain will fix itself just don't lose motivation because it does take a lot of time.

[inw]

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

[Bman56]

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 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.

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.

[inw]

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...

Edited by inw, 21 January 2013 - 11:46 PM.

[Bman56]

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...

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.

[inw]

Sounds good man thanks again, I'll post some updates every month or two.

[goldsilver]

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 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.

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.

no it is permanent, when you downregulate short term it's okay because you just "inactivate" receptors.
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?

[madamshome]

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 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.

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.

no it is permanent, when you downregulate short term it's okay because you just "inactivate" receptors.
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.