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GABA upregulation - downregulated GABA receptors

gaba a gaba b phenibut ghb receptor upregulation pea kava kava phenibut

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#31 tolerant

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Posted 29 May 2016 - 06:40 AM

tolerant are you in US right now and do you think extrapharmacy ships here reliably?

 

No, sorry, forgot to mention -- I'm in Australia. But I wouldn't imagine their to be any problems, but I only have personal experience ordering from Australia. It's kind of common knowledge it seems that Australian customs tend to be the strictest. 



#32 PeaceAndProsperity

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Posted 29 May 2016 - 12:47 PM

Just take prohormones to dht or buy actual dht. It works consistently. More than 3 months of ed usage and it still works.

It completely or almost completely removes social anxiety, and dht has affinity (or its metabolites do) for GABA-a receptors.

Mix dht-based products with something estrogenic and the feeling of masculinity and confidence is unlike anything I've felt before.



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#33 normalizing

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Posted 30 May 2016 - 01:05 AM

 

tolerant are you in US right now and do you think extrapharmacy ships here reliably?

 

No, sorry, forgot to mention -- I'm in Australia. But I wouldn't imagine their to be any problems, but I only have personal experience ordering from Australia. It's kind of common knowledge it seems that Australian customs tend to be the strictest. 

 

 

 

i see. its not so much about customs but about their reliable services. most of those e-phams are kind of scammy, but i guess it works for you and either australia or any other place if it worked it worked. it will probably take too much time overseas though but whatever

 



#34 tolerant

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Posted 30 May 2016 - 04:12 AM

By the way, I don't believe that GABAa receptors can be "downregulated" and reverse the tolerance to it. I have been unable to treat my anxiety sustainably. The only medications that work are either GABAergic or "antiglutamatergic", to which I build tolerance fast, hence my nickname. However check out this thread on a new compound, which may be sustainable.



#35 PeaceAndProsperity

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Posted 30 May 2016 - 10:32 AM

By the way, I don't believe that GABAa receptors can be "downregulated" and reverse the tolerance to it. I have been unable to treat my anxiety sustainably. The only medications that work are either GABAergic or "antiglutamatergic", to which I build tolerance fast, hence my nickname. However check out this thread on a new compound, which may be sustainable.

Read the comment made one comment below yourself.



#36 tolerant

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Posted 31 May 2016 - 12:41 AM

 

By the way, I don't believe that GABAa receptors can be "downregulated" and reverse the tolerance to it. I have been unable to treat my anxiety sustainably. The only medications that work are either GABAergic or "antiglutamatergic", to which I build tolerance fast, hence my nickname. However check out this thread on a new compound, which may be sustainable.

Read the comment made one comment below yourself.

 

 

Thanks for pointing this out to me. May I ask, how quickly did you notice results? Did you try and GABAergics before and develop tolerance to them? If so, which ones? Can you also shed light on which prohormones you're talking about, and where do you get prohormones/DHT?

 

I'm broadly aware that neurosteroids can have an anxiolytic effects through action at GABA-a receptors. I have tried taking pregnenalone with no effect. Curiously, there is a paper that specifically addresses the question of tolerance to neurosteroids -- specifically, allopregnanolone. It is quite conclusive that allopregnanolone causes tolerance to allopregnanolone itself and to other GABAergics. 



#37 normalizing

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Posted 31 May 2016 - 03:41 AM

tolerant, you had to try progesterone. not any pills, as those neurosteroids do not seem to be orally bioavailable. on the other hand progesterone CREAM does work on GABA and its nicely sedating but ive no clue if tolerance develop to it.



#38 PeaceAndProsperity

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Posted 31 May 2016 - 12:52 PM

 

 

By the way, I don't believe that GABAa receptors can be "downregulated" and reverse the tolerance to it. I have been unable to treat my anxiety sustainably. The only medications that work are either GABAergic or "antiglutamatergic", to which I build tolerance fast, hence my nickname. However check out this thread on a new compound, which may be sustainable.

Read the comment made one comment below yourself.

 

 

Thanks for pointing this out to me. May I ask, how quickly did you notice results? Did you try and GABAergics before and develop tolerance to them? If so, which ones? Can you also shed light on which prohormones you're talking about, and where do you get prohormones/DHT?

 

I'm broadly aware that neurosteroids can have an anxiolytic effects through action at GABA-a receptors. I have tried taking pregnenalone with no effect. Curiously, there is a paper that specifically addresses the question of tolerance to neurosteroids -- specifically, allopregnanolone. It is quite conclusive that allopregnanolone causes tolerance to allopregnanolone itself and to other GABAergics. 

 

Androsterone has GABAergic effects in of itself and also when it converts to dht.

Epiandrosterone supposedly does not have GABAergic effects in of itself and needs to convert to dht first.

A combo of andro and epiandro seems to induce a male teenie mentality in me, for whatever reason.

DHT cream (2.5%) itself is very effective and works every single day (for me), even after 3 months of using it daily.

It seems Ginkgo Biloba is also very effective and has a broad spectrum of effects, but it causes massive headaches in myself that last for more than 2 days, I'm talking caffeine-like headaches.

 

p5p (coenzyme B6) with l-glutamine converts partly to GABA but it seems to feel exactly like taking GABA itself - namely it's mildly effective and it actually feels like taking l-leucine in that it seems to be a "confidence" buster and energy depleter.

I haven't tried going with a higher than 30mg p5p dosage (500mg glutamine) but maybe I should just to test it. 

 

I mixed 25mg of non-micronized DHEA (soure of estrogen) with my dht cream which induced a feeling of masculinity I don't think I've felt before. Like being 13 or 16 again.


Edited by RatherBeUnknown, 31 May 2016 - 12:54 PM.

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#39 tolerant

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Posted 31 May 2016 - 01:04 PM

 

Androsterone has GABAergic effects in of itself and also when it converts to dht.

 


 

Thanks for pointing this out to me. May I ask, how quickly did you notice results? Did you try and GABAergics before and develop tolerance to them? If so, which ones? Can you also shed light on which prohormones you're talking about, and where do you get prohormones/DHT?

 

I'm broadly aware that neurosteroids can have an anxiolytic effects through action at GABA-a receptors. I have tried taking pregnenalone with no effect. Curiously, there is a paper that specifically addresses the question of tolerance to neurosteroids -- specifically, allopregnanolone. It is quite conclusive that allopregnanolone causes tolerance to allopregnanolone itself and to other GABAergics. 

 

Epiandrosterone supposedly does not have GABAergic effects in of itself and needs to convert to dht first.

A combo of andro and epiandro seems to induce a male teenie mentality in me, for whatever reason.

DHT cream (2.5%) itself is very effective and works every single day (for me), even after 3 months of using it daily.

It seems Ginkgo Biloba is also very effective and has a broad spectrum of effects, but it causes massive headaches in myself that last for more than 2 days, I'm talking caffeine-like headaches.

 

p5p (coenzyme B6) with l-glutamine converts partly to GABA but it seems to feel exactly like taking GABA itself - namely it's mildly effective and it actually feels like taking l-leucine in that it seems to be a "confidence" buster and energy depleter.

I haven't tried going with a higher than 30mg p5p dosage (500mg glutamine) but maybe I should just to test it. 

 

I mixed 25mg of non-micronized DHEA (soure of estrogen) with my dht cream which induced a feeling of masculinity I don't think I've felt before. Like being 13 or 16 again.

 

 

Thanks for this. Can I ask three questions:

 

1. Did you try drug therapy for your anxiety before going on the hormones? If you did, how did it go?

 

2. Do you experience any side effects from taking the hormones (e.g. hair loss, loss of libido)?

 

3. Do you have a reliable source for the hormones you mention. They don't seem to be pharmacy items in Australia, where I live, so I would need a reliable Internet source. 

 

Please feel free to message me.



#40 PeaceAndProsperity

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Posted 31 May 2016 - 04:28 PM

 

 

Androsterone has GABAergic effects in of itself and also when it converts to dht.

 


 

Thanks for pointing this out to me. May I ask, how quickly did you notice results? Did you try and GABAergics before and develop tolerance to them? If so, which ones? Can you also shed light on which prohormones you're talking about, and where do you get prohormones/DHT?

 

I'm broadly aware that neurosteroids can have an anxiolytic effects through action at GABA-a receptors. I have tried taking pregnenalone with no effect. Curiously, there is a paper that specifically addresses the question of tolerance to neurosteroids -- specifically, allopregnanolone. It is quite conclusive that allopregnanolone causes tolerance to allopregnanolone itself and to other GABAergics. 

 

Epiandrosterone supposedly does not have GABAergic effects in of itself and needs to convert to dht first.

A combo of andro and epiandro seems to induce a male teenie mentality in me, for whatever reason.

DHT cream (2.5%) itself is very effective and works every single day (for me), even after 3 months of using it daily.

It seems Ginkgo Biloba is also very effective and has a broad spectrum of effects, but it causes massive headaches in myself that last for more than 2 days, I'm talking caffeine-like headaches.

 

p5p (coenzyme B6) with l-glutamine converts partly to GABA but it seems to feel exactly like taking GABA itself - namely it's mildly effective and it actually feels like taking l-leucine in that it seems to be a "confidence" buster and energy depleter.

I haven't tried going with a higher than 30mg p5p dosage (500mg glutamine) but maybe I should just to test it. 

 

I mixed 25mg of non-micronized DHEA (soure of estrogen) with my dht cream which induced a feeling of masculinity I don't think I've felt before. Like being 13 or 16 again.

 

 

Thanks for this. Can I ask three questions:

 

1. Did you try drug therapy for your anxiety before going on the hormones? If you did, how did it go?

 

2. Do you experience any side effects from taking the hormones (e.g. hair loss, loss of libido)?

 

3. Do you have a reliable source for the hormones you mention. They don't seem to be pharmacy items in Australia, where I live, so I would need a reliable Internet source. 

 

Please feel free to message me.

 

1. No.

2. Neither, those won't happen.

3. Yes, but you living in Australia makes it a lost cause, unless epiandro or andro is legal (which I don't believe it is). In this case, try Ginkgo Biloba instead since it has some of the same mental effects as dht. Check and see if Ginkgo Biloba is legal in Australia.

 



#41 Heisenburger

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Posted 31 May 2016 - 06:30 PM

isnt etizolam addictive?

 

 

Etizolam is addictive, but the amazing thing about it is how hard it is to get habituated to it. I took two milligrams almost every day for almost year, quit cold turkey, and just shrugged off the worst of the withdrawal in about five days. In two weeks it was gone completely. The general consensus among people I’ve talked to about this is that my avoidance of horrific withdrawal was due to the fact that I was using pressed pills and was adamant about not escalating the dose. Although a lot of people would disagree with this, I’ve seen it stated many times that the people on Bluelight who are complaining about tortuous withdrawal are almost invariablly people who use bulk powder, and eyeball the dose instead of weighing it. Your mileage may vary.  



#42 tolerant

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Posted 31 May 2016 - 11:47 PM

 

isnt etizolam addictive?

 

 

Etizolam is addictive, but the amazing thing about it is how hard it is to get habituated to it. I took two milligrams almost every day for almost year, quit cold turkey, and just shrugged off the worst of the withdrawal in about five days. In two weeks it was gone completely. The general consensus among people I’ve talked to about this is that my avoidance of horrific withdrawal was due to the fact that I was using pressed pills and was adamant about not escalating the dose. Although a lot of people would disagree with this, I’ve seen it stated many times that the people on Bluelight who are complaining about tortuous withdrawal are almost invariablly people who use bulk powder, and eyeball the dose instead of weighing it. Your mileage may vary.  

 

 

Even though tolerance and addiction are very much related, for me at least tolerance is by far more important. I don't mind being addicted to a drug if it helps me and I don't have to escalate the dose. So can I ask you, did the drug actually alleviate your anxiety when you first started taking it and the anxiolytic effect continued right through until you quit? Did you use other benzos in the past and found that you had to escalate the dose? And what would be a reliable source for etizolam?



#43 Heisenburger

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Posted 01 June 2016 - 03:34 PM

Did you use other benzos in the past and found that you had to escalate the dose? And what would be a reliable source for etizolam?

 

I take it primarily for sleep; I rarely use it as a daytime anxiolytic, and never for more than a few days at a time. I have used benzos in the past, but was careful not to escalate the doses. My doctor gives me 30 half-milligram alprazolam tablets at a time, and that will generally last me about a year. Etizolam is quite good for sleep, but also makes a fairly good general-purpose anxiolytic as well. Etizolam used to be freely available from domestic noots vendors, but the FDA eventually put a stop to it. It’s only available from offshore vendors now. The two best ones are Mimaki Family Pharmacy and Nippon Pharmacy.



#44 tolerant

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Posted 02 June 2016 - 01:08 AM

 

Did you use other benzos in the past and found that you had to escalate the dose? And what would be a reliable source for etizolam?

 

I take it primarily for sleep; I rarely use it as a daytime anxiolytic, and never for more than a few days at a time. I have used benzos in the past, but was careful not to escalate the doses. My doctor gives me 30 half-milligram alprazolam tablets at a time, and that will generally last me about a year. Etizolam is quite good for sleep, but also makes a fairly good general-purpose anxiolytic as well. Etizolam used to be freely available from domestic noots vendors, but the FDA eventually put a stop to it. It’s only available from offshore vendors now. The two best ones are Mimaki Family Pharmacy and Nippon Pharmacy.

 

 

Thanks for your reply. Well done for using alprazolam and etizolam so carefully. So how often do you use etizolam for sleep? Is it every day? And the original dose still works? Just trying to understand whether etizolam has any advantages over benzos. Thank you also for providing the sources.



#45 Justchill

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Posted 02 June 2016 - 09:34 AM

If you didn't experience tolerance, this could mean that etizolam in fact upregulates GABA-A or induces maybe reverse tolerance after months.


About fasoracetam : I took 2 grams for a couple of weeks. It has maybe helped to upregulate GABA-B. Difficult to say. I don't have a high tolerance to phenibut (2 G)

 

I didn't notice any nootropic effects actually..


Edited by Justchill, 02 June 2016 - 09:35 AM.


#46 Heisenburger

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Posted 05 June 2016 - 09:26 PM

 

Well done for using alprazolam and etizolam so carefully. So how often do you use etizolam for sleep? Is it every day? And the original dose still works? Just trying to understand whether etizolam has any advantages over benzos.

 

 

Pretty much every day when I do use it. Very often what I’ll do is use for a few weeks to months, and then discontinue for a month or two just to “reset” and give the GABA receptors a break. It’s really a great sleep drug—very little escalation, unlike traditional benzos. And the really cool thing is that when it does stop working, all you have to do is lay off for a week or two and the receptors normalize themselves really fast. After just a week of abstinence, you’ll often feel the full force of it again even with just a normal two-milligram starter dose.



#47 Justchill

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Posted 21 June 2016 - 09:56 AM

Here is another article on anxiety I wanted to share with you guys:

 

 

These anti-anxiety drugs and supplements you have tried work on the GABA receptor mostly (as do benzodiazepine drugs). However, for reasons that I will explain, I think it is best to treat anxiety symptoms primarily using drugs/supplements that work on the NMDA receptor, not the GABA receptor.

Remember, the actual state of the neuron — that is, whether it is excited or relaxed — depends on both the GABA and NMDA receptors. NMDA excites, GABA relaxes. There is a seesaw relationship, with NMDA and GABA sitting on either side of the excited–relaxed seesaw.

Activating the NMDA receptors on a neuron will make the neuron more excited, where as activating the GABA receptors on a neuron will make the neuron more relaxed. Anxiety symptoms most likely derive from over-excited neurons (in the amygdala), so to reduce anxiety, you have to relax the neurons.

Thus for anti-anxiety purposes and to relax the neurons, you have a choice: you can either block NMDA receptor activation, or stimulate GABA receptor activation (or, for the strongest anti-anxiety effect, do both). Both will serve to relax the neurons.

However, if your anxiety symptoms are driven by NMDA receptor over-stimulation in the first place, then it would make sense to try to tackle this by blocking this NMDA receptor over-stimulation, rather than trying to compensate for it by increasing GABA receptor stimulation in order to try to keep the NMDA–GABA seesaw balanced.

To use a metaphor to help understand this: if someone is punching you hard on the chest such that you are in danger of losing your balance and falling backwards, it is best to try to block these chest punches, or eliminate the puncher entirely, rather than to get someone else to simultaneously punch you on your back with equal force, in order to achieve a balance of force and not fall over.

Thus if your anxiety symptoms arise from NMDA receptor over-stimulation, it may be best to try to block or prevent this from happening, rather than trying to over stimulate the GABA receptors in compensation.

As explained earlier in this thread, NMDA blocking is achieved using NMDA receptor antagonists such as dextromethorphan or transdermal magnesium; and preventing NMDA over-stimulation in the first place is achieved by lowering brain inflammation, which is the source of excessive amounts of compounds like glutamate and quinolinic acid that stimulate the NMDA receptor.

So by using both NMDA receptor antagonists and by reducing the brain inflammation that causes NMDA over-stimulation in the first place, you have an effective way to tackle anxiety disorder.

(The brain inflammation itself most likely derives from an infection in the brain, and/or infections in very nearby structures such as the sinus mucous membranes, and/or infections in more distant areas such as in the intestines or kidneys — toxins and cytokines from such distant infections are now known to be able to precipitate inflammation in the central nervous system. This is why supplements or drugs that reduce inflammation or infection in the gut, kidneys or sinuses, and thereby reduce brain inflammation, can be effective in reducing anxiety symptoms.)




Regarding the supplements and drugs you used:

As is well known, GABA (gamma aminobutyric acid) itself does not cross the blood-brain barrier, so supplementation with GABA will not activate the relaxing GABA receptors on the neurons, and thus as a supplement, GABA has no anti-anxiety effects.

Try the supplement picamilon instead. Picamilon is in fact a GABA molecule and a niacin molecule bonded together, and this combination does pass through the blood-brain barrier. I found picamilon to be reasonably effective, though you need to take it 3 times a day, as its effect wears of quite fast.

But the problem with compounds that have GABA receptor stimulating effects is the tolerance build-up, and possible withdrawal symptoms. There always seems to be tolerance problems with GABA receptor agonist drugs and supplements. By contrast, there do not seem to be any tolerance problems with NMDA receptor blocking drugs. So in this respect as well, NMDA receptor blocking drugs and supplements are better.

Theanine and valerian have quite weak GABA effects, so don't expect too much from them.

Taurine has both NMDA receptor blocking and GABA receptor stimulating effects. I found that you need a high dose of taurine (around 3 grams) to get a noticeable anti-anxiety effect. Thus you really need to buy taurine as a bulk powder for these sort of high doses, as bulk powder suppliers are much cheaper sources of supplements.

 

source: http://forums.phoeni...ent.6432/page-3



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#48 Justchill

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Posted 21 June 2016 - 11:28 AM

 

For me the most successful approach to treating my severe anxiety was the anti-inflammatory approach: treating the brain inflammation that I think underlies my anxiety. There are a number of anti-inflammatories that can be effective. N-acetyl-glucosamine is the star anti-inflammatory supplement, but there are many others, including:

• NAG, turmeric, flaxseed oil

• COX-2 inhibitors like: propolis, curcumin, Terminalia chebula, cat's claw — these all are anti-inflammatory

• NF-kB inhibitors like: grape seed extract, curcumin, ashwagandha — these can help lower inflammation too

Recent research is showing that brain inflammation (neuroinflammation) may be behind a number of mental symptoms or conditions, including depression, bipolar, schizophrenia. So treating anxiety by countering inflammation in the brain is a new and novel route to treatment. I think it works so well because it may target the root inflammatory cause of anxiety in many people.



Regarding GABA: there are actually several ways that you can play around with the GABAergic system:

• You can up-regulate levels of the GABA neurotransmitter, in order to increase GABA receptor activation. This is what L-theanine does, and also what SSRIs do. Although note that L-theanine also increases dopamine and serotonin levels.

• You can take a medication that agonizes the GABA receptor by mimicking the effect of the GABA neurotransmitter (a GABA memetic). This is how ashwagandha (Withania somnifera) likely works.

• You can increase the sensitivity of the GABA receptor (positive allosteric modulation). This is how skullcap (Scutellaria lateriflora) works, and also how benzodiazepines work.

• You can up-regulate the density of GABA receptors. This is how kava kava root (Piper methysticum) works.


Most of these GABA approaches have to some degree the problem tolerance and loss of effect, because the GABA receptor starts to desensitize with many of these approaches.

However, I imagine that GABA receptor desensitization will likely not occur with kava kava, because this herb actually increase the number of GABA receptors, so should increase GABA system sensitivity.

 







Also tagged with one or more of these keywords: gaba a gaba b phenibut ghb receptor upregulation pea kava kava, phenibut

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