Impressive results from using GABA-B agonists. Why is this?

[Cipher]

I said what I needed to say in order to inform members, should they be considering using kava as a daily anxiolitic, that it's not a magic bullet, and not without risks.

I understand that you are on the cautious side, which is generally a good thing. However, I'm trying to summarize what the actual scientific data says regarding the risk of kava inducing tolerance or dependence, and I have yet to find any evidence that indicates that such a risk exists.

I thought that I made it clear that this was the medical and scientific opinion shared almost wholesale by that community (including Freud, among others) well over a hundred years ago.

The argument I made was that if you look at the scientific data from that period regarding the risks of cocaine (from actual studies), I think you wouldn't find any that supported the medical opinion of the time.

To summarize my point of view:

1. There are at least 2 double-blind human studies investigating the potential of the active psychoactive compounds (kavalactones) present in kava to induce tolerance/dependence. No such risk was found. These findings must be taken in account when reviewing the effects of non-extract use of kava.
2. There is animal evidence of kava having a reverse-tolerance effect on GABA. This evidence is not strong by itself, but when taken in account when looking at all the evidence, it further supports the notion of a low risk of tolerance.
3. Kava have been used for thousands of years in the South Pacific, and even though it maybe historically was mainly used occasionally, it have of course been used daily by many people during these years, and the anecdotal evidence is unanimous; no tolerance or dependence have been observed.

And as I said earlier; the science could be stronger. But there is considerable scientific data indicating that kava does not induce tolerance, and there is no scientific data indicating the opposite (that I'm aware of). Please share if you know such data.

 

[knackers323]

Baclofen seems to downregulate your systemic inflammation by attenuating signaling through TLR4(endotoxin) pathway:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516894/

@uglevod are you aware of any other medications or treatments that have the same effect?

To those that find GABA treatments help, has anyone had any related and targeted autoimmune testing done towards the GABA pathway? Celltrend etc.

 

[sb4]

@Cipher Do you take Kava and if so what effect does it have on your symptoms?

 

[Cipher]

@Cipher Do you take Kava and if so what effect does it have on your symptoms?

I have GAD65-antibodies (because of my Type 1 Diabetes), which lowers the GAD65-enzyme activity. GAD65 converts glutamate into GABA in the brain, which I guess have a causative role in my insomnia and anxiety that I suffer from.

I've used kava daily for while now (500 mg micronized 2/day) and my anxiety have improved during this period. I haven't noticed any difference in my ME-symptoms.

 

[SmokinJoeFraz93]

Thanks for the replies guys. Before trying the phenibut and baclofen, I wanted to go down the ‘natural’ route. Kava was my first stop, and I sourced it from a guy from the UK, as American companies don’t ship straight to the UK.

I will admit, I am really disappointed with Kava. A lot of money for 20 minutes of numb gums, and that was it. It was good sourced instant Kava root also. So for me, Kava is out of the question. As for reverse tolerance, it never happened.

 

[stefanosstef]

That often means too much glutamate.Another sign would be if you feel better the next day after consuming enough alcohol to have even a mild hangover.

I get a mood boost from GABA B agonists too, not sure if it's doing anything for fatigue but if I need to go out at night and I'm tired and with not a very good mood the only drug that can turn that into positive is GHB (GBL actually), although it is a very risky drug and I don't advertise its use.For phenibut I need large dosages to feel the same, 1.5grams if I remember correctly (can't handle more than 1.6g) but it causes headaches more often than not so I stopped using it.It also needs at least 3 hours to start acting.

 

[heapsreal]

I finally decided to try pharmaceutical drugs after learning the hard way that supps like valerian and theanine alone weren’t going to sort out this ridiculously hyperexcited brain of mine.

I’m intrigued as to why I improve with GABA binding substances. I’m taking fairly low doses a handful time’s a week to avoid tolerance and withdrawal issues, but I would like to investigate this GABA issue more thoroughly, as I feel I need some sort of strong intervention daily, not just 3 days a week (preferably not pharmaceuticals).

- I call GABA the ‘Zen neurotransmitter’. An entire life of worrying over worthless shit is balanced by GABA. I can observe my thoughts and realise that they don’t hold the reality that they would if my brain was in a more excited state.

I can go from feeling profound loneliness and feeling a sense of ‘being lost’ to feeling balanced, excited for the future and I don’t feel this horrible fear that I need people on my life because of the belief that I can’t do it alone.

- When my brain is more ‘GABA balanced’, I don’t need my wheelchair. My knee pain and knee fatigue becomes dramatically reduced. My muscle have a little more energy, with recovery time from exertion reduced to the point where I can exert (and even go out doing things) daily.

- My brain feels more calmer in terms of thought processing. Normally, a thought about doing a task or something of that nature will bring on a physical response in my body. It’s like my brain doesn’t want to do anything, but when under the influence of GABA binding substances, my brain and body doesn’t react much to my thought processes.

- Severe sensory processing issues are reduced (only until the drug’s effects have worn off). I spent over a year in silence because my brain couldn’t tolerate hardly any sound, light or smell. (I now know that norepinephrine is involved here somewhere, as norepinephrine binding substances make these symptoms a whole lot worse.)

Substances used:

Phenibut 250mg - (titrated to 1 gram, but was disappointed by the higher doses).

Baclofen 50mg - (My favourite drug in terms of GABA-B agonism. Effects that last most of the day.

Can anyone suggest as to why I benefit from GABA binding substances?

Thanks.

Its quite possible baclofen is good at calming down neuro inflammation. Ive found taking it when the fog is bad and i have that tired but wired feeling, baclofen can help.

The other thing with baclofen is that it can promote deep stage 4 sleep which greatly improves regeneration of our whole body and also deep sleep is when growth hormone is released and maybe one reason for the improved regeneration.

On its own i find it not strong enough for me to sleep but adding to something like zopiclone and a sedating antihistamine, i feel it greatly improves sleep quality.

 

[EddieB]

Its quite possible baclofen is good at calming down neuro inflammation. Ive found taking it when the fog is bad and i have that tired but wired feeling, baclofen can help.

Do you take Baclofen daily or just as needed?

I’m trying to solve two problems, severe anxiety attacks and a poor functioning lower esophageal valve. Both in theory are due to low GABA. Also considering Gabapentin. I found a sublingual gaba supplement, but not sure if would be effective. Phenibut sounds a little scary, but living like this is hell.

 

[heapsreal]

Do you take Baclofen daily or just as needed?

I’m trying to solve two problems, severe anxiety attacks and a poor functioning lower esophageal valve. Both in theory are due to low GABA. Also considering Gabapentin. I found a sublingual gaba supplement, but not sure if would be effective. Phenibut sounds a little scary, but living like this is hell.

I use baclofen as required, usually an add on to other sleep meds. It would probably be ok for anxiety.

Phenibut i find i get a tolerance to it too quickly. Once per week would be a good option. I havent used it for a long time but found i needed high doses for it to work lime 4000mg and its effects lingered for quite awhile.

Gabapentine or lyrica could work well for you. I found lyrica more sedating. Id consider using all of them but not at once, but in some sort of rotation to prevent tolerance.

 

[EddieB]

Great, thanks. That was one of my questions about baclofen; if it could be used as needed.

My wife takes gabapentin every night, so there’s piles of it around here.

I like your idea of rotation. It would be great to used meds that either worked or didn’t right away. Doctors have given me anti depressants trying to balance my issues. Right idea, but it takes months to know the effects. Tapering off mirtazapine now. Horrible start up, helped for about 8 weeks, then turned evil on me.

Do you have any comment on buspirone?

 

[heapsreal]

Do you have any comment on buspirone?

No. But some sedating antidepressants can be used on an as needs basis. Doxepin is one i had success with earlier on and dose much less then for depression are all thats needed eg 10-50mg.

 

[Prefect]

Where do you get phenibut from? Unless you live in Russia it's not available readily in the west. And how is it different from Gabapentin or Lyrica? It's supposed to act on the same mechanisms but does it feel different?

 

[heapsreal]

Where do you get phenibut from? Unless you live in Russia it's not available readily in the west. And how is it different from Gabapentin or Lyrica? It's supposed to act on the same mechanisms but does it feel different?

Gabapentine and lyrica are calcium channel blockers basically and not gaba agonists.
Phenibut was available through supplement shops, unsure if still are.

 

[EddieB]

Phenibut is being sold through on line stores, look up nootropics.

 

[invisiblejungle]

Where do you get phenibut from? Unless you live in Russia it's not available readily in the west. And how is it different from Gabapentin or Lyrica? It's supposed to act on the same mechanisms but does it feel different?

This is a reliable source for phenibut:
https://liftmode.com/calming/phenibut.html

By the way, phenibut is in the same category as Gabapentin and Lyrica. They're all gabapentinoids (voltage-gated calcium channel blockers). Phenibut feels almost the same as Gabapentin but is more euphoric since it also affects dopamine.

 

[Celandine]

Just wanted to flag up Magnolia extract, particularly the honokiol component, as a natural GABA receptor agonist. I bought Swanson's Magnolia Extract 90% honokiol supplement for my daughter with ME. Didn't help her sleep at all, but I've found it to be amazing. I only take it now and again but I get the best night's sleep with no after effects the next day. I do not have ME.
Here's a paper on it:
https://www.frontiersin.org/articles/10.3389/fneur.2013.00130/full

 

[stefanosstef]

Just saw it.Don't even try 4g of phenibut, it will be a nightmare.If I remember correctly I can handle 2.2g max.Start low and see your limits.It needs a completely empty stomach to work.

 

[Jackb23]

Excessive inhibition can lead to excitation.

You can turn off a gas pedal but you can also turn off a brake to go with a car/speed analogy. Except it may be like driving with one foot for each pedal.
So maybe this is why you feel more energetic. It may also be why healthy people find alcohol more stimulating in lower doses due to the disinhibition. Could also be a totally different MOI. Study below found it
Pharmacologic Treatment with GABAB Receptor Agonist of Methamphetamine-Induced Cognitive Impairment in Mice



https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3137162/

 

[pattismith]

Its quite possible baclofen is good at calming down neuro inflammation. Ive found taking it when the fog is bad and i have that tired but wired feeling, baclofen can help.

The other thing with baclofen is that it can promote deep stage 4 sleep which greatly improves regeneration of our whole body and also deep sleep is when growth hormone is released and maybe one reason for the improved regeneration.

On its own i find it not strong enough for me to sleep but adding to something like zopiclone and a sedating antihistamine, i feel it greatly improves sleep quality.

https://forums.phoenixrising.me/threads/low-dose-naltrexone-for-charcot-neuropathy.84310/

it seems Baclofen is effective against Neuroinflammation. It has shown to reverse the course of a severe neuropathic disease, Charcot ( CMT1A ) when given at low dose in association with LDN and Sorbitol.