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Anyone else get temporary full remission from phenibut?

Discussion in 'General Treatment' started by Deltrus, Apr 26, 2015.

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Phenibut response?

  1. I get huge improvements from phenibut

    3 vote(s)
    16.7%
  2. I don't get improvements

    2 vote(s)
    11.1%
  3. I haven't tried phenibut

    13 vote(s)
    72.2%
  1. Deltrus

    Deltrus Senior Member

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    I have pretty much all the symptoms of CFS:

    • Poor sleep / cycadian rhythm
    • Extreme fatigue at all points in the day
    • Food sensitivities and crashes
    • Sickness type behavior (gravitating to only low energy activities)
    • Brain fog
    • Irritability, hard time ignoring sounds etc
    • Anhedonia
    • Fluctuating vision clarity
    • Constipation, gas, light amounts of bowel irritation.
    • Anxiety
    • Muscle pain
    Phenibut (aka bioactive GABA B) gives me full remission and utterly changes my behavior. However I can only take it once a month or so, else the effects will get weaker and the withdrawal gets worse. Effects of phenibut:

    • My mind feels perfectly clear, I notice the thousands of simple things that are pleasurable. Rain outside, the smell of my blanket, etc.
    • .I don't get pleasure from things that don't take energy to do (laying down and reading, browsing the internet. pretty much everything I normally do)
    • I don't act lazy, my body feels smooth and energetic
    • I feel like I can easily focus on stuff, like I can 100% ignore things if they aren't relevent and my mind can expand to fit even simple things that I'm thinking about.
    • It feels like time slows down, I can notice facial expressions, I can think about the recent past / future clearly. I don't feel like I'm at the bottom of a mental trench.
    • This is the strangest thing for me. I could actually get hungry and then eat and then feel energy after eating. That freaked me out, I didn't remember that every happening for me, I guess I forgot. Atm food is just something I use to keep myself from dying.
    • My digestion seems to normalize, and some sort of cellular metabolic process also seems to normalize. I poop once daily.
    GABA and inflammation studies:

    http://www.ncbi.nlm.nih.gov/pubmed/25526825
    http://www.ncbi.nlm.nih.gov/pubmed/25677654
    http://www.ncbi.nlm.nih.gov/pubmed/25848767

    GABA can also regulate several hormone systems:

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3108002/
    (lots more stuff on this, I just didn't want to go find them)

    It is a real shame that I found something that works but it only works once a month. And it doesn't really decrease the scope of what my issue is, because it has such a wide range of interactions.

    Anyone else try phenibut / baclophen and get a good result? Any comments on possible MoA's or alternatives?
     
  2. minkeygirl

    minkeygirl But I Look So Good.

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    Left Coast
    Phenibut does nothing but calm me some. And it's highly addictive so not really a fix.

    Baclofen makes me feel like I'm in speed. Go figure.

    I have good luck with kava and pain reduction and there is something like an MAO that uses an ingredient (don't quote me).

    It's on my computer So I'll look tomorrow if I remember.
     
  3. helios

    helios

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    I had a ramp up in insomnia and was having trouble sleeping though it didn't seem to effect my energy levels at the time, I still hated it. Someone at the gym said they found Phenibut great for sleep. I tried it and it definitely did help with sleep but I had to cycle it because its starting losing its effectiveness for me after 3 days, but only needed like 3 days off. I never got any dramatic improvement in my health from it though.

    What s shame your cycle downtime has to be so long for it to work again. I found Neurontin (gabapenitin) was like that for me. When I first tried it I thought it was the best thing ever. It cleared my brain fog and energized me, but it got weaker each day till day 5-6 I hardly noticed anything,so I had to cycle it. A week off only really gave me 2 days benefit. A month off and I could get 5 days benefit. so disappointing. I've been off an on it for a number of years.Lyrica never had the same effect.

    Baclofen I also tried and I liked it. I really took it to get better quality sleep (more GH) which of course has flow on health benefits for the following day. I never got any dramatic improvement from it and I also had to cycle it, but it was only a case of a couple of days on a couple of days off.
     
  4. perchance dreamer

    perchance dreamer Senior Member

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    Phenibut works on Gaba-A in addition to Gaba-B. For that reason, I don't take it more than once a week, if that often. I use it for sleep.

    Baclofen at 10 MG helps me with sleep, and I don't worry as much about it as Phenibut since Baclofen works on Gaba-B only. Still, I only take the Baclofen every 3rd night out of an abundance of caution.
     
  5. minkeygirl

    minkeygirl But I Look So Good.

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    Moclobemide is the medication I was talking about that supposedly doesn't have the same food restrictions as MAOIs. I don't remember where I got the info below.

    Kava has an active incredient,yangonin, which is a MAO-B not MAO-A.MAO-B regulates Dopamine and Phenylathylamine while MAO-A Serotoninand Norandrenaline
     
  6. Hip

    Hip Senior Member

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    In the Wikipedia article on phenibut, it says there is some controversy about whether this supplement has GABA-A effects.

    However, given the significant tolerance / withdrawal symptoms that phenibut can cause, this kind of suggests it might well be acting on GABA-A as well as GABA-B, as I believe drugs that only work on GABA-B (like baclofen) do not exhibit much tolerance / withdrawal.



    @Deltrus
    Very interesting finding, Deltrus.

    What dose of phenibut are you using to get these beneficial effects?

    Have you tried baclofen which, if it works for you, could be taken daily as there is little tolerance build up?

    When I tried baclofen at 10 mg daily, though, strangely enough it seemed to increase my anhedonia symptoms slightly. By the way, anhedonia is not really considered a part of ME/CFS, but more an additional condition you can have alongside ME/CFS.

    Also, on this thread someone said: "Baclofen does not help anhedonia, why phenibut does and baclofen doesn't is unclear."


    In terms of beating the phenibut tolerance, on this thread it was suggested that: "In theory... Fasoracetam may reverse phenibut/baclofen/GHB/GBL tolerance."

    Fasoracetam (NS-105) is on my list of drugs to try. It increases the number of GABA-B receptors. Though note although this is in the racetam class, it is still a "research chemical" not yet tested on humans (apart from the people who buy it and take it).
     
    Last edited: Apr 27, 2015
  7. Deltrus

    Deltrus Senior Member

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    Fasoracetam hasn't really had good reports yet. I tried it and didn't feel anything, haven't used it since because it is understudied.

    I'm interested in trying baclofen too, apparently it works like 3/4 phenibut, but with less tolerance. Might not have the same good effect tho. There might be certain GABA-A receptors on immune cells which phenibut is an agonist towards. See this study: http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22160261/

    It would be cool that, since we are just discovering that immune cells have gaba receptors, maybe we could make a highly specific agonist / reuptake inhibitor for only the receptors on immune cells. After all, in that article it says that there are actually 19 different GABA-A receptors, lots of which are not studied yet.

    I found this particularly interesting, from the "GABA and GABA receptors in the gastrointestinal tract: From motility to inflammation" article:

    "Different immune cells are equipped with components
    of the GABAergic system, including GAD, GABA transporters and
    GABA receptors, and GABA seems to be involved in modulating
    the immune response, mainly via a negative regulation of both
    pro-inflammatory
    cytokine production and immune cell prolifera-tion. Accumulating evidence have demonstrated that a complex
    and fine tuning of immune response within the Gut-Associated
    Lymphoid Tissue (GALT) is crucial for the maintenance of toler-ance to harmless antigens in the enteric microenvironment, i.e.
    food antigens and commensal microbiota components "​

    And then it goes on to explain how GABA may interact with GALT. Very interesting.

    Memantine is sometimes used to reset tolerance faster. Someone on /r/nootropics said they used it in order to get a high uptime on baclofen.
     
  8. Hip

    Hip Senior Member

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    Have you tried the GABA supplement? For most people this does not work (as an anti-anxiety treatment), as GABA does not cross the blood-brain barrier.

    But some people find GABA works well for them, without tolerance build-up (such as @alice111; see her post here). It's possible that people who find benefits have a slightly leaky blood-brain barrier, which lets in the GABA.


    Interesting stuff about GABA receptors in the immune system. Can't see much in that paper that might be useful for ME/CFS though. But obviously it is still a new line of research.
     
  9. Hip

    Hip Senior Member

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    Did you try fasoracetam just once or twice, or did you take it on a longer term basis? I am presuming that its effect of up-regulating GABA-B receptors will take several days or weeks of daily use before it occurs.
     
  10. Deltrus

    Deltrus Senior Member

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    Haven't tried pure GABA, I imagine it wouldn't cross the BBB and thus wouldn't effect neuroinflammation.

    Fasoracetam I just tried for 2 days. I'l wait for more research on it to come out, or better reviews, before trying it again.
     
  11. renerdrat

    renerdrat Every teardrop is a waterfall

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    Temecula
    I had horrible reaction to phenibut... like it felt good and relaxing but the rebound effect was miserable. I ended up giving it to a friend because I wanted to keep taking it but knew once it wore off I would regret it.
     
  12. Dufresne

    Dufresne almost there...

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    @Deltrus

    I got pretty much the same effect from taking GHB as you did from Phenibut. From what I've read I think the former is a better drug.

    High-dose baclofen does everything GHB does to counter my illness but doesn't relieve my PEM. However baclofen combined with opioids does.

    Contrary to what was posted earlier in this thread, I find baclofen to be a terrific antidepressant. Also, though it doesn't lead to tolerance like GABA A's, you don't want to stop taking it suddenly if you've been on it for more than a month. According to Wikipedia, withdrawal can occur after high-dose as well as low-dose use. I can attest to the negative effects of abrupt cessation.

    I'm not taking any of these drugs at the moment and I don't feel like I've incurred any lasting trouble from having experimented thoroughly with them.

    Hope that helps.
     
    Sidereal, Deltrus and Hip like this.
  13. Hip

    Hip Senior Member

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    The other supplement to consider is picamilon, which is a GABA molecule bonded to a niacin molecule, and does cross the blood-brain barrier. I used to use picamilon regularly for anti-anxiety purposes. Picamilon is much cheaper if you buy it as a bulk powder from places such as this, rather than buy as tablets.


    The study which suggests fasoracetam (NS-105) up-regulates GABA-B receptors is this one:

    Effect of a novel cognition enhancer NS-105 on learned helplessness in rats: possible involvement of GABA(B) receptor up-regulation after repeated treatment

    Unfortunately it does not say in the abstract how many days/weeks it takes for fasoracetam to take effect, and for the GABA-B receptor population to up-regulate.
     
    Last edited: Apr 28, 2015
    Changexpert likes this.
  14. Hip

    Hip Senior Member

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    @Deltrus

    Another thing you could look into for possibly minimizing the tolerance build-up to phenibut is co-administration of a NMDA receptor blocker such as high dose transdermal magnesium (search for transdermal "magnesium cream" for more info on transdermal magnesium).

    This study found that NMDA receptor antagonists reduce tolerance to benzodiazepines:

    Effect of NMDA antagonists on rapid tolerance to benzodiazepines

    Benzodiazepines are not GABA agonists as such, but it's possible that this result might also apply to GABA agonists like phenibut is suspected to be.

    NMDA receptor antagonists have a general effect in reducing tolerance build up to a range of drugs. See this thread.
     
    Last edited: Apr 28, 2015
  15. AlmostEasy

    AlmostEasy

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    I have the same experience, nearly full remission. Have you figured out anything more treatment wise? I've cycled it for weeks at a time 250mg 2 or 3x daily. I tapered slowly off and noticed no issue. Probably going to do it again. Methylation does not fix this. I'm not sure where to go with it.

    I haven't tried anti vitals but I'm doing advanced methylation and am on LDN so I'm not sure what's going to do it. Memantine helps similarly to block glutamate but it doesn't give the warm fuzzies of phenibut
     
  16. Deltrus

    Deltrus Senior Member

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    @AlmostEasy Lavender oil aroma combined with calm aid oral lavender gives a similar effect, I've read that it has effects on modulation of ion channels and peripheral cholinergic systems. However after 2 weeks it wore off and I had 2 weeks of withdrawal in which my fatigue was twice as bad.

    I'm trialing diphenhydramine (benadryl) which is an over the counter anti-cholinergic. It blocks the muscarinergic acetylcholine receptors, which are responsible for activating the parasympathetic and sympathetic nervous system, and also are responsible for muscle tension. Normal activation of these receptors results in proper muscle tension (good posture).

    There are other threads in which there are theories that overactivation of the parasypmathetic and sympathetic nervous systems can be implicated in chronic fatigue. The parasympathetic nervous system is also called the "rest and digest" mode of the nervous system. Sounds a lot like "fatigue".

    I tried taking diphenhydramine because anti-cholinergics are good for extrapyramidal symptoms, such as twitching, tremors, muscle tension etc. They are used for parkinson's.


    Unlike phenibut, there was less euphoria, but it gave me much more motivation to just ... move around and do things. Phenibut you are motivated to do things but you still choose to do pretty lazy things in my experience. Diphenhydramine gave me very similar effects to phenibut, in terms of alleviating fatigue.

    Strangely, diphenhydramine didn't give me a good response unless I did something which really aroused my brain, such as video games, stimulants, or a really exciting book, or something like that. I originally tried stacking diphenhydramine with phenibut, and it worked, but then it stopped working on the first half of the third day and I wondered why. It turns out it was probably because phenibut's dopamine enhancing effects got tolerance. I believe there is some sort of mechanism in the brain that needs acetylcholine to be balanced with dopamine, or some sort of related protein/mechanism with the two.

    Again slightly strange, is that going off diphenhydramine today, my constipation was alleviated.

    When I was on diphenhydramine, my anti-fungal immune system increased drastically, and my normally very white and "furry" tongue turned almost pink, and has a slight burning sensation on it.

    Phenibut does two major things, firstly it increases gaba b and inhibits the α2δ subunit of voltage gated calcium channels. This would lead to neurons being less likely to fire, and they would be less excitable overall. This would also effect neurons which release acetylcholine. Secondly, it releases dopamine in a very smooth way, seemingly slightly different to normal stimulants.

    I've heard that candida can inhibit dopamine, and it seems like anti-cholinergics benefit fungal immune system, so perhaps there is some sort of thing happening where the cholinergic system is overactive which allows for fungal infections, which then lower dopamine, which causes an imbalance. This is something I'l look into eventually.

    Perhaps fungi or protazoa evolved to inhibit dopamine in certain areas of the brain so that acetylcholine could upregulate and lower the anti-fungal immune system.

    I'm investigating two different drugs at the moment. These are theories that I haven't tested yet and may be completely untrue. Above this point is mostly based on some empirical evidence.

    Drug one is inositol, which reduces function of the 5ht2a and muscarinic receptors. http://www.ncbi.nlm.nih.gov/pubmed/15214506

    Second is reboxetine, a norepinephrine transporter inhibiter. http://www.ncbi.nlm.nih.gov/pubmed/25146499
    http://www.ncbi.nlm.nih.gov/pubmed/21669025

    My memory is rather shit, and this drug seems to improve memory, increase dopamine in the hippocampus, and "restore acetylcholine sterease activity".

    It makes me think, maybe dopamine and acetylcholine are the main excitatory neurotransmitters in the hippocampus, and when one is underactive, and the other overactive, then perhaps it all balances out and the body doesn't make a compensatory response. But when dopamine is heightened by this drug, then the body compensates and lowers acetylcholine too.

    Theory time over. At any rate, cycling diphenhydramine seems to have benefited me, but I'm still trialing it, so far I've been on it 3 days and off it 1 day. The doses were 25 mg 2x daily, then 50 mg 2x daily on the 3rd day. I'm trying inositol today because it just got in the mail.
     
    Last edited: Feb 22, 2016
  17. AlmostEasy

    AlmostEasy

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    Interesting, thanks for the quick response. Coincidentally I just started using benadryl in fairly high doses for a sleep aid (which works great btw) but I'd read someone using "Low Dose Benadryl" for ME/CFS symptoms in the 5mg range every 4 hours or so. I'd taken 75mg as a sleep aid and it knocked me out. I'll give that a shot though.

    I was up for a university activity at 4 am two days in a row so I was devastated by exhaustion and have been trialing a lot of new supplements so I'm not exactly sure what was doing what but I remember at one point I did wonder enough about it to investigate it's effects in ME/CFS.

    I've used Myo-Inositol to amazing effect in the 500 mg - 1,000 mg range. It is a GABA transport assistant (not quite the technical phrasing) so it doesn't agonize or antagonize but utilizes it more efficiently from what I remember, and it appeared to do just that, very effectively, with 1 major downside - fatigue. I would get just devastating fatigue that I couldn't stand. I've since gone on a much more rigorous methylation protocol so I'm considering trialing it again. Sometimes things affect me differently now. I believe the serotonin effects gave me that kind of crushing fatigue, I get the same kind of thing from 5-HTP and bromantane unfortunately. Bromantane was incredible for a dopamine enhancer but again the fatigue just wrecks me for several hours. I'll have to try these again.

    I'd also take a look at R-Phenibut. The R-isomer only. Lots of people say that it's quite a different experience, much cleaner. I do find Phenibut to be fairly dirty.
     
  18. Deltrus

    Deltrus Senior Member

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    I'm wondering if I jumped the gun and actually am getting a response from diphenhydramine, because it blocks the h1 receptor in the brain, and modulating something with inflammation. I compared the response to cetirizine, but cetirizine doesn't actually cross the BBB so the h1 receptor in the brain is still a large confounding factor. Acetylcholine probably lowered my twitches and stuff, but it is possible that the h1 receptor gave the increase in energy and mental clarity due to lowering inflammation. Or not. No way to tell at the moment.

    In other note, turns out h1 antagonists reduce gaba in the brain and reduce seizure threshhold. I have to stop taking diphenhydramine permanently because of this, I feel like my brain is so excitory that I'm bordering having siezures. I'm having strong reactions to sudden sounds, tinnitus, and I'm having trouble reading things.

    So if you are using diphenhydramine to improve sleep, you better stop, because it will lower gaba and worsen sleep in the long run.
     
  19. AlmostEasy

    AlmostEasy

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    That's kind of how I feel all the time. When something stimulates me too much my brain just short circuits and I don't even process it.

    Of course, I'm not using it chronically for sleep. Just when I need to be out.

    How did inositol go?
     
  20. Deltrus

    Deltrus Senior Member

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    I'm still trying inositol. I dosed once 1.5g and didn't notice anything super apparent, but I need to try it for a few more days.

    In other news, I think I possibly might actually have early stage early onset parkinson's, and not CFS. Parkinson's has been found to start in the lower vagus nerve in the gut, and spread upwards, going to the brain. Fatigue, memory problems, dysautomia etc can all start before the actual tremors. Parkinson's normally starts on one side of the body, and I have tight muscles on my neck, core, and shoulder on the right side. Recently my nervous system inflammation has spread to my jaw and then temple and eye. It also has spread downwards, to my hip and leg on the right side. In the last 2 months or so, I've been experiencing slight tremor, and twitches, signs that early parksinson's has reached the brain. I respond well to phenibut, something which would decrease all neuron activation, including acetylcholine, while simultaneously boosting dopamine, something very important to parkinson's. I also respond to diphenhydramine, and lavender, both of which have some anti-cholinergic properties and can be used to treat parkinson's for short periods.

    http://forums.phoenixrising.me/inde...-subsequent-risk-of-parkinsons-disease.38322/

    http://forums.phoenixrising.me/index.php?threads/how-parkinsons-spreads-from-cell-to-cell.33468/

    My fatigue is abnormal for CFS, it gets worse when I have no source of stimulation/arousal, and it gets extremely bad when I am doing things that are boring, require no thought, and require light-moderate movement movement. It is worse if I am using my right arm over extended period of time. Bursts of heavy activity do not worsen my fatigue, as heavy activity eclipses all thought anyways, it reduces the neural influence.

    https://en.wikipedia.org/wiki/Parkinson's_disease#Other
    This matches me fairly well, I can plan well, but I usually don't want to, and I also fail to carry out my plans, I'm stubborn, and in a previous thread I mention my problems with sensory gating. Although, this also matches lots of people with chronic fatigue syndrome and adhd.


    I would not be surprised if a subset of CFS is early progression parkinson's, with vagus nerve inflammation and dysfunction that will eventually spread to the brain.

    I really hope it is parkinson's and not CFS, as parkinson's pathology is much more understood than CFS and treatments are much more advanced.
     

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