GABA & derivatives, gabapentin (Neurontin), pregabalin (Lyrica), phenibut, baclofen, picamilon

JayCS · April 17, 2021, 2:52pm

version 2021-04 - newest version below

I’m kidnapping this “Gaba”-thread after success with GABA (thx to your question, @Karen6)… as a new resource thread on GABA, which is a neurotransmitter in our brain, used as a supp, and its analogs, derivatives, relatives, used as meds…

1. GABA itself, gamma-Aminobutyric acid

1.a. My GABA-experience - May 14th: 30 days very positive

After 30 really bad days & often nights before (1 moderate one), I’ve had 30 really good days and nights …
This is a list of the effects on me up to today, May 6th.
JayCS’s Fibro Blog (see summary-thread ∑) - #338 by JayCS

I wasn’t planning on this combination, but felt like making sure and found it & spontaneously decided on it. Don’t know of course if it’s necessary, as glutamic acid and passiflora didn’t do anything alone.
In the first night I took it after dozing a few hours, was up 8x, had a few side effects, but - immediately had a good day: no stiffness, no seizure, no drowsiness or numbness, no further side effects aside from tingling, bowel movement & stronger pulse at the beginning, no belly ache, no breathing problems. I was able to work 4h30 (live incl. commuting & digi), didn’t have time for table tennis, but cycling and running a bit was quite OK. At work I did have my typical mask-problems after talking a bit - altho only to single people, making me feel feverish.
In the 2nd & now 3rd night I took it almost like recommended (30’), 60’ before actually being in bed.
Hardly any side effects: dry mouth, slightly feverish-squeamish. The 2nd night slight belly pressure-pain. The dry mouth was painful, different to the one I got from amitriptyline or other things. GC dry mouth gel relieved it immediately both nights and after that sipping soy drink was sufficient.
But yesterday I cd do quite a lot. I was able to work 3h (digi) and jump around with my grandchild in the evening like I haven’t been able to for ages - not perfect, but much better. and was extremely fit & concentrated at table tennis (8:0), cd’ve done 2 more, that’s really neat. I gave it 90% for “feeling well” and “1” for pain - maybe a bit rose-red, but a great improvement.
3rd day great again… So:
4th night: No stiffness etc. but Harry Potter type dreams - yucky feeling, bowel movement → Hot Water Bottle.
Jump to Apr 28th 2021: Side effects decreased: Only 1) drowsiness & 2) sometimes vivid dreams, 3) 1.5 nose bleeds, no longer dry mouth & itchiness. Positive effects still good: Bladder sensitivity considerably reduced. Still need 9-10h sleep.
More details in above mentioned blog entry.
…
I had taken 1-2 GABA-pills once before, apparently, as well as picamilon, without an effect. Praps I needed to get pains down first?
Or is it the combination with Magnesium, glutamic acid and passiflora?

1.b. GABA

Great GABA-info-pages

General: GABA Archives - everywomanover29
Tense muscles: https://www.everywomanover29.com/blog/gaba-physical-tension-stiff-tense-muscles-type-anxiety
https://www.psychologytoday.com/us/blog/sleep-newzzz/201901/3-amazing-benefits-gaba: Brakes of the brain (valerian and hops, magnesium, and L-theanine, L-arginine, kava, passionflower, and American ginseng) (for high blood pressure, stress, anxiety, mood, muscle tone, immune & endocrine system, in gut perhaps supports motility, controls inflammation and supports immune system function, and helps regulate hormone activity)
https://www.healthline.com/health/gamma-aminobutyric-acid:

Overview: Why GABA is one of the Best Supplements for Anxiety and Sleep (Updated – Natural Stacks. (Combination recommended):
You should never take a GABA supplement on its own! It actually won’t work!
It’s strange that more people don’t know about this neurotransmitter, since it’s the most common one in our central nervous systems!
When you have a “fight or flight response” — your heart beats faster and your stomach knots up — GABA is what allows your brain to calm down again afterwards.
This is because GABA is responsible for putting the brakes on messages passing between our neurons, telling them not to fire, and thereby blocking stress response messages from being passed along to the rest of the body.
This explains why low levels of GABA or disruption of GABA receptors is associated with some forms of epilepsy and various other physical and mental disorders characterized by excitability.
So why doesn’t it work all the time?
Under normal conditions, the excitatory and inhibitory systems work in harmony to keep the nervous system in balance.
But when faced with chronic stress and fatigue, the neurotransmitters can get out of synch.
The body’s natural stress response overpowers the amount of GABA that the body can produce to compensate.
These include high blood pressure, sweating, increased secretion of gastric acid and activity of the large intestine.
Part of the production pathway for GABA takes place in the mitochondria in our cells. Stress causes inflammation and oxidative stress and, together with a nutritional imbalance, it affects mitochondrial health.

While there’s no food that contains GABA(??? - why do other sites say that there is?), you can certainly eat foods that provide glutamate and glutamic acid, the precursors that your body uses to make GABA.
Foods with lots of glutamate and glutamic acid include grass-fed meats, eggs, dairy products, fish, sea vegetables, tomatoes and mushrooms.
Other supplements which have been shown to increase GABA or enhance its function include L-thiamine, the amino acid taurine, and certain herbs including kava, passionflower and lemon balm.

The following dosages are recommended:
General stress relief
650 -800 mg per day
Divide into three or four doses during the day
Anxiety
250 – 650 mg 3x per day
Maximum dose 1950 mg per day
Improved sleep
250 – 650 mg daily
Take just before sleep
Insomnia
500 – 1000 mg
Take just before sleep. High dose ensures that more crosses the BBB
A recent study on humans showed that a supplement combining both GABA and 5-HTP reduced the time it took to fall asleep, increased the duration of sleep, and improved sleep quality. [11]

Ingredients of recommended combination:
L-CITRULINE (500MG)
ROSEMARY EXTRACT (333MG)
GRAPE SEED EXTRACT (33MG)
GABA Supplement - For Better Sleep and Relaxation - 60 Ct. – Natural Stacks

https://www.healthline.com/health/gamma-aminobutyric-acid: The only foods that contain GABA are fermented ones, such as kimchi, miso, and tempeh. ADHD & anxiety lowers GABA. Side effects: Upset stomach, headache, sleepiness, muscle weakness.

GABA-combination with 5-HTP or Tryptophan:
Sleep promoting effects of combined GABA and 5-HTP: new research - everywomanover29
e.g. 1000mg GABA and 100mg 5-HTP or better even
1000mg GABA and 1000mg tryptophan
5-HTP can increase cortisol - watch for that.

GABA helping means a leaky brain?!

How to Increase GABA and Lower Glutamate
According to Dr. Datis Kharazzian, a brain expert, if you have any effect from GABA, (positive or negative) that means you have a leaky brain. In his book, Why Isn’t My Brain Working, he explains that in a healthy brain, the junctions in the blood-brain barrier only permit nanoparticles to pass through. GABA “exceeds the nanoparticle size and does not have a blood-brain barrier transport protein.” It should not be able to cross the blood-brain barrier. If it does, then this suggests there is a leaky brain.
As a matter of fact, Dr. Kharrazian uses GABA supplementation as a screening tool to determine whether one has a leaky brain or not, calling it the GABA Challenge Test. He also states you shouldn’t take GABA supplementation, even if you have a positive effect, “because you risk shutting down your GABA receptor sites.” This is evidenced by the fact that many people experience withdrawal when they come off a GABA supplement. The fact that withdrawal is occurring tells us that the brain is downregulating responsiveness to GABA in response to the GABA supplementation. I do not encourage the use of GABA supplements unless one is coming off a benzo and uses it temporarily to get from point A to point B in recovery. If you have no effect from GABA, this is a good sign, you most likely to do not have a leaky brain. If a leaky brain is present, then many other harmful substances can be crossing the blood-brain barrier and causing additional problems.
Integrative Holistic Health Coach - Cynthia Perkins, M.Ed.

Evidence-based-wise it’s not understood if/why/how GABA itself works, it shdn’t really get into the brain (over the BBB) and there isn’t really enough research. Altho it probably reduces excitability and muscle tone, which is exactly what I’ve often thought and influence by my various relaxation techniques. It also fits to the suspicion that I might have something like RLS.

GABA has been made into analogs, gabapentin (aka Neurontin) and pregabalin, ‘chemical’ derivates, which I haven’t been wanting to take because of the far higher amount and severity of side effects. GABA is the most natural one with the least probability of side effects.
Studies:
2015: Unclear if just placebo, mechanism of action, if it praps can cross the blood-brain barrier (BBB), if it has a calming effect. Effect on brain and cognition might be exerted through BBB passage or, more indirectly, via an effect on the enteric nervous system.

Neurotransmitters as food supplements: the effects of GABA on brain and behavior - PubMed
2020: limited evidence for stress and very limited evidence for sleep benefits of oral GABA intake.
Effects of Oral Gamma-Aminobutyric Acid (GABA) Administration on Stress and Sleep in Humans: A Systematic Review - PubMed

GABA can help people to fall asleep quickly, AVLE induces deep sleep, and they function complementarily with simultaneous intake. AVLE = Apocynum venetum leaf extract
(Strange: It says these are both not poisonous, since contained in food, but all I can find to apocynum is arrow poison, poisonous milk, and I don’t know it in any way either.)
(“Since both GABA and AVLE are materials of foods and have been ingested for a long time, they can be regarded as safe and appropriate for daily intake in order to improve the quality of sleep.”)
The Improvement of Sleep by Oral Intake of GABA and Apocynum venetum Leaf Extract - PubMed

Further GABA-links
Why GABA is one of the Best Supplements for Anxiety and Sleep (Updated – Natural Stacks

Oh, on one of the pages that’s helping a lot for GABA generally I’ve also found IC/bladder/IBS: GABA Archives - everywomanover29
Throat tightening: good for esophagus block too? Everyone’s different, so start low and try. Recommends opening capsules and using it sublingually.
Challenging the leaky brain theory The Anxiety Summit - GABA: Blood brain barrier controversy, concerns, best forms and how to do a trial for eliminating anxiety - everywomanover29
German Gaba -Wirkung, Dosierung, Mangel, Nebenwirkungen -VitaminExpress here it mentions which foods contain GABA and that GAD has to do with it. ADHD-kids have less GABA… Good combinations, incl. Mg & passion flower. Studies.
How to test yourself for leaky gut. The "gaba challenge" | Integrative functional medicine blog There seem to be recent GABA-types which are absorbed better. (Dr. Craig Mortensen)
https://www.balancingbrainchemistry.co.uk/peter-smith/168/How-to-test-for-a-leaky-Blood-Brain-Barrier-with-GABA-Supplements.html
https://www.balancingbrainchemistry.co.uk/peter-smith/112/Repairing-&-Making-the-Brain-Healthy/Leaky-blood-brain-barrier-and-mental-health.html Leaky Brain
https://www.balancingbrainchemistry.co.uk/peter-smith/127/About-Peter-Smitth.html Amygdala Reprogramming…
https://www.balancingbrainchemistry.co.uk/peter-smith/167/Why-You-Shouldn’t-Take-GABA-Supplements.html Why you shouldn’t…
Magnesium 3h inside of pregabalin/gabapentin can block them. https://healthunlocked.com/rlsuk/posts/143635184/pregabalin-gabapentin-together…
Mg increases Gaba How Magnesium Relieves Anxiety & Stress (detailed review) | Be Brain Fit

Magnesium is an nmda receptor antagonist. Nmda channels regulate glutamate which is the opposite of gaba Therefore magnesium binds and blocks glutamate transmission.
https://www.reddit.com/r/Nootropics/comments/m2h7h1/how_does_magnesium_glycinate_effect_gaba/
(How to do an amino acid trial for anxiety
Amino Acids Mood Questionnaire from The Antianxiety Food Solution - everywomanover29)
Blood Brain Barrier - Chelation Community

1.c. GABA-increasing herbs:

kava, valerian, pennywort, hops, chamomile, Ginkgo biloba, passionflower (passiflora), ashwagandha, skullcap, and lemon balm.
GABA-modulating phytomedicines for anxiety: A systematic review of preclinical and clinical evidence - PubMed
Passionflower: Modulation of the γ-aminobutyric acid (GABA) system by Passiflora incarnata L - PubMed

1.d. GABA side effects (much rarer, but similar to those of the analogs)

GABA side effects https://www.gammaaminobutyricacid.org/gaba-side-effects/
GABA - much more rarely - can cause similar side effects to gabapentin & pregabalin, esp.
Anxiety, appetite increase, balance problems, blurred vision, constipation, dizziness, Drowsiness, dry mouth, irritation, itchiness, joint pain, memory problems, muscle pain, stomach
Severe Side Effects: bleeding, bruising easily, energy lack generally, fatigue, fever high, muscle pain severe, swelling of hands and feet, weight gain increased.

1.e. GABA-threads

GABA: None except this one! and
Your thoughts on GABA - #5 by Rachel_Pronyshyn where GABA was being confused with gabapentin

2. Gabapentin ('Neurontin', 'Gralise') a. effects and b. side-effects, incl. threads, c. differences to GABA

a. Gabapentin (‘Neurontin’, ‘Gralise’) was first used for epilepsy 1995 and then found to be good for neuralgia as well as RLS (restless legs). It desensitizes the nerves (cf. the CSS-hypothesis…). Takes 1-2 weeks to work properly (which GABA didn’t…) Careful with kidneys. Starting with small doses. It’s not that good for epilepsy.
English sites add: neuropathic pain, for example fibromyalgia, insomnia, and bipolar disorder.
It has no effect on the amount of GABA in the brain. Neurontin is not converted into GABA either, and acts as an anticonvulsant which also has some analgesic properties.

2.b. Gabapentin side effects

Gabapentin can cause headaches, fuzzy vision, dizziness, bladder problems, with eye movement and frequent seizures? Sometimes like pregabalin balancing, mouth dryness & shakiness. Also hallucinations, and gastrointestinal disturbances, or even suicidal thoughts, drastic behavioral changes, and difficulty breathing.

2.b. Gabapentin side effects - threads

Gabapentin:
https://forum.livingwithfibro.org/t/gabapentin/10737/8: Side effects of drowsiness & weight.
https://forum.livingwithfibro.org/t/gabapentin/3341/2: allergy, drowsiness, dizziness, stomach pain, no fibro-pain help, calm, weight, stoned, headaches upon waking.
Gabapentin - #6 by Gaila weight
Gabapentin - #3 by Rachel_Pronyshyn sleepy, dizzy, fuzzy headed, decreasing, except dizzy, problems walking,legs bruised, dizzy faded, falls didn’t.
Gabapentin Only no help, migraine instantly, dizzy, cousin of lyrica = pregabalin.

2.b. Gabapentin-posts

Gralise is an extended release form of gabapentin

https://forum.livingwithfibro.org/t/gralise-gabapentin-instead-of-lyrica-pregabalin-or-neurontin-gabapentin/3257
https://www.drugs.com/pro/gralise.html

1.c. GABA gabapentin differences

GABA and Gabapentin are two different things. Though they may have some similar effects (e.g. reducing excitability), and structurally they look alike, they both serve different purposes.
https://www.gammaaminobutyricacid.org/difference-between-gaba-gabapentin/

3. Pregabalin ('Lyrica') a. effects & b. side effects, incl. threads

a. Pregabalin (‘Lyrica’) works stronger, quicker, longer and more calculateable and is far cheaper. It seems good for neuropathy and fibromalgia. It does NOT react ‘at the GABA-receptors’.
b. Pregabalin side effects can be balancing, mouth dryness, shakiness, bruises, abnormal bleeding, sight problems, muscle pain, may be less than gabapentin. Causes addiction, is often ‘abused’, has become very popular for that in Germany. Can make you ‘happy’, but also feel drugged. Edema, weight gain. Has to be weaned off very carefully.
https://www.dailymail.co.uk/health/article-9513953/Hooked-ANXIETY-pills-experts-calling-new-VALIUM.html

Pregabalin threads

pregabalin here:
https://forum.livingwithfibro.org/t/lyrica-pregabalin-worth-trying/3540
https://forum.livingwithfibro.org/t/what-are-your-experiences-with-lyrica-pregabalin/2446

4. Phenibut

Phenibut is another GABA analogue, but concern is growing about its recreational use, because it is very psychoactive, altho it is “being marketed online as an anxiolytic and nootropic dietary supplement”. (Also seems to help with social anxiety, according to wp.) (Russia, 1960s)
https://pubmed.ncbi.nlm.nih.gov/30852710/

5. Baclofen

Baclofen is mentioned as a keyword in the phenibut-article, is GABA-related, but I’ll leave that for now.

6. Picamilon (GABA lab split with niacin (nicotinic acid)

Picamilon is a lab split of GABA and niacin (nicotinic acid), which I’ve referred to here https://forum.livingwithfibro.org/t/has-anyone-seen-the-research-on-melatonin/13416/16?u=jaycs
an acquaintance has also recommended picamilon once again. I’d tried 2 pills he’d given me a few months ago. I’m skeptical there, because it’s a lab-synthesis of GABA and niacin, which is why it is not FDA-approved, so not allowed, but semi-illegally sold in the US. While that seems scary (unregulated) I think I should compare it to having tried tilidine or taking statins for my blood fats, since picamilon is claimed to reduce these, as well as blood pressure, both of which might be better than taking the other chemicals (it doesn’t improve on statins). It was developed as a pro-drug of GABA to overcome the BBB. However since GABA works for me, that obviously isn’t my problem. Niacin is a form of vitamin B3. One of the adverse effect of picamilon is said to be skin problems, but cf. tilidine etc. Niacin: skin, bowels and more, if at all start very low.
https://en.wikipedia.org/wiki/Niacin#Adverse_effects
Flush free Niacin (Inositol?, ?inositol hexaniacinate, but see Inositol itself??)
Picamilon, Pikamilon, Pycamilon is also called N-nicotinoyl-GABA.
https://en.wikipedia.org/wiki/Picamilon

7. Mirogabalin ('Tarlige') - for neuropathy, apparently ineffective for FMS

mirogabalin is in the same family as gabapentin and pregabalin (gabapentinoid) and is not prescribed for fibro normally.
https://pubmed.ncbi.nlm.nih.gov/31284771/ “Conclusion: While both mirogabalin doses were well tolerated by most patients and showed potential for reducing pain associated with FM, the primary endpoint of significant pain reduction in patients on mirogabalin compared with placebo was not achieved in any of the three randomized controlled studies.”

List of all GABA analogues on wikipedia

(German links on GABA, gabapentin & pregabalin)

German GABA overview: https://naturaldoping.de/gaba/
German: Warning - buy GABA in Apotheke, short overview: https://schlanke-list.de/gaba-aminobuttersaeure/
https://www.krankenkassenzentrale.de/produkt/gaba (incl. few English pubmed studies)
German gabapentin overview: https://www.netdoktor.de/medikamente/gabapentin/
German gabapentin side effects https://www.onmeda.de/Wirkstoffe/Gabapenti/nebenwirkungen-medikament-10.html
German differences gabapentin - pregabalin https://esdifferent.com/differences-between-gabapentin-and-pregabalin
German pregabalin https://news.doccheck.com/de/229191/pregabalin-die-gaba-droehnung/

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GABA & derivatives, gabapentin (Neurontin), pregabalin (Lyrica), phenibut, baclofen, picamilon

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