Non-Standard Anti-Anxiety Treatment

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I am alternating the taurine with mag glycinate to avoid building tolerance to the taurine. Some of the effects are similar and some are different. I'm wondering if I have to think about the same concerns with the glycine.
 

Learner1

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You may find this interesting @L'engle

But, taurine and glycine are used in multiple places, so you might be attributing one thing to them when another is in play.

I'm not sure about a tolerance - I suspect if you start taking something, you may run out of cofactors needed for it to react snd do what it's supposed to do. Waiting before the next dose could allow the cofactors to build back up for the reaction to be more effective.
 
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Thanks @Learner1 I'm new to taking both of them. I don't actually have any signs of tolerance to either yet, I am just troubleshooting ahead to avoid potential problems. I've had too many supplements start out good and end up bad. So far they both seem to be helping but it's only been 4 days of each.
 

Hip

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Nootropics suppliers tend to stock picamilon:

https://nootropicsource.com/shop/powders/nootropic-powders/picamilon-sodium-powder/
https://science.bio/product/picamilon-sodium-powder-50g/
https://newmind.com/picamilon-sodium.html
https://www.intellimeds.net/index.php?route=product/search&search=Picamilon
https://www.supersmart.com/en/shop/brain-nutrition/picamilon-supplement-0427

Some people also find pure GABA effective for anxiety, but this did nothing for me. There is some controversy as to whether GABA can cross the blood-brain barrier. In my case, it does not seem able to, because I observed no relaxation from GABA dose up to 3 grams. But others have said it works well for their anxiety.
 

Hip

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Also, when taken, it converts to GABA and nicotinamide, a form of niacin. Both are readily available on the market.
Picamilon breaks down to GABA and niacin, but taking these two supplements is not the same as taking picamilon, because when the two supplements are bonded together to make picamilon, it crosses the blood-brain barrier, whereas GABA normally does not.
 
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Picamilon breaks down to GABA and niacin, but taking these two supplements is not the same as taking picamilon, because when the two supplements are bonded together to make picamilon, it crosses the blood-brain barrier, whereas GABA normally does not.
Interesting. What is it with russian researchers and novel gabaergics tho? Just a coincidence or what? They have picamilon , that other one you recently mentioned to me, and phenibut , plus the russian benzo that is not as good but still... why is that the area they innovate in so much ?
 

Learner1

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Picamilon breaks down to GABA and niacin, but taking these two supplements is not the same as taking picamilon, because when the two supplements are bonded together to make picamilon, it crosses the blood-brain barrier, whereas GABA normally does not.
Gaba definitely doesnt cross BBB

The BBB being impermeable simply isn't true for most patients. Inflammation, oxidative and nitrosative stress, and hypoxia can change the permeability of the BBB and gut bacteria have been found in the brain and have been linked to multiple neurological conditions.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6313445/

https://journals.sagepub.com/doi/full/10.1177/0004867418796955
 

gbells

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Brain Inflammation and Anxiety

I am posting this in case anyone is interested in the non-standard anti-anxiety approach I used to cure my extremely high levels of anxiety (generalized anxiety disorder). This approach may well help others suffering with anxiety.

This protocol may be very useful for people whose anxiety did not resolve using SSRI drugs, etc. It may also help in reducing the "wired but tired" mental state that many with chronic fatigue syndrome are all too familiar with.

NOTE: If you want the quick-to-read version, go straight to the summary at the end of this post.

After many years with horrible anxiety (by far the most unpleasant symptom of my CFS), I finally figured out that my anxiety was likely biochemically created by brain inflammation. As soon as I tried taking certain specific anti-inflammatory supplements, most of my anxiety vanished (within a day or so). Here is the anti-anxiety approach I took:

I used the herbal extract curcumin to block the NF-κB-mediated inflammation, taking curcumin in 3 or 4 daily doses of 500 to 1000 mg. You have to take it several times a day to work: say a capsule at breakfast, one at lunch, one at supper time, and one before bed. This is because the plasma half-life of curcumin is short: 3 to 6 hours, so you need to take it 3 or 4 times a day to keep up your anti-inflammatory blockade.

Another good blocker of NF-κB-mediated inflammation that can be used in place of curcumin (or in addition, if you want) is grape seed extract 500 mg daily. High doses of curcumin can occasionally slightly increase anger and irritability in some people, so keep a watch out for that; grape seed extract does not have this problem.

Either of these can rapidly lower your anxiety.

Other good NF-κB blockers that you can use are: ashwagandha (1000 mg), alpha lipoic acid (500 mg - though some may not be able to take this high dose), sulfasalazine (500 to 1000 mg); sulfasalazine is usually a well tolerated drug.

Note than you do not want to totally block NF-κB, because it is needed for other metabolic functions.

You might also want to simultaneously try a second anti-inflammatory: one that targets COX-2-mediated inflammation. This can further lower your anxiety. For this, take propolis herb, 1000 mg, on the same dosing schedule (that is, 3 or 4 times a day - not before bed, though, as propolis can keep you awake). Propolis is an potent COX-2 inhibitor. Cat's claw is another good COX-2 inhibitor, and 1000 mg of cat's claw can be used in place of propolis (or in addition, if you want).

(If neither NF-κB or COX-2 inhibitors bring relief, then consider trying a 5-LOX anti-inflammatory, such as the 5-LOXIN extract of Boswellia serrata. You may also try all 3 of these together, since more than one inflammatory mechanism can be at play. )

The idea of these anti-inflammatory approaches to treating anxiety is that they block the mechanisms that create the biochemistry of anxiety in the brain in the first place. That is, they target the actual cause of anxiety, closer to the source.



The Theory

I suspect what is happening in the brain to create this anxiety is the chronic overstimulation of the NMDA receptors — the brain cell receptors that mediate anxiety. Dr Martin Pall has examined the state of hyperexcitement of NMDA receptors in CFS (mostly in the context of excitotoxicity and the NO/ONOO cycle). But here we are interested in the NMDA hyperexcitement–anxiety connection.

The NMDA receptors are overstimulated probably because of the chronic microglial activation that is found in brain inflammation (microglia form part of the brain's immune system). Glutamate and quinolinic acid are produced as a by-product of microglial operation; glutamate will strongly activate the NMDA receptors, leading to biochemically-created anxiety. Quinolinic acid might also activate the NMDA receptors (although this study suggests not enough quinolinic acid is produced to substantially activate NMDA).

In summary: inflamed brain ➤ chronic microglial activation ➤ excess glutamate production ➤ NMDA overstimulation ➤ induces anxiety state.

Inhibiting NF-κB reduces microglial activation, which may be why this approach eliminates anxiety at source. Vitamin E (alpha tocopherol) also reduces microglia activation, as does the flavonoid genistein, and tetracycline antibiotics, so these can have an anti-anxiety effect when inflammation in the brain is the cause of anxiety. It may be worth adding say vitamin E and/or genistein to the anti-inflammatory protocol. Sesame seed oil also inhibits microglial activation. A lot of excellent research on brain inflammation's role in anxiety and depression has been done by Dr Gina Nick, and her protocol for treating brain inflammation uses similar supplements to those listed above.

Note that brain inflammation can damage the brain through excitotoxicity, so lowering this inflammation is neuroprotective.



Other Anti-Anxiety Supplements

If the above anti-inflammatory approaches to treating anxiety do not work for you (or only work to a limited degree) then you may have to use additional treatments:

Other anti-anxiety supplements I found useful are: inositol (10 to 15 grams daily).

These supplements can be taken two or three times daily: taurine (1000 mg), L-carnitine (500 mg), picamilon (100 mg), arginine pyroglutamate (2 grams), theanine (200 mg), vitamin B1 (100 mg), vitamin B6 (50 mg), vitamin B5 (1 gram).

Note that taurine inhibits NMDA receptor stimulation, by sitting on the NMDA receptors, and blocking their activation by glutamate and quinolinic acid.

Some excellent anti-anxiety herbs are: ashwagandha, which is also a good NF-κB inhibitor, and Bacopa monnieri.

Other useful anti-anxiety herbs are: chamomile (especially the apigenin extract of chamomile), lavender, passionflower.

Holy basil can dramatically improve anxiety in some people (holy basil is potent COX-2 inhibitor, however, thus its anxiolytic mechanism may actually be as an anti-inflammatory rather than a palliative; holy basil also lowers cortisol, and high cortisol is another source of some people's anxiety states - but watch out if you have low cortisol).

The antihistamines cetirizine (Zyrtec) and loratadine can reduce anxiety symptoms. Dose is 10 mg daily.

Transdermal magnesium cream used twice daily is also works quite well to reduce anxiety. Transdermal magnesium is often used in autism, where there are very high levels of internal mental anxiety. Magnesium potently lowers NMDA receptor activation, by sitting on the NMDA receptors, and blocking their activation.

Transdermal magnesium cream is generally very helpful in CFS, as magnesium has many useful functions, like supporting mitochondria.

You can make your own cheap transdermal magnesium cream, simply using Epsom Salts mixed with some hand cream. Oral magnesium may also help, but most people reach bowel tolerance (they get diarrhea) after about 500 mg or so of oral magnesium supplements. The magnesium content of Epsom Salts (magnesium sulfate MgSO4) is 20%, so 5 grams of Epsom Salts provides 1 gram of elemental magnesium. One heaped teaspoon of Epsom Salts weights about 7 grams, just for reference. You need to use at least 1 heaped teaspoon of Epsom Salts (dissolved in little bit of water, and mixed into a hand cream) on each transdermal application.



GABA and NMDA

Another approach to reducing anxiety is to stimulate the GABA receptors. GABA receptors are the opposite to NMDA receptors: when you activate GABA receptors, your brain relaxes; whereas when you activate NMDA receptors, your brain goes on alert, and higher NMDA activation leads to anxiety. Therefore, to reduce anxiety, you can either lower the activation of the NMDA receptors, or increase the activation of the GABA receptors. Or both.

Many anti-anxiety drugs and herbs work by increasing GABA stimulation, including the herb valerian, and benzodiazepines drugs. Benzodiazepine drugs include: clonazepam (Klonopin), alprazolam (Xanax), and diazepam (Valium). The trouble with these drugs, though, is that at high doses the GABA receptors build up tolerance, so the effect of the drug gets less with time. This also means that these GABA drugs can be additive, and so you will feel more anxiety on stopping them (ie, withdrawal symptoms, rebound).

This tolerance does not occur on the NMDA receptor when you block it, so in the long term it may be better to use an NMDA blocker like magnesium, rather than a GABA stimulator like benzodiazepines.

There are not that many good NMDA blockers around. Here are some NMDA antagonists: magnesium (potent), zinc, taurine, guaifenesin (possibly), huperzine A, memantine, dextromethorphan (cough medicine), amantadine (an antiviral), nitrous oxide gas (N2O), ketamine, ibogaine.

But as has been recommended above, stoping the anxiety at source, by inhibiting brain inflammation, is probably by far the best approach. If you really want to wipe out your anxiety, you can take more than one approach at the same time: that is, the recommended anti-brain inflammation supplements, plus NMDA-blocking supplements like magnesium or taurine, and whatever other supplements you find helpful.

If anyone has any further ideas or info on other mechanisms behind biochemically-generated anxiety, please post.



Summary

To try this anti-anxiety protocol, start with say grape seed extract 500 mg. Add to this 1000 mg of propolis, 3 times a day (best not to take propolis before bed - it may keep you awake). Finally, you can add vitamin E (alpha tocopherol) 400 mg twice a day. These three supplements will act to reduce brain inflammation, and thus reduce anxiety (hopefully).
Ashwagandha isn't approved for long term use due it harming the thyroid.

Lavender has strong research to treat anxiety and is nonaddicting. The most cost effective approach is organic lav essential oil, 1-2 drops stirred in 6 oz water and sipped.
 

Hip

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The BBB being impermeable simply isn't true for most patients. Inflammation, oxidative and nitrosative stress, and hypoxia can change the permeability of the BBB and gut bacteria have been found in the brain and have been linked to multiple neurological conditions.
That may be the case, but you find that GABA supplementation has no anti-anxiety effects for most people, including ME/CFS patients, indicating that very little or no GABA gets through the blood-brain barrier.

Curiously though, you get the occasional individual who finds GABA has strong anti-anxiety effects. Whether that is because they may have a very leaky blood-brain barrier, or whether it is due to some other reasons, is not clear.

Recent analysis has questioned the old belief that GABA cannot cross the BBB:
There are both a number of studies that were unable to show that GABA crosses the BBB and a number of studies that did show GABA’s ability to cross. In view of the multitude of employed methods and species, in addition to the finding that GABA metabolism might differ between rodents and humans (Errante et al., 2002), it is not possible at this time to come to a definite conclusion with regards to GABA’s BBB permeability in humans.



Interesting. What is it with russian researchers and novel gabaergics tho? Just a coincidence or what? They have picamilon , that other one you recently mentioned to me, and phenibut , plus the russian benzo that is not as good but still... why is that the area they innovate in so much ?
Yes, there are a lot of unusual Russian or Soviet-era drugs that target the brain, anxiolytics and others. Although I've not really come across any glowing reports of these drugs, suggesting efficacy is not that great.

Here is a list of Russian anxiolytics I compiled:
Selank — Russian nootropic drug with anti-anxiety properties. Also has some stimulatory effects, and has hypnosedative and muscle relaxant properties.

Semax — Russian nootropic drug with anti-anxiety properties. Helps repair the brain after stroke. Increases verbal fluency. Unfortunately it is a bit expensive.

Tenoten — Russian nootropic drug with anti-anxiety properties. Reduces anxiety, fear, irritability & emotional liability. Mechanism: antibodies against S-100 protein at ultra-low doses exert GABA-mimetic and neurotrophic actions, up-regulate stress-limiting systems, contribute to the restoration of neuroplasticity.

Mebicar (Adaptol) — Russian drug with anti-anxiety properties. Helps ADHD. Mebicar has an effect on the structure of limbic-reticular activity, particularly on hypothalamus emotional zone, as well as on all 4 basic neuromediator systems – γ aminobutyric acid (GASS), choline, serotonin and adrenergic activity. Mebicar decreases the brain noradrenaline level, exerts no effect on the dopaminergic systems, increases the brain serotonin level, and does not elicit cholinolytic action.

Bromantan (Ladasten) — Russian drug. Novel in that it is both a stimulant, and has anti-anxiety properties at the same time. Works by inhibiting the reuptake of both dopamine and serotonin in the brain. Eliminates daytime sleepiness, increased activity, improves concentration and both physical & mental performance.

Menthyl valerate, aka: validolum (Validol) — Russian drug with anti-anxiety properties. Vasodilator, lowering blood pressure. Stimulates endorphins. Sublingual tablets work in under 5 minutes. Take 1 Validol tablet 2 to 3 times daily. Non habit forming. In prolonged use may cause light nausea, dizziness, and tearing of the eyes which fade away with discontinuation. Possible manifestation of hypersensitivity.

Emoxypine (Mexidol) a Russia antioxidant similar in structure to pyridoxine (vitamin B6). Studies show it shields against stress and anxiety.

Picamilon is a Russian drug made by bonding niacin with GABA. Also sold as a supplement.

Fabomotizole (Afobazole) is an anxiolytic drug launched in Russia in the early 2000s. It produces anxiolytic and neuroprotective effects without any sedative or muscle relaxant actions

Etifoxine — is an anxiolytic and anticonvulsant drug. Binds to GABA-A receptors and mitochondrial translocator protein (TSPO), resulting in increases in endogenous neurosteroids.
 

Hip

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Lavender has strong research to treat anxiety and is nonaddicting. The most cost effective approach is organic lav essential oil, 1-2 drops stirred in 6 oz water and sipped.
When I had moderate to severe generalized anxiety disorder (severe GAD is a totally is crippling condition), I tried numerous supplements, including lavender essential oil. Lavender's effect was too mild for me to make much use of, but I did use it occasionally to help promote sleep.

This 2010 thread represents my early attempts to treat my GAD, but a later 2012 thread details better approaches that I discovered. The star anti-anxiety supplement in that thread is N-acetyl glucosamine.
 
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So in terms of nmda antagonists OR things that lower glutamate that aren't nmda antagonists... if we leave out ketamine and nitrous oxide bc of the side effects, and leave out xenon which is an expensive miracle drug, what do you have left in order of strength

How strong is taurine? How about glycine ? Magnesium injections? Magnesium iv?
 
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That may be the case, but you find that GABA supplementation has no anti-anxiety effects for most people, including ME/CFS patients, indicating that very little or no GABA gets through the blood-brain barrier.

Curiously though, you get the occasional individual who finds GABA has strong anti-anxiety effects. Whether that is because they may have a very leaky blood-brain barrier, or whether it is due to some other reasons, is not clear.

Recent analysis has questioned the old belief that GABA cannot cross the BBB:







Yes, there are a lot of unusual Russian or Soviet-era drugs that target the brain, anxiolytics and others. Although I've not really come across any glowing reports of these drugs, suggesting efficacy is not that great.

Here is a list of Russian anxiolytics I compiled:
Selank — Russian nootropic drug with anti-anxiety properties. Also has some stimulatory effects, and has hypnosedative and muscle relaxant properties.

Semax — Russian nootropic drug with anti-anxiety properties. Helps repair the brain after stroke. Increases verbal fluency. Unfortunately it is a bit expensive.

Tenoten — Russian nootropic drug with anti-anxiety properties. Reduces anxiety, fear, irritability & emotional liability. Mechanism: antibodies against S-100 protein at ultra-low doses exert GABA-mimetic and neurotrophic actions, up-regulate stress-limiting systems, contribute to the restoration of neuroplasticity.

Mebicar (Adaptol) — Russian drug with anti-anxiety properties. Helps ADHD. Mebicar has an effect on the structure of limbic-reticular activity, particularly on hypothalamus emotional zone, as well as on all 4 basic neuromediator systems – γ aminobutyric acid (GASS), choline, serotonin and adrenergic activity. Mebicar decreases the brain noradrenaline level, exerts no effect on the dopaminergic systems, increases the brain serotonin level, and does not elicit cholinolytic action.

Bromantan (Ladasten) — Russian drug. Novel in that it is both a stimulant, and has anti-anxiety properties at the same time. Works by inhibiting the reuptake of both dopamine and serotonin in the brain. Eliminates daytime sleepiness, increased activity, improves concentration and both physical & mental performance.

Menthyl valerate, aka: validolum (Validol) — Russian drug with anti-anxiety properties. Vasodilator, lowering blood pressure. Stimulates endorphins. Sublingual tablets work in under 5 minutes. Take 1 Validol tablet 2 to 3 times daily. Non habit forming. In prolonged use may cause light nausea, dizziness, and tearing of the eyes which fade away with discontinuation. Possible manifestation of hypersensitivity.

Emoxypine (Mexidol) a Russia antioxidant similar in structure to pyridoxine (vitamin B6). Studies show it shields against stress and anxiety.

Picamilon is a Russian drug made by bonding niacin with GABA. Also sold as a supplement.

Fabomotizole (Afobazole) is an anxiolytic drug launched in Russia in the early 2000s. It produces anxiolytic and neuroprotective effects without any sedative or muscle relaxant actions

Etifoxine — is an anxiolytic and anticonvulsant drug. Binds to GABA-A receptors and mitochondrial translocator protein (TSPO), resulting in increases in endogenous neurosteroids.
Well phenibut does have glowing reports. But maybe not the milder drugs on that list
 

Hip

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what do you have left in order of strength

How strong is taurine? How about glycine ? Magnesium injections? Magnesium iv?
In the list of 29 anti-anxiety supplements detailed in this post, I try to place them in approximate order of strength. This is from testing these on myself, and observing how they reduce anxiety levels.

Top supplement by far is N-acetyl glucosamine, without question.

Taurine is good, it works on both NMDA and GABA, but has a tolerance build-up (I expect due more to its GABA action, as I think GABA is much more prone to tolerance than NMDA). So I use taurine 4 grams just on days when my anxiety has flared up, but do not take it continuously.

Magnesium sulfate injections are both painful and damage veins. So I would suggest the transdermal route.




Well phenibut does have glowing reports. But maybe not the milder drugs on that list
I did not know phenibut was Russian. Yes, people rate phenibut, though I am amazed it is sold as a supplement, as I heard it can have tolerance and withdrawal symptoms as a bad as benzos.
 
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did not know phenibut was Russian. Yes, people rate phenibut, though I am amazed it is sold as a supplement, as I heard it can have tolerance and withdrawal symptoms as a bad as benzos.
Yes , I think if was developed there originally for cosmonauts or something. And more research from Russia than here for some reason

I'm aware of the downsides but let me say this: it should never be used daily, but before I had severe me/cfs, when I had more moderate illness, I used it on average three times a week with large doses, and just using it every other day was enough to prevent withdrawals. I also didnt get dramatic rebound effects.

So it can be used a lot without causing withdrawals, u just cant use it daily, which is true of many things. Also based on research but also ample personal experience it is preferable to benzos in every single way. It doesnt dull cognition at all, manages to be muscle relaxation and lower anxiety and help sleep without dulling cognition like benzos do. It is experientially like if alcohol didnt cause cognitive dulling and sickness and intense motor problems. Or if ghb had less negative effects on cognition and was a bit more stimulating.
 
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Taurine is good, it works on both NMDA and GABA, but has a tolerance build-up (I expect due more to its GABA action, as I think GABA is much more prone to tolerance than NMDA). So I use taurine 4 grams just on days when my anxiety has flared up, but do not take it continuously.

Magnesium sulfate injections are both painful and damage veins. So I would suggest the transdermal route.
Good info thanks. So you think taurine has more noticeable effects than glycine or theanine or progesterone ?

As far asmagnesium, interesting. Def dont wanna damage veins , and I also havent noticed much from subcutaneous injections but maybe the doses weren't high enough. When I did hot springs I got dramatic effects from them, they had magnesium along with other electrolytes and lithium and many trace minerals. The hot springs effects were almost as dramatic as gabaergics or even a low dose of ketamine ...