This post is for you if tried anti-anxiety meds, Cognitive Behavioral Therapy, counseling, or psychotherapy. And are looking for a natural nootropic alternative.
Or maybe you tried talking to your doctor about how you feel and didn’t get the help you need.
It may be of little comfort, but did you know there is a 77% chance that your anxiety has been misdiagnosed as some physical problem instead?[i]
Because anxiety often manifests as sweating, trembling, nausea, abdominal problems, dizziness, insomnia, heart palpitations, accelerated heart rate, chest pain, shortness of breath, pins and needles, feeling like your losing control and/or feelings of impending doom.
Instead of dealing with the real cause, maybe you were sent down the wrong path. And are still looking for answers.
Nootropic supplements may help if you’re dealing with a genuine anxiety disorder. The kind of anxiety that has you feeling constantly on-edge and an overwhelming sense of dread.
The type of anxiety where you have difficulty concentrating, you’re irritable or restless to the point you’re avoiding family and friends just to numb yourself from feelings of worry and unrelenting doom.
Here you’ll discover the real cause of your anxiety symptoms. And get some help dealing with how you feel. Concrete steps to take that doesn’t include meditation, yoga, Cognitive Behavioral Therapy, or psychoanalysis.
Table of Contents
The Root Cause of Anxiety Disorders
Something may have happened that triggered the anxiety that has turned your life upside down. But if your feelings of anxiety are hanging on and won’t let go, it’s likely because of the dysfunction of neurochemicals in your brain.[ii]
It could be problems with acetylcholine, dopamine, GABA, glutamate, norepinephrine, or serotonin.
But the challenge is figuring out which neurotransmitter is causing the problem. And why drugs like benzodiazepines, SSRIs, SNRIs, TCAs, and MAOIs are often prescribed for treating anxiety.
How to Find the Root Cause
If you have been using an anti-anxiety drug and experienced some relief in your symptoms, you have a head-start.
Because now you have a clue what could be causing your problem. And it may be easier for you to decide which nootropics to try to help you get better.
First, become familiar with the mechanism of action (or pharmacology) of the med you are using. Wikipedia.org is a good resource for this information.
Simply do a search of Wikipedia for your drug’s generic name. And scroll down to the section “Pharmacology”. Sometimes called the “mechanism of action”.
Once you understand how the drug works in your brain. And which neurotransmitter system it affects. Scroll down the list of nootropic supplements below.
And choose a nootropic that has a similar mechanism of action to the drug you were using. Then follow the dosage recommendations for that supplement and try it to see if you feel any relief.
But if you’ve never tried using a pharmaceutical to treat your anxiety, or have used one that didn’t work, you’ll need to try each nootropic separately.
And by trial and error you’ll work your way down to find the neurotransmitter system that is causing your anxiety.
Start at the beginning of the list below and try the first nootropic for 1 or 2 days. And see how you feel. If you experience relief from your anxiety symptoms, success!
Now you know which neurotransmitter to work with. You can continue using that nootropic as recommended. And look for other natural nootropic adaptogens that work on the same system.
But if the first nootropic you try doesn’t provide any comfort, put it aside. And try the next one for a couple of days again following dosage recommendations.
Go through the list one-by-one until you find a nootropic that helps you and relieves at least some of your anxiety symptoms.
Some of the nootropics on the list below are precursors. Which means it provides the chemical or molecule needed to make a specific neurotransmitter.
And others are adaptogens that affect a specific neurotransmitter system. Usually by modulating how that brain chemical works in your brain.
Let’s get started …
Neurotransmitter imbalances
Acetylcholine
Acetylcholine plays a critical role in learning and memory. And acetylcholine levels are modulated by levels of stress in several regions of your brain.
Acetylcholine levels decline as you get older. You need choline for the production of acetylcholine. Not eating enough foods high in choline can also result in insufficient acetylcholine.
In fact, choline is so vital to cognition and nerve function that, without it, we couldn’t move, think, sleep or remember anything.
Studies show that acetylcholine signaling in your hippocampus regulates social stress resilience and anxiety.[iii]
You can increase acetylcholine levels in your brain using either Alpha GPC or CDP-Choline (Citicoline).
Alpha GPC
Alpha GPC is a precursor to the neurotransmitter acetylcholine. Alpha GPC naturally occurs in your brain as a byproduct of phosphatidylcholine (PC).
When your brain needs more choline, and the choline floating around in your brain is running low, it breaks down PC from cell membranes. And turns it into Alpha GPC.
Alpha GPC, acetyl L-carnitine (ALCAR), and phosphatidylserine (PS) provide mitochondrial support and conserve growth factor receptors.
DHA (Omega-3) combines with Alpha GPC and PS to form brain cell membranes critical for neuron generation and regeneration.[iv]
Recommended dosage of Alpha GPC is 300 mg 3-times per day.
CDP-Choline (Citicoline)
CDP-Choline is a type of choline that is present in every cell in your body.
Taken as a supplement, it’s then converted to cytidine and choline in your gut. Once it crosses the blood-brain barrier it’s converted back to CDP-Choline.[v] The choline then assists cell membranes and helps create acetylcholine.
CDP-Choline is involved in memory and cognitive functions. And provides energy for the brain to conduct sustained mental effort.
Recommended CDP-Choline dosage is 250 – 500 mg per day.
Dopamine
L-Tyrosine taken as a nootropic supplement converts into the neurotransmitter dopamine.
Dopamine helps control movement in your body, is fundamental to memory, attention and problem solving.
The unused dopamine can then convert into the catecholamine neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline).
Norepinephrine is important for attentiveness, emotions, sleeping, dreaming, and learning.
Epinephrine drives your ‘flight-or-flight’ response. It’s what prompts your reaction to dangerous circumstances, emergency situations, or in stressful situations or environments.
Sleep deprivation and extreme stressors like heat and cold can deplete catecholamine levels. L-Tyrosine restores them to preserve optimal cognition and reduce anxiety.[vi]
Recommended dosage of L-Tyrosine is 500 mg 2 or 3-times per day.
GABA
GABA (Gamma-amino butyric acid) is the most abundant inhibitory neurotransmitter in your brain. And known to counterbalance the action of the excitatory neurotransmitter glutamate.
GABA has long been recognized as the main regulator of anxiety. And the GABA neurotransmitter system is the main target of benzodiazepines and other anxiety related drugs used to treat anxiety disorders.[vii]
When GABA is taken as a nootropic supplement, it binds with the GABAA receptor protein complex, and acts as an agonist: inducing changes in which the permeability of the central pore to chloride ions gets increased.
The resulting chloride flux hyperpolarizes the neuron, leading to a reduction in its excitability. And producing a general inhibitory effect on neuronal activity.[viii]
Recommended dosage of GABA is 250 – 500 mg per day
Glutamate
L-glutamine is a ‘conditionally’ essential amino acid and main precursor for the production of glutamate and GABA in your brain.
(NOTE: Don’t confuse glutamine with glutamate!)
Glutamine is the most abundant amino acid in your body. And is involved in many of your bodily functions. Including much of the activity in your brain.
But Glutamate is the main excitatory neurotransmitter in your brain.[ix] And the balance of glutamine and glutamate is critical for optimal brain function.
Glutamate plays various important positive roles in your brain including brain development, learning and memory.
And degenerative roles including stroke, traumatic brain injury, Huntington’s and Alzheimer’s disease, stress response, and anxiety disorders.
Glutamate mainly acts through ion channel receptors including NMDA receptors, AMPA receptors, and G protein-coupled metabotropic receptors (mGluR1-8).
Glutamate is involved in synaptic release of acetylcholine, adenosine, kappa opioid, GABA, and neuropeptides.[x]
Recent research shows that glutamate dysfunction is involved in fear conditioning, OCD, PTSD, anxiety disorder and social phobia.[xi]
Monosodium glutamate (MSG) which is used as a flavor enhancer has been linked to obesity, metabolic syndrome, and neuron toxicity that can lead to cell death causing stroke, epilepsy, schizophrenia, anxiety, depression, Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and amyotrophic lateral sclerosis (ALS).[xii]
Eliminating your anxiety could be as simple as avoiding all foods containing MSG.
When your neurotransmitters, including L-glutamine and glutamate are in balance, you feel motivated, productive, and energetic. And you feel calm and relaxed during downtime.
When L-glutamine levels are low you feel filled with dread, you’re constantly worried, you have racing thoughts, and you’re frequently late and disorganized.
When you are in this L-glutamine slump is when you’re tempted to resort to high carbohydrate foods, and drugs or alcohol to relax.
Recommended dosage of L-Glutamine is 2 – 5 grams per day.
But remember, glutamine and glutamate must be in balance! If you suspect your glutamate levels are too high, you can get it under control by inhibiting its NMDA and AMPA receptors.
Some antidepressant drugs relieve anxiety by inhibiting NMDA receptors.[xiii]
Try the nootropics including Cat’s Claw[xiv], and L-Theanine[xv] for inhibiting NMDA receptors. And Noopept[xvi] and many of the racetams[xvii] which inhibit AMPA receptors.
Keeping glutamate under control and helping to reduce anxiety if your condition is caused by glutamate dysfunction.
Serotonin
Serotonin plays a significant role in the development and persistence of anxiety disorders.
Several studies show that increases in serotonin increases anxiety. And when serotonin decreases you may experience a reduction in the anxiety that’s associated with OCD or PTSD[xviii].
Too much serotonin and excess serotonin signaling has been implicated in social anxiety disorders.[xix]
If you are experiencing any type of anxiety, you should avoid anything that increases serotonin. Do NOT use nootropics like L-Tryptophan or 5-HTP.
Instead, use nootropics that help modulate serotonin and bring it under control.
Bacopa Monnieri helps modulate serotonin and dopamine which produces an anxiolytic effect. Studies show that Bacopa is as effective as the anti-anxiety drug lorazepam in reducing anxiety.[xx]
Vitamin D3 and Omega-3s (EPA & DHA) helps control serotonin synthesis and action. EPA helps inhibit serotonin release and DHA influences serotonin receptors. While Vitamin D3 deficiency can contribute to anxiety. Supplementing with Omega-3s and Vitamin D3 may help reduce anxiety.[xxi]
Ginkgo Biloba acts as a monoamine oxidase inhibitor (MAOI) which helps boost dopamine in your brain. Increasing dopamine can help lower serotonin levels. The result can be a reduction in anxiety.[xxii]
Rhodiola Rosea is an adaptogen that has been used in traditional medicine for thousands of years. Rhodiola enhances stress tolerance and relieves anxiety by modulating key brain neurotransmitters such as serotonin, norepinephrine and beta-endorphins (opioid neuropeptides).[xxiii]
Anxiety Eliminated
Nootropics are a viable and potent alternative to many anti-anxiety medications.
But you first need to determine the cause of anxiety in your brain. Use the trial and error method I suggested above and work through the nootropic supplements recommended one-by-one.
But a very strong word of caution – if you are currently using any prescription anti-anxiety or antidepressant medications. Or any medications for that matter. Research each nootropic including side effects and prescription drug interactions before using them.
You can eliminate anxiety once-and-for-all with nootropics. If you do your research. And are willing to experiment until you find the one or two that is right for you.
[i] Roy-Byrne P.P., Wagner A. “Primary care perspectives on generalized anxiety disorder” The Journal of Clinical Psychiatry 2004;65 Suppl 13:20-6. (source)
[ii] Kaur S., Singh R. “ROLE OF DIFFERENT NEUROTRANSMITTERS IN ANXIETY: A SYSTEMIC REVIEW” International Journal of Pharmaceutical Sciences and Research Projected Impact Factor (2019): 1.230, CiteScore (2017): 0.27 (source)
[iii] Mineur, Y. S., Obayemi, A., Wigestrand, M. B., Fote, G. M., Calarco, C. A., Li, A. M., & Picciotto, M. R. (2013). “Cholinergic signaling in the hippocampus regulates social stress resilience and anxiety- and depression-like behavior.” Proceedings of the National Academy of Sciences of the United States of America, 110(9), 3573–3578. (source)
[iv] Kidd P. M. (2005). “Neurodegeneration from mitochondrial insufficiency: nutrients, stem cells, growth factors, and prospects for brain rebuilding using integrative management.” Alternative Medicine Review: a journal of clinical therapeutic, 10(4), 268–293. (source)
[v] Rao A.M., Hatcher J.F., Dempsey R.J. “CDP-choline: neuroprotection in transient forebrain ischemia of gerbils.” Journal of Neuroscience Research 1999 Dec 1;58(5):697-705. (source)
[vi] Hase A., Jung S.E., a het Rot M. “Behavioral and cognitive effects of tyrosine intake in healthy human adults.” Pharmacology, Biochemistry and Behavior. 2015 Jun; 133:1-6. (source)
[vii] Lydiard R. B. (2003). “The role of GABA in anxiety disorders.” The Journal of clinical psychiatry, 64 Suppl 3, 21–27. (source)
[viii] Nutt, D. J., Ballenger, J. C., Sheehan, D., & Wittchen, H. U. (2002). “Generalized anxiety disorder: comorbidity, comparative biology and treatment.” The international journal of neuropsychopharmacology, 5(4), 315–325. (source)
[ix] Meldrum B.S. “Glutamate as a Neurotransmitter in the Brain: Review of Physiology and Pathology” The Journal of Nutrition, Volume 130, Issue 4, April 2000, Pages 1007S–1015S (source)
[x] Roberts-Wolfe, D. J., & Kalivas, P. W. (2015). “Glutamate Transporter GLT-1 as a Therapeutic Target for Substance Use Disorders” CNS & neurological disorders drug targets, 14(6), 745–756. (source)
[xi] Cortese, B. M., & Phan, K. L. (2005). “The role of glutamate in anxiety and related disorders.” CNS spectrums, 10(10), 820–830. (source)
[xii] Marcincakova H., Veronika & Ostatníková, D. (2013). “Monosodium Glutamate Toxic Effects and Their Implications for Human Intake: A Review.” JMED Research. 20135171. 10.5171/2013.608765. (source)
[xiii] Petrie, R. X., Reid, I. C., & Stewart, C. A. (2000). “The N-methyl-D-aspartate receptor, synaptic plasticity, and depressive disorder. A critical review” Pharmacology & therapeutics 87(1), 11–25. (source)
[xiv] Mohamed A.F., Matsumoto K., Tabata K., Takayama H., Kitajima M., Watanabe H. “Effects of Uncaria tomentosa total alkaloid and its components on experimental amnesia in mice: elucidation using the passive avoidance test.” Journal of Pharmacy and Pharmacology. 2000 Dec;52(12):1553-61. (source)
[xv] Lu M., Gray, Oliver C. “The Neuropharmacology of L-Theanine(N-Ethyl-L-Glutamine)” Journal of Herbal Pharmacotherapy Volume 6, Issue 2, 2006 (source)
[xvi] Gudasheva T.A. et. Al. “The major metabolite of dipeptide piracetam analogue GVS-111 in rat brain and its similarity to endogenous neuropeptide cyclo-L-prolylglycine.” European Journal of Drug Metabolism and Pharmacokinetics. 1997 Jul-Sep;22(3):245-52. (source)
[xvii] Isaacson J.S., Nicoll R. A. “Aniracetam reduces glutamate receptor desensitization and slows the decay of fast excitatory synaptic currents in the hippocampus” Proceedings of the National Academy of Sciences in the United States of America vol. 88, pp. 10936-10940, December 1991 (source)
[xviii] Murphy, D. L., Moya, P. R., Fox, M. A., Rubenstein, L. M., Wendland, J. R., & Timpano, K. R. (2013). “Anxiety and affective disorder comorbidity related to serotonin and other neurotransmitter systems: obsessive-compulsive disorder as an example of overlapping clinical and genetic heterogeneity” Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 368(1615), 20120435. (source)
[xix] rick, A., Åhs, F., Engman, J., Jonasson, M., Alaie, I., Björkstrand, J., Frans, Ö., Faria, V., Linnman, C., Appel, L., Wahlstedt, K., Lubberink, M., Fredrikson, M., & Furmark, T. (2015). “Serotonin Synthesis and Reuptake in Social Anxiety Disorder: A Positron Emission Tomography Study” JAMA psychiatry, 72(8), 794–802. (source)
[xx] Bhattacharya, S. K., & Ghosal, S. (1998). “Anxiolytic activity of a standardized extract of Bacopa monniera: an experimental study” Phytomedicine: International Journal of Phytotherapy and phytopharmacology, 5(2), 77–82. (source)
[xxi] Patrick, R. P., & Ames, B. N. (2015). “Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior” FASEB journal: official publication of the Federation of American Societies for Experimental Biology, 29(6), 2207–2222. (source)
[xxii] Woelk, H., Arnoldt, K. H., Kieser, M., & Hoerr, R. (2007). “Ginkgo biloba special extract EGb 761 in generalized anxiety disorder and adjustment disorder with anxious mood: a randomized, double-blind, placebo-controlled trial” Journal of psychiatric research, 41(6), 472–480. (source)
[xxiii] Lishmanov Iu.B., Trifonova Zh.V., Tsibin A.N., Maslova L.V., Dement’eva L.A. “[Plasma beta-endorphin and stress hormones in stress and adaptation].” – in Russian Biull Eksp Biol Med. 1987 Apr;103(4):422-4. (source)
Hello
Thank you for your valuable information. I have been on and off prozac for 25 years, starting with post natal depression from a traumatic delivery. Prozac stops working after a year or 2, and I wonder if I am over producing serotonin as I experience more anxiety attacks as the years go by. My main symptoms now, over last 15 years are stress/anxiety. I would like to stop taking 20mg prozac and try: ashwaganda, Rhodiola, vitamin b.
I tried 5htp about 4 years ago and it stopped working after a month, exactly as you describe. So I guess my problem is too much serotonin causing issues with prozac?
2 years ago I had great success with Rhodiola, but I was still taking prozac at the same time. I am now more aware of issues after reading your information – thank you.
I would like to get off prozac which I think, now increases my anxiety and heal my brain etc. with adaptogens. Any suggestions from you would be greatly appreciated.
Thank you
Amy
Amy, you likely grow tolerant to Prozac after a while because it desentized synapses. Not because you have too much serotonin.
Rhodiola Rosea acts as a Monoamine Oxidase Inhibitor (MAOI) which boosts dopamine AND serotonin to some degree. Rhodiola also boosts neurogenesis which helps repair synapses.
Here is a list of adaptogens which help reduce anxiety and stress: https://nootropicsexpert.com/top-7-nootropic-adaptogens-to-conquer-anxiety-and-stress/
And Lion’s Mane Mushroom increases Nerve Growth Factor which will help repair your brain.
Hi David,
its Dan again =).
I decided now to use Tyrosine and Gaba to fix low dopamine and low gaba/high glutamate.
There is one question which bothers me, may you can help me ?
Which of the following condition could cause high glutamate/low gaba:
-low serotonin
-high serotonin
-low dopamine
-high dopamine
I came across with a few sites that claim low Serotonin can cause overstimulation trough glutamate.
Maybe im just deficient in dopamine, serotonin and gaba. I have read about studies wich claimed that people with social anxiety are often low in Dopamine and Serotonin.
Aswell another question, are there some safe Nootropics to decrease glutamate level long term ?
Dan, it’s not a simple as that. Because you just need to look at L-Glutamate for example. I quote, “Glutamine is naturally synthesized from glutamate and ammonia in brain cells called astrocytes in a reaction catalyzed by glutamine synthetase (GS).
Newly synthesized glutamine is transferred to neurons and hydrolyzed by phosphate-activated glutaminase (PAG) to then produce glutamate. A portion of which may be decarboxylated to GABA or transaminated to Aspartate.”
If you are low in the enzyme glutamine synthetase or the enzyme phosphate-activated glutaminase you’ll have problems. Or low serotonin. Or high dopamine. Or any combo of this.
It’s true that low serotonin can really cause problems. Most of that happens in your gut because 95% of serotonin is released by EC cells in your gut. Those cells are activated by 20 different bacteria. If your microbiome is out of whack you’ll have problems.
BTW, I just came across a study that showed high serotonin is the cause of social anxiety. But I didn’t save the link.
The only thing you can do is experiment with each of the precursors for these neurotransmitters while fixing your microbiome. Until you find something that works.
The safest way to keep glutamate in check is probably Resveratrol and thiamine.
Thanks for your answer.
May i need to agree that there is no easy way through science to get to my goal. I tought it would help to know if low dopamine/low serotonin can cause low gaba. But it seems to be a lot more complex like you said.
According a lot of user claims Gaba(benzos) seem to help them most with social anxiety to get relief from symptoms, but often not long term. So i personally think low Gaba in social anxiety is very often a side problem to a main problem like low serotonin/dopamine, thats why i asked.
I couldnt finish my prolonged test with Tryptophan because of lockdown (corona), so it end up again with only 2 days of Tryptophan, but i think i will keep using dopamine(Tyrosine) and gaba(cycling and using lemon balm, valerian, gaba) suppliments for now.
I never read about Resveratrol on any site.
https://link.springer.com/article/10.1007%2Fs10571-007-9152-2
according this link, it might be coinflip and decrease or increase glutamate depending on the dose.
I think it would help me to decrease glutamate at the same time while trying to work on gaba level.
What do you think about those nootropics to keep glutamate low (according a few websites):
-Taurine
-Coenzyme Q10
-PQQ
-Theanine (i dont like)
-Magnesium (already using)
-B6 (already using + Thiamine as multivitamine)
Or they might not safe for long term use and i still should try Resveratrol ?
Dan, according to a couple of studies I came across, they showed Resveratrol inhibiting glutamate while increase extracellular GABA (https://pubmed.ncbi.nlm.nih.gov/20026214/).
I haven’t the time to go through each supplement you mentioned and hunt for studies specifically on their effect on glutamate. Other than what I’ve already included in my research on each supplement. So please check those as well.
I also encourage you to look closely at (according to a few websites) and make sure that whatever you are using as an authority on this subject that they have links to peer-reviewed clinical studies supporting their claims.
Hi David,
here Dan again i lately posted on September 23, 2020.
You adviced me in case of Gaba deficiency/panic attacks CBD Oil, Ginseng, Lemon Balm, L-Theanine, and Valerian.
And im using Lemon Balm now for about ~10 days 3 times a day 450mg = 1350mg daylie.
I came incross with this discussion https://www.longecity.org/forum/topic/54028-treating-anxiety-safely-effectively/page-1
People claim that long term use of GABA RECEPTOR AGONIST’s downregulate GABA wich means instead of increasing GABA it decreases GABA long term.
What do you think about that ?
I have choosen Lemon Balm because it looked like it works similar as SSRI’s just for GABA.
Because SSRI’s inhibit uptake of serotonin -> serotonin increases.
Lemon Balm Gaba Transminase inhibit breakdown of GABA -> Gaba increases
The guy posted on that site claims that lemon balm on prolonged use aswell downregulates gaba and it should only used for short term usage or Cycling on/off.
What do you think about that ?
Can i still take it or should i stop my plan to use 1-2 month Lemon Balm ? At the moment i dont feel a lot of difference beside fatique and may problems getting asleep (may not related to lemon balm i dont know). I dont search for short term solutions but long term.
Dan, this has not been my experience using Lemon Balm. But if you are not experiencing any benefit from using Lemon Balm or your experience is negative then I’d stop using it.
Hi David,
but is it true CBD Oil, Ginseng, Lemon Balm, and Valerian downregulate Gaba on long term use ?
Would it be better using Gaba as suppliment ?
But aswell Gaba works on a gaba receptor i have read.
Maybe i should restart trial and error and do each suppliment for a week and hidden. Im still not sure gaba is the correct one.
It felt a bit better but after 2 weeks of lemon balm it feels like it gets worse again. I dont know.
I couldnt find any guide how to trial and error. If i take 1 suppliment and i experience no changes, does that mean it is the correct one ?
Dan, if you use a supplement and experience no immediate changes then it likely means it is the correct one for you. IF you have done the research and know why you’re taking it.
The effects of lot of these nootropic supplements can be very subtle. You get better the more you use them in learning to “listen to your body”.
And many of them provide better results over time of consistent daily use. Again, it depends on their mechanism of action in your brain.
None of the supplements that you mentioned will “down-regulate” receptors or neurotransmitters if you are using the recommended dose. Most of the time you are just giving your body and brain what it needs. Nutrients that you are not getting enough of from food. This is why they are called “supplements”.
GABA the neurotransmitter must connect to a GABA receptor for it to have any effect in your brain. But the herbs and adaptogens do not directly increase something like GABA. They affect its levels to make it more available in your brain. Or affect its receptors and their sensitivity.
If you use extra high doses of anything it’s not good. Because only then can you do things like desensitize receptors or synapses. This is why it is often good to use 2 or 3 supplements that do similar things so you can keep dosages of each one on the lower end.
Hello. I am following the trial and error method to find the cause of my anxiety. GABA is third on the list. But, from what I have read elsewhere, GABA does not cross the BBB. Can anyone explain this apparent inconsistency. David writes that GABA binds with the GABAa receptor protein complex inducing changes in which the permeability of the central pore to chloride ions get increased. Is it this increase in chloride ions central pore that helps with anxiety not an increase in brain GABA. Thank you for any help.
Valerie, re. GABA it’s likely either or both.
But what you’ve read about GABA not crossing the BBB is old science. It’s simply too simplistic to be true. Each neurotransmitter has an associated transporter that helps it across.
In GABA’s case it’s either a transporter. Or it’s digested in your gut and taken to your brain some other way. Probably the vagus nerve. One way or the other it does get there.
Hi David,
thanks for your great website.
I have anxiety + social anxiety for a few years, with a bunch of symptoms. Some of the most annoying are panic attacks.
I did bought almost all precursor, not Glutamine.
L-Tryptophan, L-Tyrosine, Gaba, Alpha-GPC and took each for a few days/weeks.
But it is so hard to tell if i feel better or worse. Because of peak days and peak weeks and as i understood correctly deficiencys get better after prolonged use like 1-2 months and more.
How do i understand if its the correct precursor if i need to take them for a long time to see changes, aswell i think in short usage like 1 week, if for example panic attacks/anxiety are slightly better its hard to tell if it gets worse or better because it depends on the situation aswell and sleep etc…
Sometimes you get Tryptophan/Tyrosine.. from food.. wich falsify the result or dosage is to low/high…
I take a very good Multivitamin with active forms + high amount of b6, b12.
How i can have success with trial and error please ?
Dan, great question and you’ve already hinted at the answer yourself with a caveat.
If you try a precursor for a couple of days with no negative reaction. But a slight positive improvement. You’re likely onto something. Effects with nootropics are often subtle. Which means we really need to learn to ‘listen to your body’ and what it’s telling us.
If one or two precursors resulted in a slight improvement in panic attacks and anxiety. I suggest pursuing that neurotransmitter pathway. And all the ways you can affect it.
For example, if it was a bit of success with GABA then do a search of Nootropics Expert for all the supplements that somehow work on GABA. In this case it would include CBD Oil, Ginseng, Lemon Balm, L-Theanine, and Valerian. I’d read the review of each one closely to see how it works. And then pick a couple to try.
This method applies to each major neurotransmitter. And it’s true that some of these amino acids are common in the food we eat. Which could throw things off a little. But I wouldn’t be too concerned with the food thing while you’re on this mission.
It’s also true that true deficiciences take awhile to correct. But the amino acids in particular work quickly. Fast enough to know which one looks more promising than another.
Thanks for your answer.
I need to retry all of them and store daylie results in an app.
It happens for me that for example one day it works good with Tyrosine, the next day is worse, the next day is good again… like ping pong and that happens for all precursors.
It feels like throwing a coin.
Is there maybe a way to backtrace wich Neurotransmitter could be deficient ?
For example if i never ate vegetables / fruits and dairy (because i have intolerance, not lactose), pollen allergy, a lot of stress, less sleep because of racing mind (i have really dark eye bags) and less exercise, lot of gaming.
I ate a lot of pasta, bread, rice, overall grain, meat, a bit more less fish, eggs, poultry and a daylie fat sugar. (now im working hard on my diet aswell)
It would already help if i can exclude some neurotransmitter.
Glutamate i already excluded myself because as i understood correctly panic attacks are likely some kind of overstimulation exactly what high glutamate would do or propably i get false results because B6 conversion to GABA if i take glutamine.
Should Tyrosine increase panic attacks/anxiety if it get converted to norepinephrine and epinephrine ?
On Monday i have the strongest symptoms normally.
So how i could start with the precursor. Taking Tyrosine for 2 days 2 times a day starting on Tuesday. Should i start instantly after those 2 days then with Tryptophan ? Does Tyrosine does not has after effects then ?
How i continue weekend is free of symptoms starting again on Tuesday ?
Or should i go for full week one precursor…
Or should i go crazy taking all day a different precursor and track results for a few weeks and check later on wich precursor performed best.
Do i need to put them into bags and take them hidden to prevent placebo ?
Dan, looking at your diet and I’d try eliminating pasta, bread and rice. I think you’d be amazed at the difference. I cut out everything white and/or refined. And most sugar. I get physically sick now if I have a bowl of pasta.
If you’re not eating fruit or vegetables I highly suggest using a Multi like the Performance Lab NutriGenesis Multi. Again, I think you’ll be amazed at how it makes you feel. But the Multi you choose makes a huge difference in my experience. And why I mentioned that one specifically.
L-Tyrosine turns into dopamine and then into norepinephrine. Try doing 500 mg L-Tyrosine once a day first thing. Do that for two days and see what happens. If there are no negative effects then continue that for another 2 – 3 days. And see if that makes a difference. It could be that your dose was too much in one day. L-Tyrosine is known for helping especially for stressful situations including gaming.
You’d need a much higher dose of L-Tyrosine to upset your dopamine/serotonin balance. And higher doses of L-Tyrosine can cause panic attacks and/or anxiety. But the dosage amount depends on the person.
If that plan backfires then try boosting acetylcholine with CDP-Choline or Alpha GPC following the same plan. And see what happens.
Last thing I’d try with this is L-Tryptophan. I leave it last because you don’t want to do it during the day.
But the diet thing really stands out to me. And I think could be the key or at the root of what you’re trying to do. With the rest built on that.
Ok now i finished my 2 wave of trying precursors beside glutamine.
I took them for 2 days in this order:
L-Tyrosine 29.09-30.09, L-Tryptophan 01.10-02.10, Gaba 06.10-07.10, Alpha GPC 08.10-09.10
The first day i took very comfortable, the second day i always went to a new takeaway getting food for triggering my symptoms.
I took each daylie activity and valued how it felt different. + means symptoms are better, – means symptoms are worse, * no changes. “anx” means anxiety.
Tyrosine: – anx daylie walk, + anx driving car(scary), + racing toughts, + anx gaming, -intelligence may(bad decision making/concentration-focus), * panic atks., * anx talking people, +eye contact, + enjoy continue book?, * get asleep, -tremors while panic, – length of panic atks
Tryptophan: *anx daylie walk, * anx driving car, – racing toughts, – anx gaming, -intelligence, *panic atks , +anx talking people, -eye contact, + enjoy continue book, -get asleep (less tired at night) , – fatique (tired over day), + tremors while panic(slightly), * length of panic atks
Gaba: *anx daylie walk, + anx car, * racing toughts, + anx gaming, +intelligence, +panic atks , *anx talking people, *eye contact, – enjoy continue book, *get asleep, – fatique (tired over day), + tremors while panic(slightly), + length of panic atks
Alpha GPC: *anx daylie walk,* anx car, – racing toughts, + anx gaming, *intelligence, *panic atks , *anx talking people, *eye contact, – enjoy continue book, -get asleep, * fatique (tired over day), + tremors while panic(slightly), + length of panic atks
The only problem is, my panic attacks trough the takeaway decreased because of habit… Like that the precursors i took at the beginning has higher and more symptoms while alpha gpc there were almost no symptoms anymore…
Aswell all changes feel so little it could have been random.
So at the end i have again no clue wich of those worked for me…
But i will take now Lemon Balm for a month, i cant find success with trial and error. We will see if it helps or worsen.
Dan, first, congratulations on your dedication and determination to figure out what is wrong. I’m having some difficulty understanding what you are saying about each supplement above. But I think what you are saying is that your anxiety may not be caused by neurotransmitter levels that are out of whack. Any of them. If this is true it’s important. Because you can rule it out.
Anxiety can also be caused by a variety of other things including inflammation, low BDNF or Nerve Growth Factor, faults with a receptor system like NMDA receptors or AMPA receptors. etc.
Take a look at the other adaptogens proven to be helpful with anxiety after you’ve tried Lemon Balm: https://nootropicsexpert.com/top-7-nootropic-adaptogens-to-conquer-anxiety-and-stress/.
Consider boosting BDNF: https://nootropicsexpert.com/13-nootropics-to-boost-bdnf/
Do a search of Nootropics Expert for the keyword “inflammation” and see which are the best candidates for taming inflammation.
I wish there was an easier solution for you. But I’ll do what I can if anything to help. And thank you for reporting your progress so far.
Hi David,
you have written Serotonin may increase anxiety.
What do you exactly mean by Bacopa Monnieri and Rhodiola Rosea modulate Serotonin ? Do they work like a Beta Blocker and stop uptake of Serotonin or do they even lower Serotonin ?
Do modulate mean they can rise level of Serotonin when we are low and increase level if we are high in Serotonin ?
I had a big Vitamin D3 deficiency and rare omega3 for many years, may that lead to anxiety because my system wasnt able to inhibit Serotonin correctly.
Thanks.
Paolo, Rhodiola Rosea acts like a monoamine oxidase inhibitor (MAOI) which can increase serotonin availability in your brain. Bacopa “seems” to affect serotonin levels but I’m not sure of the mechanism of action on how it does this. So both are going to have some effect on serotonin levels.
Neither nootropic supplement is a direct precursor to the synthesis of serotonin. So we’re talking about how the existing serotonin in your brain is used.
Hey David,
You put me between a rock and a hard place.
I have been dealing with some significant anxiety and some fear of panic and that has lead to some insomnia. I have been working hard at figuring out what to take to manage the anxiety and to manage the insomnia.
So far, L Theanine has been the best at managing anxiety but far from perfect.
Sleep, Gabba, Magnesium Threonate, Phosphatidylserine, and L Theanine have helped me to fall asleep but not stay, often waking up around 4 PM.
I recently introduced Tryptophan into the mix and that has improved my sleep. But I now read it can boost anxiety. I have had mixed responses to it the day after, sometimes feeling good, almost happy/normal in some ways, but also some underlying anxiety.
Is there something other than Tryptophan to consider? I have tried Melatonin but that gave me a night terror, I have tried Valerian Root too at the get go, but limited success with that.
And what can I look to that can make me good happy/good like the Tryptophan did but without risk of worsening my anxiety?
Thanks.
Adam, it’s higher doses of L-Tryptophan that can cause anxiety in some people. Try to keep your dose around 500 mg and you should be OK.
Melatonin is not a good choice for a number of reasons. But L-Tryptophan contributes to the synthesis of melatonin. You can also try Tart Cherry Juice from concentrate as a natural source of melatonin which produces minimal side effects. If any.
Try Lemon Balm and CBD Oil next. Before you try Valerian. Because chances are Valerian will result in side effects if you sometime have a negative reaction to higher doses of L-Tryptophan.
Good to know, thank you.
The Gaba has helped with falling asleep, but I still am waking up throughout the night. The trypophan definitely helped with sleeping more soundly throughout the night, so happy not to have to remove that altogether.
I have tried Lemon Balm extract and not sure I got much of an effect from it. Possibly inadequate dosage though. I did just grab some Lemon Balm tea earlier today though, so continuing to work with it. I have tried CBD once but got a little anxious a little while after taking it, which might not have had anything to do with it but has me hesitant to return to.
Anyways, thanks for the feedback!
Hello David! Thank you for all this information. You whrite about cats claw ( uncaria tomentosa) but what do you think about the chinese cats claw (uncaria rhyncophylline)?
Best regards
Inger Lindström
Inger, I don’t have any information on that type of Cat’s Claw. The only clinical studies I found for Cat’s Claw with proven nootropic value is uncaria tomentosa.
Hi David,
I’ve been on Cymbalta for 11 years, I had a baby 10 months ago and during this time Cymbalta has stopped working. I’m sure this is due to the changes in my hormones and brain chemistry. I’m positive I’m dealing with postpartum anxiety and depression. I’m oh so slowly weaning off the Cymbalta, because I’ve been on it for so long I’m afraid my doctor will cut me off and put me in a state of severe protracted acute withdrawls.I don’t want to end up on yet another SSNRI/SSRI if I can avoid it, I would much rather slow taper myself. In the meantim, my anxiety and depression have increased, my anxiety is now at an all-time high. I’ve been very interested in using Ashwagandha specifically at night to help me relax. Can I use Ashwagandha along with Cymbalta? Have you heard of anyone using both a nootropic and an SNRI/SSRI.
Cymbalta inhibits the reuptake of serotonin and norepinephrine. Serotonin more so than norepinephrine. Did it work for you? Because if it did that means you likely have a problem with serotonin. Or possibly norepinephrine. Those are the two neurotransmitters I suggest concentrating on with any nootropic you consider.
You don’t want to use Ashwagandha because it will boost the effects of Cymbalta. Not help you wean off it.
So be careful about using any nootropic that boosts serotonin or dopamine. Because you could get yourself into real trouble. Look for nootropics like Lemon Balm which works on acetylcholine and GABA instead.
Always, always look at the mechanism of action for any nootropic you are considering. To make sure it does not affect serotonin or dopamine/norepinephrine as long as you are on Cymbalta.
Hi David!
I have been taking nootropics for about six months now. Many of them were suggestions made by you in the Nootropics Expert newsletter. I would like your opinion on the “stack” I have created. I am currently taking the following: Alpha-GPC (300mg), Bacopa Monnieri (500mg), Pine Bark extract (400mg), Lion’s Mane (500mg), Jiaogulan Extract (410mg), and L-Tyrosine (1/4 teaspooon). Could you give me your expert opinion on my stack?
Thanks for your time and consideration.
-Bob
Bob, most of those nootropics are in the Mind Lab Pro formula which you should consider. It’s out of stock (once again) because its popularity has grown faster than they anticipated. But keep an eye on its availability if you’re interested. https://www.mindlabpro.com/
As for your list of supplements, do they work for you? Dosages are effective. Lion’s Mane could be higher at 1 or 2 grams. But the bottom-line is do they tame your anxiety symptoms? Is there something you remember trying that seemed to be more effective than anything else?
Hi David,
Very nice article, well written and explained. You describe anxiety disorder just how i feel! I’m struggling with anxiety, stress and depression quite some time now, it really sucks! I’m on Escitalopram 10mg a day and it’s difficult to tell if it does something?! From my i experience i do better on a lower dose, so I’m planning to go to 5mg. Btw, I’m coming from 15.
I tried lots of supplements to get relief from these mental illnesses, some did work but most did not.
The ones that works best until now are Magnesium bisglycinate, Curcumin, Vitamin D3, Fishoil, Valerian and a couple others.
I want to try Lithium Orotate for depression but I’m not sure that’s a good combo with my AD medication?! Also Lithium is quite toxic i red online, so not sure about that one.
I’m gonna try Alpha GPC, Phosphatidylserine, L-Glutamine, L-Tyrosine and Theanine from your list. And what should i try for GABA, will Valerian do?
If Ginkgo is a MAO im not sure about combining it with a SSRI? But boosting Dopamine and decreasing Serotonin for less anxiety was a theory that peeked my interest! Mostly people claim its the other way around, hence that’s why they prescribe SSRI’S and such.
I also take Collagen, do you think that’s a good enough source of above amino acids or should i try them individually?
Last, not sure about Noopept and Racetams, i want to try them but being chemical compounds manufactured in a lab in Russia makes me wonder about safety? As far as i know they are unregulated and are in a grey area for many countries, also that these pills were/are medicines needing prescription gives me the idea not to mess with them to much. Can you give me some insight about them? Are they safe? There is a lot of contradicting information online.
Paul, unless you’re getting our info from peer-reviewed clinical studies I suggest you ignore what “you read online”. Because most don’t know what they’re talking about. Don’t even trust everything I say. Click through to the clinical studies and verify everything for yourself.
Most people are deficient in Lithium. There is nothing toxic about it. Please read my review on Lithium Orotate and see for yourself: https://nootropicsexpert.com/lithium-orotate/
I suggest switching out your “fish oil” for a quality DHA supplement. I have some suggestions in the “Available Forms” section of my DHA review: https://nootropicsexpert.com/dha/
If you are having success with Valerian you can likely ignore GABA for now. Ginkgo does act like an MAOI so may be contraindicated with the drug you’re using.
And Noopept and the racetams are amazing supplements. You are correct that they started out as drugs and are still used as prescription meds in some countries. They are very effective. You just need to find that one best for you. It’s good to careful about which supplements you buy. That’s why I’ve suggested trustworthy vendors in most of the racetam reviews. They’re the companies that I get mine from.
For the amino acids I think it best to use individual supplements because you’re in control of what you are using and the dosage best for you.
David,
In the mail that sent me to this link you said that in your community someone asked about the difference between Mind Lab Pro & Performance Lab Mind, especially in congruence with Performance Lab Multi.
I am taking Performance Lab MCT, Multi & Prebiotic as well as Mind Lab Pro.
Would you say there’s any value for me to take Performance Lab Mind over Mind Lab Pro, as the latter does seem to have more overal value, even though I take Performance Lab Multi already. I’m wondering if it shouldn’t make sense for me to use Performance Lab Mind instead?
I personally think Mind Lab Pro is better, especially since you’re taking it over Performance Lab Mind as well, as seen in your ‘What I Take’ section. Yet I’d love for you to confirm that once more, as there may be other reasons that you’re doing this.
Beyond that, I have another question on the in-take regime of my supplements. It is said on the website that Prebiotic & Multi-Vit merge well together, although they shouldn’t be taken together at the same exact time as the soluble fiber may interfere with nutrient absorption. Taking that into account what would you consider a good daily regime to take the former supplements?
Currently I am doing 2 Mind Labs & 2 Multi-Vitamins with a tablespoon of MCT on an empty stomach right in the morning, then 3 prebiotics around 3 hours later so that they don’t intervene, with another set of 2 Multi-Vitamins with my evening meal. Does this sound like a solid in-take regime, or is there anything I can improve in terms of optimalisation?
As always, I greatly appreciate your expertise and insights, I’ve learned very much from the information you provide here.
Warm regards,
Yentl
Yentl, I prefer Mind Lab Pro over Performance Lab Mind because MLP has Lion’s Mane Mushroom, Bacopa Monnieri and Rhodiola Rosea. Each of these has there benefits including for mood and dopamine. But more importantly for boosting neurogenesis and brain repair.
And I wouldn’t worry about the Prebiotic messing with nutrient absorption because it bypasses most of digestion and works in your gut. Looks like your timing should work well.
Hi David,
For someone who has suffered with severe anxiety since childhood, your guide on the Root Cause of Anxiety Disorders is a God send….thank you!
I experienced a nervous breakdown in my twenties (I’m in my fifties now) and self medicated with my fathers Tranxene which got me through that difficult period. Although anxiety has improved over the decades, it has been hit or miss with with natural protocols (no prescription meds). Knowing that Clorazepate worked in my twenties I was able to follow your guide and isolate the root cause and determine what is needed…GABA! More importantly, L-glutamine and regulating serotonin since taking GABA alone brought only limited results in the past.
Now, the combination of GABA, L-Glutamine, Vitamin D, omega 3’s, passion flower (MAIO inhibitor) and other nootropics I’ve been taking, has been nothing short of miraculous. I can only describe it as the perfect storm in relieving life long anxiety and fatigue.
Also, I have never done well with any of the nootorpics that directly increase Acetylcholine. Bad reaction every time and I have noticed that other people comment having that same reaction. Any thoughts as to why this happens to some individuals like myself and not most people? I’ve read that it might have something to do with issues related to the gut/brain axis? Regardless, it could be a topic for a future guide perhaps. Just a thought.
Again, thank you for your knowledge and ability to present it in a way that is making a difference, keep up the great work!
BR,
Eric
Eric, I’m just happy you were able to figure out something that finally worked. I don’t have an answer yet for the acetylcholine thing. My wife had the same reaction the first time I gave her one Alpha GPC capsule. I’ll get it figured out some day …
Hello David,
I am a clinical Hypnotherapist with years of experience in helping people. In generally every physical manifestation of a symptom it is preceded by a mental process. We were taught otherwise by modern medicine that insisted and taught that mind and body are separate. when the opposite is the truth.. this myth is now being disproved by science but is still being propagated by some practitioners. Anxiety occurs when the mind is functioning as the imagination in a future time frame conceiving of what the person does not want which sets in motion the cosmic laws to bring that event or condition about. This affects an imbalance in the chemistry of the body. the body Our society and medical system is formulated around a war metaphor whereas eastern medicine is not. The cure for anxiety is to bring thoughts back into the present and then view the future in a positive framework as to what the person wants. If a human being is viewed as a biological computer and the way to fix the bugs or viruses is through reprogramming becomes the key. We create the majority of our negative programs while in a trance state and reprogramming needs to occur at level or at a higher spiritual level. This leads to a permanent one time solution. Body follows mind, mind follows spirit, spirit resides in the forever NOW1
Barry, I agree with you 100%.
The thing is a lot of folk are here looking to find a more natural way to deal with something they are either using a pharmaceutical, or were offered one. I’m offering that option.
And I love it when someone like you shows up and adds what I haven’t the authority to do. Thank you.
I need help , but all these different nootropics are to much for me to figure out , if I need fix fast , what would you suggest , I did try mind lab pro a while back , not sure , also on tight budget , on the edge , Scott
Scott, “thinking fast” depends on short-term memory. And this explains how it works: https://nootropicsexpert.com/best-nootropics-for-learning-and-memory/#shortterm-memory.
So try experimenting with Rhodiola Rosea, Phosphatidylserine (PS), CDP-Choline, and Bacopa Monnieri and see if they help. Mind Lab Pro contains 3 of them and works best if you use it daily.