Nootropic forums and blogs often describe depression as a neurotransmitter imbalance in the brain. And then offer suggestions on various nootropics or drugs to help lift your mood and reduce depression.
But this simplistic view of depression misses the complexity of this disease.
Recent research has shown that depression can have many possible causes. Including out of whack mood regulation by your brain, genetic problems, stressful events or living conditions, prescription medications or other medical problems.
It’s true that neurotransmitters are involved in the process that contributes to depression. But it’s usually not a matter of one neurotransmitter being too low or another too high.
Here’s the thing. You have several neurotransmitter systems, amino acids, hormones and other neurochemicals working both inside and outside neurons.
The interaction of these neurochemical reactions make up a highly dynamic system that contributes to your mood. And how you perceive and experience life.
With this level of complexity, you may have similar symptoms of depression to the person next to you. But the issues in your brain and body may be completely different. So what works best for someone else experiencing your symptoms may not be best option for you.
And this is why we often say in the nootropic community that Your Mileage May Vary (YMMV) when describing a particular nootropic supplement. And how it feels.
I this article you’ll discover other possible causes contributing to your depression. How to recognize them. How to use nootropic supplements to test different possible causes so you can narrow down what may be causing your depression.
And I’ll share some nootropic supplement suggestions that may help relieve your depression symptoms for a better quality of life.
Table of Contents
Depression and Neurogenesis
It turns out that brain cell signaling, neurogenesis and the function of neuronal circuits may play a more important role in depression than simply the levels of serotonin or dopamine.
For example, researchers in Munich studied 24 women who had a history of depression. And on average, their hippocampus was 9 – 13% smaller in the depressed women compared to healthy women. And the more bouts of depression a woman had, their hippocampus was even smaller compared to less depressed women in the study.[i]
We know that stress can play a role in depression. And research has shown that stress can suppress neurogenesis. Which would account for the smaller hippocampus in these women.
We also know that Brain-Derived Neurotrophic Factor (BDNF), a naturally occurring protein in your brain, is critical for preventing apoptosis (brain cell death), is required for the growth of new neurons (neurogenesis) and the growth and maintenance of synapses.
Please check out my article on “13 Nootropics to Boost BDNF”. Increasing BDNF is one way to combat depression. Below I’ll share a list of nootropics for you to try some of which also help to increase levels of BDNF among other benefits for a healthy brain.
If you’ve ever tried antidepressants, you know that it often takes weeks to feel any benefit. Scientists have a theory that the value of some of these medications may be in generating new neurons (neurogenesis), strengthening neuron connections, and improving brain cell signaling. Which often takes time before you can feel the result.
So now researchers speculate that new medications could be developed to specifically promote neurogenesis. As it turns out, we already have this ability with several natural nootropic supplements.
Depression and Neurotransmitters
We know that neurotransmitter dysfunction is the not only cause of depression. But we can’t discount their importance either.
Neurons are designed to communicate with each other. When a neuron is activated, it passes an ‘action potential’ down its axon to the axon terminal (synapse). Neurotransmitters are stored in synaptic vesicles.
The action potential (electrical signal) releases certain neurotransmitters into the synapse. Which then sends it over to a synapse on a dendrite connected to the receiving neuron. As the concentration of neurotransmitters rise in the synapse, they bind to receptors embedded in the membranes of the two neurons.
This release of a neurotransmitter from one neuron can activate or inhibit the second neuron. Once the first neuron has released a certain amount of neurotransmitter molecules, a feedback mechanism instructs the transmitting neuron to stop releasing neurotransmitter molecules and begin bringing them back into the 1st neuron. This process is called reuptake.
In those who are severely depressed or manic, this fine-tuned system of neuro-signaling goes out of whack. Either too much or too little of the neurotransmitter is released.
Or if the reuptake is overly efficient and mops up too many neurotransmitter molecules before they have a chance to bind to receptors. It can have a significant impact on mood.
The primary neurotransmitters that play a role in depression include:
Each one of these neurotransmitters can be boosted, or their reuptake affected by nootropic supplements (listed below).
Depression and Prescription Medication
Depression is often a side effect of certain prescription drugs. These drugs can include antimicrobials, antibiotics, antifungals, antivirals, heart and blood pressure drugs, hormones, insomnia drugs, tranquilizers, antacids, narcotic pain drugs and more.
We know from experience that many of these prescription drugs may be replaced by safer, natural nootropic supplements.
But I am NOT encouraging you to stop using whatever meds you’re currently on. Without consulting with your doctor first. I am encouraging you to learn about and possibly try safer alternatives that often do the job just as well.
CAUTION: many nootropic supplements are contraindicated with prescription SSRIs, MAOIs, tricyclics, and others that work on the same neurotransmitter system. Combining any of these ‘natural’ nootropic supplements with the wrong supplement can do serious harm. Including ending your life. Please, please read the Side Effects section of each nootropic review here on Nootropics Expert®. And if in doubt please ask me and consult with your doctor before trying a nootropic if you are using any of these prescription meds.
Depression and Stress
Nearly all of us experience stressful events. And while not everyone of us who faces stress develops depressive disorder. Stress does play an important role in depression.
Depending on how sensitive you are to stress, along with messed up neurochemistry and even genetics. A perfect storm of any or all of these influencing factors can lead to depression.
So, please read my extended article on “Best Nootropics for Anxiety” which includes several nootropic supplements that may help you deal with and conquer stress.
Recommended Nootropics for Depression
If you are currently being treated for depression. Or suspect you may be dealing with undiagnosed depression. And are looking for a more natural, safer way to treat your symptoms. Nootropics may be the answer.
You’re not alone looking for an alternative to drugs that often come with a host of side effects. Research in the United States and other countries show that significant numbers of people use ‘alternative medicine’ to treat their depression.
Researchers conducted a survey of more than 3,000 women in the USA to find out how many turned to alternative medicine for depression. Of the 220 women who said they had been officially diagnosed with depression, 54% said they used alternative medicine to treat their symptoms.[ii]
We have found that the following list of nootropics work well for different types and causes of depression.
As I mentioned before, your mileage may vary. What works for me may not work for you. Wise and careful experimentation is critical to finding a safer alternative for treating your depression.
- Aniracetam – A member of the racetam-family of nootropics, Aniracetam works with dopamine D2 and D3 receptors in your brain. And desensitizes AMPA (glutamate) receptors.
Aniracetam is one of the most effective antidepressants I’ve even tried. And its effects on dopamine in your brain can have a profound effect on anxiety symptoms as well.
- Bacopa Monnieri – One of the most powerful herbs in Ayurvedic healing. Bacopa has been used for millennia to relieve anxiety, fatigue, restore energy and boost concentration.
This adaptogen has been shown in clinical studies to work as well for depression as benzodiazepines and tricyclic antidepressants.[iii]
- Coenzyme Q10 (CoQ10) – CoQ10 contributes to your cell’s natural source of energy. Producing ATP in your mitochondria by taking fat and converting it into usable energy. CoQ10 preserves brain function, helps fight mental illness and migraines.
Major depression, bipolar disorder and schizophrenia are now being recognized as having mitochondrial dysfunction in common. With higher oxidative stress levels.[iv] Studies show that 1,200 mg per day of CoQ10 in bipolar adults experienced a significant reduction in depression.[v]
- 5-HTP – I do NOT recommend using 5-HTP for treating depression. But thought to include it here since it is promoted as a “natural antidepressant”.
This amino acid is naturally produced in your body. And synthesized from the amino acid tryptophan which you get from food. 5-HTP is the precursor needed to produce the ‘feel-good’ neurotransmitter serotonin. But a summary published in the Alternative Medicine Review noted a lack of evidence for ‘loading’ precursors to treat depression.[vi] Combining 5-HTP with SSRI’s, Tricyclics or MAOI’s will cause Serotonin Syndrome. And the side effects on its own are nasty. Or even deadly if combined with any of these prescription medications.
- Ginkgo Biloba – This tree native to China has been used for thousands of years to boost mental alertness, improve cerebral circulation and for better overall brain function. Many have found Ginkgo Biloba to be very effective for reducing anxiety and stress. And for boosting mood.
1,570 men and women in England participated in a study using 120 mg of Ginkgo Biloba extract daily for 4, 6, and 10 months. Those who used Gingko Biloba the longest experienced the most improvement in ratings for anxiety, depression, energy, drowsiness, sadness and happiness.[vii]
- Iodine – Did you know that iodine deficient populations are up to 13.5 IQ points less than those with optimal iodine levels in their system?[viii] Since iodine has largely been removed from table salt in some countries, it has been suggested that iodine deficiency is epidemic. Particularly in countries like the United States.
Iodine is essential to thyroid health and the production of thyroid hormones. Nearly every tissue in your body relies on thyroid hormones for healthy function. Not enough iodine can result in hypothyroidism. Negatively affecting acetylcholine synthesis in your brain. Affecting cognition, learning and memory, recall and mood.
- Kava – Kava is native to the South Pacific. And the islanders use kava for its sedative effects. Kava can help reduce anxiety and depression. Unlike benzodiazepines, kava does not impair cognitive function. In fact, studies show that not only will Kava improve mood. It may also boost cognitive function as well.[ix]
- Lion’s Mane Mushroom – Also called the “smart mushroom”, Lion’s Mane boosts brain nerve growth factor which increases neurogenesis. Lion’s Mane can help improve focus and attention, boost thinking and processing speed, repair brain cells, and help relieve anxiety and depression.
Women in Japan received Lion’s Mane-laced cookies for 4 weeks during a clinical trial. The researchers found that Lion’s Mane reduced anxiety and depression in these women during the trial.[x]
- Magnesium – Lack of adequate magnesium can result in brain fog, anxiety and depression. Plasticity of neuron synapses is affected by the presence of adequate magnesium in brain cells.
A study was conducted with 5,708 people in Norway. The aim of the study was to examine the association between magnesium intake and depression and anxiety. The researchers found that low magnesium intake is related to depression.[xi]
- Mucuna Pruriens (L-DOPA) – L-DOPA is synthesized from the amino acid tyrosine in your body. And is a precursor to the formation of dopamine, epinephrine and norepinephrine in your brain.
Mucuna Pruriens has been used in Ayurveda medicine since 1500 B.C. For treating things like snakebite, intestinal problems, sexual issues and melancholy mood. Research shows that supplementing with L-DOPA from Mucuna Pruriens extract can be a great natural antidepressant if you are low in dopamine.[xii]
- N-Acetyl L-Cysteine (NAC) – NAC is an amino acid that regulates the amount of glutamate and dopamine in your brain. It helps restore dysfunctional dopamine receptors. And is a precursor to Glutathione which is your master antioxidant which helps reduce free radicals and oxidative stress
A study with 75 subjects with bipolar disorder were given 1 gram of NAC twice daily for 24 weeks. Treatment with NAC resulted in a significant improvement with depression in these patients.[xiii]
- N-Acetyl L-Tyrosine (NALT) – NALT is a highly bioavailable form of the amino acid L-Tyrosine. Your brain uses tyrosine to produce dopamine and norepinephrine. Dopamine is involved in libido, memory, focus, goal-oriented concentration, is a mood elevator and antidepressant.
If you are ADHD, or have other issues with low dopamine, supplementing with NALT or L-Tyrosine may help improve your memory, boost your IQ, and relieve depression. I highly recommend NALT or L-Tyrosine for anyone using stimulants like Adderall or Ritalin for treating ADHD.
- Nefiracetam – One of the newer members of the racetam-family of nootropics, Nefiracetam is used clinically to treat and prevent seizures, severe depression and has shown neuroprotective qualities.
The structure of Nefiracetam is similar to the other great racetam antidepressant Aniracetam. Researchers at the University of Iowa did a trial with 159 stroke patients with major depression. The study concluded that Nefiracetam produced a significant improvement in the most severely depressed patients.[xiv]
- Noopept – This peptide-derived nootropic related to the racetam-family is much more potent than Piracetam. But its mechanism of action in your brain is similar to other racetams.
Noopept stimulates dopamine, nicotinic and serotonin receptors. And boosts cognition, memory, logical thinking, reflexes and mood.[xv] Noopept increases Alpha and Beta brain waves. Increasing relaxation. And moving you into super-learning, flow states and joy.
- Phenylalanine – This amino acid is a precursor to tyrosine in your brain. Tyrosine helps in the formation and utilization of dopamine, epinephrine, norepinephrine and melatonin.
One study was done with 23 patients diagnosed with depression who had not responded to standard antidepressants. They were given 50 or 100 mg of Phenylalanine daily for 15 days. The researchers found that Phenylalanine completely improved mood in 17 of the patients. Within 13 days of the 15-day trial.[xvi]
- Rhodiola Rosea – Rhodiola Rosea activates AMPA receptors in your brain. Which decreases depression and stress-related mood swings, reduces fatigue, stimulates energy and alertness, boosts cognition, and motivation.
A clinical trial with 57 patients diagnosed with depression were given Rhodiola Rosea extract, sertraline (Zoloft®), or a placebo for 12 weeks. The study found that Rhodiola Rosea was slightly less effective than sertraline for depression. But produced far fewer side effects and was better tolerated.[xvii]
- SAM-e – SAM-e is the naturally occurring amino acid methionine bound to an ATP molecule. It helps in the process of cell division and repair, and the generation of the neurotransmitters dopamine, serotonin, norepinephrine and melatonin. Which is why it’s considered a potent nootropic.
SAM-e is used to boost mood, relieve depression, improve energy levels and reduce symptoms of fibromyalgia. 20 healthy volunteers took part in a study receiving infusions of 800 mg of SAM-e or a placebo for 7 days. EEG mapping during the study identified SAM-e as an antidepressant. Targeting brain regions crucial in the therapeutic efficacy of antidepressants.[xviii]
- St. John’s wort – This herb has traditionally been used for mood disorders and wound healing. Today it’s used mostly as a treatment for anxiety, depression and stress.
St. John’s wort works like prescription SSRI’s by preventing the reuptake of serotonin in your brain. But please read the precautions for using this nootropic in the extended article. Before trying it as a nootropic supplement to treat your depression.
- Sulbutiamine – Sulbutiamine is a synthesized version of Vitamin B1 (thiamine) which easily crosses the blood-brain barrier. As a nootropic, it’s used to boost mood, memory and motivation.
A study at the University of Wales Swansea in the UK worked with 120 young adult females. Study participants took either a placebo or 50 mg thiamine for 2 months. Mood, memory and reaction times were monitored before and after taking the tablets. 2 months after supplementing with thiamine, participants were more clearheaded, felt more composed and energetic, reaction times improved, and mood was better.[xix]
- Tryptophan – This essential amino acid is a precursor to serotonin, melatonin and niacin (Vitamin B3) in your body. Adding tryptophan to your stack can help boost your serotonin levels. And should help with anxiety, ADHD, depression, insomnia, memory loss, pain and eating disorders.
- Turmeric– Turmeric is one of the main spices in curries. In parts of India where curries are eaten most often, Alzheimer’s disease is extremely rare. This spice (and its extract called curcumin) has a unique ability to reduce inflammation common to Parkinson’s, Alzheimer’s and brain tumors.
A study conducted in India looked at the efficacy and safety of using curcumin, the main active ingredient found in turmeric, for treating major depression.
60 depressed patients took either 20 mg of Prozac®, 1000 mg of curcumin, or a combination of both daily for 6 weeks. The best response during the trial was with patients using the two. And the researchers concluded that curcumin could be used as an effective and safe treatment for patients with major depression.
- Uridine Monophosphate – This precursor to Ribonucleic Acid (RNA) provides instructions from your DNA to help create memory by facilitating connections between brain neurons (synapses).
Uridine supplementation as a nootropic uplifts and stabilizes mood, is anti-stress, helps Obsessive Compulsive Disorder (OCD), is anti-anxiety and helps modulate and normalize dopamine release.[xx]
- Vitamin B6 – Vitamin B6 helps your brain make serotonin, norepinephrine and melatonin. The activated form of Vitamin B6 called P-5-P is particularly effective in boosting serotonin and GABA in your brain.
For depression, look for a P-5-P supplement or a B-Complex formula that uses P-5-P.
- Vitamin B12 – This B-vitamin plays a key role in the efficient conversion of carbohydrates to glucose which contributes to cellular fuel production (ATP). It also helps your body convert fatty acids into energy.
Supplementing with Vitamin B12 can help lower anxiety, and elevate alertness, cognition, energy, vision, elevate mood and relieve insomnia. No more mood swings!
Depressed No More
Nootropics can be a strong alternative to many antidepressant medications currently prescribed by doctors. And promoted by the Big Pharmaceutical companies.
But a very strong word of caution – if you are currently using any prescription antidepressant medications. Or any medication for that matter. Research each nootropic including side effects and prescription drug interactions before using them.
To finally beat depression, you must figure out the root cause of it. It is pointless to try otherwise without doing your research. And experimenting with various nootropic supplements until you find out what works for you.
Good luck in your search. There is hope. I know because I’ve conquered my depression. And came out the other side better than before.
[i] Frodl T. et. Al. “Reduced hippocampal volume correlates with executive dysfunctioning in major depression” Journal of Psychiatry and Neuroscience 2006 Sep; 31(5): 316–325. (source)
[ii] “Alternative medicine for depression” Harvard Medical School July 1, 2007 (source)
[iii] Bhattacharya S.K., Bhattacharya A., Sairam K., “Ghosal S. Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: an experimental study.” Phytomedicine 2000 Dec;7(6):463-9. (source)
[iv] Maes M., Galecki P., Chang Y.S., Berk M. “ A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness.” Progress in Neuropsychopharmacology and Biological Psychiatry. 2011 Apr 29;35(3):676-92. (source)
[v] Forester B.P., Zuo C.S., Ravichandran C., Harper D.G., Du F., Kim S., Cohen B.M., Renshaw P.F. “Coenzyme Q10 effects on creatine kinase activity and mood in geriatric bipolar depression.” Journal of Geriatric Psychiatry and Neurology. 2012 Mar;25(1):43-50. (source)
[vi] Meyers S. “Use of neurotransmitter precursors for treatment of depression.” Alternative Medicine Revue. 2000 Feb;5(1):64-71. (source)
[vii] Trick L., Boyle J., Hindmarch I. “The effects of Ginkgo biloba extract (LI 1370) supplementation and discontinuation on activities of daily living and mood in free living older volunteers.” Phytotherapy Research. 2004 Jul;18(7):531-7. (source)
[viii] Qian M., Wang D., Watkins W.E., Gebski V., Yan Y.Q., Li M., Chen Z.P. “The effects of iodine on intelligence in children: a meta-analysis of studies conducted in China.” Asia Pacific Journal of Clinical Nutrition 2005;14(1):32-42. (source)
[ix] Thompson R., Ruch W., Hasenöhrl R.U. “Enhanced cognitive performance and cheerful mood by standardized extracts of Piper methysticum (Kava-kava). Human Psychopharmacology. 2004 Jun;19(4):243-50. (source)
[x] Nagano M., Shimizu K., Kondo R., Hayashi C., Sato D., Kitagawa K., Ohnuki K. “Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake.” Biomedical Research. 2010 Aug;31(4):231-7. (source)
[xi] Jacka F.N. et. Al. “ Association between magnesium intake and depression and anxiety in community-dwelling adults: the Hordaland Health Study” Australian and New Zealand Journal of Psychiatry Volume 43, Issue 1, 2009 (source)
[xii] Rana D.G., Galani V.J. “Dopamine mediated antidepressant effect of Mucuna pruriens seeds in various experimental models of depression.” Ayu. 2014 Jan;35(1):90-7. (source)
[xiii] Berk M., Copolov D.L., Dean O., Lu K., Jeavons S, Schapkaitz I., Anderson-Hunt M., Bush A.I. “N-acetyl cysteine for depressive symptoms in bipolar disorder–a double-blind randomized placebo-controlled trial.” Biological Psychiatry. 2008 Sep 15;64(6):468-75 (source)
[xiv] Robinson R.G., Jorge R.E., Clarence-Smith K. “Double-blind randomized treatment of poststroke depression using nefiracetam.” Journal of Neuropsychiatry and Clinical Neurosciences. 2008 Spring;20(2):178-84. (source)
[xv] Gudasheva T.A., Konstantinopol’skii M.A., Ostrovskaya R.U., Seredenin S.B. “Anxiolytic activity of endogenous nootropic dipeptide cycloprolylglycine in elevated plus-maze test.” Bulletin of Experimental Biology and Medicine. 2001 May;131(5):464-6. (source)
[xvi] Fischer E., Heller B., Nachon M., Spatz H. “Therapy of depression by phenylalanine. Preliminary note.” Arzneimittelforschung. 1975 Jan;25(1):132. (source)
[xvii] Mao J.J., Xie S.X., Zee J., Soeller I., Li QS., Rockwell K., Amsterdam J.D. “Rhodiola rosea versus sertraline for major depressive disorder: A randomized placebo-controlled trial.” Phytomedicine. 2015 Mar 15;22(3):394-9. (source)
[xviii] Saletu B., Anderer P., Di Padova C., Assandri A., Saletu-Zyhlarz G.M. “Electrophysiological neuroimaging of the central effects of S-adenosyl-L-methionine by mapping of electroencephalograms and event-related potentials and low-resolution brain electromagnetic tomography.” American Journal of Clinical Nutrition. 2002 Nov;76(5):1162S-71S (source)
[xix] Benton D., Griffiths R., Haller J. “Thiamine supplementation mood and cognitive functioning.” Psychopharmacology 1997 Jan;129(1):66-71. (source)
[xx] Powell A. “Rx for depression: ‘Mangia, mangia!’ Harvard Gazette Archives new.harvard.edu March 03, 2005 Retrieved August 9, 2016 (source)
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i am deppressed, low energy and no motivation. I am on MLP, B cpmplex, Multi, B12, Tumeric, Sulbutamine, NAC, Mg Glycinate, Ginkgo, Pine Bark added lately, Vinpocetine Alcar, carnosine, D3, K2, Fish oil. Taurine and PL Caffeine prn late addition with no relief.
I am motivated up with a crowd. Motivated energized for 5 mins then down again. After I am not with the crowd I am same again with low mood. i wasn’t like this before when I first started these supplements.
What could be the problem? Will lithium Orotate help with my deotression? Help me Dave. Will it cancel other above?
Trazodone was prescribed but I didn’t go for it. Am 80 years old. Has aging a normal process? Just desperate. Thanks a million for your super brain breakthrough.
Marcie, it you were not like this until you started using the supplements you listed then I suggest you stop everything. And then add them one at a time. Give each on a day or two and see how you feel. If it doesn’t make you depressed, low energy or unmotivated then add the next one. Give it a couple of days and if it’s OK then add the next one, etc.
That is the only way you can figure out which one is the culprit.
And if you have not already read my article on aging I suggest you do it now. Because it details everything that happens with the aging brain and how to deal with it. Including restoring the neurotransmitters that you are low in. https://nootropicsexpert.com/best-nootropics-for-the-aging-brain/
Hello David
I read with great interest your list of nootropics for depression and now vital it is to determine the correct reason fir your depression. How does one determine that?
Would it be possible to have a consult on this matter? I am in a very bad way and truly desperate for relief from my suffering.
Could one combine sever nootropics such as ashwaganda, nac and the first one mentioned.
Thanking you for any consideration.
Maureen, often it takes trial and error and experimenting with different nootropics to find out the cause of your depression. And the outcome can be very different than someone else suffering from depression.
I’m happy to walk you through how to do that in a consultation whenever you’re ready.
BTW, there is no problem combining different nootropics. Where people get into trouble is trying to combine them with certain prescription drugs.
David, do you have any information on the effects of antidepressants on neurological pain?
Irina, this Abstract provides a good summary in the use of SNRIs and Tricyclics for neurological pain: https://pubmed.ncbi.nlm.nih.gov/15910402/
Good evening David, thanks for the quick reply. My question is what are the two best fat activators to repair damaged cells and restore receptors.
You do not need “fat activators”. You need something to increase BDNF to repair damaged cells and restore receptors: https://nootropicsexpert.com/13-nootropics-to-boost-bdnf/
Good evening David, I have been taking citalopram for depression 10mg for a year. I reduced the dose to half and after a while I reduced half to a quarter, but I could not get rid of a quarter despite the addition of tryptophan. Is there a plan or advice to get rid of this quarter?
Nothing special you can do except allow your brain to heal itself. Try a couple of supplements to boost BDNF to speed this repair process. https://nootropicsexpert.com/13-nootropics-to-boost-bdnf/
hey David, thanks for the interesting videos. Do you have experience with alpha stim( cranial elektro therapy )for depression?
Thanks in advance
Jef
Jef, I am not familiar with it. I am familiar with TMS which is administered by a doctor and it works.
Here is a summary of all the clinical reviews done with cranial electrotherapy: https://www.ncbi.nlm.nih.gov/books/NBK493135/
David, do you know of any cases where nootropics cause depression? I take over the counter noots. In the past I’ve taken alpha brain, then tried mind lab pro, and now am trying qualia mind (caffeine free because I like to drink tea throughout my day). I have been feeling depressed and struggling with motivation especially in the mornings.
I’m wondering if the different proprietary blend of qualia mind could have anything to do with this? Or perhaps there’s some sort of biochemical dependence going on?
Any and all insight is appreciated! Thanks!
Charlie, the wrong nootropic supplements can certainly contribute to depression or anxiety. Too much acetylcholine, dopamine or serotonin will cause problems.
Each one of us has unique brain chemistry. And if you upset that balance rather than support a deficiency things can go wrong.
Hi David! My doctor prescibed to me SSRI due to my lack of motivation.
I take most of suplements from your “motivation” article. I have nearly all symptoms of ADD as described on the internet, but my doctor said that serotonine is the cause and my perfectionism in life is the reason of lack of motivation to do anything. Have you ever heard about something similar?
Thank you David!
Jessica, this is the article you are referring to I think: https://nootropicsexpert.com/hacking-motivation-with-nootropics/
An SSRI for motivation is an oxymoron and is at the opposite end of the spectrum. All you need to do is study the mechanism of action for any SSRI and then read the side effects of whichever SSRI you are referring to to understand why.
Motivation is dependent on the dopamine/reward/motivation pathway. But you need to stimulate glutamate AMPA receptors to activate this pathway. Resveratrol or Berberine activates AMPK.
Hi David,
I am currently taking Bupropion or Wellbutrin twice daily. It has been for 4 years now. I also have two cups of coffee per day. Some of my depressive symptoms have decreased, but I still have brain fog and lack of focus. I wanted to know what nootropics would you recommend to combine with Wellbutrin, to help boost memory, focus, and energy.
Ashley, it sounds like part of the cause of your depression could be due to dopamine dysfunction which is why you have had some success.
But brain fog AND depression can be caused by inflammation which I explain in this article: https://nootropicsexpert.com/best-supplements-for-brain-fog/
And problems with focus and concentration can be caused by acetylcholine dysfunction including not enough acetylcholine in your brain. You can improve this by increasing acetylcholine by supplementing with CDP-Choline AND ALCAR. But you also need the B-Vitamins as cofactors to synthesize acetylcholine AND dopamine. So get yourself a good bioactive B-Complex like this one: https://amzn.to/3gXUM5D
Mr Tomen, thank you for providing insight for the way the brain works down to the microbiological level! I was diagnosed with ADD at about 7 years old and took Ritalin on and off till I was out of grade school. I also had multiple concussions. Now I’m 40, and feel like I’m not reaching my potential. Lacking memory, focus/staying-on-task and irritable and lazy after working all day. I feel like I need energy and motivation to when I get home. I feel out of rhythm when I’m home on the weekend and not getting up and going to work! I take NATURELO whole food multi which has good B levels but I think I need something additional. I’d be willing to get the mind lab pro but is there anything more basic from a vitamin/mineral level I should try first?
Colin, if you were diagnose ADD 7 years ago then you are still ADD. Just like me. Which means our brains are ‘wired’ differently compared to ‘normal people’.
Mind Lab Pro is a good start but if you want to go the ‘natural’ route then you need my ADD protocol which I detail on this page: https://nootropicsexpert.com/best-nootropics-for-adhd-add/. It is the stack in the yellow box near the top of that article. I need to update it but I have recently changed from Alpha GPC to CDP-Choline but the rest remains the same. And is what I use along with Ritalin.
Thank you, I read that in your newsletter and I will start sourcing the products from your links. I want to avoid Ritalin particularly for now due to the fact that it raised my already over average pulse rate. I’ll let you know how it goes!
Good luck Colin.
Hi David. What are your thoughts on Huperzine A for mood and cognition? Thank you.
Noel, this study shows Huperzine-A effective for learning and memory: https://nootropicsexpert.com/huperzine-a#huperzine-a-improves-learning-memory. And the next study down on cognition. But not for mood.
And remember Huperzine-A has a long half-life of 10 – 14 hours. So you can only use it every 2nd or 3rd day,
Hi David. What are your thoughts on agmatine for mood, cognition, and energy? Thank you.
Noel, I have not researched Agmatine so cannot comment on its potential benefits.
Hi, My son is age 16. He has the ADD part of ADHD. Currently on zero medication. Does use caffeine in the morning to give him a boost. In the last few years he has been slowly walking away from previous loved activities. He has confronted my wife with being sad sometimes. We brought him to a psychologist and she didn’t think medication was right at this point and he refuses a Psychiatrist. I take Nootropics for memory. Which Nootropic do you recommend as the best for motivation and depression? Thanks in advance.
Steve, depression is a ‘side effect’ of ADD. And it’s the ADD that needs to be treated with either prescription stimulants or natural nootropic supplements. Once his ADD is well managed you should see the depression subside.
Depression related to ADD is usually caused by a dopamine dysfunction. I highly recommend the stack described on this page: https://nootropicsexpert.com/best-nootropics-for-adhd-add/.
And if you’d like some help I do offer Personal Consultations. Here is a link to my calendar if you are interested: https://calendly.com/davidtomen/60min
Hello first of all thank you for dedicating your time to save our lives, I have some questions that concern me, please.
Why didn’t you include chicory root fiber extract (like Performance Lab® Prebiotic) on this list? (May not be as effective for for depression as NALT – Tryptophan and Turmeric?)
Should I take Nalt daily just because I suffer from Hypothyroid?, I take Levothyroxine and Perfonmance Lab Multi (to have the amount of Iodine, Vitamin C and Selenium) but I have a bad mood due to my condition and I am afraid that taking Nalt or Tyrosine will make it worse
I would like to know if the amount of Bioperine present in this nootropic increases the effects of T4 (Levothyroxine)
and Ibuprofen (occasionally) in dangerous form? (or it won’t hurt me to combine them)
Doctor’s Best High Absorption Curcumin
Could you give me a link where to buy “Natural desiccated thyroid” to use as an alternative to Levothyroxine ?, and tell me how much to consume? (I was thinking of starting with 65 Mg but I don’t know how I would know if I needed more or less)
Jane, a prebiotic is not normally considered for its antidepressant value. And would never be considered on a list of supplements for depression. It is true that you could experience depression if your microbiome is screwed up. And some can alleviate depression just by getting their microbiome back into balance. But it’s not considered an antidepressant.
If you are hypo then you need to be careful with L-Tyrosine. Because you can mess up your thyroid hormone levels that you worked so hard to get back on track. L-Tyrosine helps make thyroid hormone. But it depends on your system. I’m hypo and use fairly high quantities of Tyrosine without a problem. But that may not be true for you. The only way to find out is by trying it.
You need to do some research and find out which enzymes your liver uses to get Levothyroxine and Ibuprofen into your system. And see if they are the same enzymes affected by Piperine.
And Natural Desiccated Thyroid is a prescription drug. There are a couple supplements on the market but they are not consistent in their formulation to be used to consistently get your thyroid T4 and T3 levels normal. You need to find a doctor or naturopath willing to work with you and get a script for NDT.
Dear David, thanks for replying. I would just like to know about your personal experience with Hypothyroid, did it lead you to have any bad experiences when you were taking T4 at the same time as you were taking Bioperine?
– I am currently taking Rhodiola Rosea Double Wood Supplements, but the percentages are opposite of what you recommend – it is listed as 3% Salidrosides, 1% Rosavins, can you provide a link to the best for a standalone Rhodiola Rosea supplement that you recommend I buy?
I would appreciate your answer, thank you
Jane, I never noticed a problem with T4 while using BioPerine. But keep in mind that I wasn’t taking T4 on its own because Natural Desiccated Thyroid contains all the thyroid hormones that are supposed to be made by my thyroid but aren’t. Which is why I’m hypo.
Try this Rhodiola Rosea supplement and see if it helps: https://amzn.to/37rWrvB
Hello David,
I find your website very informative, useful and helpful – keep up the great work!
I’ve decided to post a comment as I’d be extremely grateful for your advice.
For as long as I can remember (now am 43), I’ve struggled a lot with being able to function normally on a day-to-day basis, and even more so with my job. I’ve always felt pretty tired, sleepy, weak and depressed. I can sleep for 12 hours or longer and still have a hard time waking up and getting up. I suspect I might be suffering from idiopathic chronic fatigue / hypersomnia (or chronic fatigue syndrome) as most of the symptoms match.
Last year I started experimenting with nootropics and some drugs. First of all, I’d like to mention that for many years I’ve been taking Tramadol (about 400 mg daily) due to chronic pain which, apart from being a potent analgesic, is also an SNRI antidepressant. I suspect that long years of taking it might’ve messed up my brain and in turn caused a major depression (plus made me an addict). I’d finally like to get better, at all costs, especially feel less sleepy and tired, more energetic, positive, optimistic and motivated, all the traits and qualities I unfortunately lack and can’t regain. Now I feel like a wreck, completely unproductive, inefficient and hopeless 🙁
LAST YEAR
I tried taking Noopept (with Choline) and it was only giving me headaches, no benefits. Then I was taking Phenylpiracetam, NALT, Flmodafinil, Armodafinil and Hydrafinil (which allegedly are supposed to be stronger than regular Modafinil) none of which had any effect on me. Then I tried Modafinil and it only resulted in me getting headaches and all jittery.
THIS YEAR
For over 2 months I’ve been taking the following with no effect whatsover (per day) – as if I wasn’t taking anything:
Acetyl L-Carnitine – 1 g
Choline citrate – 500 mg (Citicoline 500 mg was giving me headaches)
Ginkgo Biloba – 120 mg
Glutathione – 500 mg & NAC – 600 mg & Alpha lipoic acid 35 mg
Phosphatidylserine – 200 mg
Maritime Pine Bark – 175 mg
Creatine – 1 g
CoQ10 – 100 mg
Curcumin – 100 mg
DHA – 500 mg
Vinpocetine – 5 mg
Inositol – 250 mg
A mix of vitamins & minerals
The only positive effect I can feel is when I take 100 mg of Tramadol along with Ritalin 10 mg but that relatively subtle rush of energy lasts up to 2 hours and then it’s back to normal. Adding more Tramadol and Ritalin doesn’t help. To the above stack I once added Ginseng (a mix of Korean, American and Siberian) but I stopped taking it because I was afraid of getting adverse symptoms since Tramadol is an SNRI and I’m already taking Ginkgo Biloba and sometimes Ritalin.
MY LAST HOPE
After I get back to my home country this June, I want to try taking the following (it’s not available where I’m located now):
NADH
Rhodiola Rosea (I’m a bit afraid of interactions with Tramadol, Ritalin & Ginkgo Biloba)
Aniracetam or Oxiracetam (same here, afraid of interactions)
Alpha-GPC (perhaps this variety of Choline won’t give me headaches?)
Bacopa Monnieri
PQQ
Magnesium L-threonate
Medicinal mushrooms
N-Acetyl Semax
(Lithium orotate and Bromantane are unfortunately unavailable)
Now finally my question: would you add / remove / amend any items from my current stack and my June’s plan? Do you think there could be any better and more effective substances than the ones I mentioned? (except drugs such as Adderall, Desoxyn or Ketamine which I can’t get hold of anyways).
Greg, choline citrate cannot cross the blood-brain barrier. Alpha GPC and CDP-Choline both provide a choline molecule for the synthesis of acetylcholine but in different parts of that pathway that makes that neurotransmitter. It was likely Noopept that gave you the headache because of not enough acetylcholine to work withy. But try Alpha GPC instead and see if it works better for you. Some react better to one over the other.
Your “mix of vitamins and minerals” needs to be bioactive vitamins and chelated minerals. And not the cheap garbage found on most store shelves. Lack of even one vitamin or mineral may prevent something else from working in your stack. Or cause other problems in your brain and system.
I’m not going to spend the time going through each supplement in your stack. But some of your dosages are wrong and timing is off. One example, ALCAR 500 mg 2 or 3-times per day. Not one massive dose.
Your brain needs these supplements during the day and all day long. Many have a very short half-life. And you not doing anything to support dopamine in your brain. Modafinil and the other stimulants do not make dopamine. L-Tyrosine does make dopamine along with Vitamins B6, B9, & B12.
Hi,
I am curious why Niacin is not listed as a recommendation along with the other B vitamins?
Marlene, likely because when I was writing this article there weren’t any clinical studies AND niacin showing up in my research.
I’m sure they may exist and someone could make a argument that niacin deficiency is a cause of depression. That statement is purely a guess at this stage.
But I had to end this list somewhere. Otherwise, this page would have went on forever.
Should I take all of these ?
Where do I start ?
Lu, you don’t “take all of these” for a number of reasons. I suggest reading this article again from top to bottom. Maybe something will resonate while reading the causes of depression above.
Try one nootropic from the list and see if it helps. If not then move on to the next one. Trial and error until you find something that brings relief is the only way to do this.
Hi, I’m wondering if any of these nootropics for depression could interact with Lamictal (Lamotrigine) which I use as a mood stabilizer?
Anina, this is the list of contraindications for Lamotrigine: https://www.drugs.com/drug-interactions/lamotrigine-index.html. Scroll through that list and see if anything from the article above is on that list.
Hi David, It’s me Rose, from the other page, trying to help my friend Susan (71, 750mg lithium carbonate a day plus 200mgs seroquel). In reading your suggested page, above, I wondered about the COq10 if that would be okay to use in conjunction with these meds she is on. That one sounded like it could perhaps help her, though it seems a shot in the dark.
Also, may the curcumin.
Thank you in advance for your help,
Rose
Rose, both are good ideas. Just please read the “Side Effects” section of each review for CoQ10 and Turmeric (Curcumin) before you proceed.