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.
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.
In 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.
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Depression and Neurogenesis
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 not the 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’, which is a tiny electrical signal, 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 can go 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 can 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 can result as 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 drug 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 every one of us who faces stress develops depressive disorder. Stress however often 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 a natural alternative to drugs that often often associated 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 which can help control glutamate toxicity.
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 medicine. Bacopa Monnieri has been used for millennia to relieve anxiety, fatigue, restore energy and boost concentration.
- 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 only include it here since it is marketed 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 which can be deadly.
- 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 improvements 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 having enough 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 extracted from Mucuna Pruriens 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 needed to 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. It 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 synthesis of dopamine, epinephrine, and norepinephrine.
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 can decrease 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 combination. 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 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
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. Experiment with various nootropic supplements until you find what works for you.
Good luck in your search. There is hope. I know because I’ve conquered my own depression. And came out the other side better than before.
[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)
[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)
[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)
[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)
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