Nootropic forums and blogs often describe depression as a neurotransmitter imbalance in the brain. And then offer suggestions on various nootropics to help lift mood and banish 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 the brain, genetic problems, stressful events, prescription medications and 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 and another too high.
Instead, you have several neurotransmitters, 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 is responsible for 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 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.
Depression and Neurogenesis
It turns out that neuron connections, neurogenesis and the function of neuronal circuits may play a more important role in depression than levels of neurotransmitters.
For example, researchers in Munich studied 24 women who had a history of depression. And on average, the hippocampus was 9 – 13% smaller in depressed women compared to healthy women. And the more bouts of depression a woman had, the smaller the hippocampus.[i]
We know that stress plays 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, is critical for preventing apoptosis (brain cell death), growth of new neurons (neurogenesis) and growth of synapses.
Please check out this article on “13 Nootropics to Boost BDNF”. Increasing BDNF is one way to combat depression. And you’ll see some parallel between the nootropics listed below. And the list of nootropics used for boosting BDNF.
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 these medications may be in generating new neurons (neurogenesis), strengthening neuron connections, and improving neural signaling.
So now researchers speculate that new medications could be developed that specifically promote neurogenesis. As it turns out, we already have this ability with several natural nootropic supplements.
Depression and Neurotransmitters
Now that we know that neurotransmitters are not the only critical part of preventing depression. We can’t discount their importance either.
Neurons are specifically designed to communicate with each other. When a neuron is activated, it passes an ‘action potential’ down its axon to the axon terminal. Neurotransmitters are stored in vesicles in this terminal.
The action potential (signal) releases certain neurotransmitters into the synapse (space between neurons). And on to the dendrite of 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, a feedback mechanism instructs the neuron to stop putting out this neurotransmitter and begin bringing it 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 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 can be replaced by safer, natural alternatives. Like 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 seek out safer alternatives that often do the job just as well.
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 check out my extended article on “Best Nootropics for Anxiety” which includes several nootropic supplements that 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 could be the answer.
You’re not alone looking for an alternative to drugs that 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 is your cell’s natural source of energy. Fueling 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 we get from food. 5-HTP is the precursor needed to produce the ‘feel-good’ neurotransmitter serotonin. But a summary published by 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.
- Ginkgo Biloba – This tree native to China has been used for thousands of years to boost mental alertness, improve cerebral circulation and for overall brain function. Many have found Ginkgo to be very effective in 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 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 normal people?[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 nearly every tissue in your body relies on thyroid hormones. Not enough iodine can result in hypothyroidism. Negatively affecting acetylcholine synthesis in your brain. Affecting cognition, memory, learning, 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 it improve mood. But may 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, repair brain cells, and help 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 as Mucuna Pruriens extract is a great natural antidepressant.[xii]
- N-Acetyl L-Cysteine (NAC) – NAC is an amino acid that regulates the amount of glutamate and dopamine in your brain. And is a precursor to glutathione which reduces free radicals.
A study with 75 subjects with bipolar disorder were given 1 gram of NAC twice daily for 24 weeks. Treatment with NAC caused 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, a mood elevator and antidepressant.
If you are ADHD, or have other issues with low dopamine, supplementing with NALT may help improve your memory, boost your IQ, and relieve depression. I highly recommend NALT 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 activates AMPA receptors in your brain. Which decreases depression and stress-related mood swings, reduces fatigue, stimulates energy and alertness, and boosts cognition.
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 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 plant 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 taken 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 and 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, one of the active ingredients 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 to 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, 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 – your cell’s source of fuel. 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 are 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 come 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)
David,
I’m a 53 year old male w 25 years diagnosed w severe clinical depression w/anxiety and now ADHD this year.
Issues with executive functioning skills. Tested low.
Hate Aderall. What in your opinion should I research as the best stack for me to help my brain & its many disorders. Including memory loss due to repeated concussions.
Thank you,
Mark
Mark, it would be helpful to know why you hate Adderall. I do as well and use Ritalin instead. These two stimulants work differently in the brain. And I found Ritalin works better for me. I did an experiment last year for personal reasons and discontinued use of Ritalin altogether (for an entire year). I used the stack you’ll find near the top of this page > https://nootropicsexpert.com/best-nootropics-for-adhd-add/. It’s right under the sub-title “Adult ADD Nootropic Stack”. Mind Lab Pro was key to making that stack work. But it worked very well.
I did go back on (a lower dose) of Ritalin because I too have big issues with Executive Function. The stimulant works to help executive function. But it needs the support of the rest of that same stack to work efficiently. And eliminate side effects.
The combination of Aniracetam and Sulbutiamine works great for the depression I deal with. It’s not severe depression but it may be worth a try for you.
For anxiety, please see this post > https://nootropicsexpert.com/best-nootropics-for-social-anxiety/. One of the things I’ve learned is anxiety is often caused by excess norepinephrine. One of the best ways to counter that is with this > https://nootropicsexpert.com/lithium-orotate/. Lithium has a bad rap because it’s been used for decades to treat bipolar disorder and mania. I’ve found in my case it works beautifully to tame spikes in aggression and rage type feelings. They don’t happen often for me but micro-dosing lithium stops it within 15 minutes.
It’ll take some trial and error because each of use is unique. Those posts should get you started. Along the way you may find like I did that you need more dopamine. Especially at your age. So I use Mucuna Pruriens (L_DOPA). But have to amp up my serotonin. So I use small doses (25 mg) of 5-HTP which is a direct precursor to serotonin.
And for traumatic brain injury, that’ll be my next article. So please make sure you’re subscribed to the list so you’ll get an email when it’s published. Should be in the next week or so. Please report back on how you’re doing.
8/26/17
David …
Just happen 2 find your ‘great’ nootropicsexpert website …
Very impressed with your fully detailed product summaries …
Am currently reviewing ‘depression’ summary …
Adding niacin powder to ‘Emergen-C’ electrolyte drink @ 4-5 a.m. wakeup really wonders on my brain …
Begin to feel incredible ‘effect’ in my scalp/brain area starting within 2 minutes after entering bloodstream …
Then drift off into sleep without realizing that I in fact did …
Will probably follow up with future emails for your professional advice …
Keep up the good work!!!
CWHEIL
Minnesota
Chuck, you touched on a very good point and one that is often missed in the biohackers and nootropics community. And that point is that most of us are literally starved for the vitamins our body and brains need to function. We do not get them from our food supply. No matter how healthy we try to eat. The nutrients are just not there in factory-farmed food today. And the amount of toxins we’re exposed to everyday is crazy. Further depleting what vitamin stores we managed to accumulate along the way. Thanks for the compliment and enjoy Nootropics Expert!
David,
Very informative site. I took Lexapro for 10 years for social anxiety and depression and then Cymbalta for 2 when the Lexapro stopped working. I am currently weaning off Cymbalta at 1% a day. I’ve done a fair bit of research on beneficial supplements and added them to my diet. Recently I’ve been reading about microdosing mushrooms for treating depression and I’m starting to learn about nootropics. Can you recommend a nootropic stack?
Thanks,
Rob
Robert, recent research shows that depression is likely caused by inflammation. And that is one of the reasons Cymbalta works. By creating a decrease in proinflammatory cytokine activity and an increase in anti-inflammatory cytokines. So look for nootropics to replace Cymbalta with something natural that affects neurotransmitters and reduces inflammatory cytokines.
Ginseng provides these benefits. You can read the whole story here > https://nootropicsexpert.com/ginseng/. But play special attention to the right type of Ginseng and getting a quality supplement that will actually work.
You also need a high quality, bio-available B-Complex formula. Using folate (NOT folic acid) and methylcobalamin (NOT cyanocobalamin). You also require Vitamin D and Magnesium to make the neurotransmitters you need. See the review for each here on Nootropics Expert so you understand how they work.
That will get you started. I’d also investigate Rhodiola Rosea here > https://nootropicsexpert.com/rhodiola-rosea/. And possibly Aniracetam which I’ve found to be one of the best antidepressants I’ve ever used. But keep in mind that what works for me may not work for you. It’ll take some trial and error on your part. And patience.
One last thing … as long as you are using Cymbalta, pay special attention to nootropics that ‘directly increase serotonin’. And DO NOT USE THEM! You must avoid Serotonin Syndrome or you could get into a load of trouble.
Thanks for the info…
Good news is I already take Methyl Folate, methylcobalamin, vitamin D and magnesium. I’ll definitely look into the rest.
I’ve read about serotonin syndrome. As I mentioned I’m weaning off Cymbalta by 1% day. Would you recommend waiting until completely off before starting something like Aniracetam or do you think it would be safe once I’m down to a very low dose?
Aniracetam shouldn’t be a problem. I’ve flagged all the nootropics that could cause Serotonin Syndrome in each of the reviews. Look for it in either dosage notes or side effects for each.
Ouch… looks like Choline, Ginseng & Rhodiola Rosea all affect Serotonin levels. Looks like im stuck until ive completely weaned off the cymbalta… unless i can safely get started with something once im down to a very low dose?
Robert, you shouldn’t have any problem with the various choline supplements and Cymbalta. But I would stay away from Ginseng and Rhodiola. Because either of those could influence serotonin enough to possibly cause Serotonin Syndrome.
Once you’re down to a very low dose of Cymbalta, I’d still use caution because who knows who long this stuff stays in your system to cause problems. Just not worth messing around with. SSRI’s and MAOI’s are very potent pharmaceuticals. And SSRI’s are especially difficult to quit because of the withdrawal symptoms. I strongly advise finding an osteopath or naturopathic doctor who has the knowledge to walk your through this.
Sounds good.
Yeah, Cymbalta is a especially difficult to get off of. There are many sites devoted to it. Ive cut 30% so far at 1% per day. Its a long process but better safe then sorry.
I decided to go with Alpha GPC (Choline) 99% pure from healingtreeoflife and Aniracetam powder from nootropicsdepot.
If im taking 750mg Aniracetam twice a day with a spoonful of coconut oil how much Choline do i take with each dose… 500mg?
Try 500 mg of Alpha GPC (or whatever the capsule size is) each time you dose Aniracetam. And see how you feel. If you start feeling fatigued you know you’re getting too much choline. Cut the dose in half if that happens. It’s good to know the Alpha GPC is “99% pure” because many manufacturers cut it by 50% with a filler to prevent it from liquefying.
Hi Robert,
I also had a big problem weaning off of Cymbalta – the first time, experiencing a month-long headache even after getting down to 5 “balls” of the medication (from inside the capsule) per day before stopping.
By the next time I had to wean off Cymbalta, I’d learned about 5-HTP. Although Dave is correct that it’s best to be cautious, I got back down to the “5 balls” per day and then one day, just stopped all Cymbalta and started taking 50mg 5-HTP (once daily) instead. Worked wonders! No headache or other withdrawal, and similar anti-depressant effects. Since it’s a precursor to melatonin AS WELL AS serotonin, best to try this for the first time on a weekend or some other time when you are sure you don’t have to operate heavy machinery, take a test, etc. as some people are made quite sleepy by it if they are melatonin-deficient. I realize this is an old post, but just wanted to share in case you’re still searching (or for others).
hi,
I am 24 dealing with major depression and addiction. I am currently on 200 mg of Wellbutrin and deplin. I just starting reading about nootropics and I am thinking about purchasing Aniracetam. Does anyone have any ideas? I cannot get out of bed, see my friends, or do anything. I feel like a loser and committing suicide every day. Anything would help. Thank you
Brandon, Aniracetam may help but it may not be the best place for you to start with nootropic supplements. Please carefully read the full review for each of these and consider trying them:
https://nootropicsexpert.com/vitamin-d/
https://nootropicsexpert.com/lithium-orotate/
https://nootropicsexpert.com/dha/
I realize that DHA, Vitamin D and Lithium Orotate are not ‘sexy’ and seem tame by comparison to potent prescription antidepressants and some of the racetams. But you may be pleasantly surprised. Because sometimes we can correct major health issues simply by correcting imbalances in our body and brain.
When fundamentals including certain vitamins, minerals and phospholipids get out of whack it can seem like our world is coming to an end. And truth be told, if left unchecked, it will come to an end. For proof of this all you need to do is read some of the studies done over the last 100 years for lithium.
Did you know that “Deplin” is just an expensive pharmaceutical version of Vitamin B9 (folate)? Doctors prescribe it to boost folate in your body when regular antidepressants are not working as designed. What that tells me is the B-Complex vitamins are essential for normal mood and memory. And absolutely required to synthesize all the major neurotransmitters including acetylcholine, dopamine, norepinephrine, epinephrine, serotonin, and melatonin.
I take it that for treating depression St John’s Wort shouldn’t be used with NooCube?
Each NooCube capsule contains:
Alpha GPC
Cat’s Claw
Oat Straw
Huperzine A
Bacopa Monnieri
L-Theanine
L-Tyrosine
Becky, the biggest concern with St. John’s wort is Serotonin Syndrome. Please see this section of my St. John’s wort review here > https://nootropicsexpert.com/st-johns-wort/#st-johns-wort-and-serotonin-syndrome
If you are not using any other prescription medication, St. John’s wort ‘may’ be safe with NooCube. I say “may be safe” because I do not know how much of each nootropic is used in the NooCube formula. I could not find the exact dosage of each ingredient. So there is no way to tell if the nootropics in their formula that boost serotonin increase it to unsafe levels when combined with St. John’s wort.
Hi David – Researching the best nootropics for what I need has proven to be confusing and exhausting as I continually read conflicting information on blogs and ‘authoritative’ sources.
I’m wondering about hordenine and if there is a reason it wasn’t included on your above list? It apparently acts as an MAO inhibitor. I have been taking SSRI’s for many years with some benefit in mood but I have seen the most helpful affects from meds that increase dopamine (for motivation) so I’m looking for nootropics that help with either increasing production or inhibiting breakdown, of dopamine – I’m not sure which action is best at this point.
Thank you for any help.
Hordenine is on my list and haven’t gotten to it yet. If you are looking for monoamine oxidase inhibitors, please see the individual review for Methylene Blue, Rhodiola Rosea, Ginkgo Biloba, Berberine, Oat Straw and Turmeric (curcumin) which are, or act as MAOI’s.
You can also boost dopamine by using NALT or Mucuna Pruriens.
Each of us responds differently to the nootropics I’ve listed here. The key is experimenting one by one until you find the one, two or three that work best for you. The best approach is usually building a small nootropic stack for something like catecholamine-based depression.
Last suggestion is click on the “Blog” link above in the menu and scan down the list of posts. Most of them either have a recommended stack or several suggestions on what to try.
Hi Sir
Can i use tianeptine with St john’s wort. As tianeptine is not a an SSRI and is not a classical TCA antidepressant
Japneet, I highly recommend that you NOT combine St. John’s wort with tianeptine. The potential is irregular heart beat or heart attack. With the possibility of convulsions, hyperthermia and death.
Hi sir,
It’s 3 years that I suffer from IBS and 2 years I’m suffering from severe depression and generalized anxiety. I’ve tried SSRI’s but i’ve immediately stopped because they worsen my IBS symptoms. So i am very interested in using nootropics like ashwagandha,ginseng,bacopa,rhodiola ecc.. Could you please tell me what would be the best combination and does exist any supplement whith good organic combination of these adaptogens?? Thank you
Ted, I’m not aware of a combination of these herbs specifically for depression. And even it there was I wouldn’t trust it until you find out what works for you. You know your body better than anyone. So I suggest you carefully read each review and see if anything resonates with you. Find a trusted brand and try them one at a time. That is the only way to isolate and find out what works for you without side effects.
Once you read through each review, find that supplement on a site like Amazon that has a lot of reviews and read through them. You’ll be amazed what may turn up with someone dealing with issues similar to yours sharing how it worked for them.
I realize this will take time and effort. But you need to put the time and investment in if you want to get better. It took me 3 years of experimenting until I felt better. So know what you are going through to a certain extent.
thank you sir
Hi, I really appreciate the list of nootropics, but how do I get them all and in what dosages? Is the one pill that has them all (in the right dosage)? I would like to try them and go the natural way an=bout depression but nothing sofar has worked or not consistently.
What do you suggest?
Thanks, Gabriella
Gabriella, unlike what the big pharmaceuticals would like us to believe, there is no “one pill” solution. And it’s not possible to create an effective nootropic stack for depression because there are so many potential causes.
I recommend reading this post again and see if anything resonates with you. Is your depression caused by problems with dopamine, or serotonin, or inflammation? I realize there is no way to tell for sure. So to get started you’ll have to experiment with various nootropic supplements until you find the ones that work for you.
Each nootropic mentioned in this post has a live link through to a complete review of that supplement. Including recommended dosages, side effects, prescription drug interactions and more.
Start with the basics like magnesium and the B-Vitamins. And try one or two supplements like Bacopa Monnieri, Mucuna Pruriens or Kava. Other than the basic vitamins and minerals, try only one or two at a time. Because if you find something that makes you feel better, you’ll want to know what is providing that effect. Which is difficult to do when you are using too many supplements at once.
Have you looked into kratom? do you have any experience or opinion on this plant?
Robert, I’ve several years of experience with Kratom and use it daily for pain. My wife uses it for mood and sleep. Different strains work for different things and it takes a lot of trial and error to find what works.
Quality is also critical and finding the right vendor takes some doing. I just hope the American Kratom Association can convince the regulators to keep it legal in this country.
Hello David
I’m in a desperate way.. I came off psy drugs cold turkey 3 months ago after 20 years on them (drs did it as nothing helped anymore & I became intolerant), but I’m suffering massive suicidal depressive fluctuations, anxiety, confusion, panic attacks, mood swings, headaches, some times manic type stuff, blurred vision, sometimes anger.. I also have the sensation that the entire frontal lobe of my brain has gone numb/swollen/stopped functioning.. all this is accompanied with atrocious physical pains, constant cramps, nausea, chest pains & so much more.
I have no idea how much of all of this is protracted withdrawal symptoms which could take a year or a brain disfunction or something else.. all I know is I feel like I’m dying.. I’ve bought & tried so many supplements & products that it’s ridiculous.. but without guidance I don’t know what I’m doing, & may even be either worsening the problem, worsening withdrawal symptoms or even potentially putting my life into danger..
I even attempted taking an experimental drug called NSI-189 for 3 days but I think it made me worse & stopping it made me much much worse.. I’ve contacted drs, people, companies that sell me products, hospitals, er.. everyone.. I get different advice from different people..
Right now I stopped everything except omega 3 high does epa/dha content but it’s not helping much.. please, can I give you a list of everything I have by pm.. I’d really appreciate your advice as to what I should take, or not take & for how long.. It seems to much stimulants make me hyper/aggressive, notably to much seratonine..
to much of certain other neurotransmitters also worsen my anxiety & products that boost dopamine short term (for a few hours) have crash effects & thus make me more depressed & aggressive after a few hours.. in fact anything that has a short term effect makes me fluctuate worse..
Please help, I’m desperate & don’t know where to turn. Please contact me by email if this post is too long to be posted.. thank you.
Jason, first and I hate to tell you something you likely already know. You can’t quit taking antidepressant meds ‘cold turkey’ after prolonged use. Likely the best advice I can give you right now is contact Dr. Kelly Brogan (https://kellybroganmd.com/). She helps people titrate safely off of antidepressant and antianxiety meds. Abruptly quitting these types of medications is very dangerous.
I’m not a doctor and don’t even play one on TV. So please work with someone like Dr. Brogan and get at least somewhat stable again. And then we can start experimenting with nootropic supplements. And find the right stack for you.
Hi
I have bipolar and OCD.
I’ve been in a depressive state for some time now.
Tianeptine has worked wonders.
You have this long list above.
I have used some in the past.
Can you tell me the best ones on the list? The most sought after?
The strongest?
I know you may say that every person is different therefore I can’t tell you.
But please, what is the strongest and best besides Tianeptine which I love.
Tianeptine is just not doing enough right now.
There must be some that are especially good.
I am sort of desparate
What do you take, or what is the most common one, or most
common stack?
Phenibut does not work for me. Aniracetam not either.
Thank You for now.
Jon
Jon, if Tianeptine has worked for you the I suggest first learning everything you can about how it works in your brain. You can use this: https://en.wikipedia.org/wiki/Tianeptine. See the “Pharmacology” section.
Next, find nootropics that work on each of what Tianeptine does in your brain. Including boosting serotonin, BDNF, action on NMDA and AMPA receptors and boosting dopamine. I’m not aware of any nootropic that works directly on μ-opioid receptors.
This will take some work but you’ll end up with a nootropic stack that’s safer and you can use long-term without tolerance. This is not a “one pill” solution.
You should probably include selenium as a nootropic. I noticed decreased thoughts of suicide when I was taking it, and they came back when I stopped taking it. Thanks.
John, selenium is on my list of supplements to review. So thanks.
Hello David!
I’m new to the world of nootropics and I’m trying to treat depression and bipolar disorder without prescription medications.
I’m trying to achieve a more balanced and consistent life in regards to mood. For me, it is extreme ups and downs. The seesaw from one end to the other changes fast.
I strongly related to the following about serotonin:
When you have adequate serotonin levels in your brain and it’s working properly, you’ll be confident, easy-going, flexible, happy, and positive. (I admit, I’m the opposite of all of these things when I am “down” and boardline arrogant when I’m “up”. I wish I realized all of this about myself sooner, but I always blamed a current situation and am now seeing the long term pattern.)
Serotonin deficiency can result in you becoming depressed, irritable, obsessive, negative and worried.
This list is extensive and has a lot of great effects for each nootropic. I wish I could take them all because they all seem to help brain function in one way or another, but I doubt that would be sensible or even affordable for me, so how do I break these 12 down into a stack that I should take?
– Which ones work best when combined?
– Which one(s) should I start with?
– How do I figure out which ones would work best for my symptoms?
Definitely try magnesium, lithium, selenium, and vitamin D, plus whatever else David might suggest.
Michael, it’s a great question but also highlights why it is so difficult to recommend a nootropic stack for something like depression. Because it often takes a lot of experimenting until you hit the sweet spot for you.
I’d suggest starting with the basics including the vitamins and minerals mentioned in this post. At the dosage recommendations in the original review for each of these. Not on this list but often works well for mood disorders is Lithium Orotate: https://nootropicsexpert.com/lithium-orotate/
Then add something to boost serotonin, dopamine and acetylcholine. That could include L-Tryptophan (serotonin), L-Tyrosine (dopamine) and CDP-Choline (acetylcholine).
For now, you don’t know exactly what’s going on in your brain. But with this stack, if you start to see improvements then you’ll know you’re on the right track. If you find some symptoms are less but you’re more irritable for example, then you may have too much norepinephrine. So you’d cut back on the L-Tyrosine. In other words, listen to your body for the subtle differences. Instead of using a broad stroke like “depression”.
I’d also consider adding an adaptogen which works to help balance things out in your brain. Bacopa may be a good one to try.
Thank you so much for getting back to me!
You are honestly awesome for being here to answer questions like mine. Thank you so much for taking the time out of your day to do this.
I will let you know how things work out!
After a while of taking my stack, I’ve been doing great in terms of mood balance and depression management. So thank you! This stuff really does work. I’m taking:
– L-Tyrosine
– L-Tryptophan
– CDP-Choline
– Bacopa
– Magnesium L-Threonate
– Fish Oil
– Taurine
– Vit D
– B-Complex
– Occasional L-theanine and Caffeine
However, I’m having a problem 2-5pm with sluggishness. My mind is alert and energized, but my body and muscles ache and feel tired. I haven’t found a way to prevent this yet. I take my stack in the morning, and some of again them before bed.
I’m thinking of taking something in the afternoon to prevent a crash, but I’m unsure what I should use. Acetyl L-Carnitine perhaps?
Michael, I’d split your dose of the entire stack so you take half in the morning and half again at noon. But make sure your dosages are high enough and based on the recommended dosage in each nootropic review here on Nootropic Expert.
Then at noon I’d add ALCAR, L-Tyrosine (or NALT) and try your L-Theanine+caffeine stack either at noon or mid-afternoon.
Magnesium however should be taken about 90 mins. before bed.
*thumbs up* I would’ve done this, but my pills are higher mg, so next time I buy them I will get smaller. 🙂
Hello David
Is there any place in Europe where i can buy Aniracetam?
I can only find it in US, and with tax, costum and shipping to Denmark. Makes it impossible
Regards
Johnny Haugaard
Johnny, regulations seem to vary from country to country within the EU. But I didn’t come across anything specifically mentioning Aniracetam in my research. Please let us know what you find out.
Hi Johnny,
I bought mine on ebay.
Hello, I have come across your site when researching a supplement I am taking and have been on it for hours reading all the great information. I have been searching for years for the right information to help my situation and hopeful this is it.
I am 49 year old, female and have a long history of depression and ADD. I was even possibly diagnosed with Bipolar II as well in the past. I have tried a few different antidepressants, but never really stick with them for the side effects. I even caused myself some harm with taking Wellbutrim and 5htp which gave me a seizure. Although upon more examination with EEG’s a underlying seizure disorder may have always been there and my history of frequent falls may have had an answer. I was put on Depakote for about 2 years until I was tired of the weight gain and other side effects. My EEGs were normal and was weaned off the depakote – that was 2010.
I recently tried Prozac but started to gain weight again and it did not seem like it worked as well as it did in the past.
At the present I have been trying several supplements and lot of them you have mentioned. This is what I am using. I still try and through 5 htp in with this mix, not sure why I keep trying this – but I guess I keep hoping it will help.
In AM:
DL- Phenylalanine 750mg
L tyrosine 500mg
B6 100mg
Vitamin B complex Total 460mg By Nutricost
Contains Vit C, B1, B2,B3, B6, B9, B12 Methyl and B7, Inositol, Choline Bitartrate
5htp 100mg – some days
After Breakfast:
Theanine Serene with relora – GABA 500mg, Taurine 450mg, L theanine 200mg, Holy Basil leaf extract 100mg
Korean Ginseng 300mg + Ginko Biloba 160mg
Vitamin C 1000mg
Vitamin D3 5000IU
At bedtime:
GABA Soothe – GABA 100mg, theanine 100mg, Sensoril (ashwaganda) 225mg
L tryptophan 1000mg
Magnesium Glycinate chelated 400mg
At times, though I hate to, I add a nighttime allergy with chlorpheniramine and phenylephrine because my boyfriends snoring messes with my sleep.
So hoping you can see my regimen and give some tips.
Suzanne, so far it looks like you are on the right track. How are these stacks working for you and what still needs improvement?
Hi David,
I guess finding the right Nootropic for depression depends on the cause of the depression. I’ve tried many anti depressants, most did not work with the expextion of Effexor which as you know Is an SNRI.
Which Nootropics would you say have a similar function in the brain as an SNRI?
Thanks for all your help!
Michael, this is the mechanism of action for Effexor: https://en.wikipedia.org/wiki/Venlafaxine#Mechanism_of_action
So it appears that it boosts levels of serotonin AND norepinephrine in the brain. At higher dosages it also appears to boost dopamine to some extent.
The goal here is to find nootropic that boost serotonin and norepinephrine (NE). Serotonin is easy because you can try L-Tryptophan, low doses of 5-HTP and if you’re careful possibly St. John’s wort.
Norepinephrine is a bit of a challenge because it’s a step up from dopamine. So you could try boosting dopamine with Mucuna Pruriens or L-Tyrosine and hope for the best. See if they work. Otherwise, spend some time searching Nootropics Expert for all the nootropics that positively affect norepinephrine. Valerian comes to mind. And I’m sure you’ll find others.
This will likely take a combo of 4 – 5 nootropics to achieve what you are looking for. And plenty of trial and error.
have you seen Lions mane mushroom interact with zoloft….or i guess any anti depressants?
Jonathan, I haven’t come across any reported interactions with Lion’s Mane and anything including prescription antidepressants. Not to say there aren’t any. Just haven’t seen any.
Hi,
I can’t find the studies you cited, when I click them it just reopens the same page.
Also, I have 2 fundamental questions:
1. In your opinion, is there currently any nootropic on the market that actually raises IQ (however minor)?
2. Depression is sometimes described as brain damage due to chronically elevated Cortisol levels. In your opinion are there nootropics capable of repairing said (theoretical) damage?
Mike, for the studies you click on the Roman numeral next to the end of the sentence describing the study. And that click should take you down the the REFERENCES section under the review or page. Each clinical study has (source) which is a live link to the study. I just checked the ‘click’ and it seems to be working. If it isn’t for you then try updating your browser or try a different browser.
I know that L-Tyrosine has been shown to affect IQ. And there are others that I can’t think of off the top. The search function for the keyword “IQ” doesn’t seem to be working very well. I’ll have my developer look into it.
Elevated cortisol levels are associated with stress and inflammation. Several nootropics specifically address inflammation. And as I recall, a couple of them help lower cortisol levels. Bacopa Monnieri is one of them. A search for “cortisol” does work so check the search function please.
Hi David,
thanks for the very quick reply. After trying to click the source once more it finally worked. I like to check the studies myself, as sometimes the methodology isn’t great (small sample size, no control group etc.).
I wasn’t referring to Cortisol by itself, rather to the consequence of chronically elevated levels. Nevertheless, I’ll try and see what the search function brings to light.
Thanks for your reply.
Mike, check out this post for ideas > https://nootropicsexpert.com/best-nootropics-for-social-anxiety/
And this one > https://nootropicsexpert.com/top-7-nootropic-adaptogens-to-conquer-anxiety-and-stress/
Seems Ashwagandha, Gotu Kola and Lion’s Mane fit the bill. I’m already taking Bacopa, Uridine MP, Alpha GPC, Huperzine A and Ginkgo.
I’ve ordered Ashwagandha, will see how that will do. I ordered the most potent – KSM-66.
What do you reckon has the most lasting / permanent effects in terms of neurogenisis and neuronal repair? Is there a point where you reckon one can “stop” taking nootropics? After all, it is a bit pricey to keep restocking and consuming all these drugs.
On a different topic, I’ve also ordered mugwort tea. Have you ever tried it? I’ve tried Gelantamine for lucid dreaming, but it didn’t work. I’m hoping mugwort tea might work. Obviously flying and things like that are fun things to do, but I’m mainly interested in lucid dreaming as people have reported that it may help in resolving psychological issues. I’m also interested in learning during a lucid dream. But so far I’ve had zero success. Your input would be greatly appreciated.
Mike, I’ve had the most lucid dreams when using Methylene Blue. Sorry, but do not have any experience with mugwort tea.
The nootropic stack you are using which includes Lion’s Mane will have the most lasting and permanent effects on neurogenesis and brain repair. I hear you loud and clear on cost. But my experience has been I cannot afford to stop using the ALL of the stack that I am using now.
I’ve become so in-tune with how this brain and body work that if I run out of something and don’t use it for a week I can feel it. And I don’t like it.
The thing about nootropics is you can always stop using them. And for most with no withdrawal or side effects. But boy does it suck going back to feeling like you used to.
Study I’m referring to re: number 2 here:
https://developingchild.harvard.edu/wp-content/uploads/2005/05/Stress_Disrupts_Architecture_Developing_Brain-1.pdf
“Sustained activation of the stress response system
can lead to impairments in learning, memory,
and the ability to regulate certain stress
responses. In both young and adult animals,
high, sustained levels of cortisol or corticotropin-releasing
hormone (CRH), which is the brain chemical that regulates the HPA system,
result in damage to a part of the brain called the
hippocampus. This area of the brain is critical
to both learning and memory as well as to some
types of stress response regulation.