What are Nootropics?

The term nootropics refers to a wide range of artificial and natural compounds which are thought to enhance cognitive function.

How Do Nootropics Work?

Nootropics are thought to work by modulating neuronal metabolism, cerebral oxygenation, neurotransmitter availability, increasing neurotrophic factors and by affecting other cellular processes. The exact mechanism of action will depend on the compound.

Common Myths

Myth 1: Adderall is a potent cognitive enhancer.

Adderall has powerful effects on mood and motivation, but its cognitive effects appear to be small and it may actually impair already high-performing individuals on complex cognitive tasks.[1][231]

Myth 2: Nootropics are like NZT-48 from the movie Limitless

Nootropics are much less powerful than what’s depicted in the movie. They may give you an edge. They won’t completely change your life.

Considerations

Hazards

Our bodies are complex and unique, as such you can’t predict with certainty that you won’t have an adverse reaction to any particular compound. Many new and exotic compounds are not known to be safe or well-tolerated, their use confers unknown but significant risk.

Uncertainties increase when stacking multiple compounds. Each stack confers a certain level of risk. While the risk associated with an average stack may not be great, the risk associated with the practice of regularly making yourself a guinea pig for new stacks could very well be great.

The long-term risks associated with taking cognitive enhancing drugs are also mostly unknown. Some drugs have longer histories of use than others. And some drugs may end up actually being protective or health-promoting. But the safety of taking new compounds long-term can’t be guaranteed.

The uncertainties are even greater with children and young adults, since brains aren’t considered mature until about the age of twenty five.[140] It’s generally recommended for children and young adults to focus on getting enough sleep, exercising and maintaining a healthy nutrient-dense diet.

It should be assumed that nootropic herbs and drugs are NOT safe during pregnancy, there exists evidence that certain herbal compounds like vincpocetine may cause miscarriages. Be conservative and talk to your doctor before taking herbs and drugs while pregnant.

Excessive manipulation of neurotransmitter systems can lead to various unpleasant pathologies including serotonin syndrome, depression, anxiety and stimulant psychosis.[141][142][143]

Some compounds may interact with the metabolism of other drugs. This could adversely affect the safety and effectiveness of certain treatments.[144]

Some compounds can cause down-regulation and withdrawal symptoms when they’ve been taken regularly or at high-doses.[145]

Mood-lifting and dopaminergic compounds may make some people manic.[146][147][148]

Certain compounds may interfere with the quality of your sleep, especially when they’re taken at night. Not getting enough sleep can have a large impact on your health, cognitive function and mood. Sleep deprivation has also been known to induce mania in susceptible individuals.[235][236]

Mixing MAO (MAO-A) inhibitors with tyrosine supplements or foods containing tyramine, can cause serious hypertensive side effects, dubbed the “cheese effect”.[149]

If you’re measuring powders, you need a scale. User error could lead to the unintentional ingestion of dangerous or potentially lethal doses of a drug or supplement.

If accessible, a child could ingest a dangerous and potentially lethal dose of a drug or supplement.

Manufacturers of bulk powder from Alibaba and similar sites have a history of passing off inauthentic products, many suppliers use them. The risk of inauthentic product is especially high with new and exotic substances. Look for non-manufacturer certificates of analysis (COAs). Note: LabDoor supplement ratings should not be considered reliable. They don’t post their actual testing results and they have been found promoting products which were completely inauthentic.

One study have found that certain plant-based supplements including bacopa monnieri may contain concerning levels of specific mycotoxins.[222] It may be important to look for reputable sources that test for mycotoxin contamination.

The chemical structure of drug impurities are often unknown. It’s possible that some of these new or unknown impurities may turn out to be harmful.

Although we believe the companies on the reliable suppliers list are trustworthy and capable of good quality control, it’s always possible for there to be slip ups. You can reduce the possible consequences of mix ups by starting with small doses before working your way up to the standard dose.

Some people may be inclined to use nootropics to mask physical symptoms like chronic sleepiness and fatigue, which runs the risk of overlooking an underlying pathology. It’s a good idea to get checked out by a trained professional when you may be displaying symptoms of a disease or condition.

Nootropics can do certain things, but they can’t automatically make you a whole well-rounded human being. Neglecting more important life factors can make you worse off in the end. Nootropics are not a substitute for basic human needs, like exercise, sunlight, social engagement, sleep and a good diet.

The Lowest Hanging Fruit

Jog to the park

Exercise seems to have physical, psychological and cognitive benefits. A 2013 Cochrane review found exercise seems to reduce symptoms of depression.[2] At the same time aerobic exercise seems to also enhance executive function and memory.[3] Given the minimal side-effects and well documented health benefits, exercise should be considered before other interventions.

Routinely get enough sleep

Sleep is essential for good cognitive function.[4] Yet, many of us don’t sleep enough. Trouble getting to sleep on time can often be remedied by simply taking 0.5mg of melatonin, the sleep hormone, thirty minutes before you should go to bed or by reducing the intensity of light you’re exposed to at night. Exposure to high intensity light is known to suppress natural melatonin production.[5]

It’s also critically important to get bright light in the morning. This resets your circadian rhythm so your body functions properly during the day. Not getting sunlight or a similarly intense artificial light in the morning can cause depression-like symptoms and delay sleep onset. [220][221]

Blue Light

Our bodies have evolved to use blue light (~480nm) as a signal that it’s daytime.[239] Blue light is a key master regulator of our circadian rhythm and wakefulness. Blue light, in addition to repressing melatonin levels also increases our metabolic rate and alertness.[240][241] Exposure to blue light seems to have significant cognitive effects. In randomized controlled trials bright blue light seems to be able to improve attention, working memory, verbal memory and mood.[241][242][243][244][245][246][247][248] Blue light in combination with caffeine seems to increase alertness and mood more than caffeine alone.[241][243] Interestingly, blue exposure during the day actually seems to increase sleep quality.[247] Whereas blue light exposure at night has the opposite effect. The current theory for blue light’s cognitive effects has to do with ultimately increasing norepinephrine release, which is associated with alertness and mood, but it’s a complex process that may involve other important factors including the modulation of orexin (hypocretin) neurons. Blue light seems to have positive effects at intensities as low as 40 lux (which is function of the distance and the intensity of a light source), but lower intensities are not as fast acting as higher intensities of blue light. Given its low risk profile and the substantial benefits, blue light devices should be considered a cognitive enhancer with one of the best risk to reward ratios.

Standard Dose: 40-200+ lux of blue light (~480±20nm) for 10-60 minutes in the morning.

Reliable Suppliers

Devices

Philips goLITE BLU is commercially available and was used in at least several studies.[242][245] Another study used a commercially available blue LED bulbs like the Techlight® RGB, which has a blue wavelength of around 470nm. Any source of blue light at ~480±20nm that can achieve greater than 40 lux at a comfortable distance should be effective.

Side effects

May trigger mania in predisposed individuals

How should I decide what’s right for me?

First you should have in mind a target you want to improve. From there it’s good to review the relevant research to see what nootropics are thought to improve that area and of those which ones have a history of safe use. Here’s a condensed list for common goals:

Substances

Herbs and Plant derived compounds

L-Theanine

Summary

L-Theanine is one of the main psychoactive compounds found in tea. L-theanine is extremely safe and has been shown to mitigate the negative aspects of caffeine, such as anxiety, increased blood pressure and diminished sleep quality, while possibly improving upon the positive aspects.[83][84][85][223] Its ability to enhance attention has been repeatedly verified.[6][7][8][9][10][11][223] A recent systematic review of the effects of l-theanine and caffeine has confirmed that the combination seems to improve aspects of attention. [169] The combination of L-theanine and caffeine may improve attention more than caffeine alone.[6][7] L-theanine alone has been shown to boost alpha brain waves, a pattern of brain activity correlated with relaxed attention. [106] L-theanine seems to increase brain concentrations of serotonin, dopamine and GABA.[249] In one recent animal study l-theanine consumption was associated with about a 25% increase in BDNF and about a 100% increase in NGF in the hippocampus[170] L-theanine taken with caffeine is one of the most reliable and safe nootropic stacks for improving focus.

Standard Dose: 200mg L-theanine with 100mg caffeine (Note: an easy and cheap way to get 100mg of caffeine is to break 200mg no-doz or similar tablets in half.)

Reliable Suppliers

Side effects

Headaches

Questions

Does L-theanine help anxiety?

L-theanine is a mild anxiety reducer. For many people L-theanine will provide adequate anxiety reduction and relaxation. But for people with severe anxiety it’s unlikely to be enough on its own.

How often can I take L-Theanine without building a tolerance?

Indefinitely. L-theanine does not seem to build tolerance.

Does L-theanine worsen your anxiety once you stop taking it?

There isn’t any good research to say either way. Anecdotally it does not seem to make anxiety noticeably worse. If there are rebound effects they’re likely to be mild and transient.

Will L-theanine break down if I put it in a hot liquid?

No. L-theanine can be put into boiling hot water without degrading.

Does L-theanine need to be taken with caffeine?

No. But for people without anxiety issues, the nootropic value will likely greatly diminish in the absence of a stimulant like caffeine.

Which L-theanine brand is best on amazon?

Now Foods, Doctor’s Best and Jarrow are all good brands for L-theanine in capsule form. Liftmode also has a good reputation, but they sell L-theanine in powder form.

Are all “L-theanine” preparations the same?

If it says 100% L-theanine and it’s from a reputable brand with an independent CoA it’s likely to be virtually identical to other brands.

Can I just take green tea extract for L-theanine?

Green tea extract is usually standardized for its catechin content. It’s usually hard to tell exactly how much L-theanine you will be taking.

Is L-Theanine physically addictive?

No. L-theanine doesn’t show any addictive potential.

Should I still take caffeine with L-theanine if I have general anxiety?

There probably isn’t a good one size fits all answer here. It’s probably best to experiment with both. There’s reason to think people with higher levels of anxiety don’t need to add caffeine, though.

How long does L-theanine take to kick in?

About 30 minutes.

Bacopa Monnieri

Summary

Bacopa Monnieri is an herb which has been used in Ayurvedic medicine for centuries. It’s currently one of the most well tested nootropics. A 2012 review of 6 trials on Bacopa Monnieri noted large and statistically significant memory enhancing effects in older adults.[27][28] Bacopa’s primary mechanism of action is still unclear, it seems be an anti-oxidant, a weak acetylcholinesterase inhibitor and a cerebral blood flow activator.[29] In animal models, Bacopa Monnieri seems to increase cortical concentrations of acetylcholine, dopamine and serotonin.[197] Bacopa Monnieri is likely to be one of the safest and most effective memory enhancers for older adults.

Standard Dose: 300mg assuming 50% bacosides once in the morning or 750mg assuming 20% bacosides

(Note: Bacopa Monnieri’s memory enhancing effects appear with long-term continuous use, 8 weeks is a good minimum trial period)

Warnings

Bacopa Monnieri may alter the metabolism of certain drugs by changing the activities of CYP3A4, CYP2C9 and CYP2C19.[232] This may reduce the safety and effectiveness of other drugs you are taking. Talk to your doctor if you’re on any prescription medications.

Reliable Suppliers

Side Effects

Nausea, cramps, drowsiness, muscular fatigue, lethargy

Questions

Should I take bacopa in the morning or at night?

Typically it’s taken in the morning. However, people who experience drowsiness with bacopa may want to consider taking it later in the day.

What Bacopa extract should I look for?

The general consensus from user reports is that Synapsa/KeenMind is the best Bacopa Monnieri extract. It’s also the extract with the most human research.

Caffeine

Summary

Caffeine is the most popular and well known psychoactive drug. It’s commonly found in coffee, tea, energy drinks, soft drinks and even chocolate. Caffeine seems to have acute cognitive effects. It seems to be able to consistently increase alertness and attention. But whether these effects go away with regular use is still a matter of debate.[117][118][119] Caffeine exerts its effects by blocking adenosine receptors A1 and A2A. [120] The effects from the blockade of A1 receptors seems to deminish with chronic exposure, but there may be residual effects that are mediated through A2A receptors. [121] Routine moderate caffeine consumption seems to be associated with many positive outcomes including a decreased risk of parkinson’s disease, alzheimer’s disease, depression, cardiovascular disease and strokes. [122][123][124][125][126][127] Interestingly, in one study there seemed to be a relationship between extroverted personalities, caffeine intake and enhanced performance on challenging working memory tasks.[128]

Standard dose: 50-200mg caffeine

Reliable Suppliers

Possible Interactions

In patients with Parkinson’s disease, creatine intake and high caffeine use (>300mg per day) was associated faster progression of the disease as measured by the Unified Parkinson’s disease rating scale. [207] A later study indicates the involvement of a genetic mediator, the GRIN2A T allele, in this association.[237]

Side effects

Anxiety, mania, headaches, nausea, increased blood pressure

Warning

Caffeine has a relatively low lethal dose, it may be around a few grams for some people. [74][75] If you plan on buying purified caffeine then pills are recommended. They’re extremely cheap, convenient and safe. Powder is slightly cheaper, but it’s harder to use and carries a significant risk of human error when dosing.

Curcumin

Summary

Curcumin is a bright yellow polyphenol derived from turmeric. Curcumin has a long history of medicinal use in China and India. Today, curcumin is being widely studied as a therapeutic agent for diseases ranging from cancer to alzheimer’s disease. Some curcumin formulations seem to improve aspects of cognitive function in healthy older adults.[208] In animal studies curcumin seems to have an antidepressant effect, which may be caused by increased hippocampal neurogenesis. [213][214][215][216] Curcumin possesses anti-inflammatory, anti-diabetic and antioxidant properties, each of which could substantially mediate its positive effects in alzheimer’s model animals as well as healthy older populations. [209][210][211][212]

When curcumin is absorbed it is rapidly converted to curcumin glucuronide and sulfate conjugates.[217] These conjugates may have peripheral effects, but they will likely have a hard time crossing the blood brain barrier. The bioavailability of curcumin can be significantly increased by inhibiting the formation of curcumin conjugates with a substance like piperine. In one study on human volunteers curcumin bioavailability was increased 2000% with the coadministration of piperine. [218] Longvida, a solid lipid curcumin particle formulation seems to also substantially avoid the conjugation issue. 650 mg of Longvida alone seems to produce and sustain about twice the amount of free curcumin as 2 grams of curcumin with 20 milligrams of piperine.[219] Positive effects on working memory, alertness and mood have been noted in healthy older adults taking 400mg of Longvida.[208]

Standard dose: 400mg Longvida™ (solid lipid curcumin particle formulation)

Reliable Suppliers

Possible interactions

Curcumin may inhibit cytochrome P450 2C9, which could alter the safety and efficacy of other drugs.

Piperine may alter the safety and efficacy of other drugs by altering their metabolism.

Side effects

Gastrointestinal upset, chest tightness, swollen skin, yellow stool, rashes, headache

Ashwagandha

Summary

Ashwagandha is an herb from India with a history of use of over 3000 years. Ashwagandha seems to be a reliable anxiolytic (anxiety reducer).[89][90] Ashwagandha may also increase aspects of attention, but there’s only preliminary evidence here.[91] Ashwagandha’s mechanism of action isn’t entirely clear. Ashwagandha seems to have GABA-mimetic activity, which may account for its anxiolytic effects.[92] Withaferin A, a major active constituent, seems to be a fairly powerful anti-inflammatory agent.[93] Ashwagandha may also improve subclinical hypothyroidism as well as worsen hyperthyroidism. [238]

Warnings

Ashwagandha may cause liver injury in some cases. [271] To limit risk ask your doctor before taking ashwagandha and do no mix ashwagandha with other supplements or alcohol.

Ashwagandha may increase thyroid hormones and cause or worsen hyperthroidism.

Standard Dose: 300mg Ashwagandha root extract standardized to ~5% withanolides

Questions

Does ashwagandha cause withdrawal symptoms when discontinued?

Ashwagandha does not appear to cause withdrawal symptoms.[107]

Rhodiola rosea

Summary

Rhodiola rosea is a plant with a long history of medicinal use in Europe and Asia. There’s some evidence to suggest Rhodiola rosea, reduces mental fatigue, physical fatigue and symptoms of depression.[30][31][32][227] Rhodiola rosea reduces stress induced excretion of cortisol and may inhibit AChE and MAO.[33][34] Rhodiola rosea does not seem to improve cognitive function outside of reducing mental fatigue.[228] Users commonly report acute stimulant-like effects when trying rhodiola rosea for the first time. Those stimulant-like effects may diminish with long-term use.

Standard Dose: 350mg once in the morning (assuming 3% rosavins and 1% salidrosides)

Reliable Suppliers

St. John’s Wort

Summary

St. John’s Wort (Hypericum perforatum) is an herbal anti-depressant and mood enhancer. Its main active constituent seems to be Hyperforin, which seems to inhibits the uptake of serotonin, norepinephrine, dopamine and GABA.[35][155][156] A 2008 Systematic review concluded St. John’s wort seems to have similar efficacy to more traditional anti-depressants with few side effects.[36] St. John’s wort doesn’t seem to help or harm cognitive function in otherwise healthy individuals.[37]

Standard Dose: 300mg thrice daily

(extracts can vary, clinical trials were often performed with an extract standardized to contain 0.5% hyperforin)

Warnings

St. John wort is thought to be a photosensitizer, it may increase damage caused by high-intensity light leading to the development of impaired vision or cataracts. Appropriate precautions should be taken to protect the eye from intense sunlight while using st. John’s wort.[79]

St. John wort may alter the metabolism of certain drugs by altering the activity of cytochrome P450.[80] This may reduce the safety and effectiveness of other drugs you are taking. Talk to your doctor if you’re on any prescription medications.

St. John wort may cause serotonin syndrome when its taken in conjunction with other drugs, including SSRIs, SNRIs and triptans. [[266]]

Reliable Suppliers

Kava

Summary

Kava is a natural anxiolytic produced from the root of Piper methysticum. It’s use goes back thousands of years in the south Pacific. A systematic review of studies found Kava could effectively mitigate anxiety to a greater extent than placebo, with few adverse effects.[38] Kava doesn’t seem to have short-term tolerance issues greater than placebo, about 25% of placebo and kava users will want to increase their dose.[39] At low therapeutic doses kava doesn’t seem to impair cognitive function and it may actually enhance some aspects of attention.[40] Kava may also have beneficial effects on female sexual function, though this could be caused by reduced anxiety.[39]

There have been reports of kava induced liver toxicity, which led the EU, UK and Canada to put restrictions on kava. However, a direct link between liver toxicity and kava use seems to be extremely rare. In most cases there were other probable contributing factors, such as use of other medications, high alcohol consumption and medical conditions.[41] Caution should be used when taking kava. Make sure the preparation is from a company with a great reputation and derived from the root of the plant. Don’t use kava if you have any liver conditions, consume alcohol frequently or are taking other medications. The safety of long term kava use hasn’t been rigorously confirmed.

Standard Dose: 400mg of kava with %30 kavalactones (the active ingredients) once or twice a day.

Reliable Suppliers

Side effects

Drowsiness, liver toxicity

Dopamine Modulators

There appears to be an inverted U-shaped dose-response relationship between dopamine levels and working memory performance.[12] In practice this means already high-performers are less likely to benefit from dopaminergics, like methylphenidate, amphetamines and modafinil, and are more likely to have their performance impaired. Altering dopamine levels is powerful, unfortunately it’s not always clear whether you’ll benefit or be harmed.

For women optimal dopamine levels may be more inconsistent. Higher estrogen levels seem to increase dopamine synthesis and estrogen levels seem to fluctuate during the menstrual cycle.[13] For women not on birth control, there’s increase in estrogen before ovulation. This increase in estrogen seems to affect working memory performance, but how performance is affected seems to be dependent on baseline dopamine levels.[14][15]

Methylphenidate

Summary

Methylphenidate (Ritalin, Concerta) is primarily a norepinephrine-dopamine reuptake inhibitor. Norepinephrine-dopamine reuptake inhibition effectively increases the levels of norepinephrine and dopamine in the brain. Although methylphenidate an effective ADHD drug its cognitive effect don’t appear to be limited to individuals with ADHD. Methylphenidate has also been shown to be a memory enhancer for otherwise healthy people.[50][82] Methylphenidate can easily be abused.

Standard Dose: 20mg once in the morning

Side effects

Nausea, anxiety, irritability, insomnia, depressed mood, loss of appetite, increased blood pressure, palpitations

Mixed Amphetamine Salts

Summary

Adderall is a norepinephrine-dopamine reuptake inhibitor and releaser. Adderall can enhance or impair aspects of cognitive function depending it seems on one’s baseline performance. Adderall will tend to impair already high-performers but will bolster low-performers. Interestingly people seem to be fairly bad at determinely whether they’re performing better or worse because of Adderall.[1] Adderall can easily be abused.

Standard Dose: 10mg once in the morning

Side Effects

Mood changes, loss of appetite, euphoria, racing heart, increased blood pressure, palpitations, insomnia, paranoia, mania, irritability, anxiety, possible neurotoxicity, tolerance

L-Deprenyl

Summary

L-deprenyl (Selegiline) is a potent MAO-B inhibitor with a long history of use as a treatment for Parkinson’s disease. [129] As a MAO-B inhibitor L-deprenyl works to increase levels of dopamine and phenethylamine in the brain. In some animal studies L-deprenyl administration was associated with improved learning. [130] However, L-Deprenyl’s performance enhancing effects seem to be much more equivocal in humans. At least one study suggests L-Deprenyl may actually decrease performance.[201] L-Deprenyl has affinity for MAO type B inhibition at lower doses, which means usual dietary restrictions on tyramine and its precursor tyrosine may not apply. At higher doses above 10 mg L-deprenyl may lose its selectivity and begin to inhibit MOA-A, at this point it would be prudent to follow standard MAO-I dietary restrictions. [131] Although therapeutic doses of L-deprenyl are unlikely to cause a hypertensive crisis, they can still increase blood pressure when co-administered with tyramine. [132] The primary metabolites of L-deprenyl are l-methamphetamine, l-amphetamine and N-desmethylselegiline, so L-deprenyl use could be problematic for people who get drug tested. These metabolites are physiologically active, but the l-isomers of these amphetamines are much less potent than their commonly abused d-isomers and they do not give L-deprenyl a strong abuse potential. [133][134] L-Deprenyl use is generally not associated with significant side-effects or adverse reactions. Interestingly in some experiments L-deprenyl actually seemed to increase the life-span of some rodents.[135] In most countries L-deprenyl is a prescription only drug, but it’s usually not highly scheduled.

Standard dose: 5mg L-Deprenyl

Side effects

Dry mouth, insomnia, euphoria, increased libido, increased blood pressure

Warning

Female oral contraceptive may drastically increase the bioavailability of L-Deprenyl. This increased bioavailability may make the standard dose dangerous. [190]

Tyrosine

Summary

Tyrosine is a non-essential amino acid and a precursor to dopamine, epinephrine and norepinephrine. There is some evidence to suggest tyrosine supplementation can affect performance on working memory tasks under certain conditions, especially stress.[51][52][53][54] Tyrosine may enhance convergent creative thinking.[171] In one study tyrosine seemed to even ameliorate some of the detrimental effects of sleep deprivation on cognitive performance.[86] However, if tyrosine increases working memory performance by enhancing catacholamine levels the effect could easily be short-lived. Some animal studies have shown dopamine levels quickly return to baseline.[55]

Standard Dose: 2 grams on an empty stomach

Reliable Suppliers

Warning

Tyrosine is a precursor to tyramine and thus may be a significant risk for people using MAO inhibitors.

Nutrients

Creatine

Summary

Creatine acts as an energy buffer in the brain. It is converted into high-energy phosphocreatine in the body, which helps to create ATP. During times of activation the brain rapidly drains phosphocreatine to keep ATP levels constant.[19] Oral supplementation of creatine has been shown to increase brain creatine levels between 3.5-13.3% with the average being about 8%.[20] This additional buffer of energy may enhance performance on demanding tasks related to IQ.[21][88] For healthy young well-rested omnivores, creatine does not seem to enhance function in other domains.[22][23] For individuals who are sleep deprived creatine seems to consistently enhance executive function.[87] Although vegetarians and vegans seem to respond best to creatine supplementation, vegetarians and omnivores have comparable baseline brain creatine levels.[24][25] Creatine supplementation does not seem to affect levels of brain creatine or cognitive performance in children.[226]

Creatine Meta-analysis

Standard Dose: 5 grams once in the morning with plenty of water. To increase the saturation rate take 20 grams for the first week.

Reliable Suppliers

Possible Interactions

In patients with Parkinson’s disease, creatine intake and high caffeine use (>300mg per day) was associated faster progression of the disease as measured by the Unified Parkinson’s disease rating scale. [207]

Side Effects

Stomach pain, nausea, diarrhea, water retention

Questions

Do I need to take a special form of creatine?

No. Creatine monohydrate is likely to be just as good as any other form and it’s much less expensive.

CDP-choline

Summary

CDP-choline (Citicoline) is a highly bioavailable form of choline. Upon absorption CDP-choline it broken down into choline and cytidine. Cytidine is coverted in the brain to uridine phosphate, which is subsequently converted into cytidine triphosphate at the neuronal level. Its choline portion can be used to make acetylcholine, phosphatidylcholine and sphingomyelin. CDP-choline seems to increase brain glucose metabolism, ATP and phosphocreatine. [172][173] CDP-choline appears to increase the synthesis rate and release of dopamine in the striatum, possibly by stimulating tyrosine hydroxylase activity. [174][175][176] There’s evidence to suggest CDP-Choline may improve aspects of working memory and executive function for low performing young healthy individuals and aspects of attention for older people and adolescents generally.[189][57][203] For already high performing young people, CDP-choline may actually somewhat impair performance.[189] Systematic reviews have found evidence that CDP-choline helps to mitigate the memory and behavior disturbances associated with age-related cerebral disorders in the short and medium term.[179] CDP-choline seems to have an excellent safety profile and may very well be neuroprotective. [177][178]

Standard dose: 250-1000mg

Reliable Suppliers

Side effects

Anxiety, headache, leg swelling

Warning

Dietary choline can be turned into TMAO by gut bacteria. TMAO may be a factor in atherosclerosis through increasing platelet aggregation and thrombosis. [268] It’s still debatable how big of an issue TMAO is, given that fish contains a lot of TMAO and fish consumption isn’t associated with atherosclerosis. [270]

Alpha-GPC

Summary

Alpha-GPC (Choline alphoscerate) is a highly bioavailable choline source. Alpha-GPC is a product of lecithin commonly found in food and is a natural component of human breast milk. It’s also present in brain tissue as a product of phospholipid metabolism. After oral consumption, alpha-gpc is converted to phosphorylcholine which can increase acetylcholine synthesis and release.[180] By weight Alpha-GPC is likely the best acetylcholine precursor. However, alpha-GPC absorbs moisture in the air extremely rapidly, so dealing with 100% alpha-GPC powder is untenable. For that reason alpha-GPC is either pre-packaged into capsules or kept in a diluted form. No published researched suggests alpha-GPC can enhance cognitive function in otherwise healthy adults. Though, Alpha-GPC seems to score favorably when mitigating the negative effects of degenerative diseases like dementia.[181][182]

Standard dose: 100-1000mg

Reliable Suppliers

Side effects

Headache, confusion, dizziness, erythema, excitation, insomnia

Warning

Dietary choline can be turned into TMAO by gut bacteria. TMAO may be a factor in atherosclerosis through increasing platelet aggregation and thrombosis. [268] It’s still debatable how big of an issue TMAO is, given that fish contains a lot of TMAO and fish consumption isn’t associated with atherosclerosis. [270]

Acetyl-L-Carnitine

Summary

Acetyl-L-Carnitine is the acetylated form of carnitine, a naturally occurring amino acid derivative. Acetyl-L-Carnitine is produced in the body and is present in high levels in the brain.[260] Although acetyl-l-carnitine is most known for its effects on mitochondrial function and energy generation, it also has actions in the brain that go beyond that. Acetyl-L-Carnitine has been shown to modulate neurotrophic factors, like NGF and the neurotransmitter acetylecholine in animal models.[261][262][263][264] A 2014 meta-analysis found some evidence to suggest acetyl-l-carnitine may have anti-depressant effects similar to the traditional anti-depressant fluoxetine, the effects seems to be particularly apparent in older populations.[265] There’s some evidence to suggest acetyl-l-carnitine may be beneficial for people with mild cognitive impairment and mild Alzheimer’s disease.[26] There’s little evidence as of yet to suggest acetyl-l-carnitine is a cognitive enhancer in young healthy populations.

Standard dose: 1000 mg taken in the morning or afternoon after a meal

Reliable Suppliers

Side effects

Agitation, anxiety, nausea

Warning

Dietary carnitine can be turned into TMAO by gut bacteria. TMAO may be a factor in atherosclerosis through increasing platelet aggregation and thrombosis. [268][269] It’s still debatable how big of an issue TMAO is, given that fish contains a lot of TMAO and fish consumption isn’t associated with atherosclerosis. [270]

Omega-3 (EPA & DHA)

Summary

Both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may have roles to play in maintaining proper cognitive function. DHA is a major component in neuronal membranes accounting for a substantial fraction of the brain’s total weight. EPA isn’t abundant in the human brain, but it may have beneficial effects owing to it’s anti-inflammatory actions. Both EPA and DHA have anti-inflammatory as well as vasodilatory effects. DHA is also a precursor to NPD1, an anti-inflammatory and neuroprotective agent. [94]

EPA and DHA could be cognitive enhancers, but the evidence for that hypothesis is not strong. There have been some positive results published,[95][96] but there have also been many negative results. [97][98][98][100] For all the hype surrounding the cognitive effects of EPA and DHA the results have been underwhelming to date. It’s not at all clear that most healthy adults will cognitively benefit from supplementing EPA and DHA. Though there is some evidence that people who have a low dietary intake of DHA, may benefit from taking ~1200 mg of dha per day.[267]

EPA and DHA may however have synergistic effects with other compounds. There exists some evidence to suggest EPA & DHA paired with other important membrane precursors including choline and uridine monophosphate may increase synapse formation [101][102][103][104] and could potentially mitigate early stages of alzheimer’s disease. [105]

Note: There are three main forms of omega 3, alpha-Linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). ALA is commonly found in plants and can be fairly effectively converted to EPA if you don’t have a diet high in linoleic acid (most commonly found in processed foods containing cottonseed oil and sunflower seed oil). ALA does not convert well to DHA. Supplementation with DHA is most likely necessary for everyone if you don’t obtain it from your diet. Vegans can source DHA from algae derived supplements.

Standard Dose: ~1200 mg DHA, ~2,000 mg EPA

Reliable Suppliers

Tyrosine

Summary

Tyrosine is a non-essential amino acid and a precursor to dopamine, epinephrine and norepinephrine. There is some evidence to suggest tyrosine supplementation can affect performance on working memory tasks under certain conditions, especially stress.[51][52][53][54] Tyrosine may enhance convergent creative thinking.[171] In one study tyrosine seemed to even ameliorate some of the detrimental effects of sleep deprivation on cognitive performance.[86] However, if tyrosine increases working memory performance by enhancing catacholamine levels the effect could easily be short-lived. Some animal studies have shown dopamine levels quickly return to baseline.[55]

Standard Dose: 2 grams on an empty stomach

Reliable Suppliers

Warning

Tyrosine is a precursor to tyramine and thus carries a significant risk to people using MAO inhibitors.

Magnesium

Summary

Magnesium is an essential mineral involved in many biological functions including the normal modulation of NMDA receptors.[58] Surveys suggest around half of Americans consume less magnesium than what is estimated to be required.[59] Most notable dietary sources of magnesium include almonds, brazil nuts, cashews, chards and kale. Magnesium deficiencies may be linked to, fatigue, irritability, insomnia, muscle tremors and twitching.[60] Some evidence suggests magnesium L-threonate can increase learning and memory in animal models and older adults with cognitive impairment, presumably by increasing synaptic plasticity.[61][234]

Standard dose: 2 grams of magnesium l- threonate

(Other forms of magnesium include, magnesium citrate, magnesium glycinate or magnesium gluconate. These forms will be adequate for fulfilling nutritional needs, they may not have significant cognitive effects.)

(Note: excessive dosages may cause diarrhea, stomach cramps, skin flushing, dizziness. Reduce your dosage if you experience diarrhea, discontinue use if you experience stomach cramps, skin flushing or dizziness)

Reliable Suppliers

Side Effects

Diarrhea

Vitamin D

Summary

Vitamin D (cholecalciferol, vitamin D3) is a steroid hormone that is synthesized when skin is exposed to ultraviolet light. Vitamin D is also found in food such as fatty fish (salmon, tuna, and mackerel), it can be found in small amount in beef liver, cheese and egg yolks and is fortified in foods such as milk. Vitamin D’s primary role in the body is to promote calcium absorption in the gut and maintain adequate serum calcium levels to enable adequate mineralization of bone. But vitamin D seems to have more biological roles that go beyond just the regulation of calcium, the vitamin D receptor is found in most cells in the body and is estimated to be responsible for the regulation of more than 200 genes.[250] In the brain calcitriol, the active form of vitamin D seems to affect the expression of NGF and GDNF.[251][252][253][254] Vitamin D deficiency seems to be associated with a substantially increased risk of Alzheimer’s and all-cause dementia. [255] There seems to be some evidence that vitamin D supplementation may improve symptoms of depression. [256][257]. The evidence that vitamin D supplementation can improve cognitive function is mixed. A study which gave participants 5000 iu of vitamin D per day for 8 weeks failed find improvements in attention, working memory or cognitive flexibility compared to placebo.[258] But a longer 18-week randomized placebo controlled trial where participants were given 4000 iu of vitamin D per day, found significant improvements in nonverbal memory.[259]

Standard dose: 4000 iu of vitamin D3 per day taken in the morning or afternoon

Note: Vitamin D requirements are highly variable, skin color, UVB exposure, body weight and age are all important variables that contribute to a person’s vitamin D requirements.

Reliable Suppliers

Side effects

hypercalcemia, anorexia, weight loss, polyuria, heart arrhythmias, tissue calcification, kidney stones

Warning

Acute symptoms of vitamin D overdose may start to appear at doses of 10,000+ iu per day. Less acute side effects may start at lower doses.

Wakefulness Enhancers

Blue Light

Our bodies have evolved to use blue light (~480nm) as a signal that it’s daytime.[239] Blue light is a key master regulator of our circadian rhythm and wakefulness. Blue light, in addition to repressing melatonin levels also increases our metabolic rate and alertness.[240][241] Exposure to blue light seems to have significant cognitive effects. In randomized controlled trials bright blue light seems to be able to improve attention, working memory, verbal memory and mood.[241][242][243][244][245][246][247][248] Blue light in combination with caffeine seems to increase alertness and mood more than caffeine alone.[241][243] Interestingly, blue exposure during the day actually seems to increase sleep quality.[247] Whereas blue light exposure at night has the opposite effect. The current theory for blue light’s cognitive effects has to do with ultimately increasing norepinephrine release, which is associated with alertness and mood, but it’s a complex process that may involve other important factors including the modulation of orexin (hypocretin) neurons. Blue light seems to have positive effects at intensities as low as 40 lux (which is function of the distance and the intensity of a light source), but lower intensities are not as fast acting as higher intensities of blue light. Given its low risk profile and the substantial benefits, blue light devices should be considered a cognitive enhancer with one of the best risk to reward ratios.

Standard Dose: 40-200+ lux of blue light (~480±20nm) for 10-60 minutes in the morning.

Reliable Suppliers

Devices

Philips goLITE BLU is commercially available and was used in at least several studies.[242][245] Another study used a commercially available blue LED bulbs like the Techlight® RGB, which has a blue wavelength of around 470nm. Any source of blue light at ~480±20nm that can achieve greater than 40 lux at a comfortable distance should be effective.

Side effects

May trigger mania in predisposed individuals

Modafinil

Summary

Modafinil is a stimulant and wakefulness-promoting agent. It has been shown to eliminate most of the cognitive side-effects of short-term sleep deprivation. It was once believed modafinil could enhance short-term memory and executive functions in healthy non-sleep deprived populations.[42][43][44] However, larger studies have failed to note any short-term memory improvement.[202] While other studies have noted impaired performance on reaction time tasks. [183] A recent systematic review suggests modafinil may improve performance on demanding tasks.[205] The review only looked at studies done between January 1990 and December 2014. So it failed to include the largest study on modafinil to date, which came to different conclusions. It also left out a lot of studies due the the search terms employed, many of those studies were null results that the authors may have known about.[230] Modafinil’s mechanism of action is still not completely understood. The most prominent current hypothesis is modafinil increases norepinephrine and dopamine neurotransmission by modestly inhibiting dopamine and norepinephrine transport. The dopamine and norepinephrine transport inhibition does not appear to be strong enough to induce euphoria or addiction.[45] Modafinil is the most highly rated wakefulness promoter.

Note: already high performers may be less likely to benefit cognitively from modafinil.[46][47][48][49]

Standard Dose: 200mg once in the morning

Side Effects

Headache, dizziness, gastrointestinal problems, anxiety, irritability, increased blood pressure, palpitations, nausea, serious and life threatening skin conditions (ex. Stevens-Johnson syndrome)

Modafinil Warnings

Armodafinil

Summary

Armodafinil is pure R-modafinil, the most active stereoisomer found in modafinil. This means armodafinil will have slightly different effects than modafinil and a lower effective dose.

Armodafinil like modafinil, is technically illegal to buy in most countries, though the personal risk still appears to be low.

Standard Dose: 150mg once in the morning

Side Effects

Anxiety, irritability, increased blood pressure

Modafinil Warnings

Adrafinil

Summary

Adrafinil is the oldest of the modafinil family of drugs. Adrafinil is a prodrug of modafinil, which is to say it’s converted to modafinil when metabolized. However, it may not be appropriate to assume the effects are exactly the same once it’s metabolized, since adrafinil the molecule can have other effects, some of which may inhibit modafinil. There is some concern that adrafinil may be worse on one’s liver than modafinil. Adrafinil is currently unscheduled in the USA.

In 2011 French drug assessment authorities removed adrafinil’s market authorization citing: “Examination of the results of clinical studies made ​​by the laboratory does not allow to conclude on the benefit of adrafinil in disorders of arousal and alertness in the elderly. Given also known adverse effects of this drug , the Commission considers that the MA benefit / risk ratio of adrafinil is unfavorable and therefore proposes a withdrawal of the authorization for placing on the market.”[62]

Standard Dose: 300-900mg once in the morning

Side Effects

Anxiety, irritability, increased blood pressure, increased liver enzyme levels

Modafinil Warnings

Tyrosine

Summary

Tyrosine is a non-essential amino acid and a precursor to dopamine, epinephrine and norepinephrine. There is some evidence to suggest tyrosine supplementation can affect performance on working memory tasks under certain conditions, especially stress.[51][52][53][54] Tyrosine may enhance convergent creative thinking.[171] In one study tyrosine seemed to even ameliorate some of the detrimental effects of sleep deprivation on cognitive performance.[86] However, if tyrosine increases working memory performance by enhancing catacholamine levels the effect could easily be short-lived. Some animal studies have shown dopamine levels quickly return to baseline.[55]

Standard Dose: 2 grams on an empty stomach

Reliable Suppliers

Warning

Tyrosine is a precursor to tyramine and thus carries a significant risk to people using MAO inhibitors.

Creatine

Summary

Creatine acts as an energy buffer in the brain. It is converted into high-energy phosphocreatine in the body, which helps to create ATP. During times of activation the brain rapidly drains phosphocreatine to keep ATP levels constant.[19] Oral supplementation of creatine has been shown to increase brain creatine levels between 3.5-13.3% with the average being about 8%.[20] This additional buffer of energy may enhance performance on demanding tasks related to IQ.[21][88] For healthy young well-rested omnivores, creatine does not seem to enhance function in other domains.[22][23] For individuals who are sleep deprived creatine seems to consistently enhance executive function.[87] Although vegetarians and vegans seem to respond best to creatine supplementation, vegetarians and omnivores have comparable baseline brain creatine levels.[24][25]

Creatine Meta-analysis

Standard Dose: 5 grams once in the morning with plenty of water. To increase the saturation rate take 20 grams for the first week.

Reliable Suppliers

Possible Interactions

In patients with Parkinson’s disease, creatine intake and high caffeine use (>300mg per day) was associated faster progression of the disease as measured by the Unified Parkinson’s disease rating scale. [207]

Side Effects

Stomach pain, nausea, diarrhea

Questions

Do I need to take a special form of creatine?

No. Creatine monohydrate is likely to be just as good as any other form and it’s much less expensive.

Racetams and derivatives

Piracetam

Summary

The term nootropic was originally coined to describe the effects of piracetam.[63] Piracetam is the oldest and most researched drug of the racetam family. Piracetam’s mechanism of action isn’t entirely clear, the most prominent current view is that piracetam enhances neuronal function first through increasing membrane fluidity, which is usually disturbed in aged brains, then subsequently increasing mitochondrial function.[64] If this hypothesis is true then young people will likely benefit the least from piracetam. Some evidence still suggests that piracetam may increase memory in non-elderly populations.[65][66] But in a large clinical trial piracetam failed to reduce cognitive decline in patients with Mild Cognitive Impairment.[233] In one longitudinal study piracetam use was actually found to be associated with increased cognitive decline over 20 years, though the authors caution drawing conclusions given the small sample size in the piracetam group.[139]

Folk wisdom usually suggests consuming some form of choline source with piracetam, to either increase the effects or mitigate “racetam headaches”, a phenomenon a minority of users report. While choline is generally a pro-cognitive compound, especially for the elderly there likely isn’t a special requirement here. Most people can take piracetam with or without choline. But choline may have beneficial effects of its own.[57][206]

Standard Dose: 1600mg thrice a day

Side effects

Stomach pain, headaches

Questions

Do I need to take piracetam with choline?

It’s not necessary. Some people prefer it, others don’t. The relevant human studies on piracetam did not include supplemental choline.

Do I need to do an “attack dose” with piracetam?

No. A consistent dose from the start is probably preferred. However, since piracetam seems to have a wide therapeutic window, you can take considerably more than the standard dose without a major issue.

Is piracetam legal in the US?

Piracetam is not scheduled and is unregulated for consumers in the US. Piracetam suppliers in the US may be in a legal grey area if they’re advertising it for human consumption. The FDA has sent some suppliers cease and desist letters, but this is a rare occurrence.

Can I get piracetam in the UK?

Yes. the UK actually has a very laissez-faire policy when it comes to importation of prescription drugs for person use.

Can I get piracetam in Canada?

Customs can seize the piracetam, but this is rarely an issue if it’s coming from the UK or US.

Can I get piracetam in Australia?

Customs can seize the piracetam, but this is rarely an issue.

Can I get piracetam in Europe?

Customs can seize the piracetam, but this is rarely an issue.

Phenylpiracetam

Summary

Phenylpiracetam (Phenotropil, Carphedon) is a scarcely studied piracetam derivative. It’s notable for its stimulatory subjective effects. It appears on the list of banned substances for Olympic sports. In-vitro experiments suggest phenylpiracetam binds to nicotinic acetylcholine receptors. In animal models phenylpiracetam seems to increase NMDA and nicotinic acetylcholine receptor density, which may suggest it has potential as a cognitive enhancer.[204] Similarly, in animal experiments phenylpiracetam seems to exert anti-depressant effects. [111] No studies have been done to show phenylpiracetam improves cognitive performance in otherwise healthy individuals. Phenylpiracetam seems to be the most stimulatory piracetam derivative.

Standard Dose: 100mg twice a day

Questions

Does phenylpiracetam need to be taken with choline?

No.

Aniracetam

Summary

Aniracetam is the grandfather of the Ampakines, it served a model for many newer and more potent AMPA modulators. Aniracetam itself has been used in the treatment of strokes in Japan and Alzheimer’s disease in Europe. It went under the name Draganon in Japan, but has since been pulled from the market because of a failed clinical trial. [108]

Although aniracetam appears to be an AMPAkine with long-term potentiation and neurotrophic factor enhancing properties in in-vitro experiments, it may not the same profile when orally administered. Once absorbed in the gastrointestinal tract aniracetam is almost entirely metabolized, only about 0.2% reaches systemic circulation, much less than what would be necessary for significant AMPA receptor modulation. [157] It may be possible to retain aniracetam’s ampakine effects by taking it sublingually, but that method of administration isn’t well-tested. Aniracetam’s metabolites however seem to be psychoactive. Of aniracetam’s many metabolites N-anisoyl-GABA, p-anisic acid and 2-Pyrrolidinone seem to be the most important, though they aren’t well-studied. 2-Pyrrolidinone seems to facilitate AMPA receptor responses.[229] And N-anisoyl-GABA has been noted to enhance acetylcholine, serotonin and dopamine release, possibly through interacting with group II metabotropic glutamate receptors. This could account for aniracetam’s unique mood enhancing effects. [109]

In general aniracetam’s cognitive enhancing effects aren’t well documented and remain unproven. But it seems to be fairly well tolerated in the short term. [110]

Standard Dose: 750mg twice a day

Side effects

Anxiety, irritability, insomnia

Questions

Do I need to take aniracetam with food or oil for full absorption?

No. Aniracetam can be fully absorbed on an empty stomach.

Does aniracetam need to be taken with choline?

No.

Oxiracetam

Summary

Oxiracetam is a water soluble racetam which is very similar to piracetam. The main difference between piracetam and oxiracetam is oxiracetam’s lower effective dose. Similar to other racetams, oxiracetam seems to inhibit scopolamine-induced impairment.[112] Oxiracetam may improve certain age-related cognitive deficits, but oxiracetam notably failed to benefit alzheimer’s disease patients. [113][114] No studies have been done to show oxiracetam improves cognitive performance in otherwise healthy individuals.

Standard Dose: 800mg twice a day

Questions

Does oxiracetam need to be taken with choline?

No.

Pramiracetam

Summary

Pramiracetam is similar to piracetam in effects, but pramiracetam has a much lower effective dose and is fat soluble instead of water soluble. Pramiracetam shouldn’t be taken in powder form or sublingually, it may cause burning and irritation. Pramiracetam seems to partially reverse scopolamine-induced cognitive deficits. [115] Limited evidence suggests pramiracetam may be more effective than piracetam at restoring memory after brain trauma.[116] No studies have been done to show pramiracetam improves cognitive performance in otherwise healthy individuals.

Standard Dose: 300mg twice a day

Warning

Do not take pramiracetam sublingually, it can cause burning and irritation.

Questions

Does pramiracetam need to be taken with choline?

No.

Acetylcholinesterase Inhibitors

Acetylcholinesterase Inhibitors work to inhibit the breakdown of acetylcholine and thereby increasing its availability. Acetylcholinesterase inhibitors are currently a first line of treatment for dementia and Alzheimer’s disease in the US. Acetylcholinesterase inhibitors may also enhance cognitive performance for otherwise healthy individuals, at least in the short-term.[70] The use of acetylcholinesterase inhibitors is associated with side effects including: diarrhoea, nausea, vomiting, leg cramps and abnormal dreams.[71] Though, for some the abnormal dreams may be a feature rather than a bug.

Warning

Strong acetylcholinesterase Inhibitors may trigger depression.

Donepezil

Summary

Donepezil is a reversible acetylcholinesterase inhibitors commonly prescribed for treating dementia and Alzheimer’s disease. A number of studies suggest Donepezil may have the ability to enhance executive function in otherwise healthy populations.[72] More rigorous reviews of Donepezil’s efficacy in treating Mild Cognitive Impairment show strikingly underwhelming results, noting: “There is no evidence to support the use of donepezil for patients with MCI. The putative benefits are minor, short lived and associated with significant side effects.”[71]

Standard Dose: 10mg

Side Effects

Depression, diarrhea, nausea, abnormal dreams

Huperzine A

Summary

Huperzine A is a naturally occuring acetylcholinesterase inhibitor found in Huperzia serrata. Huperzia serrata has a long history of use in traditional Chinese medicine where it was used for fever, inflammation, muscle strains, and rheumatologic conditions. Like other acetylcholinesterase inhibitors, there’s evidence to suggest Huperzine A can be used to help treat Alzheimer’s disease.[73] Evidence suggesting Huperzine A can enhance otherwise health individual for the long-term is notably missing.

Standard Dose: 100mcg daily

Side Effects

Depression, diarrhea, nausea, abnormal dreams

Peptides

Semax

Summary

Semax (Met–Glu–His–Phe–Pro–Gly–Pro) is an analogue of ACTH4–10 a peptide fragment of adrenocorticotropic hormone. Unlike ACTH4–10 though, Semax is thought to be an antagonist of melanocortin 4 receptors. In Russia, Semax is used as a neuroprotective agent in post-stroke therapy.[198] In animal models Semax seems to increase hippocampal BDNF expression, trkB expression and also seems to augment the effects of stimulants.[199][225] One small Russian study suggests Semax may increase alpha brain waves and improve performance on tasks requiring focus and memory.[200]

Standard Dose: 0.1-1.0 mg via nasal spray

Noopept

Summary

Noopept (GVS-111) is a dipeptide that was synthesized to imitate a vasopressin metabolite AVP(4-9) and piracetam.[69] It’s currently sold in Russia to treat age-related cognitive decline. Noopept main anxiolytic and memory enhancing effects likely come from its metabolite cycloprolylglycine, an endogenous neuropeptide.[159][160][161][162] Noopept seems to stimulate NGF and BDNF in animals, though this finding hasn’t been replicated.[69] Some studies suggest noopept increases alpha and beta brain wave activity.[158] No studies have been done to show noopept improves cognitive performance in otherwise healthy individuals. Though it’s generally understudied, some evidence suggests noopept may down-regulate BDNF sensitive TrkB receptors with long-term use. [184]

Standard Dose: 10mg three times per day

Questions

Does noopept need to be taken with choline?

No.

Ampakines

An ampakine is a positive allosteric modulator of AMPA receptors. This means they modify the function of the receptor without affecting the binding site specifically. An ampakine alters the dynamics of AMPA receptors to prolong the channel open time and thus increase the excitatory effect. This increased excitatory current helps to facilitate the induction of LTP and subsequently leads to increases in neurotrophic factors.

Ampalex

Summary

Ampalex (CX516, BDP-12) was the first clinically significant positive allosteric modulator of AMPA receptors. Ampalex works to modify AMPA receptor dynamics to extend the the amount of time it remains open and thereby increase the excitatory signal and facilitate the induction of long-term potentiation. In several studies Ampalex has been shown to enhance memory in otherwise healthy adults.[150][151] Ampalex has a relatively short half-life of about an hour, which likely has dissuaded further investigation. However, in animal models some of the largest memory enhancements were obtained when Ampalex was administered once every 48 hours.[152] This more persistent enhancement may be due to increased BDNF expression, which is an effect commonly associated with ampakines. [153][154] Ampalex appears to be well-tolerated in the short-term.

Standard dose: 300-1200mg

Side effects

Rashes, insomnia, fatigue, heartburn, stomach pain

Other

Tianeptine

Summary

Tianeptine (Stablon) is an atypical anti-depressant and anxiolytic drug originally discovered in the 1960s. Tianeptine was first granted market authorization in France in 1987, giving it over a quarter of a century of clinical history. It has been suggested that tianeptine works by modulating glutamate or by acting as a low level μ-opioid agonist.[163][164] Despite decades of research, however, tianeptine’s true mechanism of actions remains unclear. Tianeptine seems to mitigate stress-induced structural changes in the brain. [165] In one observational study, tianeptine treatment was associated with significantly reduced depression-related cognitive impairment.[166] In animal models of stress tianeptine appears to positively affect the expression of genes related to neuroplasticity.[167] Tianeptine seems to normalize glutamate levels in the amygdala and hippocampus of animals subjected to stress, which does not appear to be the case with SSRIs.[168] In clinical trials Tianeptine seemed to be deviod of abuse potential, however post-marketing surveillance revealed that tianeptine does indeed have some abuse potential. It’s estimated that around 0.1-0.3% of tianeptine users will abuse it. The risk of abuse is especially high with people who already abuse other substances or alcohol. Tianeptine abuse can lead to subsequent withdrawal symptoms.

Note: proper dosing is essential with tianeptine, a milligram (0.001g) scale is required if you’re using powder. The risks associated with above therapeutic doses of tianepine are understudied. Case reports have documented significant side effects including, nausea, vomiting, dizziness, abdominal pain, constipation, loss of appetite, anorexia, weight loss, mydriasis, itching, frequent urination, painful urination, hepatitis and sleep disturbances. [185][186][187] There are case reports of what appear to be fatal tianeptine overdoses. [188]

Standard dose: 12.5 mg three times per day

Side effects

Nausea, dry mouth, somnolence, insomnia, intense dreams, dizziness, fainting, constipation, dependence, potential liver toxicity

NSI-189

Summary

NSI-189 is a nicotinamide derivative compound with promising potential as an anti-depressant and cognitive enhancer. NSI-189 was first discovered as part of a DARPA funded program aimed at mitigating stress-induced hippocampal atrophy, which is believed to be of particular concern for warfighting soldiers and their cognition. NSI-189 is believed to work by stimulating neurogenesis in the hippocampus, but the exact mechanism by which it achieves this is not clear. The mechanism of action is probably less understood than most because the approach to discovering the compound was somewhat different than usual methods. Instead of screening for compounds that target a specific receptor or defined mechanism, NSI-189 was found by screening compounds based on their effect on cultured human hippocampal neural stem cells. These effects seem to still be relevant in in-vivo studies as well. Some reports suggest NSI-189 can increase hippocampal volume in healthy animals up to 20%, though it’s important to note that the conditions of laboratory animals may be such that “healthy” could still be somewhat depressed, these are confined animals. NeuralStem, the company behind the drug believes NSI-189 is “reversing hippocampal atrophy and most likely increasing synaptogenesis in the hippocampus”.[136]

NSI-189 did complete phase I trials with no obvious signs of toxicity.[137][138] Depressed patients taking NSI-189 appeared to score substantially higher on a cognitive and physical functioning questionnaire, but these trials were limited by their sample size.[138] In a Phase II trial, NSI-189 failed to significantly reduce depression scores.

There are currently are no highly reputable and established sources for NSI-189 who have 3rd party tested their products. NeuroStem seems to aggressively pursue unauthorized suppliers, so buying NSI-189 at this point carries additional risks beyond unknown side effects.

Blends

Alpha Brain

Summary

Alpha Brain seems to be one of a very few group of nootropic blends that has gone through the rigor of a randomized placebo controlled trial.[224] The effort on Onnit’s part is very commendable, since it’s much easier to hype a supplement than it is to test one. The two studies seem to suggest Alpha Brain enhances performance on verbal learning tests. Both trials noted statistically significant changes on a test called the California Verbal Learning Test (CVLT). These results shouldn’t necessarily be surprising since one of Alpha Brain’s main ingredients is Bacopa Monnieri, which has substantial and well-documented effects on a similar test called the Auditory Verbal Learning Test (AVLT).

Devices

tDCS

Summary

Transcranial direct current stimulation or tDCS uses low electrical currents sent through scalp to try to elicit changes in mood and cognitive performance. TDCS is one of the more well-researched forms of neuromodulation, but conflicting evidence for its efficacy does exist. At least one systematic review was unable to find reliable cognitive effects from tDCS in healthy adults.

More on tDCS

LLLT

Summary

Low-level laser therapy or LLLT uses light at specific wavelength ranges to try to improve biological function, be it tissue repair, skin health or neuromodulation. One study suggests LLLT may have the ability to improve cognitive performance and mood.[191] The science behind LLLT is in its infancy, so the lasting consensus about if and how it works may not be known yet. LLLT is believed to be able to increase ATP production.[192] Photomodulation of cytochrome c oxidase activity is believed to be a primary mechanism for the biological effects of LLLT.

tFUS

Summary

Transcranial focused ultrasound or tFUS uses pulsed ultrasound to try to influence neural networks. Ultrasound has been shown to influence neuronal excitability.[193][194] One recent study suggests focused ultrasound may be able to enhance performance on some cognitive tasks.[195]

TMS

Summary

Transcranial magnetic stimulation or TMS uses high energy electromagnetic fields to influence neuronal function. Transcranial magnetic stimulation has been fairly extensively researched and seems to show promise for cognitive enhancement and mood enhancement.[196] TMS has been approved for clinical use in treatment-resistant depression in several countries including the US. TMS is believed to work by depolarizing neurons in specific regions it’s applied to. Specific protocols may either increase or decrease cortical activity. Evidence has been found to suggest certain TMS protocols may decrease reaction time and increase memory and other cognitive functions. Studies on TMS may have an issue with blinding participants as to which treatment group they’re in, since TMS causes clicking noises and somatosensory sensations.

How to

Measure Powders

Suppliers often include scoops with powders, these scoops are intended to transfer powders from the container to a scale. They are not intended to tell you the amount of powder you’re scooping out. To get an accurate weight determination you need a digital scale, since the density of powders can vary substantially.

The vast majority of compounds will only need a milligram scale, which you can buy for around 20 dollars. However, if a compound is effective at single milligram doses then more precision is required.

When you first get a scale you should practice reading and using the scale with a small object of known weight, such as a penny (2.5 grams or 2500 milligrams for recent pennies). Be sure to take note of where the decimal place is, misreading or misinterpreting the number could cause serious harm or death.

Store Nootropics

Keep away from children

Anything drug, supplement or herb as a rule needs to be kept out of the reach of children and other parties that may intentionally or unintentionally misuse it. This is especially true with drugs which may have a low lethal dose.

Label and isolate potentially dangerous compounds

Substances need to also be stored with proper warning labels for yourself. If it’s possible for you to accidentally spoon yourself a lethal dose, then the container for that substance needs to be labelled and isolated with compounds that have a similar therapeutic window (E.g. you don’t want your caffeine powder to be next to your creatine powder, because if you accidentally scoop caffeine powder instead of creatine powder you may be ingesting a lethal dose).

Keep cool and dry

Containers should always be well sealed and not exposed to heat or sunlight. Heat and moisture are the two biggest things you need to worry about if you’re trying to preserve pills or powders.

Measure Your Cognitive Performance

Quantified Mind and Cambridge Brain Sciences are free tools which can test your cognitive performance over time. It’s important to note though, that these games will be subject to a large initial practice effect.

Other Things to Know

Yerkes-Dodson law

The relationship between arousal and performance is known as the Yerkes–Dodson law. This relationship suggests that naturally anxiety-prone individuals may benefit from mild anxiolytics, while inattentive people may benefit from stimulants. Your baseline level of stress will have a lot to do with what works for you.

Warnings

Caffeine Warnings

  • Caffeine has a relatively low lethal dose (it may be around 3 grams for some people). Don’t be reckless with caffeine pills or powder.[74][75] Caffeine powder is not recommended due to the possibility of human error when dosing.
  • Caffeine can also cause anxiety, agitation and tachycardia (rapid heart rate) at high doses relative to your tolerance level.

Modafinil Warnings

References

Link to reference page on Reddit – Beginner’s Guide To Nootropics

What are Nootropics Stacks (Medium)

 

BROWSE OUR PRODUCTS ON SALE