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Best Nootropics For Studying

 
(Last Updated On: December 17, 2018)

How Nootropics Can Enhance Your Studying

best nootropics for studying

In this post, I thought I’d focus on how nootropics can be used to improve the efficiency of your studying.

Studying sucks, let’s face it. I think it’s reasonable to say that almost everyone reading this dislikes studying. After spending hours in class every week, it’s hard to want to spend your limited free time at home cramming your head full of even more information. It’s hard to focus, hard to remember, and hard to motivate yourself.

If you want to fully optimize your efficiency and productivity with studying, nootropics are the ultimate solution. I do have one caveat, however. Nootropics are not a replacement for hard work and discipline. Nootropics should be used as a supplement, a way to enhance your life. That’s not to say they won’t help you, but I do not want to oversell them and try to convince you that they alone will cause you to succeed academically.

The nootropics industry, like the supplement industry as a whole, has a lot of products that simply don’t work. Rest assured, all of the information on this page will be backed up with scholarly references as well as some of my own experiences.

There are two types of nootropics that make up the majority of this page: racetams and cholinergics. This is because these compounds primarily work on the acetylcholine (ACh) system, which is implicated in memory and learning [55].

It is likely that almost anything outside of this list is either very understudied or has been sensationalized with no evidence. This post will cover everything you will need to know including: how they work, where to buy them, dosages, and personal recommendations.

List of the Best Nootropics For Studying

Classic (Tier 1) Racetams

Racetams are a class of nootropics that all share a similar chemical structure. They are all known to exhibit cognitive-enhancing properties [8]. Despite this, each one of different from the next, and their mechanism of action (MoA) is elusive. As a result of this, while they do all share some affinity for the cholinergic system, they otherwise have quite a range of effects and uses. What they do share in common is that they posses extremely low toxicity and lack serious side effects [8], which is one of the most important qualities for something to be considered a true nootropic.

There are a lot of different racetams out there, over 20 in fact. The newer they are, the smaller their body of evidence, and I do not plan to cover or endorse all of them. To begin I will cover the “classical” racetams which have been around for longer and have thus been used and studied more extensively.

Piracetam

Piracetam is one of the oldest nootropics substances out there and serves as the basis for the definition of a nootropic drug. Piracetam was first discovered and synthesized in 1964 by a Romanian chemist named Corneliu E. Giurgea, who actually coined the term “nootropic”. Piracetam has sort of served as the prototypical nootropic and has been studied quite extensively. There are mixed opinions on this drug for its effectiveness and it tends to be hit or miss for people, and this likely depends on the individuals own unique neurochemistry.

Like many other racetams, Piracetam effects the acetylcholine system [1], which is implicated in regulating memory, learning, and attention. For this reason, it is recommended to take a choline precursor supplement so that your ACh levels do not get depleted when using Piracetam [16].

Piracetam increases neuronal excitation via increased glutaminergic signaling, specifically at the AMPA receptor [28][29][30]. Ordinarily, neuronal excitation is not always ideal, especially if it’s excessive. There is even a term for this called “excitotoxicity” whereby neurons are damaged or killed be excessive levels of glutamate.

Do not worry, however, as Piracetam is unique in that it’s a neuroprotective agent [28][31], and prevents against glutamate induced neurotoxicity [15][31], which appears to be among its most promising features.

Lastly, piracetam also increases cell membrane fluidity, oxygen consumption, and cerebral blood flow [9][10]. It seems to increase alpha and beta EEG activity at specific sites, specifically in the prefrontal cortex and hippocampus [11], which are very important, higher-order regions of the brain responsible for executive function [12], and the consolidation of short term memory into long term memory [13], respectively.

Piracetam is also used to promote longevity, as it is an effective agent for preventing cognitive decline due to its neuroprotective qualities. It is also extremely well tolerated and has remarkably low toxicity, meaning it’s very safe and the side effects are generally nonexistent. At worst it can cause some mild dizziness, nausea, or insomnia, but these side effects are quite rare [7].

In my own opinion, Piracetam is one of the most fascinating nootropic drugs out there, but it’s hard to say whether it’s one of the best nootropics for studying. While its effects are highly cerebral and interesting, it’s not necessarily reliable as an on-demand nootropic for something like studying. I’ve tried it many times and it’s somewhat inconsistent.

Sometimes Piracetam seemed to markedly improve my cognition, causing some sort of holistic, expansive creativity, and openness. I never really used for a studying session, but rather for experimentation and interest. So I can’t say for certain of it would benefit you.

Overall, I’d say Piracetam is better for general brain health. However, if you have never tried a racetam or any nootropic before, it’s a great one to start out with. It’s cheap, available, and safe, and you don’t have much to lose by trying it. It seems to work wonders for some people and is worth trying out, especially if you’ve never used a nootropic substance.

As a general rule, “less is more” is a good rule of thumb when determining optimal doses for a substance, but Piracetam seems to be an exception in that higher doses are almost universally more effective. And due to the fact that Piracetam has such an absurdly low toxicity, higher doses do not pose any additional risk.

The half-life of the drug is about 5-6 hours [1], and the ideal dosage should be 4.8 grams taken twice daily [3][4][5][6]. Higher doses can be taken if a 4.8g dose seems ineffective, up to 24g can be taken in one day, split between two 12g doses [2]. Many dosages are incorrect from other websites and vendors due to an improper understanding of the drug, and often recommend doses that are far too low to see any effect.

Piracetam has a slightly bitter taste, though not horrible, and some may want to purchase it in capsule form.

Aniracetam

Aniracetam is a slightly more potent, fat soluble version of Piracetam.

Like Piracetam, it appears to increase blood flow and activity in regions of the cortex responsible for collective and abstract thought. It also has strong neuroprotective effects as well. Like other racetams, Aniracetam can enhance memory and learning memory due to its affinity with the cholinergic system [17][18], and therefore should be supplemented with a choline source [14][16].

However, aniracetam differs from Piracetam in that it has more notable effects on other systems in the brain. Specifically, it effects the glutaminergic system even more so than Piracetam, and is technically classified as an ampakine [16][27]. Ampakines are a very unique class of drugs that are known for modulating the glutaminergic system via the AMPA receptor.

The AMPA receptor is itself is a type of glutamate receptor, which are responsible for neuronal excitation. The AMPA receptor is unique because unlike the other receptors, it actually prevents over-excitation (excitotoxic) effects [15]. This means that an ampakine drug like aniracetam does not have the potential for neuronal damage, which should already be a given of anything falling under the category of “nootropic”, but I digress.

Aniracetam’s modulation of the AMPA receptor (which in turn effects many other systems in the brain) also has a series of indirect, downstream effects that ultimately provide additional benefits beyond cognitive-enhancement and improved memory and learning.

These additional, indirect benefits appear to result primarily in anti-depressive and anxiolytic (anti-anxiety) qualities [19][20][21], which are most likely caused by an indirect release of dopamine and serotonin [22].

In short, Aniracetam is has the benefit of both improving cognition and mood. It has improves memory and learning, with anxiolytic and anti-depressive qualities, as well as thought enhancing properties. Aniracetam may be an effective agent for studying which requires focus and effective memory encoding.

I have found aniracetam to be a fascinating drug like Piracetam, however in my experience I could not reliably get it to work as well for me as Piracetam. Anecdotally, I have heard that many people seem to respond to either Piracetam or Aniracetam quite strongly, but usually not both.

The half-life is quite short at 35 minutes [32], so doses may need to be spread throughout the day. Typical doses are 500-750mg which are taken up to 4x a day if not more. Since it is fat-soluble, it will likely help to take with a fatty meal, though it appears to still be effective even in a fasted state, so this may not be necessary.

Oxiracetam

Following the trend, Oxiracetam is a more potent form of aniracetam and piracetam and shares many similarities.

Oxiracetam is an excitatory nootropic drug that effects the ACh system [14][23], and appears to be even more effective than Piracetam for increasing concentrations of acetylcholine in the brain [24].

Oxiracetam, also like Aniracetam, also appears to strongly modulate the AMPA receptor via increased glutamatergic signaling, which can cause increased brain activity, and when combined with increasing the release acetylcholine, appears to have a similar MoA to the other racetams.

What really sets oxiracetam apart, however, is its effect on the AMPA receptors. Oxiracetam, via modulation of the AMPA receptors, has been shown to cause long-term potentiation in the hippocampus [25][26]. Long-term potentiation is effectively a strengthening of synapses based on recent activities that were performed. The hippocampus, among many of it’s roles, is implicated in the consolidation of short-term memory into long-term memory [13].

This means that if were to spend four hours studying after taking long-term potentiator like oxiracetam, that the information, in theory, would be encoded more strongly in the synapses. Furthermore this strengthening of the synaptic connections would be effect the region of the brain that is specifically involved in memory consolidation (hippocampus).

In short, of all the first-tiered racetams out there, oxiracetam seems like it would be one of the best nootropics for studying. Like aniracetam, oxiracetam appears to be an potent ampakine, and it shows further promise by having a stronger affinity for the ACh system and for promoting long-term potentiation in the hippocampus.  However, oxiracetam is the least studied of the first-tier of racetams, and so it’s hard to say for certain if it’s truly more effective.

Personally, I found it to be among the most consistent of the three in terms of the effects. Oxiracetam, along with a choline supplement, were some of the only nootropics I regularly used in my college days, and it is my personal recommendation.

The half-life is about 108 minutes [33], which would require a 2nd or 3rd dose if you want to use it all day. A standard dose is in the range of 400-800mg, which should be taken up to 3 times daily, for a total of up to 2,400mg.

Advanced (Tier 2) Racetams

Unlike the original three racetams, these substances share the characteristics of being increasingly newer, less understood, and more stimulatory. They have stimulatory effects ranging from mild to strong. However, while all racetams do share some similarities, each one is different from the last. These three racetams are quite different from each other in some very profound ways and have very different MoA’s and subjective effects.

Pramiracetam

Pramiracetam is distinct from the first three classic racetams due to it’s a stimulatory effect. Like the others, it is known to work by targeting the acetylcholine [ACh] system [34], which means it also has the potential to enhance memory consolidation. However, it has not been studied very extensively and we do not currently know much about it pharmacology.

Pramiracetam appears to primarily work by enhancing hippocampal cholinergic neuronal activity in the brain [34][35], and it appears to have even stronger activity in the hippocampus compared to piracetam [40]. As stated previously, this is highly relevant due since one of the primary purpose of the hippocampus is the consolidation of short term memories into long term memories [13]. Pramiracetam appears to have an even higher demand for choline than the other racetams, with a stronger demand for high-affinity choline uptake [HACU] which ultimately results in an acceleration of acetylcholine turnover [34][35].

The implications of this are not currently known, but it is speculated that the stimulatory effect of pramiracetam is almost entirely due to its strong acetylcholine turnover rate, which causes increased activity in the hippocampus. This hypothesis is supported by the fact that pramiracetam has no effect on other systems in the brain, including dopaminergic, adrenergic, norepinephrine, serotonergic, GABAergic [35].

Overall, pramiracetam appears to be a very strong agent for cholinergic system, and since it is most active in the hippocampus, the site for memory consolidation, in theory it would appear to be one of the most effective agents for enhancing memory formation, but more studies are needed to know how it compares to other racetams. There have been studies which demonstrated significantly improved objective memory [36] [37] as well as improved measures of delayed recall, spatial learning, and long-term memory [38][39]. This is most certainly promising, but more research is needed.

Of all the nootropic substances, I have taken pramiracetam the least amount, and this is largely due to it being so understudied. The unique thing about pramiracetam is that it seems to almost exclusively improve memory and learning, but does not seem to have any effect on mood, thoughts, or behavior, and this is likely because it doesn’t appear to have any direct or indirect effects on other systems in the brain. If you’re looking for a drug that simply improves memory and does not come with unpredictable changes in mood and behavior, this may be a great choice.

The half-life seems to vary greatly with pramiracetam, with the average being 2-8 hours [40]. The recommended dosage is 1200mg a day, split between two 600mg doses or three 400mg doses.

Phenylpiracetam

Ah, phenylpiracetam. This was my nootropic of choice in college for studying and writing. This is my preferred choice among the “advanced” racetams, because it quite simply works. If you are looking to gain immediate benefit from a racetam and not toy around, this might be a good starting place.

Phenylpiracetam was developed in 1983 in Russia as a stimulant for Cosmonauts (Russian equivalent of an Astronaut) to maintain alertness and ward off stress while in outer space. Phenylpiracetam is also commonly used for athletic doping due to it’s strong psychostimulatory effects which include increased psychomotor activity, tolerance to cold, and reduced anxiety, and as a result is one of the banned substances in the Olympics.

That may excite some of you and may scare others. Both reactions are quite reasonable. Phenylpiracetam is one of the most aggressive nootropic out there, especially in terms of its subjective effects. Most “true” nootropics do not have particularly noticeable stimulatory effects, but rather have subtle effects that are best over the long-term.

Phenylpiracetam is different. It’s more of an on-demand, nootropic stimulant. If your goal is to have stronger focus, attention, memory, physical energy, and overall mental clarity, then look no further.

The first thing you might notice is the name of this substance. It’s “Phenyl” piracetam. This drug is simply piracetam with a phenyl ring attached to it. This allows it to easily and rapidly cross the blood brain barrier (the “filtering” mechanism of the brain) which other racetams struggle to do effectively.

Interestingly enough, as aggressive of a drug as phenylpiracetam is, it appears to have neuroprotective effects comparable to or even exceeding Piracetam [40], which means that despite its aggressive nature, it is still a true nootropic. Studies have been performed on patients in a state of cognitive decline, whereby phenylpiracetam demonstrated cognitive-enhancing qualities, including higher brain functions, improved motor coordination, memory, attention, and counting, as well as higher mobility, lowered discomfort and anxiety, and resulted in more intense alpha and beta EEG activity [44]. Phenylpiracetam also exhibits anti-depressive qualities [44][46].

Another study found that phenylpiracetam greatly improved the daily living activities of stroke patients after a year of use in contrast with the control group [45].

Now onto the stimulatory effects. Unlike every other racetam so far, phenylpiracetam has a strong affinity for dopamine. It increases the density of the d1, d2, and d3 dopamine receptors by 16%, 29%, and 62% respectively [41] which means that the dopamine is more efficiently absorbed in the synapses. In addition to this, it is also a mild dopamine reuptake inhibitor [42][43], which means that it keeps dopamine circulating in the brain by preventing it from being terminated in the synapses. It also appears to be a norepenephrine reuptake inhibitor as well [41], further increasing its utility as a stimulant.

In addition to an affinity for dopamine, it also binds to the nicotinic acetylcholine (nAChR) which can confer stimulating, anxiolytic, and cognitive benefits.

Phenylpiracetam also increased the density of the GABA-A receptor by 25% [41], which is responsible for feelings of relaxation. Phenylpiracetam has been known to decrease fear and anxiety and this is likely the main mechanism of action (MoA) behind this anxiolytic quality. This is unique among psychostimulants in that has both stimulating and relaxing characteristics.

As you can see, phenylpiracetam has a fairly wide range effects, from reducing anxiety and depression to various cognitive-enhancing properties including memory and attention. It is hard to characterize exactly who would benefit most from phenylpiracetam, but the answer is probably everyone. I would think it would be extremely beneficial nootropic for studying because it provides a very “clean” sort of stimulating effect that actually has real nootropic mechanisms, which is extremely unique among stimulants.

Overall, Phenylpiracetam is quite unlike typical stimulants such as Adderall, which is characterized by being having overly-stimulating, addictive, and unpleasant side-effects as well as nefarious long-term consequences. Phenylpiracetam, however, appears to have neuroprotective and self-regulating effects as well as more general cognitive-enhancing effects, with more moderate stimulatory effects, making it much safer for general brain health, as it does not have any serious side effects, toxicity, or potential for addiction.

In my experience, Phenylpiracetam is by far the best study/work drug. It provides a very clean, astonishingly long stimulatory effect with zen-like focus, as well as increased mental clarity and creativity. It also has the quality of not causing any anxiety, over-excitement, or euphoria (which is addicting and counter-productive).

The half-life of phenylpiracetam is about 3-5 hours. The recommended dosage is 100-200mg taken up to 3 times daily. Phenylpiracetam does not appear to have a strong affinity for the acetylcholine system, unlike other racetams, and therefore choline supplementation is not required. I have taken phenylpiracetam many times and did not notice any symptoms of a choline deficiency (anecdotally, the most common symptoms are brain fog and headaches). Phenylpiracetam is best used on an as-needed basis, as repeated daily use does result in a tolerance and diminished effectiveness.

Noopept

Noopept is another fascinating nootropic recently developed in Russia, in this case it was first synthesized in 1996 [47]. It is distinct from other racetams in that is it actually a peptide, which is a chain of linked amino acids. Some people actually do not categorize Noopept with other racetams due to its different molecular structure, but for simplicity most people categorize it because it has an otherwise similar structure and MoA to other racetams.

Noopept does not have a large body of evidence behind it, having only been around for a little over 20 years, which isn’t very long for a drug of this class. It appears to be a significantly more potent version of Piracetam, with the two sharing a similar MoA, though Noopept has some very unique qualities of its own, which I will discuss in detail.

For starters, Noopept appears to have mild psychostimulatory and anxiolytic effects [49]. And like Piracetam, it seems to increase alpha/beta EEG activity in the brain though the modulation of glutamate [48]. However, unlike Piracetam which specially targets regions of the prefrontal cortex and hippocampus, Noopept appears to increase activity in every region of the brain [48].

But what really sets Noopept apart from Piracetam is that it appears to increase levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) [51][52]. BDNF and NGF are an endogenous (produced in the body) molecules in the brain which regulate the growth, survival, and proliferation of neurons [50]. Following Noopept administration, the expression of NGF and BDNF are appear to be very active in the hippocampus [51].

In short, what this means is that Noopept promotes the growth and expansion of new neurons in the region of the brain that is responsible for memory and learning. This is extremely promising and exciting, and more studies will need to be made to determine some of the implications of such a profound mechanism of action.

Out of all the nootropics I’ve discussed so far, Noopept is the only one I would be careful not to “abuse”. My mission here is to avoid playing up the strengths of these substances and ignoring their potential risks. While I don’t like to speculate, if you do a bit of digging this is something you may come across, and I want to clear up any confusion or worry.

Some people have shown concern that increasing levels of NGF/BDNF can cause a downregulation of them over time. This is a general sort of rule of homeostasis, in that chronic overexposure of certain neurochemicals can cause them to downregulate by decreasing the baseline of these chemicals and the ability to absorb them. Most particularly, there is concern that chronic BDNF over-expression can cause the receptor site Tropomyosin receptor kinase B (TrkB, pronounced like Track-B) to downregulate.

I was able to find one study which indicated that Noopept may cause BDNF levels to decrease through downregulation of the TrkB receptor [53], however I could not access the full text and therefore do not know the full details. On the other hand, I did find a different study which found that chronic treatment of Noopept did not result in a tolerance of BDNF availability, but actually potentiated the neurotrophic effect of BDNF [51]. Another study tested Noopept administration over 28 days and also indicated increased BDNF expression, but did not say whether it caused any TRkB downregulation [52]. That study did imply that Noopept may be effective for the treatment of Alzheimers, which would not recommended if there was any downregulation of the TrkB receptor.

This part is more speculative and hypothesized, but in short, I would advise you to to cycle Noopept if you plan on using it frequently. I would strongly recommend cycling it in one month phases at the longest. When sold as a prescription, it actually recommends to cycle it on a one month on, one month off cycle.

I personally preferred to use it on an as-needed basis as I found the psychostimulatory effects to be very noticeable and was initially unaware of it profound effects on BDNF/NGF expression. The psychostimulatory effects are short lived, however. The half-life is only 1 hour, so if you’re taking it for the psychostimulatory effects, it may require dosing a few times throughout the day. But as I covered previously, Noopept’s main benefits appear to work by increasing levels of NGF/BDNF in the brain, which is not a subjective effect you would notice right away anyway. This means if you’re taking Noopept simply to increase memory and learning, you do not need to constantly redoes it if you stop “feeling it”.

A standard dose is 10-30 mg, which should be taken sublingually (under the tongue) as oral dosages do not seem to be particularly effective at getting absorbed. It does not taste bad so this shouldn’t be a problem. Just make sure you do not take it for more than 1 month at a time. Lastly, from my research it would appear that it does not necessarily need to be be taken with a choline source, as it does not appear to increase the demand for acetylcholine nor cause an increase in acetylcholine turnover. Anecdotally I can confirm that like phenylpiracetam, I did not experience any symptoms of a choline deficiency when taking Noopept.

Cholinergics

Choline is a water soluble nutrient that is present in many of the foods we eat. Eggs are one of the richest sources of this substances, and contain about 1.5g per egg [54]. In the brain, choline is converted into acetylcholine, which is one of the primary neurotransmitters in mammalian brains. Among the many roles that acetylcholine plays in the brain, the most relevant being the regulation of learning and memory [55].

Because of this fact, cholinergic nootropics are very popular for an activity such as studying where increased memory encoding and retrieval is immensely beneficial. And if you’re going to be taking a racetam to enhance your studying, choline supplementation is necessary.

CDP-Choline (also called Citicoline)

CDP-Choline (cytidine diphosphate-choline) is a real powerhouse among cholinergics, and is in fact considered a nootropic drug in and of itself. It is much more potent form of choline which has been shown to enhance acetylcholine synthesis [62] with the added benefit of producing significant levels of uridine in the body [58]. Uridine has many unique nootropic properties of its, including a chronic upregulation of dopamine and acetylcholine by increasing their receptor densities [59].

CDP-choline is a true nootropic drug and not a mere choline supplement, and it appears to have its own unique cognitive-enhancing properties. Among these, it raises levels of dopamine, acetylcholine, and norepinephrine [60][62]. Interestingly, in addition to promoting the acute release of these neurotransmitters, it also increases dopamine and acetylcholine receptor densities [61] with chronic use, which is almost certainly related to the fact that it converts into uridine in the brain. CDP-choline also appears to have a neuroprotective properties as well [60].

CDP-Choline has been shown to increase memory performance and potentiate neuroplastic mechanisms [60], which is a strengthening of the synapses, leading to long-term changes in the brain.

Overall it is an effective nootropic on it’s own, especially for learning, memory, and attention. And it has the interesting quality of increasing the density of dopamine and acetylcholine receptors, which is a rare and rather sought-out quality among nootropics. It is also extremely well tolerated and very non-toxic, with side effects being practically non-existent.

CDP-Choline is fairly expensive however, and if you’re simply looking for a choline source, it may be overkill.

In a 1000mg dose, about 185mg is bioavailable. A standard dose is about 500-2000mg, taken once or twice daily. Start with 500mg a day and increase the dosage if you do not feel much of an effect.

There are almost no side effects besides the potential for stomach pain and diarrhea.

Alpha-GPC

Alpha-GPC [L-Alpha glycerylphosphorylcholine]is a naturally occurring compound that is found in the brain. When supplemented it increases levels of acetylcholine in the brain [63][64]. Alpha-GPC has not been studied very extensively, but the studies do indicate great potential as a choline source.

When compared to CDP-Choline, it has an even higher rate of bioavailability and will rapidly deliver a large amount of choline across the blood brain, indicating to an even greater potential for acetylcholine synthesis than CDP-Choline [65].

Alpha-GPC is generally touted as being the most efficient at delivering choline to the brain, and is not generally referenced for its other nootropic benefits unlike CDP-Choline. However, it does appear to increase levels of dopamine, norepinephrine, serotonin, and gaba [66][67].

Overall, Alpha-GPC is a great alternative to CDP-Choline as it’s cheaper and requires a smaller dose, however it is fairly understudied-studied and its general nootropic qualities do not appear to be as great as with CDP-Choline, beyond possibly increasing acetylcholine levels to a larger degree. However like CDP-Choline, it provides benefits to learning, memory, and attention, and will prevent your ACh levels from getting depleted.

Alpha-GPC is a little less expensive than CDP-Choline and requires a smaller dose. If you’re simply looking to increase levels of ACh in the brain, Alpha-GPC may be a better choice.

In a 1000mg dose, about 400mg is bioavailable. Recommended dosage is 300-600mg, as with CDP-Choline it is best to start small and take larger doses if needed.

I recommend buying Alpha-GPC as a silicone dioxide mixture (totally harmless) which prevents it from turning into a gel-like substance due to its notable hygroscopic qualities.

The side effects may include GI distress, anxiety, headaches, dizziness and nausea, but these are relatively uncommon.

Acetylcarnitine

Acetylcarnitine (ALCAR), as the name suggests, is the acetylated form of carnitine, which improves it’s ability to cross the blood brain barrier.

Acetylcarnitine is an incredible nootropic. In many ways it is the epitome of a true nootropic: it has incredibly powerful neuroprotective qualities; including preventing against damage from oxidative stress, alcohol, and cognitive decline with aging [68][69][70][74], enhances cognition [71][72], improves attention [73], and is well-tolerated with almost no side effects.

ALCAR also modestly increases levels of several key neurochemicals including acetylcholine, serotonin, norepinephrine, and NGF [75][76][77][78][79].

Most interestingly, however, is ALCAR’s ability to provide choline to the brain. While not strictly a cholinergic, it indirectly causes acetylcholine synthesis in the brain through a very complex mechanism. This thread on LongeCity explains it extremely thoroughly and is well-cited, if you’re interested in the details.

Cholinergic mechanisms of ALCAR

In short, ALCAR is unlike other cholinergics in that it is not a precursor for acetylcholine synthesis in the brain, but instead indirectly causes high amounts of acetylcholine to be reliably synthesized. There have been numerous studies which have confirmed ALCARs ability to rapidly raise levels of ACh in the brain [80][81][82].

The recommended ALCAR dose is 500mg to 1000mg. You can combine it with CDP-Choline or Alpha-GPC for an exponential increase, but I would HIGHLY recommend you experiment with very small doses of either CDP-Choline or Alpha-GPC [under 100mg for either], because this can lead to a very high level of choline which is generally considered unpleasant. After much experimenting, I found ALCAR to be enough to take on its own without another cholinergic, and I found 650 mg to be the sweet spot.

A note on other cholinergics

There are a few other choline supplements out there, and I’m going to just flat out say that none of the others are worth taking. I’ll cover these in brief and point out why they are not viable alternatives to CDP-Choline, Alpha-GPC, or ALCAR.

Choline Bitartrate/Citrate

These basic forms of choline are both characterized by being inexpensive and widely available. However, they struggle to pass the blood brain barrier and have not been found to increase levels of ACh in the brain [57]. The primary benefit of these two substances appears to be for cleansing the liver, but they do not appear to have nootropic benefits due to their inability to get absorbed in the brain.

Furthermore, eating eggs would be equally efficient (and probably cheaper) at getting choline, as a single egg contains over 1g of choline [54], and would likely provide the same benefits that choline bitartrate/citrate would provide. That said, some people are more sensitive to choline than others and may not need as much, so if you’ve never tried choline before it may not be a bad starting place because of how inexpensive it is.

Anecdotally, I have tried choline bitartrate myself, but I found it very underwhelming even in very high doses. For these reasons I can’t recommend using it, because it simply is not effective at raising levels of ACh in the brain.

Lecithin

This is a fatty substance that is found in many foods and contains high amounts of phosphatidylcholines, which are a form of choline. Typically derived from soy, this is typically supplemented for lowering cholesterol. It also contains phosphatidylserine, which is purported to have some health benefits. Neither of these compounds have evidence for raising ACh levels in the brain.

DMAE

This is a compound that is purported to increase ACh levels in the brain, but there does not appear to reliable evidence that it can change the levels of ACh in the brain to any notable degree.

Centrophenoxine

This is another cholinergic that appears to be a more effective form of DMAE. However, it also severely lacking in evidence and while it does appear to effective at raising acetylcholine in the brain [85], it is very understudied and current evidence is lacking. It does appear to have neuroprotective qualities [86][87][88].

Phosphatidylcholine

This is a phospholipid which contain choline. There is one study I found that indicates it increases ACh levels [83], but otherwise studies are severely lacking for it’s efficacy and pharmacology. One study found that it did not influence ACh levels at all following administration [84].

Huperzine-A

Huperzine-A is another naturally occurring compound that is used to raise levels of ACh in the brain. However, unlike every other cholinergic so far, this one has a very different MoA. Rather than directly raising levels of ACh, it works by preventing the breakdown of circulating ACh by inhibiting the specific enzyme responsible for breaking down ACh called acetylcholinesterase [89]. ACh is not reuptaken into the synapses like other neurotransmitters but is instead broken down by this enzyme acetylcholinesterase.

Huperzine-A targets this enzyme and prevents it from breaking down ACh for long periods of time, which indirectly leads to higher levels of ACh. It also appears to be an NMDA receptor antagonist [90], which likely leads to some of its neuroprotective effects [91][92]. Huperzine-A also appears to cause neurogenesis (formation of new neurons in the brain) [93].

I have taken Huperzine-A before and I found it to have noticeable and rather unique effects that would be difficult to characterize. It appeared to have cognitive enhancing properties that made me feel more awake, interested, engaged, and sharp.

Also, if you’re going to take it anyway, PLEASE DO NOT TAKE HUPERZINE-A WITH A CHOLINE SOURCE. This can cause excessive choline levels to be present in the brain for a prolonged period (the half life of Huperzine-A is nearly 15 hours). Excessive levels of choline can cause severe depression, slowness, apathy, and other unpleasant effects.

Other Nootropics

Caffeine / L-Theanine

I’m sure many of you reading this have heard of this combination before, as it’s a fairly popular one among the nootropics community. There is an increasing body of literature which demonstrates caffeine as a nootropic on its own right [94][95], but is enhanced when taken with l-theanine.

When caffeine is taken with l-theanine, it is a completely different beast. Caffeine, as most of you are no doubt aware, is a stimulant found in many beverages, most notably coffee, which is used for it’s stimulatory properties.

While caffeine by itself does not have quite the same effect as a cup of coffee, it is still an effective stimulant on its own. Caffeine has a rather unique pharmacological profile – one of it’s primary MoA’s is antagonizing the neurotransmitter adenosine. Caffeine does this by blocking adenosine receptors, thereby preventing adenosine from getting absorbed into them [96].

Adenosine is a neurotransmitter which builds up over the course of the day and is used to signal to our body that we are tired [97]. By preventing these receptors from binding adenosine, this has the effect that we all cherish: feeling more awake and alert in times where we may otherwise feel groggy and sluggish.

One of the common side effects of caffeine is anxiety and jitteriness. Caffeine is not particularly effective for concentration or focus overall, and in fact too much caffeine can be counterproductive as it can cause too much stimulation.

This effect is known as the Yerkes-Dodson Law [98], and can be applied to just about every situation, and is especially relevant with the use of stimulants such as caffeine.

Yerkes-Dodson Law

Yerkes-Dodson Law

This is where l-theanine comes in. L-theanine is a naturally occurring analogue of the amino acid glutamate, and is found most commonly in teas, particularly black tea.

L-theanine is effective at reducing anxiety [102][103][104][105], causes relaxation while simultaneously increasing attention [99][100][101][105], improves memory and decreases stress [115][116][117][118], and has neuroprotective qualities [106][108][109].

As an analogue of glutamate, it’s main mechanism of action seems to come from modulating glutamate receptors. It binds to all three glutamate receptors (AMPA, NMDA, and kainite), acting as an antagonist of the former two and agonist of the latter [106][107][108][109].

L-theanine has the unique quality of indirectly raising levels of dopamine, gaba, BDNF and NFG in the brain [110][112][113][114], as well as mixed results with serotonin [110][111]. These effects account for some of its anxiolytic properties. The increase in BDNF and NGF levels and the neuroprotection account for some of it’s nootropic-like qualities.

For these reasons, l-theanine has known for some time to be quite synergistic (an effect greater than the sum of their separate effects) with caffeine and other stimulants. When taken together they are become more than merely the sum of the two parts. In other words, a combination of caffeine + l-theanine could be said to be 1+1=3 instead of 2 in terms of the effectiveness as a nootropic.

I have taken caffeine + l-theanine many times due to it’s relative cheapness, simplicity, and effectiveness. It’s a very reliable and well-rounded nootropic that can greatly enhance attention and can make zen-like flow states much more attainable.

Recommended dosage is either a 1:1 ratio or a 2:1 ratio of theanine to caffeine. A standard dose would then be something like 200mg of caffeine and 200mg or 400mg of theanine. I would personally recommend a 2:1 ratio as theanine does not diminish the effects of caffeine in higher doses.

Creatine

This may be a surprise to some of you, but creatine is more than just a bodybuilding supplement. The mind and body are one system and creatine is a substance which will provide benefit to both.

Creatine is another naturally occurring substance that is found in many foods, especially red meats, and is a vital nutrient for our body. When supplemented it can provide further benefits that would be hard to attain from diet alone.

Creatine is no joke, there is perhaps no supplement in history which has been studied more thoroughly than creatine. This is for a simple reason: it works. This is not a placebo supplement that doesn’t actually do anything, it has real effects and real benefits. It also is extremely inexpensive and has almost no side effects except for GI distress (which only happens if you don’t drink enough water).

While it may not be a nootropic drug strictly speaking, it can be used for nootropic purposes due to its effect on mental clarity and energy. It can be a great tool for fixing lethargy, brain fog, and poor concentration. There is are a range of conditions called cerebral creatine deficiency syndromes (CCDS) which result in mental retardation [119], and this may further drive home the point that this is not a mere bodybuilding supplement but should be considered something like a nutrient.

Overall, the main benefit of creatine for nootropic purposes is that it will provide you with more mental energy, especially in times of stress. Creatine is a molecule that provides adenosine triphosphate (ATP) to the cells, which is basically the molecular “currency” for providing cellular energy [115][116]. This provides benefits to every energy-demanding part of the body, including the brain.

The only form worth taking is creatine monohydrate which is the cheapest and most effective form. For general cognitive-enhancing purposes, it is recommended to take 5g a day with a meal. Make sure you drink plenty of water (2-3 full glasses worth) to avoid any potential GI discomfort. It is not a good idea to take it with coffee or alcohol either as you may get diarrhea. Take it with breakfast in the morning and drink plenty of water and you’ll be fine. You can take higher doses at first to “load” on it and get it saturated in your system, but these pose the risk of some mild stomach pains or general GI discomfort.

L-Tyrosine:

Tyrosine is an amino acid typically found in cheeses and meats. L-tyrosine ultimately is used to increase levels of circulating dopamine in the brain. L-tyrosine is not a direct precursor to dopamine; it is first converted into L-DOPA in the brain which is then directly used for dopamine synthesis as well as norepinerphrine and epinephrine (adrenaline) if needed. These three catecholamines are important neurotransmitters which play a large role in the regulation of attention, memory, cognition, and mood.

Catecholamines_biosynthesis

When l-tyrosine is supplemented it is converted into L-DOPA by an enzyme called tyrosine hydroxylase, which is responsible for the regulation of dopamine synthesis [120]. This process of converting l-tyrosine into L-DOPA is rate limited by the enzyme, which means that it will only convert as much tyrosine as needed, and acts sort of as a “safety” net to prevent it being oversatured.

In short, l-tyrosine is best used to keep your dopamine levels at their baseline and delaying the depletion of dopamine, which would be helpful when doing something like studying which no doubt depletes them. However l-tyrosine will not elevate dopamine levels beyond their normal threshold.

L-DOPA can also be supplemented on its own but there is no rate-limited conversion into dopamine in the brain [120]. This can lead to abnormally elevated dopamine levels in the brain. I do not recommend taking L-DOPA for this reason as it can lead to a downregulation of dopamine over time. When you saturate your brain with abnormally high levels of any neurotransmitter the body responds by decreasing the density of dopamine receptors thereby decreasing the ability of your brain to absorb dopamine in the future.

This is true with any drug that elevates neurotransmitters to unusually high levels, the brain always tries to maintain homeostasis, which means it is aiming to achieve a neurochemical equilibrium. If you start chronically elevating certain neurotransmitters it is going to respond by decreasing the ability of the brain to absorb these neurotransmitters.

For these reasons I do not recommend taking L-DOPA. L-tyrosine is much safer and poses none of the risks that L-DOPA has.

The recommended dosages are 100-150 mg/kg of bodyweight, which ranges from 7-10g for a 150lb person and 9-13.5g for a 200lb person.

Additional Information

There is one thing I want to emphasize here above all else. If your diet is poor and you’re not getting enough sleep, nootropics will only take you so far. I think of them as a complement to my life and not a primary force for change. Despite how useful these substances are, don’t fall into the mistake if thinking you can neglect your health and expect nootropics to solve all of your problems.

If you’re not taking care of yourself, you should not expect nootropics to change your life. Even if you take the highest quality and best nootropics for studying out there, at the end of the day they are not a replacement for hard work and discipline. I know that’s not a very fun thing to say, but it’s the reality and I wanted to make it clear that I am not promoting nootropics as a magical substance as portrayed in the movie Limitless.

My personal study stack recommendation:

Oxiracetam or Pramiracetam
CDP-Choline or ALCAR
Tyrosine
Caffeine
Theanine
Phenylpiracetam

Recording in which I briefly summarize the contents of this post.

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Jacob S

4 Comments

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