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The Ultimate Guide To Nootropics

your brain on nootropics

Nootropics are all the rage these days, and for good reason.

It’s an attractive pitch…

“Take this pill and you’ll be smarter, more creative, more productive.  Really, you’ll just be all around better!”

But is this really true?

Can a drug or supplement actually enhance the way our brains work? Or is this just slick marketing designed to prey on the fact that most people wish they could think/function/perform just a little bit better?

Well, that’s exactly what we’re going to get to the bottom of in this article.

We’ll go over what nootropics are, the various mechanisms underlying their effects, and which ones are actually worth using (and why).

This is the ultimate guide to nootropics.

Let’s begin…

What Are Nootropics?

Nootropics are substances which enhance cognitive function.

The term ‘nootropic’ is Greek and literally translates to ‘towards the mind’.

People often refer to these kinds of substances as ‘smart drugs’ but the word ‘nootropic’ is really just a blanket term which applies to any substance which enhances some aspect of the way our brains work.

It could be a drug, supplement, or any other chemical.

It’s a nootropic if it enhances things like:

  • memory
  • processing speed
  • reaction time
  • creativity
  • focus
  • motivation
  • productivity

Naturally, these kinds of substances are of interest to wide range of people, from college students to high performing executives.

Anyone who strives to excel in life is a potential candidate for nootropics.

How Do Nootropics Work?

Different nootropics do different things and they all work in different ways, but in the end, it (pretty much) all boils down to chemistry.

Most nootropics exert their effects by entering the brain and influencing levels of one or more neurotransmitters.

Neurotransmitters are the chemical messengers of the brain which dictate how you think and feel. Every feeling you feel and every thought you have is, on some level, the result of a mixture of neurotransmitters.

Different neurotransmitters control and/or participate in different aspects of cognitive function, but there is a lot of overlap.

For example, Dopamine and Acetylcholine are both heavily  involved with learning, attention,and memory, but they also have separate jobs which have nothing to do with each other.

In order to understand which nootropics do what, it helps to have a basic understanding of which neurotransmitters do what.

Acetylcholine

Acetylcholine is a neurotransmitter which is heavily involved in things like:

  • memory/learning
  • muscle contraction
  • sleep/dreaming

Declines in Acetylcholine levels are associated with cognitive disorders such as Dementia and Alzheimer’s so increasing Acetylcholine levels is the aim of many nootropics developed to treat those disorders.

There are two primary ways that nootropics tend to increase Acetylcholine levels:

  1. by providing Choline, the precursor to Acetylcholine
  2. by blocking Acetylcholinesterase, the enzyme that breaks down Acetylcholine

Either of these mechanisms can potentially increase Acetylcholine levels and bring about some degree of cognitive enhancement.

Dopamine

Dopamine is a neurotransmitter which is primarily involved in things like:

  • Pleasure/Reward
  • Motivation
  • Wakefulness
  • Focus/Attention
  • Sleep

It’s one of the key movers in the ‘fight or flight’ response and belongs to a group of similar molecules called Catecholamines.

Many stimulants work by increasing levels of Dopamine (and the other Catecholamines) in the brain, bringing about enhancements in certain areas of cognitive function.

It’s worth mentioning, though, that Dopamine is believed to play an important role in addiction.  Stimulants that increase Dopamine levels tend to have an addictive nature to them.

Drugs that work by massively increasing Dopamine may provide a boost of focus, energy, and motivation, but they should be used with caution.

Noradrenaline

Noradrenaline is the next step in Catecholamine synthesis, after Dopamine. Both of these neurotransmitters are heavily involved in the ‘fight or flight’ response.

Noradrenaline’s primary job is to mobilize the brain and body for action.

In the brain, it accomplishes this by

  • increasing alertness/focus/attention
  • enhancing memory formation/retrieval

Noradrenaline is one of the key neurortransmitters–along with Dopamine–targeted by many stimulant nootropics such as Adderall and Focalin.

Serotonin

Serotonin is sometimes referred to as the ‘happy neurotransmitter’.

It plays role in regulating:

  • mood
  • sleep
  • appetite

Serotonin is one of the primary neurotransmitters targeted by drugs like opiods, but some nootropics impact Serotonin as well.

Glutamate

Glutamate is the primary excitatory neurotransmitter in the brain.  It’s  job is to stimulate brain activity.

As you can imagine, many nootropics, which stimulate brain activity, do so by influencing Glutamate.

Glutamate regulates activity levels in tandem with another neurotransmitter, GABA.

GABA

GABA is the primary inhibitory neurotransmitter in the brain. It’s job is to slow down brain activity.

GABA is the target of most anti-anxiety drugs and supplements because reducing overall brain activity effectively eliminates anxiety.

Slowing down brain activity may not sound like something a nootropic should do, but many nootropics influence GABA activity in the brain.

How To Think About Neurotransmitters

We have a tendency to attribute the actions of a certain substance to one or two neurotransmitters, but in reality, most nootropics exert their effects by influencing many neurotransmitters.

There are an infinite amount of potential combinations which is why all nootropics–even the ones that work similarly–have different effects.

And of course, our own internal brain chemistry plays role as well.

We can try and predict how certain nootropics will affect us based on our knowledge of the neurotransmitters they interact with, but our actual experience may play out differently.

With that in mind, let’s take a look at some of the most popular nootropics.

A Closer Look At Some Of The Most Popular Nootropics

There are ton of different nootropics.  Anything that is believed to enhance some aspect of cognitive function can be considered a nootropic.

Some are drugs, some are supplements, and some fall into a gray area between the two.

Different nootropics have different safety profiles as well.

By definition, all nootropics are used for the purposes of enhancing cognitive function, but that’s the only thing they’re guaranteed to have in common.

We can’t simply group all nootropics together and make blanket statements like “nootropics are effective” or “nootropics don’t do anything”.

We have to look at each one on an individual basis to determine what’s it’s capable of.

So, let’s take a look at 20 of the most popular nootropics…

Alpha GPC

Alpha GPC is a choline-containing phospholipid (component of cell membranes) which is generally considered to be the most bioavailable form of Choline.

It is roughly 40% Choline by weight and easily crosses the blood brain barrier where that Choline freely converts into Acetylcholine.

Acetycholine, if you recall, is that neurotransmitter (chemical messenger) I mentioned earlier which is involved with things like memory and learning.

By supplying Choline for the production of Acetylcholine, Alpha GPC may enhance cognitive function.

Naturally, most of the studies have focused on diseases like Alzheimer’z, but there is evidence to suggest it’s effective in healthy people as well.

Additionally, Alpha GPC has been shown to boost power output during exercise, thought to be the direct result of enhanced Acetylcholine signaling.

The clinical dose for Alpha GPC is anywhere from 600-1200mg/day.

Citicoline

Citcoline is similar to Alpha GPC in that it serves as a source of Choline for the production of Acetylcholine, but it also provides a source of Uridine (which we’ll discuss next).

Studies show that Citicoline can improve memory and attention, not just in people with some sort of cognitive impairment, but in healthy people as well.

This makes it one of the most effective nootropic supplements you can take.

 

A clinically effective dosage of Citicoline is 250mg/day.

Uridine

Uridine is a unique molecule which promotes synthesis of cellular membranes.

It is believed to play a critical role in overall brain health and at least part of the reason why Citicoline is an effective nootropic.

Research shows that Uridine can increase synapse formation and enhance memory and learning capabilities.

Of course, if you’re taking Citicoline, you’re already getting some Uridine.

A clinically effective dosage of Uridine would be anywhere from 500-1000mg/day.

Phosphatidylserine

Phosphatidylserine is a phospholipid, meaning it supports the health and structural stability of every cell in the human body.  It is found in particularly high concentrations in the brain, though, where it is believed to play a major role in overall cognitive health.

Research shows that Phosphatidylserine can improve cognitive abilities in healthy subjects as well as elderly subjects and subjects with mild to moderate cognitive dysfunction.

This makes it one of the few natural nootropics which may benefit the average person, not just elderly people who’s minds are starting to slip.

Studies also show Phosphatidylserine has stress reducing properties, both subjective (perceived stress) and objective (measured by Cortisol).

A clinical dosage of Phosphatidylserine would be anywhere from 200-800mg/day.

Bacopa Monnieri

Bacopa Monnieri is an herb which has been used for centuries in Ayurveda, an ancient system of medicine which originated around present day India.

Mostly, it was used to enhance memory and support brain health in general.

Unlike most herbal nootropics, modern science has actually confirmed many of the alleged benefits of Bacopa Monnieri.

Research shows Bacopa can enhance memory, learning rate, immediate recall, and language comprehension, as well as reduce susceptibility to distraction.

It’s not quite clear how Bacopa accomplishes all this, but it appears to involve several neurotransmitters (particularly Acetylcholine, Dopamine, and Serotonin) as well as the antioxidant and anti-inflammatory properties of the herb.

One thing is for sure though…

Whether you’re an elderly person experiencing cognitive decline or healthy, young person simply looking for mental edge, Bacopa Monnieri is an effective nootropic.

Modafinil

Modafinil is a synthetic stimulant which was originally developed to treat Narcolepsy–a disease characterized by falling asleep randomly.

It’s a prescription medication in the US, though readily available from overseas.

Modafinil has been shown to promote wakefulness and enhance working memory.

Research indicates it works by influencing Dopamine in some regard, but the truth is, nobody really knows precisely how Modafinil does what it does.

One thing is for sure though…

It does work.

While I personally find Modafinil to be lacking in the focus department, it definitely removes any desire to sleep whatsoever.

An effective dose of Modafinil is anywhere from 100-200mg.

Adrafinil

Adrafinil is the precursor to Modafinil.  For all intents and purposes, it’s basically just a less effective veresion.

They work the same way, but Modafinil is much more potent.

Adrafinil has been shown to increase wakefulness in animal studies, but it has never been studied in humans.

All the alleged benefits of Adrafinil are just extrapolated from Modafinil.

Unfortunately, due to concerns over the metabolization of Adrafinil to Modafinil taking a toll on the liver, it’s not commonly advised to take it on a continuous basis.

An effective doses of Adrafinil is anywhere from 600-900mg.

Lion’s Mane

Lion’s Mane, also known as Yamabushitake, is a species of mushroom (Hericium erinaceus) which is believed to protect and repair the brain and improve cognitive function.

Research in mice indicates this may very well be true, but the only human study pertaining to cognitive function showed benefits in subjects with cognitive impairments of sorts.

This makes it more or less impossible to say how exactly Lion’s Mane impacts normal, healthy brains. Nonetheless, the preliminary research is promising so it may turn out to be an effective natural nootropic.

 

Due to a lack of human research, there is no established clinical dose for Lion’s Mane, but 2 or 3 grams per day seems to be the standard dosage.

Piracetam

Piracetam is a synthetic nootropic which belongs to a group of similar chemicals known as racetams.  It is by far the most popular, but not the most potent.

Still, due to it having a more extensive history of use and more research behind it in general, it continues to be used for the purposes of improve cognitive function, reducing social anxiety, and boosting creativity.

Research indicates it can improve cognitive function in people with cognitive impairments by enhancing Acetylcholine and Glutamate signaling.

Unfortunately, studies in healthy human subjects are in short supply.

One study did find increased brain activity, measured by electroencephalogram (EEG), in healthy subjects after consuming Piracetam which was thought to represent various brain functions cooperating on a higher level.

But measuring EEG activity isn’t the same as measuring cognitive performance over time.

Piracetam is certainly a promising nootropic, but most of what you hear about it is based on a combination of subjective experiences and studies in subjects with deteriorating brain health, not hard science.

It’s hard to say exactly how much a normal, healthy person can benefit from Piracetam.

An effective dose of Piracetam is anywhere from 1600 to 4800mg/day.

Aniracetam

Aniracetam is also a member of the racetam family but is roughly 5 times more powerful than Piracetam.

Unfortunately, it has even less research behind it then Piracetam. That said, the research which has been conducted indicates it may very well be an effective nootropic.

Like Piracetam, the mechanisms behind Aniracetam are not fully understood, but it appears to interact with an even wider selection of neurotransmitters including:

  • Glutamate
  • Acetylcholine
  • GABA
  • Dopamine

Most experienced nootropic users would say Aniracetam is better than Piracetam, but it’s not clear how.

Oxiracetam

Oxiracetam is yet another member of the racetam family which is said to be one of the most potent.

As is the case with Aniracetam, Oxiracetam lacks human studies, but preliminary research (in animals) indicates it can improve cognitive function.

It appears to mostly work by enhancing Acetylcholine signaling.  It doesn’t seem to interact with Dopamine or and may reduce GABA activity to some degree.

Oxiracetam may be slightly stimulatory, but most people don’t consider it to be stimulant, per se.

An effective dosage is anywhere from 1200-2400/day.

Phenylpiracetam

Phenylpiracetam is yet another member of the racetam family.

It is considered to be the strongest of them all, though no studies have actually compared the efficacy of different racetams against each other.

Phenylpiracetam is sold under the brand name Phenotropil in some countries, but it’s readily available in generic form from various nootropics vendors.

Research indicates it can improve memory and attention, reduce anxiety and depression, and enhance motor coordination.

Unfortunately, all of this research has either been conducted in animals or people with some sort of cognitive deficit.

There’s really no data on how Phenylpiracetam impacts cognitive function in normal, healthy people, so it’s tough to say how effective it really is as a nootropic.

Not that I would recommend believing every review or testimonial you read, but there is a lot of anecdotal evidence which indicates Phenylpiracetam is an effective nootropic.

There’s just not much in the way of empirical evidence…

Noopept

Noopept is commonly grouped in with the racetam family, but it actually isn’t a racetam.

It’s an entirely unrelated synthetic nootropic that just happens to also be aimed at improving things like:

  • memory
  • reaction time
  • ability to concentrate

Like Oxiracetam, Noopept may be mildly stimulatory, but not to an overwhelming degree.

Research shows that Noopept can improve memory and cognitive function to a greater extent than Piracetam.

In fact, it’s believed to be roughly 1000 times as powerful!

Noopept appears to exert the majority of the cognitive effects through two mechanisms:

  1. increasing Acetylcholine sensitivity
  2. triggering Neurotrophin production

Either of these things would be an effective means of improving brain function and cognitive health in general, though the latter is definitely the most unique mechanism of the two.

An effective dose of Noopept is 10-30mg/day.

DMAE

Dimethylethanolamine, more commonly referred to as  DMAE, is a cholinergic compound which is generally touted to improve overall brain health.

It works by reducing levels of beta-amyloid, a protein fragment which is associated with cognitive impairment and aging.

DMAE seemed pretty promising as a nootropic at one point but research indicates the cognitive benefits are minor at best.

Furthermore, no studies have been conducted in normal, healthy subjects.  Just subjects with some level of cognitive decline.

Effective doses are said to be in the range of 1-2g/day.

Centrophenoxene

Centrophenoxene is synthetic nootropic which is sold under the brand name ‘Lucidril’, but also widely available on the internet in generic form.

Centrophenoxene is basically just a more bioavailable form of DMAE.

This is similar to how Alpha GPC is a more bioavailable form of Choline.

Centrophenoxene has been shown to restore aspects of cognitive function in subjects with Dementia, thought to be in part due to increased cellular water retention.

Whether it’s effective in normal, healthy people remains unclear but Centrophenoxene is definitely superior to DMAE.

A clinical dose would be anywhere from 1-2g/day.

Huperzine A

Huperzine A inhibits the action of Acetylcholinesterase, an enzyme which breaks down Acetylcholine.

By blocking the action of Acetylcholinesterase, Huperzine A can increase Acetylcholine levels, potentionally resulting in some level of cognitive enhancement.

It has been shown to enhance memory and learning capabilities in children complaining of memory problems, but most of the studies have focused on cognitive disorders such as Alzheimer’s.

One study found that while Huperzine A was an effective Acetylcholinesterase inhibitor, the increase in Acetylcholine did not result in cognitive benefits in normal, healthy adults.

So, it would appear that while Huperzine A does do what it’s supposed to, not everyone is likely to benefit.

A clinically effective dosage of Huperzine A is anywhere from 50-200mcg.  Note: that’s MICROgrams no MILLIgrams, as in 1 millionth of a gram.

Sulbutiamine

Sulbutiamine a synthetic form of Thiamine (Vitamin B1) which was originally developed in Japan to treat Thiamine deficiency.

You can think of it as souped up, highly bioavailable form of Vitamin B1 (Thiamine).

It is believed to convey a variety of benefits including neuro-protection, memory enhancement, and fatigue reduction.

Unfortunately, most of these benefits are extrapolated from rodent studies.  There hasn’t been much research in humans.

A few studies (in humans) have found that Sulbutiamine may be somewhat effective for improving symptoms of chronic infection-related fatigue and fatigue brought on by Multiple Sclerosis.

Sulbutiamine appears to exert it’s effects by influencing the activity of Acetylcholine, Dopamine, and Glutamate receptors.

Average doses of Sulbutiamine range from 200-400mg/day.

Vinpocetine

Vinpocetine is a synthetic molecule derived from a naturally occurring molecule, Vincamine, found in Periwinkle.

It’s a phosphodiesterase (PDE) inhibitor which can enhance blood flow, specifically to the brain.

Vinpocetine has been used clinically for stroke recovery (where blood flow to the brain is compromised) and to treat other cognitive disorders.

Studies in healthy individuals are few and far between.

Direct infusions (injections) have been shown to increase blood flow and brain oxygenation.

One study found that 40mg of oral Vinpocetine improved reaction time and memory scanning speed in healthy, young adults.

Overall, it appears that Vinpocetine may be an effective nootropic in some respects, but only at higher doses (at least 40mg).

Most nootropics contain 5 or 10mg at most.

Adderall (Amphetamine)

Adderall is stimulant drug which contains four Amphetamine salts:

  1. Amphetamine aspartate monohydrate
  2. Amphetamine sulfate
  3. Dextroamphetamine saccharate
  4. Dextroamphetamine sulfate

In the US, Adderall is schedule II substance which requires a valid prescription to legally possess.

Typically, it’s prescribed to people with ADHD or Narcolepsy, but due to its powerful stimulant properties, it is used by all kinds of people, from students cramming for exams to high performing CEOs.

Research shows that Adderall can enhance cognitive function in both individuals with ADHD and those without, though it doesn’t ‘make you smarter’ like people think.

Adderall increases your ability to focus to a pretty overwhelming degree which provides the illusion that you’re brain is working better.

Really, you’re just more focused.

Adderall works by increasing Dopamine and Noradrenaline levels, similar to many other stimulants.

Adderall can definitely help you focus (and stay awake) whether you have ADHD or not, but it comes with serious risks which should be weighed heavily.

Besides being highly addictive, Adderall comes with a host of potential side effects, including (but not limited to):

  • jitters
  • anxiety
  • headache
  • dry mouth
  • irritability
  • hypertension
  • paranoia
  • irregular heartbeat

But the real downside to Adderall is that the more you use it, the more you tend to depend on it to focus and get things done.

Taking Adderall on a regular basis and then stopping can result in decreased motivation, inability to focus, and a decline in productivity.

So, while Adderall is technically a highly effective nootropic drug, extreme caution should be exercised when using it for off-label purposes.

Focalin (Dexmethylphenidate)

Focalin is similar to Adderall in that it is a prescription-only medication which is generally used to treat ADHD.

Chemically, however, it is related to Ritalin (Methylphenidate).  It’s not an amphetamine, but has similar effects on brain function and cognitive abilities.

Focalin has been shown to improve ADHD symptoms, similar to Adderall but whereas Adderall works (primarily) by triggering the release of Dopamine and Noradrenaline, Focalin works (primarily) by inhibiting the reuptake of these chemicals.

The result is the same though…

Improved ability to focus, more motivation, and mood enhancement.

In the US, Focalin is a schedule II controlled substance, meaning it carries the same risks and potential for abuse as Adderall.

So, yes Focalin has nootropic properties.  No, it’s not a good idea to use it regularly.

 

Phenibut

Phenibut is a synthetic drug which was originally developed by Russian scientists to treat anxiety.

It works by increasing the activity of GABA in the brain. effectively slowing down brain activity (which reduces anxiety).

In this regard it is similar to anti-anxiety drugs like Etizolam, Alprazolam, and Temazepam but, whereas these drugs bind to the benzodiazepine subsection of GABA receptors, Phenibut is a full GABA agonist.

It binds to every site on the GABA receptor, not just benzodiazepine receptors.

Phenibut is also widely believed to have nootropic properties, but there isn’t much in the way of actual evidence to back that up.  Only theories…

Furthermore, due to Phenibut causing tolerance build-up and, eventually, dependence, it doesn’t make for a very effective drug in the long-term.

The more frequently you use it, the more addicted you can become.

Effective doses of Phenibut are anywhere from 500-1500mg.

Are Nootropics Safe?

Different nootropics carry different safety profiles.

Some–like Alpha GPC, Citicoline, and Phoshatidylserine–are extremely safe.

Others–like Adderall, Focalin, and Modafinil–come with risks.

It really depends on which substance we’re talking about.

Anyone who says “nootropics are dangerous” is simply misinformed.  On the flip-side,  anyone who says “nootropics are perfectly safe” is jumping the gun.

The truth is some of these compounds can be taken forever without any fear of consequence while others can flat out ruin your life.

Nootropics That I Actually Recommend

  • Alpha GPC
  • Citicoline
  • Uridine
  • Phosphatidylserine
  • Bacopa Monnieri

The Bottom Line On Nootropics

The word ‘nootropic’ is really just a blanket term that describes any substance which improves cognitive function.

Because there are so many different ways to influence cognitive function, it doesn’t make sense to group all nootropics together and pass general judgments about them as a collective.

Instead, we need to look at them on an individual basis in order to determine how effective they are and what kinds of risks they carry.

The majority of nootropics either haven’t been proven effective or carry risks that outweigh the rewards.  There are some, however, which are both safe AND effective.

These are the nootropics you should use.

Got Anything To Add About Nootropics?  Any Experiences You’d Like To Share?  Comment Below…

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