9/14/2016 A Complete Guide to Nootropics (Smart Drugs)

Home   >   Brain   >   A Huge, Detailed Guide to Nootropics (Smart Drugs): How They Work and How to Use Them

A Huge, Detailed Guide to Nootropics (Smart

Drugs): How They Work and How to Use Them
By Adam Sinicki on August 26, 2014

Ever wished you were smarter? That you could memorise everything you read
and ace every exam? That you could run rings around people in conversation so
that you always emerged victorious? That you could come up with amazing ideas
that would gain you fortune and adulation? Well so has just about everyone else,
which is why nootropics – or ‘smart drugs’ – are a source of such discussion and
attention across the web.

But are nootropics really a safe way to increase your brain power? How do they
work? And how do you go about using them in the most e‐ective manner
possible? Consider this your complete beginners’ guide to hacking your brain
with supplements. If you’re interested in getting started, then this will help you
to understand the subject and to avoid common mistakes and pitfalls.

What Are Nootropics?

Nootropics are any compounds that can increase brain power in a speci†c
capacity; whether that means memory, focus, creativity or verbal တuency. Often
the term is used to describe speci†cally those things that a‐ect the brain in an
acute manner: which can be taken immediately before revising or before writing
in order to bene†t that speci†c task.

The most famous example of a nootropic in †ction, is perhaps ‘NZT’ which was
featured in the †lm ‘Limitless’ (itself based on the book ‘The Dark Fields’). While
on NZT, the protagonist is able to play the stock market, write best-selling
literature, network his way through organisations and recall information
thought long forgotten. That’s the aim of nootropics, but the reality is generally
a lot less extreme.

Another very ‘famous’ example of a nootropic, and one that pretty much
everyone has used at some point or another, is ca‐eine. Ca‐eine is a substance
that is able to increase our ability to focus, to stay awake and to remember
details and for many it’s a crucial part of their ritual when waking up †rst thing in
the morning.

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What Is and Isn’t a Nootropic?

Now, ca‐eine does actually have some side e‐ects and some negative e‐ects
on cognition. It can make you jittery and jumpy, it can cause headaches, it can
negatively a‐ect sleep and in the long-term it can lead to tolerance – meaning
that your brain changes in such a way as to ‘adapt’ to the ca‐eine you’re giving
it. In other words, because things like dopamine and norepinephrine get
elevated when taking ca‐eine, this then means that your brain can adapt by
reducing the amount of those neurotransmitters that it produces naturally to
try and re-establish an equilibrium. This can lead to withdrawal, and actually
that’s the reason that many people feel groggy in the morning until their †rst
co‐ee – they’re experiencing withdrawal symptoms!

Some people thus conclude that ca‐eine doesn’t count as a nootropic – because
it doesn’t purely improve the brain. Some take the stance that to classify as a
nootropic, that substance must only be bene†cial for cognition. Then again
though, the argument could be made that all substances are both positive and
negative for the brain as we will see…

It could also be argued that something like an antidepressant would be a

nootropic. Say a SSRI (Serotonin Re-Uptake Inhibitor) increases your mood
e‐ectively, and at the same time potentially improves motivation and
productivity, you might then conclude that it has enhanced your brain and is
thus a nootropic. The term isn’t normally used this way, but really there’s no
right or wrong answer – which is also an issue surrounding transhuman
technologies (is plastic surgery ‘transhumanism’?).

You could even go so far as to argue that alcohol or marijuana are ‘nootropic’ in
some senses – as they help to relax the brain and thereby (some argue) help to
stimulate creativity.

How They Work

There are a large range of nootropics, some of which are synthetic compounds,
others of which are herbal extracts and others still that are vitamins, minerals
and other nutrients in potent combinations.

All of these nootropics work di‐erently, but generally they have the same basic
underlying mechanism – which is that they a‐ect the neurotransmitters.
Neurotransmitters are the chemicals that get sent between neurons in order to
provide additional information during ‘action potentials’ (the †ring of one
neuron to communicate the next). Webs of neurons in our brain represent our
memories and provide us with all of our cognitive skills, and it’s the
neurotransmitters that get †red across the ‘synaptic gap’ (between the neurons)
that add to the data exchanged between them. Norepinephrine for instance
helps to tell us that something is important and worthy of our attention, while
other neurotransmitters add emotional content or encourage memory. Other
neurotransmitters have a wider e‐ect and make us feel tireder, or more alert
overall. By increasing and decreasing the amounts of these various chemicals,
nootropics can thus trigger a range of responses.

The way that nootropics control the amount of neurotransmitters in the brain
varies however. In some cases they work by preventing them from being
reabsorbed (thus increasing the amount of available neurotransmitters), in
others they block them from working by mimicking their ‘shape’ and †lling the
‘receptors’ that normally register them (thus decreasing their impact on the
brain – which might increase the amount of other neurotransmitters in turn),
while in others they simply provide the brain with more of said neurotransmitter
by providing more of the speci†c building blocks. For instance, the nootropic

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stack known as ‘CILTEP’ contains an amino acid called L-phenylalanine, which is a
precursor to dopamine.

For more information on how neurons and neurotransmitters work, read my

guide to the basics of neuroscience.

A List of Popular Nootropics

There are countless di‐erent nootropics you can use to increase your brain
power and this is not the place for an exhaustive list (that’s coming!).
Nevertheless, this should give you a pretty in-depth overview of the main
nootropic classes and how they work. It will further your understanding of
nootropics, but if you want to skip ahead for now then feel free to go ahead.

Racetams: Racetams are one of the oldest and most popular groups of
nootropics. The best known is Piracetam (my experiences), and most others are
derivatives of that (such as aniracetam, oxiracetam etc.). These nootropics are
particularly e‐ective in improving attention, memory and learning and work by
increasing the activity of acetylcholine – a neuromodulator (meaning that it
modulates a range of neurons rather than being used directly in synaptic
transmissions) that is implicated in learning and ‘long term potentiation’.
Acetylcholine is the most common neurotransmitter in the brain and was the
†rst to be discovered. Piracetam is a cyclic derivative of GABA, and enhances
acetylcholine receptors.

Cholinergics: Another way to increase the activity of acetylcholine in the brain is

simply to provide the body with the building blocks of acetylcholine itself. The
best way to do this is with choline, which is a precursor and is found in eggs
among other things. When using racetams like Piracetam, it makes sense to
consume extra choline. You can also get choline from sources like alpha GPC – a
substance found naturally in breast milk which provides readily bio-available
choline and easily crosses the blood-brain barrier. It is thought that alpha GPC
may help to increase the IQ of those children who are breastfed.

Acetylcholinesterase Inhibitors: Acetylcholinesterase is an enzyme that breaks

down acetylcholine. Acetylcholinesterase inhibitors work by reducing
acetylcholinesterase (try saying this sentence ten times quickly), thereby
increasing acetylcholine. A good example is huperzine A, which is also an NMDA
receptor agonist – meaning it promotes the growth of nerve cells via nerve
growth factor. It may be e‐ective in increasing neuroplasticity. Galantamine is
another substance that works by regulating the activity of enzymes in the brain.

Ampakines: Ampakines work to promote alertness, mental energy and memory

span by activating glutamatergic AMPA receptors. AMPA receptors are
responsible for the regulation of synaptic transmissions. Ampakines such as
sunifram are also stimulants.

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Eugoeroics: Eugeroics are substances that increase wakefulness and alertness,
but without some of the negative side e‐ects associated with other stimulants.
These work by increasing neurotransmitters associated with attention and
excitability, including epinephrine, norepinephrine and dopamine. Two of the
most popular examples are adra†nil and moda†nil. Moda†nil was originally
developed in order to be a treatment for narcolepsy, but has become popular
for its o‐-label use as a productivity aid, particularly among ‘executive’ types.

See more detail on the mechanisms of Moda†nil here, and my review here.

Adderall is also a popular ‘stimulant’-type nootropic, which was originally

intended for use by ADHD su‐erers. Adderall is an amphetamine (like speed)
and increases norepinephrine, dopamine and serotonin. Ritalin is a popular
alternative and another psychostimulant that works to a‐ect the central
nervous system. In this case, Ritalin works by preventing the re-uptake of
dopamine – a neurotransmitter highly implicated in attention and goal-oriented
behaviour.

GABAergics: GABAergics are nootropics that interact with GABAergic neurons.

GABA is a neurotransmitter that is implicated in sleep and relaxation and which
can help prevent stress and anxiety. They can also be used to treat insomnia, and
some bodybuilders use them to increase growth hormone production during the
night. One of the easiest ways to stimulate GABA is with pure GABA – an amino
acid derived from vitamin B6 and glutamate. Direct supplementation is
potentially pointless however as it cannot cross the blood-brain barrier.
Nevertheless it continues to be sold in a pure form. Phenibut is a derivative of
GABA which can be used to elevate levels in the brain. It also aids in the
communication of the brain across hemispheres, potentially increasing
creativity. It can however cause side e‐ects and lead to tolerance.

Serotonergics: Serotonergics meanwhile impact the availability of serotonin – a

feel good neurotransmitter implicated in mood and, pleasure and stress relief.
Tryptophan is one serotonergic that can be found in dairy food, eggs, soybeans
and poultry. As a precursor to serotonin it can improve the mood and prevent
stress. Tryptophan is also a building block for melatonin – the sleep hormone –
and thus may help improve sleep. 5 HTP meanwhile is the chemical pre-cursor of
serotonin (the by-product of tryptophan metabolism) which makes it useful for
cutting the middle man as it were.

Dopaminergic: Dopaminergics are nootropics that impact speci†cally on

dopamine levels. A good example is Tyrosine which is converted into dopamine,
epinephrine and norepinephrine increasing alertness and attention. Theanine
meanwhile, available in green tea, is a pre-cursor to serotonin as well as being
able to stimulate dopamine levels. It can be used alongside ca‐eine to reduce
anxiety and jitters.

Neurohormones: Neurohormones are hormones created by neuroendocrine

cells. These are released into the blood but can also work as neurotransmitters
in the brain when processed in the hypothalamus and released through axon
terminals along with other neurochemicals. Examples include dopamine,
epinephrine and oxytocin. Thus, substances that increase these speci†c
hormones might also have impacts on brain function. DHEA for instance is a
neurohormone with steroid-like functions acting as a building block for
testosterone and oestrogen. It is protective against certain age-related decline
and may help adrenal fatigue. Vasopressin meanwhile is an amino acid peptide
(and antidiuretic) produced in the pituitary gland. It appears to be useful for
improving short term memory and increasing deep memory
imprinting. Melatonin of course is popular as a sleep aid.

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Cognitive Metabolic Enhancers: Cognitive Metabolic Enhancers work by
increasing energy available to human brain cells via improved metabolism. This
can occur through increased vasodilation (increasing the diameter of blood
vessels to carry more blood to the brain) or by improving the function of cell
membranes (mitochondria). In turn, this leads to more energy in the brain and
stimulates the production of certain arousal-promoting neurotransmitters. One
example is Alpha Lipoic Acid (ALA) which creates more energy via the ‘Krebs’
cycle or breakdown of carbohydrates. You could also consider MCT Oil in this
category, which stimulates the production of ‘ketones’ – an alternative energy
source to glucose favoured by the brain for certain functions. Creatine – the
supplement used by many athletes – has also been shown to help increase
available energy in the brain and thus increase focus and mental energy.

Xanthines: Xanthines are stimulants and derivatives of – you guessed it –

xanthine. Xanthines reduce the e‐ects of adenosine, the build-up of which leads
to sleepiness. They also increase respiration and alertness. The most famous
example of a xanthine is ca‐eine (see HERE for more on ca‐eine), while
theobromine, found in dark chocolate, is also commonly available.

Nutrients: Many more vitamins, minerals and nutrients can be considered

nootropics due to their important roles in building and maintaining the
structures of the brain. Everything from amino acids, to vitamins, to
antioxidants, to fatty acids (especially omega 3 fatty acid) can help to improve
brain function in both the long and short term and protect against age related
decline.

Using Nootropics: What is it You’re Trying to Achieve?

When setting out to use any new nootropic, it is absolutely imperative that you
†rst decide what it is you are trying to accomplish. Nootropics as you’ve seen,
will work by increasing speci†c neurotransmitters within the brain in order to
stimulate speci†c results. The point here, is that no neurotransmitter is going to
automatically make your brain ‘better’ across modalities, but rather it will
improve you in speci†c capacities. It is thus crucial that you take the right
nootropic for the right job.

For example, if you were trying to increase creativity, you might want to take
nootropics that helped to relax the brain and increase communication between
neurons. For this a good option could be a GABAergic like phenibut. On the
other hand, if you want to increase your focus and attention, then you would do
better to take a xanthine, or a dopaminergic. Attention and focus mean we
concentrate on one idea, or one stimulus. On the other hand, creativity means
allowing the mind to ‘wander’ between di‐erent ideas. The two states are

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antithetical, so anything you take to increase your focus may actually deaden
your creativity (see here).

Likewise, using a GABAergic would be a bad idea if you were trying to promote
wakefulness. And if you wanted to improve memory and ‘long term
potentiation’/plasticity, then you would want to look more into racetams and
cholinergics.

If you’re interested in the di‐erent areas of intelligence and how intelligence is

born from activity across the brain, then check out THIS recent post.

Understanding Stacks
Some nootropics make natural partners for each other and thus enthusiasts will
often use ‘stacks’ in order to get the maximum bene†t. These are groups of
nootropics that they take together in order to get the best e‐ects.

So something like Piracetam, choline, tyrosine theanine and ca‐eine for

example would be a great ‘stack’ for learning. That’s because the tyrosine,
theanine and ca‐eine would increase the amount of dopamine in the brain as
well as epinephrine – improving your ability to focus and pay attention.
Meanwhile the theanine would also be able to reduce some of the jitteriness
created by the ca‐eine. Finally, the Piracetam would increase the availability of
acetylcholine receptors, while the choline would increase the amount of choline
for them to utilise – a combination that would ensure you retained more of what
you focused on.

Nothing Operates in a Vacuum

What’s also important to consider though is that raising one neurotransmitter
will almost always lead to an increase or reduction in others.

For instance, increasing dopamine leads to generally increased activity

throughout the brain. Thus your body interprets this as something important
happening to create such arousal and it thus produces epinephrine as a result (as
part of the ‘†ght or တight’ response) to increase your attention. Thus, it’s
possible that you might use a dopaminergic with the intention of raising
dopamine, but will also raise epinephrine as a result. Sometimes this might also
lead to production of cortisol – which is the stress hormone and which can
increase feelings of anxiety as well as leading to snacking. An elevation of
cortisol meanwhile will often lead to an elevation of serotonin however as the
brain tries to regulate the memory. Thus, in this scenario you have attempted to
target one neurotransmitter but have instead caused a cascading e‐ect to alter
many.

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Sometimes a ‘stack’ will attempt to account for this, by using other nootropics to
counteract unintended elevations or reductions in other neurotransmitters.
These nootropics however will often only create other unintended e‐ects
leading to something of a never-ending cycle.

When taking any nootropic, you will almost certainly alter levels of countless
neurotransmitters in the brain – and probably several that we don’t even know
about. This can lead to detrimental side e‐ects, so it’s important to monitor the
outcome carefully.

Measuring E⤀ꀈectiveness and Side E⤀ꀈects

Taking nootropics blindly and hoping you’ll turn into Albert Einstein is a fruitless
way of using them. You are not going to notice profound e‐ects throughout all
your mental faculties – generally these are mild impacts at best and if you aren’t
measuring them in some way, it might be hard to know whether you’re
genuinely seeing results in the areas that matter.

Some people then will use some ‘test’ of their mental performance in order to
measure the e‐ectiveness of certain nootropics and will attempt to remove
confounding factors such as sleep and diet changes. When attempting to
improve working memory for instance, some people will use the ‘Dual N-Back’
test and then look for improvements in their score. How they account for
improvements due to practice, I am unsure. If you were really serious you could
even conduct your own ‘double blind’ experiment by getting someone to give
you either the real nootropic or a sugar pill (without even them knowing which)
and then measuring your performance over a few days in order to counteract
any placebo e‐ect.

Personally I †nd it more useful simply to measure my performance in the speci†c

activity I’m hoping to improve in (I †nd that I don’t tend to need to perform the
N-back test all that often). For me that usually means writing articles – and I can
thus measure the e‐ectiveness of a placebo by looking at word count and how
often I get distracted. Is it a placebo e‐ect? It doesn’t matter – as long as I’m
writing more and getting distracted less, that’s all that counts.

Be Wary of Tolerance
Another factor to be cautious of with nootropics though is ‘tolerance’. Tolerance
is what happens when we take too much of a nootropic over an extended period
of time leading to chemical changes in the brain. In some cases this can mean
you then need more of the nootropic to achieve the same e‐ects. In other cases,
it might mean that you permanently alter your brain chemistry for the worst. In
others it can lead to dependence, addiction and withdrawal.

For instance, if you are constantly using supplements that increase dopamine in
your brain, your brain may react by reducing the amount of dopamine it usually
produces – or even reducing the number of dopamine receptors. Thus you might
actually make yourself less motivated when you’re not using the nootropic.

Does this, along with the potential for side e‐ects, mean that you shouldn’t use
nootropics at all? Not necessarily – it just means you need to be very careful and
you need to recognise that there’s ‘no such thing as a free lunch’ (as Tim Ferriss
says). Remember that even the foods you eat, sunlight, sleep and exercise alter
brain chemistry and thus change your mental performance – using nootropics
means you’re simply taking conscious control of this manipulation. You just have
to be careful.

Best Practice
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Once you have found what works for you, the best way to avoid tolerance is to
avoid taking any nootropic that has a powerful acute e‐ect for long periods of
time. This way you not only avoid permanent, unintended changes to your brain
chemistry, but you also ensure that the nootropic remains potent and e‐ective.
For instance, moda†nil is a substance I have spoken about in the past and found
to be very e‐ective though also potentially risky due to numerous side e‐ects.
The only safe way to use it, would be to take it very rarely when doing an intense
cramming session. The same would go for any other stimulant-type or
relaxation-type nootropics. Consider these tools to be used with laser precision.
Personally though, I don’t actually recommend the use of moda†nil speci†cally
at all (remember too though, everyone is di‐erent and everyone reacts
di‐erently to di‐erent nootropics).

On the other hand, those vitamins, minerals and nutrients that act to maintain
and improve brain health over the long term such as omega 3 fatty acid and
antioxidants are safe and recommended for long-term, regular use. These won’t
lead to huge, immediate bene†ts, but they will help to improve your brain’s
health and general performance.

Even more important are lifestyle considerations such as ensuring you get
enough sleep (the number one ‘nootropic’) as well as exercise (which stimulates
endorphins as well as neurogenesis – the birth of new brain cells). Brain training
also has its place when used correctly (and particularly when used in conjunction
with nootropics).

And that’s an article for another time…

About Adam Sinicki

Hi there! My name is Adam Sinicki, I'm an entrepreneur, psychology graduate and amateur
bodybuilder interested in ⤀褅tness, self improvement, technology and transhumanism. I run an
online business (NQR Productions) which allows me to live the lifestyle I want: getting time to
hit the gym and to work on my projects and apps. Stick around and I'll be sharing my
experiments and adventures in brain training, bodybuilding, productivity, business and
technology.

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4 Comments The Bioneer 
1  Login

Robert Dinse • 8 hours ago − ⚑
Generally a very good introduction to nootropics however there is one error.

"Cognitive Metabolic Enhancers: Cognitive Metabolic Enhancers work by
increasing energy available to human brain cells via improved
metabolism. This can occur through increased vasodilation (increasing
the diameter of blood vessels to carry more blood to the brain) or by
improving the function of cell membranes (mitochondria)"

Mitochondria are not cell membranes, they are organelles within the cell that are the
cells energy factory producing ATP. There are substances that help the function of
mitochondria and/or stimulate their proliferation so that there are more mitochondria
within the cells, PQQ comes to mind, and there are substances which improve the
function of cell membranes, omega3's come to mind, but they are two distinctly
separate things.
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Silk • a year ago − ⚑
Great Job Adam, you articles about nootropics have helped a great deal in
understanding the topic better. Nevertheless, I haven't find any articles where you
have been talking about adaptogens like bacopa, rhodiuma, ginseng ashwagandha.
Maybe I missed it out, but if not it would be great to hear your opinion about it.
△   ▽ • Reply • Share ›

Gav • 2 years ago − ⚑
One of the few accurate, balanced articles on nootropics I've come across ­ well done.
△   ▽ • Reply • Share ›

thebioneer  Mod   > Gav •  2 years ago − ⚑

Thanks a lot! I'm glad you enjoyed it :­) If you're interested, this article:
http://www.thebioneer.com/best... deals with my most up­to­date views on the
subject as well as my current stack. Thanks for reading!
△   ▽ • Reply • Share ›

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