A brief guide to cognitive enhancing substances (Nootropics).

A brief guide to cognitive enhancing substances (Nootropics).
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Nootropics are a general ‘blanket’ term to describe any compound capable of improving several different aspects of cognitive function, such as memory, focus or creativity, without causing many adverse side effects.

This term was coined in 1972 by a Romanian chemist, Corneliu E. Giurgea.

He was the pioneer of nootropics research in his time and created a very strict set of guidelines to define what the characteristics of nootropics really were:

  1. They should enhance the resistance of learned behaviors/memories to conditions which tend to disrupt them (e.g. electroconvulsive shock, hypoxia).
  2. They should protect the brain against various physical or chemical injuries (e.g. barbiturates, scopalamine).
  3. They should increase the efficacy of the tonic cortical/subcortical control mechanisms.
  4. They should lack the usual pharmacology of other psychotropic drugs (e.g. sedation, motor stimulation) and possess very few side effects and extremely low toxicity.

This original definition rules out many of the compounds we see in rampant use today to improve cognitive performance. For the purposes of this blog, we will cover all potential compounds that are commonly used today to improve cognitive performance, even if they don’t fit the strict definition as set out by Corneliu many years ago.

Therefore, the modern category of nootropics or cognitive enhancing substances can be broken down to include natural supplements/compounds (those synthesised by the body, found in foods or those found in nature e.g. herbal/mushroom types), pharmaceutical drugs (smart drugs) and synthetic nootropics.

In this article, we will go over these different types of Nootropics and cognitive enhancing substances, what they can be used for, and whether or not they can be beneficial for you depending on your goals and what you’re trying to achieve.

In general, we can see that our society is being directed towards a more productive, high performance state. We are now increasingly idolising entrepreneurs, scientists and CEO’s such as Elon Musk instead of athletes and pure physical performance. We aspire to be more like them. To work harder, smarter, be more focused, have direction and more clarity towards our goals.

This is why we believe it’s so important to use all of the amazing tools at our disposal — tools such as Nootropics, Smart drugs and other cognitive enhancing technologies.

Being able to positively affect and alter our own biochemistry and biology is crucial for becoming more efficient and effective humans, both in today’s society and the society of the future.

Smart drugs and Nootropics are generally taken and used for their ability to increase vital aspects of cognition, such as focus, alertness, memory recall and mental clarity as well as reduce mental fatigue and lower stress.

Imagine having an exam block in a 3rd or 4th year engineering or computer science degree, and knowing you have 2–3 weeks of studying 12–14 hours per day if you have any hope of passing the subjects and graduating.

At this point, you are willing to try almost anything to get an edge or make your life over the next few weeks a bit easier. This is where nootropics come in. Just like an elite athlete who may choose to use performance enhancing drugs or other legal sports supplements to improve their performance, an academic student or professional may choose to use nootropics for the same purpose.

The general population are almost unknowingly daily consumers of one of the most studied and tested nootropic substances, caffeine. It’s almost second nature for us to buy a coffee or energy drink to get through a day of work or study. But caffeine is just the beginning of a long list of substances that can be used to increase mental performance and cognition.

In the world of the niche & dedicated smart drug users, substances such as Modafinil, Ritalin and Dextroamphetamine are an extremely popular option to significantly enhance focus and wakefulness, despite being prescription drugs.

Modafinil is a pharmaceutical medication that is traditionally used to treat narcolepsy or shift work sleep disorder. It is what is known as a Eugeroic, or “wakefulness promoting agent”. The pharmacodynamics or mechanism of action for Modafinil is still largely unknown. It has been shown to act as a weak but very selective dopamine reuptake inhibitor and therefore the wakefulness and stimulating properties of Modafinil may be due to increased dopamine levels among several other knock-on effects.

This is the substance that most university student’s opt for. It’s powerful and easy to buy online. The only problem is it is technically illegal to use recreationally or for performance enhancement in Australia, unless you have a prescription from a medical professional.

Modafinil virtually eliminates fatigue, allowing you to stay awake and alert for long periods of time. Modafinil can be useful when taken cyclically for short periods at a time e.g. for large assignments with an upcoming deadline or during a few days of exam period.

Problems such as extreme irritability can arise if you take it too frequently, and don’t give your body enough rest in between periods of use. People may also experience effects such as increased anxiety, excessive sweat, headaches or an upset stomach. These are typical side effects for stimulants and substances such as modafinil, although they may not be very pronounced unless you’re taking large dosages or taking it frequently. Everyone’s biology is different, so some may be prone to much larger and much worse side effects, so be weary. This is a powerful medication.

Ritalin (Methylphenidate) and Dextroamphetamine are Central Nervous System (CNS) stimulants prescribed to those with ADHD and narcolepsy. They are often taken in the same way and for the same reason as Modafinil, because of their proven effects and ability to enhance cognition. These substances work primarily by increasing levels of neurotransmitters such as dopamine and norepinephrine in the brain by inhibiting their reuptake into neurons.

These are known to be powerful substances, and could result in addiction or harm if taken too frequently or at high dosages.

It’s easy to see why the use of smart drugs is rising in our youth and across our universities today, it’s a simple tool that can be used to give everyone an edge in their academic pursuits.

I do believe that nootropic substances can and should be used when necessary, but I do not necessarily recommend ordering prescription drugs such as Modafinil from dodgy suppliers in India every time you wish to get your nootropic fix.

If you wish to look into these substances for your own personal use, or you think you have a disorder such as ADHD or narcolepsy that requires treatment, we recommend you see and consult with your physician.

Natural compounds or supplements are another way to potentially boost and maximise your cognitive output.

These can include substances created within the body, those found in foods or those found in nature.

Vitamins, Minerals, Amino acids (Micronutrients)

The human body is able to synthesise certain amino acids, but it requires most to be taken from food. We also need food intake to get all our vitamins, essential minerals such as magnesium, iron, calcium and the omega 3 and 6 fatty acids.

We also require certain foods to help create important neurotransmitters.

Choline can be found in foods such as fish and eggs and that helps our body to synthesise acetylcholine, the neurotransmitter vital for memory and learning.

Better forms of choline such as Alpha-GPC or Citicholine can also be supplemented. These forms have a much higher bioavailability and can cross the Blood-Brain-Barrier (BBB) with ease to exert their effect much more efficiently within the brain.

As such, it is recommended to eat a well balanced, whole food diet to ensure your intake of essential micronutrients such as vitamins, minerals and amino acids is taken care of.

If you feel like you’re deficient in any particular micronutrient, it is recommended to get your blood work tested. You can easily rectify this by supplementing with the necessary nutrient or improving your diet.

In society today, the highest rate of deficiency is in minerals such as iron, calcium, magnesium and Vitamins A, B12, D and in Omega 3 fatty acids. All of these substances are vital for overall health, but also vital for brain function and performance, particularly Magnesium and Omega 3’s.

Magnesium can be taken supplementally in many different forms. Most suffer from bad bioavailability issues and GI distress issues. The form we recommend for brain function is Magnesium-L-Threonate. This is a relatively new form of magnesium that goes by the brand name of Magtein. It is the most bioavailable form of magnesium for the brain and crosses the Blood-Brain-Barrier (BBB) easily to exert its effects.

Omega 3’s can be supplemented through fish oil or kill oil capsules if you think you don’t get enough seafood or nuts in your diet. Both of these are excellent sources of DHA and EPA, but some argue that krill oil actually confers more benefit in the human body.

Coffee, Green Tea, Turmeric

Coffee, green tea and turmeric are just a few of the most popular nootropics and health foods/beverages in use across the globe.

Whilst these foods don’t classify as “essential nutrients” they have all been proven as safe for use, and can even confer great health benefit, as well as acutely improve performance when ingested due to the beneficial and unique compounds they each contain.

Coffee & caffeine

Coffee obviously contains the active ingredient caffeine we all know and love.

Caffeine is a central nervous system (CNS) stimulant that improves wakefulness and reduces fatigue.

Caffeine’s primary mechanism of action is binding to adenosine receptors and therefore preventing the onset of drowsiness caused by adenosines action.

Coffee can improve both physical peformance as well as cognitive performance.

It also contains polyphenol antioxidants that act on various pathways. Research has found that long term use of coffee/caffeine MAY have a protective effect against Alzheimer’s disease or other forms of dementia.

So go on, drink that morning cuppa. It’s good for you.

Actually, try stick to no more than 400mg of caffeine per day, this seems to be the safest bet for most healthy adults.

Upgraded coffee is a new trend in which startups and companies are infusing regular coffee with other beneficial superfoods, nootropics and herbals.

The most famous example is Bulletproof coffee, founded by Dave Asprey in the U.S. They tout to improve your daily coffee by adding in healthy fats, high quality MCT and sticking to the “Bulletproof lifestyle”.

There is another Australian based company, called Beforeyouspeak Coffee that have recently emerged and are poised to be a leader in this space.

They have created a unique instant coffee formula that includes MCT powder, turmeric, black pepper extract, and ginseng without any sugar or artifical colours/flavours/sweeteners.

This is definitely a brand I get behind and could not recommend more, especially for those looking to enhance their performance and not take in any heavy calories (just mix with it hot water). I will personally be stacking their coffee with our Boost Nootropic, which is being designed to pair perfectly with your daily coffee.

Green tea & L-Theanine

Another favourite beverage around the globe is Green tea, and for good reason. Green tea is a fantastic blend of many different natural compounds. Not only does it contain reasonable amounts of caffeine per cup, but also plenty of polyphenols (Anti-oxidants) such as EGCG ( Epigallocatechin Gallate). These polyphenols help reduce inflammation, and fight off free-radicals that damage cells within the body.

Watch out for some supplements out there which use concentrated green tea extracts, some are known to have such huge concentrations of EGCG that can actually cause serious kidney damage. You have been warned.

Another huge kicker for green tea is one of its main constituents, L-Theanine. L-Theanine is an amino acid that is structurally similar to the excitatory neurotransmitter glutamate, and thus binds to its receptors, preventing glutamate from providing its excitatory effects.

It also increases the activity of the inhibitory neurotransmitter GABA, which produces further inhibitory or anti-anxiety effects.

L-theanine seems to provide its calming and relaxing effect without causing a sedating effect, or making you feel sleepy.

Another fascinating effect is that L-Theanine actually promotes alpha brain wave activity. This brain wave frequency is associated with a relaxed wakefulness or meditative state. This state is often associated with a feeling of presence, or being in the now. It is the perfect “Flow state” or peak performance state to get into the zone without high anxiety levels or negative self talk.

[QUICK SIDE NOTE: Brain waves refer to the electrical activity within the brain. Specifically it is the frequency or “rate” at which large masses of neurons communicate with each other. The alpha brain wave frequency corresponds to 8–12 Hz, or 8–12 cycles per second]

L-Theanine is found in green tea at a fairly small dose, but can be supplemented separately. Most clinical studies look at doses of 100–400mg of L-Theanine, and this seems to confer the most benefit.

But, let’s take it another step further. The combination of caffeine and theanine is one of the most studied combinations of natural ingredients, and for good reason. This unique synergy is what gives green tea its unique feeling when compared to straight coffee or caffeine by itself.

Studies show that this combination is able to significantly improve cognitive performance [1], and reduce the vasoconstrictive and behavioural effects of caffeine [2].

What this means, is that you can enjoy your cup of coffee (with added theanine) or your green tea, and enjoy the benefits of caffeine without the drawbacks such as excessive sweats, irritation or anxiety feelings.

Turmeric & Curcumin.

Turmeric is a spice, often used in traditional curry dishes, that comes from the Turmeric or Curcuma Longa plant of the ginger family. This is the spice that gives curry its very distinct yellow colour.

Turmeric contains many bioactive compounds called curcuminoids, of which Curcumin is the most popular. It is a powerful anti inflammatory and anti oxidant compound.

Whilst it would be hugely difficult to get any substantial amount of Curcumin from just eating Turmeric spice, it is possible to supplement it separately in order to receive the full benefit.

Be careful though, the bioavailability of curcumin is poor, unless you mix it with an asborption enhance such as Piperine, a black pepper extract, that can increase its bioavailability by up to 2000%.

The reason why Curcumin is so important is due to its anti inflammatory properties.

Inflammation is a phenomenon of the human body, which is hugely important as a way to fight infection and protect the body from foreign invaders.

This type of short, acute inflammation is essential for our survival, but it becomes a problem when it becomes a chronic underlying inflammation.

Scientists are now seriously looking into the role that chronic, low level inflammation plays on most of the Western worlds diseases like cancer, heart disease, metabolic syndrome, alzheimers and other denegerative diseases. [1] [2].

I’ve attached some review papers here looking at Curcumin’s health properties and ability to tackle certain diseases/ailments [1] [2].

A daily dose of around 500mg-2g of curcumin seems to confer the most benefit according to clinical research.

REMEMBER: Stack this with piperine, a form of black pepper extract.

Herbal & Mushroom Nootropics

There are a bunch of interesting compounds found in different herbs and mushroom species throughout the planet, that when consumed, can have positive effects on our physiology and especially our cognition.

Most of the herbal and mushroom compounds we will look at have been used for centuries in ancient chinese or indian traditions (Ayurveda) and many other ancient cultures for medicinal or health purposes.

Herbal Nootropics

  1. Bacopa Monnieri

Bacopa or Brahmi is a herb native to the wetlands of southern and Eastern India, Australia, Europe, Africa, Asia and America.

Bacopa contains numerous compounds called Bacosides which contribute to its potent, memory and brain enhancing effects.

There are studies that show that supplementing 150mg of standardized extract of Bacopa called Bacognize, twice daily, over a period of six weeks provided statistically significant improvements in cognitive function.

Bacopa is proven specifically to improve memory in multiple studies, and is a very well known and respected cognitive enhancer.

  • anti-oxidant neuroprotection (via redox and enzyme induction)
  • acetylcholinesterase inhibition and/or choline acetyltransferase activation
  • β-amyloid reduction
  • increased cerebral blood flow
  • neurotransmitter modulation (acetylcholine [ACh], 5-hydroxytryptamine [5-HT], dopamine [DA])

Bacopa is one of few very well studied nootropic compounds. For this reason, it is one of our flagship ingredients in our daily neurovitamin, Enhance.

Be weary, however, anecdotally some users report to have reduced feelings of motivation after consuming Bacopa. This may be due to the fact that some standardized extracts contain higher amounts of Serotonin Active Bacopa Glycosides (SABG’s) which may contribute to higher serotonin and thus give a more calming effect.

We are controlling/countering this in our Enhance Nootropic by utilising the Synapsa brand of standardised Bacopa extract, and also suggesting that the dosage be split to morning/night.

2. Adaptogens (Rhodiola Rosea, Ginseng, Ashwaghanda, Shisandra)

Adaptogens are a class of herbal compounds that aim to stabilize physiological processes, and in particular, regulate stress within the body.

They do this largely by interacting with the hypothalamic-pituitary-adrenal (HPA) axis and the sympathoadrenal system. Adaptogens may alter levels of stress hormones such as cortisol within the human body.

Adaptogens hold great promise, but more human clinical data is needed. So far, a lot of the clinical research has been done on rodents and cell models to show their efficacy.

Ashwaghanda in particular, has been shown to reduce stress and anxiety as well as improve various other aspects of cognitive function.

In particular, the standardised extract called KSM-66, has a large body of clinical research supporting its efficacy. This is one of our flagship ingredients in Calm, our relaxation and sleep nootropic. [1] [2].

3. Huperzia Seratta

Huperzia Seratta is a chinese club moss plant, which contains the well known nootropic compound Huperzine A.

Huperzine A is a known acetylcholinesterase inhibitor. This means it inhibits the enzyme involved with the breakdown of acetylcholine in the body.

Huperzine A has been shown to improve cognitive deficits in a broad range of animal models and has shown some promise in helping the elderly affected by Alzheimers disease. [1]

Whilst Huperzine A looks very promising for staving off neurodegeneration or helping those with cognitive deficits, more research into efficacy within healthy humans would be great, as well as longer term safety studies.

There is some potential for semi-serious side effects with Huperzine A, which typically comes from too much choline, such as headaches, nausea and sweating.

Mushroom Nootropics

  1. Lions mane mushroom

Lions mane mushroom (Hericium Erinaceus) is a medicinal mushroom native to North America, Europe and Asia. It is the mushroom most associated with improving brain function and so I think its hugely important to talk about.

Lions mane contains a number of natural compounds called polysaccharides such as Beta Glucans and Heteroglucans which have very beneficial effects.

There is clinical research showing that Lions Mane is able to promote the synthesis of neurotrophins such as Nerve Growth Factor (NGF) in cell models. This protein helps neuronal growth and repair. [1]

Also, rodent models show that Lions mane mycelium “ enriched with its active compounds is capable of delaying neuronal cell death in rats with neurodegenerative diseases, such as ischemic stroke, Parkinson’s disease, Alzheimer’s disease, and depression”.

Lions mane shows quite some promise for those suffering from mild cognitive impairment, with one study showing significant improvements in cognitive scores over a 16 week period. The participants all took 3g of Lions mane per day.

Lions mane has some really promising initial clinical data, but I would love to see more studies on healthy humans.

The most common dose I see anecdotally for Lions mane mushroom seems to be around 500mg-1g per day, whether this confers the same benefit as 3g is yet to be confirmed. This is one ingredient I am definitely big on!

Other notable mushrooms: Reishi, Cordyceps, Turkey tail.

The Racetams are a class of synthetic or man-made nootropics that are used rampantly amongst “biohackers and neurohackers” in order to get the edge.

They were hugely popularised by Bulletproof founder Dave Asprey when he came out about his long history of use with these substances, claiming almost magical cognitive enhancing benefits.

The first racetam, Piracetam was discovered by Corneliu whilst he was searching for a sleep and relaxation inducer. He quickly noticed however that it had great potential to boost alertness and cognitive performance instead.

Piracetam seems to improve the function of acetylcholine (the all important neurotransmitter for learning that we saw earlier), as well as modulate AMPA receptors, leading to increased glutamate levels.

Studies show that racetams like Piracetam and its derivatives Oxiracetam, Aniracetam, Phenylpiracetam etc all act on a large number of pathways and receptors, but all similarly seem to exert neuroprotective effects. [1] [2] [3].

There is a huge library of research showing the benefits of Racetams on improving the outcomes of cognitive impairment and neurodegeneration.

Be weary, however, racetams and similar substances (such as noopept) are scheduled in Australia as Schedule 4 substances, meaning they are not approved for over the counter sale by the TGA (Therapeutic Good Administration).

These substances require a prescription from a medical professional to be purchased. This is why you don’t see companies within Australia that manufacture or supply these compounds direct to consumer.

If you wish to experiment with these compounds, please do so at your own risk. Be sure to stack it with a source of Choline such as Alpha-GPC or Citicholine to prevent any headaches or further negative effects.

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