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An Introduction To Cognitive Enhancement
What are nootropics?
Nootropics are natural or synthetic compounds that are purported to enhance cognitive function. They run the gambit from vitamins to obscure Russian research chemicals. Some nootropics are risky and untested; others are commonplace and vouched for by the American Medical Association (e.g., Vitamin D).
What’s the definition of “nootropic”? I’m glad you asked!
In order for something to be classified as a nootropic, it must meet the following criteria:
- Benign at conventional dosages (the dose makes the poison)
- Improve cognitive function in at least one area, such as:
- motivation
- attention
- working memory
- cognitive flexibility
- It must not impair cognitive functioning in any way
*Working memory and cognitive flexibility are much more difficult to enhance than attention and motivation. Working memory is tightly correlated with IQ.
Adderall (mixed amphetamine salts) markedly enhances concentration and motivation but may impair cognitive flexibility and creativity. Adderall may also be neurotoxic in high doses and has serious side effects.
For these reasons, it’s not really considered a nootropic. Some people for genetic reasons may experience cognitive improvement across the board with Adderall. This is probably related to polymorphisms affecting dopamine receptors.
It’s a point of contention whether mood brightening compounds are truly nootropic. I tend to think that mood enhancement is a form of cognitive enhancement.
The antidepressant tianeptine is marketed as a nootropic in the United States due to its mood-elevating effects. But strictly speaking, it’s unclear that mood enhancement in itself constitutes cognitive enhancement.
Examples of Common Nootropics
| Compound | Classification | Mechanism |
|---|---|---|
| Caffeine | Coffee | Adenosine receptor antagonist; increases catecholamine release; phosphodiesterase inhibitor |
| Nicotine | Tobacco | Nicotinic acetylcholine receptor agonist |
| Piracetam | Racetam | Allosteric AMPA-type glutamate receptor modulator |
| CDP-choline | Choline precursor | Increase acetylcholine synthesis |
| Modkafinil | Wakefulness enhancing prescription drug | Glutamate/GABA, orexin/histamine, dopamine/norepinephrine, gap junctions |
Who Uses Nootropics?
Millennials seem to be the largest demographic that uses nootropics.
Nootropics are more popular amongst entrepreneurs and people with careers in technology and computer science.
There are many active nootropics communities on the internet. These stand out:
- The nootropics subreddit /r/nootropics
- The Longecity Forum
How Do Nootropics Work?
Nootropics can act through many mechanisms to enhance cognitive function. The common themes in the mechanism of action of nootropics are:
Increase Catecholamines
Psychostimulants like Adderall and Ritalin may improve aspects of cognitive performance by increasing catecholamine release.
Catecholamines are neurotransmitters like dopamine and norepinephrine that increase the activity of the sympathetic (fight-or-flight) nervous system.
Increase Neurotrophic Factors
Examples of neurotrophic factors include brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). These are proteins (neuropepetides) that affect synaptic plasticity, They serve as pro-survival signals for neurons.
I’m personally biased toward nootropics that target NGF and BDNF because these neuropeptides are neuroprotective and neurorestorative.
Increase Cerebral Blood Flow or Cerebral Oxygen Utilization
Cacao is an example of a natural substance that markedly improves cerebral blood flow. It makes a lot of intuitive sense that a brain a better perfused brain will perform better.
Increase Cholinergic Function
Acetylcholine is the neurotransmitter that plays a role in memory and the parasympathetic (rest-and-digest) nervous system.
Examples of cholinergics include acetylcholinesterase inhibitors like:
- Donepzil (used to treat Alzheimer’s disease)
- choline precursors like CDP-choline or Alpha GPC
- high-affinity choline uptake enhancers like coluracetam or pramiracetam
- acetylcholine receptor agonists like the alkaloid nicotine
Decrease Oxidative Stress
Antioxidants protect the brain from neurological insults like irradiation or trauma. Examples of common antioxidants include drugs like methylene blue or minocycline, vitamins like vitamin C and E, neurohormones like melatonin, and mixtures of compounds found in food like blueberries.
Arousal and Cognitive Performance
Yerkes–Dodson Law
The Yerkes-Dodson law reflects the idea that an optimal level of arousal exists to facilitate cognitive performance.
A state of hyperarousal can impair functioning. For example, excessive test anxiety can impede academic academic performance But also, too little arousal (e.g. sleepiness, apathy or amotivation) will also negatively impact performance.
Low baseline levels of arousal are associated with a number of diseases.
For example, narcolepsy, hypothyroidism, ADHD, chronic fatigue syndrome, depression, “chemo brain”, obstructive sleep apnea (OSA) are disorders that can decrease arousal.
Drugs like modafinil (Provigil) are wakefulness enhancers that likely elicit nootropic effects if your baseline level of motivation and arousal is below normal. Psychostimulants like amphetamines or methylphenidate also tend to increase arousal. Subjects with ADHD often have a “paradoxical reaction” to stimulants, where they’re calmed down instead of activated. This effects is therapeutic because individuals with ADHD are, by definition, hyperactive.
Brain Health
There’s no question how important the health of your brain is to general well being.
The ability to think clearly and cultivate good habits of thought is essential to mental health and living well.
There are many factors that affect cognitive function. These include lifestyle factors like diet and exercise, exposure to toxins (like pesticides), your early childhood environment, and many others. Even drugs prescribed by your doctor can adversely affect cognitive health.
The anticholinergic burden scale was developed as a system to keep track of the severity of anticholinergic effects of a given drug. For example, tricyclic antidepressants like amitryptaline have a score of 3/3. This means that amitryptaline has a high anticholingeric burden. The higher the anticholinergic burden, the more likely the drug is to impair cognitive function and contribute to dementia. Older patients (>65 years old) should stay away from anticholinergic drugs completely, unless advised by a doctor.
In order for a substance to be classified as a nootropic, it must meet a couple of criteria. First, it can’t be harmful or injurious at suggested dosages. Second, it must improve the functioning of at least one cognitive domain (like attention, motivation, working memory, complex problem solving, etc).
Consider the example of caffeine, a substance that billions of people consume every day. Caffeine has nootropic effects – it improves attention and arousal – positively affecting cognition and productivity.
Other examples of nootropics include:
- Piracetam
- Nicotine
- CDP-choline
You might be wondering: how powerful are nootropics? Do they really have tangible effects? The extent to which nootropics benefit cognitive performance is controversial. Studies have been mixed.
It’s unlikely that any substance will result in a permanent and dramatic increase in your IQ. But it is well established that certain nootropics can modestly improve cognitive performance by enhancing attention, working memory, or motivation.
Actually, it’s much easier to improve mood and drive than it is to improve working memory or complex problem solving. The only substance that reliably increases working memory seems to be nicotine. Nicotine is a nicotinic acetylcholine agonist – it activates these receptors in the brain which play a role in memory storage and retrieval.
If you’re perfectly healthy and already perform well intellectually, it’s unlikely you’ll realize any tangible benefits from nootropics. The benefits of nootropics are most obvious if you’re performing below baseline due to a medical condition, like depression or hypertension.
Let’s consider the example of anxiety. If you have generalized anxiety disorder, then anxiety-relieving nootropics like magnesium, lavender, l-theanine, and phenibut may improve your intellectual performance by reducing your anxiety.
Obviously, there’s no substitute for being evaluated and treated by an experienced physician. But if for some reason taking standard anxiety medication weren’t a possibility, then “anxiolytic” nootropics might be able to help.
Nootropics can be grouped or classified in the following manner:
- Racetams (like phenylpiracetam or piracetam)
- Nootropic foods (like blueberries or cacao)
- Amino acids or amino acid analogues (like l-tyrosine creatine, or l-theanine)
- Vitamins and dietary supplements (vitamin B12, vitamin E)
- Cholinergic drugs and choline sources (alpha-GPC, CDP-choline, huperzine A, nicotine)
- Natural and synthetic antioxidants (pterostilbene, methylene blue) Of course, there are other ways to classify nootropics, and this list is certainly not definitive.
Guidelines for Using Nootropics
It’s important to use nootropics responsibly.
Just because nootropics are safe at suggested dosages does not mean that you won’t overdose on them if you take too much. Indeed, the dose often makes the poison.
It’s also best to only try one or two nootropics at a time. Taking multiple nootropics simultaneously can make it impossible to draw any conclusions about what’s helpful or injurious.
A reddit post aptly summarizes some key lessons about the responsible use of nootropics:
- Like any community, the nootropics scene periodically undergoes trends, fads and changing consensuses.
- Anecdotally, I’ve found the best nootropics tend to be Russian.
- My responses to various substances have evolved over time.
- The often-discussed U-shaped response curve applies to nearly everything.
- Simple stacks are often best; distilling a stack down to its most effective components is underrated.
- At some point, you have to really ask yourself about personal risk tolerances.
- Figure out your lowest-hanging fruit and target that first.
- Know thyself – otherwise, it’s easy to get caught up on others’ glowing reports.
- Take breaks from time to time.
- Some of the best nootropics are often not things you can find in a pill.