Nootropics: An Unconventional Guide


Photo courtesy of Brandon O’Connor

Nootropics are a generic term for any substance that improves your brain’s performance.

Whether it be IQ, memory, being in the flow, or a greater tolerance for annoying in-laws, if a pill can circle-jerk your cognition in the right direction it’s given the nootropic title.

Despite their vast popularity most of the information on nootropic supplements is unsettled.  Their mechanisms of action are diverse, clinical trials on them are scarce, and the brain is still a poorly understood organism.

If you want to get the skinny on what they’re good for you’re better off reading Longecity than PubMed.

However, the murkiness around their efficacy has done nothing to stop rampant experimentation with how you can use them.  Most of the time these self-experiments are harmless but at their worst people have done serious damage to themselves that’s all but impossible to undo because no one’s sure why the problems began in the first place.

This account of someone who gave himself mercury poisoning by overdoing it with his nootropic cocktail is a good example.  After 6 months he couldn’t even get a doctor to figure out what was wrong with him.

If you’re excited about the possibility of becoming smarter and more focused there’s probably nothing I can do to stop you from trying a nootropic for yourself.  And even if I could I wouldn’t because I’m not that pushy.  However, if you’re hellbent on ramping up your Acetylcholine production from 0-75 you ought to at least have a cursory understanding of how these things work and what they might do for you.

So that’s what we’re going to discuss today.

Here’s a round-the-world tour of the various types of nootropics.

Acetylcholine Precursors

Acetylcholine is an important neurotransmitter that controls a lot of brain functions tied to cognition.  When you’re alert you’re usually making a lot of it and when you go senile your brain’s usually in short supply.

A lot of alzheimer’s treatments are elaborate ways of playing humpty-dumpty with your brain so it can start making acetylcholine again.

When it comes to improving acetylcholine levels there are two ways to get it done:

  1. Give your body material to make more of it
  2. Stop your body from breaking it down.

Both are important.  Let’s talk about #1 for now.

Acetylcholine is made from choline, a fairly common compound found in eggs, meats and soy beans.

The point of most acetylcholine precursors is to supply choline to the brain.  It’s just a matter of what compounds deliver it most effectively.

There are two that have proven to be particularly effective: Alpha-GPC and UDP-choline.

Alpha GPC

Alpha GPC is the storage form of choline, which is the reason it has a high absorption rate into the brain.  When you eat lecithin your body breaks it down into Alpha GPC, where it gets stored in your brain’s phospholipids and so it can drop-ship choline as needed.

Pound for pound Alpha GPC is the best supplementary source of choline you can use, with oral doses resulting in 40%+ increases in serum choline concentrations afterwards.

Alpha-GPC also slightly increases the body’s ability to produce serotonin and dopamine, a feature unique unto itself among acetylcholine precursors.


UDP-Choline works in two ways:  it provides choline to the brain, and it also supplies the body with cytidine, which is eventually used to make uridine, another cholinergic compound that has effects very similar to choline, with the added benefit that it increases cell differentiation within the nervous system.  This latter benefit is the reason it provides a boost to working memory independent of its effect on acetylcholine.

Acetylcholine precursors exert their effect slowly.  You’ll need to take them for about a month before you notice a significant difference.  Their glacial mechanism of action is also what makes them safe.  Using either of these allows your brain to gradually ramp up its production of Ach without experiencing weird jolts of attention or deleterious side effects.

You ought to take about 500-1500 mg of either, although Alpha GPC has shown to have positive benefits with doses as large as 6 grams.

Acetylcholine Esterase Inhibitors

Acetylcholine esterase is the enzyme your body uses to breakdown acetylcholine into choline and acetate, its metabolic waste products.

If you turn off the Ach E faucet your brain will instantly start stockpiling the neurotransmitter where it can be used for other things.

Ach E inhibitors exert their effect quickly.  Lots of nootropic compounds that advertise themselves as “Instant Focus” or something similar usually use an Ach E inhibitor to generate the effect.

There’s one in particular that’s especially popular:  Huperzine A.

Huperzine A

Hup A is an extract of the Huperziaceae family of plants that’s long been used to improve mental acuity and it works almost entirely as an Ach E inhibitor.

If you’re new to Hup A taking it is often a revealing experience.  Your alertness and focus go up a notch that you’ve never felt before and you’ll feel closer to self-enlightenment than you ever have in the past.

Sounds great, right?

It is…….unless you over do it.

Ach E inhibitors jack up your Ach levels in ways that aren’t organic to your body’s natural processes and too much Ach causes serious problems that are almost mirror opposites of what increasing it is supposed to accomplish:

  • Brain fog
  • Drowsiness
  • Diminished memory
  • Feelings of depression

Even worse, artificially increasing your Ach levels can cause your body to downregulate its Ach receptors, making your body less receptive to the Ach it naturally produces, thus creating a mini-dependence.

So if you’re already mentally acute (and if you’re reading this you probably are) there’s no need to take it on a regular basis.  The right place to draw the line in the sand with regards to Hup A varies from person to person, but 50-200mcg is usually the sweet spot that works for most people.

Ach precursors like Alpha-GPC and UDP-choline are better choices for day-to-day supplementation.


The racetams come in a variety of flavors:

  • Amiracetam
  • Piracetam
  • Noopept
  • Oxiracetam
  • Pramiracetam

However, they’re all derived from their parent molecule piracetam and have the same basic chemical structure:  an oxopyrrolidine ring.  The different versions of the racetams have different functional groups around this ring which change their rate of absorption, affinity for specific tissues, or add modifications to their basic biological function.

Racetams were invented under the guise that they’d be potent cognition enhancers that aid in memory and spatial learning but so far they haven’t lived up to their reputation.  In healthy people they do not seem to improve cognitive function very much.

They do however seem to have a benefit for preserving cognition among the elderly.  This might be because their primary function within the body is to preserve the redox potential within your mitochondria and enhance membrane fluidity, both of which begin to go sour once you get past the age of 50.

In this sense the effect of racetams are a mix of two other supplements already discussed on this blog:  MitoQ and lecithin.

Brains fed racetams have an enhanced ability to consume glucose and oxygen, and if your metabolism is already healthy then the additional benefit of taking racetams is likely to be small.

Neuroamine Enhancers

There are plenty of supplements you can take to enhance your body’s production of dopamine and serotonin, two chemicals which have very important effects on your mood, physical alertness and sense of well-being.

It’s important to understand that while serotonin and dopamine both have important effects on your state of mind, they are not interchangeable.  They act through different pathways and boosting one will produce very different side effects compared to the other.

So with that said……

Serotonin Enhancers:  Tryptophan & 5-HTP

Your body makes serotonin from tryptophan, albeit not very efficiently.  After you digest tryptophan it gets shuttled to your liver where it’ll get used to make NAD (activated B3), Acetoacetyl CoA, and Kynurenate in addition to serotonin.

For this reason 5-HTP is usually the preferred choice among people looking to give their serotonin levels a boost.  In your brain it’s the rate liming step in serotonin synthesis and supplementary 5-HTP crosses the blood brain barrier fairly easily, making it an effective way to increase the amount in circulation.

5-HTP is roughly 8x as effective in increasing serotonin levels as tryptophan so you’d need much more of the latter to get the same effect as the former.  Serotonin is eventually converted into melatonin so large doses of 5-HTP usually result in better sleep as well.

While a serotonin buzz can feel better than getting high it’s not always a good idea to get as much of it as you can.  Too much can alter your body’s tendency produce it on its own and the serotonin syndrome is a condition that results from lifelong overuse of anti-depressants that can result in increased chances of cardiovascular events, seizure and cognitive impairment.

Dopamine Enhancers:  Phenylalanine, L-Tyrosine, L-Dopa, Mucuna Pruriens

Dopamine is the neurotransmitter responsible for reward-motivated behavior.  That buzz you get after a status-boosting accomplishment or intense bout of exercise is a little money shot of dopamine being released from the neurons in your medulla and adrenal gland.

Your body takes phenylalanine and turns it into tyrosine and then turns it into L-Dopa which is then turned into dopamine.  So each of these can be taken to increase dopamine levels with increasing efficiency.  You can think of L-Dopa as the physiological equivalent of 5-HTP, except for dopamine instead of serotonin.

Mucuna pruriens is a bean that contains unusually large amounts of L-Dopa and is used medicinally for this reason.

While dopamine and serotonin both make you feel good, dopamine confers a wide variety of changes in the body outside of mood.  Not all of them will be useful depending on your situation.

Dopamine affects hormone production and very high dopamine levels are usually concomitant with increased in growth hormone and testosterone.  Dopamine also influences your sexuality and feelings of excitement and sense for adventure.  If you’re sexually labile a megadose of L-Dopa might even catapult your libido into uncharted territory.

If this effect goes too far dopamine can eventually influence your sense of aggression in a way you wouldn’t want your mother to see.

Methyl Donors

sam-e, creatine, methyl folate, b12, glycine, TMG (betaine)

The methylation cycle has been getting a lot of press lately as the next big health issue everyone’s neglecting.

The process begins with folate and b12 and eventually ends up as a molecule called sam-E, a very important compound that actually does most of the heavy lifting.

For people that are under methylated a dose of sam-E can be a breath of fresh air.  Mood swings can go away, your headaches can subside, and those nagging lapses in concentration can dissipate.

So does that mean anyone looking for a brainlift can just pop some sam-E and its complimentary methylators, relax, and enjoy popcorn while their problems go away?

Not quite.

If you’re under methylated too much sam-E can be a very mixed experience.  Whatever pre-existing inflammatory conditions will likely get worse because your body’s histamine production can become disregulated.  Sleep issues can creep up as well since methylation is involved in the production of melatonin.

So it’s best to start slowly because it’s hard to predict what’ll change in your body until you actually try.

My favorite supplement for methylation that doesn’t get its fair credit is creatine, which has an effect on the body similar to sam-E since that’s what most of your body’s sam-E is used for.  Taking creatine frees it up to do other things.  It’s an important supplement for mental health.

Creatine can be taken in large quantities without invasive side effects and its benefits on the body are fairly gentle and widespread.  It also helps without power output and physical performance so it’s a solid “Win” for overall well being.


Vinpocetine is good for increasing blood flow to the brain.  It acts quickly and its effects usually take place 10-15 minutes after digestion.

For this reason it has a modest neuroprotective and antioxidant effect that’s most strongly felt among the elderly.

Its ability to increase oxygen flow to the brain might assist in short-term memory improvement although these effects are almost certainly modest.

It has some unique health benefits at very high doses but these are probably not relevant for most people who are taking 10-40 mg/dose.  It is probably more useful than the racetams for quick hitting cognitive enhancement.


I saved the best for last.

Of all the supplements put under the nootropic umbrella modafinil is by far the most interesting.

It was originally developed as a pharmaceutical to help prevent narcolepsy but in the decades since its inception it’s been used – effectively – for an extremely wide variety of cognitive enhancements.

One of its more interesting capabilities is an ability to raise IQ.

Narcolepsy is a sleeping disorder where people spontaneously fall asleep.  The latest cognitive research suggests low-IQ people have parts of their brain that function as if they’re asleep while they’re awake…..they’re conscious but functionally snoozing with their cognitive faculties.

If I use my own personal experience I’d have to agree with this observation.  I have poor spatial reasoning and my brain very easily blanks out on mundane details involving where things go, as if there was never any recognition of what was going on while it happened.

So modafinil’s ability to promote wakefulness has a side effect of enhancing IQ sensitive activities like short-term memory, complex problem solving and cognitive motor.   It’s especially beneficial for one’s ability to improve routine/boring tasks by reducing error rate.  Ie, being “asleep at the wheel”

It’s also been used to improve attention span, depress symptoms of ADHD, treatment resistant depression and shizophrenia.

In terms of its ability to promote cognitive function modafinil’s the real deal.  It’s also only available via prescription, so you’ll need a doctor’s help in order to get your hands on it.

Here’s a useful table that summarizes the clinical research on modafinil’s effect on cognition to date.  It’s impressive stuff and is the only nootropic that truly deserves the title.

If half its effects are generalizable to the general population it ought to be sprinkled in the water like fluoride.

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