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Wakefulness, Cognitive Enhancement, AND Improved Mood?

Promising research suggests wide uses for this nootropic!

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The 10almonds Team
February 27, 2023

Remember: No man is an island, except in the bathtub.

It’s Research Review Monday here at 10almonds, and our main feature today looks at the growing evidence for modafinil as a cognitive enhancer and antidepressant, not just as a sleep disorder remedy! In today’s newsletter, we have:

  • Save hours, in minutes—with Dr. Amina Yonis

  • Modafinil—and its many potential benefits

  • What would Prof. Huberman say?—Try out this fun (and informative!) AI

  • Play Bold—How to win the business game through creative destruction (without messing it all up!)

👀 WATCH AND LEARN

⏱ Save Hours… In Minutes!

Dr. Amina Yonis has four one-minute habits that save her 20+ hours per week:

We saved you a minute by skipping to where she actually starts sharing the tips 😉

⚕️ MAIN FEATURE

💊 Old Drug, New Tricks?

Modafinil (also known by brand names including Modalert and Provigil) is a dopamine uptake inhibitor.

What does that mean? It means it won’t put any extra dopamine in your brain, but it will slow down the rate at which your brain removes naturally-occuring dopamine.

The result is that your brain will get to make more use of the dopamine it does have.

(dopamine is a neutrotransmitter that allows you to feel wakeful and happy, and perform complex cognitive tasks)

Modafinil is prescribed for treatment of excessive daytime sleepiness. Often that's caused by shift work sleep disorder, sleep apnea, restless leg syndrome, or narcolepsy.

Many studies done on humans (rather than rats) have been military experiments to reduce the effects of sleep deprivation:

They've found modafinil to be helpful, and more effective and more long-lasting than caffeine, without the same “crash” later. This is for two reasons:

1) while caffeine works by blocking adenosine (so you don’t feel how tired you are) and by constricting blood vessels (so you feel more ready-for-action), modafinil works by allowing your brain to accumulate more dopamine (so you’re genuinely more wakeful, and you get to keep the dopamine)

2) the biological half-life of modafinil is 12–15 hours, as opposed to 4–8 hours* for caffeine.

*Note: a lot of sources quote 5–6 hours for caffeine, but this average is misleading. In reality, we are each genetically predetermined to be either a fast caffeine metabolizer (nearer 4 hours) or a slow caffeine metabolizer (nearer 8 hours).

What’s a biological half-life (also called: elimination half-life)?

A substance’s biological half-life is the time it takes for the amount in the body to be reduced by exactly half.

For example: Let’s say you’re a fast caffeine metabolizer and you have a double-espresso (containing 100mg caffeine) at 8am.

By midday, you’ll have 50mg of caffeine left in your body. So far, so simple.

By 4pm you might expect it to be gone, but instead you have 25mg remaining (because the amount halves every four hours).

By 8pm, you have 12.5mg remaining.

When midnight comes and you’re tucking yourself into bed, you still have 6.25mg of caffeine remaining from your morning coffee!

Use as a nootropic

Many healthy people who are not sleep-deprived use modafinil “off-label” as a nootropic (i.e., a cognitive enhancer).

Important Note: modafinil is prescription-controlled, and only FDA-approved for sleep disorders.

To get around this, a lot of perfectly healthy biohackers describe the symptoms of sleep pattern disorder to their doctor, to get a prescription.

We do not recommend lying to your healthcare provider, and nor do we recommend turning to the online “grey market”.

Such websites often use anonymized private doctors to prescribe on an “informed consent” basis, rather than making a full examination. Those websites then dispense the prescribed medicines directly to the patient with no further questions asked (i.e. very questionable practices).

Caveat emptor!

A new mood-brightener?

Modafinil was recently tested head-to-head against Citalapram for the treatment of depression, and scored well:

How does it work? Modafinil does for dopamine what a lot of anti-depressants do for serotonin. Both dopamine and serotonin promote happiness and wakefulness.

This is very promising, especially as modafinil (in most people, at least) has fewer unwanted side-effects than a lot of common anti-depressant medications.

👀 CHECK IT OUT

❓ What would Prof. Huberman Say?

This AI listened to every episode of Prof. Huberman’s podcast, and you can now ask it questions and it will reply as Prof. Huberman! It draws directly from the content of the podcasts, so you’ll get better results asking it about health science (especially neurobiology) than you will asking it about, for example, gardening or car maintenance.

We asked it “Is modafinil useful?” and it answered:

❝Yes, there is evidence that modafinil will improve learning and memory. It is also used to treat narcolepsy and is gaining popularity as an alternative to Adderall and Ritalin. It is most effective in people who are deprived of sleep, but there is limited data on its effectiveness in well-rested people.❞

📖 ONE-MINUTE BOOK REVIEW

Play Bold - by Magnus Penker

This book is very different to what you might expect, from the title.

We often see: “play bold, believe in yourself, the universe rewards action” etc... Instead, this one is more: “play bold, pay attention to the data, use these metrics, learn from what these businesses did and what their results were”, etc.

We often see: “here’s an anecdote about a historical figure and/or celebrity who made a tremendous bluff and it worked out well so you should too” etc... Instead, this one is more: “see how what we think of as safety is actually anything but! And how by embracing change quickly (or ideally: proactively), we can stay ahead of disaster that may otherwise hit us”.

Penker’s background is also relevant here. He has decades of experience, having “launched 10 start-ups and acquired, turned around, and sold over 30 SMEs all over Europe”. Importantly, he's also "still in the game"... So, unlike many authors whose last experience in the industry was in the 1970s and who wonder why people aren't reaping the same rewards today!

Penker is the therefore opposite of many who advocate to “play bold” but simply mean “fail fast, fail often”... While quietly relying on their family’s capital and privilege to leave a trail of financial destruction behind them, and simultaneously gloating about their imagined business expertise.

In short: boldness does not equate to foolhardiness, and foolhardiness does not equate to boldness.

As for telling the difference? Well, for that we recommend reading the book—It's a highly instructive one.

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Wishing you a bold day of health and productivity,

The 10almonds Team