One curious thing that leaps out looking at the graphs is that the estimated underlying standard deviations differ: the nicotine days have a strikingly large standard deviation, indicating greater variability in scores - both higher and lower, since the means weren’t very different. The difference in standard deviations is just 6.6% below 0, so the difference almost reaches our usual frequentist levels of confidence too, which we can verify by testing:
Herbs and plants have been used for cognitive enhancement for at least 5,000 years in Indian and Chinese medicine, long before the first synthetic nootropic was created. The practice of Indian Ayurvedic medicine includes the use of a group of nootropic plants known as Medhya Rasayana, the four primary plants of which are Mandukaparni, Yastimadhu, Duduchi and Shankhapushpi, though other lesser known plants are also used. One of the most common supplements in Ayurvedic medicine is Brahmi, known scientifically as “Bacopa monnieri” or “B. monnieri “ and more commonly as water hyssop, Thyme-leaved Gratiola, herb of grace or Indian pennywort. It is named after Lord Brahma, the creator God and originator of Ayurveda, and has been used for centuries to treat disorders ranging from pain and epilepsy to inflammation and memory dysfunction. The exact mechanism behind its action is not fully understood, but it is believed to promote antioxidant activity as well as protect neurons in the prefrontal cortex, hippocampus and corpus striatum against cytotoxicity and DNA damage associated with Alzheimer’s. The prefrontal cortex is critical in rational, social and personality behavior, the hippocampus is believed to be the seat of memory and the autonomic nervous system and the striatum play a role in the reward system of action, so the protection Brahmi provides is extremely helpful in preventing the degeneration of many important cognitive faculties. An effective dose ranges from 300 to 450 mg per day. Winter cherry (ashwagandha) is another well-known Ayurvedic supplement that can promote improved cognitive development, memory and intelligence and reduce the effects of neurodegenerative diseases such as Parkinson’s, Huntington’s and Alzheimer’s. The optimal dose is 6,000 mg per day divided into three 2,000 mg doses. Aloeweed (shankhpushpi) is also used in Ayurvedic medicine to improve memory and intellect as well as treat hypertension, epilepsy and diabetes. Effective doses for most neuroenhancing benefits range as high as 40 g per day.
The truth is that, almost 20 years ago when my brain was failing and I was fat and tired, I did not know to follow this advice. I bought $1000 worth of smart drugs from Europe, took them all at once out of desperation, and got enough cognitive function to save my career and tackle my metabolic problems. With the information we have now, you don’t need to do that. Please learn from my mistakes!
However, normally when you hear the term nootropic kicked around, people really mean a “cognitive enhancer” — something that does benefit thinking in some way (improved memory, faster speed-of-processing, increased concentration, or a combination of these, etc.), but might not meet the more rigorous definition above. “Smart drugs” is another largely-interchangeable term.
Ginkgo Biloba, Bacopa Monnieri, and Lion’s Mane: This particular unique blend boosts mental focus, memory, learning, and cognitive performance while reducing anxiety and depression, and I’ve found that it can significantly boost mental alertness for around six hours at a time without any jitteriness or irritability – or any significant amounts of caffeine. It’s important to allow for a grace period of about 12 weeks before you feel the stack’s full potential, so don’t expect immediate results with this combination.
I can test fish oil for mood, since the other claimed benefits like anti-schizophrenia are too hard to test. The medical student trial (Kiecolt-Glaser et al 2011) did not see changes until visit 3, after 3 weeks of supplementation. (Visit 1, 3 weeks, visit 2, supplementation started for 3 weeks, visit 3, supplementation continued 3 weeks, visit 4 etc.) There were no tests in between the test starting week 1 and starting week 3, so I can’t pin it down any further. This suggests randomizing in 2 or 3 week blocks. (For an explanation of blocking, see the footnote in the Zeo page.)
I was contacted by the Longecity user lostfalco, and read through some of his writings on the topic. I had never heard of LLLT before, but the mitochondria mechanism didn’t sound impossible (although I wondered whether it made sense at a quantity level14151617), and there was at least some research backing it; more importantly, lostfalco had discovered that devices for LLLT could be obtained as cheap as $15. (Clearly no one will be getting rich off LLLT or affiliate revenue any time soon.) Nor could I think of any way the LLLT could be easily harmful: there were no drugs involved, physical contact was unnecessary, power output was too low to directly damage through heating, and if it had no LLLT-style effect but some sort of circadian effect through hitting photoreceptors, using it in the morning wouldn’t seem to interfere with sleep.
Microdosing with Iboga: Native to the rainforests in Central Africa, Iboga is an evergreen shrub, with high concentrations found in the root bark. It has a rich history amongst practitioners in the indigenous Bwiti religion in Africa and has recently found its way into Western practices, primarily for extremely effective therapy for drug addictions, but also for physical energy, cognitive performance in smaller microdoses, and a surge in positive emotions (See additional studies here and here.). To microdose with Iboga, you will want to find it in tincture or root bark form (the root bark form is typically encapsulated). If using a tincture, find a source that has the root bark extracted into its purest form, combined with Iboga alkaloids, which keeps the full spectrum of the plant untouched. Just a single drop of an Iboga tincture equates to about 0.5 milligrams and suffices as a microdose. For the root bark of Iboga, a dose of 300-500 milligrams is also an effective dose. I’ve personally found Iboga to be most useful prior to a workout or an effort that combines both brain and body demands, such as tennis or basketball – but it makes you hyperactive and jittery if taken prior to a day of desk work. This makes sense when you consider that African tribes traditionally whipped themselves into a frenzied pre-battle state on Iboga.
Adderall is a mix of 4 amphetamine salts (FDA adverse events), and not much better than the others (but perhaps less addictive); as such, like caffeine or methamphetamine, it is not strictly a nootropic but a cognitive enhancer and can be tricky to use right (for how one should use stimulants, see How To Take Ritalin Correctly). I ordered 10x10mg Adderall IR off Silk Road (Wikipedia). On the 4th day after confirmation from seller, the package arrived. It was a harmless looking little padded mailer. Adderall as promised: 10 blue pills with markings, in a double ziplock baggy (reasonable, it’s not cocaine or anything). They matched pretty much exactly the descriptions of the generic I had found online. (Surprisingly, apparently both the brand name and the generic are manufactured by the same pharmacorp.)
Manually mixing powders is too annoying, and pre-mixed pills are expensive in bulk. So if I’m not actively experimenting with something, and not yet rich, the best thing is to make my own pills, and if I’m making my own pills, I might as well make a custom formulation using the ones I’ve found personally effective. And since making pills is tedious, I want to not have to do it again for years. 3 years seems like a good interval - 1095 days. Since one is often busy and mayn’t take that day’s pills (there are enough ingredients it has to be multiple pills), it’s safe to round it down to a nice even 1000 days. What sort of hypothetical stack could I make? What do the prices come out to be, and what might we omit in the interests of protecting our pocketbook?
So, I thought I might as well experiment since I have it. I put the 23 remaining pills into gel capsules with brown rice as filling, made ~30 placebo capsules, and will use the one-bag blinding/randomization method. I don’t want to spend the time it would take to n-back every day, so I will simply look for an effect on my daily mood/productivity self-rating; hopefully Noopept will add a little on average above and beyond my existing practices like caffeine+piracetam (yes, Noopept may be as good as piracetam, but since I still have a ton of piracetam from my 3kg order, I am primarily interested in whether Noopept adds onto piracetam rather than replaces). 10mg doses seem to be on the low side for Noopept users, weakening the effect, but on the other hand, if I were to take 2 capsules at a time, then I’d halve the sample size; it’s not clear what is the optimal tradeoff between dose and n for statistical power.
With just 16 predictions, I can’t simply bin the predictions and say yep, that looks good. Instead, we can treat each prediction as equivalent to a bet and see what my winnings (or losses) were; the standard such proper scoring rule is the logarithmic rule which pretty simple: you earn the logarithm of the probability if you were right, and the logarithm of the negation if you were wrong; he who racks up the fewest negative points wins. We feed in a list and get back a number:
Since each 400mg pill takes up 2 00 pills, that’s 4 gel caps a day to reach 800mg magnesium citrate (ie. 136mg elemental magnesium), or 224 gel caps (2x120) for the first batch of Solgar magnesium pills. Turning the Solgar tablets into gel capsules was difficult enough that I switched to NOW Food’s 227g magnesium citrate powder for the second batch.
Clinical psychiatrist Emily Deans has a private practice in Massachusetts and teaches at Harvard Medical School. She told me by phone that, in principle, there's "probably nothing dangerous" about the occasional course of nootropics for a hunting trip, finals week, or some big project. Beyond that, she suggests considering that it's possible to build up a tolerance to many neuroactive products if you use them often enough.
But notice that most of the cost imbalance is coming from the estimate of the benefit of IQ - if it quadrupled to a defensible $8000, that would be close to the experiment cost! So in a way, what this VoI calculation tells us is that what is most valuable right now is not that iodine might possibly increase IQ, but getting a better grip on how much any IQ intervention is worth.
I’m sure your office already has a coffee maker, but if you’re in the mood for a refreshing coffee twist at the office, try this cold brew option from Chameleon Cold Brew. They use a highly select blend of 100% organic, fair trade certified Arabica coffee beans and filtered Texas Hill Country water. The result is a super smooth, less acidic and highly caffeinated coffee, which can be enjoyed hot or cold.
Research on animals has shown that intermittent fasting — limiting caloric intake at least two days a week — can help improve neural connections in the hippocampus and protect against the accumulation of plaque, a protein prevalent in the brains of people with Alzheimer’s disease. Research has also shown that intermittent fasting helped reduce anxiety in mice.
Nor am I sure how important the results are - partway through, I haven’t noticed anything bad, at least, from taking Noopept. And any effect is going to be subtle: people seem to think that 10mg is too small for an ingested rather than sublingual dose and I should be taking twice as much, and Noopept’s claimed to be a chronic gradual sort of thing, with less of an acute effect. If the effect size is positive, regardless of statistical-significance, I’ll probably think about doing a bigger real self-experiment (more days blocked into weeks or months & 20mg dose)
Powders are good for experimenting with (easy to vary doses and mix), but not so good for regular taking. I use OO gel capsules with a Capsule Machine: it’s hard to beat $20, it works, it’s not that messy after practice, and it’s not too bad to do 100 pills. However, I once did 3kg of piracetam + my other powders, and doing that nearly burned me out on ever using capsules again. If you’re going to do that much, something more automated is a serious question! (What actually wound up infuriating me the most was when capsules would stick in either the bottom or top try - requiring you to very gingerly pull and twist them out, lest the two halves slip and spill powder - or when the two halves wouldn’t lock and you had to join them by hand. In contrast: loading the gel caps could be done automatically without looking, after some experience.)
Encouraged by TruBrain’s magnesium & my magnesium l-threonate use, I design and run a blind random self-experiment to see whether magnesium citrate supplementation would improve my mood or productivity. I collected ~200 days of data at two dose levels. The analysis finds that the net effect was negative, but a more detailed look shows time-varying effects with a large initial benefit negated by an increasingly-negative effect. Combined with my expectations, the long half-life, and the higher-than-intended dosage, I infer that I overdosed on the magnesium. To verify this, I will be running a followup experiment with a much smaller dose.
Low level laser therapy (LLLT) is a curious treatment based on the application of a few minutes of weak light in specific near-infrared wavelengths (the name is a bit of a misnomer as LEDs seem to be employed more these days, due to the laser aspect being unnecessary and LEDs much cheaper). Unlike most kinds of light therapy, it doesn’t seem to have anything to do with circadian rhythms or zeitgebers. Proponents claim efficacy in treating physical injuries, back pain, and numerous other ailments, recently extending it to case studies of mental issues like brain fog. (It’s applied to injured parts; for the brain, it’s typically applied to points on the skull like F3 or F4.) And LLLT is, naturally, completely safe without any side effects or risk of injury.
It wasn't always helpful, but it does work sometimes. The first two days gave me stomach and head pain, so I began to test with taking before or after food, and with or without food. The bottle says to take before food, but I preferred taking this with food, more food is better. This doesn't go well in the stomach with something like chocolate, so take this with something like bread or a meal. More importantly, stay very hydrated unless you want a headache, these pills are very hydro-demanding. The pills also work better if you get your blood moving, just a short walk is fine. Energy drinks and coffee go very well with these, as I had a very clear minded experience when taking these with a Monster Java, it was like a cool breeze blowing away the mental fog.
Methylphenidate was accepted into medical practice in 1960 as a way to treat narcolepsy and ADHD. It works by inhibiting the reuptake of dopamine and norepinephrine into the nervous system, causing a flooding of dopamine and norepinephrine in the synapse between the nerves, which in turn leads to amplified signaling between neurons. It’s been said that these effects are basically the same as those of amphetamines (see more details below), which are synthetic, addictive, mood-altering drugs, used illegally in sports as a stimulant and also legally as a prescription drug – like Ritalin – to treat children with ADD and adults with narcolepsy.
And many people swear by them. Neal Thakkar, for example, is an entrepreneur from Marlboro, New Jersey, who claims nootropics improved his life so profoundly that he can’t imagine living without them. His first breakthrough came about five years ago, when he tried a piracetam/choline combination, or “stack,” and was amazed by his increased verbal fluency. (Piracetam is a cognitive-enhancement drug permitted for sale in the U. S. as a dietary supplement; choline is a natural substance.)
As Sulbutiamine crosses the blood-brain barrier very easily, it has a positive effect on the cholinergic and the glutamatergic receptors that are responsible for vital activities impacting memory, concentration, and mood. The compound is also fat soluble, which means it circulates rapidly and widely throughout the body and the brain, ensuring positive results. Thus, patients with schizophrenia and Parkinson’s disease will find the drug to be very effective.
Blinding stymied me for a few months since the nasty taste was unmistakable and I couldn’t think of any gums with a similar flavor to serve as placebo. (The nasty taste does not seem to be due to the nicotine despite what one might expect; Vaniver plausibly suggested the bad taste might be intended to prevent over-consumption, but nothing in the Habitrol ingredient list seemed to be noted for its bad taste, and a number of ingredients were sweetening sugars of various sorts. So I couldn’t simply flavor some gum.)
Racetams, such as piracetam, oxiracetam, and aniracetam, which are often marketed as cognitive enhancers and sold over-the-counter. Racetams are often referred to as nootropics, but this property is not well established. The racetams have poorly understood mechanisms, although piracetam and aniracetam are known to act as positive allosteric modulators of AMPA receptors and appear to modulate cholinergic systems.