But Baldino may have been overly modest. In 2002, researchers at Cambridge University gave 60 healthy young male volunteers a battery of standard cognitive tests. One group received modafinil, the other a placebo. The modafinil group performed better on several tasks, such as the "digit span" test, in which subjects are asked to repeat increasingly longer strings of numbers forwards, then backwards. They also did better in recognising repeated visual patterns and at a spatial-planning challenge known as the Tower of London task. (It's not nearly as fun as it sounds.) Writing in the journal Psychopharmacology, the study's authors said the results suggested that "modafinil offers significant potential as a cognitive enhancer".
Too much caffeine may be bad for bone health because it can deplete calcium. Overdoing the caffeine also may affect the vitamin D in your body, which plays a critical role in your body’s bone metabolism. However, the roles of vitamin D as well as caffeine in the development of osteoporosis continue to be a source of debate. Significance: Caffeine may interfere with your body’s metabolism of vitamin D, according to a 2007 Journal of Steroid Biochemistry & Molecular Biology study. You have vitamin D receptors, or VDRs, in your osteoblast cells. These large cells are responsible for the mineralization and synthesis of bone in your body. They create a sheet on the surface of your bones. The D receptors are nuclear hormone receptors that control the action of vitamin D-3 by controlling hormone-sensitive gene expression. These receptors are critical to good bone health. For example, a vitamin D metabolism disorder in which these receptors don’t work properly causes rickets.
I had tried 8 randomized days like the Adderall experiment to see whether I was one of the people whom modafinil energizes during the day. (The other way to use it is to skip sleep, which is my preferred use.) I rarely use it during the day since my initial uses did not impress me subjectively. The experiment was not my best - while it was double-blind randomized, the measurements were subjective, and not a good measure of mental functioning like dual n-back (DNB) scores which I could statistically compare from day to day or against my many previous days of dual n-back scores. Between my high expectation of finding the null result, the poor experiment quality, and the minimal effect it had (eliminating an already rare use), the value of this information was very small.

Some work has been done on estimating the value of IQ, both as net benefits to the possessor (including all zero-sum or negative-sum aspects) and as net positive externalities to the rest of society. The estimates are substantial: in the thousands of dollars per IQ point. But since increasing IQ post-childhood is almost impossible barring disease or similar deficits, and even increasing childhood IQs is very challenging, much of these estimates are merely correlations or regressions, and the experimental childhood estimates must be weakened considerably for any adult - since so much time and so many opportunities have been lost. A wild guess: $1000 net present value per IQ point. The range for severely deficient children was 10-15 points, so any normal (somewhat deficient) adult gain must be much smaller and consistent with Fitzgerald 2012’s ceiling on possible effect sizes (small).
Alpha GPC + AC-11 + Bacopa Monniera + Huperzine: This combination is found in the supplement Alpha Brain, created by the company Onnit. According to a clinical trial that was conducted by the Boston Center for Memory, this combination has demonstrated a notable increase in cognitive performance for healthy individuals and shows particular potential to boost the memory and learning capacity of users. AC-11 is derived from a rainforest herb, and studies have found that it may be able to help people in a variety of ways such as slowing the growth of cancer due to its DNA repairing antioxidant properties. This stack seems to work best if you take it daily for at about two weeks. After that, effects become more pronounced over time, so, similar to the Gingko, Bacopa, Lion’s Mane stack above you need to allow this blend to build up in your system before you judge its overall effectiveness.
Some nootropics are more commonly used than others. These include nutrients like Alpha GPC, huperzine A, L-Theanine, bacopa monnieri, and vinpocetine. Other types of nootropics are still gaining traction. With all that in mind, to claim there is a “best” nootropic for everyone would be the wrong approach since every person is unique and looking for different benefits.
Choline works best when stacked with nootropics. Stacking choline with a nootropic can also help prevent or reduce side effects. Often, people find that they get headaches when they take nootropics by themselves and that stacking them with choline helps reduce this problem. It is usually suggested to stack nootropics with a choline source, especially if you do not get enough from your diet.
Effect of Brain Pill on working memory capacity will be accessed by improvement in mean response time and accuracy measured by working memory battery from baseline to end of the study. Effect of Brain Pill is also accessed on Neurophysiological improvement in working memory as measured by electroencephelogram (EEG) from baseline to end of the study. Also improvement in attention and concentration will be accessed from baseline to end of the study by Picture recognition test.
So how do I pull off this stack? It’s quite simple, really. I order 1-milligram nicotine toothpicks on Amazon that I suck on when I’m downing a cup of coffee (the cinnamon flavor blends quite nicely with a cup o’ joe) and I also keep a dispenser of 1.5-milligram nicotine mints in my office. Warning: nicotine can be addictive. I recommend limiting yourself to no more than 1-2 toothpicks and 1-2 mints per day, and only using on more cognitively demanding days. As a bonus, both caffeine and nicotine are potent ergogenic, physical performance-enhancing aids (albeit in higher amounts, closer to 100+ milligrams for caffeine and 2.5+ milligrams for nicotine).
My answer is that this is not a lot of research or very good research (not nearly as good as the research on nicotine, eg.), and assuming it’s true, I don’t value long-term memory that much because LTM is something that is easily assisted or replaced (personal archives, and spaced repetition). For me, my problems tend to be more about akrasia and energy and not getting things done, so even if a stimulant comes with a little cost to long-term memory, it’s still useful for me. I’m going continue to use the caffeine. It’s not so bad in conjunction with tea, is very cheap, and I’m already addicted, so why not? Caffeine is extremely cheap, addictive, has minimal effects on health (and may be beneficial, from the various epidemiological associations with tea/coffee/chocolate & longevity), and costs extra to remove from drinks popular regardless of their caffeine content (coffee and tea again). What would be the point of carefully investigating it? Suppose there was conclusive evidence on the topic, the value of this evidence to me would be roughly $0 or since ignorance is bliss, negative money - because unless the negative effects were drastic (which current studies rule out, although tea has other issues like fluoride or metal contents), I would not change anything about my life. Why? I enjoy my tea too much. My usual tea seller doesn’t even have decaffeinated oolong in general, much less various varieties I might want to drink, apparently because de-caffeinating is so expensive it’s not worthwhile. What am I supposed to do, give up my tea and caffeine just to save on the cost of caffeine? Buy de-caffeinating machines (which I couldn’t even find any prices for, googling)? This also holds true for people who drink coffee or caffeinated soda. (As opposed to a drug like modafinil which is expensive, and so the value of a definitive answer is substantial and would justify some more extensive calculating of cost-benefit.)
I posted a link to the survey on my Google+ account, and inserted the link at the top of all gwern.net pages; 51 people completed all 11 binary choices (most of them coming from North America & Europe), which seems adequate since the 11 questions are all asking the same question, and 561 responses to one question is quite a few. A few different statistical tests seem applicable: a chi-squared test whether there’s a difference between all the answers, a two-sample test on the averages, and most meaningfully, summing up the responses as a single pair of numbers and doing a binomial test:
I have lots of problems with procrastination and productivity, most likely due to a mild case of ADHD, and recently it's been getting worse and worse. I was a bit hesitant to take Addium at first because I, like most people, had heard about it as a tool for students to use for cramming and it's results sound a little bit like the results of taking Adderall recreationally, which isn't my cup of tea. I was also hesitant to try it because it's marketing just makes it seem like it's a scam pill, and I unfortunately take quality of advertising rather seriously. I changed my mind (after another particularly trying week at work) after a friend of mine actually recommended it for me and told me that she was having great results from it. In my mind, I figured that if a real person,someone I know and trust, tells me in real life that I should maybe try it...then I may as well give it a shot. I ordered the Addium and as soon as I got it, I started taking it immediately. The Addium actually works. I can't believe it. It's helped a lot with my productivity at work. I'm taking just one tablet per day and it seems to be doing the trick. I think the best part about it is that it's not something that you have to continuously take every day.

She speaks from professional and personal experience. When she first moved to the United States from Italy at age 24 she was struck by how shifting from the Mediterranean-style diet she grew up on to a standard American diet negatively impacted her physical health and work performance. The experience led her to more closely study nutrition and the link between diet and brain health. In this excerpt from a longer interview, she discusses the brain foods you should be eating.
Modafinil is a stimulant specifically designed to reduce fatigue and sleepiness. It was approved for treatment of narcolepsy in 1998, and although the exact mechanism behind its effects is not fully understood, most research indicates that modafinil also works by inhibiting reuptake of dopamine, which produces effects similar to those of methylphenidate. It’s also believed that by inhibiting dopamine uptake, more acetylcholine (another neurotransmitter) is released by the hippocampus, which leads to improved cognitive performance, specifically memory.
The hormone testosterone (Examine.com; FDA adverse events) needs no introduction. This is one of the scariest substances I have considered using: it affects so many bodily systems in so many ways that it seems almost impossible to come up with a net summary, either positive or negative. With testosterone, the problem is not the usual nootropics problem that that there is a lack of human research, the problem is that the summary constitutes a textbook - or two. That said, the 2011 review The role of testosterone in social interaction (excerpts) gives me the impression that testosterone does indeed play into risk-taking, motivation, and social status-seeking; some useful links and a representative anecdote:
Nootropic (new-tro-pik) is the term for supplements, also known as smart drugs, that improve brain function. They can be food substances like phenethylamine and L-Theanine, found in chocolate and green tea, respectively. Nootropics also include extracted and purified components of medicinal plants, as well as substances synthesized from chemical precursors, such as piracetam, the world's first official nootropic (piracetam was created in 1964 in Belgium by a team of scientists whose leader, Dr. Corneliu E. Giurgea, coined the term). Since then piracetam has been widely used as a cognitive enhancer and to treat neurological diseases like Alzheimer's.
-Raw cacao is rich in theobromine, a powerful antioxidant known to support cellular aging and reduce the risk of heart disease. Its effects are similar to those of caffeine, as they both are vasodilators and improve blood flow to the brain [except cacao won’t give you jitters]...You can use raw cacao to make cacao tea, or in your smoothies. Dark chocolate with cocoa content of 80% or higher is also rich in theobromine and natural antioxidants. Besides, chocolate makes you happy. I have a small piece of high-quality dark chocolate, like 85% or 90% dark, every day.
Even the best of today’s nootropics only just barely scratch the surface. You might say that we are in the “Nokia 1100” phase of taking nootropics, and as better tools and more data come along, the leading thinkers in the space see a powerful future. For example, they are already beginning to look past biochemistry to the epigenome. Not only is the epigenome the code that runs much of your native biochemistry, we now know that experiences in life can be recorded in your epigenome and then passed onto future generations. There is every reason to believe that you are currently running epigenetic code that you inherited from your great-grandmother’s life experiences. And there is every reason to believe that the epigenome can be hacked – that the nootropics of the future can not only support and enhance our biochemistry, but can permanently change the epigenetic code that drives that biochemistry and that we pass onto our children.
Caffeine + L-Theanine: Since caffeine can produce unwanted side effects in high amounts (such as jitteriness and headaches), most people, and especially “slow caffeine oxidizers” find that by adding L-Theanine to a caffeine source such as coffee, any negative side effects of caffeine can be controlled. Caffeine and L-Theanine in combination have been researched and proven to boost concentration, attention, and energy while reducing anxiety. For this stack, use a ratio of four parts L-Theanine to one part caffeine, such as 400 milligrams of L-Theanine along with 100 milligrams of caffeine. You may want to start out with a smaller dose such as 200 milligrams of L-Theanine and 50 milligrams of caffeine and work your way up to find the best dose for you (the average cup of coffee has about 100mg of caffeine).
The acid is also known to restore the vitamin C and E levels in the body. Alpha Lipoic Acid’s efficient antioxidant property protects brain cells from damage during any injury. This helps in making sure that your brain functions normally even if there is any external or internal brain injury. OptiMind, one of the best nootropic supplements that you can find today contains Alpha Lipoic Acid that can help in enhancing your brain’s capabilities.
So how do I pull off this stack? It’s quite simple, really. I order 1-milligram nicotine toothpicks on Amazon that I suck on when I’m downing a cup of coffee (the cinnamon flavor blends quite nicely with a cup o’ joe) and I also keep a dispenser of 1.5-milligram nicotine mints in my office. Warning: nicotine can be addictive. I recommend limiting yourself to no more than 1-2 toothpicks and 1-2 mints per day, and only using on more cognitively demanding days. As a bonus, both caffeine and nicotine are potent ergogenic, physical performance-enhancing aids (albeit in higher amounts, closer to 100+ milligrams for caffeine and 2.5+ milligrams for nicotine).
A key ingredient of Noehr’s chemical “stack” is a stronger racetam called Phenylpiracetam. He adds a handful of other compounds considered to be mild cognitive enhancers. One supplement, L-theanine, a natural constituent in green tea, is claimed to neutralise the jittery side-effects of caffeine. Another supplement, choline, is said to be important for experiencing the full effects of racetams. Each nootropic is distinct and there can be a lot of variation in effect from person to person, says Lawler. Users semi-annonymously compare stacks and get advice from forums on sites such as Reddit. Noehr, who buys his powder in bulk and makes his own capsules, has been tweaking chemicals and quantities for about five years accumulating more than two dozens of jars of substances along the way. He says he meticulously researches anything he tries, buys only from trusted suppliers and even blind-tests the effects (he gets his fiancée to hand him either a real or inactive capsule).

This tendency is exacerbated by general inefficiencies in the nootropics market - they are manufactured for vastly less than they sell for, although the margins aren’t as high as they are in other supplement markets, and not nearly as comical as illegal recreational drugs. (Global Price Fixing: Our Customers are the Enemy (Connor 2001) briefly covers the vitamin cartel that operated for most of the 20th century, forcing food-grade vitamins prices up to well over 100x the manufacturing cost.) For example, the notorious Timothy Ferriss (of The Four-hour Work Week) advises imitators to find a niche market with very high margins which they can insert themselves into as middlemen and reap the profits; one of his first businesses specialized in… nootropics & bodybuilding. Or, when Smart Powders - usually one of the cheapest suppliers - was dumping its piracetam in a fire sale of half-off after the FDA warning, its owner mentioned on forums that the piracetam was still profitable (and that he didn’t really care because selling to bodybuilders was so lucrative); this was because while SP was selling 2kg of piracetam for ~$90, Chinese suppliers were offering piracetam on AliBaba for $30 a kilogram or a third of that in bulk. (Of course, you need to order in quantities like 30kg - this is more or less the only problem the middlemen retailers solve.) It goes without saying that premixed pills or products are even more expensive than the powders.


It would be like saying: 'No, you can't use a cell phone. It might increase productivity!'" If we eventually decide that neuroenhancers work, and are basically safe, will we one day enforce their use? Lawmakers might compel certain workers - A&E doctors, air-traffic controllers - to take them. (Indeed, the US Air Force already makes modafinil available to pilots embarking on long missions.) For the rest of us, the pressure will be subtler - that queasy feeling I get when I remember that my younger colleague is taking Provigil to meet deadlines. All this may be leading to a kind of society I'm not sure I want to live in: a society where we're even more overworked and driven by technology than we already are, and where we have to take drugs to keep up; a society where we give children academic steroids along with their daily vitamins.

My first impression of ~1g around 12:30PM was that while I do not feel like running around, within an hour I did feel like the brain fog was lighter than before. The effect wasn’t dramatic, so I can’t be very confident. Operationalizing brain fog for an experiment might be hard: it doesn’t necessarily feel like I would do better on dual n-back. I took 2 smaller doses 3 and 6 hours later, to no further effect. Over the following weeks and months, I continued to randomly alternate between potassium & non-potassium days. I noticed no effects other than sleep problems.


I’m wary of others, though. The trouble with using a blanket term like “nootropics” is that you lump all kinds of substances in together. Technically, you could argue that caffeine and cocaine are both nootropics, but they’re hardly equal. With so many ways to enhance your brain function, many of which have significant risks, it’s most valuable to look at nootropics on a case-by-case basis. Here’s a list of 13 nootropics, along with my thoughts on each.
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.
Nootropics (/noʊ.əˈtrɒpɪks/ noh-ə-TROP-iks) (colloquial: smart drugs and cognitive enhancers) are drugs, supplements, and other substances that may improve cognitive function, particularly executive functions, memory, creativity, or motivation, in healthy individuals.[1] While many substances are purported to improve cognition, research is at a preliminary stage as of 2018, and the effects of the majority of these agents are not fully determined.
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