The research literature, while copious, is messy and varied: methodologies and devices vary substantially, sample sizes are tiny, the study designs vary from paper to paper, metrics are sometimes comically limited (one study measured speed of finishing a RAPM IQ test but not scores), blinding is rare and unclear how successful, etc. Relevant papers include Chung et al 2012, Rojas & Gonzalez-Lima 2013, & Gonzalez-Lima & Barrett 2014. Another Longecity user ran a self-experiment, with some design advice from me, where he performed a few cognitive tests over several periods of LLLT usage (the blocks turned out to be ABBA), using his father and towels to try to blind himself as to condition. I analyzed his data, and his scores did seem to improve, but his scores improved so much in the last part of the self-experiment I found myself dubious as to what was going on - possibly a failure of randomness given too few blocks and an temporal exogenous factor in the last quarter which was responsible for the improvement.


One should note the serious caveats here: it is a small in vitro study of a single category of human cells with an effect size that is not clear on a protein which feeds into who-knows-what pathways. It is not a result in a whole organism on any clinically meaningful endpoint, even if we take it at face-value (many results never replicate). A look at followup work citing Rapuri et al 2007 is not encouraging: Google Scholar lists no human studies of any kind, much less high-quality studies like RCTs; just some rat followups on the calcium effect. This is not to say Rapuri et al 2007 is a bad study, just that it doesn’t bear the weight people are putting on it: if you enjoy caffeine, this is close to zero evidence that you should reduce or drop caffeine consumption; if you’re taking too much caffeine, you already have plenty of reasons to reduce; if you’re drinking lots of coffee, you already have plenty of reasons to switch to tea; etc.
The fish oil can be considered a free sunk cost: I would take it in the absence of an experiment. The empty pill capsules could be used for something else, so we’ll put the 500 at $5. Filling 500 capsules with fish and olive oil will be messy and take an hour. Taking them regularly can be added to my habitual morning routine for vitamin D and the lithium experiment, so that is close to free but we’ll call it an hour over the 250 days. Recording mood/productivity is also free a sunk cost as it’s necessary for the other experiments; but recording dual n-back scores is more expensive: each round is ~2 minutes and one wants >=5, so each block will cost >10 minutes, so 18 tests will be >180 minutes or >3 hours. So >5 hours. Total: 5 + (>5 \times 7.25) = >41.
Price discrimination is aided by barriers such as ignorance and oligopolies. An example of the former would be when I went to a Food Lion grocery store in search of spices, and noticed that there was a second selection of spices in the Hispanic/Latino ethnic food aisle, with unit prices perhaps a fourth of the regular McCormick-brand spices; I rather doubt that regular cinnamon varies that much in quality. An example of the latter would be using veterinary drugs on humans - any doctor to do so would probably be guilty of medical malpractice even if the drugs were manufactured in the same factories (as well they might be, considering economies of scale). Similarly, we can predict that whenever there is a veterinary drug which is chemically identical to a human drug, the veterinary drug will be much cheaper, regardless of actual manufacturing cost, than the human drug because pet owners do not value their pets more than themselves. Human drugs are ostensibly held to a higher standard than veterinary drugs; so if veterinary prices are higher, then there will be an arbitrage incentive to simply buy the cheaper human version and downgrade them to veterinary drugs.

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.
Low-dose lithium orotate is extremely cheap, ~$10 a year. There is some research literature on it improving mood and impulse control in regular people, but some of it is epidemiological (which implies considerable unreliability); my current belief is that there is probably some effect size, but at just 5mg, it may be too tiny to matter. I have ~40% belief that there will be a large effect size, but I’m doing a long experiment and I should be able to detect a large effect size with >75% chance. So, the formula is NPV of the difference between taking and not taking, times quality of information, times expectation: \frac{10 - 0}{\ln 1.05} \times 0.75 \times 0.40 = 61.4, which justifies a time investment of less than 9 hours. As it happens, it took less than an hour to make the pills & placebos, and taking them is a matter of seconds per week, so the analysis will be the time-consuming part. This one may actually turn a profit.

The evidence? Ritalin is FDA-approved to treat ADHD. It has also been shown to help patients with traumatic brain injury concentrate for longer periods, but does not improve memory in those patients, according to a 2016 meta-analysis of several trials. A study published in 2012 found that low doses of methylphenidate improved cognitive performance, including working memory, in healthy adult volunteers, but high doses impaired cognitive performance and a person’s ability to focus. (Since the brains of teens have been found to be more sensitive to the drug’s effect, it’s possible that methylphenidate in lower doses could have adverse effects on working memory and cognitive functions.)
Farah was one of several scholars who contributed to a recent article in Nature, "Towards Responsible Use of Cognitive Enhancing Drugs by the Healthy". The optimistic tone of the article suggested that some bioethicists are leaning towards endorsing neuroenhancement. "Like all new technologies, cognitive enhancement can be used well or poorly," the article declared. "We should welcome new methods of improving our brain function. In a world in which human workspans and lifespans are increasing, cognitive-enhancement tools - including the pharmacological - will be increasingly useful for improved quality of life and extended work productivity, as well as to stave off normal and pathological age-related cognitive declines. Safe and effective cognitive enhancers will benefit both the individual and society." The BMA report offered a similarly upbeat observation: "Universal access to enhancing interventions would bring up the baseline level of cognitive ability, which is generally seen to be a good thing."

After informally testing various formulas of Qualia OS on themselves and friends, Collective founders did an unblinded pilot study with nine volunteers that Dr. Stickler says showed significant benefits in cognitive function and stress response in eight of the subjects. Still, he admits this isn’t airtight scientific proof that the product works. He says the Collective is hoping to do a placebo-controlled study, but in the meantime, he’s confident the stack works because of the results he’s seen in patients.
Dr. Lisa Mosconi, whose research spans an extraordinary range of specialties including brain science, the microbiome, and nutritional genomics, notes that the dietary needs of the brain are substantially different from those of the other organs, yet few of us have any idea what they might be. Her innovative approach to cognitive health incorporates concepts that most doctors have yet to learn. Busting through advice based on pseudoscience, Dr. Mosconi provides recommendations for a complete food plan, while calling out noteworthy surprises, including why that paleo diet you are following may not be ideal, why avoiding gluten may be a terrible mistake, and how simply getting enough water can dramatically improve alertness.
In this large population-based cohort, we saw consistent robust associations between cola consumption and low BMD in women. The consistency of pattern across cola types and after adjustment for potential confounding variables, including calcium intake, supports the likelihood that this is not due to displacement of milk or other healthy beverages in the diet. The major differences between cola and other carbonated beverages are caffeine, phosphoric acid, and cola extract. Although caffeine likely contributes to lower BMD, the result also observed for decaffeinated cola, the lack of difference in total caffeine intake across cola intake groups, and the lack of attenuation after adjustment for caffeine content suggest that caffeine does not explain these results. A deleterious effect of phosphoric acid has been proposed (26). Cola beverages contain phosphoric acid, whereas other carbonated soft drinks (with some exceptions) do not.
The price is not as good as multivitamins or melatonin. The studies showing effects generally use pretty high dosages, 1-4g daily. I took 4 capsules a day for roughly 4g of omega acids. The jar of 400 is 100 days’ worth, and costs ~$17, or around 17¢ a day. The general health benefits push me over the edge of favoring its indefinite use, but looking to economize. Usually, small amounts of packaged substances are more expensive than bulk unprocessed, so I looked at fish oil fluid products; and unsurprisingly, liquid is more cost-effective than pills (but like with the powders, straight fish oil isn’t very appetizing) in lieu of membership somewhere or some other price-break. I bought 4 bottles (16 fluid ounces each) for $53.31 total (thanks to coupons & sales), and each bottle lasts around a month and a half for perhaps half a year, or ~$100 for a year’s supply. (As it turned out, the 4 bottles lasted from 4 December 2010 to 17 June 2011, or 195 days.) My next batch lasted 19 August 2011-20 February 2012, and cost $58.27. Since I needed to buy empty 00 capsules (for my lithium experiment) and a book (Stanovich 2010, for SIAI work) from Amazon, I bought 4 more bottles of 16fl oz Nature’s Answer (lemon-lime) at $48.44, which I began using 27 February 2012. So call it ~$70 a year.

When you start taking legit nootropics, you get to leave all of that behind you.  You may never achieve perfect concentration (most of us never will), but you should find you are able to concentrate on the task at hand for much longer than you do now.  You will end up taking fewer breaks, and you might start finishing up your work on time each day again—or even early!
50 pairs of active/placebos or 100 days. With 120 tablets and 4 tablets used up, that leaves me 58 doses. That might seem adequate except the paired t-test approximation is overly-optimistic, and I also expect the non-randomized non-blinded correlation is too high which means that is overly-optimistic as well. The power would be lower than I’d prefer. I decided to simply order another bottle of Solgar’s & double the sample size to be safe.
It seems like we're constantly bombarded by the newest superfoods, how matcha is the coffee, and why Himalayan salt is "so much better" than sea salt (spoiler alert: it's not, but its pink hue definitely makes cooking more fun). Dieting has always been an on/off kind of activity in my life which is why I've struggled to jump on this train for a while.
Breathing carefully, I clutched the Costco special edition family size 1.5-liter glass bottle of vodka and carefully extracted 10 milliliters with a miniature glass pipette, which I then transferred into a small amber glass bottle. Then, with my nine-year-old son’s tiny set of school scissors, I snipped exactly 1/10 of LSD from the blotter square I’d ordered from a psychedelic research chemical supplier website the week prior, with a cloaked browser, of course, so the feds didn’t come knocking at my door. I dropped the LSD into the bottle, gave it a thirty-second shake, then placed the bottle in the pantry, next to my protein powder and creatine. I smiled. Within 24 hours, I’d be ready to sample my first homemade, volumetric “microdose” of a drug reported to increase lateral thinking patterns, improve creativity, massively boost productivity and much, much more.

A passionate singer, yogi, and vegan baker, you can usually count on Jessica to be writing songs, inventing recipes, or doing handstands. Most notably, Jessica is recognized (by her parents) for a 3 minute vocal solo at Carnegie Hall (at 13), by her friends for her amazing Raw Vegan Peanut Butter Chocolate Chip Cookie recipe, and also by her yogi friends for her recent mastery of Camel Pose. In all seriousness, Jessica is beyond excited to write for SnackNation, and to share her passion for health, wellness, and delicious foods.
When asked if there’s a discrepancy between Qualia’s claims and that disclaimer, Dr. Stickler points out that products such as OS aren’t promising to treat or cure any diseases. That’s the line these companies can’t cross. They can claim their product makes you smarter or more focused without data from clinical trials, but they can’t claim their pill treats traumatic brain injury, ADHD, or Alzheimer’s.
I’ve been taking nootropics on and off for a month, and despite my spurts of productivity, I’m still not 100 percent sure that they’re working. I could well be placebo-ing myself into thinking I'm working harder and focusing better than I typically do. But apparently enough people are feeling some effect, placebo or not, because nootropics start-ups are thriving. There’s truBrain, Nootrobrain, Nootroo, and a host of others. Nootrobox, the company that makes my pills, says that it’s selling "five figures" worth of cognitive supplements monthly to customers that include top Silicon Valley executives and Hollywood moguls.
I tried taking whole pills at 1 and 3 AM. I felt kind of bushed at 9 AM after all the reading, and the 50 minute nap didn’t help much - I was sleep only around 10 minutes and spent most of it thinking or meditation. Just as well the 3D driver is still broken; I doubt the scores would be reasonable. Began to perk up again past 10 AM, then felt more bushed at 1 PM, and so on throughout the day; kind of gave up and began watching & finishing anime (Amagami and Voices of a Distant Star) for the rest of the day with occasional reading breaks (eg. to start James C. Scotts Seeing Like A State, which is as described so far). As expected from the low quality of the day, the recovery sleep was bigger than before: a full 10 hours rather than 9:40; the next day, I slept a normal 8:50, and the following day ~8:20 (woken up early); 10:20 (slept in); 8:44; 8:18 (▁▇▁▁). It will be interesting to see whether my excess sleep remains in the hour range for ’good modafinil nights and two hours for bad modafinil nights.
And when it comes to your brain, it’s full of benefits, too. Coconut oil works as a natural anti-inflammatory, suppressing cells responsible for inflammation. It can help with memory loss as you age and destroy bad bacteria that hangs out in your gut. (5) Get your dose of coconut oil in this Baked Grouper with Coconut Cilantro Sauce or Coconut Crust Pizza.
Most of the most solid fish oil results seem to meliorate the effects of age; in my 20s, I’m not sure they are worth the cost. But I would probably resume fish oil in my 30s or 40s when aging really becomes a concern. So the experiment at most will result in discontinuing for a decade. At $X a year, that’s a net present value of sum $ map (\n -> 70 / (1 + 0.05)^n) [1..10] = $540.5.

Even party drugs are going to work: Biohackers are taking recreational drugs like LSD, psilocybin mushrooms, and mescaline in microdoses—about a tenth of what constitutes a typical dose—with the goal of becoming more focused and creative. Many who’ve tried it report positive results, but real research on the practice—and its safety—is a long way off. “Whether microdosing with LSD improves creativity and cognition remains to be determined in an objective experiment using double-blind, placebo-controlled methodology,” Sahakian says.

One thing I did do was piggyback on my Noopept self-experiment: I blinded & randomized the Noopept for a real experiment, but simply made sure to vary the Magtein without worrying about blinding or randomizing it. (The powder is quite bulky.) The correlation the experiment turned in was a odds-ratio of 1.9; interesting and in the right direction (higher is better), but since the magnesium part wasn’t random or blind, not a causal result.

I do recommend a few things, like modafinil or melatonin, to many adults, albeit with misgivings about any attempt to generalize like that. (It’s also often a good idea to get powders, see the appendix.) Some of those people are helped; some have told me that they tried and the suggestion did little or nothing. I view nootropics as akin to a biological lottery; one good discovery pays for all. I forge on in the hopes of further striking gold in my particular biology. Your mileage will vary. All you have to do, all you can do is to just try it. Most of my experiences were in my 20s as a right-handed 5’11 white male weighing 190-220lbs, fitness varying over time from not-so-fit to fairly fit. In rough order of personal effectiveness weighted by costs+side-effects, I rank them as follows:
People with failing memory and worried about Alzheimer’s disease are sometimes seduced by advertisements for Huperzine A, extracted from a type of moss. Some studies have shown that it increases levels of acetylcholine in the brain, a chemical that is in short supply in Alzheimer’s. But despite increasing acetylcholine, aside from a few questionable studies in China, there is no evidence that it improves memory. Unfortunately when it comes to memory pills, they are best forgotten. There is, however, hope that a nasal spray containing insulin can increase the absorption of glucose into brain cells and improve cognitive function. But in the meantime, the best bet to maintain good brain function is to monitor blood glucose and blood pressure, eat a diet rich in fruits, vegetables and whole grains, and low in simple carbs and saturated fat. And don’t forget that physical exercise also exercises your brain.

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:
"More and more of our young people are using these drugs to help them work. They've got their laptop, their iPhone, and their Adderall. This rising generation of workers and leaders may have a subtly different style of thinking and working, because they're using these drugs or because they learned to work using these drugs, so that even if you take the drugs away they'll still have a certain approach. I'm a little concerned that we could be raising a generation of very focused accountants."

Your brain loves omega-3 fatty acids, which are thought to play an important role in cognitive function. According to the New York Times describing research in the journal Neurology, low levels of these unsaturated fats in the blood are linked with smaller brain volume and worse performance on certain tests of mental function. Omega-3s, which are found in salmon and other cold-water fish like tuna, may improve the retention of brain cells and also bolster the brainpower of younger adults. According to University of Pittsburgh research published last year, adults under age 25 who increased their omega-3 intake over six months improved their scores on tests measuring working memory.
Talk to your doctor, too, before diving in "to ensure that they do not conflict with current meds or cause a detrimental effect," Hohler says. You also want to consider what you already know about your health and body – if you have anxiety or are already sensitive to caffeine, for example, you may find that some of the supplements work a little too well and just enhance anxiety or make it difficult to sleep, Barbour says. Finances matter, too, of course: The retail price for Qualia Mind is $139 for 22 seven-capsule "servings"; the suggestion is to take one serving a day, five days a week. The retail price for Alpha Brain is $79.95 for 90 capsules; adults are advised to take two a day.

Common issues such as poor sleep during pregnancy and sleep deprivation following the birth can often heighten cravings for stimulants and sugary foods, which may seem like a good option for quick sources of energy, however, these foods can often cause further issues with energy and lead to fatigue and low mood. Eating foods that are high in refined sugar and refined grains such as commercial white bread, pastries, cakes and biscuits, give us an unsustainable source of energy. The brain is a very metabolically active organ; despite it only being 7% of the body’s weight, it can take up to 20% of the body’s metabolic needs (2), meaning that it is very energy hungry. This is why it is important to nourish the brain with foods that are nutrient rich, providing the body the building blocks to produce neurotransmitters, as well as a sustainable source of energy. The best options are fresh, unprocessed foods such as wholegrains (brown bread, brown rice, quinoa, rye and oats), pulses, vegetables, good quality sources of protein (meat, poultry and fish) and healthy fats such as those found in olive oil, coconut oil, avocados and oily fish. 
As mentioned above, eating foods that are rich in indigestible fibre such as vegetables and fruits, as well as eating good fats that are found in grass-fed butter, nuts and seeds, olive oil, coconut oil and avocado, provide bacteria with prebiotics that help to produce the ‘friendly’ short-chain fatty acids such as butyrate. Avoiding processed foods that contain calcium propionate, which lead to higher levels of propionic acid - the not so friendly short-chain fatty acid - is also another key strategy to support the gut-brain link.
A study published in the Journal of Environmental Healths Perspective stated that "researchers, physicians, and others poked around in the dark crevices of the gene, (are) trying to untangle the clues that suggested gene function could be altered by more than just changes in sequence." This ties in perfectly with what Dr. Lisa mentions about how our lifestyles play a crucial role in how/if we manifest a certain cognitive disfunction. Which brings us to our next question: What kind of "brain diet" can help support this lifestyle?
Green tea is widely drunk in many cultures, especially in Asia, and is known to have potent health benefits. These benefits are attributed to its polyphenol content (particularly the flavanols and flavonols). In cell cultures and animal studies, the polyphenols have been proven to prevent neurotoxin-induced cell injury. Green tea also has anti-inflammatory properties and, according to a study performed on aged mice, may delay memory regression. It’s safe to drink several cups of green tea per day, though it may be more efficacious to take a green tea extract supplement to reach a daily dose of 400 to 500 mg of EGCG, one of the main active components of green tea.
Most people I talk to about modafinil seem to use it for daytime usage; for me that has not ever worked out well, but I had nothing in particular to show against it. So, as I was capping the last of my piracetam-caffeine mix and clearing off my desk, I put the 4 remaining Modalerts pills into capsules with the last of my creatine powder and then mixed them with 4 of the theanine-creatine pills. Like the previous Adderall trial, I will pick one pill blindly each day and guess at the end which it was. If it was active (modafinil-creatine), take a break the next day; if placebo (theanine-creatine), replace the placebo and try again the next day. We’ll see if I notice anything on DNB or possibly gwern.net edits.
In this large population-based cohort, we saw consistent robust associations between cola consumption and low BMD in women. The consistency of pattern across cola types and after adjustment for potential confounding variables, including calcium intake, supports the likelihood that this is not due to displacement of milk or other healthy beverages in the diet. The major differences between cola and other carbonated beverages are caffeine, phosphoric acid, and cola extract. Although caffeine likely contributes to lower BMD, the result also observed for decaffeinated cola, the lack of difference in total caffeine intake across cola intake groups, and the lack of attenuation after adjustment for caffeine content suggest that caffeine does not explain these results. A deleterious effect of phosphoric acid has been proposed (26). Cola beverages contain phosphoric acid, whereas other carbonated soft drinks (with some exceptions) do not.
Dallas Michael Cyr, a 41-year-old life coach and business mentor in San Diego, California, also says he experienced a mental improvement when he regularly took another product called Qualia Mind, which its makers say enhances focus, energy, mental clarity, memory and even creativity and mood. "One of the biggest things I noticed was it was much more difficult to be distracted," says Cyr, who took the supplements for about six months but felt their effects last longer. While he's naturally great at starting projects and tasks, the product allowed him to be a "great finisher" too, he says.
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