Be patient.  Even though you may notice some improvements right away (sometimes within the first day), you should give your brain supplement at least several months to work.  The positive effects are cumulative, and most people do not max out their brain potential on a supplement until they have used it for at least 90 days.  That is when the really dramatic effects start kicking in!
So with these 8 results in hand, what do I think? Roughly, I was right 5 of the days and wrong 3 of them. If not for the sleep effect on #4, which is - in a way - cheating (one hopes to detect modafinil due to good effects), the ratio would be 5:4 which is awfully close to a coin-flip. Indeed, a scoring rule ranks my performance at almost identical to a coin flip: -5.49 vs -5.5420. (The bright side is that I didn’t do worse than a coin flip: I was at least calibrated.)
But when aficionados talk about nootropics, they usually refer to substances that have supposedly few side effects and low toxicity. Most often they mean piracetam, which Giurgea first synthesized in 1964 and which is approved for therapeutic use in dozens of countries for use in adults and the elderly. Not so in the United States, however, where officially it can be sold only for research purposes.

Amphetamine – systematic reviews and meta-analyses report that low-dose amphetamine improved cognitive functions (e.g., inhibitory control, episodic memory, working memory, and aspects of attention) in healthy people, and in individuals with ADHD.[21][22][23][25] A 2014 systematic review noted that low doses of amphetamine also improved memory consolidation, in turn leading to improved recall of information in non-ADHD youth.[23] It also improved task saliency (motivation to perform a task) and performance on tedious tasks that required a high degree of effort.[22][24][25]

A constituent of the turmeric spice, curcumin was first discovered for its brain health benefits when epidemiological studies revealed those in regions with a high consumption of the curry spice turmeric had fewer reported cases of cognitive diseases. It is theorized that the unmatched anti-inflammatory power of curcumin, in combination with its unique antioxidant make-up, inhibits the formation of amyloid build up in the brain.
This is not 100% clear from the data and just blindly using a plausible amount carries the risk of the negative effects, so I intend to run another large experiment. I will reuse the NOW Foods Magnesium Citrate Powder, but this time, I will use longer blocks (to make cumulative overdosing more evident) and try to avoid any doses >150mg of elemental magnesium.
Intrigued by old scientific results & many positive anecdotes since, I experimented with microdosing LSD - taking doses ~10μg, far below the level at which it causes its famous effects. At this level, the anecdotes claim the usual broad spectrum of positive effects on mood, depression, ability to do work, etc. After researching the matter a bit, I discovered that as far as I could tell, since the original experiment in the 1960s, no one had ever done a blind or even a randomized self-experiment on it.
This is a small water plant native to India. Bacopa is an adaptogen – it helps your body adapt to stress. It also improves memory in healthy adults[12] and enhances attention and mood in people over 65. [13] Scientists still don’t fully understand how Bacopa works, but they do know it takes time to work; study participants didn’t feel its memory-enhancing effects until they’d been supplementing with it daily for 4 weeks, so if you try Bacopa, stick with it for a month before you give up on it.
With subtle effects, we need a lot of data, so we want at least half a year (6 blocks) or better yet, a year (12 blocks); this requires 180 actives and 180 placebos. This is easily covered by $11 for Doctor’s Best Best Lithium Orotate (5mg), 200-Count (more precisely, Lithium 5mg (from 125mg of lithium orotate)) and $14 for 1000x1g empty capsules (purchased February 2012). For convenience I settled on 168 lithium & 168 placebos (7 pill-machine batches, 14 batches total); I can use them in 24 paired blocks of 7-days/1-week each (48 total blocks/48 weeks). The lithium expiration date is October 2014, so that is not a problem
The ‘Brain-Gut Axis’ is a term used to describe the two-way communication system between our digestive tract and the brain. A growing body of research into this axis demonstrates how much influence the gut can have over the brain and vice versa (1). When we speak about reactions to foods, we most commonly understand them as immediate and often dangerous allergic responses, such as the constriction of the throat and trouble breathing, or dizziness and fainting. It is usually easy to pinpoint the food that causes these reactions because of the immediate immune system response, caused by a type of immune cell known as IgE antibodies. In contrast to this, food intolerances are mediated by IgG antibodies and these reactions can take up to 48 hours to have an effect. Symptoms related to IgG reactions can often be manifested as chronic issues like joint ache, IBS and depression or anxiety, which are often overlooked and not associated with what we eat.
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.
3 days later, I’m fairly miserable (slept poorly, had a hair-raising incident, and a big project was not received as well as I had hoped), so well before dinner (and after a nap) I brew up 2 wooden-spoons of Malaysia Green (olive-color dust). I drank it down; tasted slightly better than the first. I was feeling better after the nap, and the kratom didn’t seem to change that.
At dose #9, I’ve decided to give up on kratom. It is possible that it is helping me in some way that careful testing (eg. dual n-back over weeks) would reveal, but I don’t have a strong belief that kratom would help me (I seem to benefit more from stimulants, and I’m not clear on how an opiate-bearer like kratom could stimulate me). So I have no reason to do careful testing. Oh well.
To our partners, community supporters, and funders: The Brainfood journey has taken us many places, and at each fork in the road we discovered an amazing network of youth advocates ready to help lift our work to the next level. Whether you donated pro-bono consulting hours, connected us to allies in the city, or came in to meet our students and see a class, you helped us build something really special. Thanks for believing in us.
On 8 April 2011, I purchased from Smart Powders (20g for $8); as before, some light searching seemed to turn up SP as the best seller given shipping overhead; it was on sale and I planned to cap it so I got 80g. This may seem like a lot, but I was highly confident that theanine and I would get along since I already drink so much tea and was a tad annoyed at the edge I got with straight caffeine. So far I’m pretty happy with it. My goal was to eliminate the physical & mental twitchiness of caffeine, which subjectively it seems to do.
As it happened, Health Supplement Wholesalers (since renamed Powder City) offered me a sample of their products, including their 5g Noopept powder ($13). I’d never used HSW before & they had some issues in the past; but I haven’t seen any recent complaints, so I was willing to try them. My 5g from batch #130830 arrived quickly (photos: packaging, powder contents). I tried some (tastes just slightly unpleasant, like an ultra-weak piracetam), and I set about capping the fluffy white flour-like powder with the hilariously tiny scoop they provide.
Or in other words, since the standard deviation of my previous self-ratings is 0.75 (see the Weather and my productivity data), a mean rating increase of >0.39 on the self-rating. This is, unfortunately, implying an extreme shift in my self-assessments (for example, 3s are ~50% of the self-ratings and 4s ~25%; to cause an increase of 0.25 while leaving 2s alone in a sample of 23 days, one would have to push 3s down to ~25% and 4s up to ~47%). So in advance, we can see that the weak plausible effects for Noopept are not going to be detected here at our usual statistical levels with just the sample I have (a more plausible experiment might use 178 pairs over a year, detecting down to d>=0.18). But if the sign is right, it might make Noopept worthwhile to investigate further. And the hardest part of this was just making the pills, so it’s not a waste of effort.
More photos from this reportage are featured in Quartz’s new book The Objects that Power the Global Economy. You may not have seen these objects before, but they’ve already changed the way you live. Each chapter examines an object that is driving radical change in the global economy. This is from the chapter on the drug modafinil, which explores modifying the mind for a more productive life. 
We recently held an informative event in London with Dr Gill Hart, a biochemist and expert in the field of food intolerances and their global effect on health and we wanted to share some of the highlights of what Dr Hart covered. Based on some of her recent research (1), the talk offered some interesting insights into how food intolerances may have a role to play in our mental health. It honed in on the differences between food allergies and food intolerances within our immune system; some of the ways that our immune system, gut and brain are believed to influence each other, and how food intolerances, therefore, can play a role in mental health symptoms. She also spoke about how to go about testing and managing these intolerances through elimination diet strategies.
This calculation - reaping only \frac{7}{9} of the naive expectation - gives one pause. How serious is the sleep rebound? In another article, I point to a mice study that sleep deficits can take 28 days to repay. What if the gain from modafinil is entirely wiped out by repayment and all it did was defer sleep? Would that render modafinil a waste of money? Perhaps. Thinking on it, I believe deferring sleep is of some value, but I cannot decide whether it is a net profit.
While it’s no miracle pill, it can certainly give you the edge when it comes to enhanced mental and cognitive processing, as well as boosting your focus and memory retention. So, if you’re the kind of person who’s looking to optimize your performance and get the best results possible, then using an effective nootropic like the Brain Pill is a smart decision that will quickly pay dividends when it’s used in the appropriate way.
I have no particularly compelling story for why this might be a correlation and not causation. It could be placebo, but I wasn’t expecting that. It could be selection effect (days on which I bothered to use the annoying LED set are better days) but then I’d expect the off-days to be below-average and compared to the 2 years of trendline before, there doesn’t seem like much of a fall.
After a month of testing nootropics, I’m not ready to commit to them permanently. They’re simply too untested, and while “move fast and break things” might be a good approach to building software, it’s not what I want for my brain. Still, I think we’ll likely hear more about nootropics, especially as recreational users of more powerful prescription drugs like Adderall and modafinil look for less harsh alternatives. Sometimes, when you’re working, you don’t want to put your brain on jet fuel—a little unleaded gas will do. And for those moments, nootropics could be a fertile testing ground for the intrepid body-hacker.
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.
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.

I have elsewhere remarked on the apparent lack of benefit to taking multivitamins and the possible harm; so one might well wonder about a specific vitamin like vitamin D. However, a multivitamin is not vitamin D, so it’s no surprise that they might do different things. If a multivitamin had no vitamin D in it, or if it had vitamin D in different doses, or if it had substances which interacted with vitamin D (such as calcium), or if it had substances which had negative effects which outweigh the positive (such as vitamin A?), we could well expect differing results. In this case, all of those are true to varying extents. Some multivitamins I’ve had contained no vitamin D. The last multivitamin I was taking both contains vitamins used in the negative trials and also some calcium; the listed vitamin D dosage was a trivial ~400IU, while I take >10x as much now (5000IU).
For example, a study published in the journal Psychopharmacology in 2000 found that ginkgo improved attention. A 2001 study in the journal Human Psychopharmacology suggested that it improves memory. Nevertheless, in a review of studies on ginkgo in healthy people, researchers found no good evidence that it improved mental abilities, according to a 2002 report in Psychopharmacology Bulletin.

Another traditional Chinese brain booster is Danggui-Shaoyao-San (DSS). It has been suggested that DSS has potent beneficial angiogenesis and neurogenesis effects that may make it a potential treatment for ischemic stroke therapy. DSS is also known to beneficially impact free radical-mediated neurological diseases, exhibit anti-inflammatory and antioxidant activities and reduce cell death in the hippocampus, thereby promoting greater emotional, memory-related and autonomic nervous system function. Currently, there is limited research on proper dosage, but you can learn more about DSS in this fantastic summary article on it’s interplay with Alzheimer’s.

…The Fate of Nicotine in the Body also describes Battelle’s animal work on nicotine absorption. Using C14-labeled nicotine in rabbits, the Battelle scientists compared gastric absorption with pulmonary absorption. Gastric absorption was slow, and first pass removal of nicotine by the liver (which transforms nicotine into inactive metabolites) was demonstrated following gastric administration, with consequently low systemic nicotine levels. In contrast, absorption from the lungs was rapid and led to widespread distribution. These results show that nicotine absorbed from the stomach is largely metabolized by the liver before it has a chance to get to the brain. That is why tobacco products have to be puffed, smoked or sucked on, or absorbed directly into the bloodstream (i.e., via a nicotine patch). A nicotine pill would not work because the nicotine would be inactivated before it reached the brain.
Mercury exposure is among several other heavy metals, such as lead, aluminium and cadmium, that have been implicated in the aetiology of ADHD. Childhood exposure to mercury is predominantly through the consumption of seafood, dental amalgams and vaccines containing thimerosal. The reason why mercury can be so problematic, as well as other metals, is that it is capable of breaching the blood brain barrier. This is the brain’s ‘high fortress’, an intelligent gateway system that filters through molecules that are needed in the brain such as cells, nutrients and signalling molecules, and filters out pathogens and toxins.

The original magnesium l-threonate caused me no apparent problems by the time I finished off the powder and usage correlated with better days, further supporting the hypothesis that magnesium helps it. But l-threonate would be difficult to cap (and hence blind self-experiment) and is ruinously expensive on a per-dose basis. So I looked around for alternatives for the followup; one of the most common compounds suggested was the citrate form because it is reasonably well-absorbed and causes fewer digestive problems, so I could just take that. Magnesium oxide is widely available it looks cheap, but the absorption/bioavailability problem makes it unattractive: at a 3:5 ratio, an estimate of 4% absorption, a ZMA formulation of an impressive-sounding 500mg would be 500 \times \frac{3}{5} \times 0.04 = 12mg or a small fraction of RDAs for male adults like 400mg elemental. (Calcium shouldn’t be a problem since I get 220mg of calcium from my multivitamin and I enjoy dairy products daily.)

Jump up ^ EFSA Panel on Dietetic Products, Nutrition and Allergies; European Food Safety Authority (EFSA), Parma, Italy (2011). "Scientific Opinion on the substantiation of health claims related to L-theanine from Camellia sinensis (L.) Kuntze (tea) and improvement of cognitive function (ID 1104, 1222, 1600, 1601, 1707, 1935, 2004, 2005), alleviation of psychological stress (ID 1598, 1601), maintenance of normal sleep (ID 1222, 1737, 2004) and reduction of menstrual discomfort (ID 1599) pursuant to Article 13(1) of Regulation (EC) No 1924/2006". EFSA Journal. 9 (6): 2238. doi:10.2903/j.efsa.2011.2238.