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
Sarter is downbeat, however, about the likelihood of the pharmaceutical industry actually turning candidate smart drugs into products. Its interest in cognitive enhancers is shrinking, he says, “because these drugs are not working for the big indications, which is the market that drives these developments. Even adult ADHD has not been considered a sufficiently attractive large market.”
Nootroo and Nootrobox are two San Francisco nootropics startups that launched last year. Their founders come from the tech scene and their products are squarely aimed at the tech crowd seeking the convenience of not having to build their own combinations. Each claims big-name Silicon Valley entrepreneurs and investors among their users, though neither will name them.

First off, overwhelming evidence suggests that smart drugs actually work. A meta-analysis by researchers at Harvard Medical School and Oxford showed that Modafinil has significant cognitive benefits for those who do not suffer from sleep deprivation. The drug improves their ability to plan and make decisions and has a positive effect on learning and creativity. Another study, by researchers at Imperial College London, showed that Modafinil helped sleep-deprived surgeons become better at planning, redirecting their attention, and being less impulsive when making decisions.
Given the size of the literature just reviewed, it is surprising that so many basic questions remain open. Although d-AMP and MPH appear to enhance retention of recently learned information and, in at least some individuals, also enhance working memory and cognitive control, there remains great uncertainty regarding the size and robustness of these effects and their dependence on dosage, individual differences, and specifics of the task.
After my rudimentary stacking efforts flamed out in unspectacular fashion, I tried a few ready-made stacks—brand-name nootropic cocktails that offer to eliminate the guesswork for newbies. They were just as useful. And a lot more expensive. Goop’s Braindust turned water into tea-flavored chalk. But it did make my face feel hot for 45 minutes. Then there were the two pills of Brain Force Plus, a supplement hawked relentlessly by Alex Jones of InfoWars infamy. The only result of those was the lingering guilt of knowing that I had willingly put $19.95 in the jorts pocket of a dipshit conspiracy theorist.
70 pairs is 140 blocks; we can drop to 36 pairs or 72 blocks if we accept a power of 0.5/50% chance of reaching significance. (Or we could economize by hoping that the effect size is not 3.5 but maybe twice the pessimistic guess; a d=0.5 at 50% power requires only 12 pairs of 24 blocks.) 70 pairs of blocks of 2 weeks, with 2 pills a day requires (70 \times 2) \times (2 \times 7) \times 2 = 3920 pills. I don’t even have that many empty pills! I have <500; 500 would supply 250 days, which would yield 18 2-week blocks which could give 9 pairs. 9 pairs would give me a power of:
For 2 weeks, upon awakening I took close-up photographs of my right eye. Then I ordered two jars of Life-Extension Sea-Iodine (60x1mg) (1mg being an apparently safe dose), and when it arrived on 10 September 2012, I stopped the photography and began taking 1 iodine pill every other day. I noticed no ill effects (or benefits) after a few weeks and upped the dose to 1 pill daily. After the first jar of 60 pills was used up, I switched to the second jar, and began photography as before for 2 weeks. The photographs were uploaded, cropped by hand in Gimp, and shrunk to more reasonable dimensions; both sets are available in a Zip file.
Since coffee drinking may lead to a worsening of calcium balance in humans, we studied the serial changes of serum calcium, PTH, 1,25-dihydroxyvitamin D (1,25(OH)2D) vitamin D and calcium balance in young and adult rats after daily administration of caffeine for 4 weeks. In the young rats, there was an increase in urinary calcium and endogenous fecal calcium excretion after four days of caffeine administration that persisted for the duration of the experiment. Serum calcium decreased on the fourth day of caffeine administration and then returned to control levels. In contrast, the serum PTH and 1,25(OH)2D remained unchanged initially, but increased after 2 weeks of caffeine administration…In the adult rat group, an increase in the urinary calcium and endogenous fecal calcium excretion and serum levels of PTH was found after caffeine administration. However, the serum 1,25(OH)2D levels and intestinal absorption coefficient of calcium remained the same as in the adult control group.
Piracetam is a reliable supplement for improving creativity. It is an entry level racetam due to its lack of severe side effects and relative subtlety. Piracetam’s effects take hold over time through continual use. There is less instant gratification compared to other brain enhancers. Additionally, this nootropic can enhance holistic thinking, verbal memory, and mental energy levels.
Another factor to consider is whether the nootropic is natural or synthetic. Natural nootropics generally have effects which are a bit more subtle, while synthetic nootropics can have more pronounced effects. It’s also important to note that there are natural and synthetic nootropics. Some natural nootropics include Ginkgo biloba and ginseng. One benefit to using natural nootropics is they boost brain function and support brain health. They do this by increasing blood flow and oxygen delivery to the arteries and veins in the brain. Moreover, some nootropics contain Rhodiola rosea, panxax ginseng, and more. 
The next cheap proposition to test is that the 2ml dose is so large that the sedation/depressive effect of nicotine has begun to kick in. This is easy to test: take much less, like half a ml. I do so two or three times over the next day, and subjectively the feeling seems to be the same - which seems to support that proposition (although perhaps I’ve been placebo effecting myself this whole time, in which case the exact amount doesn’t matter). If this theory is true, my previous sleep results don’t show anything; one would expect nicotine-as-sedative to not hurt sleep or improve it. I skip the day (no cravings or addiction noticed), and take half a ml right before bed at 11:30; I fall asleep in 12 minutes and have a ZQ of ~105. The next few days I try putting one or two drops into the tea kettle, which seems to work as well (or poorly) as before. At that point, I was warned that there were some results that nicotine withdrawal can kick in with delays as long as a week, so I shouldn’t be confident that a few days off proved an absence of addiction; I immediately quit to see what the week would bring. 4 or 7 days in, I didn’t notice anything. I’m still using it, but I’m definitely a little nonplussed and disgruntled - I need some independent source of nicotine to compare with!
Noopept is a nootropic that belongs to the ampakine family. It is known for promoting learning, boosting mood, and improving logical thinking. It has been popular as a study drug for a long time but has recently become a popular supplement for improving vision. Users report seeing colors more brightly and feeling as if their vision is more vivid after taking noopept.

One of the most obscure -racetams around, coluracetam (Smarter Nootropics, Ceretropic, Isochroma) acts in a different way from piracetam - piracetam apparently attacks the breakdown of acetylcholine while coluracetam instead increases how much choline can be turned into useful acetylcholine. This apparently is a unique mechanism. A crazy Longecity user, ScienceGuy ponied up $16,000 (!) for a custom synthesis of 500g; he was experimenting with 10-80mg sublingual doses (the ranges in the original anti-depressive trials) and reported a laundry list of effects (as does Isochroma): primarily that it was anxiolytic and increased work stamina. Unfortunately for my stack, he claims it combines poorly with piracetam. He offered free 2g samples for regulars to test his claims. I asked & received some.


Dr. Larry Cleary’s Lucidal – the critically acclaimed secret formula that has been created, revised, and optimized to the point that it’s Dr. Cleary-approved. As a product of Dr. Cleary’s extensive years and expertise in the industry, it is his brainchild. Heavily marketed as the pill for reversing memory loss, whilst aiding focus, it’s seen some popularity in the last few years. In light of all the hubbub and controversy, we put their claims to the test, to see whether or not Lucidal is able to come forth with flying colors, just as all its acclamation has it to be… Learn More...

“Cavin’s enthusiasm and drive to help those who need it is unparalleled! He delivers the information in an easy to read manner, no PhD required from the reader. 🙂 Having lived through such trauma himself he has real empathy for other survivors and it shows in the writing. This is a great read for anyone who wants to increase the health of their brain, injury or otherwise! Read it!!!”
Minnesota-based Medtronic offers a U.S. Food and Drug Administration (FDA)-cleared smart pill called PillCam COLON, which provides clear visualization of the colon and is complementary to colonoscopy. It is an alternative for patients who refuse invasive colon exams, have bleeding or sedation risks or inflammatory bowel disease, or have had a previous incomplete colonoscopy. PillCam COLON allows  more  people  to  get  screened  for  colorectal  cancer with  a  minimally  invasive, radiation-free option. The research focus for WCEs is on effective localization, steering and control of capsules. Device development relies on leveraging applied science and technologies for better system performance, rather than completely reengineering the pill.
Competitors of importance in the smart pills market have been recorded and analyzed in MRFR's report. These market players include RF Co., Ltd., CapsoVision, Inc., JINSHAN Science & Technology, BDD Limited, MEDTRONIC, Check-Cap, PENTAX Medical, INTROMEDIC, Olympus Corporation, FUJIFILM Holdings Corporation, MEDISAFE, and Proteus Digital Health, Inc.
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:
And yet aside from anecdotal evidence, we know very little about the use of these drugs in professional settings. The Financial Times has claimed that they are “becoming popular among city lawyers, bankers, and other professionals keen to gain a competitive advantage over colleagues.” Back in 2008 the narcolepsy medication Modafinil was labeled the “entrepreneur’s drug of choice” by TechCrunch. That same year, the magazine Nature asked its readers whether they use cognitive-enhancing drugs; of the 1,400 respondents, one in five responded in the affirmative.

Your mileage will vary. There are so many parameters and interactions in the brain that any of them could be the bottleneck or responsible pathway, and one could fall prey to the common U-shaped dose-response curve (eg. Yerkes-Dodson law; see also Chemistry of the adaptive mind & de Jongh et al 2007) which may imply that the smartest are those who benefit least23 but ultimately they all cash out in a very few subjective assessments like energetic or motivated, with even apparently precise descriptions like working memory or verbal fluency not telling you much about what the nootropic actually did. It’s tempting to list the nootropics that worked for you and tell everyone to go use them, but that is merely generalizing from one example (and the more nootropics - or meditation styles, or self-help books, or getting things done systems - you try, the stronger the temptation is to evangelize). The best you can do is read all the testimonials and studies and use that to prioritize your list of nootropics to try. You don’t know in advance which ones will pay off and which will be wasted. You can’t know in advance. And wasted some must be; to coin a Umeshism: if all your experiments work, you’re just fooling yourself. (And the corollary - if someone else’s experiments always work, they’re not telling you everything.)
Natural-sourced ingredients can also help to enhance your brain. Superfood, herbal or Amino A ingredient cognitive enhancers are more natural and are largely directly derived from food or plants. Panax ginseng, matcha tea and choline (found in foods like broccoli) are included under this umbrella. There are dozens of different natural ingredients /herbs purported to help cognition, many of which have been used medicinally for hundreds of years.
Aniracetam is known as one of the smart pills with the widest array of uses. From benefits for dementia patients and memory boost in adults with healthy brains, to the promotion of brain damage recovery. It also improves the quality of sleep, what affects the overall increase in focus during the day. Because it supports the production of dopamine and serotonin, it elevates our mood and helps fight depression and anxiety.
Actually, researchers are studying substances that may improve mental abilities. These substances are called "cognitive enhancers" or "smart drugs" or "nootropics." ("Nootropic" comes from Greek - "noos" = mind and "tropos" = changed, toward, turn). The supposed effects of cognitive enhancement can be several things. For example, it could mean improvement of memory, learning, attention, concentration, problem solving, reasoning, social skills, decision making and planning.
Like caffeine, nicotine tolerates rapidly and addiction can develop, after which the apparent performance boosts may only represent a return to baseline after withdrawal; so nicotine as a stimulant should be used judiciously, perhaps roughly as frequent as modafinil. Another problem is that nicotine has a half-life of merely 1-2 hours, making regular dosing a requirement. There is also some elevated heart-rate/blood-pressure often associated with nicotine, which may be a concern. (Possible alternatives to nicotine include cytisine, 2’-methylnicotine, GTS-21, galantamine, Varenicline, WAY-317,538, EVP-6124, and Wellbutrin, but none have emerged as clearly superior.)
Popular among computer programmers, oxiracetam, another racetam, has been shown to be effective in recovery from neurological trauma and improvement to long-term memory. It is believed to effective in improving attention span, memory, learning capacity, focus, sensory perception, and logical thinking. It also acts as a stimulant, increasing mental energy, alertness, and motivation.
The main concern with pharmaceutical drugs is adverse effects, which also apply to nootropics with undefined effects. Long-term safety evidence is typically unavailable for nootropics.[13] Racetams — piracetam and other compounds that are structurally related to piracetam — have few serious adverse effects and low toxicity, but there is little evidence that they enhance cognition in people having no cognitive impairments.[19]
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