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 take my piracetam in the form of capped pills consisting (in descending order) of piracetam, choline bitartrate, anhydrous caffeine, and l-tyrosine. On 8 December 2012, I happened to run out of them and couldn’t fetch more from my stock until 27 December. This forms a sort of (non-randomized, non-blind) short natural experiment: did my daily 1-5 mood/productivity ratings fall during 8-27 December compared to November 2012 & January 2013? The graphed data28 suggests to me a decline:
Metabolic function smart drugs provide mental benefits by generally facilitating the body’s metabolic processes related to the production of new tissues and the release of energy from food and fat stores. Creatine, a long-time favorite performance-enhancement drug for competitive athletes, was in the news recently when it was found in a double-blind, placebo-controlled crossover trial to have significant cognitive benefits – including both general speed of cognition and improvements in working memory. Ginkgo Biloba is another metabolic function smart drug used to increase memory and improve circulation – however, news from recent studies raises questions about these purported effects.
The methodology would be essentially the same as the vitamin D in the morning experiment: put a multiple of 7 placebos in one container, the same number of actives in another identical container, hide & randomly pick one of them, use container for 7 days then the other for 7 days, look inside them for the label to determine which period was active and which was placebo, refill them, and start again.
White, Becker-Blease, & Grace-Bishop (2006) 2002 Large university undergraduates and graduates (N = 1,025) 16.2% (lifetime) 68.9%: improve attention; 65.2:% partying; 54.3%: improve study habits; 20%: improve grades; 9.1%: reduce hyperactivity 15.5%: 2–3 times per week; 33.9%: 2–3 times per month; 50.6%: 2–3 times per year 58%: easy or somewhat easy to obtain; write-in comments indicated many obtaining stimulants from friends with prescriptions
Serotonin, or 5-hydroxytryptamine (5-HTP), is another primary neurotransmitter and controls major features of the mental landscape including mood, sleep and appetite. Serotonin is produced within the body by exposure, which is one reason that the folk-remedy of “getting some sun” to fight depression is scientifically credible. Many foods contain natural serotonergic (serotonin-promoting or releasing) compounds, including the well-known chemical L-Tryptophan found in turkey, which can promote sleep after big Thanksgiving dinners.
There’s been a lot of talk about the ketogenic diet recently—proponents say that minimizing the carbohydrates you eat and ingesting lots of fat can train your body to burn fat more effectively. It’s meant to help you both lose weight and keep your energy levels constant. The diet was first studied and used in patients with epilepsy, who suffered fewer seizures when their bodies were in a state of ketosis. Because seizures originate in the brain, this discovery showed researchers that a ketogenic diet can definitely affect the way the brain works. Brain hackers naturally started experimenting with diets to enhance their cognitive abilities, and now a company called HVMN even sells ketone esters in a bottle; to achieve these compounds naturally, you’d have to avoid bread and cake. Here are 6 ways exercise makes your brain better.
Another interpretation of the mixed results in the literature is that, in some cases at least, individual differences in response to stimulants have led to null results when some participants in the sample are in fact enhanced and others are not. This possibility is not inconsistent with the previously mentioned ones; both could be at work. Evidence has already been reviewed that ability level, personality, and COMT genotype modulate the effect of stimulants, although most studies in the literature have not broken their samples down along these dimensions. There may well be other as-yet-unexamined individual characteristics that determine drug response. The equivocal nature of the current literature may reflect a mixture of substantial cognitive-enhancement effects for some individuals, diluted by null effects or even counteracted by impairment in others.
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.

Natural nootropic supplements derive from various nutritional studies. Research shows the health benefits of isolated vitamins, nutrients, and herbs. By increasing your intake of certain herbal substances, you can enhance brain function. Below is a list of the top categories of natural and herbal nootropics. These supplements are mainstays in many of today’s best smart pills.
Stimulants are the smart drugs most familiar to people, starting with widely-used psychostimulants caffeine and nicotine, and the more ill-reputed subclass of amphetamines. Stimulant drugs generally function as smart drugs in the sense that they promote general wakefulness and put the brain and body “on alert” in a ready-to-go state. Basically, any drug whose effects reduce drowsiness will increase the functional IQ, so long as the user isn’t so over-stimulated they’re shaking or driven to distraction.
(If I am not deficient, then supplementation ought to have no effect.) The previous material on modern trends suggests a prior >25%, and higher than that if I were female. However, I was raised on a low-salt diet because my father has high blood pressure, and while I like seafood, I doubt I eat it more often than weekly. I suspect I am somewhat iodine-deficient, although I don’t believe as confidently as I did that I had a vitamin D deficiency. Let’s call this one 75%.
Two additional studies used other spatial working memory tasks. Barch and Carter (2005) required subjects to maintain one of 18 locations on the perimeter of a circle in working memory and then report the name of the letter that appeared there in a similarly arranged circle of letters. d-AMP caused a speeding of responses but no change in accuracy. Fleming et al. (1995) referred to a spatial delay response task, with no further description or citation. They reported no effect of d-AMP in the task except in the zero-delay condition (which presumably places minimal demand on working memory).

AMP was first investigated as an asthma medication in the 1920s, but its psychological effects were soon noticed. These included increased feelings of energy, positive mood, and prolonged physical endurance and mental concentration. These effects have been exploited in a variety of medical and nonmedical applications in the years since they were discovered, including to treat depression, to enhance alertness in military personnel, and to provide a competitive edge in athletic competition (Rasmussen, 2008). Today, AMP remains a widely used and effective treatment for ADHD (Wilens, 2006).
While the primary effect of the drug is massive muscle growth the psychological side effects actually improved his sanity by an absurd degree. He went from barely functional to highly productive. When one observes that the decision to not attempt to fulfill one’s CEV at a given moment is a bad decision it follows that all else being equal improved motivation is improved sanity.
Googling, you sometimes see correlational studies like Intake of Flavonoid-Rich Wine, Tea, and Chocolate by Elderly Men and Women Is Associated with Better Cognitive Test Performance; in this one, the correlated performance increase from eating chocolate was generally fairly modest (say, <10%), and the maximum effects were at 10g/day of what was probably milk chocolate, which generally has 10-40% chocolate liquor in it, suggesting any experiment use 1-4g. More interesting is the blind RCT experiment Consumption of cocoa flavanols results in acute improvements in mood and cognitive performance during sustained mental effort11, which found improvements at ~1g; the most dramatic improvement of the 4 tasks (on the Threes correct) saw a difference of 2 to 6 at the end of the hour of testing, while several of the other tests converged by the end or saw the controls winning (Sevens correct). Crews et al 2008 found no cognitive benefit, and an fMRI experiment found the change in brain oxygen levels it wanted but no improvement to reaction times.
As already mentioned, AMPs and MPH are classified by the U.S. Food and Drug Administration (FDA) as Schedule II substances, which means that buying or selling them is a felony offense. This raises the question of how the drugs are obtained by students for nonmedical use. Several studies addressed this question and yielded reasonably consistent answers.
Participants (n=205) [young adults aged 18-30 years] were recruited between July 2010 and January 2011, and were randomized to receive either a daily 150 µg (0.15mg) iodine supplement or daily placebo supplement for 32 weeks…After adjusting for baseline cognitive test score, examiner, age, sex, income, and ethnicity, iodine supplementation did not significantly predict 32 week cognitive test scores for Block Design (p=0.385), Digit Span Backward (p=0.474), Matrix Reasoning (p=0.885), Symbol Search (p=0.844), Visual Puzzles (p=0.675), Coding (p=0.858), and Letter-Number Sequencing (p=0.408).
Drugs and catastrophe are seemingly never far apart, whether in laboratories, real life or Limitless. Downsides are all but unavoidable: if a drug enhances one particular cognitive function, the price may be paid by other functions. To enhance one dimension of cognition, you’ll need to appropriate resources that would otherwise be available for others.
The abuse of drugs is something that can lead to large negative outcomes. If you take Ritalin (Methylphenidate) or Adderall (mixed amphetamine salts) but don’t have ADHD, you may experience more focus. But what many people don’t know is that the drug is very similar to amphetamines. And the use of Ritalin is associated with serious adverse events of drug dependence, overdose and suicide attempts [80]. Taking a drug for another reason than originally intended is stupid, irresponsible and very dangerous.

Finally, a workforce high on stimulants wouldn’t necessarily be more productive overall. “One thinks ‘are these things dangerous?’ – and that’s important to consider in the short term,” says Huberman. “But there’s also a different question, which is: ‘How do you feel the day afterwards?’ Maybe you’re hyper-focused for four hours, 12 hours, but then you’re below baseline for 24 or 48.”


Historically used to help people with epilepsy, piracetam is used in some cases of myoclonus, or muscle twitching. Its actual mechanism of action is unclear: It doesn’t act exactly as a sedative or stimulant, but still influences cognitive function, and is believed to act on receptors for acetylcholine in the brain. Piracetam is used off-label as a 'smart drug' to help focus and concentration or sometimes as a way to allegedly boost your mood. Again, piracetam is a prescription-only drug - any supply to people without a prescription is illegal, and supplying it may result in a fine or prison sentence.

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.

Some smart drugs can be found in health food stores; others are imported or are drugs that are intended for other disorders such as Alzheimer's disease and Parkinson's disease. There are many Internet web sites, books, magazines and newspaper articles detailing the supposed effects of smart drugs. There are also plenty of advertisements and mail-order businesses that try to sell "smart drugs" to the public. However, rarely do these businesses or the popular press report results that show the failure of smart drugs to improve memory or learning. Rather, they try to show that their products have miraculous effects on the brain and can improve mental functioning. Wouldn't it be easy to learn something by "popping a pill" or drinking a soda laced with a smart drug? This would be much easier than taking the time to study. Feeling dull? Take your brain in for a mental tune up by popping a pill!


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]
×