We included studies of the effects of these drugs on cognitive processes including learning, memory, and a variety of executive functions, including working memory and cognitive control. These studies are listed in Table 2, along with each study’s sample size, gender, age and tasks administered. Given our focus on cognition enhancement, we excluded studies whose measures were confined to perceptual or motor abilities. Studies of attention are included when the term attention refers to an executive function but not when it refers to the kind of perceptual process taxed by, for example, visual search or dichotic listening or when it refers to a simple vigilance task. Vigilance may affect cognitive performance, especially under conditions of fatigue or boredom, but a more vigilant person is not generally thought of as a smarter person, and therefore, vigilance is outside of the focus of the present review. The search and selection process is summarized in Figure 2.
Ngo has experimented with piracetam himself (“The first time I tried it, I thought, ‘Wow, this is pretty strong for a supplement.’ I had a little bit of reflux, heartburn, but in general it was a cognitive enhancer. . . . I found it helpful”) and the neurotransmitter DMEA (“You have an idea, it helps you finish the thought. It’s for when people have difficulty finishing that last connection in the brain”).
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I don’t believe there’s any need to control for training with repeated within-subject sampling, since there will be as many samples on both control and active days drawn from the later trained period as with the initial untrained period. But yes, my D5B scores seem to have plateaued pretty much and only very slowly increase; you can look at the stats file yourself.
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Low-tech methods of cognitive enhancement include many components of what has traditionally been viewed as a healthy lifestyle, such as exercise, good nutrition, adequate sleep, and stress management. These low-tech methods nevertheless belong in a discussion of brain enhancement because, in addition to benefiting cognitive performance, their effects on brain function have been demonstrated (Almeida et al., 2002; Boonstra, Stins, Daffertshofer, & Beek, 2007; Hillman, Erickson, & Kramer, 2008; Lutz, Slagter, Dunne, & Davidson, 2008; Van Dongen, Maislin, Mullington, & Dinges, 2003).
As discussed in my iodine essay (FDA adverse events), iodine is a powerful health intervention as it eliminates cretinism and improves average IQ by a shocking magnitude. If this effect were possible for non-fetuses in general, it would be the best nootropic ever discovered, and so I looked at it very closely. Unfortunately, after going through ~20 experiments looking for ones which intervened with iodine post-birth and took measures of cognitive function, my meta-analysis concludes that: the effect is small and driven mostly by one outlier study. Once you are born, it’s too late. But the results could be wrong, and iodine might be cheap enough to take anyway, or take for non-IQ reasons. (This possibility was further weakened for me by an August 2013 blood test of TSH which put me at 3.71 uIU/ml, comfortably within the reference range of 0.27-4.20.)

If this is the case, this suggests some thoughtfulness about my use of nicotine: there are times when use of nicotine will not be helpful, but times where it will be helpful. I don’t know what makes the difference, but I can guess it relates to over-stimulation: on some nights during the experiment, I had difficult concentrating on n-backing because it was boring and I was thinking about the other things I was interested in or working on - in retrospect, I wonder if those instances were nicotine nights.
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I can’t try either of the products myself – I am pregnant and my doctor doesn’t recommend it – but my husband agrees to. He describes the effect of the Nootrobox product as like having a cup of coffee but not feeling as jittery. “I had a very productive day, but I don’t know if that was why,” he says. His Nootroo experience ends after one capsule. He gets a headache, which he is convinced is related, and refuses to take more. “It is just not a beginner friendly cocktail,” offers Noehr.
None of that has kept entrepreneurs and their customers from experimenting and buying into the business of magic pills, however. In 2015 alone, the nootropics business raked in over $1 billion dollars, and web sites like the nootropics subreddit, the Bluelight forums, and Bulletproof Exec are popular and packed with people looking for easy ways to boost their mental performance. Still, this bizarre, Philip K. Dick-esque world of smart drugs is a tough pill to swallow. To dive into the topic and explain, I spoke to Kamal Patel, Director of evidence-based medical database Examine.com, and even tried a few commercially-available nootropics myself.

Cocoa flavanols (CF) positively influence physiological processes in ways which suggest that their consumption may improve aspects of cognitive function. This study investigated the acute cognitive and subjective effects of CF consumption during sustained mental demand. In this randomized, controlled, double-blinded, balanced, three period crossover trial 30 healthy adults consumed drinks containing 520 mg, 994 mg CF and a matched control, with a 3-day washout between drinks. Assessments included the state anxiety inventory and repeated 10-min cycles of a Cognitive Demand Battery comprising of two serial subtraction tasks (Serial Threes and Serial Sevens), a Rapid Visual Information Processing (RVIP) task and a mental fatigue scale, over the course of 1 h. Consumption of both 520 mg and 994 mg CF significantly improved Serial Threes performance. The 994 mg CF beverage significantly speeded RVIP responses but also resulted in more errors during Serial Sevens. Increases in self-reported mental fatigue were significantly attenuated by the consumption of the 520 mg CF beverage only. This is the first report of acute cognitive improvements following CF consumption in healthy adults. While the mechanisms underlying the effects are unknown they may be related to known effects of CF on endothelial function and blood flow.

28,61,36,25,61,57,39,56,23,37,24,50,54,32,50,33,16,42,41,40,34,33,31,65,23,36,29,51,46,31,45,52,30, 50,29,36,57,60,34,48,32,41,48,34,51,40,53,73,56,53,53,57,46,50,35,50,60,62,30,60,48,46,52,60,60,48, 47,34,50,51,45,54,70,48,61,43,53,60,44,57,50,50,52,37,55,40,53,48,50,52,44,50,50,38,43,66,40,24,67, 60,71,54,51,60,41,58,20,28,42,53,59,42,31,60,42,58,36,48,53,46,25,53,57,60,35,46,32,26,68,45,20,51, 56,48,25,62,50,54,47,42,55,39,60,44,32,50,34,60,47,70,68,38,47,48,70,51,42,41,35,36,39,23,50,46,44,56,50,39
Table 3 lists the results of 24 tasks from 22 articles on the effects of d-AMP or MPH on learning, assessed by a variety of declarative and nondeclarative memory tasks. Results for the 24 tasks are evenly split between enhanced learning and null results, but they yield a clearer pattern when the nature of the learning task and the retention interval are taken into account. In general, with single exposures of verbal material, no benefits are seen immediately following learning, but later recall and recognition are enhanced. Of the six articles reporting on memory performance (Camp-Bruno & Herting, 1994; Fleming, Bigelow, Weinberger, & Goldberg, 1995; Rapoport, Busbaum, & Weingartner, 1980; Soetens, D’Hooge, & Hueting, 1993; Unrug, Coenen, & van Luijtelaar, 1997; Zeeuws & Soetens 2007), encompassing eight separate experiments, only one of the experiments yielded significant memory enhancement at short delays (Rapoport et al., 1980). In contrast, retention was reliably enhanced by d-AMP when subjects were tested after longer delays, with recall improved after 1 hr through 1 week (Soetens, Casaer, D’Hooge, & Hueting, 1995; Soetens et al., 1993; Zeeuws & Soetens, 2007). Recognition improved after 1 week in one study (Soetens et al., 1995), while another found recognition improved after 2 hr (Mintzer & Griffiths, 2007). The one long-term memory study to examine the effects of MPH found a borderline-significant reduction in errors when subjects answered questions about a story (accompanied by slides) presented 1 week before (Brignell, Rosenthal, & Curran, 2007).
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 ware 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.
Productivity is the most cited reason for using nootropics. With all else being equal, smart drugs are expected to give you that mental edge over other and advance your career. Nootropics can also be used for a host of other reasons. From studying to socialising. And from exercise and health to general well-being. Different nootropics cater to different audiences.

The search to find more effective drugs to increase mental ability and intelligence capacity with neither toxicity nor serious side effects continues. But there are limitations. Although the ingredients may be separately known to have cognition-enhancing effects, randomized controlled trials of the combined effects of cognitive enhancement compounds are sparse.
Amphetamines have a long track record as smart drugs, from the workaholic mathematician Paul Erdös, who relied on them to get through 19-hour maths binges, to the writer Graham Greene, who used them to write two books at once. More recently, there are plenty of anecdotal accounts in magazines about their widespread use in certain industries, such as journalism, the arts and finance.

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.
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.
Ginsenoside Rg1, a molecule found in the plant genus panax (ginseng), is being increasingly researched as an effect nootropic. Its cognitive benefits including increasing learning ability and memory acquisition, and accelerating neural development. It targets mainly the NMDA receptors and nitric oxide synthase, which both play important roles in personal and emotional intelligence. The authors of the study cited above, say that their research findings thus far have boosted their confidence in a "bright future of cognitive drug development."
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.
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.
DNB-wise, eyeballing my stats file seems to indicate a small increase: when I compare peak scores D4B scores, I see mostly 50s and a few 60s before piracetam, and after starting piracetam, a few 70s mixed into the 50s and 60s. Natural increase from training? Dunno - I’ve been stuck on D4B since June, so 5 or 10% in a week or 3 seems a little suspicious. A graph of the score series26:
(In particular, I don’t think it’s because there’s a sudden new surge of drugs. FDA drug approval has been decreasing over the past few decades, so this is unlikely a priori. More specifically, many of the major or hot drugs go back a long time. Bacopa goes back millennia, melatonin I don’t even know, piracetam was the ’60s, modafinil was ’70s or ’80s, ALCAR was ’80s AFAIK, Noopept & coluracetam were ’90s, and so on.)
Vitamin B12 is also known as Cobalamin and is a water-soluble essential vitamin.  A (large) deficiency of Vitamin B12 will ultimately lead to cognitive impairment [52]. Older people and people who don’t eat meat are at a higher risk than young people who eat more meat. And people with depression have less Vitamin B12 than the average population [53].
Feeling behind, I resolved to take some armodafinil the next morning, which I did - but in my hurry I failed to recall that 200mg armodafinil was probably too much to take during the day, with its long half life. As a result, I felt irritated and not that great during the day (possibly aggravated by some caffeine - I wish some studies would be done on the possible interaction of modafinil and caffeine so I knew if I was imagining it or not). Certainly not what I had been hoping for. I went to bed after midnight (half an hour later than usual), and suffered severe insomnia. The time wasn’t entirely wasted as I wrote a short story and figured out how to make nicotine gum placebos during the hours in the dark, but I could have done without the experience. All metrics omitted because it was a day usage.
Sometimes called smart drugs, brain boosters, or memory-enhancing drugs, the term "nootropics" was coined by scientist Dr. Corneliu E. Giurgea, who developed the compound piracetam as a brain enhancer, according to The Atlantic. The word is derived from the Greek noo, meaning mind, and trope, which means "change" in French. In essence, all nootropics aim to change your mind by enhancing functions like memory or attention.

Though coffee gives instant alertness, the effect lasts only for a short while. People who drink coffee every day may develop caffeine tolerance; this is the reason why it is still important to control your daily intake. It is advisable that an individual should not consume more than 300 mg of coffee a day. Caffeine, the world’s favorite nootropic has fewer side effects, but if consumed abnormally in excess, it can result in nausea, restlessness, nervousness, and hyperactivity. This is the reason why people who need increased sharpness would instead induce L-theanine, or some other Nootropic, along with caffeine. Today, you can find various smart drugs that contain caffeine in them. OptiMind, one of the best and most sought-after nootropics in the U.S, containing caffeine, is considered best brain supplement for adults and kids when compared to other focus drugs present in the market today.

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.

Take at 11 AM; distractions ensue and the Christmas tree-cutting also takes up much of the day. By 7 PM, I am exhausted and in a bad mood. While I don’t expect day-time modafinil to buoy me up, I do expect it to at least buffer me against being tired, and so I conclude placebo this time, and with more confidence than yesterday (65%). I check before bed, and it was placebo.


I almost resigned myself to buying patches to cut (and let the nicotine evaporate) and hope they would still stick on well enough afterwards to be indistinguishable from a fresh patch, when late one sleepless night I realized that a piece of nicotine gum hanging around on my desktop for a week proved useless when I tried it, and that was the answer: if nicotine evaporates from patches, then it must evaporate from gum as well, and if gum does evaporate, then to make a perfect placebo all I had to do was cut some gum into proper sizes and let the pieces sit out for a while. (A while later, I lost a piece of gum overnight and consumed the full 4mg to no subjective effect.) Google searches led to nothing indicating I might be fooling myself, and suggested that evaporation started within minutes in patches and a patch was useless within a day. Just a day is pushing it (who knows how much is left in a useless patch?), so I decided to build in a very large safety factor and let the gum sit for around a month rather than a single day.
Though their product includes several vitamins including Bacopa, it seems to be missing the remaining four of the essential ingredients: DHA Omega 3, Huperzine A, Phosphatidylserine and N-Acetyl L-Tyrosine. It missed too many of our key criteria and so we could not endorse this product of theirs. Simply, if you don’t mind an insufficient amount of essential ingredients for improved brain and memory function and an inclusion of unwanted ingredients – then this could be a good fit for you.
Over the last few months, as part of a new research project, I have talked with five people who regularly use drugs at work. They are all successful in their jobs, financially secure, in stable relationships, and generally content with their lives. None of them have plans to stop using the drugs, and so far they have kept the secret from their employers. But as their colleagues become more likely to start using the same drugs (people talk, after all), will they continue to do so?
Finally, two tasks measuring subjects’ ability to control their responses to monetary rewards were used by de Wit et al. (2002) to assess the effects of d-AMP. When subjects were offered the choice between waiting 10 s between button presses for high-probability rewards, which would ultimately result in more money, and pressing a button immediately for lower probability rewards, d-AMP did not affect performance. However, when subjects were offered choices between smaller rewards delivered immediately and larger rewards to be delivered at later times, the normal preference for immediate rewards was weakened by d-AMP. That is, subjects were more able to resist the impulse to choose the immediate reward in favor of the larger reward.
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.
The concept of neuroenhancement and the use of substances to improve cognitive functioning in healthy individuals, is certainly not a new one. In fact, one of the first cognitive enhancement drugs, Piracetam, was developed over fifty years ago by psychologist and chemist C.C. Giurgea. Although he did not know the exact mechanism, Giurgia believed the drug boosted brain power and so began his exploration into "smart pills", or nootropics, a term he coined from the Greek nous, meaning "mind," and trepein, meaning "to bend.  
Furthermore, there is no certain way to know whether you’ll have an adverse reaction to a particular substance, even if it’s natural. This risk is heightened when stacking multiple substances because substances can have synergistic effects, meaning one substance can heighten the effects of another. However, using nootropic stacks that are known to have been frequently used can reduce the chances of any negative side effects.
In addition, the cognitive enhancing effects of stimulant drugs often depend on baseline performance. So whilst stimulants enhance performance in people with low baseline cognitive abilities, they often impair performance in those who are already at optimum. Indeed, in a study by Randall et al., modafinil only enhanced cognitive performance in subjects with a lower (although still above-average) IQ.
The Stroop task tests the ability to inhibit the overlearned process of reading by presenting color names in colored ink and instructing subjects to either read the word (low need for cognitive control because this is the habitual response to printed words) or name the ink color (high need for cognitive control). Barch and Carter (2005) administered this task to normal control subjects on placebo and d-AMP and found speeding of responses with the drug. However, the speeding was roughly equivalent for the conditions with low and high cognitive control demands, suggesting that the observed facilitation may not have been specific to cognitive control.

I never watch SNL. I just happen to know about every skit, every line of dialogue because I'm a stable genius.Hey Donnie, perhaps you are unaware that:1) The only Republican who is continually obsessed with how he or she is portrayed on SNL is YOU.2) SNL has always been laden with political satire.3) There is something called the First Amendment that would undermine your quest for retribution.
Schroeder, Mann-Koepke, Gualtieri, Eckerman, and Breese (1987) assessed the performance of subjects on placebo and MPH in a game that allowed subjects to switch between two different sectors seeking targets to shoot. They did not observe an effect of the drug on overall level of performance, but they did find fewer switches between sectors among subjects who took MPH, and perhaps because of this, these subjects did not develop a preference for the more fruitful sector.

(As I was doing this, I reflected how modafinil is such a pure example of the money-time tradeoff. It’s not that you pay someone else to do something for you, which necessarily they will do in a way different from you; nor is it that you have exchanged money to free yourself of a burden of some future time-investment; nor have you paid money for a speculative return of time later in life like with many medical expenses or supplements. Rather, you have paid for 8 hours today of your own time.)
Both nootropics startups provide me with samples to try. In the case of Nootrobox, it is capsules called Sprint designed for a short boost of cognitive enhancement. They contain caffeine – the equivalent of about a cup of coffee, and L-theanine – about 10 times what is in a cup of green tea, in a ratio that is supposed to have a synergistic effect (all the ingredients Nootrobox uses are either regulated as supplements or have a “generally regarded as safe” designation by US authorities)

Interesting. On days ranked 2 (below-average mood/productivity), nicotine seems to have boosted scores; on days ranked 3, nicotine hurts scores; there aren’t enough 4’s to tell, but even ’5 days seem to see a boost from nicotine, which is not predicted by the theory. But I don’t think much of a conclusion can be drawn: not enough data to make out any simple relationship. Some modeling suggests no relationship in this data either (although also no difference in standard deviations, leading me to wonder if I screwed up the data recording - not all of the DNB scores seem to match the input data in the previous analysis). So although the 2 days in the graph are striking, the theory may not be right.


The stop-signal task has been used in a number of laboratories to study the effects of stimulants on cognitive control. In this task, subjects are instructed to respond as quickly as possible by button press to target stimuli except on certain trials, when the target is followed by a stop signal. On those trials, they must try to avoid responding. The stop signal can follow the target stimulus almost immediately, in which case it is fairly easy for subjects to cancel their response, or it can come later, in which case subjects may fail to inhibit their response. The main dependent measure for stop-signal task performance is the stop time, which is the average go reaction time minus the interval between the target and stop signal at which subjects inhibit 50% of their responses. De Wit and colleagues have published two studies of the effects of d-AMP on this task. De Wit, Crean, and Richards (2000) reported no significant effect of the drug on stop time for their subjects overall but a significant effect on the half of the subjects who were slowest in stopping on the baseline trials. De Wit et al. (2002) found an overall improvement in stop time in addition to replicating their earlier finding that this was primarily the result of enhancement for the subjects who were initially the slowest stoppers. In contrast, Filmore, Kelly, and Martin (2005) used a different measure of cognitive control in this task, simply the number of failures to stop, and reported no effects of d-AMP.

With so many different ones to choose from, choosing the best nootropics for you can be overwhelming at times. As usual, a decision this important will require research. Study up on the top nootropics which catch your eye the most. The nootropics you take will depend on what you want the enhancement for. The ingredients within each nootropic determine its specific function. For example, some nootropics contain ginkgo biloba, which can help memory, thinking speed, and increase attention span. Check the nootropic ingredients as you determine what end results you want to see. Some nootropics supplements can increase brain chemicals such as dopamine and serotonin. An increase in dopamine levels can be very useful for memory, alertness, reward and more. Many healthy adults, as well as college students take nootropics. This really supports the central nervous system and the brain.

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