Nootropics – sometimes called smart drugs – are compounds that enhance brain function. They’re becoming a popular way to give your mind an extra boost. According to one Telegraph report, up to 25% of students at leading UK universities have taken the prescription smart drug modafinil [1], and California tech startup employees are trying everything from Adderall to LSD to push their brains into a higher gear [2].
Since the discovery of the effect of nootropics on memory and focus, the number of products on the market has increased exponentially. The ingredients used in a supplement can tell you about the effectiveness of the product. Brain enhancement pills that produce the greatest benefit are formulated with natural vitamins and substances, rather than caffeine and synthetic ingredients. In addition to better results, natural supplements are less likely to produce side effects, compared with drugs formulated with chemical ingredients.
Many of the most popular “smart drugs” (Piracetam, Sulbutiamine, Ginkgo Biloba, etc.) have been around for decades or even millenia but are still known only in medical circles or among esoteric practicioners of herbal medicine. Why is this? If these compounds have proven cognitive benefits, why are they not ubiquitous? How come every grade-school child gets fluoride for the development of their teeth (despite fluoride’s being a known neurotoxin) but not, say, Piracetam for the development of their brains? Why does the nightly news slant stories to appeal more to a fear-of-change than the promise of a richer cognitive future?

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Stayed up with the purpose of finishing my work for a contest. This time, instead of taking the pill as a single large dose (I feel that after 3 times, I understand what it’s like), I will take 4 doses over the new day. I took the first quarter at 1 AM, when I was starting to feel a little foggy but not majorly impaired. Second dose, 5:30 AM; feeling a little impaired. 8:20 AM, third dose; as usual, I feel physically a bit off and mentally tired - but still mentally sharp when I actually do something. Early on, my heart rate seemed a bit high and my limbs trembling, but it’s pretty clear now that that was the caffeine or piracetam. It may be that the other day, it was the caffeine’s fault as I suspected. The final dose was around noon. The afternoon crash wasn’t so pronounced this time, although motivation remains a problem. I put everything into finishing up the spaced repetition literature review, and didn’t do any n-backing until 11:30 PM: 32/34/31/54/40%.
When you drink tea, you’re getting some caffeine (less than the amount in coffee), plus an amino acid called L-theanine that has been shown in studies to increase activity in the brain’s alpha frequency band, which can lead to relaxation without drowsiness. These calming-but-stimulating effects might contribute to tea’s status as the most popular beverage aside from water. People have been drinking it for more than 4,000 years, after all, but modern brain hackers try to distill and enhance the benefits by taking just L-theanine as a nootropic supplement. Unfortunately, that means they’re missing out on the other health effects that tea offers. It’s packed with flavonoids, which are associated with longevity, reduced inflammation, weight loss, cardiovascular health, and cancer prevention.
Even though smart drugs come with a long list of benefits, their misuse can cause negative side effects. Excess use can cause anxiety, fear, headaches, increased blood pressure, and more. Considering this, it is imperative to study usage instructions: how often can you take the pill, the correct dosage and interaction with other medication/supplements.
The use of cognitive enhancers by healthy individuals sparked debate about ethics and safety. Cognitive enhancement by pharmaceutical means was considered a form of illicit drug use in some places, even while other cognitive enhancers, such as caffeine and nicotine, were freely available. The conflict therein raised the possibility for further acceptance of smart drugs in the future. However, the long-term effects of smart drugs on otherwise healthy brains were unknown, delaying safety assessments.
So the chi-squared believes there is a statistically-significant difference, the two-sample test disagrees, and the binomial also disagrees. Since I regarded it as a dubious theory, can’t see a difference, and the binomial seems like the most appropriate test, I conclude that several months of 1mg iodine did not change my eye color. (As a final test, when I posted the results on the Longecity forum where people were claiming the eye color change, I swapped the labels on the photos to see if anyone would claim something along the lines when I look at the photos, I can see a difference!. I thought someone might do that, which would be a damning demonstration of their biases & wishful thinking, but no one did.)
(I was more than a little nonplussed when the mushroom seller included a little pamphlet educating one about how papaya leaves can cure cancer, and how I’m shortening my life by decades by not eating many raw fruits & vegetables. There were some studies cited, but usually for points disconnected from any actual curing or longevity-inducing results.)
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.

2 commenters point out that my possible lack of result is due to my mistaken assumption that if nicotine is absorbable through skin, mouth, and lungs it ought to be perfectly fine to absorb it through my stomach by drinking it (rather than vaporizing it and breathing it with an e-cigarette machine) - it’s apparently known that absorption differs in the stomach.
The idea of a digital pill that records when it has been consumed is a sound one, but as the FDA notes, there is no evidence to say it actually increases the likelihood patients that have a history of inconsistent consumption will follow their prescribed course of treatment. There is also a very strange irony in schizophrenia being the first condition this technology is being used to target.
Flow diagram of cognitive neuroscience literature search completed July 2, 2010. Search terms were dextroamphetamine, Aderrall, methylphenidate, or Ritalin, and cognitive, cognition, learning, memory, or executive function, and healthy or normal. Stages of subsequent review used the information contained in the titles, abstracts, and articles to determine whether articles reported studies meeting the inclusion criteria stated in the text.
The surveys just reviewed indicate that many healthy, normal students use prescription stimulants to enhance their cognitive performance, based in part on the belief that stimulants enhance cognitive abilities such as attention and memorization. Of course, it is possible that these users are mistaken. One possibility is that the perceived cognitive benefits are placebo effects. Another is that the drugs alter students’ perceptions of the amount or quality of work accomplished, rather than affecting the work itself (Hurst, Weidner, & Radlow, 1967). A third possibility is that stimulants enhance energy, wakefulness, or motivation, which improves the quality and quantity of work that students can produce with a given, unchanged, level of cognitive ability. To determine whether these drugs enhance cognition in normal individuals, their effects on cognitive task performance must be assessed in relation to placebo in a masked study design.
Even if you eat foods that contain these nutrients, Hogan says their beneficial effects are in many ways cumulative—meaning the brain perks don’t emerge unless you’ve been eating them for long periods of time. Swallowing more of these brain-enhancing compounds at or after middle-age “may be beyond the critical period” when they’re able to confer cognitive enhancements, he says.
Going back to the 1960s, although it was a Romanian chemist who is credited with discovering nootropics, a substantial amount of research on racetams was conducted in the Soviet Union. This resulted in the birth of another category of substances entirely: adaptogens, which, in addition to benefiting cognitive function were thought to allow the body to better adapt to stress.
Another study on the olfactory impact of essential oils like lavender and rosemary revealed that they produced positive effects on cognitive performance and mood.16 And in another study on the inhalation of essential oils like grapefruit, fennel, Estragon, and black pepper essential oil, inhalation of the oils resulted in modulation of sympathetic activity in adults.17,18

…Four subjects correctly stated when they received nicotine, five subjects were unsure, and the remaining two stated incorrectly which treatment they received on each occasion of testing. These numbers are sufficiently close to chance expectation that even the four subjects whose statements corresponded to the treatments received may have been guessing.
Sulbutiamine, mentioned earlier as a cholinergic smart drug, can also be classed a dopaminergic, although its mechanism is counterintuitive: by reducing the release of dopamine in the brain’s prefrontal cortex, the density of dopamine receptors actually increase after continued Sulbutiamine exposure, through a compensatory mechanism. (This provides an interesting example of how dividing smart drugs into sensible “classes” is a matter of taste as well as science, especially since many of them create their discernable neural effects through still undefined mechanisms.)

Proteus Digital Health (Redwood City, Calif.) offers an FDA-approved microchip—an ingestible pill that tracks medication-taking behavior and how the body is responding to medicine. Through the company’s Digital Health Feedback System, the sensor monitors blood flow, body temperature and other vital signs for people with heart problems, schizophrenia or Alzheimer’s disease.
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.
The blood half-life is 12-36 hours; hence two or three days ought to be enough to build up and wash out. A week-long block is reasonable since that gives 5 days for effects to manifest, although month-long blocks would not be a bad choice either. (I prefer blocks which fit in round periods because it makes self-experiments easier to run if the blocks fit in normal time-cycles like day/week/month. The most useless self-experiment is the one abandoned halfway.)

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.
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.
Smart pills have huge potential and several important applications, particularly in diagnosis. Smart pills are growing as a highly effective method of endoscopy, particularly for gastrointestinal diseases. Urbanization and rapid lifestyle changes leaning toward unhealthy diets and poor eating habits have led to distinctive increasing lifestyle disorders such as gastroesophageal reflux disease (GERD), obesity, and gastric ulcers.
One of the most widely known classes of smart drugs on the market, Racetams, have a long history of use and a lot of evidence of their effectiveness. They hasten the chemical exchange between brain cells, directly benefiting our mental clarity and learning process. They are generally not controlled substances and can be purchased without a prescription in a lot of locations globally.
The resurgent popularity of nootropics—an umbrella term for supplements that purport to boost creativity, memory, and cognitive ability—has more than a little to do with the recent Silicon Valley-induced obsession with disrupting literally everything, up to and including our own brains. But most of the appeal of smart drugs lies in the simplicity of their age-old premise: Take the right pill and you can become a better, smarter, as-yet-unrealized version of yourself—a person that you know exists, if only the less capable you could get out of your own way.
“Cavin, you are phemomenal! An incredulous journey of a near death accident scripted by an incredible man who chose to share his knowledge of healing his own broken brain. I requested our public library purchase your book because everyone, those with and without brain injuries, should have access to YOUR brain and this book. Thank you for your legacy to mankind!”
Of course, there are drugs out there with more transformative powers. “I think it’s very clear that some do work,” says Andrew Huberman, a neuroscientist based at Stanford University. In fact, there’s one category of smart drugs which has received more attention from scientists and biohackers – those looking to alter their own biology and abilities – than any other. These are the stimulants.
There is evidence to suggest that modafinil, methylphenidate, and amphetamine enhance cognitive processes such as learning and working memory...at least on certain laboratory tasks. One study found that modafinil improved cognitive task performance in sleep-deprived doctors. Even in non-sleep deprived healthy volunteers, modafinil improved planning and accuracy on certain cognitive tasks. Similarly, methylphenidate and amphetamine also enhanced performance of healthy subjects in certain cognitive tasks.
Vinh Ngo, a San Francisco family practice doctor who specializes in hormone therapy, has become familiar with piracetam and other nootropics through a changing patient base. His office is located in the heart of the city’s tech boom and he is increasingly sought out by young, male tech workers who tell him they are interested in cognitive enhancement.
Smart Pill is formulated with herbs, amino acids, vitamins and co-factors to provide nourishment for the brain, which may enhance memory, cognitive function, and clarity. , which may enhance memory, cognitive function, and clarity. In a natural base containing potent standardized extract 24% flavonoid glycosides. Fast acting super potent formula. A unique formulation containing a blend of essential nutrients, herbs and co-factors.

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Research on animals has shown that intermittent fasting — limiting caloric intake at least two days a week — can help improve neural connections in the hippocampus and protect against the accumulation of plaque, a protein prevalent in the brains of people with Alzheimer’s disease. Research has also shown that intermittent fasting helped reduce anxiety in mice.
The use of cognitive enhancers by healthy individuals sparked debate about ethics and safety. Cognitive enhancement by pharmaceutical means was considered a form of illicit drug use in some places, even while other cognitive enhancers, such as caffeine and nicotine, were freely available. The conflict therein raised the possibility for further acceptance of smart drugs in the future. However, the long-term effects of smart drugs on otherwise healthy brains were unknown, delaying safety assessments.
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”).

The compound is one of the best brain enhancement supplements that includes memory enhancement and protection against brain aging. Some studies suggest that the compound is an effective treatment for disorders like vascular dementia, Alzheimer’s, brain stroke, anxiety, and depression. However, there are some side effects associated with Alpha GPC, like a headache, heartburn, dizziness, skin rashes, insomnia, and confusion.
So I eventually got around to ordering another thing of nicotine gum, Habitrol Nicotine Gum, 4mg MINT flavor COATED gum. 96 pieces per box. Gum should be easier to double-blind myself with than nicotine patches - just buy some mint gum. If 4mg is too much, cut the gum in half or whatever. When it arrived, my hopes were borne out: the gum was rectangular and soft, which made it easy to cut into fourths.
Those who have taken them swear they do work – though not in the way you might think. Back in 2015, a review of the evidence found that their impact on intelligence is “modest”. But most people don’t take them to improve their mental abilities. Instead, they take them to improve their mental energy and motivation to work. (Both drugs also come with serious risks and side effects – more on those later).
There is evidence to suggest that modafinil, methylphenidate, and amphetamine enhance cognitive processes such as learning and working memory...at least on certain laboratory tasks. One study found that modafinil improved cognitive task performance in sleep-deprived doctors. Even in non-sleep deprived healthy volunteers, modafinil improved planning and accuracy on certain cognitive tasks. Similarly, methylphenidate and amphetamine also enhanced performance of healthy subjects in certain cognitive tasks.

…Phenethylamine is intrinsically a stimulant, although it doesn’t last long enough to express this property. In other words, it is rapidly and completely destroyed in the human body. It is only when a number of substituent groups are placed here or there on the molecule that this metabolic fate is avoided and pharmacological activity becomes apparent.
Because smart drugs like modafinil, nicotine, and Adderall come with drawbacks, I developed my own line of nootropics, including Forbose and SmartMode, that’s safe, widely available, and doesn’t require a prescription. Forskolin, found in Forbose, has been a part of Indian Ayurvedic medicine for thousands of years. In addition to being fun to say, forskolin increases cyclic adenosine monophosphate (cAMP), a molecule essential to learning and memory formation. [8]
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