A Romanian psychologist and chemist named Corneliu Giurgea started using the word nootropic in the 1970s to refer to substances that improve brain function, but humans have always gravitated toward foods and chemicals that make us feel sharper, quicker, happier, and more content. Our brains use about 20 percent of our energy when our bodies are at rest (compared with 8 percent for apes), according to National Geographic, so our thinking ability is directly affected by the calories we’re taking in as well as by the nutrients in the foods we eat. Here are the nootropics we don’t even realize we’re using, and an expert take on how they work.
One symptom of Alzheimer's disease is a reduced brain level of the neurotransmitter called acetylcholine. It is thought that an effective treatment for Alzheimer's disease might be to increase brain levels of acetylcholine. Another possible treatment would be to slow the death of neurons that contain acetylcholine. Two drugs, Tacrine and Donepezil, are both inhibitors of the enzyme (acetylcholinesterase) that breaks down acetylcholine. These drugs are approved in the US for treatment of Alzheimer's disease.
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.
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.

(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.)
Took pill 1:27 PM. At 2 my hunger gets the best of me (despite my usual tea drinking and caffeine+piracetam pills) and I eat a large lunch. This makes me suspicious it was placebo - on the previous days I had noted a considerable appetite-suppressant effect. 5:25 PM: I don’t feel unusually tired, but nothing special about my productivity. 8 PM; no longer so sure. Read and excerpted a fair bit of research I had been putting off since the morning. After putting away all the laundry at 10, still feeling active, I check. It was Adderall. I can’t claim this one either way. By 9 or 10 I had begun to wonder whether it was really Adderall, but I didn’t feel confident saying it was; my feeling could be fairly described as 50%.
Known widely as ‘Brahmi,’ the Bacopa Monnieri or Water Hyssop, is a small herb native to India that finds mention in various Ayurvedic texts for being the best natural cognitive enhancer. It has been used traditionally for memory enhancement, asthma, epilepsy and improving mood and attention of people over 65. It is known to be one of the best brain supplement in the world.

The prefrontal cortex at the front of the brain is the zone that produces such representations, and it is the focus of Arnsten’s work. “The way the prefrontal cortex creates these representations is by having pyramidal cells – they’re actually shaped like little pyramids – exciting each other. They keep each other firing, even when there’s no information coming in from the environment to stimulate the circuits,” she explains.
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.
Take at 10 AM; seem a bit more active but that could just be the pressure of the holiday season combined with my nice clean desk. I do the chores without too much issue and make progress on other things, but nothing major; I survive going to The Sitter without too much tiredness, so ultimately I decide to give the palm to it being active, but only with 60% confidence. I check the next day, and it was placebo. Oops.

Let's start with the basics of what smart drugs are and what they aren't.  The field of cosmetic psychopharmacology is still in its infancy, but the use of smart drugs is primed to explode during our lifetimes, as researchers gain increasing understanding of which substances affect the brain and how they do so.  For many people, the movie Limitless was a first glimpse into the possibility of "a pill that can make you smarter," and while that fiction is a long way from reality, the possibilities - in fact, present-day certainties visible in the daily news - are nevertheless extremely exciting.

Long-term use is different, and research-backed efficacy is another question altogether. The nootropic market is not regulated, so a company can make claims without getting in trouble for making those claims because they’re not technically selling a drug. This is why it’s important to look for well-known brands and standardized nootropic herbs where it’s easier to calculate the suggested dose and be fairly confident about what you’re taking.

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.


We’ve talk about how caffeine affects the body in great detail, but the basic idea is that it can improve your motivation and focus by increasing catecholamine signaling. Its effects can be dampened over time, however, as you start to build a caffeine tolerance. Research on L-theanine, a common amino acid, suggests it promotes neuronal health and can decrease the incidence of cold and flu symptoms by strengthening the immune system. And one study, published in the journal Biological Psychology, found that L-theanine reduces psychological and physiological stress responses—which is why it’s often taken with caffeine. In fact, in a 2014 systematic review of 11 different studies, published in the journal Nutrition Review, researchers found that use of caffeine in combination with L-theanine promoted alertness, task switching, and attention. The reviewers note the effects are most pronounced during the first two hours post-dose, and they also point out that caffeine is the major player here, since larger caffeine doses were found to have more of an effect than larger doses of L-theanine.
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.
These days, young, ambitious professionals prefer prescription stimulants—including methylphenidate (usually sold as Ritalin) and Adderall—that are designed to treat people with attention deficit hyperactivity disorder (ADHD) and are more common and more acceptable than cocaine or nicotine (although there is a black market for these pills). ADHD makes people more likely to lose their focus on tasks and to feel restless and impulsive. Diagnoses of the disorder have been rising dramatically over the past few decades—and not just in kids: In 2012, about 16 million Adderall prescriptions were written for adults between the ages of 20 and 39, according to a report in the New York Times. Both methylphenidate and Adderall can improve sustained attention and concentration, says Barbara Sahakian, professor of clinical neuropsychology at the University of Cambridge and author of the 2013 book Bad Moves: How Decision Making Goes Wrong, and the Ethics of Smart Drugs. But the drugs do have side effects, including insomnia, lack of appetite, mood swings, and—in extreme cases—hallucinations, especially when taken in amounts the exceed standard doses. Take a look at these 10 foods that help you focus.
Maj. Jamie Schwandt, USAR, is a logistics officer and has served as an operations officer, planner and commander. He is certified as a Department of the Army Lean Six Sigma Master Black Belt, certified Red Team Member, and holds a doctorate from Kansas State University. This article represents his own personal views, which are not necessarily those of the Department of the Army.

As Sulbutiamine crosses the blood-brain barrier very easily, it has a positive effect on the cholinergic and the glutamatergic receptors that are responsible for essential activities impacting memory, concentration, and mood. The compound is also fat-soluble, which means it circulates rapidly and widely throughout the body and the brain, ensuring positive results. Thus, patients with schizophrenia and Parkinson’s disease will find the drug to be very effective.
Also known as Arcalion or Bisbuthiamine and Enerion, Sulbutiamine is a compound of the Sulphur group and is an analog to vitamin B1, which is known to pass the blood-brain barrier easily. Sulbutiamine is found to circulate faster than Thiamine from blood to brain. It is recommended for patients suffering from mental fatigue caused due to emotional and psychological stress. The best part about this compound is that it does not have most of the common side effects linked with a few nootropics.
The intradimensional– extradimensional shift task from the CANTAB battery was used in two studies of MPH and measures the ability to shift the response criterion from one dimension to another, as in the WCST, as well as to measure other abilities, including reversal learning, measured by performance in the trials following an intradimensional shift. With an intradimensional shift, the learned association between values of a given stimulus dimension and reward versus no reward is reversed, and participants must learn to reverse their responses accordingly. Elliott et al. (1997) reported finding no effects of the drug on ability to shift among dimensions in the extradimensional shift condition and did not describe performance on the intradimensional shift. Rogers et al. (1999) found that accuracy improved but responses slowed with MPH on trials requiring a shift from one dimension to another, which leaves open the question of whether the drug produced net enhancement, interference, or neither on these trials once the tradeoff between speed and accuracy is taken into account. For intradimensional shifts, which require reversal learning, these authors found drug-induced impairment: significantly slower responding accompanied by a borderline-significant impairment of accuracy.

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.
(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.)
Adaptogens are plant-derived chemicals whose activity helps the body maintain or regain homeostasis (equilibrium between the body’s metabolic processes). Almost without exception, adaptogens are available over-the-counter as dietary supplements, not controlled drugs. Well-known adaptogens include Ginseng, Kava Kava, Passion Flower, St. Johns Wort, and Gotu Kola. Many of these traditional remedies border on being “folk wisdom,” and have been in use for hundreds or thousands of years, and are used to treat everything from anxiety and mild depression to low libido. While these smart drugs work in a many different ways (their commonality is their resultant function within the body, not their chemical makeup), it can generally be said that the cognitive boost users receive is mostly a result of fixing an imbalance in people with poor diets, body toxicity, or other metabolic problems, rather than directly promoting the growth of new brain cells or neural connections.
The infinite promise of stacking is why, whatever weight you attribute to the evidence of their efficacy, nootropics will never go away: With millions of potential iterations of brain-enhancing regimens out there, there is always the tantalizing possibility that seekers haven’t found the elusive optimal combination of pills and powders for them—yet. Each “failure” is but another step in the process-of-elimination journey to biological self-actualization, which may be just a few hundred dollars and a few more weeks of amateur alchemy away.

Racetams, specifically Piracetam, an ingredient popular in over-the-counter nootropics, are synthetic stimulants designed to improve brain function. Patel notes Piracetam is the granddaddy of all racetams, and the term “nootropic” was originally coined to describe its effects. However, despite its popularity and how long it’s been around and in use, researchers don’t know what its mechanism of action is. Patel explained that the the most prominent hypothesis suggests Piracetam enhances neuronal function by increasing membrane fluidity in the brain, but that hasn’t been confirmed yet. And Patel elaborated that most studies on Piracetam aren’t done with the target market for nootropics in mind, the young professional:

However, they fell short in several categories. The key issue with their product is that it does not contain DHA Omega 3 and the other essential vitamins and nutrients needed to support the absorption of Huperzine A and Phosphatidylserine. Without having DHA Omega 3 it will not have an essential piece to maximum effectiveness. This means that you would need to take a separate pill of DHA Omega 3 and several other essential vitamins to ensure you are able to reach optimal memory support. They also are still far less effective than our #1 pick’s complete array of the 3 essential brain supporting ingredients and over 30 supporting nutrients, making their product less effective.
There are certain risks associated with smart pills that might restrain their use. A smart pill usually leaves the body within two weeks. Sometimes, the pill might get lodged in the digestive tract rather than exiting the body via normal bowel movements. The risk might be higher in people with a tumor, Crohns disease, or some surgery within that area that lead to narrowing of the digestive tract. CT scan is usually performed in people with high-risk to assess the narrowing of the tract. However, the pill might still be lodged even if the results are negative for the CT scan, which might lead to bowel obstruction and can be removed either by surgery or traditional endoscopy. Smart pills might lead to skin irritation, which results in mild redness and need to be treated topically. It may also lead to capsule aspiration, which involves the capsule going down the wrong pipe and entering the airway instead of the esophagus. This might result in choking and death if immediate bronchoscopic extraction is not performed. Patients with comorbidities related to brain injury or chronic obstructive pulmonary disease may be at a higher risk. So, the health risks associated with the use of smart pills are hindering the smart pills technology market. The other factors, such as increasing cost with technological advancement and ethical constraints are also hindering the market.
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.
Companies already know a great deal about how their employees live their lives. With the help of wearable technologies and health screenings, companies can now analyze the relation between bodily activities — exercise, sleep, nutrition, etc. — and work performance. With the justification that healthy employees perform better, some companies have made exercise mandatory by using sanctions against those who refuse to perform. And according to The Kaiser Family Foundation, of the large U.S. companies that offer health screenings, nearly half of them use financial incentives to persuade employees to participate.

I took the pill at 11 PM the evening of (technically, the day before); that day was a little low on sleep than usual, since I had woken up an hour or half-hour early. I didn’t yawn at all during the movie (merely mediocre to my eyes with some questionable parts)22. It worked much the same as it did the previous time - as I walked around at 5 AM or so, I felt perfectly alert. I made good use of the hours and wrote up my memories of ICON 2011.

Adrafinil is a prodrug for Modafinil, which means it can be metabolized into Modafinil to give you a similar effect. And you can buy it legally just about anywhere. But there are a few downsides. Patel explains that you have to take a lot more to achieve a similar effect as Modafinil, wait longer for it to kick in (45-60 minutes), there are more potential side effects, and there aren’t any other benefits to taking it.
NGF may sound intriguing, but the price is a dealbreaker: at suggested doses of 1-100μg (NGF dosing in humans for benefits is, shall we say, not an exact science), and a cost from sketchy suppliers of $1210/100μg/$470/500μg/$750/1000μg/$1000/1000μg/$1030/1000μg/$235/20μg. (Levi-Montalcini was presumably able to divert some of her lab’s production.) A year’s supply then would be comically expensive: at the lowest doses of 1-10μg using the cheapest sellers (for something one is dumping into one’s eyes?), it could cost anywhere up to $10,000.
It arrived as described, a little bottle around the volume of a soda can. I had handy a plastic syringe with milliliter units which I used to measure out the nicotine-water into my tea. I began with half a ml the first day, 1ml the second day, and 2ml the third day. (My Zeo sleep scores were 85/103/86 (▁▇▁), and the latter had a feline explanation; these values are within normal variation for me, so if nicotine affects my sleep, it does so to a lesser extent than Adderall.) Subjectively, it’s hard to describe. At half a ml, I didn’t really notice anything; at 1 and 2ml, I thought I began to notice it - sort of a cleaner caffeine. It’s nice so far. It’s not as strong as I expected. I looked into whether the boiling water might be breaking it down, but the answer seems to be no - boiling tobacco is a standard way to extract nicotine, actually, and nicotine’s own boiling point is much higher than water; nor do I notice a drastic difference when I take it in ordinary water. And according to various e-cigarette sources, the liquid should be good for at least a year.
The principal metric would be mood, however defined. Zeo’s web interface & data export includes a field for Day Feel, which is a rating 1-5 of general mood & quality of day. I can record a similar metric at the end of each day. 1-5 might be a little crude even with a year of data, so a more sophisticated measure might be in order. The first mood study is paywalled so I’m not sure what they used, but Shiotsuki 2008 used State-Trait of Anxiety Inventory (STAI) and Profiles of Mood States Test (POMS). The full POMS sounds too long to use daily, but the Brief POMS might work. In the original 1987 paper A brief POMS measure of distress for cancer patients, patients answering this questionnaire had a mean total mean of 10.43 (standard deviation 8.87). Is this the best way to measure mood? I’ve asked Seth Roberts; he suggested using a 0-100 scale, but personally, there’s no way I can assess my mood on 0-100. My mood is sufficiently stable (to me) that 0-5 is asking a bit much, even.
More recently, the drug modafinil (brand name: Provigil) has become the brain-booster of choice for a growing number of Americans. According to the FDA, modafinil is intended to bolster “wakefulness” in people with narcolepsy, obstructive sleep apnea or shift work disorder. But when people without those conditions take it, it has been linked with improvements in alertness, energy, focus and decision-making. A 2017 study found evidence that modafinil may enhance some aspects of brain connectivity, which could explain these benefits.
No. There are mission essential jobs that require you to live on base sometimes. Or a first term person that is required to live on base. Or if you have proven to not be as responsible with rent off base as you should be so your commander requires you to live on base. Or you’re at an installation that requires you to live on base during your stay. Or the only affordable housing off base puts you an hour away from where you work. It isn’t simple. The fact that you think it is tells me you are one of the “dumb@$$es” you are referring to above.

A number of so-called ‘smart drugs’ or cognitive enhancers have captured attention recently, from stimulants such as modafinil, to amphetamines (often prescribed under the name Adderall) and methylphenidate (also known by its brand name Ritalin). According to widespread news reports, students have begun using these drugs to enhance their performance in school and college, and are continuing to do so in their professional lives.
In my last post, I talked about the idea that there is a resource that is necessary for self-control…I want to talk a little bit about the candidate for this resource, glucose. Could willpower fail because the brain is low on sugar? Let’s look at the numbers. A well-known statistic is that the brain, while only 2% of body weight, consumes 20% of the body’s energy. That sounds like the brain consumes a lot of calories, but if we assume a 2,400 calorie/day diet - only to make the division really easy - that’s 100 calories per hour on average, 20 of which, then, are being used by the brain. Every three minutes, then, the brain - which includes memory systems, the visual system, working memory, then emotion systems, and so on - consumes one (1) calorie. One. Yes, the brain is a greedy organ, but it’s important to keep its greediness in perspective… Suppose, for instance, that a brain in a person exerting their willpower - resisting eating brownies or what have you - used twice as many calories as a person not exerting willpower. That person would need an extra one third of a calorie per minute to make up the difference compared to someone not exerting willpower. Does exerting self control burn more calories?
There is no official data on their usage, but nootropics as well as other smart drugs appear popular in the Silicon Valley. “I would say that most tech companies will have at least one person on something,” says Noehr. It is a hotbed of interest because it is a mentally competitive environment, says Jesse Lawler, a LA based software developer and nootropics enthusiast who produces the podcast Smart Drug Smarts. “They really see this as translating into dollars.” But Silicon Valley types also do care about safely enhancing their most prized asset – their brains – which can give nootropics an added appeal, he says.

Zach was on his way to being a doctor when a personal health crisis changed all of that. He decided that he wanted to create wellness instead of fight illness. He lost over a 100 lbs through functional nutrition and other natural healing protocols. He has since been sharing his knowledge of nutrition and functional medicine for the last 12 years as a health coach and health educator.
Smart pills containing Aniracetam may also improve communication between the brain’s hemispheres. This benefit makes Aniracetam supplements ideal for enhancing creativity and stabilizing mood. But, the anxiolytic effects of Aniracetam may be too potent for some. There are reports of some users who find that it causes them to feel unmotivated or sedated. Though, it may not be an issue if you only seek the anti-stress and anxiety-reducing effects.
Nootrobox co-founder Geoffrey Woo declines a caffeinated drink in favour of a capsule of his newest product when I meet him in a San Francisco coffee shop. The entire industry has a “wild west” aura about it, he tells me, and Nootrobox wants to fix it by pushing for “smarter regulation” so safe and effective drugs that are currently unclassified can be brought into the fold. Predictably, both companies stress the higher goal of pushing forward human cognition. “I am trying to make a smarter, better populace to solve all the problems we have created,” says Nootroo founder Eric Matzner.
I took 1.5mg of melatonin, and went to bed at ~1:30AM; I woke up around 6:30, took a modafinil pill/200mg, and felt pretty reasonable. By noon my mind started to feel a bit fuzzy, and lunch didn’t make much of it go away. I’ve been looking at studies, and users seem to degrade after 30 hours; I started on mid-Thursday, so call that 10 hours, then 24 (Friday), 24 (Saturday), and 14 (Sunday), totaling 72hrs with <20hrs sleep; this might be equivalent to 52hrs with no sleep, and Wikipedia writes:

One curious thing that leaps out looking at the graphs is that the estimated underlying standard deviations differ: the nicotine days have a strikingly large standard deviation, indicating greater variability in scores - both higher and lower, since the means weren’t very different. The difference in standard deviations is just 6.6% below 0, so the difference almost reaches our usual frequentist levels of confidence too, which we can verify by testing:
There is an ancient precedent to humans using natural compounds to elevate cognitive performance. Incan warriors in the 15th century would ingest coca leaves (the basis for cocaine) before battle. Ethiopian hunters in the 10th century developed coffee bean paste to improve hunting stamina. Modern athletes ubiquitously consume protein powders and hormones to enhance their training, recovery, and performance. The most widely consumed psychoactive compound today is caffeine. Millions of people use coffee and tea to be more alert and focused.
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.
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