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.
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.
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.
Exercise and nutrition also play an important role in neuroplasticity. Many vitamins and ingredients found naturally in food products have been shown to have cognitive enhancing effects. Some of these include vitamins B6 and B12, caffeine, phenethylamine found in chocolate and l-theanine, found in green tea, whose combined effects with caffeine are more extensively researched.

CDP-Choline is also known as Citicoline or Cytidine Diphosphocholine. It has been enhanced to allow improved crossing of the blood-brain barrier. Your body converts it to Choline and Cytidine. The second then gets converted to Uridine (which crosses the blood-brain barrier). CDP-Choline is found in meats (liver), eggs (yolk), fish, and vegetables (broccoli, Brussels sprout).
If stimulants truly enhance cognition but do so to only a small degree, this raises the question of whether small effects are of practical use in the real world. Under some circumstances, the answer would undoubtedly be yes. Success in academic and occupational competitions often hinges on the difference between being at the top or merely near the top. A scholarship or a promotion that can go to only one person will not benefit the runner-up at all. Hence, even a small edge in the competition can be important.
as scientific papers become much more accessible online due to Open Access, digitization by publishers, and cheap hosting for pirates, the available knowledge about nootropics increases drastically. This reduces the perceived risk by users, and enables them to educate themselves and make much more sophisticated estimates of risk and side-effects and benefits. (Take my modafinil page: in 1997, how could an average person get their hands on any of the papers available up to that point? Or get detailed info like the FDA’s prescribing guide? Even assuming they had a computer & Internet?)
Instead of buying expensive supplements, Lebowitz recommends eating heart-healthy foods, like those found in the MIND diet. Created by researchers at Rush University, MIND combines the Mediterranean and DASH eating plans, which have been shown to reduce the risk of heart problems. Fish, nuts, berries, green leafy vegetables and whole grains are MIND diet staples. Lebowitz says these foods likely improve your cognitive health by keeping your heart healthy.

And yet aside from anecdotal evidence, we know very little about the use of these drugs in professional settings. The Financial Times has claimed that they are “becoming popular among city lawyers, bankers, and other professionals keen to gain a competitive advantage over colleagues.” Back in 2008 the narcolepsy medication Modafinil was labeled the “entrepreneur’s drug of choice” by TechCrunch. That same year, the magazine Nature asked its readers whether they use cognitive-enhancing drugs; of the 1,400 respondents, one in five responded in the affirmative.
Frustrated by the lack of results, pharmaceutical companies have been shutting down their psychiatric drug research programmes. Traditional methods, such as synthesising new molecules and seeing what effect they have on symptoms, seem to have run their course. A shift of strategy is looming, towards research that focuses on genes and brain circuitry rather than chemicals. The shift will prolong the wait for new blockbuster drugs further, as the new systems are developed, and offers no guarantees of results.

While the mechanism is largely unknown, one commonly mechanism possibility is that light of the relevant wavelengths is preferentially absorbed by the protein cytochrome c oxidase, which is a key protein in mitochondrial metabolism and production of ATP, substantially increasing output, and this extra output presumably can be useful for cellular activities like healing or higher performance.
First off, overwhelming evidence suggests that smart drugs actually work. A meta-analysis by researchers at Harvard Medical School and Oxford showed that Modafinil has significant cognitive benefits for those who do not suffer from sleep deprivation. The drug improves their ability to plan and make decisions and has a positive effect on learning and creativity. Another study, by researchers at Imperial College London, showed that Modafinil helped sleep-deprived surgeons become better at planning, redirecting their attention, and being less impulsive when making decisions.
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.

Since LLLT was so cheap, seemed safe, was interesting, just trying it would involve minimal effort, and it would be a favor to lostfalco, I decided to try it. I purchased off eBay a $13 48 LED illuminator light IR Infrared Night Vision+Power Supply For CCTV. Auto Power-On Sensor, only turn-on when the surrounding is dark. IR LED wavelength: 850nm. Powered by DC 12V 500mA adaptor. It arrived in 4 days, on 7 September 2013. It fits handily in my palm. My cellphone camera verified it worked and emitted infrared - important because there’s no visible light at all (except in complete darkness I can make out a faint red light), no noise, no apparent heat (it took about 30 minutes before the lens or body warmed up noticeably when I left it on a table). This was good since I worried that there would be heat or noise which made blinding impossible; all I had to do was figure out how to randomly turn the power on and I could run blinded self-experiments with it.
Depending on where you live, some nootropics may not be sold over the counter, but they are usually available online. The law regarding nootropics can vary massively around the world, so be sure to do your homework before you purchase something for the first time. Be particularly cautious when importing smart drugs, because quality control and regulations abroad are not always as stringent as they are in the US. Do not put your health at risk if all you are trying to do is gain an edge in a competitive sport.
At this point I began to get bored with it and the lack of apparent effects, so I began a pilot trial: I’d use the LED set for 10 minutes every few days before 2PM, record, and in a few months look for a correlation with my daily self-ratings of mood/productivity (for 2.5 years I’ve asked myself at the end of each day whether I did more, the usual, or less work done that day than average, so 2=below-average, 3=average, 4=above-average; it’s ad hoc, but in some factor analyses I’ve been playing with, it seems to load on a lot of other variables I’ve measured, so I think it’s meaningful).
There is much to be appreciated in a brain supplement like BrainPill (never mind the confusion that may stem from the generic-sounding name) that combines tried-and-tested ingredients in a single one-a-day formulation. The consistency in claims and what users see in real life is an exemplary one, which convinces us to rate this powerhouse as the second on this review list. Feeding one’s brain with nootropics and related supplements entails due diligence in research and seeking the highest quality, and we think BrainPill is up to task. Learn More...
Upon examining the photographs, I noticed no difference in eye color, but it seems that my move had changed the ambient lighting in the morning and so there was a clear difference between the two sets of photographs! The before photographs had brighter lighting than the after photographs. Regardless, I decided to run a small survey on QuickSurveys/Toluna to confirm my diagnosis of no-change; the survey was 11 forced-choice pairs of photographs (before-after), with the instructions as follows:
There are some other promising prescription drugs that may have performance-related effects on the brain. But at this point, all of them seem to involve a roll of the dice. You may experience a short-term brain boost, but you could also end up harming your brain (or some other aspect of your health) in the long run. “To date, there is no safe drug that may increase cognition in healthy adults,” Fond says of ADHD drugs, modafinil and other prescription nootropics.
Most epidemiological research on nonmedical stimulant use has been focused on issues relevant to traditional problems of drug abuse and addiction, and so, stimulant use for cognitive enhancement is not generally distinguished from use for other purposes, such as staying awake or getting high. As Boyd and McCabe (2008) pointed out, the large national surveys of nonmedical prescription drug use have so far failed to distinguish the ways and reasons that people use the drugs, and this is certainly true where prescription stimulants are concerned. The largest survey to investigate prescription stimulant use in a nationally representative sample of Americans, the National Survey on Drug Use and Health (NSDUH), phrases the question about nonmedical use as follows: “Have you ever, even once, used any of these stimulants when they were not prescribed for you or that you took only for the experience or feeling they caused?” (Snodgrass & LeBaron 2007). This phrasing does not strictly exclude use for cognitive enhancement, but it emphasizes the noncognitive effects of the drugs. In 2008, the NSDUH found a prevalence of 8.5% for lifetime nonmedical stimulant use by Americans over the age of 12 years and a prevalence of 12.3% for Americans between 21 and 25 (Substance Abuse and Mental Health Services Administration, 2009).
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.
2ml is supposed to translate to 24mg, which is a big dose. I do not believe any of the commercial patches go much past that. I asked Wedrifid, whose notes inspired my initial interest, and he was taking perhaps 2-4mg, and expressed astonishment that I might be taking 24mg. (2mg is in line with what I am told by another person - that 2mg was so much that they actually felt a little sick. On the other hand, in one study, the subjects could not reliably distinguish between 1mg and placebo24.) 24mg is particularly troubling in that I weigh ~68kg, and nicotine poisoning and the nicotine LD50 start, for me, at around 68mg of nicotine. (I reflected that the entire jar could be a useful murder weapon, although nicotine presumably would be caught in an autopsy’s toxicology screen; I later learned nicotine was an infamous weapon in the 1800s before any test was developed. It doesn’t seem used anymore, but there are still fatal accidents due to dissolved nicotine.) The upper end of the range, 10mg/kg or 680mg for me, is calculated based on experienced smokers. Something is wrong here - I can’t see why I would have nicotine tolerance comparable to a hardened smoker, inasmuch as my maximum prior exposure was second-hand smoke once in a blue moon. More likely is that either the syringe is misleading me or the seller NicVape sold me something more dilute than 12mg/ml. (I am sure that it’s not simply plain water; when I mix the drops with regular water, I can feel the propylene glycol burning as it goes down.) I would rather not accuse an established and apparently well-liked supplier of fraud, nor would I like to simply shrug and say I have a mysterious tolerance and must experiment with doses closer to the LD50, so the most likely problem is a problem with the syringe. The next day I altered the procedure to sucking up 8ml, squirting out enough fluid to move the meniscus down to 7ml, and then ejecting the rest back into the container. The result was another mild clean stimulation comparable to the previous 1ml days. The next step is to try a completely different measuring device, which doesn’t change either.
Speaking of addictive substances, some people might have considered cocaine a nootropic (think: the finance industry in Wall Street in the 1980s). The incredible damage this drug can do is clear, but the plant from which it comes has been used to make people feel more energetic and less hungry, and to counteract altitude sickness in Andean South American cultures for 5,000 years, according to an opinion piece that Bolivia’s president, Evo Morales Ayma, wrote for the New York Times.
Does little alone, but absolutely necessary in conjunction with piracetam. (Bought from Smart Powders.) When turning my 3kg of piracetam into pills, I decided to avoid the fishy-smelling choline and go with 500g of DMAE (Examine.com); it seemed to work well when I used it before with oxiracetam & piracetam, since I had no piracetam headaches, and be considerably less bulky.

The effect? 3 or 4 weeks later, I’m not sure. When I began putting all of my nootropic powders into pill-form, I put half a lithium pill in each, and nevertheless ran out of lithium fairly quickly (3kg of piracetam makes for >4000 OO-size pills); those capsules were buried at the bottom of the bucket under lithium-less pills. So I suddenly went cold-turkey on lithium. Reflecting on the past 2 weeks, I seem to have been less optimistic and productive, with items now lingering on my To-Do list which I didn’t expect to. An effect? Possibly.


An unusual intervention is infrared/near-infrared light of particular wavelengths (LLLT), theorized to assist mitochondrial respiration and yielding a variety of therapeutic benefits. Some have suggested it may have cognitive benefits. LLLT sounds strange but it’s simple, easy, cheap, and just plausible enough it might work. I tried out LLLT treatment on a sporadic basis 2013-2014, and statistically, usage correlated strongly & statistically-significantly with increases in my daily self-ratings, and not with any sleep disturbances. Excited by that result, I did a randomized self-experiment 2014-2015 with the same procedure, only to find that the causal effect was weak or non-existent. I have stopped using LLLT as likely not worth the inconvenience.
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.
Federal law classifies most nootropics as dietary supplements, which means that the Food and Drug Administration does not regulate manufacturers’ statements about their benefits (as the giant “This product is not intended to diagnose, treat, cure, or prevent any disease” disclaimer on the label indicates). And the types of claims that the feds do allow supplement companies to make are often vague and/or supported by less-than-compelling scientific evidence. “If you find a study that says that an ingredient caused neurons to fire on rat brain cells in a petri dish,” says Pieter Cohen, an assistant professor at Harvard Medical School, “you can probably get away with saying that it ‘enhances memory’ or ‘promotes brain health.’”

The term “smart pills” refers to miniature electronic devices that are shaped and designed in the mold of pharmaceutical capsules but perform highly advanced functions such as sensing, imaging and drug delivery. They may include biosensors or image, pH or chemical sensors. Once they are swallowed, they travel along the gastrointestinal tract to capture information that is otherwise difficult to obtain, and then are easily eliminated from the system. Their classification as ingestible sensors makes them distinct from implantable or wearable sensors.
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.

I do recommend a few things, like modafinil or melatonin, to many adults, albeit with misgivings about any attempt to generalize like that. (It’s also often a good idea to get powders, see the appendix.) Some of those people are helped; some have told me that they tried and the suggestion did little or nothing. I view nootropics as akin to a biological lottery; one good discovery pays for all. I forge on in the hopes of further striking gold in my particular biology. Your mileage will vary. All you have to do, all you can do is to just try it. Most of my experiences were in my 20s as a right-handed 5’11 white male weighing 190-220lbs, fitness varying over time from not-so-fit to fairly fit. In rough order of personal effectiveness weighted by costs+side-effects, I rank them as follows:
Took pill #6 at 12:35 PM. Hard to be sure. I ultimately decided that it was Adderall because I didn’t have as much trouble as I normally would in focusing on reading and then finishing my novel (Surface Detail) despite my family watching a movie, though I didn’t notice any lack of appetite. Call this one 60-70% Adderall. I check the next evening and it was Adderall.

Took pill 12:11 PM. I am not certain. While I do get some things accomplished (a fair amount of work on the Silk Road article and its submission to places), I also have some difficulty reading through a fiction book (Sum) and I seem kind of twitchy and constantly shifting windows. I am weakly inclined to think this is Adderall (say, 60%). It’s not my normal feeling. Next morning - it was Adderall.
The U.S. Centers for Disease Control and Prevention estimates that gastrointestinal diseases affect between 60 and 70 million Americans every year. This translates into tens of millions of endoscopy procedures. Millions of colonoscopy procedures are also performed to diagnose or screen for colorectal cancers. Conventional, rigid scopes used for these procedures are uncomfortable for patients and may cause internal bruising or lead to infection because of reuse on different patients. Smart pills eliminate the need for invasive procedures: wireless communication allows the transmission of real-time information; advances in batteries and on-board memory make them useful for long-term sensing from within the body. The key application areas of smart pills are discussed below.
I was contacted by the Longecity user lostfalco, and read through some of his writings on the topic. I had never heard of LLLT before, but the mitochondria mechanism didn’t sound impossible (although I wondered whether it made sense at a quantity level14151617), and there was at least some research backing it; more importantly, lostfalco had discovered that devices for LLLT could be obtained as cheap as $15. (Clearly no one will be getting rich off LLLT or affiliate revenue any time soon.) Nor could I think of any way the LLLT could be easily harmful: there were no drugs involved, physical contact was unnecessary, power output was too low to directly damage through heating, and if it had no LLLT-style effect but some sort of circadian effect through hitting photoreceptors, using it in the morning wouldn’t seem to interfere with sleep.

Some work has been done on estimating the value of IQ, both as net benefits to the possessor (including all zero-sum or negative-sum aspects) and as net positive externalities to the rest of society. The estimates are substantial: in the thousands of dollars per IQ point. But since increasing IQ post-childhood is almost impossible barring disease or similar deficits, and even increasing childhood IQs is very challenging, much of these estimates are merely correlations or regressions, and the experimental childhood estimates must be weakened considerably for any adult - since so much time and so many opportunities have been lost. A wild guess: $1000 net present value per IQ point. The range for severely deficient children was 10-15 points, so any normal (somewhat deficient) adult gain must be much smaller and consistent with Fitzgerald 2012’s ceiling on possible effect sizes (small).
By the end of 2009, at least 25 studies reported surveys of college students’ rates of nonmedical stimulant use. Of the studies using relatively smaller samples, prevalence was, in chronological order, 16.6% (lifetime; Babcock & Byrne, 2000), 35.3% (past year; Low & Gendaszek, 2002), 13.7% (lifetime; Hall, Irwin, Bowman, Frankenberger, & Jewett, 2005), 9.2% (lifetime; Carroll, McLaughlin, & Blake, 2006), and 55% (lifetime, fraternity students only; DeSantis, Noar, & Web, 2009). Of the studies using samples of more than a thousand students, somewhat lower rates of nonmedical stimulant use were found, although the range extends into the same high rates as the small studies: 2.5% (past year, Ritalin only; Teter, McCabe, Boyd, & Guthrie, 2003), 5.4% (past year; McCabe & Boyd, 2005), 4.1% (past year; McCabe, Knight, Teter, & Wechsler, 2005), 11.2% (past year; Shillington, Reed, Lange, Clapp, & Henry, 2006), 5.9% (past year; Teter, McCabe, LaGrange, Cranford, & Boyd, 2006), 16.2% (lifetime; White, Becker-Blease, & Grace-Bishop, 2006), 1.7% (past month; Kaloyanides, McCabe, Cranford, & Teter, 2007), 10.8% (past year; Arria, O’Grady, Caldeira, Vincent, & Wish, 2008); 5.3% (MPH only, lifetime; Du-Pont, Coleman, Bucher, & Wilford, 2008); 34% (lifetime; DeSantis, Webb, & Noar, 2008), 8.9% (lifetime; Rabiner et al., 2009), and 7.5% (past month; Weyandt et al., 2009).
Do you start your day with a cup (or two, or three) of coffee? It tastes delicious, but it’s also jump-starting your brain because of its caffeine content. Caffeine is definitely a nootropic substance—it’s a mild stimulant that can alleviate fatigue and improve concentration, according to the Mayo Clinic. Current research shows that coffee drinkers don’t suffer any ill effects from drinking up to about four cups of coffee per day. Caffeine is also found in tea, soda, and energy drinks. Not too surprisingly, it’s also in many of the nootropic supplements that are being marketed to people looking for a mental boost. Take a look at these 7 genius brain boosters to try in the morning.
As with any thesis, there are exceptions to this general practice. For example, theanine for dogs is sold under the brand Anxitane is sold at almost a dollar a pill, and apparently a month’s supply costs $50+ vs $13 for human-branded theanine; on the other hand, this thesis predicts downgrading if the market priced pet versions higher than human versions, and that Reddit poster appears to be doing just that with her dog.↩
Many laboratory tasks have been developed to study working memory, each of which taxes to varying degrees aspects such as the overall capacity of working memory, its persistence over time, and its resistance to interference either from task-irrelevant stimuli or among the items to be retained in working memory (i.e., cross-talk). Tasks also vary in the types of information to be retained in working memory, for example, verbal or spatial information. The question of which of these task differences correspond to differences between distinct working memory systems and which correspond to different ways of using a single underlying system is a matter of debate (e.g., D’Esposito, Postle, & Rypma, 2000; Owen, 2000). For the present purpose, we ignore this question and simply ask, Do MPH and d-AMP affect performance in the wide array of tasks that have been taken to operationalize working memory? If the literature does not yield a unanimous answer to this question, then what factors might be critical in determining whether stimulant effects are manifest?
Several new medications are on the market and in development for Alzheimer's disease, a progressive neurological disease leading to memory loss, language deterioration, and confusion that afflicts about 4.5 million Americans and is expected to strike millions more as the baby boom generation ages. Yet the burning question for those who aren't staring directly into the face of Alzheimer's is whether these medications might make us smarter.
On 15 March 2014, I disabled light sensor: the complete absence of subjective effects since the first sessions made me wonder if the LED device was even turning on - a little bit of ambient light seems to disable it thanks to the light sensor. So I stuffed the sensor full of putty, verified it was now always-on with the cellphone camera, and began again; this time it seemed to warm up much faster, making me wonder if all the previous sessions’ sense of warmth was simply heat from my hand holding the LEDs
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.
Clarke and Sokoloff (1998) remarked that although [a] common view equates concentrated mental effort with mental work…there appears to be no increased energy utilization by the brain during such processes (p. 664), and …the areas that participate in the processes of such reasoning represent too small a fraction of the brain for changes in their functional and metabolic activities to be reflected in the energy metabolism of the brain… (p. 675).
Instead of buying expensive supplements, Lebowitz recommends eating heart-healthy foods, like those found in the MIND diet. Created by researchers at Rush University, MIND combines the Mediterranean and DASH eating plans, which have been shown to reduce the risk of heart problems. Fish, nuts, berries, green leafy vegetables and whole grains are MIND diet staples. Lebowitz says these foods likely improve your cognitive health by keeping your heart healthy.
Table 4 lists the results of 27 tasks from 23 articles on the effects of d-AMP or MPH on working memory. The oldest and most commonly used type of working memory task in this literature is the Sternberg short-term memory scanning paradigm (Sternberg, 1966), in which subjects hold a set of items (typically letters or numbers) in working memory and are then presented with probe items, to which they must respond “yes” (in the set) or “no” (not in the set). The size of the set, and hence the working memory demand, is sometimes varied, and the set itself may be varied from trial to trial to maximize working memory demands or may remain fixed over a block of trials. Taken together, the studies that have used a version of this task to test the effects of MPH and d-AMP on working memory have found mixed and somewhat ambiguous results. No pattern is apparent concerning the specific version of the task or the specific drug. Four studies found no effect (Callaway, 1983; Kennedy, Odenheimer, Baltzley, Dunlap, & Wood, 1990; Mintzer & Griffiths, 2007; Tipper et al., 2005), three found faster responses with the drugs (Fitzpatrick, Klorman, Brumaghim, & Keefover, 1988; Ward et al., 1997; D. E. Wilson et al., 1971), and one found higher accuracy in some testing sessions at some dosages, but no main effect of drug (Makris et al., 2007). The meaningfulness of the increased speed of responding is uncertain, given that it could reflect speeding of general response processes rather than working memory–related processes. Aspects of the results of two studies suggest that the effects are likely due to processes other than working memory: D. E. Wilson et al. (1971) reported comparable speeding in a simple task without working memory demands, and Tipper et al. (2005) reported comparable speeding across set sizes.
Remembering what Wedrifid told me, I decided to start with a quarter of a piece (~1mg). The gum was pretty tasteless, which ought to make blinding easier. The effects were noticeable around 10 minutes - greater energy verging on jitteriness, much faster typing, and apparent general quickening of thought. Like a more pleasant caffeine. While testing my typing speed in Amphetype, my speed seemed to go up >=5 WPM, even after the time penalties for correcting the increased mistakes; I also did twice the usual number without feeling especially tired. A second dose was similar, and the third dose was at 10 PM before playing Ninja Gaiden II seemed to stop the usual exhaustion I feel after playing through a level or so. (It’s a tough game, which I have yet to master like Ninja Gaiden Black.) Returning to the previous concern about sleep problems, though I went to bed at 11:45 PM, it still took 28 minutes to fall sleep (compared to my more usual 10-20 minute range); the next day I use 2mg from 7-8PM while driving, going to bed at midnight, where my sleep latency is a more reasonable 14 minutes. I then skipped for 3 days to see whether any cravings would pop up (they didn’t). I subsequently used 1mg every few days for driving or Ninja Gaiden II, and while there were no cravings or other side-effects, the stimulation definitely seemed to get weaker - benefits seemed to still exist, but I could no longer describe any considerable energy or jitteriness.
The evidence? Ritalin is FDA-approved to treat ADHD. It has also been shown to help patients with traumatic brain injury concentrate for longer periods, but does not improve memory in those patients, according to a 2016 meta-analysis of several trials. A study published in 2012 found that low doses of methylphenidate improved cognitive performance, including working memory, in healthy adult volunteers, but high doses impaired cognitive performance and a person’s ability to focus. (Since the brains of teens have been found to be more sensitive to the drug’s effect, it’s possible that methylphenidate in lower doses could have adverse effects on working memory and cognitive functions.)
So, I have started a randomized experiment; should take 2 months, given the size of the correlation. If that turns out to be successful too, I’ll have to look into methods of blinding - for example, some sort of electronic doohickey which turns on randomly half the time and which records whether it’s on somewhere one can’t see. (Then for the experiment, one hooks up the LED, turns the doohickey on, and applies directly to forehead, checking the next morning to see whether it was really on or off).

Sure, those with a mental illness may very well need a little more monitoring to make sure they take their medications, but will those suffering from a condition with hallmark symptoms of paranoia and anxiety be helped by consuming a technology that quite literally puts a tracking device inside their body? For patients hearing voices telling them that they're being watched, a monitoring device may be a hard pill to swallow.
And there are other uses that may make us uncomfortable. The military is interested in modafinil as a drug to maintain combat alertness. A drug such as propranolol could be used to protect soldiers from the horrors of war. That could be considered a good thing – post-traumatic stress disorder is common in soldiers. But the notion of troops being unaffected by their experiences makes many feel uneasy.

This doesn’t fit the U-curve so well: while 60mg is substantially negative as one would extrapolate from 30mg being ~0, 48mg is actually better than 15mg. But we bought the estimates of 48mg/60mg at a steep price - we ignore the influence of magnesium which we know influences the data a great deal. And the higher doses were added towards the end, so may be influenced by the magnesium starting/stopping. Another fix for the missingness is to impute the missing data. In this case, we might argue that the placebo days of the magnesium experiment were identical to taking no magnesium at all and so we can classify each NA as a placebo day, and rerun the desired analysis:
While these two compounds may not be as exciting as a super pill that instantly unlocks the full potential of your brain, they currently have the most science to back them up. And, as Patel explains, they’re both relatively safe for healthy individuals of most ages. Patel explains that a combination of caffeine and L-theanine is the most basic supplement stack (or combined dose) because the L-theanine can help blunt the anxiety and “shakiness” that can come with ingesting too much caffeine.

The ethics of cognitive enhancement have been extensively debated in the academic literature (e.g., Bostrom & Sandberg, 2009; Farah et al., 2004; Greely et al., 2008; Mehlman, 2004; Sahakian & Morein-Zamir, 2007). We do not attempt to review this aspect of the problem here. Rather, we attempt to provide a firmer empirical basis for these discussions. Despite the widespread interest in the topic and its growing public health implications, there remains much researchers do not know about the use of prescription stimulants for cognitive enhancement.


Two studies investigated the effects of MPH on reversal learning in simple two-choice tasks (Clatworthy et al., 2009; Dodds et al., 2008). In these tasks, participants begin by choosing one of two stimuli and, after repeated trials with these stimuli, learn that one is usually rewarded and the other is usually not. The rewarded and nonrewarded stimuli are then reversed, and participants must then learn to choose the new rewarded stimulus. Although each of these studies found functional neuroimaging correlates of the effects of MPH on task-related brain activity (increased blood oxygenation level-dependent signal in frontal and striatal regions associated with task performance found by Dodds et al., 2008, using fMRI and increased dopamine release in the striatum as measured by increased raclopride displacement by Clatworthy et al., 2009, using PET), neither found reliable effects on behavioral performance in these tasks. The one significant result concerning purely behavioral measures was Clatworthy et al.’s (2009) finding that participants who scored higher on a self-report personality measure of impulsivity showed more performance enhancement with MPH. MPH’s effect on performance in individuals was also related to its effects on individuals’ dopamine activity in specific regions of the caudate nucleus.
For obvious reasons, it’s difficult for researchers to know just how common the “smart drug” or “neuro-enhancing” lifestyle is. However, a few recent studies suggest cognition hacking is appealing to a growing number of people. A survey conducted in 2016 found that 15% of University of Oxford students were popping pills to stay competitive, a rate that mirrored findings from other national surveys of UK university students. In the US, a 2014 study found that 18% of sophomores, juniors, and seniors at Ivy League colleges had knowingly used a stimulant at least once during their academic career, and among those who had ever used uppers, 24% said they had popped a little helper on eight or more occasions. Anecdotal evidence suggests that pharmacological enhancement is also on the rise within the workplace, where modafinil, which treats sleep disorders, has become particularly popular.
Adderall is a mix of 4 amphetamine salts (FDA adverse events), and not much better than the others (but perhaps less addictive); as such, like caffeine or methamphetamine, it is not strictly a nootropic but a cognitive enhancer and can be tricky to use right (for how one should use stimulants, see How To Take Ritalin Correctly). I ordered 10x10mg Adderall IR off Silk Road (Wikipedia). On the 4th day after confirmation from seller, the package arrived. It was a harmless looking little padded mailer. Adderall as promised: 10 blue pills with markings, in a double ziplock baggy (reasonable, it’s not cocaine or anything). They matched pretty much exactly the descriptions of the generic I had found online. (Surprisingly, apparently both the brand name and the generic are manufactured by the same pharmacorp.)

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.

“It is important to note that Abilify MyCite’s prescribing information (labeling) notes that the ability of the product to improve patient compliance with their treatment regimen has not been shown. Abilify MyCite should not be used to track drug ingestion in “real-time” or during an emergency because detection may be delayed or may not occur,” the FDA said in a statement.
My predictions were substantially better than random chance7, so my default belief - that Adderall does affect me and (mostly) for the better - is borne out. I usually sleep very well and 3 separate incidents of horrible sleep in a few weeks seems rather unlikely (though I didn’t keep track of dates carefully enough to link the Zeo data with the Adderall data). Between the price and the sleep disturbances, I don’t think Adderall is personally worthwhile.

Not all drug users are searching for a chemical escape hatch. A newer and increasingly normalized drug culture is all about heightening one’s current relationship to reality—whether at work or school—by boosting the brain’s ability to think under stress, stay alert and productive for long hours, and keep track of large amounts of information. In the name of becoming sharper traders, medical interns, or coders, people are taking pills typically prescribed for conditions including ADHD, narcolepsy, and Alzheimer’s. Others down “stacks” of special “nootropic” supplements.
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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