In addition, large national surveys, including the NSDUH, have generally classified prescription stimulants with other stimulants including street drugs such as methamphetamine. For example, since 1975, the National Institute on Drug Abuse–sponsored Monitoring the Future (MTF) survey has gathered data on drug use by young people in the United States (Johnston, O’Malley, Bachman, & Schulenberg, 2009a, 2009b). Originally, MTF grouped prescription stimulants under a broader class of stimulants so that respondents were asked specifically about MPH only after they had indicated use of some drug in the category of AMPs. As rates of MPH prescriptions increased and anecdotal reports of nonmedical use grew, the 2001 version of the survey was changed to include a separate standalone question about MPH use. This resulted in more than a doubling of estimated annual use among 12th graders, from 2.4% to 5.1%. More recent data from the MTF suggests Ritalin use has declined (3.4% in 2008). However, this may still underestimate use of MPH, as the question refers specifically to Ritalin and does not include other brand names such as Concerta (an extended release formulation of MPH).
The chemical Huperzine-A (Examine.com) is extracted from a moss. It is an acetylcholinesterase inhibitor (instead of forcing out more acetylcholine like the -racetams, it prevents acetylcholine from breaking down). My experience report: One for the null hypothesis files - Huperzine-A did nothing for me. Unlike piracetam or fish oil, after a full bottle (Source Naturals, 120 pills at 200μg each), I noticed no side-effects, no mental improvements of any kind, and no changes in DNB scores from straight Huperzine-A.
Remember: The strictest definition of nootropics today says that for a substance to be a true brain-boosting nootropic it must have low toxicity and few side effects. Therefore, by definition, a nootropic is safe to use. However, when people start stacking nootropics indiscriminately, taking megadoses, or importing them from unknown suppliers that may have poor quality control, it’s easy for safety concerns to start creeping in.

Another well-known smart drug classed as a cholinergic is Sulbutiamine, a synthetic derivative of thiamine which crosses the blood-brain barrier and has been shown to improve memory while reducing psycho-behavioral inhibition. While Sulbutiamine has been shown to exhibit cholinergic regulation within the hippocampus, the reasons for the drug’s discernable effects on the brain remain unclear. This smart drug, available over the counter as a nutritional supplement, has a long history of use, and appears to have no serious side effects at therapeutic levels.
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.
Running low on gum (even using it weekly or less, it still runs out), I decided to try patches. Reading through various discussions, I couldn’t find any clear verdict on what patch brands might be safer (in terms of nicotine evaporation through a cut or edge) than others, so I went with the cheapest Habitrol I could find as a first try of patches (Nicotine Transdermal System Patch, Stop Smoking Aid, 21 mg, Step 1, 14 patches) in May 2013. I am curious to what extent nicotine might improve a long time period like several hours or a whole day, compared to the shorter-acting nicotine gum which feels like it helps for an hour at most and then tapers off (which is very useful in its own right for kicking me into starting something I have been procrastinating on). I have not decided whether to try another self-experiment.
The word “nootropic” was coined in 1972 by a Romanian scientist, Corneliu Giurgea, who combined the Greek words for “mind” and “bending.” Caffeine and nicotine can be considered mild nootropics, while prescription Ritalin, Adderall and Provigil (modafinil, a drug for treating narcolepsy) lie at the far end of the spectrum when prescribed off-label as cognitive enhancers. Even microdosing of LSD is increasingly viewed as a means to greater productivity.
With subtle effects, we need a lot of data, so we want at least half a year (6 blocks) or better yet, a year (12 blocks); this requires 180 actives and 180 placebos. This is easily covered by $11 for Doctor’s Best Best Lithium Orotate (5mg), 200-Count (more precisely, Lithium 5mg (from 125mg of lithium orotate)) and $14 for 1000x1g empty capsules (purchased February 2012). For convenience I settled on 168 lithium & 168 placebos (7 pill-machine batches, 14 batches total); I can use them in 24 paired blocks of 7-days/1-week each (48 total blocks/48 weeks). The lithium expiration date is October 2014, so that is not a problem
That study is also interesting for finding benefits to chronic piracetam+choline supplementation in the mice, which seems connected to a Russian study which reportedly found that piracetam (among other more obscure nootropics) increased secretion of BDNF in mice. See also Drug heuristics on a study involving choline supplementation in pregnant rats.↩
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.
ADHD medication sales are growing rapidly, with annual revenues of $12.9 billion in 2015. These drugs can be obtained legally by those who have a prescription, which also includes those who have deliberately faked the symptoms in order to acquire the desired medication. (According to an experiment published in 2010, it is difficult for medical practitioners to separate those who feign the symptoms from those who actually have them.) That said, faking might not be necessary if a doctor deems your desired productivity level or your stress around a big project as reason enough to prescribe medication.
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.
…The Fate of Nicotine in the Body also describes Battelle’s animal work on nicotine absorption. Using C14-labeled nicotine in rabbits, the Battelle scientists compared gastric absorption with pulmonary absorption. Gastric absorption was slow, and first pass removal of nicotine by the liver (which transforms nicotine into inactive metabolites) was demonstrated following gastric administration, with consequently low systemic nicotine levels. In contrast, absorption from the lungs was rapid and led to widespread distribution. These results show that nicotine absorbed from the stomach is largely metabolized by the liver before it has a chance to get to the brain. That is why tobacco products have to be puffed, smoked or sucked on, or absorbed directly into the bloodstream (i.e., via a nicotine patch). A nicotine pill would not work because the nicotine would be inactivated before it reached the brain.
On 8 April 2011, I purchased from Smart Powders (20g for $8); as before, some light searching seemed to turn up SP as the best seller given shipping overhead; it was on sale and I planned to cap it so I got 80g. This may seem like a lot, but I was highly confident that theanine and I would get along since I already drink so much tea and was a tad annoyed at the edge I got with straight caffeine. So far I’m pretty happy with it. My goal was to eliminate the physical & mental twitchiness of caffeine, which subjectively it seems to do.

It’s basic economics: the price of a good must be greater than cost of producing said good, but only under perfect competition will price = cost. Otherwise, the price is simply whatever maximizes profit for the seller. (Bottled water doesn’t really cost $2 to produce.) This can lead to apparently counter-intuitive consequences involving price discrimination & market segmentation - such as damaged goods which are the premium product which has been deliberately degraded and sold for less (some Intel CPUs, some headphones etc.). The most famous examples were railroads; one notable passage by French engineer-economist Jules Dupuit describes the motivation for the conditions in 1849:


Capsule Connection sells 1000 00 pills (the largest pills) for $9. I already have a pill machine, so that doesn’t count (a sunk cost). If we sum the grams per day column from the first table, we get 9.75 grams a day. Each 00 pill can take around 0.75 grams, so we need 13 pills. (Creatine is very bulky, alas.) 13 pills per day for 1000 days is 13,000 pills, and 1,000 pills is $9 so we need 13 units and 13 times 9 is $117.
The Nature commentary is ivory tower intellectualism at its best. The authors state that society must prepare for the growing demand of such drugs; that healthy adults should be allowed drugs to enhance cognitive ability; that this is "morally equivalent" and no more unnatural than diet, sleep, or the use of computers; that we need an evidence-based approach to evaluate the risks; and that we need legal and ethical policies to ensure fair and equitable use.
Blinding stymied me for a few months since the nasty taste was unmistakable and I couldn’t think of any gums with a similar flavor to serve as placebo. (The nasty taste does not seem to be due to the nicotine despite what one might expect; Vaniver plausibly suggested the bad taste might be intended to prevent over-consumption, but nothing in the Habitrol ingredient list seemed to be noted for its bad taste, and a number of ingredients were sweetening sugars of various sorts. So I couldn’t simply flavor some gum.)
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.
Although piracetam has a history of “relatively few side effects,” it has fallen far short of its initial promise for treating any of the illnesses associated with cognitive decline, according to Lon Schneider, a professor of psychiatry and behavioral sciences at the Keck School of Medicine at the University of Southern California. “We don’t use it at all and never have.”
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.

Due to the synthetic nature of racetams, you won’t find them in many of the best smart pills on the market. The intentional exclusion is not because racetams are ineffective. Instead, the vast majority of users trust natural smart drugs more. The idea of using a synthetic substance to alter your brain’s operating system is a big turn off for most people. With synthetic nootropics, you’re a test subject until more definitive studies arise.

Enhanced learning was also observed in two studies that involved multiple repeated encoding opportunities. Camp-Bruno and Herting (1994) found MPH enhanced summed recall in the Buschke Selective Reminding Test (Buschke, 1973; Buschke & Fuld, 1974) when 1-hr and 2-hr delays were combined, although individually only the 2-hr delay approached significance. Likewise, de Wit, Enggasser, and Richards (2002) found no effect of d-AMP on the Hopkins Verbal Learning Test (Brandt, 1991) after a 25-min delay. Willett (1962) tested rote learning of nonsense syllables with repeated presentations, and his results indicate that d-AMP decreased the number of trials needed to reach criterion.


One of the other suggested benefits is for boosting serotonin levels; low levels of serotonin are implicated in a number of issues like depression. I’m not yet sure whether tryptophan has helped with motivation or happiness. Trial and error has taught me that it’s a bad idea to take tryptophan in the morning or afternoon, however, even smaller quantities like 0.25g. Like melatonin, the dose-response curve is a U: ~1g is great and induces multiple vivid dreams for me, but ~1.5g leads to an awful night and a headache the next day that was worse, if anything, than melatonin. (One morning I woke up with traces of at least 7 dreams, although I managed to write down only 2. No lucid dreams, though.)
l-theanine (Examine.com) is occasionally mentioned on Reddit or Imminst or LessWrong32 but is rarely a top-level post or article; this is probably because theanine was discovered a very long time ago (>61 years ago), and it’s a pretty straightforward substance. It’s a weak relaxant/anxiolytic (Google Scholar) which is possibly responsible for a few of the health benefits of tea, and which works synergistically with caffeine (and is probably why caffeine delivered through coffee feels different from the same amount consumed in tea - in one study, separate caffeine and theanine were a mixed bag, but the combination beat placebo on all measurements). The half-life in humans seems to be pretty short, with van der Pijl 2010 putting it ~60 minutes. This suggests to me that regular tea consumption over a day is best, or at least that one should lower caffeine use - combining caffeine and theanine into a single-dose pill has the problem of caffeine’s half-life being much longer so the caffeine will be acting after the theanine has been largely eliminated. The problem with getting it via tea is that teas can vary widely in their theanine levels and the variations don’t seem to be consistent either, nor is it clear how to estimate them. (If you take a large dose in theanine like 400mg in water, you can taste the sweetness, but it’s subtle enough I doubt anyone can actually distinguish the theanine levels of tea; incidentally, r-theanine - the useless racemic other version - anecdotally tastes weaker and less sweet than l-theanine.)
In 2011, as part of the Silk Road research, I ordered 10x100mg Modalert (5btc) from a seller. I also asked him about his sourcing, since if it was bad, it’d be valuable to me to know whether it was sourced from one of the vendors listed in my table. He replied, more or less, I get them from a large Far Eastern pharmaceuticals wholesaler. I think they’re probably the supplier for a number of the online pharmacies. 100mg seems likely to be too low, so I treated this shipment as 5 doses:
10:30 AM; no major effect that I notice throughout the day - it’s neither good nor bad. This smells like placebo (and part of my mind is going how unlikely is it to get placebo 3 times in a row!, which is just the Gambler’s fallacy talking inasmuch as this is sampling with replacement). I give it 60% placebo; I check the next day right before taking, and it is. Man!
“I am nearly four years out from my traumatic brain injury and I have been through 100’s of hours of rehabilitation therapy. I have been surprised by how little attention is given to adequate nutrition for recovering from TBI. I’m always looking for further opportunities to recover and so this book fell into the right hands. Cavin outlines the science and reasoning behind the diet he suggests, but the real power in this book comes when he writes, “WE.” WE can give our brains proper nutrition. Now I’m excited to drink smoothies and eat breakfasts that look like dinners! I will recommend this book to my friends.
Creatine is a substance that’s produced in the human body. It is initially produced in the kidneys, and the process is completed in the liver. It is then stored in the brain tissues and muscles, to support the energy demands of a human body. Athletes and bodybuilders use creatine supplements to relieve fatigue and increase the recovery of the muscle tissues affected by vigorous physical activities. Apart from helping the tissues to recover faster, creatine also helps in enhancing the mental functions in sleep-deprived adults, and it also improves the performance of difficult cognitive tasks.
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Organizations, and even entire countries, are struggling with “always working” cultures. Germany and France have adopted rules to stop employees from reading and responding to email after work hours. Several companies have explored banning after-hours email; when one Italian company banned all email for one week, stress levels dropped among employees. This is not a great surprise: A Gallup study found that among those who frequently check email after working hours, about half report having a lot of stress.
Even party drugs are going to work: Biohackers are taking recreational drugs like LSD, psilocybin mushrooms, and mescaline in microdoses—about a tenth of what constitutes a typical dose—with the goal of becoming more focused and creative. Many who’ve tried it report positive results, but real research on the practice—and its safety—is a long way off. “Whether microdosing with LSD improves creativity and cognition remains to be determined in an objective experiment using double-blind, placebo-controlled methodology,” Sahakian says.
AMP was first investigated as an asthma medication in the 1920s, but its psychological effects were soon noticed. These included increased feelings of energy, positive mood, and prolonged physical endurance and mental concentration. These effects have been exploited in a variety of medical and nonmedical applications in the years since they were discovered, including to treat depression, to enhance alertness in military personnel, and to provide a competitive edge in athletic competition (Rasmussen, 2008). Today, AMP remains a widely used and effective treatment for ADHD (Wilens, 2006).
Phenotropil is an over-the-counter supplement similar in structure to Piracetam (and Noopept). This synthetic smart drug has been used to treat stroke, epilepsy and trauma recovery. A 2005 research paper also demonstrated that patients diagnosed with natural lesions or brain tumours see improvements in cognition. Phenylpiracetam intake can also result in minimised feelings of anxiety and depression. This is one of the more powerful unscheduled Nootropics available.
Somewhat ironically given the stereotypes, while I was in college I dabbled very little in nootropics, sticking to melatonin and tea. Since then I have come to find nootropics useful, and intellectually interesting: they shed light on issues in philosophy of biology & evolution, argue against naive psychological dualism and for materialism, offer cases in point on the history of technology & civilization or recent psychology theories about addiction & willpower, challenge our understanding of the validity of statistics and psychology - where they don’t offer nifty little problems in statistics and economics themselves, and are excellent fodder for the young Quantified Self movement4; modafinil itself demonstrates the little-known fact that sleep has no accepted evolutionary explanation. (The hard drugs also have more ramifications than one might expect: how can one understand the history of Southeast Asia and the Vietnamese War without reference to heroin, or more contemporaneously, how can one understand the lasting appeal of the Taliban in Afghanistan and the unpopularity & corruption of the central government without reference to the Taliban’s frequent anti-drug campaigns or the drug-funded warlords of the Northern Alliance?)
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.
Caffeine (Examine.com; FDA adverse events) is of course the most famous stimulant around. But consuming 200mg or more a day, I have discovered the downside: it is addictive and has a nasty withdrawal - headaches, decreased motivation, apathy, and general unhappiness. (It’s a little amusing to read academic descriptions of caffeine addiction9; if caffeine were a new drug, I wonder what Schedule it would be in and if people might be even more leery of it than modafinil.) Further, in some ways, aside from the ubiquitous placebo effect, caffeine combines a mix of weak performance benefits (Lorist & Snel 2008, Nehlig 2010) with some possible decrements, anecdotally and scientifically:
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?)
Tyrosine (Examine.com) is an amino acid; people on the Imminst.org forums (as well as Wikipedia) suggest that it helps with energy and coping with stress. I ordered 4oz (bought from Smart Powders) to try it out, and I began taking 1g with my usual caffeine+piracetam+choline mix. It does not dissolve easily in hot water, and is very chalky and not especially tasty. I have not noticed any particular effects from it.
Organizations, and even entire countries, are struggling with “always working” cultures. Germany and France have adopted rules to stop employees from reading and responding to email after work hours. Several companies have explored banning after-hours email; when one Italian company banned all email for one week, stress levels dropped among employees. This is not a great surprise: A Gallup study found that among those who frequently check email after working hours, about half report having a lot of stress.
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.
After I ran out of creatine, I noticed the increased difficulty, and resolved to buy it again at some point; many months later, there was a Smart Powders sale so bought it in my batch order, $12 for 1000g. As before, it made Taekwondo classes a bit easier. I paid closer attention this second time around and noticed that as one would expect, it only helped with muscular fatigue and did nothing for my aerobic issues. (I hate aerobic exercise, so it’s always been a weak point.) I eventually capped it as part of a sulbutiamine-DMAE-creatine-theanine mix. This ran out 1 May 2013. In March 2014, I spent $19 for 1kg of micronized creatine monohydrate to resume creatine use and also to use it as a placebo in a honey-sleep experiment testing Seth Roberts’s claim that a few grams of honey before bedtime would improve sleep quality: my usual flour placebo being unusable because the mechanism might be through simple sugars, which flour would digest into. (I did not do the experiment: it was going to be a fair amount of messy work capping the honey and creatine, and I didn’t believe Roberts’s claims for a second - my only reason to do it would be to prove the claim wrong but he’d just ignore me and no one else cares.) I didn’t try measuring out exact doses but just put a spoonful in my tea each morning (creatine is tasteless). The 1kg lasted from 25 March to 18 September or 178 days, so ~5.6g & $0.11 per day.
A new all-in-one nootropic mix/company run by some people active on /r/nootropics; they offered me a month’s supply for free to try & review for them. At ~$100 a month (it depends on how many months one buys), it is not cheap (John Backus estimates one could buy the raw ingredients for $25/month) but it provides convenience & is aimed at people uninterested in spending a great deal of time reviewing research papers & anecdotes or capping their own pills (ie. people with lives) and it’s unlikely I could spare the money to subscribe if TruBrain worked well for me - but certainly there was no harm in trying it out.
But he has also seen patients whose propensity for self-experimentation to improve cognition got out of hand. One chief executive he treated, Ngo said, developed an unhealthy predilection for albuterol, because he felt the asthma inhaler medicine kept him alert and productive long after others had quit working. Unfortunately, the drug ended up severely imbalancing his electrolytes, which can lead to dehydration, headaches, vision and cardiac problems, muscle contractions and, in extreme cases, seizures.
Because executive functions tend to work in concert with one another, these three categories are somewhat overlapping. For example, tasks that require working memory also require a degree of cognitive control to prevent current stimuli from interfering with the contents of working memory, and tasks that require planning, fluency, and reasoning require working memory to hold the task goals in mind. The assignment of studies to sections was based on best fit, according to the aspects of executive function most heavily taxed by the task, rather than exclusive category membership. Within each section, studies are further grouped according to the type of task and specific type of learning, working memory, cognitive control, or other executive function being assessed.
Caffeine (Examine.com; FDA adverse events) is of course the most famous stimulant around. But consuming 200mg or more a day, I have discovered the downside: it is addictive and has a nasty withdrawal - headaches, decreased motivation, apathy, and general unhappiness. (It’s a little amusing to read academic descriptions of caffeine addiction9; if caffeine were a new drug, I wonder what Schedule it would be in and if people might be even more leery of it than modafinil.) Further, in some ways, aside from the ubiquitous placebo effect, caffeine combines a mix of weak performance benefits (Lorist & Snel 2008, Nehlig 2010) with some possible decrements, anecdotally and scientifically:
When you hear about nootropics, often called “smart drugs,” you probably picture something like the scene above from Limitless, where Bradley Cooper’s character becomes brilliant after downing a strange pill. The drugs and supplements currently available don’t pack that strong of a punch, but the concept is basically the same. Many nootropics have promising benefits, like boosting memory, focus, or motivation, and there’s research to support specific uses. But the most effective nootropics, like Modafinil, aren’t intended for use without a prescription to treat a specific condition. In fact, recreational use of nootropics is hotly-debated among doctors and medical researchers. Many have concerns about the possible adverse effects of long-term use, as well as the ethics of using cognitive enhancers to gain an advantage in school, sports, or even everyday work.
First half at 6 AM; second half at noon. Wrote a short essay I’d been putting off and napped for 1:40 from 9 AM to 10:40. This approach seems to work a little better as far as the aboulia goes. (I also bother to smell my urine this time around - there’s a definite off smell to it.) Nights: 10:02; 8:50; 10:40; 7:38 (2 bad nights of nasal infections); 8:28; 8:20; 8:43 (▆▃█▁▂▂▃).
In contrast to the types of memory discussed in the previous section, which are long-lasting and formed as a result of learning, working memory is a temporary store of information. Working memory has been studied extensively by cognitive psychologists and cognitive neuroscientists because of its role in executive function. It has been likened to an internal scratch pad; by holding information in working memory, one keeps it available to consult and manipulate in the service of performing tasks as diverse as parsing a sentence and planning a route through the environment. Presumably for this reason, working memory ability correlates with measures of general intelligence (Friedman et al., 2006). The possibility of enhancing working memory ability is therefore of potential real-world interest.
After 7 days, I ordered a kg of choline bitartrate from Bulk Powders. Choline is standard among piracetam-users because it is pretty universally supported by anecdotes about piracetam headaches, has support in rat/mice experiments27, and also some human-related research. So I figured I couldn’t fairly test piracetam without some regular choline - the eggs might not be enough, might be the wrong kind, etc. It has a quite distinctly fishy smell, but the actual taste is more citrus-y, and it seems to neutralize the piracetam taste in tea (which makes things much easier for me).
The question of whether stimulants are smart pills in a pragmatic sense cannot be answered solely by consideration of the statistical significance of the difference between stimulant and placebo. A drug with tiny effects, even if statistically significant, would not be a useful cognitive enhancer for most purposes. We therefore report Cohen’s d effect size measure for published studies that provide either means and standard deviations or relevant F or t statistics (Thalheimer & Cook, 2002). More generally, with most sample sizes in the range of a dozen to a few dozen, small effects would not reliably be found.

Some smart drugs can be found in health food stores; others are imported or are drugs that are intended for other disorders such as Alzheimer's disease and Parkinson's disease. There are many Internet web sites, books, magazines and newspaper articles detailing the supposed effects of smart drugs. There are also plenty of advertisements and mail-order businesses that try to sell "smart drugs" to the public. However, rarely do these businesses or the popular press report results that show the failure of smart drugs to improve memory or learning. Rather, they try to show that their products have miraculous effects on the brain and can improve mental functioning. Wouldn't it be easy to learn something by "popping a pill" or drinking a soda laced with a smart drug? This would be much easier than taking the time to study. Feeling dull? Take your brain in for a mental tune up by popping a pill!
Caffeine keeps you awake, which keeps you coding. It may also be a nootropic, increasing brain-power. Both desirable results. However, it also inhibits vitamin D receptors, and as such decreases the body’s uptake of this-much-needed-vitamin. OK, that’s not so bad, you’re not getting the maximum dose of vitamin D. So what? Well, by itself caffeine may not cause you any problems, but combined with cutting off a major source of the vitamin - the production via sunlight - you’re leaving yourself open to deficiency in double-quick time.
Given the size of the literature just reviewed, it is surprising that so many basic questions remain open. Although d-AMP and MPH appear to enhance retention of recently learned information and, in at least some individuals, also enhance working memory and cognitive control, there remains great uncertainty regarding the size and robustness of these effects and their dependence on dosage, individual differences, and specifics of the task.
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.

Piracetam is a reliable supplement for improving creativity. It is an entry level racetam due to its lack of severe side effects and relative subtlety. Piracetam’s effects take hold over time through continual use. There is less instant gratification compared to other brain enhancers. Additionally, this nootropic can enhance holistic thinking, verbal memory, and mental energy levels.
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.)
(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.)

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.
Some of the newest substances being used as ‘smart drugs’ are medically prescribed for other conditions. For example, methylphenidate, commonly known as Ritalin, is used to treat attention deficit hyperactivity disorder (ADHD). So is Adderall, a combination drug containing two forms of amphetamine. These are among a suite of pharmaceuticals now being used by healthy people, particularly university students, to enhance their capabilities for learning or working. 

Remember: The strictest definition of nootropics today says that for a substance to be a true brain-boosting nootropic it must have low toxicity and few side effects. Therefore, by definition, a nootropic is safe to use. However, when people start stacking nootropics indiscriminately, taking megadoses, or importing them from unknown suppliers that may have poor quality control, it’s easy for safety concerns to start creeping in.
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.
These pills don’t work. The reality is that MOST of these products don’t work effectively. Maybe we’re cynical, but if you simply review the published studies on memory pills, you can quickly eliminate many of the products that don’t have “the right stuff.” The active ingredients in brain and memory health pills are expensive and most companies sell a watered down version that is not effective for memory and focus. The more brands we reviewed, the more we realized that many of these marketers are slapping slick labels on low-grade ingredients.
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.
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%.

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%.
The fish oil can be considered a free sunk cost: I would take it in the absence of an experiment. The empty pill capsules could be used for something else, so we’ll put the 500 at $5. Filling 500 capsules with fish and olive oil will be messy and take an hour. Taking them regularly can be added to my habitual morning routine for vitamin D and the lithium experiment, so that is close to free but we’ll call it an hour over the 250 days. Recording mood/productivity is also free a sunk cost as it’s necessary for the other experiments; but recording dual n-back scores is more expensive: each round is ~2 minutes and one wants >=5, so each block will cost >10 minutes, so 18 tests will be >180 minutes or >3 hours. So >5 hours. Total: 5 + (>5 \times 7.25) = >41.
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.
To make things more interesting, I think I would like to try randomizing different dosages as well: 12mg, 24mg, and 36mg (1-3 pills); on 5 May 2014, because I wanted to finish up the experiment earlier, I decided to add 2 larger doses of 48 & 60mg (4-5 pills) as options. Then I can include the previous pilot study as 10mg doses, and regress over dose amount.
Among the questions to be addressed in the present article are, How widespread is the use of prescription stimulants for cognitive enhancement? Who uses them, for what specific purposes? Given that nonmedical use of these substances is illegal, how are they obtained? Furthermore, do these substances actually enhance cognition? If so, what aspects of cognition do they enhance? Is everyone able to be enhanced, or are some groups of healthy individuals helped by these drugs and others not? The goal of this article is to address these questions by reviewing and synthesizing findings from the existing scientific literature. We begin with a brief overview of the psychopharmacology of the two most commonly used prescription stimulants.
Eugeroics (armodafinil and modafinil) – are classified as "wakefulness promoting" agents; modafinil increased alertness, particularly in sleep deprived individuals, and was noted to facilitate reasoning and problem solving in non-ADHD youth.[23] In a systematic review of small, preliminary studies where the effects of modafinil were examined, when simple psychometric assessments were considered, modafinil intake appeared to enhance executive function.[27] Modafinil does not produce improvements in mood or motivation in sleep deprived or non-sleep deprived individuals.[28]
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