Participants (n=205) [young adults aged 18-30 years] were recruited between July 2010 and January 2011, and were randomized to receive either a daily 150 µg (0.15mg) iodine supplement or daily placebo supplement for 32 weeks…After adjusting for baseline cognitive test score, examiner, age, sex, income, and ethnicity, iodine supplementation did not significantly predict 32 week cognitive test scores for Block Design (p=0.385), Digit Span Backward (p=0.474), Matrix Reasoning (p=0.885), Symbol Search (p=0.844), Visual Puzzles (p=0.675), Coding (p=0.858), and Letter-Number Sequencing (p=0.408).
Results: Women with high caffeine intakes had significantly higher rates of bone loss at the spine than did those with low intakes (−1.90 ± 0.97% compared with 1.19 ± 1.08%; P = 0.038). When the data were analyzed according to VDR genotype and caffeine intake, women with the tt genotype had significantly (P = 0.054) higher rates of bone loss at the spine (−8.14 ± 2.62%) than did women with the TT genotype (−0.34 ± 1.42%) when their caffeine intake was >300 mg/d…In 1994, Morrison et al (22) first reported an association between vitamin D receptor gene (VDR) polymorphism and BMD of the spine and hip in adults. After this initial report, the relation between VDR polymorphism and BMD, bone turnover, and bone loss has been extensively evaluated. The results of some studies support an association between VDR polymorphism and BMD (23-,25), whereas other studies showed no evidence for this association (26,27)…At baseline, no significant differences existed in serum parathyroid hormone, serum 25-hydroxyvitamin D, serum osteocalcin, and urinary N-telopeptide between the low- and high-caffeine groups (Table 1⇑). In the longitudinal study, the percentage of change in serum parathyroid hormone concentrations was significantly lower in the high-caffeine group than in the low-caffeine group (Table 2⇑). However, no significant differences existed in the percentage of change in serum 25-hydroxyvitamin D
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.
However, normally when you hear the term nootropic kicked around, people really mean a “cognitive enhancer” — something that does benefit thinking in some way (improved memory, faster speed-of-processing, increased concentration, or a combination of these, etc.), but might not meet the more rigorous definition above.  “Smart drugs” is another largely-interchangeable term.

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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.

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?
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.
Noopept shows a much greater affinity for certain receptor sites in the brain than racetams, allowing doses as small as 10-30mg to provide increased focus, improved logical thinking function, enhanced short and long-term memory functions, and increased learning ability including improved recall. In addition, users have reported a subtle psychostimulatory effect.
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.)
Phenserine, as well as the drugs Aricept and Exelon, which are already on the market, work by increasing the level of acetylcholine, a neurotransmitter that is deficient in people with the disease. A neurotransmitter is a chemical that allows communication between nerve cells in the brain. In people with Alzheimer's disease, many brain cells have died, so the hope is to get the most out of those that remain by flooding the brain with acetylcholine.
I have elsewhere remarked on the apparent lack of benefit to taking multivitamins and the possible harm; so one might well wonder about a specific vitamin like vitamin D. However, a multivitamin is not vitamin D, so it’s no surprise that they might do different things. If a multivitamin had no vitamin D in it, or if it had vitamin D in different doses, or if it had substances which interacted with vitamin D (such as calcium), or if it had substances which had negative effects which outweigh the positive (such as vitamin A?), we could well expect differing results. In this case, all of those are true to varying extents. Some multivitamins I’ve had contained no vitamin D. The last multivitamin I was taking both contains vitamins used in the negative trials and also some calcium; the listed vitamin D dosage was a trivial ~400IU, while I take >10x as much now (5000IU).
Despite decades of study, a full picture has yet to emerge of the cognitive effects of the classic psychostimulants and modafinil. Part of the problem is that getting rats, or indeed students, to do puzzles in laboratories may not be a reliable guide to the drugs’ effects in the wider world. Drugs have complicated effects on individuals living complicated lives. Determining that methylphenidate enhances cognition in rats by acting on their prefrontal cortex doesn’t tell you the potential impact that its effects on mood or motivation may have on human cognition.
Another prescription stimulant medication, modafinil (known by the brand name Provigil), is usually prescribed to patients suffering from narcolepsy and shift-work sleep disorder, but it might turn out to have broader applications. “We have conducted at the University of Cambridge double-blind, placebo-controlled studies in healthy people using modafinil and have found improvements in cognition, including in working memory,” Sahakian says. However, she doesn’t think everyone should start using the drug off-label. “There are no long-term safety and efficacy studies of modafinil in healthy people, and so it is unclear what the risks might be.”
On the plus side: - I noticed the less-fatigue thing to a greater extent, getting out of my classes much less tired than usual. (Caveat: my sleep schedule recently changed for the saner, so it’s possible that’s responsible. I think it’s more the piracetam+choline, though.) - One thing I wasn’t expecting was a decrease in my appetite - nobody had mentioned that in their reports.I don’t like being bothered by my appetite (I know how to eat fine without it reminding me), so I count this as a plus. - Fidgeting was reduced further

In general, I feel a little bit less alert, but still close to normal. By 6PM, I have a mild headache, but I try out 30 rounds of gbrainy (haven’t played it in months) and am surprised to find that I reach an all-time high; no idea whether this is due to DNB or not, since Gbrainy is very heavily crystallized (half the challenge disappears as you learn how the problems work), but it does indicate I’m not deluding myself about mental ability. (To give a figure: my last score well before I did any DNB was 64, and I was doing well that day; on modafinil, I had a 77.) I figure the headache might be food related, eat, and by 7:30 the headache is pretty much gone and I’m fine up to midnight.
Nootropics, also known as ‘brain boosters,’ ‘brain supplements’ or ‘cognitive enhancers’ are made up of a variety of artificial and natural compounds. These compounds help in enhancing the cognitive activities of the brain by regulating or altering the production of neurochemicals and neurotransmitters in the brain. It improves blood flow, stimulates neurogenesis (the process by which neurons are produced in the body by neural stem cells), enhances nerve growth rate, modifies synapses, and improves cell membrane fluidity. Thus, positive changes are created within your body, which helps you to function optimally irrespective of your current lifestyle and individual needs.
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:
Smart drugs act within the brain speeding up chemical transfers, acting as neurotransmitters, or otherwise altering the exchange of brain chemicals. There are typically very few side effects, and they are considered generally safe when used as indicated. Special care should be used by those who have underlying health conditions, are on other medications, pregnant women, and children, as there is no long-term data on the use and effects of nootropics in these groups.

During the 1920s, Amphetamine was being researched as an asthma medication when its cognitive benefits were accidentally discovered. In many years that followed, this enhancer was exploited in a number of medical and nonmedical applications, for instance, to enhance alertness in military personnel, treat depression, improve athletic performance, etc.

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.
Powders are good for experimenting with (easy to vary doses and mix), but not so good for regular taking. I use OO gel capsules with a Capsule Machine: it’s hard to beat $20, it works, it’s not that messy after practice, and it’s not too bad to do 100 pills. However, I once did 3kg of piracetam + my other powders, and doing that nearly burned me out on ever using capsules again. If you’re going to do that much, something more automated is a serious question! (What actually wound up infuriating me the most was when capsules would stick in either the bottom or top try - requiring you to very gingerly pull and twist them out, lest the two halves slip and spill powder - or when the two halves wouldn’t lock and you had to join them by hand. In contrast: loading the gel caps could be done automatically without looking, after some experience.)

Kennedy et al. (1990) administered what they termed a grammatical reasoning task to subjects, in which a sentence describing the order of two letters, A and B, is presented along with the letter pair, and subjects must determine whether or not the sentence correctly describes the letter pair. They found no effect of d-AMP on performance of this task.


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%.
(On a side note, I think I understand now why modafinil doesn’t lead to a Beggars in Spain scenario; BiS includes massive IQ and motivation boosts as part of the Sleepless modification. Just adding 8 hours a day doesn’t do the world-changing trick, no more than some researchers living to 90 and others to 60 has lead to the former taking over. If everyone were suddenly granted the ability to never need sleep, many of them would have no idea what to do with the extra 8 or 9 hours and might well be destroyed by the gift; it takes a lot of motivation to make good use of the time, and if one cannot, then it is a curse akin to the stories of immortals who yearn for death - they yearn because life is not a blessing to them, though that is a fact more about them than life.)
Soldiers should never be treated like children; because then they will act like them. However, There’s a reason why the 1SG is known as the Mother of the Company and the Platoon Sergeant is known as a Platoon Daddy. Because they run the day to day operations of the household, get the kids to school so to speak, and focus on the minutia of readiness and operational execution in all its glory. Officers forget they are the second link in the Chain of Command and a well operating duo of Team Leader and Squad Leader should be handling 85% of all Soldier issues, while the Platoon sergeant handles the other 15% with 1SG. Platoon Leaders and Commanders should always be present; training, leading by example, focusing on culture building, tracking and supporting NCO’s. They should be focused on big business sides of things, stepping in to administer punishment or award and reward performance. If an officer at any level is having to step into a Soldier's day to day lives an NCO at some level is failing. Officers should be junior Officers and junior Enlisted right along side their counterparts instead of eating their young and touting their “maturity” or status. If anything Officers should be asking their NCO’s where they should effect, assist, support or provide cover toward intitiatives and plans that create consistency and controlled chaos for growth of individuals two levels up and one level down of operational capabilities at every echelon of command.

I can test fish oil for mood, since the other claimed benefits like anti-schizophrenia are too hard to test. The medical student trial (Kiecolt-Glaser et al 2011) did not see changes until visit 3, after 3 weeks of supplementation. (Visit 1, 3 weeks, visit 2, supplementation started for 3 weeks, visit 3, supplementation continued 3 weeks, visit 4 etc.) There were no tests in between the test starting week 1 and starting week 3, so I can’t pin it down any further. This suggests randomizing in 2 or 3 week blocks. (For an explanation of blocking, see the footnote in the Zeo page.)

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?


Medication can be ineffective if the drug payload is not delivered at its intended place and time. Since an oral medication travels through a broad pH spectrum, the pill encapsulation could dissolve at the wrong time. However, a smart pill with environmental sensors, a feedback algorithm and a drug release mechanism can give rise to smart drug delivery systems. This can ensure optimal drug delivery and prevent accidental overdose.
Even though smart drugs come with a long list of benefits, their misuse can cause negative side effects. Excess use can cause anxiety, fear, headaches, increased blood pressure, and more. Considering this, it is imperative to study usage instructions: how often can you take the pill, the correct dosage and interaction with other medication/supplements.
The 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.
Elaborating on why the psychological side effects of testosterone injection are individual dependent: Not everyone get the same amount of motivation and increased goal seeking from the steroid and most people do not experience periods of chronic avolition. Another psychological effect is a potentially drastic increase in aggression which in turn can have negative social consequences. In the case of counterfactual Wedrifid he gets a net improvement in social consequences. He has observed that aggression and anger are a prompt for increased ruthless self-interested goal seeking. Ruthless self-interested goal seeking involves actually bothering to pay attention to social politics. People like people who do social politics well. Most particularly it prevents acting on contempt which is what Wedrifid finds prompts the most hostility and resentment in others. Point is, what is a sanity promoting change in one person may not be in another.
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.
But, if we find in 10 or 20 years that the drugs don't do damage, what are the benefits? These are stimulants that help with concentration. College students take such drugs to pass tests; graduates take them to gain professional licenses. They are akin to using a calculator to solve an equation. Do you really want a doctor who passed his boards as a result of taking speed — and continues to depend on that for his practice?
MPH was developed more recently and marketed primarily for ADHD, although it is sometimes prescribed off label or used nonmedically to increase alertness, energy, or concentration in conditions other than ADHD. Both MPH and AMP are on the list of substances banned from sports competitions by the World Anti-Doping Agency (Docherty, 2008). Both also have the potential for abuse and dependence, which detracts from their usefulness and is the reason for their classification as Schedule II controlled substances. Although the risk of developing dependence on these drugs is believed to be low for individuals taking them for ADHD, the Schedule II classification indicates that these drugs have a high potential for abuse and that abuse may lead to severe dependence.
I posted a link to the survey on my Google+ account, and inserted the link at the top of all gwern.net pages; 51 people completed all 11 binary choices (most of them coming from North America & Europe), which seems adequate since the 11 questions are all asking the same question, and 561 responses to one question is quite a few. A few different statistical tests seem applicable: a chi-squared test whether there’s a difference between all the answers, a two-sample test on the averages, and most meaningfully, summing up the responses as a single pair of numbers and doing a binomial test:
We reviewed recent studies concerning prescription stimulant use specifically among students in the United States and Canada, using the method illustrated in Figure 1. Although less informative about the general population, these studies included questions about students’ specific reasons for using the drugs, as well as frequency of use and means of obtaining them. These studies typically found rates of use greater than those reported by the nationwide NSDUH or the MTF surveys. This probably reflects a true difference in rates of usage among the different populations. In support of that conclusion, the NSDUH data for college age Americans showed that college students were considerably more likely than nonstudents of the same age to use prescription stimulants nonmedically (odds ratio: 2.76; Herman-Stahl, Krebs, Kroutil, & Heller, 2007).
The majority of studies seem to be done on types of people who are NOT buying nootropics. Like the elderly, people with blatant cognitive deficits, etc. This is analogous to some of the muscle-building research but more extreme. Like there are studies on some compound increasing muscle growth in elderly patients or patients with wasting, and supplement companies use some of those studies to back their supplements.
This world is a competitive place. If you’re not seeking an advantage, you’ll get passed by those who do. Whether you’re studying for a final exam or trying to secure a big business deal, you need a definitive mental edge. Are smart drugs and brain-boosting pills the answer for cognitive enhancement in 2019? If you’re not cheating, you’re not trying, right? Bad advice for some scenarios, but there is a grain of truth to every saying—even this one.

Similar to the way in which some athletes used anabolic steroids (muscle-building hormones) to artificially enhance their physique, some students turned to smart drugs, particularly Ritalin and Adderall, to heighten their intellectual abilities. A 2005 study reported that, at some universities in the United States, as many as 7 percent of respondents had used smart drugs at least once in their lifetime and 2.1 percent had used smart drugs in the past month. Modafinil was used increasingly by persons who sought to recover quickly from jet lag and who were under heavy work demands. Military personnel were given the same drug when sent on missions with extended flight times.


From the standpoint of absorption, the drinking of tobacco juice and the interaction of the infusion or concoction with the small intestine is a highly effective method of gastrointestinal nicotine administration. The epithelial area of the intestines is incomparably larger than the mucosa of the upper tract including the stomach, and the small intestine represents the area with the greatest capacity for absorption (Levine 1983:81-83). As practiced by most of the sixty-four tribes documented here, intoxicated states are achieved by drinking tobacco juice through the mouth and/or nose…The large intestine, although functionally little equipped for absorption, nevertheless absorbs nicotine that may have passed through the small intestine.

It isn’t unlikely to hear someone from Silicon Valley say the following: “I’ve just cycled off a stack of Piracetam and CDP-Choline because I didn’t get the mental acuity I was expecting. I will try a blend of Noopept and Huperzine A for the next two weeks and see if I can increase my output by 10%. We don’t have immortality yet and I would really like to join the three comma club before it’s all over.”
If this is the case, this suggests some thoughtfulness about my use of nicotine: there are times when use of nicotine will not be helpful, but times where it will be helpful. I don’t know what makes the difference, but I can guess it relates to over-stimulation: on some nights during the experiment, I had difficult concentrating on n-backing because it was boring and I was thinking about the other things I was interested in or working on - in retrospect, I wonder if those instances were nicotine nights.
Turning to analyses related specifically to the drugs that are the subject of this article, reanalysis of the 2002 NSDUH data by Kroutil and colleagues (2006) found past-year nonmedical use of stimulants other than methamphetamine by 2% of individuals between the ages of 18 and 25 and by 0.3% of individuals 26 years of age and older. For ADHD medications in particular, these rates were 1.3% and 0.1%, respectively. Finally, Novak, Kroutil, Williams, and Van Brunt (2007) surveyed a sample of over four thousand individuals from the Harris Poll Online Panel and found that 4.3% of those surveyed between the ages of 18 and 25 had used prescription stimulants nonmedically in the past year, compared with only 1.3% between the ages of 26 and 49.
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.
As I am not any of the latter, I didn’t really expect a mental benefit. As it happens, I observed nothing. What surprised me was something I had forgotten about: its physical benefits. My performance in Taekwondo classes suddenly improved - specifically, my endurance increased substantially. Before, classes had left me nearly prostrate at the end, but after, I was weary yet fairly alert and happy. (I have done Taekwondo since I was 7, and I have a pretty good sense of what is and is not normal performance for my body. This was not anything as simple as failing to notice increasing fitness or something.) This was driven home to me one day when in a flurry before class, I prepared my customary tea with piracetam, choline & creatine; by the middle of the class, I was feeling faint & tired, had to take a break, and suddenly, thunderstruck, realized that I had absentmindedly forgot to actually drink it! This made me a believer.

Nootropics are a specific group of smart drugs. But nootropics aren’t the only drugs out there that promise you some extra productivity. More students and office workers are using drugs to increase their productivity than ever before [79]. But unlike with nootropics, many have side-effects. And that is precisely what is different between nootropics and other enhancing drugs, nootropics have little to no negative side-effects.
For 2 weeks, upon awakening I took close-up photographs of my right eye. Then I ordered two jars of Life-Extension Sea-Iodine (60x1mg) (1mg being an apparently safe dose), and when it arrived on 10 September 2012, I stopped the photography and began taking 1 iodine pill every other day. I noticed no ill effects (or benefits) after a few weeks and upped the dose to 1 pill daily. After the first jar of 60 pills was used up, I switched to the second jar, and began photography as before for 2 weeks. The photographs were uploaded, cropped by hand in Gimp, and shrunk to more reasonable dimensions; both sets are available in a Zip file.

To judge from recent reports in the popular media, healthy people have also begun to use MPH and AMPs for cognitive enhancement. Major daily newspapers such as The New York Times, The LA Times, and The Wall Street Journal; magazines including Time, The Economist, The New Yorker, and Vogue; and broadcast news organizations including the BBC, CNN, and NPR have reported a trend toward growing use of prescription stimulants by healthy people for the purpose of enhancing school or work performance.


This looks interesting: the Noopept effect is positive for all the dose levels, but it looks like a U-curve - low at 10mg, high at 15mg, lower at 20mg, and even lower at 30mg 48mg and 60mg aren’t estimated because they are hit by the missingness problem: the magnesium citrate variable is unavailable for the days the higher doses were taken on, and so their days are omitted and those levels of the factor are not estimated. One way to fix this is to drop magnesium from the model entirely, at the cost of fitting the data much more poorly and losing a lot of R2:
That first night, I had severe trouble sleeping, falling asleep in 30 minutes rather than my usual 19.6±11.9, waking up 12 times (5.9±3.4), and spending ~90 minutes awake (18.1±16.2), and naturally I felt unrested the next day; I initially assumed it was because I had left a fan on (moving air keeps me awake) but the new potassium is also a possible culprit. When I asked, Kevin said:

28,61,36,25,61,57,39,56,23,37,24,50,54,32,50,33,16,42,41,40,34,33,31,65,23,36,29,51,46,31,45,52,30, 50,29,36,57,60,34,48,32,41,48,34,51,40,53,73,56,53,53,57,46,50,35,50,60,62,30,60,48,46,52,60,60,48, 47,34,50,51,45,54,70,48,61,43,53,60,44,57,50,50,52,37,55,40,53,48,50,52,44,50,50,38,43,66,40,24,67, 60,71,54,51,60,41,58,20,28,42,53,59,42,31,60,42,58,36,48,53,46,25,53,57,60,35,46,32,26,68,45,20,51, 56,48,25,62,50,54,47,42,55,39,60,44,32,50,34,60,47,70,68,38,47,48,70,51,42,41,35,36,39,23,50,46,44,56,50,39


2 break days later, I took the quarter-pill at 11:22 PM. I had discovered I had for years physically possessed a very long interview not available online, and transcribing that seemed like a good way to use up a few hours. I did some reading, some Mnemosyne, and started it around midnight, finishing around 2:30 AM. There seemed a mental dip around 30 minutes after the armodafinil, but then things really picked up and I made very good progress transcribing the final draft of 9000 words in that period. (In comparison, The Conscience of the Otaking parts 2 & 4 were much easier to read than the tiny font of the RahXephon booklet, took perhaps 3 hours, and totaled only 6500 words. The nicotine is probably also to thank.) By 3:40 AM, my writing seems to be clumsier and my mind fogged. Began DNB at 3:50: 61/53/44. Went to bed at 4:05, fell asleep in 16 minutes, slept for 3:56. Waking up was easier and I felt better, so the extra hour seemed to help.


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.

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.)
It isn’t unlikely to hear someone from Silicon Valley say the following: “I’ve just cycled off a stack of Piracetam and CDP-Choline because I didn’t get the mental acuity I was expecting. I will try a blend of Noopept and Huperzine A for the next two weeks and see if I can increase my output by 10%. We don’t have immortality yet and I would really like to join the three comma club before it’s all over.”
The placebos can be the usual pills filled with olive oil. The Nature’s Answer fish oil is lemon-flavored; it may be worth mixing in some lemon juice. In Kiecolt-Glaser et al 2011, anxiety was measured via the Beck Anxiety scale; the placebo mean was 1.2 on a standard deviation of 0.075, and the experimental mean was 0.93 on a standard deviation of 0.076. (These are all log-transformed covariates or something; I don’t know what that means, but if I naively plug those numbers into Cohen’s d, I get a very large effect: \frac{1.2 - 0.93}{0.076}=3.55.)

Unfortunately, cognitive enhancement falls between the stools of research funding, which makes it unlikely that such research programs will be carried out. Disease-oriented funders will, by definition, not support research on normal healthy individuals. The topic intersects with drug abuse research only in the assessment of risk, leaving out the study of potential benefits, as well as the comparative benefits of other enhancement methods. As a fundamentally applied research question, it will not qualify for support by funders of basic science. The pharmaceutical industry would be expected to support such research only if cognitive enhancement were to be considered a legitimate indication by the FDA, which we hope would happen only after considerably more research has illuminated its risks, benefits, and societal impact. Even then, industry would have little incentive to delve into all of the issues raised here, including the comparison of drug effects to nonpharmaceutical means of enhancing cognition.
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.
Low-tech methods of cognitive enhancement include many components of what has traditionally been viewed as a healthy lifestyle, such as exercise, good nutrition, adequate sleep, and stress management. These low-tech methods nevertheless belong in a discussion of brain enhancement because, in addition to benefiting cognitive performance, their effects on brain function have been demonstrated (Almeida et al., 2002; Boonstra, Stins, Daffertshofer, & Beek, 2007; Hillman, Erickson, & Kramer, 2008; Lutz, Slagter, Dunne, & Davidson, 2008; Van Dongen, Maislin, Mullington, & Dinges, 2003).
Lebowitz says that if you're purchasing supplements to improve your brain power, you're probably wasting your money. "There is nothing you can buy at your local health food store that will improve your thinking skills," Lebowitz says. So that turmeric latte you've been drinking everyday has no additional brain benefits compared to a regular cup of java.
MPH was developed more recently and marketed primarily for ADHD, although it is sometimes prescribed off label or used nonmedically to increase alertness, energy, or concentration in conditions other than ADHD. Both MPH and AMP are on the list of substances banned from sports competitions by the World Anti-Doping Agency (Docherty, 2008). Both also have the potential for abuse and dependence, which detracts from their usefulness and is the reason for their classification as Schedule II controlled substances. Although the risk of developing dependence on these drugs is believed to be low for individuals taking them for ADHD, the Schedule II classification indicates that these drugs have a high potential for abuse and that abuse may lead to severe dependence.

When Giurgea coined the word nootropic (combining the Greek words for mind and bending) in the 1970s, he was focused on a drug he had synthesized called piracetam. Although it is approved in many countries, it isn’t categorized as a prescription drug in the United States. That means it can be purchased online, along with a number of newer formulations in the same drug family (including aniracetam, phenylpiracetam, and oxiracetam). Some studies have shown beneficial effects, including one in the 1990s that indicated possible improvement in the hippocampal membranes in Alzheimer’s patients. But long-term studies haven’t yet borne out the hype.
The hormone testosterone (Examine.com; FDA adverse events) needs no introduction. This is one of the scariest substances I have considered using: it affects so many bodily systems in so many ways that it seems almost impossible to come up with a net summary, either positive or negative. With testosterone, the problem is not the usual nootropics problem that that there is a lack of human research, the problem is that the summary constitutes a textbook - or two. That said, the 2011 review The role of testosterone in social interaction (excerpts) gives me the impression that testosterone does indeed play into risk-taking, motivation, and social status-seeking; some useful links and a representative anecdote:
Racetams are the best-known smart drugs on the market, and have decades of widespread use behind them. Piracetam is a leading smart drug, commonly prescribed to seniors with Alzheimer’s or pre-dementia symptoms – but studies have shown Piracetam’s beneficial effects extend to people of all ages, as young as university students. The Racetams speed up chemical exchange between brain cells. Effects include increases in verbal learning, mental clarity, and general IQ. Other members of the Racetam family include Pramiracetam, Oxiracetam, аnԁ Aniracetam, which differ from Piracetam primarily in their potency, not their actual effects.

The next cheap proposition to test is that the 2ml dose is so large that the sedation/depressive effect of nicotine has begun to kick in. This is easy to test: take much less, like half a ml. I do so two or three times over the next day, and subjectively the feeling seems to be the same - which seems to support that proposition (although perhaps I’ve been placebo effecting myself this whole time, in which case the exact amount doesn’t matter). If this theory is true, my previous sleep results don’t show anything; one would expect nicotine-as-sedative to not hurt sleep or improve it. I skip the day (no cravings or addiction noticed), and take half a ml right before bed at 11:30; I fall asleep in 12 minutes and have a ZQ of ~105. The next few days I try putting one or two drops into the tea kettle, which seems to work as well (or poorly) as before. At that point, I was warned that there were some results that nicotine withdrawal can kick in with delays as long as a week, so I shouldn’t be confident that a few days off proved an absence of addiction; I immediately quit to see what the week would bring. 4 or 7 days in, I didn’t notice anything. I’m still using it, but I’m definitely a little nonplussed and disgruntled - I need some independent source of nicotine to compare with!
More than once I have seen results indicating that high-IQ types benefit the least from random nootropics; nutritional deficits are the premier example, because high-IQ types almost by definition suffer from no major deficiencies like iodine. But a stimulant modafinil may be another such nootropic (see Cognitive effects of modafinil in student volunteers may depend on IQ, Randall et al 2005), which mentions:
And as before, around 9 AM I began to feel the peculiar feeling that I was mentally able and apathetic (in a sort of aboulia way); so I decided to try what helped last time, a short nap. But this time, though I took a full hour, I slept not a wink and my Zeo recorded only 2 transient episodes of light sleep! A back-handed sort of proof of alertness, I suppose. I didn’t bother trying again. The rest of the day was mediocre, and I wound up spending much of it on chores and whatnot out of my control. Mentally, I felt better past 3 PM.
Can brain enhancing pills actually improve memory? This is a common question and the answer varies, depending on the product you are considering. The top 25 brain enhancement supplements appear to produce results for many users. Research and scientific studies have demonstrated the brain boosting effects of nootropic ingredients in the best quality supplements. At Smart Pill Guide, you can read nootropics reviews and discover how to improve memory for better performance in school or at work.

This formula presents a relatively high price and one bottle of 60 tables, at the recommended dosage of two tablets per day with a meal, a bottle provides a month’s supply. The secure online purchase is available on the manufacturer’s site as well as at several online retailers. Although no free trials or money back guarantees are available at this time, the manufacturer provides free shipping if the desired order exceeds a certain amount. With time different online retailers could offer some advantages depending on the amount purchased, so an online research is advised before purchase, as to assess the market and find the best solution.
Because these drugs modulate important neurotransmitter systems such as dopamine and noradrenaline, users take significant risks with unregulated use. There has not yet been any definitive research into modafinil's addictive potential, how its effects might change with prolonged sleep deprivation, or what side effects are likely at doses outside the prescribed range.
Medication can be ineffective if the drug payload is not delivered at its intended place and time. Since an oral medication travels through a broad pH spectrum, the pill encapsulation could dissolve at the wrong time. However, a smart pill with environmental sensors, a feedback algorithm and a drug release mechanism can give rise to smart drug delivery systems. This can ensure optimal drug delivery and prevent accidental overdose.
Piracetam is well studied and is credited by its users with boosting their memory, sharpening their focus, heightening their immune system, even bettering their personalities. But it’s only one of many formulations in the racetam drug family. Newer ones include aniracetam, phenylpiracetam and oxiracetam. All are available online, where their efficacy and safety are debated and reviewed on message boards and in podcasts.
The smart pill industry has popularized many herbal nootropics. Most of them first appeared in Ayurveda and traditional Chinese medicine. Ayurveda is a branch of natural medicine originating from India. It focuses on using herbs as remedies for improving quality of life and healing ailments. Evidence suggests our ancestors were on to something with this natural approach.
Most diehard nootropic users have considered using racetams for enhancing brain function. Racetams are synthetic nootropic substances first developed in Russia. These smart drugs vary in potency, but they are not stimulants. They are unlike traditional ADHD medications (Adderall, Ritalin, Vyvanse, etc.). Instead, racetams boost cognition by enhancing the cholinergic system.
Jesper Noehr, 30, reels off the ingredients in the chemical cocktail he’s been taking every day before work for the past six months. It’s a mixture of exotic dietary supplements and research chemicals that he says gives him an edge in his job without ill effects: better memory, more clarity and focus and enhanced problem-solving abilities. “I can keep a lot of things on my mind at once,” says Noehr, who is chief technology officer for a San Francisco startup.
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.
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.
Even though smart drugs come with a long list of benefits, their misuse can cause negative side effects. Excess use can cause anxiety, fear, headaches, increased blood pressure, and more. Considering this, it is imperative to study usage instructions: how often can you take the pill, the correct dosage and interaction with other medication/supplements.
Before you try nootropics, I suggest you start with the basics: get rid of the things in your diet and life that reduce cognitive performance first. That is easiest. Then, add in energizers like Brain Octane and clean up your diet. Then, go for the herbals and the natural nootropics. Use the pharmaceuticals selectively only after you’ve figured out your basics.
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