That it is somewhat valuable is clear if we consider it under another guise. Imagine you received the same salary you do, but paid every day. Accounting systems would incur considerable costs handling daily payments, since they would be making so many more and so much smaller payments, and they would have to know instantly whether you showed up to work that day and all sorts of other details, and the recipients themselves would waste time dealing with all these checks or looking through all the deposits to their account, and any errors would be that much harder to track down. (And conversely, expensive payday loans are strong evidence that for poor people, a bi-weekly payment is much too infrequent.) One might draw a comparison to batching or buffers in computers: by letting data pile up in buffers, the computer can then deal with them in one batch, amortizing overhead over many items rather than incurring the overhead again and again. The downside, of course, is that latency will suffer and performance may drop based on that or the items becoming outdated & useless. The right trade-off will depend on the specifics; one would not expect random buffer-sizes to be optimal, but one would have to test and see what works best.
Do note that this isn’t an extensive list by any means, there are plenty more ‘smart drugs’ out there purported to help focus and concentration. Most (if not all) are restricted under the Psychoactive Substances Act, meaning they’re largely illegal to sell. We strongly recommend against using these products off-label, as they can be dangerous both due to side effects and their lack of regulation on the grey/black market.

I split the 2 pills into 4 doses for each hour from midnight to 4 AM. 3D driver issues in Debian unstable prevented me from using Brain Workshop, so I don’t have any DNB scores to compare with the armodafinil DNB scores. I had the subjective impression that I was worse off with the Modalert, although I still managed to get a fair bit done so the deficits couldn’t’ve been too bad. The apathy during the morning felt worse than armodafinil, but that could have been caused by or exacerbated by an unexpected and very stressful 2 hour drive through rush hour and multiple accidents; the quick hour-long nap at 10 AM was half-waking half-light-sleep according to the Zeo, but seemed to help a bit. As before, I began to feel better in the afternoon and by evening felt normal, doing my usual reading. That night, the Zeo recorded my sleep as lasting ~9:40, when it was usually more like 8:40-9:00 (although I am not sure that this was due to the modafinil inasmuch as once a week or so I tend to sleep in that long, as I did a few days later without any influence from the modafinil); assuming the worse, the nap and extra sleep cost me 2 hours for a net profit of ~7 hours. While it’s not clear how modafinil affects recovery sleep (see the footnote in the essay), it’s still interesting to ponder the benefits of merely being able to delay sleep18.


Core body temperature, local pH and internal pressure are important indicators of patient well-being. While a thermometer can give an accurate reading during regular checkups, the monitoring of professionals in high-intensity situations requires a more accurate inner body temperature sensor. An ingestible chemical sensor can record acidity and pH levels along the gastrointestinal tract to screen for ulcers or tumors. Sensors also can be built into medications to track compliance.
While these two compounds may not be as exciting as a super pill that instantly unlocks the full potential of your brain, they currently have the most science to back them up. And, as Patel explains, they’re both relatively safe for healthy individuals of most ages. Patel explains that a combination of caffeine and L-theanine is the most basic supplement stack (or combined dose) because the L-theanine can help blunt the anxiety and “shakiness” that can come with ingesting too much caffeine.
The absence of a suitable home for this needed research on the current research funding landscape exemplifies a more general problem emerging now, as applications of neuroscience begin to reach out of the clinical setting and into classrooms, offices, courtrooms, nurseries, marketplaces, and battlefields (Farah, 2011). Most of the longstanding sources of public support for neuroscience research are dedicated to basic research or medical applications. As neuroscience is increasingly applied to solving problems outside the medical realm, it loses access to public funding. The result is products and systems reaching the public with less than adequate information about effectiveness and/or safety. Examples include cognitive enhancement with prescription stimulants, event-related potential and fMRI-based lie detection, neuroscience-based educational software, and anti-brain-aging computer programs. Research and development in nonmedical neuroscience are now primarily the responsibility of private corporations, which have an interest in promoting their products. Greater public support of nonmedical neuroscience research, including methods of cognitive enhancement, will encourage greater knowledge and transparency concerning the efficacy and safety of these products and will encourage the development of products based on social value rather than profit value.
Up to 20% of Ivy League college students have already tried “smart drugs,” so we can expect these pills to feature prominently in organizations (if they don’t already). After all, the pressure to perform is unlikely to disappear the moment students graduate. And senior employees with demanding jobs might find these drugs even more useful than a 19-year-old college kid does. Indeed, a 2012 Royal Society report emphasized that these “enhancements,” along with other technologies for self-enhancement, are likely to have far-reaching implications for the business world.
If I stop tonight and do nothing Monday (and I sleep the normal eight hours and do not pay any penalty), then that’ll be 4 out of 5 days on modafinil, each saving 3 or 4 hours. Each day took one pill which cost me $1.20, but each pill saved let’s call it 3.5 hours; if I value my time at minimum wage, or 7.25/hr (federal minimum wage), then that 3.5 hours is worth $25.37, which is much more than $1.20, ~21x more.
Price discrimination is aided by barriers such as ignorance and oligopolies. An example of the former would be when I went to a Food Lion grocery store in search of spices, and noticed that there was a second selection of spices in the Hispanic/Latino ethnic food aisle, with unit prices perhaps a fourth of the regular McCormick-brand spices; I rather doubt that regular cinnamon varies that much in quality. An example of the latter would be using veterinary drugs on humans - any doctor to do so would probably be guilty of medical malpractice even if the drugs were manufactured in the same factories (as well they might be, considering economies of scale). Similarly, we can predict that whenever there is a veterinary drug which is chemically identical to a human drug, the veterinary drug will be much cheaper, regardless of actual manufacturing cost, than the human drug because pet owners do not value their pets more than themselves. Human drugs are ostensibly held to a higher standard than veterinary drugs; so if veterinary prices are higher, then there will be an arbitrage incentive to simply buy the cheaper human version and downgrade them to veterinary drugs.
Some suggested that the lithium would turn me into a zombie, recalling the complaints of psychiatric patients. But at 5mg elemental lithium x 200 pills, I’d have to eat 20 to get up to a single clinical dose (a psychiatric dose might be 500mg of lithium carbonate, which translates to ~100mg elemental), so I’m not worried about overdosing. To test this, I took on day 1 & 2 no less than 4 pills/20mg as an attack dose; I didn’t notice any large change in emotional affect or energy levels. And it may’ve helped my motivation (though I am also trying out the tyrosine).

This research is in contrast to the other substances I like, such as piracetam or fish oil. I knew about withdrawal of course, but it was not so bad when I was drinking only tea. And the side-effects like jitteriness are worse on caffeine without tea; I chalk this up to the lack of theanine. (My later experiences with theanine seems to confirm this.) These negative effects mean that caffeine doesn’t satisfy the strictest definition of nootropic (having no negative effects), but is merely a cognitive enhancer (with both benefits & costs). One might wonder why I use caffeine anyway if I am so concerned with mental ability.

The stimulant now most popular in news articles as a legitimate “smart drug” is Modafinil, which came to market as an anti-narcolepsy drug, but gained a following within the military, doctors on long shifts, and college students pulling all-nighters who needed a drug to improve alertness without the “wired” feeling associated with caffeine. Modafinil is a relatively new smart drug, having gained widespread use only in the past 15 years. More research is needed before scientists understand this drug’s function within the brain – but the increase in alertness it provides is uncontested.
My worry about the MP variable is that, plausible or not, it does seem relatively weak against manipulation; other variables I could look at, like arbtt window-tracking of how I spend my computer time, # or size of edits to my files, or spaced repetition performance, would be harder to manipulate. If it’s all due to MP, then if I remove the MP and LLLT variables, and summarize all the other variables with factor analysis into 2 or 3 variables, then I should see no increases in them when I put LLLT back in and look for a correlation between the factors & LLLT with a multivariate regression.
Though their product includes several vitamins including Bacopa, it seems to be missing the remaining four of the essential ingredients: DHA Omega 3, Huperzine A, Phosphatidylserine and N-Acetyl L-Tyrosine. It missed too many of our key criteria and so we could not endorse this product of theirs. Simply, if you don’t mind an insufficient amount of essential ingredients for improved brain and memory function and an inclusion of unwanted ingredients – then this could be a good fit for you.
Smart pills have revolutionized the diagnosis of gastrointestinal disorders and could replace conventional diagnostic techniques such as endoscopy. Traditionally, an endoscopy probe is inserted into a patient’s esophagus, and subsequently the upper and lower gastrointestinal tract, for diagnostic purposes. There is a risk of perforation or tearing of the esophageal lining, and the patient faces discomfort during and after the procedure. A smart pill or wireless capsule endoscopy (WCE), however, can easily be swallowed and maneuvered to capture images, and requires minimal patient preparation, such as sedation. The built-in sensors allow the measurement of all fluids and gases in the gut, giving the physician a multidimensional picture of the human body.

Another study on the olfactory impact of essential oils like lavender and rosemary revealed that they produced positive effects on cognitive performance and mood.16 And in another study on the inhalation of essential oils like grapefruit, fennel, Estragon, and black pepper essential oil, inhalation of the oils resulted in modulation of sympathetic activity in adults.17,18
(If I am not deficient, then supplementation ought to have no effect.) The previous material on modern trends suggests a prior >25%, and higher than that if I were female. However, I was raised on a low-salt diet because my father has high blood pressure, and while I like seafood, I doubt I eat it more often than weekly. I suspect I am somewhat iodine-deficient, although I don’t believe as confidently as I did that I had a vitamin D deficiency. Let’s call this one 75%.
So it's no surprise that as soon as medical science develops a treatment for a disease, we often ask if it couldn't perhaps make a healthy person even healthier. Take Viagra, for example: developed to help men who couldn't get erections, it's now used by many who function perfectly well without a pill but who hope it will make them exceptionally virile.
Texas-based entrepreneur and podcaster Mansal Denton takes phenylpiracetam, a close relative of piracetam originally developed by the Soviet Union as a medication for cosmonauts, to help them endure the stresses of life in space. “I have a much easier time articulating certain things when I take it, so I typically do a lot of recording [of podcasts] on those days,” he says.
On the other end of the spectrum is the nootropic stack, a practice where individuals create a cocktail or mixture of different smart drugs for daily intake. The mixture and its variety actually depend on the goals of the user. Many users have said that nootropic stacking is more effective for delivering improved cognitive function in comparison to single nootropics.
Amphetamines have a long track record as smart drugs, from the workaholic mathematician Paul Erdös, who relied on them to get through 19-hour maths binges, to the writer Graham Greene, who used them to write two books at once. More recently, there are plenty of anecdotal accounts in magazines about their widespread use in certain industries, such as journalism, the arts and finance.
Competitors of importance in the smart pills market have been recorded and analyzed in MRFR's report. These market players include RF Co., Ltd., CapsoVision, Inc., JINSHAN Science & Technology, BDD Limited, MEDTRONIC, Check-Cap, PENTAX Medical, INTROMEDIC, Olympus Corporation, FUJIFILM Holdings Corporation, MEDISAFE, and Proteus Digital Health, Inc.
A provisional conclusion about the effects of stimulants on learning is that they do help with the consolidation of declarative learning, with effect sizes varying widely from small to large depending on the task and individual study. Indeed, as a practical matter, stimulants may be more helpful than many of the laboratory tasks indicate, given the apparent dependence of enhancement on length of delay before testing. Although, as a matter of convenience, experimenters tend to test memory for learned material soon after the learning, this method has not generally demonstrated stimulant-enhanced learning. However, when longer periods intervene between learning and test, a more robust enhancement effect can be seen. Note that the persistence of the enhancement effect well past the time of drug action implies that state-dependent learning is not responsible. In general, long-term effects on learning are of greater practical value to people. Even students cramming for exams need to retain information for more than an hour or two. We therefore conclude that stimulant medication does enhance learning in ways that may be useful in the real world.

But how to blind myself? I used my pill maker to make 9 OO pills of piracetam mix, and then 9 OO pills of piracetam mix+the Adderall, then I put them in a baggy. The idea is that I can blind myself as to what pill I am taking that day since at the end of the day, I can just look in the baggy and see whether a placebo or Adderall pill is missing: the big capsules are transparent so I can see whether there is a crushed-up blue Adderall in the end or not. If there are fewer Adderall than placebo, I took an Adderall, and vice-versa. Now, since I am checking at the end of each day, I also need to remove or add the opposite pill to maintain the ratio and make it easy to check the next day; more importantly I need to replace or remove a pill, because otherwise the odds will be skewed and I will know how they are skewed. (Imagine I started with 4 Adderalls and 4 placebos, and then 3 days in a row I draw placebos but I don’t add or remove any pills; the next day, because most of the placebos have been used up, there’s only a small chance I will get a placebo…)
…It is without activity in man! Certainly not for the lack of trying, as some of the dosage trials that are tucked away in the literature (as abstracted in the Qualitative Comments given above) are pretty heavy duty. Actually, I truly doubt that all of the experimenters used exactly that phrase, No effects, but it is patently obvious that no effects were found. It happened to be the phrase I had used in my own notes.
Took pill 12:11 PM. I am not certain. While I do get some things accomplished (a fair amount of work on the Silk Road article and its submission to places), I also have some difficulty reading through a fiction book (Sum) and I seem kind of twitchy and constantly shifting windows. I am weakly inclined to think this is Adderall (say, 60%). It’s not my normal feeling. Next morning - it was Adderall.

In the United States, people consume more coffee than fizzy drink, tea and juice combined. Alas, no one has ever estimated its impact on economic growth – but plenty of studies have found myriad other benefits. Somewhat embarrassingly, caffeine has been proven to be better than the caffeine-based commercial supplement that Woo’s company came up with, which is currently marketed at $17.95 for 60 pills.
Some people aren’t satisfied with a single supplement—the most devoted self-improvers buy a variety of different compounds online and create their own custom regimens, which they call “stacks.” According to Kaleigh Rogers, writing in Vice last year, companies will now take their customers’ genetic data from 23andMe or another source and use it to recommend the right combinations of smart drugs to optimize each individual’s abilities. The problem with this practice is that there’s no evidence the practice works. (And remember, the FDA doesn’t regulate supplements.) Find out the 9 best foods to boost your brain health.
It’s not clear that there is much of an effect at all. This makes it hard to design a self-experiment - how big an effect on, say, dual n-back should I be expecting? Do I need an arduous long trial or an easy short one? This would principally determine the value of information too; chocolate seems like a net benefit even if it does not affect the mind, but it’s also fairly costly, especially if one likes (as I do) dark chocolate. Given the mixed research, I don’t think cocoa powder is worth investigating further as a nootropic.
Chocolate or cocoa powder (Examine.com), contains the stimulants caffeine and the caffeine metabolite theobromine, so it’s not necessarily surprising if cocoa powder was a weak stimulant. It’s also a witch’s brew of chemicals such as polyphenols and flavonoids some of which have been fingered as helpful10, which all adds up to an unclear impact on health (once you control for eating a lot of sugar).
Fatty acids are well-studied natural smart drugs that support many cognitive abilities. They play an essential role in providing structural support to cell membranes. Fatty acids also contribute to the growth and repair of neurons. Both functions are crucial for maintaining peak mental acuity as you age. Among the most prestigious fatty acids known to support cognitive health are:
My first impression of ~1g around 12:30PM was that while I do not feel like running around, within an hour I did feel like the brain fog was lighter than before. The effect wasn’t dramatic, so I can’t be very confident. Operationalizing brain fog for an experiment might be hard: it doesn’t necessarily feel like I would do better on dual n-back. I took 2 smaller doses 3 and 6 hours later, to no further effect. Over the following weeks and months, I continued to randomly alternate between potassium & non-potassium days. I noticed no effects other than sleep problems.
Alpha Lipoic Acid is a vitamin-like chemical filled with antioxidant properties, that naturally occur in broccoli, spinach, yeast, kidney, liver, and potatoes. The compound is generally prescribed to patients suffering from nerve-related symptoms of diabetes because it helps in preventing damage to the nerve cells and improves the functioning of neurons. It can be termed as one of the best memory boosting supplements.
These days, young, ambitious professionals prefer prescription stimulants—including methylphenidate (usually sold as Ritalin) and Adderall—that are designed to treat people with attention deficit hyperactivity disorder (ADHD) and are more common and more acceptable than cocaine or nicotine (although there is a black market for these pills). ADHD makes people more likely to lose their focus on tasks and to feel restless and impulsive. Diagnoses of the disorder have been rising dramatically over the past few decades—and not just in kids: In 2012, about 16 million Adderall prescriptions were written for adults between the ages of 20 and 39, according to a report in the New York Times. Both methylphenidate and Adderall can improve sustained attention and concentration, says Barbara Sahakian, professor of clinical neuropsychology at the University of Cambridge and author of the 2013 book Bad Moves: How Decision Making Goes Wrong, and the Ethics of Smart Drugs. But the drugs do have side effects, including insomnia, lack of appetite, mood swings, and—in extreme cases—hallucinations, especially when taken in amounts the exceed standard doses. Take a look at these 10 foods that help you focus.
A number of different laboratory studies have assessed the acute effect of prescription stimulants on the cognition of normal adults. In the next four sections, we review this literature, with the goal of answering the following questions: First, do MPH (e.g., Ritalin) and d-AMP (by itself or as the main ingredient in Adderall) improve cognitive performance relative to placebo in normal healthy adults? Second, which cognitive systems are affected by these drugs? Third, how do the effects of the drugs depend on the individual using them?
Supplements, medications, and coffee certainly might play a role in keeping our brains running smoothly at work or when we’re trying to remember where we left our keys. But the long-term effects of basic lifestyle practices can’t be ignored. “For good brain health across the life span, you should keep your brain active,” Sahakian says. “There is good evidence for ‘use it or lose it.’” She suggests brain-training apps to improve memory, as well as physical exercise. “You should ensure you have a healthy diet and not overeat. It is also important to have good-quality sleep. Finally, having a good work-life balance is important for well-being.” Try these 8 ways to get smarter while you sleep.
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.

Bought 5,000 IU soft-gels of Vitamin D-333 (Examine.com; FDA adverse events) because I was feeling very apathetic in January 2011 and not getting much done, even slacking on regular habits like Mnemosyne spaced repetition review or dual n-back or my Wikipedia watchlist. Introspecting, I was reminded of depression & dysthymia & seasonal affective disorder.


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.
I can’t try either of the products myself – I am pregnant and my doctor doesn’t recommend it – but my husband agrees to. He describes the effect of the Nootrobox product as like having a cup of coffee but not feeling as jittery. “I had a very productive day, but I don’t know if that was why,” he says. His Nootroo experience ends after one capsule. He gets a headache, which he is convinced is related, and refuses to take more. “It is just not a beginner friendly cocktail,” offers Noehr.

With all these studies pointing to the nootropic benefits of some essential oils, it can logically be concluded then that some essential oils can be considered “smart drugs.” However, since essential oils have so much variety and only a small fraction of this wide range has been studied, it cannot be definitively concluded that absolutely all essential oils have brain-boosting benefits. The connection between the two is strong, however.

An entirely different set of questions concerns cognitive enhancement in younger students, including elementary school and even preschool children. Some children can function adequately in school without stimulants but perform better with them; medicating such children could be considered a form of cognitive enhancement. How often does this occur? What are the roles and motives of parents, teachers, and pediatricians in these cases? These questions have been discussed elsewhere and deserve continued attention (Diller, 1996; Singh & Keller, 2010).
One might suggest just going to the gym or doing other activities which may increase endogenous testosterone secretion. This would be unsatisfying to me as it introduces confounds: the exercise may be doing all the work in any observed effect, and certainly can’t be blinded. And blinding is especially important because the 2011 review discusses how some studies report that the famed influence of testosterone on aggression (eg. Wedrifid’s anecdote above) is a placebo effect caused by the folk wisdom that testosterone causes aggression & rage!
Coconut oil was recommended by Pontus Granström on the Dual N-Back mailing list for boosting energy & mental clarity. It is fairly cheap (~$13 for 30 ounces) and tastes surprisingly good; it has a very bad reputation in some parts, but seems to be in the middle of a rehabilitation. Seth Robert’s Buttermind experiment found no mental benefits to coconut oil (and benefits to eating butter), but I wonder.
Another classic approach to the assessment of working memory is the span task, in which a series of items is presented to the subject for repetition, transcription, or recognition. The longest series that can be reproduced accurately is called the forward span and is a measure of working memory capacity. The ability to reproduce the series in reverse order is tested in backward span tasks and is a more stringent test of working memory capacity and perhaps other working memory functions as well. The digit span task from the Wechsler (1981) IQ test was used in four studies of stimulant effects on working memory. One study showed that d-AMP increased digit span (de Wit et al., 2002), and three found no effects of d-AMP or MPH (Oken, Kishiyama, & Salinsky, 1995; Schmedtje, Oman, Letz, & Baker, 1988; Silber, Croft, Papafotiou, & Stough, 2006). A spatial span task, in which subjects must retain and reproduce the order in which boxes in a scattered spatial arrangement change color, was used by Elliott et al. (1997) to assess the effects of MPH on working memory. For subjects in the group receiving placebo first, MPH increased spatial span. However, for the subjects who received MPH first, there was a nonsignificant opposite trend. The group difference in drug effect is not easily explained. The authors noted that the subjects in the first group performed at an overall lower level, and so, this may be another manifestation of the trend for a larger enhancement effect for less able subjects.
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:
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.

As it happened, Health Supplement Wholesalers (since renamed Powder City) offered me a sample of their products, including their 5g Noopept powder ($13). I’d never used HSW before & they had some issues in the past; but I haven’t seen any recent complaints, so I was willing to try them. My 5g from batch #130830 arrived quickly (photos: packaging, powder contents). I tried some (tastes just slightly unpleasant, like an ultra-weak piracetam), and I set about capping the fluffy white flour-like powder with the hilariously tiny scoop they provide.
Last spring, 100 people showed up at a Peak Performance event where psychedelic psychologist James Fadiman said the key to unleashing the cognition-enhancing effects of LSD — which he listed as less anxiety, better focus, improved sleep, greater creativity — was all in the dosage. He recommended a tenth of a “party dose” — enough to give you “the glow” and enhance your cognitive powers without “the trip.”
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.
If you want to focus on boosting your brain power, Lebowitz says you should primarily focus on improving your cardiovascular health, which is "the key to good thinking." For example, high blood pressure and cholesterol, which raise the risk of heart disease, can cause arteries to harden, which can decrease blood flow to the brain. The brain relies on blood to function normally.
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!
Many of the most popular “smart drugs” (Piracetam, Sulbutiamine, Ginkgo Biloba, etc.) have been around for decades or even millenia but are still known only in medical circles or among esoteric practicioners of herbal medicine. Why is this? If these compounds have proven cognitive benefits, why are they not ubiquitous? How come every grade-school child gets fluoride for the development of their teeth (despite fluoride’s being a known neurotoxin) but not, say, Piracetam for the development of their brains? Why does the nightly news slant stories to appeal more to a fear-of-change than the promise of a richer cognitive future?
Texas-based entrepreneur and podcaster Mansal Denton takes phenylpiracetam, a close relative of piracetam originally developed by the Soviet Union as a medication for cosmonauts, to help them endure the stresses of life in space. “I have a much easier time articulating certain things when I take it, so I typically do a lot of recording [of podcasts] on those days,” he says.

Absorption of nicotine across biological membranes depends on pH. Nicotine is a weak base with a pKa of 8.0 (Fowler, 1954). In its ionized state, such as in acidic environments, nicotine does not rapidly cross membranes…About 80 to 90% of inhaled nicotine is absorbed during smoking as assessed using C14-nicotine (Armitage et al., 1975). The efficacy of absorption of nicotine from environmental smoke in nonsmoking women has been measured to be 60 to 80% (Iwase et al., 1991)…The various formulations of nicotine replacement therapy (NRT), such as nicotine gum, transdermal patch, nasal spray, inhaler, sublingual tablets, and lozenges, are buffered to alkaline pH to facilitate the absorption of nicotine through cell membranes. Absorption of nicotine from all NRTs is slower and the increase in nicotine blood levels more gradual than from smoking (Table 1). This slow increase in blood and especially brain levels results in low abuse liability of NRTs (Henningfield and Keenan, 1993; West et al., 2000). Only nasal spray provides a rapid delivery of nicotine that is closer to the rate of nicotine delivery achieved with smoking (Sutherland et al., 1992; Gourlay and Benowitz, 1997; Guthrie et al., 1999). The absolute dose of nicotine absorbed systemically from nicotine gum is much less than the nicotine content of the gum, in part, because considerable nicotine is swallowed with subsequent first-pass metabolism (Benowitz et al., 1987). Some nicotine is also retained in chewed gum. A portion of the nicotine dose is swallowed and subjected to first-pass metabolism when using other NRTs, inhaler, sublingual tablets, nasal spray, and lozenges (Johansson et al., 1991; Bergstrom et al., 1995; Lunell et al., 1996; Molander and Lunell, 2001; Choi et al., 2003). Bioavailability for these products with absorption mainly through the mucosa of the oral cavity and a considerable swallowed portion is about 50 to 80% (Table 1)…Nicotine is poorly absorbed from the stomach because it is protonated (ionized) in the acidic gastric fluid, but is well absorbed in the small intestine, which has a more alkaline pH and a large surface area. Following the administration of nicotine capsules or nicotine in solution, peak concentrations are reached in about 1 h (Benowitz et al., 1991; Zins et al., 1997; Dempsey et al., 2004). The oral bioavailability of nicotine is about 20 to 45% (Benowitz et al., 1991; Compton et al., 1997; Zins et al., 1997). Oral bioavailability is incomplete because of the hepatic first-pass metabolism. Also the bioavailability after colonic (enema) administration of nicotine (examined as a potential therapy for ulcerative colitis) is low, around 15 to 25%, presumably due to hepatic first-pass metabolism (Zins et al., 1997). Cotinine is much more polar than nicotine, is metabolized more slowly, and undergoes little, if any, first-pass metabolism after oral dosing (Benowitz et al., 1983b; De Schepper et al., 1987; Zevin et al., 1997).

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.”
As expected since most of the data overlaps with the previous LLLT analysis, the LLLT variable correlates strongly; the individual magnesium variables may look a little more questionable but were justified in the magnesium citrate analysis. The Noopept result looks a little surprising - almost zero effect? Let’s split by dose (which was the point of the whole rigmarole of changing dose levels):
Dosage is apparently 5-10mg a day. (Prices can be better elsewhere; selegiline is popular for treating dogs with senile dementia, where those 60x5mg will cost $2 rather than $3531. One needs a veterinarian’s prescription to purchase from pet-oriented online pharmacies, though.) I ordered it & modafinil from Nubrain.com at $35 for 60x5mg; Nubrain delayed and eventually canceled my order - and my enthusiasm. Between that and realizing how much of a premium I was paying for Nubrain’s deprenyl, I’m tabling deprenyl along with nicotine & modafinil for now. Which is too bad, because I had even ordered 20g of PEA from Smart Powders to try out with the deprenyl. (My later attempt to order some off the Silk Road also failed when the seller canceled the order.)

Since dietary supplements do not require double-blind, placebo-controlled, pharmaceutical-style human studies before going to market, there is little incentive for companies to really prove that something does what they say it does. This means that, in practice, nootropics may not live up to all the grandiose, exuberant promises advertised on the bottle in which they come. The flip side, though? There’s no need to procure a prescription in order to try them out. Good news for aspiring biohackers—and for people who have no aspirations to become biohackers, but still want to be Bradley Cooper in Limitless (me).
The soft gels are very small; one needs to be a bit careful - Vitamin D is fat-soluble and overdose starts in the range of 70,000 IU35, so it would take at least 14 pills, and it’s unclear where problems start with chronic use. Vitamin D, like many supplements, follows a U-shaped response curve (see also Melamed et al 2008 and Durup et al 2012) - too much can be quite as bad as too little. Too little, though, is likely very bad. The previously cited studies with high acute doses worked out to <1,000 IU a day, so they may reassure us about the risks of a large acute dose but not tell us much about smaller chronic doses; the mortality increases due to too-high blood levels begin at ~140nmol/l and reading anecdotes online suggest that 5k IU daily doses tend to put people well below that (around 70-100nmol/l). I probably should get a blood test to be sure, but I have something of a needle phobia.
Second, users are concerned with the possibility of withdrawal if they stop taking the nootropics. They worry that if they stop taking nootropics they won’t be as smart as when they were taking nootropics, and will need to continue taking them to function. Some users report feeling a slight brain fog when discontinuing nootropics, but that isn’t a sign of regression.
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