Finally, a workforce high on stimulants wouldn’t necessarily be more productive overall. “One thinks ‘are these things dangerous?’ – and that’s important to consider in the short term,” says Huberman. “But there’s also a different question, which is: ‘How do you feel the day afterwards?’ Maybe you’re hyper-focused for four hours, 12 hours, but then you’re below baseline for 24 or 48.”
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:
While the commentary makes effective arguments — that this isn't cheating, because cheating is based on what the rules are; that this is fair, because hiring a tutor isn't outlawed for being unfair to those who can't afford it; that this isn't unnatural, because humans with computers and antibiotics have been shaping what is natural for millennia; that this isn't drug abuse anymore than taking multivitamins is — the authors seem divorced from reality in the examples they provide of effective stimulant use today.
I noticed on SR something I had never seen before, an offer for 150mgx10 of Waklert for ฿13.47 (then, ฿1 = $3.14). I searched and it seemed Sun was somehow manufacturing armodafinil! Interesting. Maybe not cost-effective, but I tried out of curiosity. They look and are packaged the same as the Modalert, but at a higher price-point: 150 rather than 81 rupees. Not entirely sure how to use them: assuming quality is the same, 150mg Waklert is still 100mg less armodafinil than the 250mg Nuvigil pills.
As opposed to what it might lead you to believe, Ginkgo Smart is not simply a Ginkgo Biloba supplement. In all actuality, it’s much more than that – a nootropic (Well duh, we wouldn’t be reviewing it otherwise). Ginkgo Smart has actually been seeing quite some popularity lately, possibly riding on the popularity of Ginkgo Biloba as a supplement, which has been storming through the US lately, and becoming one of the highest selling supplement in the US. We were pleasantly pleased at the fact that it wasn’t too hard to find Ginkgo Smart’s ingredients… Learn More...

It is not because of the few thousand francs which would have to be spent to put a roof [!] over the third-class carriages or to upholster the third-class seats that some company or other has open carriages with wooden benches. What the company is trying to do is to prevent the passengers who can pay the second class fare from traveling third class; it hits the poor, not because it wants to hurt them, but to frighten the rich. And it is again for the same reason that the companies, having proved almost cruel to the third-class passengers and mean to the second-class ones, become lavish in dealing with first-class passengers. Having refused the poor what is necessary, they give the rich what is superfluous.


Similarly, Mehta et al 2000 noted that the positive effects of methylphenidate (40 mg) on spatial working memory performance were greatest in those volunteers with lower baseline working memory capacity. In a study of the effects of ginkgo biloba in healthy young adults, Stough et al 2001 found improved performance in the Trail-Making Test A only in the half with the lower verbal IQ.
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.
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).
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.

As discussed in my iodine essay (FDA adverse events), iodine is a powerful health intervention as it eliminates cretinism and improves average IQ by a shocking magnitude. If this effect were possible for non-fetuses in general, it would be the best nootropic ever discovered, and so I looked at it very closely. Unfortunately, after going through ~20 experiments looking for ones which intervened with iodine post-birth and took measures of cognitive function, my meta-analysis concludes that: the effect is small and driven mostly by one outlier study. Once you are born, it’s too late. But the results could be wrong, and iodine might be cheap enough to take anyway, or take for non-IQ reasons. (This possibility was further weakened for me by an August 2013 blood test of TSH which put me at 3.71 uIU/ml, comfortably within the reference range of 0.27-4.20.)


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.)

Ongoing studies are looking into the possible pathways by which nootropic substances function. Researchers have postulated that the mental health advantages derived from these substances can be attributed to their effects on the cholinergic and dopaminergic systems of the brain. These systems regulate two important neurotransmitters, acetylcholine and dopamine.


One study of helicopter pilots suggested that 600 mg of modafinil given in three doses can be used to keep pilots alert and maintain their accuracy at pre-deprivation levels for 40 hours without sleep.[60] However, significant levels of nausea and vertigo were observed. Another study of fighter pilots showed that modafinil given in three divided 100 mg doses sustained the flight control accuracy of sleep-deprived F-117 pilots to within about 27% of baseline levels for 37 hours, without any considerable side effects.[61] In an 88-hour sleep loss study of simulated military grounds operations, 400 mg/day doses were mildly helpful at maintaining alertness and performance of subjects compared to placebo, but the researchers concluded that this dose was not high enough to compensate for most of the effects of complete sleep loss.
Fortunately, there are some performance-enhancing habits that have held up under rigorous scientific scrutiny. They are free, and easy to pronounce. Unfortunately, they are also the habits you were perhaps hoping to forego by using nootropics instead. “Of all the things that are supposed to be ‘good for the brain,’” says Stanford neurology professor Sharon Sha, “there is more evidence for exercise than anything else.” Next time you’re facing a long day, you could take a pill and see what happens.
Cocoa flavanols (CF) positively influence physiological processes in ways which suggest that their consumption may improve aspects of cognitive function. This study investigated the acute cognitive and subjective effects of CF consumption during sustained mental demand. In this randomized, controlled, double-blinded, balanced, three period crossover trial 30 healthy adults consumed drinks containing 520 mg, 994 mg CF and a matched control, with a 3-day washout between drinks. Assessments included the state anxiety inventory and repeated 10-min cycles of a Cognitive Demand Battery comprising of two serial subtraction tasks (Serial Threes and Serial Sevens), a Rapid Visual Information Processing (RVIP) task and a mental fatigue scale, over the course of 1 h. Consumption of both 520 mg and 994 mg CF significantly improved Serial Threes performance. The 994 mg CF beverage significantly speeded RVIP responses but also resulted in more errors during Serial Sevens. Increases in self-reported mental fatigue were significantly attenuated by the consumption of the 520 mg CF beverage only. This is the first report of acute cognitive improvements following CF consumption in healthy adults. While the mechanisms underlying the effects are unknown they may be related to known effects of CF on endothelial function and blood flow.
Accordingly, we searched the literature for studies in which MPH or d-AMP was administered orally to nonelderly adults in a placebo-controlled design. Some of the studies compared the effects of multiple drugs, in which case we report only the results of stimulant–placebo comparisons; some of the studies compared the effects of stimulants on a patient group and on normal control subjects, in which case we report only the results for control subjects. The studies varied in many other ways, including the types of tasks used, the specific drug used, the way in which dosage was determined (fixed dose or weight-dependent dose), sample size, and subject characteristics (e.g., age, college sample or not, gender). Our approach to the classic splitting versus lumping dilemma has been to take a moderate lumping approach. We group studies according to the general type of cognitive process studied and, within that grouping, the type of task. The drug and dose are reported, as well as sample characteristics, but in the absence of pronounced effects of these factors, we do not attempt to make generalizations about them.

There are seven primary classes used to categorize smart drugs: Racetams, Stimulants, Adaptogens, Cholinergics, Serotonergics, Dopaminergics, and Metabolic Function Smart Drugs. Despite considerable overlap and no clear border in the brain and body’s responses to these substances, each class manifests its effects through a different chemical pathway within the body.
Other drugs, like cocaine, are used by bankers to manage their 18-hour workdays [81]. Unlike nootropics, dependency is very likely and not only mentally but also physically. Bankers and other professionals who take drugs to improve their productivity will become dependent. Almost always, the negative consequences outweigh any positive outcomes from using drugs.
the rise of IP scofflaw countries which enable the manufacture of known drugs: India does not respect the modafinil patents, enabling the cheap generics we all use, and Chinese piracetam manufacturers don’t give a damn about the FDA’s chilling-effect moves in the US. If there were no Indian or Chinese manufacturers, where would we get our modafinil? Buy them from pharmacies at $10 a pill or worse? It might be worthwhile, but think of the chilling effect on new users.
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).

But, thanks to the efforts of a number of remarkable scientists, researchers and plain-old neurohackers, we are beginning to put together a “whole systems” model of how all the different parts of the human brain work together and how they mesh with the complex regulatory structures of the body. It’s going to take a lot more data and collaboration to dial this model in, but already we are empowered to design stacks that can meaningfully deliver on the promise of nootropics “to enhance the quality of subjective experience and promote cognitive health, while having extremely low toxicity and possessing very few side effects.” It’s a type of brain hacking that is intended to produce noticeable cognitive benefits.

Analyzing the results is a little tricky because I was simultaneously running the first magnesium citrate self-experiment, which turned out to cause a quite complex result which looks like a gradually-accumulating overdose negating an initial benefit for net harm, and also toying with LLLT, which turned out to have a strong correlation with benefits. So for the potential small Noopept effect to not be swamped, I need to include those in the analysis. I designed the experiment to try to find the best dose level, so I want to look at an average Noopept effect but also the estimated effect at each dose size in case some are negative (especially in the case of 5-pills/60mg); I included the pilot experiment data as 10mg doses since they were also blind & randomized. Finally, missingness affects analysis: because not every variable is recorded for each date (what was the value of the variable for the blind randomized magnesium citrate before and after I finished that experiment? what value do you assign the Magtein variable before I bought it and after I used it all up?), just running a linear regression may not work exactly as one expects as various days get omitted because part of the data was missing.
Many of the food-derived ingredients that are often included in nootropics—omega-3s in particular, but also flavonoids—do seem to improve brain health and function. But while eating fatty fish, berries and other healthy foods that are high in these nutrients appears to be good for your brain, the evidence backing the cognitive benefits of OTC supplements that contain these and other nutrients is weak.
Weyandt et al. (2009) Large public university undergraduates (N = 390) 7.5% (past 30 days) Highest rated reasons were to perform better on schoolwork, perform better on tests, and focus better in class 21.2% had occasionally been offered by other students; 9.8% occasionally or frequently have purchased from other students; 1.4% had sold to other students
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:
The question of how much nonmedical use of stimulants occurs on college campuses is only partly answered by the proportion of students using the drugs in this way. The other part of the answer is how frequently they are used by those students. Three studies addressed this issue. Low and Gendaszek (2002) found a high past-year rate of 35.3%, but only 10% and 8% of this population used monthly and weekly, respectively. White et al. (2006) found a larger percentage used frequently: 15.5% using two to three times per week and 33.9% using two to three times per month. Teter et al. (2006) found that most nonmedical users take prescription stimulants sporadically, with well over half using five or fewer times and nearly 40% using only once or twice in their lives. DeSantis et al. (2008) offered qualitative evidence on the issue, reporting that students often turned to stimulants at exam time only, particularly when under pressure to study for multiple exams at the same time. Thus, there appears to be wide variation in the regularity of stimulant use, with the most common pattern appearing to be infrequent use.
If you’re considering taking pharmaceutical nootropics, then it’s important that you learn as much as you can about how they work and that you seek professional advice before taking them. Be sure to read the side effects and contraindications of the nootropic that you are considering taking, and do not use it if you have any pre-existing medical conditions or allergies. If you’re taking other medications, then discuss your plans with a doctor or pharmacist to make sure that your nootropic is safe for you to use.
Smart pills have huge potential and several important applications, particularly in diagnosis. Smart pills are growing as a highly effective method of endoscopy, particularly for gastrointestinal diseases. Urbanization and rapid lifestyle changes leaning toward unhealthy diets and poor eating habits have led to distinctive increasing lifestyle disorders such as gastroesophageal reflux disease (GERD), obesity, and gastric ulcers.
DNB-wise, eyeballing my stats file seems to indicate a small increase: when I compare peak scores D4B scores, I see mostly 50s and a few 60s before piracetam, and after starting piracetam, a few 70s mixed into the 50s and 60s. Natural increase from training? Dunno - I’ve been stuck on D4B since June, so 5 or 10% in a week or 3 seems a little suspicious. A graph of the score series26:
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.
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.
“Cavin Balaster knows brain injury as well as any specialist. He survived a horrific accident and came out on the other side stronger than ever. His book, “How To Feed A Brain” details how changing his diet helped him to recover further from the devastating symptoms of brain injury such as fatigue and brain fog. Cavin is able to thoroughly explain complex issues in a simplified manner so the reader does not need a medical degree to understand. The book also includes comprehensive charts to simplify what the body needs and how to provide the necessary foods. “How To Feed A Brain” is a great resource for anyone looking to improve their health through diet, brain injury not required.”
Several studies have assessed the effect of MPH and d-AMP on tasks tapping various other aspects of spatial working memory. Three used the spatial working memory task from the CANTAB battery of neuropsychological tests (Sahakian & Owen, 1992). In this task, subjects search for a target at different locations on a screen. Subjects are told that locations containing a target in previous trials will not contain a target in future trials. Efficient performance therefore requires remembering and avoiding these locations in addition to remembering and avoiding locations already searched within a trial. Mehta et al. (2000) found evidence of greater accuracy with MPH, and Elliott et al. (1997) found a trend for the same. In Mehta et al.’s study, this effect depended on subjects’ working memory ability: the lower a subject’s score on placebo, the greater the improvement on MPH. In Elliott et al.’s study, MPH enhanced performance for the group of subjects who received the placebo first and made little difference for the other group. The reason for this difference is unclear, but as mentioned above, this may reflect ability differences between the groups. More recently, Clatworthy et al. (2009) undertook a positron emission tomography (PET) study of MPH effects on two tasks, one of which was the CANTAB spatial working memory task. They failed to find consistent effects of MPH on working memory performance but did find a systematic relation between the performance effect of the drug in each individual and its effect on individuals’ dopamine activity in the ventral striatum.
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 ethics of cognitive enhancement have been extensively debated in the academic literature (e.g., Bostrom & Sandberg, 2009; Farah et al., 2004; Greely et al., 2008; Mehlman, 2004; Sahakian & Morein-Zamir, 2007). We do not attempt to review this aspect of the problem here. Rather, we attempt to provide a firmer empirical basis for these discussions. Despite the widespread interest in the topic and its growing public health implications, there remains much researchers do not know about the use of prescription stimulants for cognitive enhancement.
Caffeine dose dependently decreased the 1,25(OH)(2)D(3) induced VDR expression and at concentrations of 1 and 10mM, VDR expression was decreased by about 50-70%, respectively. In addition, the 1,25(OH)(2)D(3) induced alkaline phosphatase activity was also reduced at similar doses thus affecting the osteoblastic function. The basal ALP activity was not affected with increasing doses of caffeine. Overall, our results suggest that caffeine affects 1,25(OH)(2)D(3) stimulated VDR protein expression and 1,25(OH)(2)D(3) mediated actions in human osteoblast cells.

You have the highest density of mitochondria in your brain’s prefrontal cortex, which helps to explain why I feel Unfair Advantage in my head first. You have the second highest density in your heart, which is probably why I feel it in the center of my chest next. Mitochondrial energizers can have profound nootropic effects! At higher doses mitochondrial energizers also make for an excellent pre-workout supplements.
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