Do you start your day with a cup (or two, or three) of coffee? It tastes delicious, but it’s also jump-starting your brain because of its caffeine content. Caffeine is definitely a nootropic substance—it’s a mild stimulant that can alleviate fatigue and improve concentration, according to the Mayo Clinic. Current research shows that coffee drinkers don’t suffer any ill effects from drinking up to about four cups of coffee per day. Caffeine is also found in tea, soda, and energy drinks. Not too surprisingly, it’s also in many of the nootropic supplements that are being marketed to people looking for a mental boost. Take a look at these 7 genius brain boosters to try in the morning.
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.
The first night I was eating some coconut oil, I did my n-backing past 11 PM; normally that damages my scores, but instead I got 66/66/75/88/77% (▁▁▂▇▃) on D4B and did not feel mentally exhausted by the end. The next day, I performed well on the Cambridge mental rotations test. An anecdote, of course, and it may be due to the vitamin D I simultaneously started. Or another day, I was slumped under apathy after a promising start to the day; a dose of fish & coconut oil, and 1 last vitamin D, and I was back to feeling chipper and optimist. Unfortunately I haven’t been testing out coconut oil & vitamin D separately, so who knows which is to thank. But still interesting.
Proteus Digital Health (Redwood City, Calif.) offers an FDA-approved microchip—an ingestible pill that tracks medication-taking behavior and how the body is responding to medicine. Through the company’s Digital Health Feedback System, the sensor monitors blood flow, body temperature and other vital signs for people with heart problems, schizophrenia or Alzheimer’s disease.
Even the best of today’s nootropics only just barely scratch the surface. You might say that we are in the “Nokia 1100” phase of taking nootropics, and as better tools and more data come along, the leading thinkers in the space see a powerful future. For example, they are already beginning to look past biochemistry to the epigenome. Not only is the epigenome the code that runs much of your native biochemistry, we now know that experiences in life can be recorded in your epigenome and then passed onto future generations. There is every reason to believe that you are currently running epigenetic code that you inherited from your great-grandmother’s life experiences. And there is every reason to believe that the epigenome can be hacked – that the nootropics of the future can not only support and enhance our biochemistry, but can permanently change the epigenetic code that drives that biochemistry and that we pass onto our children. This is why many healthy individuals use nootropics. They have great benefits and can promote brain function and reduce oxidative stress. They can also improve sleep quality.
Bacopa is a supplement herb often used for memory or stress adaptation. Its chronic effects reportedly take many weeks to manifest, with no important acute effects. Out of curiosity, I bought 2 bottles of Bacognize Bacopa pills and ran a non-randomized non-blinded ABABA quasi-self-experiment from June 2014 to September 2015, measuring effects on my memory performance, sleep, and daily self-ratings of mood/productivity. Because of the very slow onset, small effective sample size, definite temporal trends probably unrelated to Bacopa, and noise in the variables, the results were as expected, ambiguous, and do not strongly support any correlation between Bacopa and memory/sleep/self-rating (+/-/- respectively).

The Nootroo arrives in a shiny gold envelope with the words “proprietary blend” and “intended for use only in neuroscience research” written on the tin. It has been designed, says Matzner, for “hours of enhanced learning and memory”. The capsules contain either Phenylpiracetam or Noopept (a peptide with similar effects and similarly uncategorised) and are distinguished by real flakes of either edible silver or gold. They are to be alternated between daily, allowing about two weeks for the full effect to be felt. Also in the capsules are L-Theanine, a form of choline, and a types of caffeine which it is claimed has longer lasting effects.
This would be a very time-consuming experiment. Any attempt to combine this with other experiments by ANOVA would probably push the end-date out by months, and one would start to be seriously concerned that changes caused by aging or environmental factors would contaminate the results. A 5-year experiment with 7-month intervals will probably eat up 5+ hours to prepare <12,000 pills (active & placebo); each switch and test of mental functioning will probably eat up another hour for 32 hours. (And what test maintains validity with no practice effects over 5 years? Dual n-back would be unusable because of improvements to WM over that period.) Add in an hour for analysis & writeup, that suggests >38 hours of work, and 38 \times 7.25 = 275.5. 12,000 pills is roughly $12.80 per thousand or $154; 120 potassium iodide pills is ~$9, so \frac{365.25}{120} \times 9 \times 5 = 137.
But there would also be significant downsides. Amphetamines are structurally similar to crystal meth – a potent, highly addictive recreational drug which has ruined countless lives and can be fatal. Both Adderall and Ritalin are known to be addictive, and there are already numerous reports of workers who struggled to give them up. There are also side effects, such as nervousness, anxiety, insomnia, stomach pains, and even hair loss, among others.

A total of 330 randomly selected Saudi adolescents were included. Anthropometrics were recorded and fasting blood samples were analyzed for routine analysis of fasting glucose, lipid levels, calcium, albumin and phosphorous. Frequency of coffee and tea intake was noted. 25-hydroxyvitamin D levels were measured using enzyme-linked immunosorbent assays…Vitamin D levels were significantly highest among those consuming 9-12 cups of tea/week in all subjects (p-value 0.009) independent of age, gender, BMI, physical activity and sun exposure.

And the drugs are not terribly difficult to get, depending on where you’re located. Modafinil has an annual global share of $700 million, with high estimated off-label use. Although these drugs can be purchased over the internet, their legal status varies between countries. For example, it is legal to possess and use Modafinil in the United Kingdom without a prescription, but not in United States.
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).

“I love this book! As someone that deals with an autoimmune condition, I deal with sever brain fog. I’m currently in school and this has had a very negative impact on my learning. I have been looking for something like this to help my brain function better. This book has me thinking clearer, and my memory has improved. I’m eating healthier and overall feeling much better. This book is very easy to follow and also has some great recipes included.”
(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%.
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.
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).
Sulbutiamine, mentioned earlier as a cholinergic smart drug, can also be classed a dopaminergic, although its mechanism is counterintuitive: by reducing the release of dopamine in the brain’s prefrontal cortex, the density of dopamine receptors actually increase after continued Sulbutiamine exposure, through a compensatory mechanism. (This provides an interesting example of how dividing smart drugs into sensible “classes” is a matter of taste as well as science, especially since many of them create their discernable neural effects through still undefined mechanisms.)
1 PM; overall this was a pretty productive day, but I can’t say it was very productive. I would almost say even odds, but for some reason I feel a little more inclined towards modafinil. Say 55%. That night’s sleep was vile: the Zeo says it took me 40 minutes to fall asleep, I only slept 7:37 total, and I woke up 7 times. I’m comfortable taking this as evidence of modafinil (half-life 10 hours, 1 PM to midnight is only 1 full halving), bumping my prediction to 75%. I check, and sure enough - modafinil.

When I spoke with Jesse Lawler, who hosts the podcast Smart Drugs Smarts, about breakthroughs in brain health and neuroscience, he was unsurprised to hear of my disappointing experience. Many nootropics are supposed to take time to build up in the body before users begin to feel their impact. But even then, says Barry Gordon, a neurology professor at the Johns Hopkins Medical Center, positive results wouldn’t necessarily constitute evidence of a pharmacological benefit.


Smart pills are defined as drugs or prescription medication used to treat certain mental disorders, from milder ones such as brain fog, to some more severe like ADHD. They are often referred to as ‘nootropics’ but even though the two terms are often used interchangeably, smart pills and nootropics represent two different types of cognitive enhancers.
Your mileage will vary. There are so many parameters and interactions in the brain that any of them could be the bottleneck or responsible pathway, and one could fall prey to the common U-shaped dose-response curve (eg. Yerkes-Dodson law; see also Chemistry of the adaptive mind & de Jongh et al 2007) which may imply that the smartest are those who benefit least23 but ultimately they all cash out in a very few subjective assessments like energetic or motivated, with even apparently precise descriptions like working memory or verbal fluency not telling you much about what the nootropic actually did. It’s tempting to list the nootropics that worked for you and tell everyone to go use them, but that is merely generalizing from one example (and the more nootropics - or meditation styles, or self-help books, or getting things done systems - you try, the stronger the temptation is to evangelize). The best you can do is read all the testimonials and studies and use that to prioritize your list of nootropics to try. You don’t know in advance which ones will pay off and which will be wasted. You can’t know in advance. And wasted some must be; to coin a Umeshism: if all your experiments work, you’re just fooling yourself. (And the corollary - if someone else’s experiments always work, they’re not telling you everything.)
The idea of a digital pill that records when it has been consumed is a sound one, but as the FDA notes, there is no evidence to say it actually increases the likelihood patients that have a history of inconsistent consumption will follow their prescribed course of treatment. There is also a very strange irony in schizophrenia being the first condition this technology is being used to target.
The acid is also known to restore the vitamin C and E levels in the body. Alpha Lipoic Acid’s potent antioxidant property protects brain cells from damage during an injury. This helps in making sure that your brain functions normally even if there is any external or internal brain injury. OptiMind, one of the best nootropic supplements that you can find today contains Alpha Lipoic Acid that can help in enhancing your brain’s capabilities.

Nevertheless, a drug that improved your memory could be said to have made you smarter. We tend to view rote memory, the ability to memorize facts and repeat them, as a dumber kind of intelligence than creativity, strategy, or interpersonal skills. "But it is also true that certain abilities that we view as intelligence turn out to be in fact a very good memory being put to work," Farah says.
Factor analysis. The strategy: read in the data, drop unnecessary data, impute missing variables (data is too heterogeneous and collected starting at varying intervals to be clean), estimate how many factors would fit best, factor analyze, pick the ones which look like they match best my ideas of what productive is, extract per-day estimates, and finally regress LLLT usage on the selected factors to look for increases.
With subtle effects, we need a lot of data, so we want at least half a year (6 blocks) or better yet, a year (12 blocks); this requires 180 actives and 180 placebos. This is easily covered by $11 for Doctor’s Best Best Lithium Orotate (5mg), 200-Count (more precisely, Lithium 5mg (from 125mg of lithium orotate)) and $14 for 1000x1g empty capsules (purchased February 2012). For convenience I settled on 168 lithium & 168 placebos (7 pill-machine batches, 14 batches total); I can use them in 24 paired blocks of 7-days/1-week each (48 total blocks/48 weeks). The lithium expiration date is October 2014, so that is not a problem
Another moral concern is that these drugs — especially when used by Ivy League students or anyone in an already privileged position — may widen the gap between those who are advantaged and those who are not. But others have inverted the argument, saying these drugs can help those who are disadvantaged to reduce the gap. In an interview with the New York Times, Dr. Michael Anderson explains that he uses ADHD (a diagnosis he calls “made up”) as an excuse to prescribe Adderall to the children who really need it — children from impoverished backgrounds suffering from poor academic performance.
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.
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.
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:
…researchers have added a new layer to the smart pill conversation. Adderall, they’ve found, makes you think you’re doing better than you actually are….Those subjects who had been given Adderall were significantly more likely to report that the pill had caused them to do a better job….But the results of the new University of Pennsylvania study, funded by the U.S. Navy and not yet published but presented at the annual Society for Neuroscience conference last month, are consistent with much of the existing research. As a group, no overall statistically-significant improvement or impairment was seen as a result of taking Adderall. The research team tested 47 subjects, all in their 20s, all without a diagnosis of ADHD, on a variety of cognitive functions, from working memory-how much information they could keep in mind and manipulate-to raw intelligence, to memories for specific events and faces….The last question they asked their subjects was: How and how much did the pill influence your performance on today’s tests? Those subjects who had been given Adderall were significantly more likely to report that the pill had caused them to do a better job on the tasks they’d been given, even though their performance did not show an improvement over that of those who had taken the placebo. According to Irena Ilieva…it’s the first time since the 1960s that a study on the effects of amphetamine, a close cousin of Adderall, has asked how subjects perceive the effect of the drug on their performance.

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.
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.
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.
Organizations, and even entire countries, are struggling with “always working” cultures. Germany and France have adopted rules to stop employees from reading and responding to email after work hours. Several companies have explored banning after-hours email; when one Italian company banned all email for one week, stress levels dropped among employees. This is not a great surprise: A Gallup study found that among those who frequently check email after working hours, about half report having a lot of stress.

2 commenters point out that my possible lack of result is due to my mistaken assumption that if nicotine is absorbable through skin, mouth, and lungs it ought to be perfectly fine to absorb it through my stomach by drinking it (rather than vaporizing it and breathing it with an e-cigarette machine) - it’s apparently known that absorption differs in the stomach.
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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.)
When I worked on the Bulletproof Diet book, I wanted to verify that the effects I was getting from Bulletproof Coffee were not coming from modafinil, so I stopped using it and measured my cognitive performance while I was off of it. What I found was that on Bulletproof Coffee and the Bulletproof Diet, my mental performance was almost identical to my performance on modafinil. I still travel with modafinil, and I’ll take it on occasion, but while living a Bulletproof lifestyle I rarely feel the need.
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