The power calculation indicates a 20% chance of getting useful information. My quasi-experiment has <70% chance of being right, and I preserve a general skepticism about any experiment, even one as well done as the medical student one seems to be, and give that one a <80% chance of being right; so let’s call it 70% the effect exists, or 30% it doesn’t exist (which is the case in which I save money by dropping fish oil for 10 years).
Yet some researchers point out these drugs may not be enhancing cognition directly, but simply improving the user’s state of mind – making work more pleasurable and enhancing focus. “I’m just not seeing the evidence that indicates these are clear cognition enhancers,” says Martin Sarter, a professor at the University of Michigan, who thinks they may be achieving their effects by relieving tiredness and boredom. “What most of these are actually doing is enabling the person who’s taking them to focus,” says Steven Rose, emeritus professor of life sciences at the Open University. “It’s peripheral to the learning process itself.”
These are the most popular nootropics available at the moment. Most of them are the tried-and-tested and the benefits you derive from them are notable (e.g. Guarana). Others are still being researched and there haven’t been many human studies on these components (e.g. Piracetam). As always, it’s about what works for you and everyone has a unique way of responding to different nootropics.
These are the most popular nootropics available at the moment. Most of them are the tried-and-tested and the benefits you derive from them are notable (e.g. Guarana). Others are still being researched and there haven’t been many human studies on these components (e.g. Piracetam). As always, it’s about what works for you and everyone has a unique way of responding to different nootropics.
Some supplement blends, meanwhile, claim to work by combining ingredients – bacopa, cat's claw, huperzia serrata and oat straw in the case of Alpha Brain, for example – that have some support for boosting cognition and other areas of nervous system health. One 2014 study in Frontiers in Aging Neuroscience, suggested that huperzia serrata, which is used in China to fight Alzheimer's disease, may help slow cell death and protect against (or slow the progression of) neurodegenerative diseases. The Alpha Brain product itself has also been studied in a company-funded small randomized controlled trial, which found Alpha Brain significantly improved verbal memory when compared to adults who took a placebo.
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.”
With so many different ones to choose from, choosing the best nootropics for you can be overwhelming at times. As usual, a decision this important will require research. Study up on the top nootropics which catch your eye the most. The nootropics you take will depend on what you want the enhancement for. The ingredients within each nootropic determine its specific function. For example, some nootropics contain ginkgo biloba, which can help memory, thinking speed, and increase attention span. Check the nootropic ingredients as you determine what end results you want to see. Some nootropics supplements can increase brain chemicals such as dopamine and serotonin. An increase in dopamine levels can be very useful for memory, alertness, reward and more. Many healthy adults, as well as college students take nootropics. This really supports the central nervous system and the brain.
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!
A new all-in-one nootropic mix/company run by some people active on /r/nootropics; they offered me a month’s supply for free to try & review for them. At ~$100 a month (it depends on how many months one buys), it is not cheap (John Backus estimates one could buy the raw ingredients for $25/month) but it provides convenience & is aimed at people uninterested in spending a great deal of time reviewing research papers & anecdotes or capping their own pills (ie. people with lives) and it’s unlikely I could spare the money to subscribe if TruBrain worked well for me - but certainly there was no harm in trying it out.

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
Going back to the 1960s, although it was a Romanian chemist who is credited with discovering nootropics, a substantial amount of research on racetams was conducted in the Soviet Union. This resulted in the birth of another category of substances entirely: adaptogens, which, in addition to benefiting cognitive function were thought to allow the body to better adapt to stress.
I’ve been actively benefitting from nootropics since 1997, when I was struggling with cognitive performance and ordered almost $1000 worth of smart drugs from Europe (the only place where you could get them at the time). I remember opening the unmarked brown package and wondering whether the pharmaceuticals and natural substances would really enhance my brain.
One possibility is that when an individual takes a drug like noopept, they experience greater alertness and mental clarity. So, while the objective ability to see may not actually improve, the ability to process visual stimuli increases, resulting in the perception of improved vision. This allows individuals to process visual cues more quickly, take in scenes more easily, and allows for the increased perception of smaller details.

Long-term use is different, and research-backed efficacy is another question altogether. The nootropic market is not regulated, so a company can make claims without getting in trouble for making those claims because they’re not technically selling a drug. This is why it’s important to look for well-known brands and standardized nootropic herbs where it’s easier to calculate the suggested dose and be fairly confident about what you’re taking.
A week later: Golden Sumatran, 3 spoonfuls, a more yellowish powder. (I combined it with some tea dregs to hopefully cut the flavor a bit.) Had a paper to review that night. No (subjectively noticeable) effect on energy or productivity. I tried 4 spoonfuls at noon the next day; nothing except a little mental tension, for lack of a better word. I think that was just the harbinger of what my runny nose that day and the day before was, a head cold that laid me low during the evening.
Dallas Michael Cyr, a 41-year-old life coach and business mentor in San Diego, California, also says he experienced a mental improvement when he regularly took another product called Qualia Mind, which its makers say enhances focus, energy, mental clarity, memory and even creativity and mood. "One of the biggest things I noticed was it was much more difficult to be distracted," says Cyr, who took the supplements for about six months but felt their effects last longer. While he's naturally great at starting projects and tasks, the product allowed him to be a "great finisher" too, he says.

An unusual intervention is infrared/near-infrared light of particular wavelengths (LLLT), theorized to assist mitochondrial respiration and yielding a variety of therapeutic benefits. Some have suggested it may have cognitive benefits. LLLT sounds strange but it’s simple, easy, cheap, and just plausible enough it might work. I tried out LLLT treatment on a sporadic basis 2013-2014, and statistically, usage correlated strongly & statistically-significantly with increases in my daily self-ratings, and not with any sleep disturbances. Excited by that result, I did a randomized self-experiment 2014-2015 with the same procedure, only to find that the causal effect was weak or non-existent. I have stopped using LLLT as likely not worth the inconvenience.
Power times prior times benefit minus cost of experimentation: (0.20 \times 0.30 \times 540) - 41 = -9. So the VoI is negative: because my default is that fish oil works and I am taking it, weak information that it doesn’t work isn’t enough. If the power calculation were giving us 40% reliable information, then the chance of learning I should drop fish oil is improved enough to make the experiment worthwhile (going from 20% to 40% switches the value from -$9 to +$23.8).
Barbara Sahakian, a neuroscientist at Cambridge University, doesn’t dismiss the possibility of nootropics to enhance cognitive function in healthy people. She would like to see society think about what might be considered acceptable use and where it draws the line – for example, young people whose brains are still developing. But she also points out a big problem: long-term safety studies in healthy people have never been done. Most efficacy studies have only been short-term. “Proving safety and efficacy is needed,” she says.

Googling, you sometimes see correlational studies like Intake of Flavonoid-Rich Wine, Tea, and Chocolate by Elderly Men and Women Is Associated with Better Cognitive Test Performance; in this one, the correlated performance increase from eating chocolate was generally fairly modest (say, <10%), and the maximum effects were at 10g/day of what was probably milk chocolate, which generally has 10-40% chocolate liquor in it, suggesting any experiment use 1-4g. More interesting is the blind RCT experiment Consumption of cocoa flavanols results in acute improvements in mood and cognitive performance during sustained mental effort11, which found improvements at ~1g; the most dramatic improvement of the 4 tasks (on the Threes correct) saw a difference of 2 to 6 at the end of the hour of testing, while several of the other tests converged by the end or saw the controls winning (Sevens correct). Crews et al 2008 found no cognitive benefit, and an fMRI experiment found the change in brain oxygen levels it wanted but no improvement to reaction times.
I noticed what may have been an effect on my dual n-back scores; the difference is not large (▃▆▃▃▂▂▂▂▄▅▂▄▂▃▅▃▄ vs ▃▄▂▂▃▅▂▂▄▁▄▃▅▂▃▂▄▂▁▇▃▂▂▄▄▃▃▂▃▂▂▂▃▄▄▃▆▄▄▂▃▄▃▁▂▂▂▃▂▄▂▁▁▂▄▁▃▂▄) and appears mostly in the averages - Toomim’s quick two-sample t-test gave p=0.23, although a another analysis gives p=0.138112. One issue with this before-after quasi-experiment is that one would expect my scores to slowly rise over time and hence a fish oil after would yield a score increase - the 3.2 point difference could be attributable to that, placebo effect, or random variation etc. But an accidentally noticed effect (d=0.28) is a promising start. An experiment may be worth doing given that fish oil does cost a fair bit each year: randomized blocks permitting an fish-oil-then-placebo comparison would take care of the first issue, and then blinding (olive oil capsules versus fish oil capsules?) would take care of the placebo worry.
Remember: The strictest definition of nootropics today says that for a substance to be a true brain-boosting nootropic it must have low toxicity and few side effects. Therefore, by definition, a nootropic is safe to use. However, when people start stacking nootropics indiscriminately, taking megadoses, or importing them from unknown suppliers that may have poor quality control, it’s easy for safety concerns to start creeping in.
Nootropics. You might have heard of them. The “limitless pill” that keeps Billionaires rich. The ‘smart drugs’ that students are taking to help boost their hyperfocus. The cognitive enhancers that give corporate executives an advantage. All very exciting. But as always, the media are way behind the curve. Yes, for the past few decades, cognitive enhancers were largely sketchy substances that people used to grasp at a short term edge at the expense of their health and well being. But the days of taking prescription pills to pull an all-nighter are so 2010. The better, safer path isn’t with these stimulants but with nootropics. Nootropics consist of dietary supplements and substances which enhance your cognition, in particular when it comes to motivation, creativity, memory, and other executive functions. They play an important role in supporting memory and promoting optimal brain function. 
Table 5 lists the results of 16 tasks from 13 articles on the effects of d-AMP or MPH on cognitive control. One of the simplest tasks used to study cognitive control is the go/no-go task. Subjects are instructed to press a button as quickly as possible for one stimulus or class of stimuli (go) and to refrain from pressing for another stimulus or class of stimuli (no go). De Wit et al. (2002) used a version of this task to measure the effects of d-AMP on subjects’ ability to inhibit a response and found enhancement in the form of decreased false alarms (responses to no-go stimuli) and increased speed of correct go responses. They also found that subjects who made the most errors on placebo experienced the greatest enhancement from the drug.
Most research on these nootropics suggest they have some benefits, sure, but as Barbara Sahakian and Sharon Morein-Zamir explain in the journal Nature, nobody knows their long-term effects. And we don’t know how extended use might change your brain chemistry in the long run. Researchers are getting closer to what makes these substances do what they do, but very little is certain right now. If you’re looking to live out your own Limitless fantasy, do your research first, and proceed with caution.
There is a similar substance which can be purchased legally almost anywhere in the world called adrafinil. This is a prodrug for modafinil. You can take it, and then the body will metabolize it into modafinil, providing similar beneficial effects. Unfortunately, it takes longer for adrafinil to kick in—about an hour—rather than a matter of minutes. In addition, there are more potential side-effects to taking the prodrug as compared to the actual drug.
The power calculation indicates a 20% chance of getting useful information. My quasi-experiment has <70% chance of being right, and I preserve a general skepticism about any experiment, even one as well done as the medical student one seems to be, and give that one a <80% chance of being right; so let’s call it 70% the effect exists, or 30% it doesn’t exist (which is the case in which I save money by dropping fish oil for 10 years).
Another popular option is nicotine. Scientists are increasingly realising that this drug is a powerful nootropic, with the ability to improve a person’s memory and help them to focus on certain tasks – though it also comes with well-documented obvious risks and side effects. “There are some very famous neuroscientists who chew Nicorette in order to enhance their cognitive functioning. But they used to smoke and that’s their substitute,” says Huberman.

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.


Rogers RD, Blackshaw AJ, Middleton HC, Matthews K, Hawtin K, Crowley C, Robbins TW. Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults: Implications for the monoaminergic basis of impulsive behaviour. Psychopharmacology. 1999;146:482–491. doi: 10.1007/PL00005494. [PubMed] [CrossRef]
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.

Take at 11 AM; distractions ensue and the Christmas tree-cutting also takes up much of the day. By 7 PM, I am exhausted and in a bad mood. While I don’t expect day-time modafinil to buoy me up, I do expect it to at least buffer me against being tired, and so I conclude placebo this time, and with more confidence than yesterday (65%). I check before bed, and it was placebo.
Two studies investigated the effects of MPH on reversal learning in simple two-choice tasks (Clatworthy et al., 2009; Dodds et al., 2008). In these tasks, participants begin by choosing one of two stimuli and, after repeated trials with these stimuli, learn that one is usually rewarded and the other is usually not. The rewarded and nonrewarded stimuli are then reversed, and participants must then learn to choose the new rewarded stimulus. Although each of these studies found functional neuroimaging correlates of the effects of MPH on task-related brain activity (increased blood oxygenation level-dependent signal in frontal and striatal regions associated with task performance found by Dodds et al., 2008, using fMRI and increased dopamine release in the striatum as measured by increased raclopride displacement by Clatworthy et al., 2009, using PET), neither found reliable effects on behavioral performance in these tasks. The one significant result concerning purely behavioral measures was Clatworthy et al.’s (2009) finding that participants who scored higher on a self-report personality measure of impulsivity showed more performance enhancement with MPH. MPH’s effect on performance in individuals was also related to its effects on individuals’ dopamine activity in specific regions of the caudate nucleus.
Smart drug, also called nootropic or cognitive enhancer, any of a group of pharmaceutical agents used to improve the intellectual capacity of persons suffering from neurological diseases and psychological disorders. The use of such drugs by healthy individuals in order to improve concentration, to study longer, and to better manage stress is a subject of controversy.

This is one of the few times we’ve actually seen a nootropic supplement take a complete leverage on the nootropic industry with the name Smart Pill. To be honest, we don’t know why other companies haven’t followed suit yet – it’s an amazing name. Simple, and to the point. Coming from supplement maker, Only Natural, Smart Pill makes some pretty bold claims regarding their pills being completely natural, whilst maintaining good quality. This is their niche – or Only Natural’s niche, for that matter. They create supplements, in this case Smart Pill, with the… Learn More...

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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