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.

Cognition is a suite of mental phenomena that includes memory, attention and executive functions, and any drug would have to enhance executive functions to be considered truly ‘smart’. Executive functions occupy the higher levels of thought: reasoning, planning, directing attention to information that is relevant (and away from stimuli that aren’t), and thinking about what to do rather than acting on impulse or instinct. You activate executive functions when you tell yourself to count to 10 instead of saying something you may regret. They are what we use to make our actions moral and what we think of when we think about what makes us human.


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.

Aniracetam is known as one of the smart pills with the widest array of uses. From benefits for dementia patients and memory boost in adults with healthy brains, to the promotion of brain damage recovery. It also improves the quality of sleep, what affects the overall increase in focus during the day. Because it supports the production of dopamine and serotonin, it elevates our mood and helps fight depression and anxiety.

The magnesium was neither randomized nor blinded and included mostly as a covariate to avoid confounding (the Noopept coefficient & t-value increase somewhat without the Magtein variable), so an OR of 1.9 is likely too high; in any case, this experiment was too small to reliably detect any effect (~26% power, see bootstrap power simulation in the magnesium section) so we can’t say too much.
Another factor to consider is whether the nootropic is natural or synthetic. Natural nootropics generally have effects which are a bit more subtle, while synthetic nootropics can have more pronounced effects. It’s also important to note that there are natural and synthetic nootropics. Some natural nootropics include Ginkgo biloba and ginseng. One benefit to using natural nootropics is they boost brain function and support brain health. They do this by increasing blood flow and oxygen delivery to the arteries and veins in the brain. Moreover, some nootropics contain Rhodiola rosea, panxax ginseng, and more. 

Popular smart drugs on the market include methylphenidate (commonly known as Ritalin) and amphetamine (Adderall), stimulants normally used to treat attention deficit hyperactivity disorder or ADHD. In recent years, another drug called modafinil has emerged as the new favourite amongst college students. Primarily used to treat excessive sleepiness associated with the sleep disorder narcolepsy, modafinil increases alertness and energy.
“You know how they say that we can only access 20% of our brain?” says the man who offers stressed-out writer Eddie Morra a fateful pill in the 2011 film Limitless. “Well, what this does, it lets you access all of it.” Morra is instantly transformed into a superhuman by the fictitious drug NZT-48. Granted access to all cognitive areas, he learns to play the piano in three days, finishes writing his book in four, and swiftly makes himself a millionaire.
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.)

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.
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):
The evidence? Although everyone can benefit from dietary sources of essential fatty acids, supplementation is especially recommended for people with heart disease. A small study published in 2013 found that DHA may enhance memory and reaction time in healthy young adults. However, a more recent review suggested that there is not enough evidence of any effect from omega 3 supplementation in the general population.
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.
Took pill around 6 PM; I had a very long drive to and from an airport ahead of me, ideal for Adderall. In case it was Adderall, I chewed up the pill - by making it absorb faster, more of the effect would be there when I needed it, during driving, and not lingering in my system past midnight. Was it? I didn’t notice any change in my pulse, I yawned several times on the way back, my conversation was not more voluminous than usual. I did stay up later than usual, but that’s fully explained by walking to get ice cream. All in all, my best guess was that the pill was placebo, and I feel fairly confident but not hugely confident that it was placebo. I’d give it ~70%. And checking the next morning… I was right! Finally.
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 100mg dose of caffeine (half of a No-Doz or one cup of strong coffee) with 200mg of L-theanine is what the nootropics subreddit recommends in their beginner’s FAQ, and many nootropic sellers, like Peak Nootropics, suggest the same. In my own experiments, I used a pre-packaged combination from Nootrobox called Go Cubes. They’re essentially chewable coffee cubes (not as gross as it sounds) filled with that same beginner dose of caffeine, L-theanine, as well as a few B vitamins thrown into the mix. After eating an entire box of them (12 separate servings—not all at once), I can say eating them made me feel more alert and energetic, but less jittery than my usual three cups of coffee every day. I noticed enough of a difference in the past two weeks that I’ll be looking into getting some L-theanine supplements to take with my daily coffee.
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.
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]
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.
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
“I enjoyed this book. It was full of practical information. It was easy to understand. I implemented some of the ideas in the book and they have made a positive impact for me. Not only is this book a wealth of knowledge it helps you think outside the box and piece together other ideas to research and helps you understand more about TBI and the way food might help you mitigate symptoms.”
The above are all reasons to expect that even if I do excellent single-subject design self-experiments, there will still be the old problem of internal validity versus external validity: an experiment may be wrong or erroneous or unlucky in some way (lack of internal validity) or be right but not matter to anyone else (lack of external validity). For example, alcohol makes me sad & depressed; I could run the perfect blind randomized experiment for hundreds of trials and be extremely sure that alcohol makes me less happy, but would that prove that alcohol makes everyone sad or unhappy? Of course not, and as far as I know, for a lot of people alcohol has the opposite effect. So my hypothetical alcohol experiment might have tremendous internal validity (it does prove that I am sadder after inebriating), and zero external validity (someone who has never tried alcohol learns nothing about whether they will be depressed after imbibing). Keep this in mind if you are minded to take the experiments too seriously.
There are hundreds of cognitive enhancing pills (so called smart pills) on the market that simply do NOT work! With each of them claiming they are the best, how can you find the brain enhancing supplements that are both safe and effective? Our top brain enhancing pills have been picked by sorting and ranking the top brain enhancing products yourself. Our ratings are based on the following criteria.

Over the last few months, as part of a new research project, I have talked with five people who regularly use drugs at work. They are all successful in their jobs, financially secure, in stable relationships, and generally content with their lives. None of them have plans to stop using the drugs, and so far they have kept the secret from their employers. But as their colleagues become more likely to start using the same drugs (people talk, after all), will they continue to do so?

A quick search for drugs that make you smarter will lead you to the discovery of piracetam. Piracetam is the first synthetic smart drug of its kind. All other racetams derive from Piracetam. Some are far more potent, but they may also carry more side effects. Piracetam is an allosteric modulator of acetylcholine receptors. In other words, it enhances acetylcholine synthesis which boosts cognitive function.
But perhaps the biggest difference between Modafinil and other nootropics like Piracetam, according to Patel, is that Modafinil studies show more efficacy in young, healthy people, not just the elderly or those with cognitive deficits. That’s why it’s great for (and often prescribed to) military members who are on an intense tour, or for those who can’t get enough sleep for physiological reasons. One study, by researchers at Imperial College London, and published in Annals of Surgery, even showed that Modafinil helped sleep-deprived surgeons become better at planning, redirecting their attention, and being less impulsive when making decisions.
Known widely as ‘Brahmi,’ the Bacopa Monnieri or Water Hyssop, is a small herb native to India that finds mention in various Ayurvedic texts for being the best natural cognitive enhancer. It has been used traditionally for memory enhancement, asthma, epilepsy and improving mood and attention of people over 65. It is known to be one of the best brain supplement in the world.

Government restrictions and difficulty getting approval for various medical devices is expected to impede market growth. The stringency of approval by regulatory authorities is accompanied by the high cost of smart pills to challenge the growth of the smart pills market. However, the demand for speedy diagnosis, and improving reimbursement policies are likely to reveal market opportunities.
In addition, while the laboratory research reviewed here is of interest concerning the effects of stimulant drugs on specific cognitive processes, it does not tell us about the effects on cognition in the real world. How do these drugs affect academic performance when used by students? How do they affect the total knowledge and understanding that students take with them from a course? How do they affect various aspects of occupational performance? Similar questions have been addressed in relation to students and workers with ADHD (Barbaresi, Katusic, Colligan, Weaver, & Jacobsen, 2007; Halmøy, Fasmer, Gillberg, & Haavik, 2009; see also Advokat, 2010) but have yet to be addressed in the context of cognitive enhancement of normal individuals.

So I eventually got around to ordering another thing of nicotine gum, Habitrol Nicotine Gum, 4mg MINT flavor COATED gum. 96 pieces per box. Gum should be easier to double-blind myself with than nicotine patches - just buy some mint gum. If 4mg is too much, cut the gum in half or whatever. When it arrived, my hopes were borne out: the gum was rectangular and soft, which made it easy to cut into fourths.
He recommends a 10mg dose, but sublingually. He mentions COLURACETAM’s taste is more akin to that of PRAMIRACETAM than OXIRACETAM, in that it tastes absolutely vile (not a surprise), so it is impossible to double-blind a sublingual administration - even if I knew of an inactive equally-vile-tasting substitute, I’m not sure I would subject myself to it. To compensate for ingesting the coluracetam, it would make sense to double the dose to 20mg (turning the 2g into <100 doses). Whether the effects persist over multiple days is not clear; I’ll assume it does not until someone says it does, since this makes things much easier.
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.

I started with the 10g of Vitality Enhanced Blend, a sort of tan dust. Used 2 little-spoonfuls (dust tastes a fair bit like green/oolong tea dust) into the tea mug and then some boiling water. A minute of steeping and… bleh. Tastes sort of musty and sour. (I see why people recommended sweetening it with honey.) The effects? While I might’ve been more motivated - I hadn’t had caffeine that day and was a tad under the weather, a feeling which seemed to go away perhaps half an hour after starting - I can’t say I experienced any nausea or very noticeable effects. (At least the flavor is no longer quite so offensive.)


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.
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.
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.
In my last post, I talked about the idea that there is a resource that is necessary for self-control…I want to talk a little bit about the candidate for this resource, glucose. Could willpower fail because the brain is low on sugar? Let’s look at the numbers. A well-known statistic is that the brain, while only 2% of body weight, consumes 20% of the body’s energy. That sounds like the brain consumes a lot of calories, but if we assume a 2,400 calorie/day diet - only to make the division really easy - that’s 100 calories per hour on average, 20 of which, then, are being used by the brain. Every three minutes, then, the brain - which includes memory systems, the visual system, working memory, then emotion systems, and so on - consumes one (1) calorie. One. Yes, the brain is a greedy organ, but it’s important to keep its greediness in perspective… Suppose, for instance, that a brain in a person exerting their willpower - resisting eating brownies or what have you - used twice as many calories as a person not exerting willpower. That person would need an extra one third of a calorie per minute to make up the difference compared to someone not exerting willpower. Does exerting self control burn more calories?
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.

Related to the famous -racetams but reportedly better (and much less bulky), Noopept is one of the many obscure Russian nootropics. (Further reading: Google Scholar, Examine.com, Reddit, Longecity, Bluelight.ru.) Its advantages seem to be that it’s far more compact than piracetam and doesn’t taste awful so it’s easier to store and consume; doesn’t have the cloud hanging over it that piracetam does due to the FDA letters, so it’s easy to purchase through normal channels; is cheap on a per-dose basis; and it has fans claiming it is better than piracetam.

Burke says he definitely got the glow. “The first time I took it, I was working on a business plan. I had to juggle multiple contingencies in my head, and for some reason a tree with branches jumped into my head. I was able to place each contingency on a branch, retract and go back to the trunk, and in this visual way I was able to juggle more information.”
But though it’s relatively new on the scene with ambitious young professionals, creatine has a long history with bodybuilders, who have been taking it for decades to improve their muscle #gains. In the US, sports supplements are a multibillion-dollar industry – and the majority contain creatine. According to a survey conducted by Ipsos Public Affairs last year, 22% of adults said they had taken a sports supplement in the last year. If creatine was going to have a major impact in the workplace, surely we would have seen some signs of this already.
Now, what is the expected value (EV) of simply taking iodine, without the additional work of the experiment? 4 cans of 0.15mg x 200 is $20 for 2.1 years’ worth or ~$10 a year or a NPV cost of $205 (\frac{10}{\ln 1.05}) versus a 20% chance of $2000 or $400. So the expected value is greater than the NPV cost of taking it, so I should start taking iodine.
^ EFSA Panel on Dietetic Products, Nutrition and Allergies; European Food Safety Authority (EFSA), Parma, Italy (2011). "Scientific Opinion on the substantiation of health claims related to L-theanine from Camellia sinensis (L.) Kuntze (tea) and improvement of cognitive function (ID 1104, 1222, 1600, 1601, 1707, 1935, 2004, 2005), alleviation of psychological stress (ID 1598, 1601), maintenance of normal sleep (ID 1222, 1737, 2004) and reduction of menstrual discomfort (ID 1599) pursuant to Article 13(1) of Regulation (EC) No 1924/2006". EFSA Journal. 9 (6): 2238. doi:10.2903/j.efsa.2011.2238.
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