It’s that time of the year again. It’s Blue Monday. We’re halfway into January, trudging through the deepest and darkest of the winter months, as we try to keep our heads high after the Christmas festivities with the motivation of our New Year’s resolutions. Some of you may have never heard of Blue Monday and let’s just say you’re not exactly missing out.
She provides many examples of observational studies where lower intakes of a certain nutrient were correlated with cognitive impairment. Obviously, if someone is deficient in a vitamin or other nutrient, the deficiency should be corrected. But she doesn’t have any evidence from prospective interventional studies showing that, in practice, altering diet significantly improves cognition for people who are deficient, much less in people who are not deficient.
Modafinil, also known as Provigil, Modalert, and Alertec, was originally made and marketed for sleep disorders, and has been prescribed in the US for this reason since 1998. It was found only by chance to help with focus and concentration, and it is only approved for the treatment of narcolepsy, shift work sleep disorder, and obstructive sleep apnea.

One of the most popular legal stimulants in the world, nicotine is often conflated with the harmful effects of tobacco; considered on its own, it has performance & possibly health benefits. Nicotine is widely available at moderate prices as long-acting nicotine patches, gums, lozenges, and suspended in water for vaping. While intended for smoking cessation, there is no reason one cannot use a nicotine patch or nicotine gum for its stimulant effects.


The Neurohacker Collective is a group of scientists, academics, and creatives who, among other things, sell nootropics. One of its premier products is Qualia Original Stack (OS), which has 41 ingredients. The large print says it improves focus, mood, and energy within 30 minutes and “supports long-term brain health.” A 22-dose supply costs $129. Such stacks operate on the idea that synergies among ingredients yield additional benefits.

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.
Nootropics still exist largely in an unregulated gray area, which makes users somewhat hesitant to discuss their regimens. But I did speak to several people who told tales of increased productivity and sharpened focus. Bob Carter, a financial analyst for a start-up called LendingHome, says that nootropics have replaced his other morning stimulant. “I basically think of it as a substitute for coffee,” he says. “I think the problem with a cappuccino from Starbucks is that it gives you the feeling of being jittery. Whereas with this particular supplement, I feel more calm.”

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.
Panax ginseng – A review by the Cochrane Collaboration concluded that "there is a lack of convincing evidence to show a cognitive enhancing effect of Panax ginseng in healthy participants and no high quality evidence about its efficacy in patients with dementia."[36] According to the National Center for Complementary and Integrative Health, "[a]lthough Asian ginseng has been widely studied for a variety of uses, research results to date do not conclusively support health claims associated with the herb."[37]
The blood half-life is 12-36 hours; hence two or three days ought to be enough to build up and wash out. A week-long block is reasonable since that gives 5 days for effects to manifest, although month-long blocks would not be a bad choice either. (I prefer blocks which fit in round periods because it makes self-experiments easier to run if the blocks fit in normal time-cycles like day/week/month. The most useless self-experiment is the one abandoned halfway.)
I don’t believe there’s any need to control for training with repeated within-subject sampling, since there will be as many samples on both control and active days drawn from the later trained period as with the initial untrained period. But yes, my D5B scores seem to have plateaued pretty much and only very slowly increase; you can look at the stats file yourself.
Tuesday: I went to bed at 1am, and first woke up at 6am, and I wrote down a dream; the lucid dreaming book I was reading advised that waking up in the morning and then going back for a short nap often causes lucid dreams, so I tried that - and wound up waking up at 10am with no dreams at all. Oops. I take a pill, but the whole day I don’t feel so hot, although my conversation and arguments seem as cogent as ever. I’m also having a terrible time focusing on any actual work. At 8 I take another; I’m behind on too many things, and it looks like I need an all-nighter to catch up. The dose is no good; at 11, I still feel like at 8, possibly worse, and I take another along with the choline+piracetam (which makes a total of 600mg for the day). Come 12:30, and I disconsolately note that I don’t seem any better, although I still seem to understand the IQ essays I am reading. I wonder if this is tolerance to modafinil, or perhaps sleep catching up to me? Possibly it’s just that I don’t remember what the quasi-light-headedness of modafinil felt like. I feel this sort of zombie-like state without change to 4am, so it must be doing something, when I give up and go to bed, getting up at 7:30 without too much trouble. Some N-backing at 9am gives me some low scores but also some pretty high scores (38/43/66/40/24/67/60/71/54 or ▂▂▆▂▁▆▅▇▄), which suggests I can perform normally if I concentrate. I take another pill and am fine the rest of the day, going to bed at 1am as usual.
The available literature on cognitive enhancing practices at times appears to lump together nootropics and “smart drugs.” Smart drugs are not officially defined, but references to this group generally include Provigil (modafinil), Adderall and Ritalin. Any confusion about the addiction potential of different brain-enhancing drugs can spread misinformation about the individual drugs. There are many nootropics on the market, so the best practice is to focus on the addiction potential of each nootropic of interest or concern.

There are over a thousand websites and hundreds of reference guides chock full of complicated methods for combining many of the compounds you’ve just discovered. There’s a reason for this: the practice of “stacking” nootropics and smart drugs into specific combinations can be far more powerful and efficacious than consuming a single, lonely compound in isolation. For example, dosing choline sources with your morning coffee can make your brain feel fresh for hours or mixing curcumin with black pepper can dramatically amp up the neural anti-inflammatory effects of both compounds. Ultimately, a teaspoon of lion’s mane extract just isn’t as titillating as lion’s mane blended with caffeine, theanine, nicotine and a touch of vinpocetine.


This calculation - reaping only \frac{7}{9} of the naive expectation - gives one pause. How serious is the sleep rebound? In another article, I point to a mice study that sleep deficits can take 28 days to repay. What if the gain from modafinil is entirely wiped out by repayment and all it did was defer sleep? Would that render modafinil a waste of money? Perhaps. Thinking on it, I believe deferring sleep is of some value, but I cannot decide whether it is a net profit.
Please take care when you’re out there on the web or in the world shopping for something to help that in progress novel or craft project of yours along. Take all care when planning on taking anything, be it a nootropic, smart drug, or brain enhancer, and do your research before buying. Make sure your so-called ‘best brain pill’ really is the best brain pill for you.
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.
The most common front-line of treatment for ADHD is medication and cognitive behavioural therapy (CBT). Prescriptions for ADHD drugs such as Ritalin, have doubled to 922,000 a year in the last decade, and whilst it offers symptom management for many, it has also been found to have significant negative side effects such as weight loss, liver toxicity, and suicidal thoughts, and in the short term may suppress pubertal growth. The aetiology of ADHD is multifactorial, meaning that there are varying influencing factors that drive the symptoms. This is perhaps why this condition has been hard to study and find effective treatment for.

There are a number of treatments for the last. I already use melatonin. I sort of have light therapy from a full-spectrum fluorescent desk lamp. But I get very little sunlight; the surprising thing would be if I didn’t have a vitamin D deficiency. And vitamin D deficiencies have been linked with all sorts of interesting things like near-sightedness, with time outdoors inversely correlating with myopia and not reading or near-work time. (It has been claimed that caffeine interferes with vitamin D absorption and so people like me especially need to take vitamin D, on top of the deficits caused by our vampiric habits, but I don’t think this is true35.) Unfortunately, there’s not very good evidence that vitamin D supplementation helps with mood/SAD/depression: there’s ~6 small RCTs with some findings of benefits, with their respective meta-analysis turning in a positive but currently non-statistically-significant result. Better confirmed is reducing all-cause mortality in elderly people (see, in order of increasing comprehensiveness: Evidence Syntheses 2013, Chung et al 2009, Autier & Gandini 2007, Bolland et al 2014).


50 pairs of active/placebos or 100 days. With 120 tablets and 4 tablets used up, that leaves me 58 doses. That might seem adequate except the paired t-test approximation is overly-optimistic, and I also expect the non-randomized non-blinded correlation is too high which means that is overly-optimistic as well. The power would be lower than I’d prefer. I decided to simply order another bottle of Solgar’s & double the sample size to be safe.
The advantage of adrafinil is that it is legal & over-the-counter in the USA, so one removes the small legal risk of ordering & possessing modafinil without a prescription, and the retailers may be more reliable because they are not operating in a niche of dubious legality. Based on comments from others, the liver problem may have been overblown, and modafinil vendors post-2012 seem to have become more unstable, so I may give adrafinil (from another source than Antiaging Central) a shot when my modafinil/armodafinil run out.
We can read off the results from the table or graph: the nicotine days average 1.1% higher, for an effect size of 0.24; however, the 95% credible interval (equivalent of confidence interval) goes all the way from 0.93 to -0.44, so we cannot exclude 0 effect and certainly not claim confidence the effect size must be >0.1. Specifically, the analysis gives a 66% chance that the effect size is >0.1. (One might wonder if any increase is due purely to a training effect - getting better at DNB. Probably not26.)

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Farah has also been considering the ethical complications resulting from the rise of smart drugs. Don't neuroenhancers confer yet another advantage on the kind of people who already can afford private tutors? Writing last year in the Cavalier Daily, the student newspaper of the University of Virginia, a columnist named Greg Crapanzano argued that neuroenhancers "create an unfair advantage for the users who are willing to break the law in order to gain an edge. These students create work that is dependent on the use of a pill rather than their own work ethic." Of course, it's hard to imagine a university administration that would require students to pee in a cup before entering an exam hall. And even with the aid of a neuroenhancer, you still have to write the essay, conceive the screenplay or finish the grant proposal. Moreover, if you can take credit for work you've done on caffeine or nicotine, then you can take credit for work produced on Provigil.


Chatterjee told me that many people who come to his clinic are cognitively preoccupied versions of what doctors call the "worried well". He had just seen a middle-aged woman, a successful Philadelphia lawyer, who mentioned having to struggle a bit to come up with certain names. "Here's an example of someone who by most measures is doing perfectly fine," Chatterjee said. "She's not having any trouble at work. But she notices she's having some problems, and it's very hard to know how much of that is just getting older." Of course, people in her position could strive to get regular exercise and plenty of intellectual stimulation, both of which have been shown to help maintain cognitive function. But maybe they're already doing so and want a bigger mental rev-up, or maybe they want something easier than sweaty workouts and Russian novels: they want a pill.
Last summer, I visited Phillips in the high desert resort town of Bend, Oregon, where he lives with his wife, Kathleen, and their two daughters, Ivy and Ruby. Phillips, who is now 36, took me for coffee at a cheery café called Thump. Wearing shorts, flip-flops and a black T-shirt, he said: "Poker is about sitting in one place, watching your opponents for a long time, and making better observations about them than they make about you." With Provigil, he "could process all the information about what was going on at the table and do something about it". Though there is no question that Phillips became much more successful at poker after taking neuroenhancers, I asked him if his improvement could be explained by a placebo effect, or by coincidence. He doubted it, but allowed that it could. Still, he said, "there's a sort of clarity I get with Provigil. With Adderall, I'd characterise the effect as correction - correction of an underlying condition. Provigil feels like enhancement." And, whereas Adderall made him "jittery", Provigil's effects were "completely limited to my brain". He had "zero difficulty sleeping".
“Who doesn’t want to maximize their cognitive ability? Who doesn’t want to maximize their muscle mass?” asks Murali Doraiswamy, who has led several trials of cognitive enhancers at Duke University Health System and has been an adviser to pharmaceutical and supplement manufacturers as well as the Food and Drug Administration. He attributes the demand to an increasingly knowledge-based society that values mental quickness and agility above all else.
Choline is very important for cognitive function because it is a precursor to Acteylcholine. Your body needs enough choline to convert into Acteylcholine to keep your brain healthy. For this reason, choline supplements are often considered great nootropics, even by themselves. CDP-Choline and Alpha GPC are the best sources for supplemental Choline.
One of the most popular legal stimulants in the world, nicotine is often conflated with the harmful effects of tobacco; considered on its own, it has performance & possibly health benefits. Nicotine is widely available at moderate prices as long-acting nicotine patches, gums, lozenges, and suspended in water for vaping. While intended for smoking cessation, there is no reason one cannot use a nicotine patch or nicotine gum for its stimulant effects.
Walnuts in particular are excellent brain food. These wrinkly nuts—which kind of resemble the human brain—are rich in vitamin E. Researchers at Chicago’s Rush University Medical Center studied the lifestyle habits of 6,000 people who were unaffected by Alzheimer’s the memory-robbing condition, and found that those who ate the most vitamin E-rich foods had a reduced risk of developing the memory-robbing condition. Vitamin E may trap free radicals that can damage brain cells, according to the Alzheimer’s Research Center. Here’s some more brain food that your noggin will thank you for eating.
Some people warn of the dangers of modafinil. There are anecdotal personal accounts online of people becoming dependent on this drug. Modafinil is the generic of the brand Provigil, a nootropic. Provigil is FDA-approved to stimulate wakefulness in people suffering from sleep disorders, such as narcolepsy and sleep apnea. Initially, Provigil was thought to have a benign, non-addiction-forming profile. As such, the Drug Enforcement Administration classifies Provigil as a Schedule IV drug, a category reserved for drugs with low abuse potential; however, recent research conducted by the National Institute on Drug Abuse (NIDA) has found that Provigil may in fact be addictive.[10]

Take quarter at midnight, another quarter at 2 AM. Night runs reasonably well once I remember to eat a lot of food (I finish a big editing task I had put off for weeks), but the apathy kicks in early around 4 AM so I gave up and watched Scott Pilgrim vs. the World, finishing around 6 AM. I then read until it’s time to go to a big shotgun club function, which occupies the rest of the morning and afternoon; I had nothing to do much of the time and napped very poorly on occasion. By the time we got back at 4 PM, the apathy was completely gone and I started some modafinil research with gusto (interrupted by going to see Puss in Boots). That night: Zeo recorded 8:30 of sleep, gap of about 1:50 in the recording, figure 10:10 total sleep; following night, 8:33; third night, 8:47; fourth, 8:20 (▇▁▁▁).

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as scientific papers become much more accessible online due to Open Access, digitization by publishers, and cheap hosting for pirates, the available knowledge about nootropics increases drastically. This reduces the perceived risk by users, and enables them to educate themselves and make much more sophisticated estimates of risk and side-effects and benefits. (Take my modafinil page: in 1997, how could an average person get their hands on any of the papers available up to that point? Or get detailed info like the FDA’s prescribing guide? Even assuming they had a computer & Internet?)

Jump up ^ Sattler, Sebastian; Mehlkop, Guido; Graeff, Peter; Sauer, Carsten (February 1, 2014). "Evaluating the drivers of and obstacles to the willingness to use cognitive enhancement drugs: the influence of drug characteristics, social environment, and personal characteristics". Substance Abuse Treatment, Prevention, and Policy. BioMed Central Ltd. p. 8. doi:10.1186/1747-597X-9-8. ISSN 1747-597X. Retrieved April 5, 2014.
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