As mentioned earlier, cognitive control is needed not only for inhibiting actions, but also for shifting from one kind of action or mental set to another. The WCST taxes cognitive control by requiring the subject to shift from sorting cards by one dimension (e.g., shape) to another (e.g., color); failures of cognitive control in this task are manifest as perseverative errors in which subjects continue sorting by the previously successful dimension. Three studies included the WCST in their investigations of the effects of d-AMP on cognition (Fleming et al., 1995; Mattay et al., 1996, 2003), and none revealed overall effects of facilitation. However, Mattay et al. (2003) subdivided their subjects according to COMT genotype and found differences in both placebo performance and effects of the drug. Subjects who were homozygous for the val allele (associated with lower prefrontal dopamine activity) made more perseverative errors on placebo than other subjects and improved significantly with d-AMP. Subjects who were homozygous for the met allele performed best on placebo and made more errors on d-AMP.

Two additional studies assessed the effects of d-AMP on visual–motor sequence learning, a form of nondeclarative, procedural learning, and found no effect (Kumari et al., 1997; Makris, Rush, Frederich, Taylor, & Kelly, 2007). In a related experimental paradigm, Ward, Kelly, Foltin, and Fischman (1997) assessed the effect of d-AMP on the learning of motor sequences from immediate feedback and also failed to find an effect.

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.


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?)
Caffeine keeps you awake, which keeps you coding. It may also be a nootropic, increasing brain-power. Both desirable results. However, it also inhibits vitamin D receptors, and as such decreases the body’s uptake of this-much-needed-vitamin. OK, that’s not so bad, you’re not getting the maximum dose of vitamin D. So what? Well, by itself caffeine may not cause you any problems, but combined with cutting off a major source of the vitamin - the production via sunlight - you’re leaving yourself open to deficiency in double-quick time.
The data from 2-back and 3-back tasks are more complex. Three studies examined performance in these more challenging tasks and found no effect of d-AMP on average performance (Mattay et al., 2000, 2003; Mintzer & Griffiths, 2007). However, in at least two of the studies, the overall null result reflected a mixture of reliably enhancing and impairing effects. Mattay et al. (2000) examined the performance of subjects with better and worse working memory capacity separately and found that subjects whose performance on placebo was low performed better on d-AMP, whereas subjects whose performance on placebo was high were unaffected by d-AMP on the 2-back and impaired on the 3-back tasks. Mattay et al. (2003) replicated this general pattern of data with subjects divided according to genotype. The specific gene of interest codes for the production of Catechol-O-methyltransferase (COMT), an enzyme that breaks down dopamine and norepinephrine. A common polymorphism determines the activity of the enzyme, with a substitution of methionine for valine at Codon 158 resulting in a less active form of COMT. The met allele is thus associated with less breakdown of dopamine and hence higher levels of synaptic dopamine than the val allele. Mattay et al. (2003) found that subjects who were homozygous for the val allele were able to perform the n-back faster with d-AMP; those homozygous for met were not helped by the drug and became significantly less accurate in the 3-back condition with d-AMP. In the case of the third study finding no overall effect, analyses of individual differences were not reported (Mintzer & Griffiths, 2007).
“I cannot overstate how grateful I am to Cavin for having published this book (and launched his podcast) before I needed it. I am 3.5 months out from a concussion and struggling to recover that final 25% or so of my brain and function. I fully believe that diet and lifestyle can help heal many of our ills, and this book gives me a path forward right now. Gavin’s story is inspiring, and his book is well-researched and clearly written. I am a food geek and so innately understand a lot of his advice — I’m not intimidated by the thought of drastically changing my diet because I know well how to shop and cook for myself — but I so appreciate how his gentle approach and stories about his own struggles with a new diet might help people who would find it all daunting. I am in week 2 of following his advice (and also Dr. Titus Chiu’s BrainSave plan). It’s not an instantaneous miracle cure, but I do feel better in several ways that just might be related to this diet.”
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It can easily pass through the blood-brain barrier and is known to protect the nerve tissues present in the brain. There is evidence that the acid plays an instrumental role in preventing strokes in adults by decreasing the number of free radicals in the body.  It increases the production of acetylcholine, a neurotransmitter that most Alzheimer’s patients are a deficit in.
Capsule Connection sells 1000 00 pills (the largest pills) for $9. I already have a pill machine, so that doesn’t count (a sunk cost). If we sum the grams per day column from the first table, we get 9.75 grams a day. Each 00 pill can take around 0.75 grams, so we need 13 pills. (Creatine is very bulky, alas.) 13 pills per day for 1000 days is 13,000 pills, and 1,000 pills is $9 so we need 13 units and 13 times 9 is $117.

So is there a future in smart drugs? Some scientists are more optimistic than others. Gary Lynch, a professor in the School of Medicine at the University of California, Irvine argues that recent advances in neuroscience have opened the way for the smart design of drugs, configured for specific biological targets in the brain. “Memory enhancement is not very far off,” he says, although the prospects for other kinds of mental enhancement are “very difficult to know… To me, there’s an inevitability to the thing, but a timeline is difficult.”

“Certain people might benefit from certain combinations of certain things,” he told me. “But across populations, there is still no conclusive proof that substances of this class improve cognitive functions.” And with no way to reliably measure the impact of a given substance on one’s mental acuity, one’s sincere beliefs about “what works” probably have a lot to do with, say, how demanding their day was, or whether they ate breakfast, or how susceptible they are to the placebo effect.
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...
The goal of this article has been to synthesize what is known about the use of prescription stimulants for cognitive enhancement and what is known about the cognitive effects of these drugs. We have eschewed discussion of ethical issues in favor of simply trying to get the facts straight. Although ethical issues cannot be decided on the basis of facts alone, neither can they be decided without relevant facts. Personal and societal values will dictate whether success through sheer effort is as good as success with pharmacologic help, whether the freedom to alter one’s own brain chemistry is more important than the right to compete on a level playing field at school and work, and how much risk of dependence is too much risk. Yet these positions cannot be translated into ethical decisions in the real world without considerable empirical knowledge. Do the drugs actually improve cognition? Under what circumstances and for whom? Who will be using them and for what purposes? What are the mental and physical health risks for frequent cognitive-enhancement users? For occasional users?
Before taking any supplement or chemical, people want to know if there will be long term effects or consequences, When Dr. Corneliu Giurgea first authored the term “nootropics” in 1972, he also outlined the characteristics that define nootropics. Besides the ability to benefit memory and support the cognitive processes, Dr. Giurgea believed that nootropics should be safe and non-toxic.
This tendency is exacerbated by general inefficiencies in the nootropics market - they are manufactured for vastly less than they sell for, although the margins aren’t as high as they are in other supplement markets, and not nearly as comical as illegal recreational drugs. (Global Price Fixing: Our Customers are the Enemy (Connor 2001) briefly covers the vitamin cartel that operated for most of the 20th century, forcing food-grade vitamins prices up to well over 100x the manufacturing cost.) For example, the notorious Timothy Ferriss (of The Four-hour Work Week) advises imitators to find a niche market with very high margins which they can insert themselves into as middlemen and reap the profits; one of his first businesses specialized in… nootropics & bodybuilding. Or, when Smart Powders - usually one of the cheapest suppliers - was dumping its piracetam in a fire sale of half-off after the FDA warning, its owner mentioned on forums that the piracetam was still profitable (and that he didn’t really care because selling to bodybuilders was so lucrative); this was because while SP was selling 2kg of piracetam for ~$90, Chinese suppliers were offering piracetam on AliBaba for $30 a kilogram or a third of that in bulk. (Of course, you need to order in quantities like 30kg - this is more or less the only problem the middlemen retailers solve.) It goes without saying that premixed pills or products are even more expensive than the powders.
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 true34.) 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).
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.
In nootropic stacks, it’s almost always used as a counterbalance to activating ingredients like caffeine. L-Theanine, in combination with caffeine, increases alertness, reaction time, and general attention [40, 41]. At the same time, it reduces possible headaches and removes the jitteriness caused by caffeine [42]. It takes the edge of other nootropic compounds.
Smart pills containing Aniracetam may also improve communication between the brain’s hemispheres. This benefit makes Aniracetam supplements ideal for enhancing creativity and stabilizing mood. But, the anxiolytic effects of Aniracetam may be too potent for some. There are reports of some users who find that it causes them to feel unmotivated or sedated. Though, it may not be an issue if you only seek the anti-stress and anxiety-reducing effects.
It’s not clear that there is much of an effect at all. This makes it hard to design a self-experiment - how big an effect on, say, dual n-back should I be expecting? Do I need an arduous long trial or an easy short one? This would principally determine the value of information too; chocolate seems like a net benefit even if it does not affect the mind, but it’s also fairly costly, especially if one likes (as I do) dark chocolate. Given the mixed research, I don’t think cocoa powder is worth investigating further as a nootropic.
To make things more interesting, I think I would like to try randomizing different dosages as well: 12mg, 24mg, and 36mg (1-3 pills); on 5 May 2014, because I wanted to finish up the experiment earlier, I decided to add 2 larger doses of 48 & 60mg (4-5 pills) as options. Then I can include the previous pilot study as 10mg doses, and regress over dose amount.
(I was more than a little nonplussed when the mushroom seller included a little pamphlet educating one about how papaya leaves can cure cancer, and how I’m shortening my life by decades by not eating many raw fruits & vegetables. There were some studies cited, but usually for points disconnected from any actual curing or longevity-inducing results.)
Noopept is a Russian stimulant sometimes suggested for nootropics use as it may be more effective than piracetam or other -racetams, and its smaller doses make it more convenient & possibly safer. Following up on a pilot study, I ran a well-powered blind randomized self-experiment between September 2013 and August 2014 using doses of 12-60mg Noopept & pairs of 3-day blocks to investigate the impact of Noopept on self-ratings of daily functioning in addition to my existing supplementation regimen involving small-to-moderate doses of piracetam. A linear regression, which included other concurrent experiments as covariates & used multiple imputation for missing data, indicates a small benefit to the lower dose levels and harm from the highest 60mg dose level, but no dose nor Noopept as a whole was statistically-significant. It seems Noopept’s effects are too subtle to easily notice if they exist, but if one uses it, one should probably avoid 60mg+.
Many of these supplements include exotic-sounding ingredients. Ginseng root and an herb called bacopa are two that have shown some promising memory and attention benefits, says Dr. Guillaume Fond, a psychiatrist with France’s Aix-Marseille University Medical School who has studied smart drugs and cognitive enhancement. “However, data are still lacking to definitely confirm their efficacy,” he adds.
“Certain people might benefit from certain combinations of certain things,” he told me. “But across populations, there is still no conclusive proof that substances of this class improve cognitive functions.” And with no way to reliably measure the impact of a given substance on one’s mental acuity, one’s sincere beliefs about “what works” probably have a lot to do with, say, how demanding their day was, or whether they ate breakfast, or how susceptible they are to the placebo effect.
Rabiner et al. (2009) 2007 One public and one private university undergraduates (N = 3,390) 8.9% (while in college), 5.4% (past 6 months) Most common reasons endorsed: to concentrate better while studying, to be able to study longer, to feel less restless while studying 48%: from a friend with a prescription; 19%: purchased it from a friend with a prescription; 6%: purchased it from a friend without a prescription
I’m wary of others, though. The trouble with using a blanket term like “nootropics” is that you lump all kinds of substances in together. Technically, you could argue that caffeine and cocaine are both nootropics, but they’re hardly equal. With so many ways to enhance your brain function, many of which have significant risks, it’s most valuable to look at nootropics on a case-by-case basis. Here’s a list of 9 nootropics, along with my thoughts on each.
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