The main concern with pharmaceutical drugs is adverse effects, which also apply to nootropics with undefined effects. Long-term safety evidence is typically unavailable for nootropics.[13] Racetams — piracetam and other compounds that are structurally related to piracetam — have few serious adverse effects and low toxicity, but there is little evidence that they enhance cognition in people having no cognitive impairments.[19]
Low-dose lithium orotate is extremely cheap, ~$10 a year. There is some research literature on it improving mood and impulse control in regular people, but some of it is epidemiological (which implies considerable unreliability); my current belief is that there is probably some effect size, but at just 5mg, it may be too tiny to matter. I have ~40% belief that there will be a large effect size, but I’m doing a long experiment and I should be able to detect a large effect size with >75% chance. So, the formula is NPV of the difference between taking and not taking, times quality of information, times expectation: \frac{10 - 0}{\ln 1.05} \times 0.75 \times 0.40 = 61.4, which justifies a time investment of less than 9 hours. As it happens, it took less than an hour to make the pills & placebos, and taking them is a matter of seconds per week, so the analysis will be the time-consuming part. This one may actually turn a profit.
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.
As far as anxiety goes, psychiatrist Emily Deans has an overview of why the Kiecolt-Glaser et al 2011 study is nice; she also discusses why fish oil seems like a good idea from an evolutionary perspective. There was also a weaker earlier 2005 study also using healthy young people, which showed reduced anger/anxiety/depression plus slightly faster reactions. The anti-stress/anxiolytic may be related to the possible cardiovascular benefits (Carter et al 2013).
Some critics argue that Modafinil is an expression of that, a symptom of a new 24/7 work routine. But what if the opposite is true? Let’s say you could perform a task in significantly less time than usual. You could then use the rest of your time differently, spending it with family, volunteering, or taking part in a leisure activity. And imagine that a drug helped you focus on clearing your desk and inbox before leaving work. Wouldn’t that help you relax once you get home?

It was a productive hour, sure. But it also bore a remarkable resemblance to the normal editing process. I had imagined that the magical elixir coursing through my bloodstream would create towering storm clouds in my brain which, upon bursting, would rain cinematic adjectives onto the page as fast my fingers could type them. Unfortunately, the only thing that rained down were Google searches that began with the words "synonym for"—my usual creative process.
I have a needle phobia, so injections are right out; but from the images I have found, it looks like testosterone enanthate gels using DMSO resemble other gels like Vaseline. This suggests an easy experimental procedure: spoon an appropriate dose of testosterone gel into one opaque jar, spoon some Vaseline gel into another, and pick one randomly to apply while not looking. If one gel evaporates but the other doesn’t, or they have some other difference in behavior, the procedure can be expanded to something like and then half an hour later, take a shower to remove all visible traces of the gel. Testosterone itself has a fairly short half-life of 2-4 hours, but the gel or effects might linger. (Injections apparently operate on a time-scale of weeks; I’m not clear on whether this is because the oil takes that long to be absorbed by surrounding materials or something else.) Experimental design will depend on the specifics of the obtained substance. As a controlled substance (Schedule III in the US), supplies will be hard to obtain; I may have to resort to the Silk Road.
As for newer nootropic drugs, there are unknown risks. “Piracetam has been studied for decades,” says cognitive neuroscientist Andrew Hill, the founder of a neurofeedback company in Los Angeles called Peak Brain Institute. But “some of [the newer] compounds are things that some random editor found in a scientific article, copied the formula down and sent it to China and had a bulk powder developed three months later that they’re selling. Please don’t take it, people!”
Either prescription or illegal, daily use of testosterone would not be cheap. On the other hand, if I am one of the people for whom testosterone works very well, it would be even more valuable than modafinil, in which case it is well worth even arduous experimenting. Since I am on the fence on whether it would help, this suggests the value of information is high.

Bought 5,000 IU soft-gels of Vitamin D-333 (Examine.com; FDA adverse events) because I was feeling very apathetic in January 2011 and not getting much done, even slacking on regular habits like Mnemosyne spaced repetition review or dual n-back or my Wikipedia watchlist. Introspecting, I was reminded of depression & dysthymia & seasonal affective disorder.


Critics will often highlight ethical issues and the lack of scientific evidence for these drugs. Ethical arguments typically take the form of “tampering with nature.” Alena Buyx discusses this argument in a neuroethics project called Smart Drugs: Ethical Issues. She says that critics typically ask if it is ethically superior to accept what is “given” instead of striving for what is “made”. My response to this is simple. Just because it is natural does not mean it is superior.
Null results are generally less likely to be published. Consistent with the operation of such a bias in the present literature, the null results found in our survey were invariably included in articles reporting the results of multiple tasks or multiple measures of a single task; published single-task studies with exclusively behavioral measures all found enhancement. This suggests that some single-task studies with null results have gone unreported. The present mixed results are consistent with those of other recent reviews that included data from normal subjects, using more limited sets of tasks or medications (Advokat, 2010; Chamberlain et al., 2010; Repantis, Schlattmann, Laisney, & Heuser, 2010).
the larger size of the community enables economies of scale and increases the peak sophistication possible. In a small nootropics community, there is likely to be no one knowledgeable about statistics/experimentation/biochemistry/neuroscience/whatever-you-need-for-a-particular-discussion, and the available funds increase: consider /r/Nootropics’s testing program, which is doable only because it’s a large lucrative community to sell to so the sellers are willing to donate funds for independent lab tests/Certificates of Analysis (COAs) to be done. If there were 1000 readers rather than 23,295, how could this ever happen short of one of those 1000 readers being very altruistic?
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.
Finally, it’s not clear that caffeine results in performance gains after long-term use; homeostasis/tolerance is a concern for all stimulants, but especially for caffeine. It is plausible that all caffeine consumption does for the long-term chronic user is restore performance to baseline. (Imagine someone waking up and drinking coffee, and their performance improves - well, so would the performance of a non-addict who is also slowly waking up!) See for example, James & Rogers 2005, Sigmon et al 2009, and Rogers et al 2010. A cross-section of thousands of participants in the Cambridge brain-training study found caffeine intake showed negligible effect sizes for mean and component scores (participants were not told to use caffeine, but the training was recreational & difficult, so one expects some difference).

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 not25.)
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.

Popular among computer programmers, oxiracetam, another racetam, has been shown to be effective in recovery from neurological trauma and improvement to long-term memory. It is believed to effective in improving attention span, memory, learning capacity, focus, sensory perception, and logical thinking. It also acts as a stimulant, increasing mental energy, alertness, and motivation.
Racetams are often used as a smart drug by finance workers, students, and individuals in high-pressure jobs as a way to help them get into a mental flow state and work for long periods of time. Additionally, the habits and skills that an individual acquires while using a racetam can still be accessed when someone is not taking racetams because it becomes a habit.

I bought 500g of piracetam (Examine.com; FDA adverse events) from Smart Powders (piracetam is one of the cheapest nootropics and SP was one of the cheapest suppliers; the others were much more expensive as of October 2010), and I’ve tried it out for several days (started on 7 September 2009, and used it steadily up to mid-December). I’ve varied my dose from 3 grams to 12 grams (at least, I think the little scoop measures in grams), taking them in my tea or bitter fruit juice. Cranberry worked the best, although orange juice masks the taste pretty well; I also accidentally learned that piracetam stings horribly when I got some on a cat scratch. 3 grams (alone) didn’t seem to do much of anything while 12 grams gave me a nasty headache. I also ate 2 or 3 eggs a day.


More photos from this reportage are featured in Quartz’s new book The Objects that Power the Global Economy. You may not have seen these objects before, but they’ve already changed the way you live. Each chapter examines an object that is driving radical change in the global economy. This is from the chapter on the drug modafinil, which explores modifying the mind for a more productive life. 
If you could take a pill that would help you study and get better grades, would you? Off-label use of “smart drugs” – pharmaceuticals meant to treat disorders like ADHD, narcolepsy, and Alzheimer’s – are becoming increasingly popular among college students hoping to get ahead, by helping them to stay focused and alert for longer periods of time. But is this cheating? Should their use as cognitive enhancers be approved by the FDA, the medical community, and society at large? Do the benefits outweigh the risks?

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.
AMP and MPH increase catecholamine activity in different ways. MPH primarily inhibits the reuptake of dopamine by pre-synaptic neurons, thus leaving more dopamine in the synapse and available for interacting with the receptors of the postsynaptic neuron. AMP also affects reuptake, as well as increasing the rate at which neurotransmitter is released from presynaptic neurons (Wilens, 2006). These effects are manifest in the attention systems of the brain, as already mentioned, and in a variety of other systems that depend on catecholaminergic transmission as well, giving rise to other physical and psychological effects. Physical effects include activation of the sympathetic nervous system (i.e., a fight-or-flight response), producing increased heart rate and blood pressure. Psychological effects are mediated by activation of the nucleus accumbens, ventral striatum, and other parts of the brain’s reward system, producing feelings of pleasure and the potential for dependence.

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.


Metabolic function smart drugs provide mental benefits by generally facilitating the body’s metabolic processes related to the production of new tissues and the release of energy from food and fat stores. Creatine, a long-time favorite performance-enhancement drug for competitive athletes, was in the news recently when it was found in a double-blind, placebo-controlled crossover trial to have significant cognitive benefits – including both general speed of cognition and improvements in working memory. Ginkgo Biloba is another metabolic function smart drug used to increase memory and improve circulation – however, news from recent studies raises questions about these purported effects.
Due to the synthetic nature of racetams, you won’t find them in many of the best smart pills on the market. The intentional exclusion is not because racetams are ineffective. Instead, the vast majority of users trust natural smart drugs more. The idea of using a synthetic substance to alter your brain’s operating system is a big turn off for most people. With synthetic nootropics, you’re a test subject until more definitive studies arise.
As far as anxiety goes, psychiatrist Emily Deans has an overview of why the Kiecolt-Glaser et al 2011 study is nice; she also discusses why fish oil seems like a good idea from an evolutionary perspective. There was also a weaker earlier 2005 study also using healthy young people, which showed reduced anger/anxiety/depression plus slightly faster reactions. The anti-stress/anxiolytic may be related to the possible cardiovascular benefits (Carter et al 2013).
If this is the case, this suggests some thoughtfulness about my use of nicotine: there are times when use of nicotine will not be helpful, but times where it will be helpful. I don’t know what makes the difference, but I can guess it relates to over-stimulation: on some nights during the experiment, I had difficult concentrating on n-backing because it was boring and I was thinking about the other things I was interested in or working on - in retrospect, I wonder if those instances were nicotine nights.
Some people aren’t satisfied with a single supplement—the most devoted self-improvers buy a variety of different compounds online and create their own custom regimens, which they call “stacks.” According to Kaleigh Rogers, writing in Vice last year, companies will now take their customers’ genetic data from 23andMe or another source and use it to recommend the right combinations of smart drugs to optimize each individual’s abilities. The problem with this practice is that there’s no evidence the practice works. (And remember, the FDA doesn’t regulate supplements.) Find out the 9 best foods to boost your brain health.
the larger size of the community enables economies of scale and increases the peak sophistication possible. In a small nootropics community, there is likely to be no one knowledgeable about statistics/experimentation/biochemistry/neuroscience/whatever-you-need-for-a-particular-discussion, and the available funds increase: consider /r/Nootropics’s testing program, which is doable only because it’s a large lucrative community to sell to so the sellers are willing to donate funds for independent lab tests/Certificates of Analysis (COAs) to be done. If there were 1000 readers rather than 23,295, how could this ever happen short of one of those 1000 readers being very altruistic?
The compound is one of the best brain enhancement supplements that includes memory enhancement and protection against brain aging. Some studies suggest that the compound is an effective treatment for disorders like vascular dementia, Alzheimer’s, brain stroke, anxiety, and depression. However, there are some side effects associated with Alpha GPC, like a headache, heartburn, dizziness, skin rashes, insomnia, and confusion.
When you hear about nootropics, often called “smart drugs,” you probably picture something like the scene above from Limitless, where Bradley Cooper’s character becomes brilliant after downing a strange pill. The drugs and supplements currently available don’t pack that strong of a punch, but the concept is basically the same. Many nootropics have promising benefits, like boosting memory, focus, or motivation, and there’s research to support specific uses. But the most effective nootropics, like Modafinil, aren’t intended for use without a prescription to treat a specific condition. In fact, recreational use of nootropics is hotly-debated among doctors and medical researchers. Many have concerns about the possible adverse effects of long-term use, as well as the ethics of using cognitive enhancers to gain an advantage in school, sports, or even everyday work.
Using prescription ADHD medications, racetams, and other synthetic nootropics can boost brain power. Yes, they can work. Even so, we advise against using them long-term since the research on their safety is still new. Use them at your own risk. For the majority of users, stick with all natural brain supplements for best results. What is your favorite smart pill for increasing focus and mental energy? Tell us about your favorite cognitive enhancer in the comments below.
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.
Four of the studies focused on middle and high school students, with varied results. Boyd, McCabe, Cranford, and Young (2006) found a 2.3% lifetime prevalence of nonmedical stimulant use in their sample, and McCabe, Teter, and Boyd (2004) found a 4.1% lifetime prevalence in public school students from a single American public school district. Poulin (2001) found an 8.5% past-year prevalence in public school students from four provinces in the Atlantic region of Canada. A more recent study of the same provinces found a 6.6% and 8.7% past-year prevalence for MPH and AMP use, respectively (Poulin, 2007).
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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