Another important epidemiological question about the use of prescription stimulants for cognitive enhancement concerns the risk of dependence. MPH and d-AMP both have high potential for abuse and addiction related to their effects on brain systems involved in motivation. On the basis of their reanalysis of NSDUH data sets from 2000 to 2002, Kroutil and colleagues (2006) estimated that almost one in 20 nonmedical users of prescription ADHD medications meets criteria for dependence or abuse. This sobering estimate is based on a survey of all nonmedical users. The immediate and long-term risks to individuals seeking cognitive enhancement remain unknown.
Drugs and catastrophe are seemingly never far apart, whether in laboratories, real life or Limitless. Downsides are all but unavoidable: if a drug enhances one particular cognitive function, the price may be paid by other functions. To enhance one dimension of cognition, you’ll need to appropriate resources that would otherwise be available for others.
Although piracetam has a history of “relatively few side effects,” it has fallen far short of its initial promise for treating any of the illnesses associated with cognitive decline, according to Lon Schneider, a professor of psychiatry and behavioral sciences at the Keck School of Medicine at the University of Southern California. “We don’t use it at all and never have.”
Adaptogens are plant-derived chemicals whose activity helps the body maintain or regain homeostasis (equilibrium between the body’s metabolic processes). Almost without exception, adaptogens are available over-the-counter as dietary supplements, not controlled drugs. Well-known adaptogens include Ginseng, Kava Kava, Passion Flower, St. Johns Wort, and Gotu Kola. Many of these traditional remedies border on being “folk wisdom,” and have been in use for hundreds or thousands of years, and are used to treat everything from anxiety and mild depression to low libido. While these smart drugs work in a many different ways (their commonality is their resultant function within the body, not their chemical makeup), it can generally be said that the cognitive boost users receive is mostly a result of fixing an imbalance in people with poor diets, body toxicity, or other metabolic problems, rather than directly promoting the growth of new brain cells or neural connections.
Most diehard nootropic users have considered using racetams for enhancing brain function. Racetams are synthetic nootropic substances first developed in Russia. These smart drugs vary in potency, but they are not stimulants. They are unlike traditional ADHD medications (Adderall, Ritalin, Vyvanse, etc.). Instead, racetams boost cognition by enhancing the cholinergic system.
Table 4 lists the results of 27 tasks from 23 articles on the effects of d-AMP or MPH on working memory. The oldest and most commonly used type of working memory task in this literature is the Sternberg short-term memory scanning paradigm (Sternberg, 1966), in which subjects hold a set of items (typically letters or numbers) in working memory and are then presented with probe items, to which they must respond “yes” (in the set) or “no” (not in the set). The size of the set, and hence the working memory demand, is sometimes varied, and the set itself may be varied from trial to trial to maximize working memory demands or may remain fixed over a block of trials. Taken together, the studies that have used a version of this task to test the effects of MPH and d-AMP on working memory have found mixed and somewhat ambiguous results. No pattern is apparent concerning the specific version of the task or the specific drug. Four studies found no effect (Callaway, 1983; Kennedy, Odenheimer, Baltzley, Dunlap, & Wood, 1990; Mintzer & Griffiths, 2007; Tipper et al., 2005), three found faster responses with the drugs (Fitzpatrick, Klorman, Brumaghim, & Keefover, 1988; Ward et al., 1997; D. E. Wilson et al., 1971), and one found higher accuracy in some testing sessions at some dosages, but no main effect of drug (Makris et al., 2007). The meaningfulness of the increased speed of responding is uncertain, given that it could reflect speeding of general response processes rather than working memory–related processes. Aspects of the results of two studies suggest that the effects are likely due to processes other than working memory: D. E. Wilson et al. (1971) reported comparable speeding in a simple task without working memory demands, and Tipper et al. (2005) reported comparable speeding across set sizes.
Productivity is the most cited reason for using nootropics. With all else being equal, smart drugs are expected to give you that mental edge over other and advance your career. Nootropics can also be used for a host of other reasons. From studying to socialising. And from exercise and health to general well-being. Different nootropics cater to different audiences.
I have also tried to get in contact with senior executives who have experience with these drugs (either themselves or in their firms), but without success. I have to wonder: Are they completely unaware of the drugs’ existence? Or are they actively suppressing the issue? For now, companies can ignore the use of smart drugs. And executives can pretend as if these drugs don’t exist in their workplaces. But they can’t do it forever.
Nootrobox co-founder Geoffrey Woo declines a caffeinated drink in favour of a capsule of his newest product when I meet him in a San Francisco coffee shop. The entire industry has a “wild west” aura about it, he tells me, and Nootrobox wants to fix it by pushing for “smarter regulation” so safe and effective drugs that are currently unclassified can be brought into the fold. Predictably, both companies stress the higher goal of pushing forward human cognition. “I am trying to make a smarter, better populace to solve all the problems we have created,” says Nootroo founder Eric Matzner.
The price is not as good as multivitamins or melatonin. The studies showing effects generally use pretty high dosages, 1-4g daily. I took 4 capsules a day for roughly 4g of omega acids. The jar of 400 is 100 days’ worth, and costs ~$17, or around 17¢ a day. The general health benefits push me over the edge of favoring its indefinite use, but looking to economize. Usually, small amounts of packaged substances are more expensive than bulk unprocessed, so I looked at fish oil fluid products; and unsurprisingly, liquid is more cost-effective than pills (but like with the powders, straight fish oil isn’t very appetizing) in lieu of membership somewhere or some other price-break. I bought 4 bottles (16 fluid ounces each) for $53.31 total (thanks to coupons & sales), and each bottle lasts around a month and a half for perhaps half a year, or ~$100 for a year’s supply. (As it turned out, the 4 bottles lasted from 4 December 2010 to 17 June 2011, or 195 days.) My next batch lasted 19 August 2011-20 February 2012, and cost $58.27. Since I needed to buy empty 00 capsules (for my lithium experiment) and a book (Stanovich 2010, for SIAI work) from Amazon, I bought 4 more bottles of 16fl oz Nature’s Answer (lemon-lime) at $48.44, which I began using 27 February 2012. So call it ~$70 a year.
(As I was doing this, I reflected how modafinil is such a pure example of the money-time tradeoff. It’s not that you pay someone else to do something for you, which necessarily they will do in a way different from you; nor is it that you have exchanged money to free yourself of a burden of some future time-investment; nor have you paid money for a speculative return of time later in life like with many medical expenses or supplements. Rather, you have paid for 8 hours today of your own time.)
Using the 21mg patches, I cut them into quarters. What I would do is I would cut out 1 quarter, and then seal the two edges with scotch tape, and put the Pac-Man back into its sleeve. Then the next time I would cut another quarter, seal the new edge, and so on. I thought that 5.25mg might be too much since I initially found 4mg gum to be too much, but it’s delivered over a long time and it wound up feeling much more like 1mg gum used regularly. I don’t know if the tape worked, but I did not notice any loss of potency. I didn’t like them as much as the gum because I would sometimes forget to take off a patch at the end of the day and it would interfere with sleep, and because the onset is much slower and I find I need stimulants more for getting started than for ongoing stimulation so it is better to have gum which can be taken precisely when needed and start acting quickly. (One case where the patches were definitely better than the gum was long car trips where slow onset is fine, since you’re most alert at the start.) When I finally ran out of patches in June 2016 (using them sparingly), I ordered gum instead.
Also known as Arcalion or Bisbuthiamine and Enerion, Sulbutiamine is a compound of the Sulphur group and is an analog to vitamin B1, which is known to pass the blood-brain barrier easily. Sulbutiamine is found to circulate faster than Thiamine from blood to brain. It is recommended for patients suffering from mental fatigue caused due to emotional and psychological stress. The best part about this compound is that it does not have most of the common side effects linked with a few nootropics.

Some of the newest substances being used as ‘smart drugs’ are medically prescribed for other conditions. For example, methylphenidate, commonly known as Ritalin, is used to treat attention deficit hyperactivity disorder (ADHD). So is Adderall, a combination drug containing two forms of amphetamine. These are among a suite of pharmaceuticals now being used by healthy people, particularly university students, to enhance their capabilities for learning or working. 
The placebos can be the usual pills filled with olive oil. The Nature’s Answer fish oil is lemon-flavored; it may be worth mixing in some lemon juice. In Kiecolt-Glaser et al 2011, anxiety was measured via the Beck Anxiety scale; the placebo mean was 1.2 on a standard deviation of 0.075, and the experimental mean was 0.93 on a standard deviation of 0.076. (These are all log-transformed covariates or something; I don’t know what that means, but if I naively plug those numbers into Cohen’s d, I get a very large effect: \frac{1.2 - 0.93}{0.076}=3.55.)
P.S. Even though Thrive Natural’s Super Brain Renew is the best brain and memory supplement we have found, we would still love to hear about other Brain and Memory Supplements that you have tried! If you have had a great experience with a memory supplement that we did not cover in this article, let us know! E-mail me at : [email protected] We’ll check it out for you and if it looks good, we’ll post it on our site!
“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.
Nature magazine conducted a poll asking its readers about their cognitive-enhancement practices and their attitudes toward cognitive enhancement. Hundreds of college faculty and other professionals responded, and approximately one fifth reported using drugs for cognitive enhancement, with Ritalin being the most frequently named (Maher, 2008). However, the nature of the sample—readers choosing to answer a poll on cognitive enhancement—is not representative of the academic or general population, making the results of the poll difficult to interpret. By analogy, a poll on Vermont vacations, asking whether people vacation in Vermont, what they think about Vermont, and what they do if and when they visit, would undoubtedly not yield an accurate estimate of the fraction of the population that takes its vacations in Vermont.
Of course, there are drugs out there with more transformative powers. “I think it’s very clear that some do work,” says Andrew Huberman, a neuroscientist based at Stanford University. In fact, there’s one category of smart drugs which has received more attention from scientists and biohackers – those looking to alter their own biology and abilities – than any other. These are the stimulants.
the rise of IP scofflaw countries which enable the manufacture of known drugs: India does not respect the modafinil patents, enabling the cheap generics we all use, and Chinese piracetam manufacturers don’t give a damn about the FDA’s chilling-effect moves in the US. If there were no Indian or Chinese manufacturers, where would we get our modafinil? Buy them from pharmacies at $10 a pill or worse? It might be worthwhile, but think of the chilling effect on new users.
(In particular, I don’t think it’s because there’s a sudden new surge of drugs. FDA drug approval has been decreasing over the past few decades, so this is unlikely a priori. More specifically, many of the major or hot drugs go back a long time. Bacopa goes back millennia, melatonin I don’t even know, piracetam was the ’60s, modafinil was ’70s or ’80s, ALCAR was ’80s AFAIK, Noopept & coluracetam were ’90s, and so on.)
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.
While these two compounds may not be as exciting as a super pill that instantly unlocks the full potential of your brain, they currently have the most science to back them up. And, as Patel explains, they’re both relatively safe for healthy individuals of most ages. Patel explains that a combination of caffeine and L-theanine is the most basic supplement stack (or combined dose) because the L-theanine can help blunt the anxiety and “shakiness” that can come with ingesting too much caffeine.
Up to 20% of Ivy League college students have already tried “smart drugs,” so we can expect these pills to feature prominently in organizations (if they don’t already). After all, the pressure to perform is unlikely to disappear the moment students graduate. And senior employees with demanding jobs might find these drugs even more useful than a 19-year-old college kid does. Indeed, a 2012 Royal Society report emphasized that these “enhancements,” along with other technologies for self-enhancement, are likely to have far-reaching implications for the business world.
So with these 8 results in hand, what do I think? Roughly, I was right 5 of the days and wrong 3 of them. If not for the sleep effect on #4, which is - in a way - cheating (one hopes to detect modafinil due to good effects), the ratio would be 5:4 which is awfully close to a coin-flip. Indeed, a scoring rule ranks my performance at almost identical to a coin flip: -5.49 vs -5.5419. (The bright side is that I didn’t do worse than a coin flip: I was at least calibrated.)

Participants (n=205) [young adults aged 18-30 years] were recruited between July 2010 and January 2011, and were randomized to receive either a daily 150 µg (0.15mg) iodine supplement or daily placebo supplement for 32 weeks…After adjusting for baseline cognitive test score, examiner, age, sex, income, and ethnicity, iodine supplementation did not significantly predict 32 week cognitive test scores for Block Design (p=0.385), Digit Span Backward (p=0.474), Matrix Reasoning (p=0.885), Symbol Search (p=0.844), Visual Puzzles (p=0.675), Coding (p=0.858), and Letter-Number Sequencing (p=0.408).

The word “nootropic” was coined in 1972 by a Romanian scientist, Corneliu Giurgea, who combined the Greek words for “mind” and “bending.” Caffeine and nicotine can be considered mild nootropics, while prescription Ritalin, Adderall and Provigil (modafinil, a drug for treating narcolepsy) lie at the far end of the spectrum when prescribed off-label as cognitive enhancers. Even microdosing of LSD is increasingly viewed as a means to greater productivity.
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But, if we find in 10 or 20 years that the drugs don't do damage, what are the benefits? These are stimulants that help with concentration. College students take such drugs to pass tests; graduates take them to gain professional licenses. They are akin to using a calculator to solve an equation. Do you really want a doctor who passed his boards as a result of taking speed — and continues to depend on that for his practice?

My first impression of ~1g around 12:30PM was that while I do not feel like running around, within an hour I did feel like the brain fog was lighter than before. The effect wasn’t dramatic, so I can’t be very confident. Operationalizing brain fog for an experiment might be hard: it doesn’t necessarily feel like I would do better on dual n-back. I took 2 smaller doses 3 and 6 hours later, to no further effect. Over the following weeks and months, I continued to randomly alternate between potassium & non-potassium days. I noticed no effects other than sleep problems.


Given the size of the literature just reviewed, it is surprising that so many basic questions remain open. Although d-AMP and MPH appear to enhance retention of recently learned information and, in at least some individuals, also enhance working memory and cognitive control, there remains great uncertainty regarding the size and robustness of these effects and their dependence on dosage, individual differences, and specifics of the task.
Smart drugs, formally known as nootropics, are medications, supplements, and other substances that improve some aspect of mental function. In the broadest sense, smart drugs can include common stimulants such as caffeine, herbal supplements like ginseng, and prescription medications for conditions such as ADHD, Alzheimer's disease, and narcolepsy. These substances can enhance concentration, memory, and learning.

Many of the positive effects of cognitive enhancers have been seen in experiments using rats. For example, scientists can train rats on a specific test, such as maze running, and then see if the "smart drug" can improve the rats' performance. It is difficult to see how many of these data can be applied to human learning and memory. For example, what if the "smart drug" made the rat hungry? Wouldn't a hungry rat run faster in the maze to receive a food reward than a non-hungry rat? Maybe the rat did not get any "smarter" and did not have any improved memory. Perhaps the rat ran faster simply because it was hungrier. Therefore, it was the rat's motivation to run the maze, not its increased cognitive ability that affected the performance. Thus, it is important to be very careful when interpreting changes observed in these types of animal learning and memory experiments.
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.
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.
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