Let's start with the basics of what smart drugs are and what they aren't. The field of cosmetic psychopharmacology is still in its infancy, but the use of smart drugs is primed to explode during our lifetimes, as researchers gain increasing understanding of which substances affect the brain and how they do so. For many people, the movie Limitless was a first glimpse into the possibility of "a pill that can make you smarter," and while that fiction is a long way from reality, the possibilities - in fact, present-day certainties visible in the daily news - are nevertheless extremely exciting.
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.
Other drugs, like cocaine, are used by bankers to manage their 18-hour workdays . 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.
Herbal supplements have been used for centuries to treat a wide range of medical conditions. Studies have shown that certain herbs may improve memory and cognition, and they can be used to help fight the effects of dementia and Alzheimer's disease. These herbs are considered safe when taken in normal doses, but care should be taken as they may interfere with other medications.
Taurine (Examine.com) was another gamble on my part, based mostly on its inclusion in energy drinks. I didn’t do as much research as I should have: it came as a shock to me when I read in Wikipedia that taurine has been shown to prevent oxidative stress induced by exercise and was an antioxidant - oxidative stress is a key part of how exercise creates health benefits and antioxidants inhibit those benefits.
One reason I like modafinil is that it enhances dopamine release, but it binds to your dopamine receptors differently than addictive substances like cocaine and amphetamines do, which may be part of the reason modafinil shares many of the benefits of other stimulants but doesn’t cause addiction or withdrawal symptoms.   It does increase focus, problem-solving abilities, and wakefulness, but it is not in the same class of drugs as Adderall, and it is not a classical stimulant. Modafinil is off of patent, so you can get it generically, or order it from India. It’s a prescription drug, so you need to talk to a physician.
Taken together, these considerations suggest that the cognitive effects of stimulants for any individual in any task will vary based on dosage and will not easily be predicted on the basis of data from other individuals or other tasks. Optimizing the cognitive effects of a stimulant would therefore require, in effect, a search through a high-dimensional space whose dimensions are dose; individual characteristics such as genetic, personality, and ability levels; and task characteristics. The mixed results in the current literature may be due to the lack of systematic optimization.
An additional complexity, related to individual differences, concerns dosage. This factor, which varies across studies and may be fixed or determined by participant body weight within a study, undoubtedly influences the cognitive effects of stimulant drugs. Furthermore, single-unit recordings with animals and, more recently, imaging of humans indicate that the effects of stimulant dose are nonmonotonic; increases enhance prefrontal function only up to a point, with further increases impairing function (e.g., Arnsten, 1998; Mattay et al., 2003; Robbins & Arnsten, 2009). Yet additional complexity comes from the fact that the optimal dosage depends on the same kinds of individual characteristics just discussed and on the task (Mattay et al., 2003).
However, normally when you hear the term nootropic kicked around, people really mean a “cognitive enhancer” — something that does benefit thinking in some way (improved memory, faster speed-of-processing, increased concentration, or a combination of these, etc.), but might not meet the more rigorous definition above. “Smart drugs” is another largely-interchangeable term.
Smart drugs could lead to enhanced cognitive abilities in the military. Also known as nootropics, smart drugs can be viewed similarly to medical enhancements. What’s important to remember though, is that smart drugs do not increase your intelligence; however, they may improve cognitive and executive functions leading to an increase in intelligence.
(We already saw that too much iodine could poison both adults and children, and of course too little does not help much - iodine would seem to follow a U-curve like most supplements.) The listed doses at iherb.com often are ridiculously large: 10-50mg! These are doses that seems to actually be dangerous for long-term consumption, and I believe these are doses that are designed to completely suffocate the thyroid gland and prevent it from absorbing any more iodine - which is useful as a short-term radioactive fallout prophylactic, but quite useless from a supplementation standpoint. Fortunately, there are available doses at Fitzgerald 2012’s exact dose, which is roughly the daily RDA: 0.15mg. Even the contrarian materials seem to focus on a modest doubling or tripling of the existing RDA, so the range seems relatively narrow. I’m fairly confident I won’t overshoot if I go with 0.15-1mg, so let’s call this 90%.
The peculiar tired-sharp feeling was there as usual, and the DNB scores continue to suggest this is not an illusion, as they remain in the same 30-50% band as my normal performance. I did not notice the previous aboulia feeling; instead, around noon, I was filled with a nervous energy and a disturbingly rapid pulse which meditation & deep breathing did little to help with, and which didn’t go away for an hour or so. Fortunately, this was primarily at church, so while I felt irritable, I didn’t actually interact with anyone or snap at them, and was able to keep a lid on it. I have no idea what that was about. I wondered if it might’ve been a serotonin storm since amphetamines are some of the drugs that can trigger storms but the Adderall had been at 10:50 AM the previous day, or >25 hours (the half-lives of the ingredients being around 13 hours). An hour or two previously I had taken my usual caffeine-piracetam pill with my morning tea - could that have interacted with the armodafinil and the residual Adderall? Or was it caffeine+modafinil? Speculation, perhaps. A house-mate was ill for a few hours the previous day, so maybe the truth is as prosaic as me catching whatever he had.
Still, the scientific backing and ingredient sourcing of nootropics on the market varies widely, and even those based in some research won't necessarily immediately, always or ever translate to better grades or an ability to finally crank out that novel. Nor are supplements of any kind risk-free, says Jocelyn Kerl, a pharmacist in Madison, Wisconsin.
A record of nootropics I have tried, with thoughts about which ones worked and did not work for me. These anecdotes should be considered only as anecdotes, and one’s efforts with nootropics a hobby to put only limited amounts of time into due to the inherent limits of drugs as a force-multiplier compared to other things like programming1; for an ironic counterpoint, I suggest the reader listen to a video of Jonathan Coulton’s I Feel Fantastic while reading.
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?)
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.
It is known that American college students have embraced cognitive enhancement, and some information exists about the demographics of the students most likely to practice cognitive enhancement with prescription stimulants. Outside of this narrow segment of the population, very little is known. What happens when students graduate and enter the world of work? Do they continue using prescription stimulants for cognitive enhancement in their first jobs and beyond? How might the answer to this question depend on occupation? For those who stay on campus to pursue graduate or professional education, what happens to patterns of use? To what extent do college graduates who did not use stimulants as students begin to use them for cognitive enhancement later in their careers? To what extent do workers without college degrees use stimulants to enhance job performance? How do the answers to these questions differ for countries outside of North America, where the studies of Table 1 were carried out?
Competitors of importance in the smart pills market have been recorded and analyzed in MRFR's report. These market players include RF Co., Ltd., CapsoVision, Inc., JINSHAN Science & Technology, BDD Limited, MEDTRONIC, Check-Cap, PENTAX Medical, INTROMEDIC, Olympus Corporation, FUJIFILM Holdings Corporation, MEDISAFE, and Proteus Digital Health, Inc.
“Cavin’s personal experience and humble writing to help educate, not only people who have suffered brain injuries, but anyone interested in the best nutritional advice for optimum brain function is a great introduction to proper nutrition filled with many recommendations of how you can make a changes to your diet immediately. This book provides amazing personal insight related to Cavin’s recovery accompanied with well cited peer reviewed sources throughout the entire book detailing the most recent findings around functional neurology!
…researchers have added a new layer to the smart pill conversation. Adderall, they’ve found, makes you think you’re doing better than you actually are….Those subjects who had been given Adderall were significantly more likely to report that the pill had caused them to do a better job….But the results of the new University of Pennsylvania study, funded by the U.S. Navy and not yet published but presented at the annual Society for Neuroscience conference last month, are consistent with much of the existing research. As a group, no overall statistically-significant improvement or impairment was seen as a result of taking Adderall. The research team tested 47 subjects, all in their 20s, all without a diagnosis of ADHD, on a variety of cognitive functions, from working memory-how much information they could keep in mind and manipulate-to raw intelligence, to memories for specific events and faces….The last question they asked their subjects was: How and how much did the pill influence your performance on today’s tests? Those subjects who had been given Adderall were significantly more likely to report that the pill had caused them to do a better job on the tasks they’d been given, even though their performance did not show an improvement over that of those who had taken the placebo. According to Irena Ilieva…it’s the first time since the 1960s that a study on the effects of amphetamine, a close cousin of Adderall, has asked how subjects perceive the effect of the drug on their performance.
I am not alone in thinking of the potential benefits of smart drugs in the military. In their popular novel Ghost Fleet: A Novel of the Next World War, P.W. Singer and August Cole tell the story of a future war using drug-like nootropic implants and pills, such as Modafinil. DARPA is also experimenting with neurological technology and enhancements such as the smart drugs discussed here. As demonstrated in the following brain initiatives: Targeted Neuroplasticity Training (TNT), Augmented Cognition, and High-quality Interface Systems such as their Next-Generational Nonsurgical Neurotechnology (N3).
In addition, large national surveys, including the NSDUH, have generally classified prescription stimulants with other stimulants including street drugs such as methamphetamine. For example, since 1975, the National Institute on Drug Abuse–sponsored Monitoring the Future (MTF) survey has gathered data on drug use by young people in the United States (Johnston, O’Malley, Bachman, & Schulenberg, 2009a, 2009b). Originally, MTF grouped prescription stimulants under a broader class of stimulants so that respondents were asked specifically about MPH only after they had indicated use of some drug in the category of AMPs. As rates of MPH prescriptions increased and anecdotal reports of nonmedical use grew, the 2001 version of the survey was changed to include a separate standalone question about MPH use. This resulted in more than a doubling of estimated annual use among 12th graders, from 2.4% to 5.1%. More recent data from the MTF suggests Ritalin use has declined (3.4% in 2008). However, this may still underestimate use of MPH, as the question refers specifically to Ritalin and does not include other brand names such as Concerta (an extended release formulation of MPH).
In a broad sense, this is enhancement; in a stricter one, it’s optimisation. “I think people think about smart drugs the way they think about steroids in athletics,” Arnsten says, “but it’s not a proper analogy, because with steroids you’re creating more muscle. With smart drugs, all you’re doing is taking the brain that you have and putting it in its optimal chemical state. You’re not taking Homer Simpson and making him into Einstein.”
These days, nootropics are beginning to take their rightful place as a particularly powerful tool in the Neurohacker’s toolbox. After all, biochemistry is deeply foundational to neural function. Whether you are trying to fix the damage that is done to your nervous system by a stressful and toxic environment or support and enhance your neural functioning, getting the chemistry right is table-stakes. And we are starting to get good at getting it right. What’s changed?
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.
Another empirical question concerns the effects of stimulants on motivation, which can affect academic and occupational performance independent of cognitive ability. Volkow and colleagues (2004) showed that MPH increased participants’ self-rated interest in a relatively dull mathematical task. This is consistent with student reports that prescription stimulants make schoolwork seem more interesting (e.g., DeSantis et al., 2008). To what extent are the motivational effects of prescription stimulants distinct from their cognitive effects, and to what extent might they be more robust to differences in individual traits, dosage, and task? Are the motivational effects of stimulants responsible for their usefulness when taken by normal healthy individuals for cognitive enhancement?
In avoiding experimenting with more Russian Noopept pills and using instead the easily-purchased powder form of Noopept, there are two opposing considerations: Russian Noopept is reportedly the best, so we might expect anything I buy online to be weaker or impure or inferior somehow and the effect size smaller than in the pilot experiment; but by buying my own supply & using powder I can double or triple the dose to 20mg or 30mg (to compensate for the original under-dosing of 10mg) and so the effect size larger than in the pilot experiment.
That study is also interesting for finding benefits to chronic piracetam+choline supplementation in the mice, which seems connected to a Russian study which reportedly found that piracetam (among other more obscure nootropics) increased secretion of BDNF in mice. See also Drug heuristics on a study involving choline supplementation in pregnant rats.↩
I split the 2 pills into 4 doses for each hour from midnight to 4 AM. 3D driver issues in Debian unstable prevented me from using Brain Workshop, so I don’t have any DNB scores to compare with the armodafinil DNB scores. I had the subjective impression that I was worse off with the Modalert, although I still managed to get a fair bit done so the deficits couldn’t’ve been too bad. The apathy during the morning felt worse than armodafinil, but that could have been caused by or exacerbated by an unexpected and very stressful 2 hour drive through rush hour and multiple accidents; the quick hour-long nap at 10 AM was half-waking half-light-sleep according to the Zeo, but seemed to help a bit. As before, I began to feel better in the afternoon and by evening felt normal, doing my usual reading. That night, the Zeo recorded my sleep as lasting ~9:40, when it was usually more like 8:40-9:00 (although I am not sure that this was due to the modafinil inasmuch as once a week or so I tend to sleep in that long, as I did a few days later without any influence from the modafinil); assuming the worse, the nap and extra sleep cost me 2 hours for a net profit of ~7 hours. While it’s not clear how modafinil affects recovery sleep (see the footnote in the essay), it’s still interesting to ponder the benefits of merely being able to delay sleep18.
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.
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.
These days, young, ambitious professionals prefer prescription stimulants—including methylphenidate (usually sold as Ritalin) and Adderall—that are designed to treat people with attention deficit hyperactivity disorder (ADHD) and are more common and more acceptable than cocaine or nicotine (although there is a black market for these pills). ADHD makes people more likely to lose their focus on tasks and to feel restless and impulsive. Diagnoses of the disorder have been rising dramatically over the past few decades—and not just in kids: In 2012, about 16 million Adderall prescriptions were written for adults between the ages of 20 and 39, according to a report in the New York Times. Both methylphenidate and Adderall can improve sustained attention and concentration, says Barbara Sahakian, professor of clinical neuropsychology at the University of Cambridge and author of the 2013 book Bad Moves: How Decision Making Goes Wrong, and the Ethics of Smart Drugs. But the drugs do have side effects, including insomnia, lack of appetite, mood swings, and—in extreme cases—hallucinations, especially when taken in amounts the exceed standard doses. Take a look at these 10 foods that help you focus.
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. 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.