“One of my favorites is 1, 3, 7-trimethylxanthine,” says Dr. Mark Moyad, director of preventive and alternative medicine at the University of Michigan. He says this chemical boosts many aspects of cognition by improving alertness. It’s also associated with some memory benefits. “Of course,” Moyad says, “1, 3, 7-trimethylxanthine goes by another name—caffeine.”
So the chi-squared believes there is a statistically-significant difference, the two-sample test disagrees, and the binomial also disagrees. Since I regarded it as a dubious theory, can’t see a difference, and the binomial seems like the most appropriate test, I conclude that several months of 1mg iodine did not change my eye color. (As a final test, when I posted the results on the Longecity forum where people were claiming the eye color change, I swapped the labels on the photos to see if anyone would claim something along the lines when I look at the photos, I can see a difference!. I thought someone might do that, which would be a damning demonstration of their biases & wishful thinking, but no one did.)

Methylphenidate, commonly known as Ritalin, is a stimulant first synthesised in the 1940s. More accurately, it’s a psychostimulant - often prescribed for ADHD - that is intended as a drug to help focus and concentration. It also reduces fatigue and (potentially) enhances cognition. Similar to Modafinil, Ritalin is believed to reduce dissipation of dopamine to help focus. Ritalin is a Class B drug in the UK, and possession without a prescription can result in a 5 year prison sentence. Please note: Side Effects Possible. See this article for more on Ritalin.
“Cavin has done an amazing job in all aspects of his life. Overcoming the horrific life threatening accident, and then going on to do whatever he can to help others with his contagious wonderful attitude. This book is an easy to understand fact filled manual for anyone, but especially those who are or are caregivers for a loved one with tbi. I also highly recommend his podcast series.”
Took pill 1:27 PM. At 2 my hunger gets the best of me (despite my usual tea drinking and caffeine+piracetam pills) and I eat a large lunch. This makes me suspicious it was placebo - on the previous days I had noted a considerable appetite-suppressant effect. 5:25 PM: I don’t feel unusually tired, but nothing special about my productivity. 8 PM; no longer so sure. Read and excerpted a fair bit of research I had been putting off since the morning. After putting away all the laundry at 10, still feeling active, I check. It was Adderall. I can’t claim this one either way. By 9 or 10 I had begun to wonder whether it was really Adderall, but I didn’t feel confident saying it was; my feeling could be fairly described as 50%.

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Because smart drugs like modafinil, nicotine, and Adderall come with drawbacks, I developed my own line of nootropics, including Forbose and SmartMode, that’s safe, widely available, and doesn’t require a prescription. Forskolin, found in Forbose, has been a part of Indian Ayurvedic medicine for thousands of years. In addition to being fun to say, forskolin increases cyclic adenosine monophosphate (cAMP), a molecule essential to learning and memory formation. [8]
The smart pill that FDA approved is called Abilify MyCite. This tiny pill has a drug and an ingestible sensor. The sensor gets activated when it comes into contact with stomach fluid to detect when the pill has been taken. The data is then transmitted to a wearable patch that eventually conveys the information to a paired smartphone app. Doctors and caregivers, with the patient’s consent, can then access the data via a web portal.
12:18 PM. (There are/were just 2 Adderall left now.) I manage to spend almost the entire afternoon single-mindedly concentrating on transcribing two parts of a 1996 Toshio Okada interview (it was very long, and the formatting more challenging than expected), which is strong evidence for Adderall, although I did feel fairly hungry while doing it. I don’t go to bed until midnight and & sleep very poorly - despite taking triple my usual melatonin! Inasmuch as I’m already fairly sure that Adderall damages my sleep, this makes me even more confident (>80%). When I grumpily crawl out of bed and check: it’s Adderall. (One Adderall left.)
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.
One should note the serious caveats here: it is a small in vitro study of a single category of human cells with an effect size that is not clear on a protein which feeds into who-knows-what pathways. It is not a result in a whole organism on any clinically meaningful endpoint, even if we take it at face-value (many results never replicate). A look at followup work citing Rapuri et al 2007 is not encouraging: Google Scholar lists no human studies of any kind, much less high-quality studies like RCTs; just some rat followups on the calcium effect. This is not to say Rapuri et al 2007 is a bad study, just that it doesn’t bear the weight people are putting on it: if you enjoy caffeine, this is close to zero evidence that you should reduce or drop caffeine consumption; if you’re taking too much caffeine, you already have plenty of reasons to reduce; if you’re drinking lots of coffee, you already have plenty of reasons to switch to tea; etc.
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).
Many over the counter and prescription smart drugs fall under the category of stimulants. These substances contribute to an overall feeling of enhanced alertness and attention, which can improve concentration, focus, and learning. While these substances are often considered safe in moderation, taking too much can cause side effects such as decreased cognition, irregular heartbeat, and cardiovascular problems.
If you could take a drug to boost your brainpower, would you? This question, faced by Bradley Cooper’s character in the big-budget movie Limitless, is now facing students who are frantically revising for exams. Although they are nowhere near the strength of the drug shown in the film, mind-enhancing drugs are already on the pharmacy shelves, and many people are finding the promise of sharper thinking through chemistry highly seductive.

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).

Certain pharmaceuticals could also qualify as nootropics. For at least the past 20 years, a lot of people—students, especially—have turned to attention deficit hyperactivity disorder (ADHD) drugs like Ritalin and Adderall for their supposed concentration-strengthening effects. While there’s some evidence that these stimulants can improve focus in people without ADHD, they have also been linked, in both people with and without an ADHD diagnosis, to insomnia, hallucinations, seizures, heart trouble and sudden death, according to a 2012 review of the research in the journal Brain and Behavior. They’re also addictive.
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.
But though it’s relatively new on the scene with ambitious young professionals, creatine has a long history with bodybuilders, who have been taking it for decades to improve their muscle #gains. In the US, sports supplements are a multibillion-dollar industry – and the majority contain creatine. According to a survey conducted by Ipsos Public Affairs last year, 22% of adults said they had taken a sports supplement in the last year. If creatine was going to have a major impact in the workplace, surely we would have seen some signs of this already.
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.
The term “smart pills” refers to miniature electronic devices that are shaped and designed in the mold of pharmaceutical capsules but perform highly advanced functions such as sensing, imaging and drug delivery. They may include biosensors or image, pH or chemical sensors. Once they are swallowed, they travel along the gastrointestinal tract to capture information that is otherwise difficult to obtain, and then are easily eliminated from the system. Their classification as ingestible sensors makes them distinct from implantable or wearable sensors.
Noopept was developed in Russia in the 90s, and is alleged to improve learning. This drug modifies acetylcholine and AMPA receptors, increasing the levels of these neurotransmitters in the brain. This is believed to account for reports of its efficacy as a 'study drug'. Noopept in the UK is illegal, as the 2016 Psychoactive Substances Act made it an offence to sell this drug in the UK - selling it could even lead to 7 years in prison. To enhance its nootropic effects, some users have been known to snort Noopept.
In terms of legal status, Adrafinil is legal in the United States but is unregulated. You need to purchase this supplement online, as it is not a prescription drug at this time. Modafinil on the other hand, is heavily regulated throughout the United States. It is being used as a narcolepsy drug, but isn’t available over the counter. You will need to obtain a prescription from your doctor, which is why many turn to Adrafinil use instead.
Two variants of the Towers of London task were used by Elliott et al. (1997) to study the effects of MPH on planning. The object of this task is for subjects to move game pieces from one position to another while adhering to rules that constrain the ways in which they can move the pieces, thus requiring subjects to plan their moves several steps ahead. Neither version of the task revealed overall effects of the drug, but one version showed impairment for the group that received the drug first, and the other version showed enhancement for the group that received the placebo first.
Noopept shows a much greater affinity for certain receptor sites in the brain than racetams, allowing doses as small as 10-30mg to provide increased focus, improved logical thinking function, enhanced short and long-term memory functions, and increased learning ability including improved recall. In addition, users have reported a subtle psychostimulatory effect.
Another well-known smart drug classed as a cholinergic is Sulbutiamine, a synthetic derivative of thiamine which crosses the blood-brain barrier and has been shown to improve memory while reducing psycho-behavioral inhibition. While Sulbutiamine has been shown to exhibit cholinergic regulation within the hippocampus, the reasons for the drug’s discernable effects on the brain remain unclear. This smart drug, available over the counter as a nutritional supplement, has a long history of use, and appears to have no serious side effects at therapeutic levels.

SOURCES: Marvin Hausman, MD, CEO, Axonyx Inc. Axel Unterbeck, PhD, president, chief scientific officer, Memory Pharmaceuticals. Martha Farah, PhD, professor, department of psychiatry, University of Pennsylvania. Howard Gardner, PhD, Hobbs Professor of Education and Cognition, Harvard Graduate School of Education. Nature Reviews Neuroscience, May 2004. Neurology, July 2002. Alzheimer's Association.
Yet some researchers point out these drugs may not be enhancing cognition directly, but simply improving the user’s state of mind – making work more pleasurable and enhancing focus. “I’m just not seeing the evidence that indicates these are clear cognition enhancers,” says Martin Sarter, a professor at the University of Michigan, who thinks they may be achieving their effects by relieving tiredness and boredom. “What most of these are actually doing is enabling the person who’s taking them to focus,” says Steven Rose, emeritus professor of life sciences at the Open University. “It’s peripheral to the learning process itself.”
ADHD medication sales are growing rapidly, with annual revenues of $12.9 billion in 2015. These drugs can be obtained legally by those who have a prescription, which also includes those who have deliberately faked the symptoms in order to acquire the desired medication. (According to an experiment published in 2010, it is difficult for medical practitioners to separate those who feign the symptoms from those who actually have them.) That said, faking might not be necessary if a doctor deems your desired productivity level or your stress around a big project as reason enough to prescribe medication.
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.
One fairly powerful nootropic substance that, appropriately, has fallen out of favor is nicotine. It’s the chemical that gives tobacco products their stimulating kick. It isn’t what makes them so deadly, but it does make smoking very addictive. When Europeans learned about tobacco’s use from indigenous tribes they encountered in the Americas in the 15th and 16th centuries, they got hooked on its mood-altering effects right away and even believed it could cure joint pain, epilepsy, and the plague. Recently, researchers have been testing the effects of nicotine that’s been removed from tobacco, and they believe that it might help treat neurological disorders including Parkinson’s disease and schizophrenia; it may also improve attention and focus. But, please, don’t start smoking or vaping. Check out these 14 weird brain exercises that make you smarter.
Even party drugs are going to work: Biohackers are taking recreational drugs like LSD, psilocybin mushrooms, and mescaline in microdoses—about a tenth of what constitutes a typical dose—with the goal of becoming more focused and creative. Many who’ve tried it report positive results, but real research on the practice—and its safety—is a long way off. “Whether microdosing with LSD improves creativity and cognition remains to be determined in an objective experiment using double-blind, placebo-controlled methodology,” Sahakian says.
Even party drugs are going to work: Biohackers are taking recreational drugs like LSD, psilocybin mushrooms, and mescaline in microdoses—about a tenth of what constitutes a typical dose—with the goal of becoming more focused and creative. Many who’ve tried it report positive results, but real research on the practice—and its safety—is a long way off. “Whether microdosing with LSD improves creativity and cognition remains to be determined in an objective experiment using double-blind, placebo-controlled methodology,” Sahakian says.
This mental stimulation is what increases focus and attention span in the user. The FDA permitted treatments for Modafinil include extreme sleepiness and shift work disorder. It can also get prescribed for narcolepsy, and obstructive sleep apnea. Modafinil is not FDA approved for the treatment of ADHD. Yet, many medical professionals feel it is a suitable Adderall alternative.
Looking at the prices, the overwhelming expense is for modafinil. It’s a powerful stimulant - possibly the single most effective ingredient in the list - but dang expensive. Worse, there’s anecdotal evidence that one can develop tolerance to modafinil, so we might be wasting a great deal of money on it. (And for me, modafinil isn’t even very useful in the daytime: I can’t even notice it.) If we drop it, the cost drops by a full $800 from $1761 to $961 (almost halving) and to $0.96 per day. A remarkable difference, and if one were genetically insensitive to modafinil, one would definitely want to remove it.
Many of the most popular “smart drugs” (Piracetam, Sulbutiamine, Ginkgo Biloba, etc.) have been around for decades or even millenia but are still known only in medical circles or among esoteric practicioners of herbal medicine. Why is this? If these compounds have proven cognitive benefits, why are they not ubiquitous? How come every grade-school child gets fluoride for the development of their teeth (despite fluoride’s being a known neurotoxin) but not, say, Piracetam for the development of their brains? Why does the nightly news slant stories to appeal more to a fear-of-change than the promise of a richer cognitive future?
“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!
After 7 days, I ordered a kg of choline bitartrate from Bulk Powders. Choline is standard among piracetam-users because it is pretty universally supported by anecdotes about piracetam headaches, has support in rat/mice experiments27, and also some human-related research. So I figured I couldn’t fairly test piracetam without some regular choline - the eggs might not be enough, might be the wrong kind, etc. It has a quite distinctly fishy smell, but the actual taste is more citrus-y, and it seems to neutralize the piracetam taste in tea (which makes things much easier for me).
Adrafinil is a prodrug for Modafinil, which means it can be metabolized into Modafinil to give you a similar effect. And you can buy it legally just about anywhere. But there are a few downsides. Patel explains that you have to take a lot more to achieve a similar effect as Modafinil, wait longer for it to kick in (45-60 minutes), there are more potential side effects, and there aren’t any other benefits to taking it.

Besides Adderall, I also purchased on Silk Road 5x250mg pills of armodafinil. The price was extremely reasonable, 1.5btc or roughly $23 at that day’s exchange rate; I attribute the low price to the seller being new and needing feedback, and offering a discount to induce buyers to take a risk on him. (Buyers bear a large risk on Silk Road since sellers can easily physically anonymize themselves from their shipment, but a buyer can be found just by following the package.) Because of the longer active-time, I resolved to test the armodafinil not during the day, but with an all-nighter.
In most cases, cognitive enhancers have been used to treat people with neurological or mental disorders, but there is a growing number of healthy, "normal" people who use these substances in hopes of getting smarter. Although there are many companies that make "smart" drinks, smart power bars and diet supplements containing certain "smart" chemicals, there is little evidence to suggest that these products really work. Results from different laboratories show mixed results; some labs show positive effects on memory and learning; other labs show no effects. There are very few well-designed studies using normal healthy people.
Caffeine (Examine.com; FDA adverse events) is of course the most famous stimulant around. But consuming 200mg or more a day, I have discovered the downside: it is addictive and has a nasty withdrawal - headaches, decreased motivation, apathy, and general unhappiness. (It’s a little amusing to read academic descriptions of caffeine addiction9; if caffeine were a new drug, I wonder what Schedule it would be in and if people might be even more leery of it than modafinil.) Further, in some ways, aside from the ubiquitous placebo effect, caffeine combines a mix of weak performance benefits (Lorist & Snel 2008, Nehlig 2010) with some possible decrements, anecdotally and scientifically:
Among the questions to be addressed in the present article are, How widespread is the use of prescription stimulants for cognitive enhancement? Who uses them, for what specific purposes? Given that nonmedical use of these substances is illegal, how are they obtained? Furthermore, do these substances actually enhance cognition? If so, what aspects of cognition do they enhance? Is everyone able to be enhanced, or are some groups of healthy individuals helped by these drugs and others not? The goal of this article is to address these questions by reviewing and synthesizing findings from the existing scientific literature. We begin with a brief overview of the psychopharmacology of the two most commonly used prescription stimulants.
The title question, whether prescription stimulants are smart pills, does not find a unanimous answer in the literature. The preponderance of evidence is consistent with enhanced consolidation of long-term declarative memory. For executive function, the overall pattern of evidence is much less clear. Over a third of the findings show no effect on the cognitive processes of healthy nonelderly adults. Of the rest, most show enhancement, although impairment has been reported (e.g., Rogers et al., 1999), and certain subsets of participants may experience impairment (e.g., higher performing participants and/or those homozygous for the met allele of the COMT gene performed worse on drug than placebo; Mattay et al., 2000, 2003). Whereas the overall trend is toward enhancement of executive function, the literature contains many exceptions to this trend. Furthermore, publication bias may lead to underreporting of these exceptions.
If you haven’t seen the movie, imagine unfathomable brain power in capsule form. Picture a drug from another universe. It can transform an unsuccessful couch potato into a millionaire financial mogul. Ingesting the powerful smart pill boosts intelligence and turns you into a prodigy. Its results are instant. Sounds great, right? If only it were real.
Most people I talk to about modafinil seem to use it for daytime usage; for me that has not ever worked out well, but I had nothing in particular to show against it. So, as I was capping the last of my piracetam-caffeine mix and clearing off my desk, I put the 4 remaining Modalerts pills into capsules with the last of my creatine powder and then mixed them with 4 of the theanine-creatine pills. Like the previous Adderall trial, I will pick one pill blindly each day and guess at the end which it was. If it was active (modafinil-creatine), take a break the next day; if placebo (theanine-creatine), replace the placebo and try again the next day. We’ll see if I notice anything on DNB or possibly gwern.net edits.
After I ran out of creatine, I noticed the increased difficulty, and resolved to buy it again at some point; many months later, there was a Smart Powders sale so bought it in my batch order, $12 for 1000g. As before, it made Taekwondo classes a bit easier. I paid closer attention this second time around and noticed that as one would expect, it only helped with muscular fatigue and did nothing for my aerobic issues. (I hate aerobic exercise, so it’s always been a weak point.) I eventually capped it as part of a sulbutiamine-DMAE-creatine-theanine mix. This ran out 1 May 2013. In March 2014, I spent $19 for 1kg of micronized creatine monohydrate to resume creatine use and also to use it as a placebo in a honey-sleep experiment testing Seth Roberts’s claim that a few grams of honey before bedtime would improve sleep quality: my usual flour placebo being unusable because the mechanism might be through simple sugars, which flour would digest into. (I did not do the experiment: it was going to be a fair amount of messy work capping the honey and creatine, and I didn’t believe Roberts’s claims for a second - my only reason to do it would be to prove the claim wrong but he’d just ignore me and no one else cares.) I didn’t try measuring out exact doses but just put a spoonful in my tea each morning (creatine is tasteless). The 1kg lasted from 25 March to 18 September or 178 days, so ~5.6g & $0.11 per day.
In addition, the cognitive enhancing effects of stimulant drugs often depend on baseline performance. So whilst stimulants enhance performance in people with low baseline cognitive abilities, they often impair performance in those who are already at optimum. Indeed, in a study by Randall et al., modafinil only enhanced cognitive performance in subjects with a lower (although still above-average) IQ.
Actually, researchers are studying substances that may improve mental abilities. These substances are called "cognitive enhancers" or "smart drugs" or "nootropics." ("Nootropic" comes from Greek - "noos" = mind and "tropos" = changed, toward, turn). The supposed effects of cognitive enhancement can be several things. For example, it could mean improvement of memory, learning, attention, concentration, problem solving, reasoning, social skills, decision making and planning.
I noticed what may have been an effect on my dual n-back scores; the difference is not large (▃▆▃▃▂▂▂▂▄▅▂▄▂▃▅▃▄ vs ▃▄▂▂▃▅▂▂▄▁▄▃▅▂▃▂▄▂▁▇▃▂▂▄▄▃▃▂▃▂▂▂▃▄▄▃▆▄▄▂▃▄▃▁▂▂▂▃▂▄▂▁▁▂▄▁▃▂▄) and appears mostly in the averages - Toomim’s quick two-sample t-test gave p=0.23, although a another analysis gives p=0.138112. One issue with this before-after quasi-experiment is that one would expect my scores to slowly rise over time and hence a fish oil after would yield a score increase - the 3.2 point difference could be attributable to that, placebo effect, or random variation etc. But an accidentally noticed effect (d=0.28) is a promising start. An experiment may be worth doing given that fish oil does cost a fair bit each year: randomized blocks permitting an fish-oil-then-placebo comparison would take care of the first issue, and then blinding (olive oil capsules versus fish oil capsules?) would take care of the placebo worry.
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.
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