Flow diagram of cognitive neuroscience literature search completed July 2, 2010. Search terms were dextroamphetamine, Aderrall, methylphenidate, or Ritalin, and cognitive, cognition, learning, memory, or executive function, and healthy or normal. Stages of subsequent review used the information contained in the titles, abstracts, and articles to determine whether articles reported studies meeting the inclusion criteria stated in the text.
This world is a competitive place. If you’re not seeking an advantage, you’ll get passed by those who do. Whether you’re studying for a final exam or trying to secure a big business deal, you need a definitive mental edge. Are smart drugs and brain-boosting pills the answer for cognitive enhancement in 2019? If you’re not cheating, you’re not trying, right? Bad advice for some scenarios, but there is a grain of truth to every saying—even this one.
Does little alone, but absolutely necessary in conjunction with piracetam. (Bought from Smart Powders.) When turning my 3kg of piracetam into pills, I decided to avoid the fishy-smelling choline and go with 500g of DMAE (Examine.com); it seemed to work well when I used it before with oxiracetam & piracetam, since I had no piracetam headaches, and be considerably less bulky.

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.
So I eventually got around to ordering another thing of nicotine gum, Habitrol Nicotine Gum, 4mg MINT flavor COATED gum. 96 pieces per box. Gum should be easier to double-blind myself with than nicotine patches - just buy some mint gum. If 4mg is too much, cut the gum in half or whatever. When it arrived, my hopes were borne out: the gum was rectangular and soft, which made it easy to cut into fourths.
Took pill 12:11 PM. I am not certain. While I do get some things accomplished (a fair amount of work on the Silk Road article and its submission to places), I also have some difficulty reading through a fiction book (Sum) and I seem kind of twitchy and constantly shifting windows. I am weakly inclined to think this is Adderall (say, 60%). It’s not my normal feeling. Next morning - it was Adderall.
Unfortunately, cognitive enhancement falls between the stools of research funding, which makes it unlikely that such research programs will be carried out. Disease-oriented funders will, by definition, not support research on normal healthy individuals. The topic intersects with drug abuse research only in the assessment of risk, leaving out the study of potential benefits, as well as the comparative benefits of other enhancement methods. As a fundamentally applied research question, it will not qualify for support by funders of basic science. The pharmaceutical industry would be expected to support such research only if cognitive enhancement were to be considered a legitimate indication by the FDA, which we hope would happen only after considerably more research has illuminated its risks, benefits, and societal impact. Even then, industry would have little incentive to delve into all of the issues raised here, including the comparison of drug effects to nonpharmaceutical means of enhancing cognition.

By the end of 2009, at least 25 studies reported surveys of college students’ rates of nonmedical stimulant use. Of the studies using relatively smaller samples, prevalence was, in chronological order, 16.6% (lifetime; Babcock & Byrne, 2000), 35.3% (past year; Low & Gendaszek, 2002), 13.7% (lifetime; Hall, Irwin, Bowman, Frankenberger, & Jewett, 2005), 9.2% (lifetime; Carroll, McLaughlin, & Blake, 2006), and 55% (lifetime, fraternity students only; DeSantis, Noar, & Web, 2009). Of the studies using samples of more than a thousand students, somewhat lower rates of nonmedical stimulant use were found, although the range extends into the same high rates as the small studies: 2.5% (past year, Ritalin only; Teter, McCabe, Boyd, & Guthrie, 2003), 5.4% (past year; McCabe & Boyd, 2005), 4.1% (past year; McCabe, Knight, Teter, & Wechsler, 2005), 11.2% (past year; Shillington, Reed, Lange, Clapp, & Henry, 2006), 5.9% (past year; Teter, McCabe, LaGrange, Cranford, & Boyd, 2006), 16.2% (lifetime; White, Becker-Blease, & Grace-Bishop, 2006), 1.7% (past month; Kaloyanides, McCabe, Cranford, & Teter, 2007), 10.8% (past year; Arria, O’Grady, Caldeira, Vincent, & Wish, 2008); 5.3% (MPH only, lifetime; Du-Pont, Coleman, Bucher, & Wilford, 2008); 34% (lifetime; DeSantis, Webb, & Noar, 2008), 8.9% (lifetime; Rabiner et al., 2009), and 7.5% (past month; Weyandt et al., 2009).
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.
After my rudimentary stacking efforts flamed out in unspectacular fashion, I tried a few ready-made stacks—brand-name nootropic cocktails that offer to eliminate the guesswork for newbies. They were just as useful. And a lot more expensive. Goop’s Braindust turned water into tea-flavored chalk. But it did make my face feel hot for 45 minutes. Then there were the two pills of Brain Force Plus, a supplement hawked relentlessly by Alex Jones of InfoWars infamy. The only result of those was the lingering guilt of knowing that I had willingly put $19.95 in the jorts pocket of a dipshit conspiracy theorist.
On the other metric, suppose we removed the creatine? Dropping 4 grams of material means we only need to consume 5.75 grams a day, covered by 8 pills (compared to 13 pills). We save 5,000 pills, which would have cost $45 and also don’t spend the $68 for the creatine; assuming a modafinil formulation, that drops our $1761 down to $1648 or $1.65 a day. Or we could remove both the creatine and modafinil, for a grand total of $848 or $0.85 a day, which is pretty reasonable.

And there are other uses that may make us uncomfortable. The military is interested in modafinil as a drug to maintain combat alertness. A drug such as propranolol could be used to protect soldiers from the horrors of war. That could be considered a good thing – post-traumatic stress disorder is common in soldiers. But the notion of troops being unaffected by their experiences makes many feel uneasy.

Some suggested that the lithium would turn me into a zombie, recalling the complaints of psychiatric patients. But at 5mg elemental lithium x 200 pills, I’d have to eat 20 to get up to a single clinical dose (a psychiatric dose might be 500mg of lithium carbonate, which translates to ~100mg elemental), so I’m not worried about overdosing. To test this, I took on day 1 & 2 no less than 4 pills/20mg as an attack dose; I didn’t notice any large change in emotional affect or energy levels. And it may’ve helped my motivation (though I am also trying out the tyrosine).
A total of 330 randomly selected Saudi adolescents were included. Anthropometrics were recorded and fasting blood samples were analyzed for routine analysis of fasting glucose, lipid levels, calcium, albumin and phosphorous. Frequency of coffee and tea intake was noted. 25-hydroxyvitamin D levels were measured using enzyme-linked immunosorbent assays…Vitamin D levels were significantly highest among those consuming 9-12 cups of tea/week in all subjects (p-value 0.009) independent of age, gender, BMI, physical activity and sun exposure.

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.
A large review published in 2011 found that the drug aids with the type of memory that allows us to explicitly remember past events (called long-term conscious memory), as opposed to the type that helps us remember how to do things like riding a bicycle without thinking about it (known as procedural or implicit memory.) The evidence is mixed on its effect on other types of executive function, such as planning or ability on fluency tests, which measure a person’s ability to generate sets of data—for example, words that begin with the same letter. 

Soldiers should never be treated like children; because then they will act like them. However, There’s a reason why the 1SG is known as the Mother of the Company and the Platoon Sergeant is known as a Platoon Daddy. Because they run the day to day operations of the household, get the kids to school so to speak, and focus on the minutia of readiness and operational execution in all its glory. Officers forget they are the second link in the Chain of Command and a well operating duo of Team Leader and Squad Leader should be handling 85% of all Soldier issues, while the Platoon sergeant handles the other 15% with 1SG. Platoon Leaders and Commanders should always be present; training, leading by example, focusing on culture building, tracking and supporting NCO’s. They should be focused on big business sides of things, stepping in to administer punishment or award and reward performance. If an officer at any level is having to step into a Soldier's day to day lives an NCO at some level is failing. Officers should be junior Officers and junior Enlisted right along side their counterparts instead of eating their young and touting their “maturity” or status. If anything Officers should be asking their NCO’s where they should effect, assist, support or provide cover toward intitiatives and plans that create consistency and controlled chaos for growth of individuals two levels up and one level down of operational capabilities at every echelon of command.

I almost resigned myself to buying patches to cut (and let the nicotine evaporate) and hope they would still stick on well enough afterwards to be indistinguishable from a fresh patch, when late one sleepless night I realized that a piece of nicotine gum hanging around on my desktop for a week proved useless when I tried it, and that was the answer: if nicotine evaporates from patches, then it must evaporate from gum as well, and if gum does evaporate, then to make a perfect placebo all I had to do was cut some gum into proper sizes and let the pieces sit out for a while. (A while later, I lost a piece of gum overnight and consumed the full 4mg to no subjective effect.) Google searches led to nothing indicating I might be fooling myself, and suggested that evaporation started within minutes in patches and a patch was useless within a day. Just a day is pushing it (who knows how much is left in a useless patch?), so I decided to build in a very large safety factor and let the gum sit for around a month rather than a single day.
And in his followup work, An opportunity cost model of subjective effort and task performance (discussion). Kurzban seems to have successfully refuted the blood-glucose theory, with few dissenters from commenting researchers. The more recent opinion seems to be that the sugar interventions serve more as a reward-signal indicating more effort is a good idea, not refueling the engine of the brain (which would seem to fit well with research on procrastination).↩
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.
Neuroplasticity, or the brain's ability to change and reorganize itself in response to intrinsic and extrinsic factors, indicates great potential for us to enhance brain function by medical or other interventions. Psychotherapy has been shown to induce structural changes in the brain. Other interventions that positively influence neuroplasticity include meditation, mindfulness , and compassion.
One curious thing that leaps out looking at the graphs is that the estimated underlying standard deviations differ: the nicotine days have a strikingly large standard deviation, indicating greater variability in scores - both higher and lower, since the means weren’t very different. The difference in standard deviations is just 6.6% below 0, so the difference almost reaches our usual frequentist levels of confidence too, which we can verify by testing:
To judge from recent reports in the popular media, healthy people have also begun to use MPH and AMPs for cognitive enhancement. Major daily newspapers such as The New York Times, The LA Times, and The Wall Street Journal; magazines including Time, The Economist, The New Yorker, and Vogue; and broadcast news organizations including the BBC, CNN, and NPR have reported a trend toward growing use of prescription stimulants by healthy people for the purpose of enhancing school or work performance.
There is no official data on their usage, but nootropics as well as other smart drugs appear popular in the Silicon Valley. “I would say that most tech companies will have at least one person on something,” says Noehr. It is a hotbed of interest because it is a mentally competitive environment, says Jesse Lawler, a LA based software developer and nootropics enthusiast who produces the podcast Smart Drug Smarts. “They really see this as translating into dollars.” But Silicon Valley types also do care about safely enhancing their most prized asset – their brains – which can give nootropics an added appeal, he says.
A rough translation for the word “nootropic” comes from the Greek for “to bend or shape the mind.” And already, there are dozens of over-the-counter (OTC) products—many of which are sold widely online or in stores—that claim to boost creativity, memory, decision-making or other high-level brain functions. Some of the most popular supplements are a mixture of food-derived vitamins, lipids, phytochemicals and antioxidants that studies have linked to healthy brain function. One popular pick on Amazon, for example, is an encapsulated cocktail of omega-3s, B vitamins and plant-derived compounds that its maker claims can improve memory, concentration and focus.
The abuse of drugs is something that can lead to large negative outcomes. If you take Ritalin (Methylphenidate) or Adderall (mixed amphetamine salts) but don’t have ADHD, you may experience more focus. But what many people don’t know is that the drug is very similar to amphetamines. And the use of Ritalin is associated with serious adverse events of drug dependence, overdose and suicide attempts [80]. Taking a drug for another reason than originally intended is stupid, irresponsible and very dangerous.
Only two of the eight experiments reviewed in this section found that stimulants enhanced performance, on a nonverbal fluency task in one case and in Raven’s Progressive Matrices in the other. The small number of studies of any given type makes it difficult to draw general conclusions about the underlying executive function systems that might be influenced.
A television advertisement goes: "It's time to let Focus Factor be your memory-fog lifter." But is this supplement up to task? Focus Factor wastes no time, whether paid airtime or free online presence: it claims to be America's #1 selling brain health supplement with more than 4 million bottles sold and millions across the country actively caring for their brain health. It deems itself instrumental in helping anyone stay focused and on top of his game at home, work, or school. Learn More...

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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.


A “smart pill” is a drug that increases the cognitive ability of anyone taking it, whether the user is cognitively impaired or normal. The Romanian neuroscientist Corneliu Giurgea is often credited with first proposing, in the 1960s, that smart pills should be developed to increase the intelligence of the general population (see Giurgea, 1984). He is quoted as saying, “Man is not going to wait passively for millions of years before evolution offers him a better brain” (Gazzaniga, 2005, p. 71). In their best-selling book, Smart Drugs and Nutrients, Dean and Morgenthaler (1990) reviewed a large number of substances that have been used by healthy individuals with the goal of increasing cognitive ability. These include synthetic and natural products that affect neurotransmitter levels, neurogenesis, and blood flow to the brain. Although many of these substances have their adherents, none have become widely used. Caffeine and nicotine may be exceptions to this generalization, as one motivation among many for their use is cognitive enhancement (Julien, 2001).

Nootropics are a broad classification of cognition-enhancing compounds that produce minimal side effects and are suitable for long-term use. These compounds include those occurring in nature or already produced by the human body (such as neurotransmitters), and their synthetic analogs. We already regularly consume some of these chemicals: B vitamins, caffeine, and L-theanine, in our daily diets.

Finally, two tasks measuring subjects’ ability to control their responses to monetary rewards were used by de Wit et al. (2002) to assess the effects of d-AMP. When subjects were offered the choice between waiting 10 s between button presses for high-probability rewards, which would ultimately result in more money, and pressing a button immediately for lower probability rewards, d-AMP did not affect performance. However, when subjects were offered choices between smaller rewards delivered immediately and larger rewards to be delivered at later times, the normal preference for immediate rewards was weakened by d-AMP. That is, subjects were more able to resist the impulse to choose the immediate reward in favor of the larger reward.
Like caffeine, nicotine tolerates rapidly and addiction can develop, after which the apparent performance boosts may only represent a return to baseline after withdrawal; so nicotine as a stimulant should be used judiciously, perhaps roughly as frequent as modafinil. Another problem is that nicotine has a half-life of merely 1-2 hours, making regular dosing a requirement. There is also some elevated heart-rate/blood-pressure often associated with nicotine, which may be a concern. (Possible alternatives to nicotine include cytisine, 2’-methylnicotine, GTS-21, galantamine, Varenicline, WAY-317,538, EVP-6124, and Wellbutrin, but none have emerged as clearly superior.)
In the nearer future, Lynch points to nicotinic receptor agents – molecules that act on the neurotransmitter receptors affected by nicotine – as ones to watch when looking out for potential new cognitive enhancers. Sarter agrees: a class of agents known as α4β2* nicotinic receptor agonists, he says, seem to act on mechanisms that control attention. Among the currently known candidates, he believes they come closest “to fulfilling the criteria for true cognition enhancers.”
You’ll find several supplements that can enhance focus, energy, creativity, and mood. These brain enhancers can work very well, and their benefits often increase over time. Again, nootropics won’t dress you in a suit and carry you to Wall Street. That is a decision you’ll have to make on your own. But, smart drugs can provide the motivation boost you need to make positive life changes.

My answer is that this is not a lot of research or very good research (not nearly as good as the research on nicotine, eg.), and assuming it’s true, I don’t value long-term memory that much because LTM is something that is easily assisted or replaced (personal archives, and spaced repetition). For me, my problems tend to be more about akrasia and energy and not getting things done, so even if a stimulant comes with a little cost to long-term memory, it’s still useful for me. I’m going continue to use the caffeine. It’s not so bad in conjunction with tea, is very cheap, and I’m already addicted, so why not? Caffeine is extremely cheap, addictive, has minimal effects on health (and may be beneficial, from the various epidemiological associations with tea/coffee/chocolate & longevity), and costs extra to remove from drinks popular regardless of their caffeine content (coffee and tea again). What would be the point of carefully investigating it? Suppose there was conclusive evidence on the topic, the value of this evidence to me would be roughly $0 or since ignorance is bliss, negative money - because unless the negative effects were drastic (which current studies rule out, although tea has other issues like fluoride or metal contents), I would not change anything about my life. Why? I enjoy my tea too much. My usual tea seller doesn’t even have decaffeinated oolong in general, much less various varieties I might want to drink, apparently because de-caffeinating is so expensive it’s not worthwhile. What am I supposed to do, give up my tea and caffeine just to save on the cost of caffeine? Buy de-caffeinating machines (which I couldn’t even find any prices for, googling)? This also holds true for people who drink coffee or caffeinated soda. (As opposed to a drug like modafinil which is expensive, and so the value of a definitive answer is substantial and would justify some more extensive calculating of cost-benefit.)

As Sulbutiamine crosses the blood-brain barrier very easily, it has a positive effect on the cholinergic and the glutamatergic receptors that are responsible for essential activities impacting memory, concentration, and mood. The compound is also fat-soluble, which means it circulates rapidly and widely throughout the body and the brain, ensuring positive results. Thus, patients with schizophrenia and Parkinson’s disease will find the drug to be very effective.

Nootropics. You might have heard of them. The “limitless pill” that keeps Billionaires rich. The ‘smart drugs’ that students are taking to help boost their hyperfocus. The cognitive enhancers that give corporate executives an advantage. All very exciting. But as always, the media are way behind the curve. Yes, for the past few decades, cognitive enhancers were largely sketchy substances that people used to grasp at a short term edge at the expense of their health and well being. But the days of taking prescription pills to pull an all-nighter are so 2010. The better, safer path isn’t with these stimulants but with nootropics. Nootropics consist of dietary supplements and substances which enhance your cognition, in particular when it comes to motivation, creativity, memory, and other executive functions. They play an important role in supporting memory and promoting optimal brain function. 
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