“The author’s story alone is a remarkable account of not just survival, but transcendence of a near-death experience. Cavin went on to become an advocate for survival and survivors of traumatic brain injuries, discovering along the way the key role played by nutrition. But this book is not just for injury survivors. It is for anyone who wants to live (and eat) well.”
The goal of this article has been to synthesize what is known about the use of prescription stimulants for cognitive enhancement and what is known about the cognitive effects of these drugs. We have eschewed discussion of ethical issues in favor of simply trying to get the facts straight. Although ethical issues cannot be decided on the basis of facts alone, neither can they be decided without relevant facts. Personal and societal values will dictate whether success through sheer effort is as good as success with pharmacologic help, whether the freedom to alter one’s own brain chemistry is more important than the right to compete on a level playing field at school and work, and how much risk of dependence is too much risk. Yet these positions cannot be translated into ethical decisions in the real world without considerable empirical knowledge. Do the drugs actually improve cognition? Under what circumstances and for whom? Who will be using them and for what purposes? What are the mental and physical health risks for frequent cognitive-enhancement users? For occasional users?
Jesper Noehr, 30, reels off the ingredients in the chemical cocktail he’s been taking every day before work for the past six months. It’s a mixture of exotic dietary supplements and research chemicals that he says gives him an edge in his job without ill effects: better memory, more clarity and focus and enhanced problem-solving abilities. “I can keep a lot of things on my mind at once,” says Noehr, who is chief technology officer for a San Francisco startup.
Barbaresi WJ, Katusic SK, Colligan RC, Weaver AL, Jacobsen SJ. Modifiers of long-term school outcomes for children with attention-deficit/hyperactivity disorder: Does treatment with stimulant medication make a difference? Results from a population-based study. Journal of Developmental and Behavioral Pediatrics. 2007;28:274–287. doi: 10.1097/DBP.0b013e3180cabc28. [PubMed] [CrossRef]
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.
We included studies of the effects of these drugs on cognitive processes including learning, memory, and a variety of executive functions, including working memory and cognitive control. These studies are listed in Table 2, along with each study’s sample size, gender, age and tasks administered. Given our focus on cognition enhancement, we excluded studies whose measures were confined to perceptual or motor abilities. Studies of attention are included when the term attention refers to an executive function but not when it refers to the kind of perceptual process taxed by, for example, visual search or dichotic listening or when it refers to a simple vigilance task. Vigilance may affect cognitive performance, especially under conditions of fatigue or boredom, but a more vigilant person is not generally thought of as a smarter person, and therefore, vigilance is outside of the focus of the present review. The search and selection process is summarized in Figure 2.
Speaking of addictive substances, some people might have considered cocaine a nootropic (think: the finance industry in Wall Street in the 1980s). The incredible damage this drug can do is clear, but the plant from which it comes has been used to make people feel more energetic and less hungry, and to counteract altitude sickness in Andean South American cultures for 5,000 years, according to an opinion piece that Bolivia’s president, Evo Morales Ayma, wrote for the New York Times.
We’d want 53 pairs, but Fitzgerald 2012’s experimental design called for 32 weeks of supplementation for a single pair of before-after tests - so that’d be 1664 weeks or ~54 months or ~4.5 years! We can try to adjust it downwards with shorter blocks allowing more frequent testing; but problematically, iodine is stored in the thyroid and can apparently linger elsewhere - many of the cited studies used intramuscular injections of iodized oil (as opposed to iodized salt or kelp supplements) because this ensured an adequate supply for months or years with no further compliance by the subjects. If the effects are that long-lasting, it may be worthless to try shorter blocks than ~32 weeks.
This continued up to 1 AM, at which point I decided not to take a second armodafinil (why spend a second pill to gain what would likely be an unproductive set of 8 hours?) and finish up the experiment with some n-backing. My 5 rounds: 60/38/62/44/5023. This was surprising. Compare those scores with scores from several previous days: 39/42/44/40/20/28/36. I had estimated before the n-backing that my scores would be in the low-end of my usual performance (20-30%) since I had not slept for the past 41 hours, and instead, the lowest score was 38%. If one did not know the context, one might think I had discovered a good nootropic! Interesting evidence that armodafinil preserves at least one kind of mental performance.
Sleep itself is an underrated cognition enhancer. It is involved in enhancing long-term memories as well as creativity. For instance, it is well established that during sleep memories are consolidated-a process that "fixes" newly formed memories and determines how they are shaped. Indeed, not only does lack of sleep make most of us moody and low on energy, cutting back on those precious hours also greatly impairs cognitive performance. Exercise and eating well also enhance aspects of cognition. It turns out that both drugs and "natural" enhancers produce similar physiological changes in the brain, including increased blood flow and neuronal growth in structures such as the hippocampus. Thus, cognition enhancers should be welcomed but not at the expense of our health and well being.
In sum, the evidence concerning stimulant effects of working memory is mixed, with some findings of enhancement and some null results, although no findings of overall performance impairment. A few studies showed greater enhancement for less able participants, including two studies reporting overall null results. When significant effects have been found, their sizes vary from small to large, as shown in Table 4. Taken together, these results suggest that stimulants probably do enhance working memory, at least for some individuals in some task contexts, although the effects are not so large or reliable as to be observable in all or even most working memory studies.

How exactly – and if – nootropics work varies widely. Some may work, for example, by strengthening certain brain pathways for neurotransmitters like dopamine, which is involved in motivation, Barbour says. Others aim to boost blood flow – and therefore funnel nutrients – to the brain to support cell growth and regeneration. Others protect brain cells and connections from inflammation, which is believed to be a factor in conditions like Alzheimer's, Barbour explains. Still others boost metabolism or pack in vitamins that may help protect the brain and the rest of the nervous system, explains Dr. Anna Hohler, an associate professor of neurology at Boston University School of Medicine and a fellow of the American Academy of Neurology.
When taken as prescribed, Modafinil is safer than Adderall with fewer side effects. Smart pill enthusiasts find a heightened sense of alertness and motivation with Modafinil. In healthy individuals, Modafinil will reliably boost energy levels. If you find that it gives you headaches, add a choline supplement to your stack. With that said, you should only use Modafinil in moderation on an as-needed basis.
NGF may sound intriguing, but the price is a dealbreaker: at suggested doses of 1-100μg (NGF dosing in humans for benefits is, shall we say, not an exact science), and a cost from sketchy suppliers of $1210/100μg/$470/500μg/$750/1000μg/$1000/1000μg/$1030/1000μg/$235/20μg. (Levi-Montalcini was presumably able to divert some of her lab’s production.) A year’s supply then would be comically expensive: at the lowest doses of 1-10μg using the cheapest sellers (for something one is dumping into one’s eyes?), it could cost anywhere up to $10,000.

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.”
I largely ignored this since the discussions were of sub-RDA doses, and my experience has usually been that RDAs are a poor benchmark and frequently far too low (consider the RDA for vitamin D). This time, I checked the actual RDA - and was immediately shocked and sure I was looking at a bad reference: there was no way the RDA for potassium was seriously 3700-4700mg or 4-5 grams daily, was there? Just as an American, that implied that I was getting less than half my RDA. (How would I get 4g of potassium in the first place? Eat a dozen bananas a day⸮) I am not a vegetarian, nor is my diet that fantastic: I figured I was getting some potassium from the ~2 fresh tomatoes I was eating daily, but otherwise my diet was not rich in potassium sources. I have no blood tests demonstrating deficiency, but given the figures, I cannot see how I could not be deficient.
So it's no surprise that as soon as medical science develops a treatment for a disease, we often ask if it couldn't perhaps make a healthy person even healthier. Take Viagra, for example: developed to help men who couldn't get erections, it's now used by many who function perfectly well without a pill but who hope it will make them exceptionally virile.
There are seven primary classes used to categorize smart drugs: Racetams, Stimulants, Adaptogens, Cholinergics, Serotonergics, Dopaminergics, and Metabolic Function Smart Drugs. Despite considerable overlap and no clear border in the brain and body’s responses to these substances, each class manifests its effects through a different chemical pathway within the body.
the larger size of the community enables economies of scale and increases the peak sophistication possible. In a small nootropics community, there is likely to be no one knowledgeable about statistics/experimentation/biochemistry/neuroscience/whatever-you-need-for-a-particular-discussion, and the available funds increase: consider /r/Nootropics’s testing program, which is doable only because it’s a large lucrative community to sell to so the sellers are willing to donate funds for independent lab tests/Certificates of Analysis (COAs) to be done. If there were 1000 readers rather than 23,295, how could this ever happen short of one of those 1000 readers being very altruistic?
Other drugs, like cocaine, are used by bankers to manage their 18-hour workdays [81]. 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.
We reached out to several raw material manufacturers and learned that Phosphatidylserine and Huperzine A are in short supply. We also learned that these ingredients can be pricey, incentivizing many companies to cut corners.  A company has to have the correct ingredients in the correct proportions in order for a brain health formula to be effective. We learned that not just having the two critical ingredients was important – but, also that having the correct supporting ingredients was essential in order to be effective.
Running low on gum (even using it weekly or less, it still runs out), I decided to try patches. Reading through various discussions, I couldn’t find any clear verdict on what patch brands might be safer (in terms of nicotine evaporation through a cut or edge) than others, so I went with the cheapest Habitrol I could find as a first try of patches (Nicotine Transdermal System Patch, Stop Smoking Aid, 21 mg, Step 1, 14 patches) in May 2013. I am curious to what extent nicotine might improve a long time period like several hours or a whole day, compared to the shorter-acting nicotine gum which feels like it helps for an hour at most and then tapers off (which is very useful in its own right for kicking me into starting something I have been procrastinating on). I have not decided whether to try another self-experiment.
An unusual intervention is infrared/near-infrared light of particular wavelengths (LLLT), theorized to assist mitochondrial respiration and yielding a variety of therapeutic benefits. Some have suggested it may have cognitive benefits. LLLT sounds strange but it’s simple, easy, cheap, and just plausible enough it might work. I tried out LLLT treatment on a sporadic basis 2013-2014, and statistically, usage correlated strongly & statistically-significantly with increases in my daily self-ratings, and not with any sleep disturbances. Excited by that result, I did a randomized self-experiment 2014-2015 with the same procedure, only to find that the causal effect was weak or non-existent. I have stopped using LLLT as likely not worth the inconvenience.
Companies already know a great deal about how their employees live their lives. With the help of wearable technologies and health screenings, companies can now analyze the relation between bodily activities — exercise, sleep, nutrition, etc. — and work performance. With the justification that healthy employees perform better, some companies have made exercise mandatory by using sanctions against those who refuse to perform. And according to The Kaiser Family Foundation, of the large U.S. companies that offer health screenings, nearly half of them use financial incentives to persuade employees to participate.
Powders are good for experimenting with (easy to vary doses and mix), but not so good for regular taking. I use OO gel capsules with a Capsule Machine: it’s hard to beat $20, it works, it’s not that messy after practice, and it’s not too bad to do 100 pills. However, I once did 3kg of piracetam + my other powders, and doing that nearly burned me out on ever using capsules again. If you’re going to do that much, something more automated is a serious question! (What actually wound up infuriating me the most was when capsules would stick in either the bottom or top try - requiring you to very gingerly pull and twist them out, lest the two halves slip and spill powder - or when the two halves wouldn’t lock and you had to join them by hand. In contrast: loading the gel caps could be done automatically without looking, after some experience.)
I decided to try out day-time usage on 2 consecutive days, taking the 100mg at noon or 1 PM. On both days, I thought I did feel more energetic but nothing extraordinary (maybe not even as strong as the nicotine), and I had trouble falling asleep on Halloween, thinking about the meta-ethics essay I had been writing diligently on both days. Not a good use compared to staying up a night.
But how, exactly, does he do it? Sure, Cruz typically eats well, exercises regularly and tries to get sufficient sleep, and he's no stranger to coffee. But he has another tool in his toolkit that he finds makes a noticeable difference in his ability to efficiently and effectively conquer all manner of tasks: Alpha Brain, a supplement marketed to improve memory, focus and mental quickness.
Nicotine’s stimulant effects are general and do not come with the same tweakiness and aggression associated with the amphetamines, and subjectively are much cleaner with less of a crash. I would say that its stimulant effects are fairly strong, around that of modafinil. Another advantage is that nicotine operates through nicotinic receptors and so doesn’t cross-tolerate with dopaminergic stimulants (hence one could hypothetically cycle through nicotine, modafinil, amphetamines, and caffeine, hitting different receptors each time).
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.
Modafinil is not addictive, but there may be chances of drug abuse and memory impairment. This can manifest in people who consume it to stay up for way too long; as a result, this would probably make them ill. Long-term use of Modafinil may reduce plasticity and may harm the memory of some individuals. Hence, it is sold only on prescription by a qualified physician.
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Potassium citrate powder is neither expensive nor cheap: I purchased 453g for $21. The powder is crystalline white, dissolves instantly in water, and largely tasteless (sort of saline & slightly unpleasant). The powder is 37% potassium by weight (the formula is C6H5K3O7) so 453g is actually 167g of potassium, so 80-160 days’ worth depending on dose.
Many laboratory tasks have been developed to study working memory, each of which taxes to varying degrees aspects such as the overall capacity of working memory, its persistence over time, and its resistance to interference either from task-irrelevant stimuli or among the items to be retained in working memory (i.e., cross-talk). Tasks also vary in the types of information to be retained in working memory, for example, verbal or spatial information. The question of which of these task differences correspond to differences between distinct working memory systems and which correspond to different ways of using a single underlying system is a matter of debate (e.g., D’Esposito, Postle, & Rypma, 2000; Owen, 2000). For the present purpose, we ignore this question and simply ask, Do MPH and d-AMP affect performance in the wide array of tasks that have been taken to operationalize working memory? If the literature does not yield a unanimous answer to this question, then what factors might be critical in determining whether stimulant effects are manifest?
It can easily pass through the blood-brain barrier and is known to protect the nerve tissues present in the brain. There is evidence that the acid plays an instrumental role in preventing strokes in adults by decreasing the number of free radicals in the body.  It increases the production of acetylcholine, a neurotransmitter that most Alzheimer’s patients are a deficit in.
The choline-based class of smart drugs play important cognitive roles in memory, attention, and mood regulation. Acetylcholine (ACh) is one of the brain’s primary neurotransmitters, and also vital in the proper functioning of the peripheral nervous system. Studies with rats have shown that certain forms of learning and neural plasticity seem to be impossible in acetylcholine-depleted areas of the brain. This is particularly worth mentioning because (as noted above under the Racetams section), the Racetam class of smart drugs tends to deplete cholines from the brain, so one of the classic “supplement stacks” – chemical supplements that are used together – are Piracetam and Choline Bitartrate. Cholines can also be found in normal food sources, like egg yolks and soybeans.
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l-Theanine – A 2014 systematic review and meta-analysis found that concurrent caffeine and l-theanine use had synergistic psychoactive effects that promoted alertness, attention, and task switching;[29] these effects were most pronounced during the first hour post-dose.[29] However, the European Food Safety Authority reported that, when L-theanine is used by itself (i.e. without caffeine), there is insufficient information to determine if these effects exist.[34]
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