Federal law classifies most nootropics as dietary supplements, which means that the Food and Drug Administration does not regulate manufacturers’ statements about their benefits (as the giant “This product is not intended to diagnose, treat, cure, or prevent any disease” disclaimer on the label indicates). And the types of claims that the feds do allow supplement companies to make are often vague and/or supported by less-than-compelling scientific evidence. “If you find a study that says that an ingredient caused neurons to fire on rat brain cells in a petri dish,” says Pieter Cohen, an assistant professor at Harvard Medical School, “you can probably get away with saying that it ‘enhances memory’ or ‘promotes brain health.’”
One possibility is that when an individual takes a drug like noopept, they experience greater alertness and mental clarity. So, while the objective ability to see may not actually improve, the ability to process visual stimuli increases, resulting in the perception of improved vision. This allows individuals to process visual cues more quickly, take in scenes more easily, and allows for the increased perception of smaller details.
And the drugs are not terribly difficult to get, depending on where you’re located. Modafinil has an annual global share of $700 million, with high estimated off-label use. Although these drugs can be purchased over the internet, their legal status varies between countries. For example, it is legal to possess and use Modafinil in the United Kingdom without a prescription, but not in United States.
The main area of the brain effected by smart pills is the prefrontal cortex, where representations of our goals for the future are created. Namely, the prefrontal cortex consists of pyramidal cells that keep each other firing. However in some instances they can become disconnected due to chemical imbalances, or due to being tired, stressed, and overworked.
Instead, I urge the military to examine the use of smart drugs and the potential benefits they bring to the military. If they are safe, and pride cognitive enhancement to servicemembers, then we should discuss their use in the military. Imagine the potential benefits on the battlefield. They could potentially lead to an increase in the speed and tempo of our individual and collective OODA loop. They could improve our ability to become aware and make observations. Improve the speed of orientation and decision-making. Lastly, smart drugs could improve our ability to act and adapt to rapidly changing situations.
Another class of substances with the potential to enhance cognition in normal healthy individuals is the class of prescription stimulants used to treat attention-deficit/hyperactivity disorder (ADHD). These include methylphenidate (MPH), best known as Ritalin or Concerta, and amphetamine (AMP), most widely prescribed as mixed AMP salts consisting primarily of dextroamphetamine (d-AMP), known by the trade name Adderall. These medications have become familiar to the general public because of the growing rates of diagnosis of ADHD children and adults (Froehlich et al., 2007; Sankaranarayanan, Puumala, & Kratochvil, 2006) and the recognition that these medications are effective for treating ADHD (MTA Cooperative Group, 1999; Swanson et al., 2008).
I was contacted by the Longecity user lostfalco, and read through some of his writings on the topic. I had never heard of LLLT before, but the mitochondria mechanism didn’t sound impossible (although I wondered whether it made sense at a quantity level14151617), and there was at least some research backing it; more importantly, lostfalco had discovered that devices for LLLT could be obtained as cheap as $15. (Clearly no one will be getting rich off LLLT or affiliate revenue any time soon.) Nor could I think of any way the LLLT could be easily harmful: there were no drugs involved, physical contact was unnecessary, power output was too low to directly damage through heating, and if it had no LLLT-style effect but some sort of circadian effect through hitting photoreceptors, using it in the morning wouldn’t seem to interfere with sleep.
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.
I bought 500g of piracetam (Examine.com; FDA adverse events) from Smart Powders (piracetam is one of the cheapest nootropics and SP was one of the cheapest suppliers; the others were much more expensive as of October 2010), and I’ve tried it out for several days (started on 7 September 2009, and used it steadily up to mid-December). I’ve varied my dose from 3 grams to 12 grams (at least, I think the little scoop measures in grams), taking them in my tea or bitter fruit juice. Cranberry worked the best, although orange juice masks the taste pretty well; I also accidentally learned that piracetam stings horribly when I got some on a cat scratch. 3 grams (alone) didn’t seem to do much of anything while 12 grams gave me a nasty headache. I also ate 2 or 3 eggs a day.
“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!
In this large population-based cohort, we saw consistent robust associations between cola consumption and low BMD in women. The consistency of pattern across cola types and after adjustment for potential confounding variables, including calcium intake, supports the likelihood that this is not due to displacement of milk or other healthy beverages in the diet. The major differences between cola and other carbonated beverages are caffeine, phosphoric acid, and cola extract. Although caffeine likely contributes to lower BMD, the result also observed for decaffeinated cola, the lack of difference in total caffeine intake across cola intake groups, and the lack of attenuation after adjustment for caffeine content suggest that caffeine does not explain these results. A deleterious effect of phosphoric acid has been proposed (26). Cola beverages contain phosphoric acid, whereas other carbonated soft drinks (with some exceptions) do not.
More than once I have seen results indicating that high-IQ types benefit the least from random nootropics; nutritional deficits are the premier example, because high-IQ types almost by definition suffer from no major deficiencies like iodine. But a stimulant modafinil may be another such nootropic (see Cognitive effects of modafinil in student volunteers may depend on IQ, Randall et al 2005), which mentions:
Of all the smart drugs in the world, Modafinil is most often touted as the best. It’s a powerful cognitive enhancer, great for boosting alertness, and has very few, mild side effects that most healthy users will never experience. And no, you can’t have any. Sorry. Modafinil is a prescription medication used to treat disorders like narcolepsy, shift work sleep disorder, and for those who suffer from obstructive sleep apnea.
Another moral concern is that these drugs — especially when used by Ivy League students or anyone in an already privileged position — may widen the gap between those who are advantaged and those who are not. But others have inverted the argument, saying these drugs can help those who are disadvantaged to reduce the gap. In an interview with the New York Times, Dr. Michael Anderson explains that he uses ADHD (a diagnosis he calls “made up”) as an excuse to prescribe Adderall to the children who really need it — children from impoverished backgrounds suffering from poor academic performance.
The Defense Department reports rely on data collected by the private real estate firms that operate base housing in partnership with military branches. The companies' compensation is partly determined by the results of resident satisfaction surveys. I had to re-read this sentence like 5 times to make sure I understood it correctly. I just can't even. Seriously, in what universe did anyone think that this would be a good idea?
(In particular, I don’t think it’s because there’s a sudden new surge of drugs. FDA drug approval has been decreasing over the past few decades, so this is unlikely a priori. More specifically, many of the major or hot drugs go back a long time. Bacopa goes back millennia, melatonin I don’t even know, piracetam was the ’60s, modafinil was ’70s or ’80s, ALCAR was ’80s AFAIK, Noopept & coluracetam were ’90s, and so on.)
I can’t try either of the products myself – I am pregnant and my doctor doesn’t recommend it – but my husband agrees to. He describes the effect of the Nootrobox product as like having a cup of coffee but not feeling as jittery. “I had a very productive day, but I don’t know if that was why,” he says. His Nootroo experience ends after one capsule. He gets a headache, which he is convinced is related, and refuses to take more. “It is just not a beginner friendly cocktail,” offers Noehr.
l-theanine (Examine.com) is occasionally mentioned on Reddit or Imminst or LessWrong32 but is rarely a top-level post or article; this is probably because theanine was discovered a very long time ago (>61 years ago), and it’s a pretty straightforward substance. It’s a weak relaxant/anxiolytic (Google Scholar) which is possibly responsible for a few of the health benefits of tea, and which works synergistically with caffeine (and is probably why caffeine delivered through coffee feels different from the same amount consumed in tea - in one study, separate caffeine and theanine were a mixed bag, but the combination beat placebo on all measurements). The half-life in humans seems to be pretty short, with van der Pijl 2010 putting it ~60 minutes. This suggests to me that regular tea consumption over a day is best, or at least that one should lower caffeine use - combining caffeine and theanine into a single-dose pill has the problem of caffeine’s half-life being much longer so the caffeine will be acting after the theanine has been largely eliminated. The problem with getting it via tea is that teas can vary widely in their theanine levels and the variations don’t seem to be consistent either, nor is it clear how to estimate them. (If you take a large dose in theanine like 400mg in water, you can taste the sweetness, but it’s subtle enough I doubt anyone can actually distinguish the theanine levels of tea; incidentally, r-theanine - the useless racemic other version - anecdotally tastes weaker and less sweet than l-theanine.)
Too much caffeine may be bad for bone health because it can deplete calcium. Overdoing the caffeine also may affect the vitamin D in your body, which plays a critical role in your body’s bone metabolism. However, the roles of vitamin D as well as caffeine in the development of osteoporosis continue to be a source of debate. Significance: Caffeine may interfere with your body’s metabolism of vitamin D, according to a 2007 Journal of Steroid Biochemistry & Molecular Biology study. You have vitamin D receptors, or VDRs, in your osteoblast cells. These large cells are responsible for the mineralization and synthesis of bone in your body. They create a sheet on the surface of your bones. The D receptors are nuclear hormone receptors that control the action of vitamin D-3 by controlling hormone-sensitive gene expression. These receptors are critical to good bone health. For example, a vitamin D metabolism disorder in which these receptors don’t work properly causes rickets.
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 . It takes the edge of other nootropic compounds.
I had tried 8 randomized days like the Adderall experiment to see whether I was one of the people whom modafinil energizes during the day. (The other way to use it is to skip sleep, which is my preferred use.) I rarely use it during the day since my initial uses did not impress me subjectively. The experiment was not my best - while it was double-blind randomized, the measurements were subjective, and not a good measure of mental functioning like dual n-back (DNB) scores which I could statistically compare from day to day or against my many previous days of dual n-back scores. Between my high expectation of finding the null result, the poor experiment quality, and the minimal effect it had (eliminating an already rare use), the value of this information was very small.
Began double-blind trial. Today I took one pill blindly at 1:53 PM. at the end of the day when I have written down my impressions and guess whether it was one of the Adderall pills, then I can look in the baggy and count and see whether it was. there are many other procedures one can take to blind oneself (have an accomplice mix up a sequence of pills and record what the sequence was; don’t count & see but blindly take a photograph of the pill each day, etc.) Around 3, I begin to wonder whether it was Adderall because I am arguing more than usual on IRC and my heart rate seems a bit high just sitting down. 6 PM: I’ve started to think it was a placebo. My heart rate is back to normal, I am having difficulty concentrating on long text, and my appetite has shown up for dinner (although I didn’t have lunch, I don’t think I had lunch yesterday and yesterday the hunger didn’t show up until past 7). Productivity wise, it has been a normal day. All in all, I’m not too sure, but I think I’d guess it was Adderall with 40% confidence (another way of saying placebo with 60% confidence). When I go to examine the baggie at 8:20 PM, I find out… it was an Adderall pill after all. Oh dear. One little strike against Adderall that I guessed wrong. It may be that the problem is that I am intrinsically a little worse today (normal variation? come down from Adderall?).
Since coffee drinking may lead to a worsening of calcium balance in humans, we studied the serial changes of serum calcium, PTH, 1,25-dihydroxyvitamin D (1,25(OH)2D) vitamin D and calcium balance in young and adult rats after daily administration of caffeine for 4 weeks. In the young rats, there was an increase in urinary calcium and endogenous fecal calcium excretion after four days of caffeine administration that persisted for the duration of the experiment. Serum calcium decreased on the fourth day of caffeine administration and then returned to control levels. In contrast, the serum PTH and 1,25(OH)2D remained unchanged initially, but increased after 2 weeks of caffeine administration…In the adult rat group, an increase in the urinary calcium and endogenous fecal calcium excretion and serum levels of PTH was found after caffeine administration. However, the serum 1,25(OH)2D levels and intestinal absorption coefficient of calcium remained the same as in the adult control group.
Took pill #6 at 12:35 PM. Hard to be sure. I ultimately decided that it was Adderall because I didn’t have as much trouble as I normally would in focusing on reading and then finishing my novel (Surface Detail) despite my family watching a movie, though I didn’t notice any lack of appetite. Call this one 60-70% Adderall. I check the next evening and it was Adderall.
The Nature commentary is ivory tower intellectualism at its best. The authors state that society must prepare for the growing demand of such drugs; that healthy adults should be allowed drugs to enhance cognitive ability; that this is "morally equivalent" and no more unnatural than diet, sleep, or the use of computers; that we need an evidence-based approach to evaluate the risks; and that we need legal and ethical policies to ensure fair and equitable use.
With something like creatine, you’d know if it helps you pump out another rep at the gym on a sustainable basis. With nootropics, you can easily trick yourself into believing they help your mindset. The ideal is to do a trial on yourself. Take identical looking nootropic pills and placebo pills for a couple weeks each, then see what the difference is. With only a third party knowing the difference, of course.
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?
Creatine is a substance that’s produced in the human body. It is initially produced in the kidneys, and the process is completed in the liver. It is then stored in the brain tissues and muscles, to support the energy demands of a human body. Athletes and bodybuilders use creatine supplements to relieve fatigue and increase the recovery of the muscle tissues affected by vigorous physical activities. Apart from helping the tissues to recover faster, creatine also helps in enhancing the mental functions in sleep-deprived adults, and it also improves the performance of difficult cognitive tasks.
At this point, I began thinking about what I was doing. Black-market Adderall is fairly expensive; $4-10 a pill vs prescription prices which run more like $60 for 120 20mg pills. It would be a bad idea to become a fan without being quite sure that it is delivering bang for the buck. Now, why the piracetam mix as the placebo as opposed to my other available powder, creatine powder, which has much smaller mental effects? Because the question for me is not whether the Adderall works (I am quite sure that the amphetamines have effects!) but whether it works better for me than my cheap legal standbys (piracetam & caffeine)? (Does Adderall have marginal advantage for me?) Hence, I want to know whether Adderall is better than my piracetam mix. People frequently underestimate the power of placebo effects, so it’s worth testing. (Unfortunately, it seems that there is experimental evidence that people on Adderall know they are on Adderall and also believe they have improved performance, when they do not5. So the blind testing does not buy me as much as it could.)
Another prescription stimulant medication, modafinil (known by the brand name Provigil), is usually prescribed to patients suffering from narcolepsy and shift-work sleep disorder, but it might turn out to have broader applications. “We have conducted at the University of Cambridge double-blind, placebo-controlled studies in healthy people using modafinil and have found improvements in cognition, including in working memory,” Sahakian says. However, she doesn’t think everyone should start using the drug off-label. “There are no long-term safety and efficacy studies of modafinil in healthy people, and so it is unclear what the risks might be.”
Nootrobox co-founder Geoffrey Woo declines a caffeinated drink in favour of a capsule of his newest product when I meet him in a San Francisco coffee shop. The entire industry has a “wild west” aura about it, he tells me, and Nootrobox wants to fix it by pushing for “smarter regulation” so safe and effective drugs that are currently unclassified can be brought into the fold. Predictably, both companies stress the higher goal of pushing forward human cognition. “I am trying to make a smarter, better populace to solve all the problems we have created,” says Nootroo founder Eric Matzner.
Results: Women with high caffeine intakes had significantly higher rates of bone loss at the spine than did those with low intakes (−1.90 ± 0.97% compared with 1.19 ± 1.08%; P = 0.038). When the data were analyzed according to VDR genotype and caffeine intake, women with the tt genotype had significantly (P = 0.054) higher rates of bone loss at the spine (−8.14 ± 2.62%) than did women with the TT genotype (−0.34 ± 1.42%) when their caffeine intake was >300 mg/d…In 1994, Morrison et al (22) first reported an association between vitamin D receptor gene (VDR) polymorphism and BMD of the spine and hip in adults. After this initial report, the relation between VDR polymorphism and BMD, bone turnover, and bone loss has been extensively evaluated. The results of some studies support an association between VDR polymorphism and BMD (23-,25), whereas other studies showed no evidence for this association (26,27)…At baseline, no significant differences existed in serum parathyroid hormone, serum 25-hydroxyvitamin D, serum osteocalcin, and urinary N-telopeptide between the low- and high-caffeine groups (Table 1⇑). In the longitudinal study, the percentage of change in serum parathyroid hormone concentrations was significantly lower in the high-caffeine group than in the low-caffeine group (Table 2⇑). However, no significant differences existed in the percentage of change in serum 25-hydroxyvitamin D
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.
Smart drug, also called nootropic or cognitive enhancer, any of a group of pharmaceutical agents used to improve the intellectual capacity of persons suffering from neurological diseases and psychological disorders. The use of such drugs by healthy individuals in order to improve concentration, to study longer, and to better manage stress is a subject of controversy.
I’ve been actively benefitting from nootropics since 1997, when I was struggling with cognitive performance and ordered almost $1000 worth of smart drugs from Europe (the only place where you could get them at the time). I remember opening the unmarked brown package and wondering whether the pharmaceuticals and natural substances would really enhance my brain.