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.
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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?
Between midnight and 1:36 AM, I do four rounds of n-back: 50/39/30/55%. I then take 1/4th of the pill and have some tea. At roughly 1:30 AM, AngryParsley linked a SF anthology/novel, Fine Structure, which sucked me in for the next 3-4 hours until I finally finished the whole thing. At 5:20 AM, circumstances forced me to go to bed, still having only taken 1/4th of the pill and that determines this particular experiment of sleep; I quickly do some n-back: 29/20/20/54/42. I fall asleep in 13 minutes and sleep for 2:48, for a ZQ of 28 (a full night being ~100). I did not notice anything from that possible modafinil+caffeine interaction. Subjectively upon awakening: I don’t feel great, but I don’t feel like 2-3 hours of sleep either. N-back at 10 AM after breakfast: 25/54/44/38/33. These are not very impressive, but seem normal despite taking the last armodafinil ~9 hours ago; perhaps the 3 hours were enough. Later that day, at 11:30 PM (just before bed): 26/56/47.
It is known that American college students have embraced cognitive enhancement, and some information exists about the demographics of the students most likely to practice cognitive enhancement with prescription stimulants. Outside of this narrow segment of the population, very little is known. What happens when students graduate and enter the world of work? Do they continue using prescription stimulants for cognitive enhancement in their first jobs and beyond? How might the answer to this question depend on occupation? For those who stay on campus to pursue graduate or professional education, what happens to patterns of use? To what extent do college graduates who did not use stimulants as students begin to use them for cognitive enhancement later in their careers? To what extent do workers without college degrees use stimulants to enhance job performance? How do the answers to these questions differ for countries outside of North America, where the studies of Table 1 were carried out?
Flaxseed oil is, ounce for ounce, about as expensive as fish oil, and also must be refrigerated and goes bad within months anyway. Flax seeds on the other hand, do not go bad within months, and cost dollars per pound. Various resources I found online estimated that the ALA component of human-edible flaxseed to be around 20% So Amazon’s 6lbs for $14 is ~1.2lbs of ALA, compared to 16fl-oz of fish oil weighing ~1lb and costing ~$17, while also keeping better and being a calorically useful part of my diet. The flaxseeds can be ground in an ordinary food processor or coffee grinder. It’s not a hugely impressive cost-savings, but I think it’s worth trying when I run out of fish oil.
Adderall is an amphetamine, used as a drug to help focus and concentration in people with ADHD, and promote wakefulness for sufferers of narcolepsy. Adderall increases levels of dopamine and norepinephrine in the brain, along with a few other chemicals and neurotransmitters. It’s used off-label as a study drug, because, as mentioned, it is believed to increase focus and concentration, improve cognition and help users stay awake. Please note: Side Effects Possible.
The effect? 3 or 4 weeks later, I’m not sure. When I began putting all of my nootropic powders into pill-form, I put half a lithium pill in each, and nevertheless ran out of lithium fairly quickly (3kg of piracetam makes for >4000 OO-size pills); those capsules were buried at the bottom of the bucket under lithium-less pills. So I suddenly went cold-turkey on lithium. Reflecting on the past 2 weeks, I seem to have been less optimistic and productive, with items now lingering on my To-Do list which I didn’t expect to. An effect? Possibly.
Remember: The strictest definition of nootropics today says that for a substance to be a true brain-boosting nootropic it must have low toxicity and few side effects. Therefore, by definition, a nootropic is safe to use. However, when people start stacking nootropics indiscriminately, taking megadoses, or importing them from unknown suppliers that may have poor quality control, it’s easy for safety concerns to start creeping in.
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So, I thought I might as well experiment since I have it. I put the 23 remaining pills into gel capsules with brown rice as filling, made ~30 placebo capsules, and will use the one-bag blinding/randomization method. I don’t want to spend the time it would take to n-back every day, so I will simply look for an effect on my daily mood/productivity self-rating; hopefully Noopept will add a little on average above and beyond my existing practices like caffeine+piracetam (yes, Noopept may be as good as piracetam, but since I still have a ton of piracetam from my 3kg order, I am primarily interested in whether Noopept adds onto piracetam rather than replaces). 10mg doses seem to be on the low side for Noopept users, weakening the effect, but on the other hand, if I were to take 2 capsules at a time, then I’d halve the sample size; it’s not clear what is the optimal tradeoff between dose and n for statistical power.
That doesn’t necessarily mean all smart drugs – now and in the future – will be harmless, however. The brain is complicated. In trying to upgrade it, you risk upsetting its intricate balance. “It’s not just about more, it’s about having to be exquisitely and exactly right. And that’s very hard to do,” says Arnstein. “What’s good for one system may be bad for another system,” adds Trevor Robbins, Professor of Cognitive Neuroscience at the University of Cambridge. “It’s clear from the experimental literature that you can affect memory with pharmacological agents, but the problem is keeping them safe.”
The word “nootropic” was coined in 1972 by a Romanian scientist, Corneliu Giurgea, who combined the Greek words for “mind” and “bending.” Caffeine and nicotine can be considered mild nootropics, while prescription Ritalin, Adderall and Provigil (modafinil, a drug for treating narcolepsy) lie at the far end of the spectrum when prescribed off-label as cognitive enhancers. Even microdosing of LSD is increasingly viewed as a means to greater productivity.
As already mentioned, AMPs and MPH are classified by the U.S. Food and Drug Administration (FDA) as Schedule II substances, which means that buying or selling them is a felony offense. This raises the question of how the drugs are obtained by students for nonmedical use. Several studies addressed this question and yielded reasonably consistent answers.
Regarding other methods of cognitive enhancement, little systematic research has been done on their prevalence among healthy people for the purpose of cognitive enhancement. One exploratory survey found evidence of modafinil use by people seeking cognitive enhancement (Maher, 2008), and anecdotal reports of this can be found online (e.g., Arrington, 2008; Madrigal, 2008). Whereas TMS requires expensive equipment, tDCS can be implemented with inexpensive and widely available materials, and online chatter indicates that some are experimenting with this method.
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).
I split the 2 pills into 4 doses for each hour from midnight to 4 AM. 3D driver issues in Debian unstable prevented me from using Brain Workshop, so I don’t have any DNB scores to compare with the armodafinil DNB scores. I had the subjective impression that I was worse off with the Modalert, although I still managed to get a fair bit done so the deficits couldn’t’ve been too bad. The apathy during the morning felt worse than armodafinil, but that could have been caused by or exacerbated by an unexpected and very stressful 2 hour drive through rush hour and multiple accidents; the quick hour-long nap at 10 AM was half-waking half-light-sleep according to the Zeo, but seemed to help a bit. As before, I began to feel better in the afternoon and by evening felt normal, doing my usual reading. That night, the Zeo recorded my sleep as lasting ~9:40, when it was usually more like 8:40-9:00 (although I am not sure that this was due to the modafinil inasmuch as once a week or so I tend to sleep in that long, as I did a few days later without any influence from the modafinil); assuming the worse, the nap and extra sleep cost me 2 hours for a net profit of ~7 hours. While it’s not clear how modafinil affects recovery sleep (see the footnote in the essay), it’s still interesting to ponder the benefits of merely being able to delay sleep18.
“I have a bachelors degree in Nutrition Science. Cavin’s Balaster’s How to Feed a Brain is one the best written health nutrition books that I have ever read. It is evident that through his personal journey with a TBI and many years of research Cavin has gained a great depth of understanding on the biomechanics of nutrition has how it relates to the structure of the brain and nervous system, as well as how all of the body systems intercommunicate with one another. He then takes this complicated knowledge and breaks it down into a concise and comprehensive book. If you or your loved one is suffering from ANY neurological disorder or TBI please read this book.”
Smart pills have revolutionized the diagnosis of gastrointestinal disorders and could replace conventional diagnostic techniques such as endoscopy. Traditionally, an endoscopy probe is inserted into a patient’s esophagus, and subsequently the upper and lower gastrointestinal tract, for diagnostic purposes. There is a risk of perforation or tearing of the esophageal lining, and the patient faces discomfort during and after the procedure. A smart pill or wireless capsule endoscopy (WCE), however, can easily be swallowed and maneuvered to capture images, and requires minimal patient preparation, such as sedation. The built-in sensors allow the measurement of all fluids and gases in the gut, giving the physician a multidimensional picture of the human body.
Adrafinil is Modafinil’s predecessor, because the scientists tested it as a potential narcolepsy drug. It was first produced in 1974 and immediately showed potential as a wakefulness-promoting compound. Further research showed that Adrafinil is metabolized into its component parts in the liver, that is into inactive modafinil acid. Ultimately, Modafinil has been proclaimed the primary active compound in Adrafinil.
Christopher Wanjek is the Bad Medicine columnist for Live Science and a health and science writer based near Washington, D.C. He is the author of two health books, "Food at Work" (2005) and "Bad Medicine" (2003), and a comical science novel, "Hey Einstein" (2012). For Live Science, Christopher covers public health, nutrition and biology, and he occasionally opines with a great deal of healthy skepticism. His "Food at Work" book and project, commissioned by the U.N.'s International Labor Organization, concerns workers health, safety and productivity. Christopher has presented this book in more than 20 countries and has inspired the passage of laws to support worker meal programs in numerous countries. Christopher holds a Master of Health degree from Harvard School of Public Health and a degree in journalism from Temple University. He has two Twitter handles, @wanjek (for science) and @lostlenowriter (for jokes).
Taken together, the available results are mixed, with slightly more null results than overall positive findings of enhancement and evidence of impairment in one reversal learning task. As the effect sizes listed in Table 5 show, the effects when found are generally substantial. When drug effects were assessed as a function of placebo performance, genotype, or self-reported impulsivity, enhancement was found to be greatest for participants who performed most poorly on placebo, had a COMT genotype associated with poorer executive function, or reported being impulsive in their everyday lives. In sum, the effects of stimulants on cognitive control are not robust, but MPH and d-AMP appear to enhance cognitive control in some tasks for some people, especially those less likely to perform well on cognitive control tasks.
Ngo has experimented with piracetam himself (“The first time I tried it, I thought, ‘Wow, this is pretty strong for a supplement.’ I had a little bit of reflux, heartburn, but in general it was a cognitive enhancer. . . . I found it helpful”) and the neurotransmitter DMEA (“You have an idea, it helps you finish the thought. It’s for when people have difficulty finishing that last connection in the brain”).
Taking the tryptophan is fairly difficult. The powder as supplied by Bulk Nutrition is extraordinarily dry and fine; it seems to be positively hydrophobic. The first time I tried to swallow a teaspoon, I nearly coughed it out - the power had seemed to explode in my mouth and go down my lungs. Thenceforth I made sure to have a mouth of water first. After a while, I took a different tack: I mixed in as much Hericium as would fit in the container. The mushroom powder is wetter and chunkier than the tryptophan, and seems to reduce the problem. Combining the mix with chunks of melatonin inside a pill works even better.
MPH was developed more recently and marketed primarily for ADHD, although it is sometimes prescribed off label or used nonmedically to increase alertness, energy, or concentration in conditions other than ADHD. Both MPH and AMP are on the list of substances banned from sports competitions by the World Anti-Doping Agency (Docherty, 2008). Both also have the potential for abuse and dependence, which detracts from their usefulness and is the reason for their classification as Schedule II controlled substances. Although the risk of developing dependence on these drugs is believed to be low for individuals taking them for ADHD, the Schedule II classification indicates that these drugs have a high potential for abuse and that abuse may lead to severe dependence.
If stimulants truly enhance cognition but do so to only a small degree, this raises the question of whether small effects are of practical use in the real world. Under some circumstances, the answer would undoubtedly be yes. Success in academic and occupational competitions often hinges on the difference between being at the top or merely near the top. A scholarship or a promotion that can go to only one person will not benefit the runner-up at all. Hence, even a small edge in the competition can be important.
Not included in the list below are prescription psychostimulants such as Adderall and Ritalin. Non-medical, illicit use of these drugs for the purpose of cognitive enhancement in healthy individuals comes with a high cost, including addiction and other adverse effects. Although these drugs are prescribed for those with attention deficit hyperactivity disorder (ADHD) to help with focus, attention and other cognitive functions, they have been shown to in fact impair these same functions when used for non-medical purposes. More alarming, when taken in high doses, they have the potential to induce psychosis.
Several new medications are on the market and in development for Alzheimer's disease, a progressive neurological disease leading to memory loss, language deterioration, and confusion that afflicts about 4.5 million Americans and is expected to strike millions more as the baby boom generation ages. Yet the burning question for those who aren't staring directly into the face of Alzheimer's is whether these medications might make us smarter.
I noticed on SR something I had never seen before, an offer for 150mgx10 of Waklert for ฿13.47 (then, ฿1 = $3.14). I searched and it seemed Sun was somehow manufacturing armodafinil! Interesting. Maybe not cost-effective, but I tried out of curiosity. They look and are packaged the same as the Modalert, but at a higher price-point: 150 rather than 81 rupees. Not entirely sure how to use them: assuming quality is the same, 150mg Waklert is still 100mg less armodafinil than the 250mg Nuvigil pills.
That it is somewhat valuable is clear if we consider it under another guise. Imagine you received the same salary you do, but paid every day. Accounting systems would incur considerable costs handling daily payments, since they would be making so many more and so much smaller payments, and they would have to know instantly whether you showed up to work that day and all sorts of other details, and the recipients themselves would waste time dealing with all these checks or looking through all the deposits to their account, and any errors would be that much harder to track down. (And conversely, expensive payday loans are strong evidence that for poor people, a bi-weekly payment is much too infrequent.) One might draw a comparison to batching or buffers in computers: by letting data pile up in buffers, the computer can then deal with them in one batch, amortizing overhead over many items rather than incurring the overhead again and again. The downside, of course, is that latency will suffer and performance may drop based on that or the items becoming outdated & useless. The right trade-off will depend on the specifics; one would not expect random buffer-sizes to be optimal, but one would have to test and see what works best.
I posted a link to the survey on my Google+ account, and inserted the link at the top of all gwern.net pages; 51 people completed all 11 binary choices (most of them coming from North America & Europe), which seems adequate since the 11 questions are all asking the same question, and 561 responses to one question is quite a few. A few different statistical tests seem applicable: a chi-squared test whether there’s a difference between all the answers, a two-sample test on the averages, and most meaningfully, summing up the responses as a single pair of numbers and doing a binomial test:
Deficiencies in B vitamins can cause memory problems, mood disorders, and cognitive impairment. B vitamins will not make you smarter on their own. Still, they support a wide array of cognitive functions. Most of the B complex assists in some fashion with brain activity. Vitamin B12 (Methylcobalamin) is the most critical B vitamin for mental health.
The flanker task is designed to tax cognitive control by requiring subjects to respond based on the identity of a target stimulus (H or S) and not the more numerous and visually salient stimuli that flank the target (as in a display such as HHHSHHH). Servan-Schreiber, Carter, Bruno, and Cohen (1998) administered the flanker task to subjects on placebo and d-AMP. They found an overall speeding of responses but, more importantly, an increase in accuracy that was disproportionate for the incongruent conditions, that is, the conditions in which the target and flankers did not match and cognitive control was needed.
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.
Qualia Mind, meanwhile, combines more than two dozen ingredients that may support brain and nervous system function – and even empathy, the company claims – including vitamins B, C and D, artichoke stem and leaf extract, taurine and a concentrated caffeine powder. A 2014 review of research on vitamin C, for one, suggests it may help protect against cognitive decline, while most of the research on artichoke extract seems to point to its benefits to other organs like the liver and heart. A small company-lead pilot study on the product found users experienced improvements in reasoning, memory, verbal ability and concentration five days after beginning Qualia Mind.
Despite decades of study, a full picture has yet to emerge of the cognitive effects of the classic psychostimulants and modafinil. Part of the problem is that getting rats, or indeed students, to do puzzles in laboratories may not be a reliable guide to the drugs’ effects in the wider world. Drugs have complicated effects on individuals living complicated lives. Determining that methylphenidate enhances cognition in rats by acting on their prefrontal cortex doesn’t tell you the potential impact that its effects on mood or motivation may have on human cognition.
as scientific papers become much more accessible online due to Open Access, digitization by publishers, and cheap hosting for pirates, the available knowledge about nootropics increases drastically. This reduces the perceived risk by users, and enables them to educate themselves and make much more sophisticated estimates of risk and side-effects and benefits. (Take my modafinil page: in 1997, how could an average person get their hands on any of the papers available up to that point? Or get detailed info like the FDA’s prescribing guide? Even assuming they had a computer & Internet?)
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.’”
Either prescription or illegal, daily use of testosterone would not be cheap. On the other hand, if I am one of the people for whom testosterone works very well, it would be even more valuable than modafinil, in which case it is well worth even arduous experimenting. Since I am on the fence on whether it would help, this suggests the value of information is high.
“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.”
Some nootropics are more commonly used than others. These include nutrients like Alpha GPC, huperzine A, L-Theanine, bacopa monnieri, and vinpocetine. Other types of nootropics ware still gaining traction. With all that in mind, to claim there is a “best” nootropic for everyone would be the wrong approach since every person is unique and looking for different benefits.