2 commenters point out that my possible lack of result is due to my mistaken assumption that if nicotine is absorbable through skin, mouth, and lungs it ought to be perfectly fine to absorb it through my stomach by drinking it (rather than vaporizing it and breathing it with an e-cigarette machine) - it’s apparently known that absorption differs in the stomach.
In most cases, cognitive enhancers have been used to treat people with neurological or mental disorders, but there is a growing number of healthy, "normal" people who use these substances in hopes of getting smarter. Although there are many companies that make "smart" drinks, smart power bars and diet supplements containing certain "smart" chemicals, there is little evidence to suggest that these products really work. Results from different laboratories show mixed results; some labs show positive effects on memory and learning; other labs show no effects. There are very few well-designed studies using normal healthy people.
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.
Finally, a workforce high on stimulants wouldn’t necessarily be more productive overall. “One thinks ‘are these things dangerous?’ – and that’s important to consider in the short term,” says Huberman. “But there’s also a different question, which is: ‘How do you feel the day afterwards?’ Maybe you’re hyper-focused for four hours, 12 hours, but then you’re below baseline for 24 or 48.”
Smart drugs could lead to enhanced cognitive abilities in the military. Also known as nootropics, smart drugs can be viewed similarly to medical enhancements. What’s important to remember though, is that smart drugs do not increase your intelligence; however, they may improve cognitive and executive functions leading to an increase in intelligence.
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.
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.)
The infinite promise of stacking is why, whatever weight you attribute to the evidence of their efficacy, nootropics will never go away: With millions of potential iterations of brain-enhancing regimens out there, there is always the tantalizing possibility that seekers haven’t found the elusive optimal combination of pills and powders for them—yet. Each “failure” is but another step in the process-of-elimination journey to biological self-actualization, which may be just a few hundred dollars and a few more weeks of amateur alchemy away.
The first night I was eating some coconut oil, I did my n-backing past 11 PM; normally that damages my scores, but instead I got 66/66/75/88/77% (▁▁▂▇▃) on D4B and did not feel mentally exhausted by the end. The next day, I performed well on the Cambridge mental rotations test. An anecdote, of course, and it may be due to the vitamin D I simultaneously started. Or another day, I was slumped under apathy after a promising start to the day; a dose of fish & coconut oil, and 1 last vitamin D, and I was back to feeling chipper and optimist. Unfortunately I haven’t been testing out coconut oil & vitamin D separately, so who knows which is to thank. But still interesting.
But, thanks to the efforts of a number of remarkable scientists, researchers and plain-old neurohackers, we are beginning to put together a “whole systems” model of how all the different parts of the human brain work together and how they mesh with the complex regulatory structures of the body. It’s going to take a lot more data and collaboration to dial this model in, but already we are empowered to design stacks that can meaningfully deliver on the promise of nootropics “to enhance the quality of subjective experience and promote cognitive health, while having extremely low toxicity and possessing very few side effects.” It’s a type of brain hacking that is intended to produce noticeable cognitive benefits.
Other drugs, like cocaine, are used by bankers to manage their 18-hour workdays . 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.
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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.
One study of helicopter pilots suggested that 600 mg of modafinil given in three doses can be used to keep pilots alert and maintain their accuracy at pre-deprivation levels for 40 hours without sleep. However, significant levels of nausea and vertigo were observed. Another study of fighter pilots showed that modafinil given in three divided 100 mg doses sustained the flight control accuracy of sleep-deprived F-117 pilots to within about 27% of baseline levels for 37 hours, without any considerable side effects. In an 88-hour sleep loss study of simulated military grounds operations, 400 mg/day doses were mildly helpful at maintaining alertness and performance of subjects compared to placebo, but the researchers concluded that this dose was not high enough to compensate for most of the effects of complete sleep loss.
Going back to the 1960s, although it was a Romanian chemist who is credited with discovering nootropics, a substantial amount of research on racetams was conducted in the Soviet Union. This resulted in the birth of another category of substances entirely: adaptogens, which, in addition to benefiting cognitive function were thought to allow the body to better adapt to stress.
…Four subjects correctly stated when they received nicotine, five subjects were unsure, and the remaining two stated incorrectly which treatment they received on each occasion of testing. These numbers are sufficiently close to chance expectation that even the four subjects whose statements corresponded to the treatments received may have been guessing.
But, if we find in 10 or 20 years that the drugs don't do damage, what are the benefits? These are stimulants that help with concentration. College students take such drugs to pass tests; graduates take them to gain professional licenses. They are akin to using a calculator to solve an equation. Do you really want a doctor who passed his boards as a result of taking speed — and continues to depend on that for his practice?
One often-cited study published in the British Journal of Pharmacology looked at cognitive function in the elderly and showed that racetam helped to improve their brain function.19 Another study, which was published in Psychopharmacology, looked at adult volunteers (including those who are generally healthy) and found that piracetam helped improve their memory.20
The general cost of fish oil made me interested in possible substitutes. Seth Roberts uses exclusively flaxseed oil or flaxseed meal, and this seems to work well for him with subjective effects (eg. noticing his Chinese brands seemed to not work, possibly because they were unrefrigerated and slightly rancid). It’s been studied much less than fish oil, but omega acids are confusing enough in general (is there a right ratio? McCluskey’s roundup gives the impression claims about ratios may have been overstated) that I’m not convinced ALA is a much inferior replacement for fish oil’s mixes of EPA & DHA.
American employers are already squeezing more productivity out of fewer workers, so one wonders whether we might feel pressure to enhance our brainpower pharmaceutically, should the state of the art develop so far. Already, workers may be tempted to seek prescriptions for Provigil, a drug that treats daytime sleepiness. Provigil was originally approved as a treatment for narcolepsy and was subsequently approved for use by people who work swing shifts and suffer from excessive daytime sleepiness.
Factor analysis. The strategy: read in the data, drop unnecessary data, impute missing variables (data is too heterogeneous and collected starting at varying intervals to be clean), estimate how many factors would fit best, factor analyze, pick the ones which look like they match best my ideas of what productive is, extract per-day estimates, and finally regress LLLT usage on the selected factors to look for increases.
For the sake of organizing the review, we have divided the literature according to the general type of cognitive process being studied, with sections devoted to learning and to various kinds of executive function. Executive function is a broad and, some might say, vague concept that encompasses the processes by which individual perceptual, motoric, and mnemonic abilities are coordinated to enable appropriate, flexible task performance, especially in the face of distracting stimuli or alternative competing responses. Two major aspects of executive function are working memory and cognitive control, responsible for the maintenance of information in a short-term active state for guiding task performance and responsible for inhibition of irrelevant information or responses, respectively. A large enough literature exists on the effects of stimulants on these two executive abilities that separate sections are devoted to each. In addition, a final section includes studies of miscellaneous executive abilities including planning, fluency, and reasoning that have also been the subjects of published studies.
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.
One of the most widely known classes of smart drugs on the market, Racetams, have a long history of use and a lot of evidence of their effectiveness. They hasten the chemical exchange between brain cells, directly benefiting our mental clarity and learning process. They are generally not controlled substances and can be purchased without a prescription in a lot of locations globally.
My predictions were substantially better than random chance7, so my default belief - that Adderall does affect me and (mostly) for the better - is borne out. I usually sleep very well and 3 separate incidents of horrible sleep in a few weeks seems rather unlikely (though I didn’t keep track of dates carefully enough to link the Zeo data with the Adderall data). Between the price and the sleep disturbances, I don’t think Adderall is personally worthwhile.
Common environmental toxins – pesticides, for example – cause your brain to release glutamate (a neurotransmitter). Your brain needs glutamate to function, but when you create too much of it it becomes toxic and starts killing neurons. Oxaloacetate protects rodents from glutamate-induced brain damage. Of course, we need more research to determine whether or not oxaloacetate has the same effect on humans.