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.
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.
In her new book, Brain Food: The Surprising Science of Eating for Cognitive Power (Avery/ Penguin Random House), Dr. Lisa Mosconi, PhD, INHC, Associate Director of the Alzheimer’s Prevention Clinic at Weill Cornell Medical College, highlights the connection between diet and brain function and shares approachable, actionable tips to put that research into practice.
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.
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That left me with 329 days of data. The results are that (correcting for the magnesium citrate self-experiment I was running during the time period which did not turn out too great) days on which I happened to use my LED device for LLLT were much better than regular days. Below is a graph showing the entire MP dataseries with LOESS-smoothed lines showing LLLT vs non-LLLT days:
This research is in contrast to the other substances I like, such as piracetam or fish oil. I knew about withdrawal of course, but it was not so bad when I was drinking only tea. And the side-effects like jitteriness are worse on caffeine without tea; I chalk this up to the lack of theanine. (My later experiences with theanine seems to confirm this.) These negative effects mean that caffeine doesn’t satisfy the strictest definition of nootropic (having no negative effects), but is merely a cognitive enhancer (with both benefits & costs). One might wonder why I use caffeine anyway if I am so concerned with mental ability.
I’ve been taking nootropics on and off for a month, and despite my spurts of productivity, I’m still not 100 percent sure that they’re working. I could well be placebo-ing myself into thinking I'm working harder and focusing better than I typically do. But apparently enough people are feeling some effect, placebo or not, because nootropics start-ups are thriving. There’s truBrain, Nootrobrain, Nootroo, and a host of others. Nootrobox, the company that makes my pills, says that it’s selling "five figures" worth of cognitive supplements monthly to customers that include top Silicon Valley executives and Hollywood moguls.
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 vital 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.
Here’s how it works: Donepezil boosts serotonin and acetylcholine in the brain, chemicals that are usually found in high concentrations in the brains of young children which naturally decrease with age. As a cholinesterase inhibitor, Donezepil boosts brain function by increasing the amount of acetylcholine around nerve endings. In dementia and Alzheimer’s patients, the drug has been shown to improve memory function.
Huperzine A: This compound is found in a firmoss plant called Huperzia serrata. Studies conducted on Huperzine A so far have not used the best methodology, so scientists are still not sure how beneficial this compound is for preventing or treating Alzheimer’s disease. But one review of studies on Huperzine A concluded that the compound “appears to have beneficial effects on improvement of cognitive function, daily living activity, and global clinical assessment in participants with Alzheimer’s disease.”
Alex recalled one week during his junior year when he had four term papers due. Minutes after waking on Monday, around 7.30am, he swallowed some "immediate-release" Adderall. The drug, along with a steady stream of caffeine, helped him to concentrate during classes and meetings, but he noticed some odd effects; at a morning tutorial, he explained to me in an email, "I alternated between speaking too quickly and thoroughly on some subjects and feeling awkwardly quiet during other points of the discussion." Lunch was a blur: "It's always hard to eat much when on Adderall." That afternoon he went to the library, where he spent "too much time researching a paper rather than actually writing it - a problem that is common to all intellectually curious students on stimulants". At eight he attended a two-hour meeting "with a group focused on student mental health issues". Alex then "took an extended-release Adderall" and worked productively on the paper all night. At eight the next morning he attended a meeting of his student organisation; he felt like "a zombie" and went back to his room. He fell asleep until noon, waking "in time to polish my first paper and hand it in".
Last April the scientific journal Nature published the results of an informal online poll asking whether readers attempted to sharpen "their focus, concentration, or memory" by taking drugs such as Ritalin and Provigil, a newer kind of stimulant, known generically as modafinil, which was developed to treat narcolepsy. One in five respondents said they did. A majority of the 1,400 readers who responded said that healthy adults should be permitted to take brain boosters for non-medical reasons, and 69% said that mild side-effects were an acceptable risk. Though a majority said that such drugs should not be made available to children who had no diagnosed medical condition, a third admitted that they would feel pressure to give "smart drugs" to their kids if they learned that other parents were doing so.
The principal metric would be mood, however defined. Zeo’s web interface & data export includes a field for Day Feel, which is a rating 1-5 of general mood & quality of day. I can record a similar metric at the end of each day. 1-5 might be a little crude even with a year of data, so a more sophisticated measure might be in order. The first mood study is paywalled so I’m not sure what they used, but Shiotsuki 2008 used State-Trait of Anxiety Inventory (STAI) and Profiles of Mood States Test (POMS). The full POMS sounds too long to use daily, but the Brief POMS might work. In the original 1987 paper A brief POMS measure of distress for cancer patients, patients answering this questionnaire had a mean total mean of 10.43 (standard deviation 8.87). Is this the best way to measure mood? I’ve asked Seth Roberts; he suggested using a 0-100 scale, but personally, there’s no way I can assess my mood on 0-100. My mood is sufficiently stable (to me) that 0-5 is asking a bit much, even.
By the way, since I’ll throw around the term a few more times in this article, I should probably clarify what an adaptogen actually is. The actual name adaptogen gives some hint as to what these fascinating compounds do: they help you to adapt, specifically by stimulating a physiological adaptive response to some mild, hormesis-like stressor. A process known as general adaptation syndrome (GAS) was first described by the 20th-century physician and organic chemist Hans Selye, who defined GAS as the body’s response to the demands placed upon it. When these demands are excessive and consistent, it can result in the common deleterious symptoms now associated with long-term exposure to chronic stress. GAS is comprised of an alarm stage (characterized by a burst of energy), a resistance stage (characterized by resistance or adaptation to the stressor), and – in the case of excessive and chronic stress – an exhaustion stage (characterized by energy depletion). Adaptogens are plant-derived compounds capable of modulating these phases of GAS by either downregulating stress reactions in the alarm phase or inhibiting the onset of the exhaustion phase, thus providing some degree of protection against damage from stress.
We already knew that rosemary oil has a variety of benefits, but did you know that the herb does, too? Carnosic acid, one of the main ingredients in rosemary, helps protect the brain from neurodegeneration. It does this by protecting the brain against chemical free radicals, which are linked to neurodegeneration, Alzheimer’s, strokes and normal aging in the brain. (10)
Of course learning, working memory and cognitive control represent just a few aspects of thinking. Farah concluded that studies looking at other kinds of cognition - verbal fluency, for instance - were too few and too contradictory to tell us much. Both Chatterjee and Farah have wondered whether drugs that heighten users' focus might dampen their creativity. After all, some of our best ideas come to us not when we sit down at a desk but rather when we're in the shower or walking the dog - letting our minds roam. Jimi Hendrix reported that the inspiration for "Purple Haze" came to him in a dream; the chemist Friedrich August Kekule claimed that he discovered the ring structure of benzene during a reverie in which he saw the image of a snake biting its tail. Farah told me: "There is some evidence that suggests that individuals who are better able to focus on one thing and filter out distractions tend to be less creative.
Or in other words, since the standard deviation of my previous self-ratings is 0.75 (see the Weather and my productivity data), a mean rating increase of >0.39 on the self-rating. This is, unfortunately, implying an extreme shift in my self-assessments (for example, 3s are ~50% of the self-ratings and 4s ~25%; to cause an increase of 0.25 while leaving 2s alone in a sample of 23 days, one would have to push 3s down to ~25% and 4s up to ~47%). So in advance, we can see that the weak plausible effects for Noopept are not going to be detected here at our usual statistical levels with just the sample I have (a more plausible experiment might use 178 pairs over a year, detecting down to d>=0.18). But if the sign is right, it might make Noopept worthwhile to investigate further. And the hardest part of this was just making the pills, so it’s not a waste of effort.
The powder itself is quite bulky; the recommended dose to hit 200mg of absorbed magnesium leads to ~7g of powder (so capping will be difficult) and the container provides only 30 doses’ worth (or each dose costs $1!). It’s described as lemon-flavored, and it is, but it’s sickly-sweet unpleasant and since it’s so much powder, takes half a glass of water to dissolve it entirely and wash it down. Subjectively, I notice nothing after taking it for a week. I may try a simple A-B-A analysis of sleep or Mnemosyne, but I’m not optimistic. And given the large expense of LEF’s Magtein, it’s probably a non-starter even if there seems to be an effect. For sleep effects, I will have to look at more reasonably priced magnesium sources.
…The first time I took supplemental potassium (50% US RDA in a lot of water), it was like a brain fog lifted that I never knew I had, and I felt profoundly energized in a way that made me feel exercise was reasonable and prudent, which resulted in me and the roommate that had just supplemented potassium going for an hour long walk at 2AM. Experiences since then have not been quite so profound (which probably was so stark for me as I was likely fixing an acute deficiency), but I can still count on a moderately large amount of potassium to give me a solid, nearly side effect free performance boost for a few hours…I had been doing Bikram yoga on and off, and I think I wasn’t keeping up the practice because I wasn’t able to properly rehydrate myself.
Learning how products have worked for other users can help you feel more confident in your purchase. Similarly, your opinion may help others find a good quality supplement. After you have started using a particular supplement and experienced the benefits of nootropics for memory, concentration, and focus, we encourage you to come back and write your own review to share your experience with others.
This tendency is exacerbated by general inefficiencies in the nootropics market - they are manufactured for vastly less than they sell for, although the margins aren’t as high as they are in other supplement markets, and not nearly as comical as illegal recreational drugs. (Global Price Fixing: Our Customers are the Enemy (Connor 2001) briefly covers the vitamin cartel that operated for most of the 20th century, forcing food-grade vitamins prices up to well over 100x the manufacturing cost.) For example, the notorious Timothy Ferriss (of The Four-hour Work Week) advises imitators to find a niche market with very high margins which they can insert themselves into as middlemen and reap the profits; one of his first businesses specialized in… nootropics & bodybuilding. Or, when Smart Powders - usually one of the cheapest suppliers - was dumping its piracetam in a fire sale of half-off after the FDA warning, its owner mentioned on forums that the piracetam was still profitable (and that he didn’t really care because selling to bodybuilders was so lucrative); this was because while SP was selling 2kg of piracetam for ~$90, Chinese suppliers were offering piracetam on AliBaba for $30 a kilogram or a third of that in bulk. (Of course, you need to order in quantities like 30kg - this is more or less the only problem the middlemen retailers solve.) It goes without saying that premixed pills or products are even more expensive than the powders.
The methodology would be essentially the same as the vitamin D in the morning experiment: put a multiple of 7 placebos in one container, the same number of actives in another identical container, hide & randomly pick one of them, use container for 7 days then the other for 7 days, look inside them for the label to determine which period was active and which was placebo, refill them, and start again.
-Phosphatidylserine, which occurs naturally in high concentrations in the brain and has been shown to lower stress, cortisol and physical fatigue, improve attention-deficit and forgetfulness and increase mental processing and memory. Research indicates an effective dose of 100 mg three times daily, but anything over that may lead to adverse side effects like insomnia.
I can test fish oil for mood, since the other claimed benefits like anti-schizophrenia are too hard to test. The medical student trial (Kiecolt-Glaser et al 2011) did not see changes until visit 3, after 3 weeks of supplementation. (Visit 1, 3 weeks, visit 2, supplementation started for 3 weeks, visit 3, supplementation continued 3 weeks, visit 4 etc.) There were no tests in between the test starting week 1 and starting week 3, so I can’t pin it down any further. This suggests randomizing in 2 or 3 week blocks. (For an explanation of blocking, see the footnote in the Zeo page.)
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.
10:30 AM; no major effect that I notice throughout the day - it’s neither good nor bad. This smells like placebo (and part of my mind is going how unlikely is it to get placebo 3 times in a row!, which is just the Gambler’s fallacy talking inasmuch as this is sampling with replacement). I give it 60% placebo; I check the next day right before taking, and it is. Man!
Over the years, science has looked into the validity of this date being the most blue of all dates, however there is little evidence to prove this. There is some research that suggests how weekends are a time when people generally feel happier and less anxious, mostly for those that work full-time Monday-Friday, however there is little difference with subjective mood for other days of the week. Some charities such as MIND, have even said that Blue Monday, which is used mainly as a marketing tool to sell products and stories, can also be dangerously misleading and have even set up the hashtag #BlueAnyDay to help dispel the myth of this date.The idea that as a population we are more likely to feel down on the third of fourth Monday of the year can not only trivialise depression as a medical illness that can be life threatening but can also affect those that live with depression and know too well that feelings associated to this illness are not dictated by a single date in the diary.
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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.
Alex remains enthusiastic about Adderall, but he also has a slightly jaundiced critique of it. "It only works as a cognitive enhancer insofar as you are dedicated to accomplishing the task at hand," he said. "The number of times I've taken Adderall late at night and decided that, rather than starting my paper, hey, I'll organise my entire music library! I've seen people obsessively cleaning their rooms on it." Alex thought that generally the drug helped him to bear down on his work, but it also tended to produce writing with a characteristic flaw. "Often I've looked back at papers I've written on Adderall, and they're verbose. They're labouring a point, trying to create this airtight argument. I'd produce two pages on something that could be said in a couple of sentences." Nevertheless, his Adderall-assisted papers usually earned him at least a B. They got the job done. As Alex put it: "Productivity is a good thing."
Choline is a nootropic: it enhances your ability to pay attention and learn efficiently, probably because you use a lot of acetylcholine during mentally-demanding tasks, and choline helps you synthesize enough to work harder and go longer. Choline also links to decreased brain inflammation in a dose-dependent manner — the more choline you eat, the less inflamed your brain tends to be.
It’s basic economics: the price of a good must be greater than cost of producing said good, but only under perfect competition will price = cost. Otherwise, the price is simply whatever maximizes profit for the seller. (Bottled water doesn’t really cost $2 to produce.) This can lead to apparently counter-intuitive consequences involving price discrimination & market segmentation - such as damaged goods which are the premium product which has been deliberately degraded and sold for less (some Intel CPUs, some headphones etc.). The most famous examples were railroads; one notable passage by French engineer-economist Jules Dupuit describes the motivation for the conditions in 1849:
There are a variety of substances to get magnesium from. Considerable enthusiasm for the new compound magnesium l-threonate was stirred by 2 small animal rat studies finding that magnesium l-threonate was able to increase magnesium levels in the brain and improve learning/memory tasks. (There are no published human trials as of October 2015, and evidence of publication bias, which I take as evidence against there being large effects in humans.) Animal studies mean very little, of course (see the appendix), but I thought it’d be interesting to try using l-threonate, so I bought the $30 Life Extension Neuro-Mag Magnesium L-Threonate with Calcium and Vitamin D3 (205g), which according to the LEF product page works out to ~60g of Magtein™ magnesium L-threonate and ~4.31g elemental magnesium inasmuch as LEF claims 2000mg of threonate powder provides 144mg elemental magnesium or a 14:1 ratio. (I don’t need the calcium or vitamin D3, but this was the only magnesium l-threonate on Amazon.) Experiment-wise, I’ll probably look at sleep metrics and Mnemosyne performance; I put off designing a blind self-experiment until after trying some.
Research on animals has shown that intermittent fasting — limiting caloric intake at least two days a week — can help improve neural connections in the hippocampus and protect against the accumulation of plaque, a protein prevalent in the brains of people with Alzheimer’s disease. Research has also shown that intermittent fasting helped reduce anxiety in mice.
(On a side note, I think I understand now why modafinil doesn’t lead to a Beggars in Spain scenario; BiS includes massive IQ and motivation boosts as part of the Sleepless modification. Just adding 8 hours a day doesn’t do the world-changing trick, no more than some researchers living to 90 and others to 60 has lead to the former taking over. If everyone were suddenly granted the ability to never need sleep, many of them would have no idea what to do with the extra 8 or 9 hours and might well be destroyed by the gift; it takes a lot of motivation to make good use of the time, and if one cannot, then it is a curse akin to the stories of immortals who yearn for death - they yearn because life is not a blessing to them, though that is a fact more about them than life.)
Is 200 enough? There are no canned power functions for the ordinal logistic regression I would be using, so the standard advice is to estimate power by simulation: generating thousands of new datasets where we know by construction that the binary magnesium variable increases MP by 0.27 (such as by bootstrapping the original Noopept experiment’s data), and seeing how often in this collection the cutoff of statistical-significance is passed when the usual analysis is done (background: CrossValidated or Power Analysis and Sample Size Estimation using Bootstrap). In this case, we leave alpha at 0.05, reuse the Noopept experiment’s data with its Magtein correlation, and ask for the power when n=200
Recent findings also suggest that taking extra vitamins could help preserve memory, especially as we age. Researchers at Australia's University of Sydney tested 117 people in a retirement home by putting them through a battery of mental tests that included remembering a string of words, listing as many words as possible that begin with a certain letter of the alphabet, and doing mental addition and subtraction. Those who regularly took vitamin C, they found, scored higher on the tests.
“Over the years, I have learned so much from the work of Dr. Mosconi, whose accomplished credentials spanning both neuroscience and nutrition are wholly unique. This book represents the first time her studies on the interaction between food and long-term cognitive function reach a general audience. Dr. Mosconi always makes the point that we would eat differently and treat our brains better if only we could see what we are doing to them. From the lab to the kitchen, this is extremely valuable and urgent advice, complete with recommendations that any one of us can take.”
Farah was one of several scholars who contributed to a recent article in Nature, "Towards Responsible Use of Cognitive Enhancing Drugs by the Healthy". The optimistic tone of the article suggested that some bioethicists are leaning towards endorsing neuroenhancement. "Like all new technologies, cognitive enhancement can be used well or poorly," the article declared. "We should welcome new methods of improving our brain function. In a world in which human workspans and lifespans are increasing, cognitive-enhancement tools - including the pharmacological - will be increasingly useful for improved quality of life and extended work productivity, as well as to stave off normal and pathological age-related cognitive declines. Safe and effective cognitive enhancers will benefit both the individual and society." The BMA report offered a similarly upbeat observation: "Universal access to enhancing interventions would bring up the baseline level of cognitive ability, which is generally seen to be a good thing."
Get plenty of sleep. It can be a real challenge to get seven to nine hours of restful sleep each night with a busy fulltime work schedule, but rest is essential to optimum brain functioning! A healthy nootropic pill can help to clear up brain fog and sharpen your concentration, but it cannot work miracles. If you are trying to power through on four to five hours of sleep each night, nothing is going to cut it.
Cognizin– this is a derivative of citicoline. It increases* the levels of acetylcholine neurotransmitters, dopamine, and noradrenaline in the brain. These are neurotransmitters essential for brain functioning. Besides this, Cognizin maintains the functioning and stamina of neuronal cell membranes and enhance* energy production from the frontal cortex. With this, you will have increased mental reaction time, expanded focusing ability, improved* immediate and short-term verbal memory and augment the brain’s metabolism.
One of the most common strategies to beat this is cycling. Users who cycle their nootropics take them for a predetermined period, (usually around five days) before taking a two-day break from using them. Once the two days are up, they resume the cycle. By taking a break, nootropic users reduce the tolerance for nootropics and lessen the risk of regression and tolerance symptoms.