Vinpocetine: This chemical is a semi-synthetic derivative of an extract from periwinkle.  It acts as a potent anti-inflammatory agent, and has also received some testing as a supplement for memory enhancement.  While research results are inconclusive right now, this chemical has been shown to increase blood circulation and metabolism in the brain and may slow down neuron loss.  Some tests have also shown that it can improve concentration and attention.


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.
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 are 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.
Stayed up with the purpose of finishing my work for a contest. This time, instead of taking the pill as a single large dose (I feel that after 3 times, I understand what it’s like), I will take 4 doses over the new day. I took the first quarter at 1 AM, when I was starting to feel a little foggy but not majorly impaired. Second dose, 5:30 AM; feeling a little impaired. 8:20 AM, third dose; as usual, I feel physically a bit off and mentally tired - but still mentally sharp when I actually do something. Early on, my heart rate seemed a bit high and my limbs trembling, but it’s pretty clear now that that was the caffeine or piracetam. It may be that the other day, it was the caffeine’s fault as I suspected. The final dose was around noon. The afternoon crash wasn’t so pronounced this time, although motivation remains a problem. I put everything into finishing up the spaced repetition literature review, and didn’t do any n-backing until 11:30 PM: 32/34/31/54/40%.
Hunters will go to great lengths to gain an edge over their prey. You never know where the margin between success and failure may lie, so you wake up extra early, say a prayer, spray bottled deer piss on your boots, and do whatever else you think might increase your odds. My schedule recently got more demanding thanks to a new baby. With less time to kill and another mouth to feed, I've had to step up my game.
11:30 AM. By 2:30 PM, my hunger is quite strong and I don’t feel especially focused - it’s difficult to get through the tab-explosion of the morning, although one particularly stupid poster on the DNB ML makes me feel irritated like I might on Adderall. I initially figure the probability at perhaps 60% for Adderall, but when I wake up at 2 AM and am completely unable to get back to sleep, eventually racking up a Zeo score of 73 (compared to the usual 100s), there’s no doubt in my mind (95%) that the pill was Adderall. And it was the last Adderall pill indeed.
There are many books about nutrition and cognitive functions. The authors ground their nutrition protocol on what humans ate during the paleolithic era. Often these authors contradict each other. For some, we were better hunters than gatherers so we ate mostly meat. For others, we were better gatherers and ate primarily nuts, plants, fruits. Others advance our digestive system can’t tolerate grains because it was a modern invention of the first agricultural revolution (about 10,000 years ago).
…Phenethylamine is intrinsically a stimulant, although it doesn’t last long enough to express this property. In other words, it is rapidly and completely destroyed in the human body. It is only when a number of substituent groups are placed here or there on the molecule that this metabolic fate is avoided and pharmacological activity becomes apparent.

The reality is that cognitive impairment and dementia are also on the rise, and sometimes symptoms of forgetfulness and confusion are not so innocuous.  According to the Alzheimer’s Association, someone in the United States is diagnosed with Alzheimer’s disease every 66 seconds.  By the middle of this century, that is expected to grow to every 33 seconds.

Qualia claims that its product stems from a new approach to science based on “principled meta-analysis and synthesis of existing research” to optimize “memory, focus, the speed of information processing, and pattern analysis.” The bottom line, however, is in its online medical disclaimer, which says: “These statements have not been evaluated by the Food and Drug Administration. . . . No claims are made about the safety of this product, nor are any medical or psychological benefits claimed.”


And if you obtain your vitamin C from a multivitamin, you receive other key nutrients that many studies over the years have linked to healthy brain function, including beta carotene, iron, zinc, B12 and folic acid. In the June 1999 issue of the Journal of Biology and Psychiatry, for instance, researchers at Sweden's Gotenborg University reported that older people were more likely to score poorly on word memory tests if they had low levels of folic acid.
The original magnesium l-threonate caused me no apparent problems by the time I finished off the powder and usage correlated with better days, further supporting the hypothesis that magnesium helps it. But l-threonate would be difficult to cap (and hence blind self-experiment) and is ruinously expensive on a per-dose basis. So I looked around for alternatives for the followup; one of the most common compounds suggested was the citrate form because it is reasonably well-absorbed and causes fewer digestive problems, so I could just take that. Magnesium oxide is widely available it looks cheap, but the absorption/bioavailability problem makes it unattractive: at a 3:5 ratio, an estimate of 4% absorption, a ZMA formulation of an impressive-sounding 500mg would be 500 \times \frac{3}{5} \times 0.04 = 12mg or a small fraction of RDAs for male adults like 400mg elemental. (Calcium shouldn’t be a problem since I get 220mg of calcium from my multivitamin and I enjoy dairy products daily.)
Farah told me: "These drugs will definitely help some technically normal people - that is, people who don't meet the diagnostic criteria for ADHD or any kind of cognitive impairment." But, she emphasised, "They will help people in the lower end of the ability range more than in the higher end." One explanation for this phenomenon might be that the more adept you are at a given task, the less room you have to improve. Farah has a hunch that there may be another reason that existing drugs - so far, at least - don't offer as much help to people with greater intellectual abilities. Drugs like Ritalin and Adderall work in part by elevating the amount of dopamine in the brain. Dopamine is something you want just enough of: too little, and you may not be as alert and motivated as you need to be; too much, and you may feel overstimulated. Neuroscientists have discovered that some people have a gene that leads the brain to break down dopamine faster, leaving less of it available; such people are generally a little worse at certain cognitive tasks. People with more available dopamine are generally somewhat better at the same tasks. It makes sense, then, that people with naturally low dopamine would benefit more from an artificial boost.
Using neuroenhancers, Seltzer said, "is like customising yourself - customising your brain". For some people, he added, it was important to enhance their mood, so they took antidepressants; but for people like him it was more important "to increase mental horsepower". He said: "It's fundamentally a choice you're making about how you want to experience consciousness." Whereas the 1990s had been about "the personalisation of technology", this decade was about the personalisation of the brain - what some enthusiasts have begun to call "mind hacking".

Tuesday: I went to bed at 1am, and first woke up at 6am, and I wrote down a dream; the lucid dreaming book I was reading advised that waking up in the morning and then going back for a short nap often causes lucid dreams, so I tried that - and wound up waking up at 10am with no dreams at all. Oops. I take a pill, but the whole day I don’t feel so hot, although my conversation and arguments seem as cogent as ever. I’m also having a terrible time focusing on any actual work. At 8 I take another; I’m behind on too many things, and it looks like I need an all-nighter to catch up. The dose is no good; at 11, I still feel like at 8, possibly worse, and I take another along with the choline+piracetam (which makes a total of 600mg for the day). Come 12:30, and I disconsolately note that I don’t seem any better, although I still seem to understand the IQ essays I am reading. I wonder if this is tolerance to modafinil, or perhaps sleep catching up to me? Possibly it’s just that I don’t remember what the quasi-light-headedness of modafinil felt like. I feel this sort of zombie-like state without change to 4am, so it must be doing something, when I give up and go to bed, getting up at 7:30 without too much trouble. Some N-backing at 9am gives me some low scores but also some pretty high scores (38/43/66/40/24/67/60/71/54 or ▂▂▆▂▁▆▅▇▄), which suggests I can perform normally if I concentrate. I take another pill and am fine the rest of the day, going to bed at 1am as usual.

Reason: Vitamin B12 supports brain health in critical ways. The water-soluble B vitamin helps the body convert carbohydrates and fats into energy the brain needs to function properly. It also helps reduce the brain shrinkage often associated with cognitive disorders, supports healthy sleep-wake cycles (incredibly important, given what we now know about sleep and Alzheimer’s risk), and aids the proper “firing” of communications between neurons.
More photos from this reportage are featured in Quartz’s new book The Objects that Power the Global Economy. You may not have seen these objects before, but they’ve already changed the way you live. Each chapter examines an object that is driving radical change in the global economy. This is from the chapter on the drug modafinil, which explores modifying the mind for a more productive life. 
Clinical psychiatrist Emily Deans has a private practice in Massachusetts and teaches at Harvard Medical School. She told me by phone that, in principle, there's "probably nothing dangerous" about the occasional course of nootropics for a hunting trip, finals week, or some big project. Beyond that, she suggests considering that it's possible to build up a tolerance to many neuroactive products if you use them often enough.
Mosconi holds a dual PhD in neuroscience and nuclear medicine. She is the associate director of the Alzheimer’s Prevention Clinic at Weill Cornell Medical College/New York-Presbyterian Hospital, and the founder of the Nutrition and Brain Fitness Lab at New York University School of Medicine. With her training and experience, she ought to understand and practice rigorous science. She makes all the right noises about scientific literacy and recognizing pseudoscience, but she seems unable to look in the mirror and see her own errors.
Most of the most solid fish oil results seem to meliorate the effects of age; in my 20s, I’m not sure they are worth the cost. But I would probably resume fish oil in my 30s or 40s when aging really becomes a concern. So the experiment at most will result in discontinuing for a decade. At $X a year, that’s a net present value of sum $ map (\n -> 70 / (1 + 0.05)^n) [1..10] = $540.5.
This would be a very time-consuming experiment. Any attempt to combine this with other experiments by ANOVA would probably push the end-date out by months, and one would start to be seriously concerned that changes caused by aging or environmental factors would contaminate the results. A 5-year experiment with 7-month intervals will probably eat up 5+ hours to prepare <12,000 pills (active & placebo); each switch and test of mental functioning will probably eat up another hour for 32 hours. (And what test maintains validity with no practice effects over 5 years? Dual n-back would be unusable because of improvements to WM over that period.) Add in an hour for analysis & writeup, that suggests >38 hours of work, and 38 \times 7.25 = 275.5. 12,000 pills is roughly $12.80 per thousand or $154; 120 potassium iodide pills is ~$9, so \frac{365.25}{120} \times 9 \times 5 = 137.
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.
In August 2011, after winning the spaced repetition contest and finishing up the Adderall double-blind testing, I decided the time was right to try nicotine again. I had since learned that e-cigarettes use nicotine dissolved in water, and that nicotine-water was a vastly cheaper source of nicotine than either gum or patches. So I ordered 250ml of water at 12mg/ml (total cost: $18.20). A cigarette apparently delivers around 1mg of nicotine, so half a ml would be a solid dose of nicotine, making that ~500 doses. Plenty to experiment with. The question is, besides the stimulant effect, nicotine also causes habit formation; what habits should I reinforce with nicotine? Exercise, and spaced repetition seem like 2 good targets.

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During pregnancy and after pregnancy there is often a concern for the potential depletion of the maternal nutrient reservoir due to the needs of the growing foetus. A nutrient that is particularly important for mental wellbeing and is also essential for the growth of the foetus’s brain, is DHA. This is an omega 3 fatty acid that is found in oily fish and is the primary structural component of brain tissue, as well as playing a crucial role in the maintenance of brain cells and neurotransmitter metabolism (our body can also convert plant sources of omegas 3’s into DHA, such as those found in flaxseeds or chia seeds into DHA, but the conversion can often very poor). Deficiency in this nutrient during pregnancy is common, namely because of lack of seafood intake (the most bioavailable source of DHA) due to poor eating habits and concerns of mercury levels in fish during pregnancy, as well as higher requirements during foetal growth, which can lead to depletion. Due to the role that DHA plays in neurotransmitter metabolism, deficiency in this nutrient has been correlated to symptoms of depression during pregnancy (7). In order, to support your intake of omega 3, aim to have 3 portions of oily fish a week from sources that are low in mercury. These are mainly small fish that have a short life-span such as sardines, mackerel and herring. If you are vegetarian or vegan, although omega 3 is less readily available, it is still possible to get this nutrient from your diet through flax seeds, chia seeds, walnuts and seaweed. If you feel you may not be getting enough through your diet, you may want to consider using a good quality fish oil supplement (or algae based supplement if vegan) as an option. With fish oils, aim to choose a supplement that has been filtered for heavy metals and other pollutants to make sure you're getting the full benefits of the omega 3 oils.


Past noon, I began to feel better, but since I would be driving to errands around 4 PM, I decided to not risk it and take an hour-long nap, which went well, as did the driving. The evening was normal enough that I forgot I had stayed up the previous night, and indeed, I didn’t much feel like going to bed until past midnight. I then slept well, the Zeo giving me a 108 ZQ (not an all-time record, but still unusual).
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.
Pre and Post-Natal Depression are both complex conditions that can have multifactorial underlying drivers, including genetic and environmental influences. These are currently poorly investigated and the gold standard of treatment is often medication to help stabilise mood. Whilst SSRIs and other types of antidepressants have proven to be helpful for many, they do not address potential causes or drivers of poor mental health and can often mask symptoms. Antidepressants are also not regularly recommended during pregnancy, which is why being more mindful of nutrition and lifestyle habits can be a safer option for you and your baby. There are some natural, evidence-based steps you can take to help support optimal mental wellbeing:

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".
Why? Just think for a moment how much visual, auditory, and sensory information you’re exposed to and required to process every day.  From constant background sounds to big city noise pollution, the phone ringing, artificial lighting, chemical-laden air fresheners circulating smells of fresh linen, electromagnetic fields piercing through your brain, the new procedure you have to learn at work, and a host of other sensory stimuli, the human brain has to organize and deal with this information all while keeping you upright and going. Although the brain has incredible skills and unimaginable capabilities, modern living creates unprecedented stress and sensory overload from all of the information that must be processed every single day.  Sensory overload has even been shown to cause irritability, anxiety, mood swings, depression, ADHD, fibromyalgia, PTSD and chronic fatigue syndrome. The ability of your brain to continue learning, processing, and forming new neural connections is key to maintaining optimal brain health and longevity.

If I assume that the coefficient of +1.22 for as.logical(Magnesium.citrate)TRUE’s effect on MP in the previous analysis represents the true causal effect of 0.156g elemental magnesium without any overdose involved and that magnesium would have a linear increase (up until overdose), then one might argue that optimistically 0.078 would cause an increase of ~0.61. Or one could eyeball the graph and note that the LOESS lines look like at the magnesium peak improved by <+0.5 over the long-run baseline of ~3 Then one could do a power estimate with those 2 estimates.


This is not 100% clear from the data and just blindly using a plausible amount carries the risk of the negative effects, so I intend to run another large experiment. I will reuse the NOW Foods Magnesium Citrate Powder, but this time, I will use longer blocks (to make cumulative overdosing more evident) and try to avoid any doses >150mg of elemental magnesium.
Finally, it’s not clear that caffeine results in performance gains after long-term use; homeostasis/tolerance is a concern for all stimulants, but especially for caffeine. It is plausible that all caffeine consumption does for the long-term chronic user is restore performance to baseline. (Imagine someone waking up and drinking coffee, and their performance improves - well, so would the performance of a non-addict who is also slowly waking up!) See for example, James & Rogers 2005, Sigmon et al 2009, and Rogers et al 2010. A cross-section of thousands of participants in the Cambridge brain-training study found caffeine intake showed negligible effect sizes for mean and component scores (participants were not told to use caffeine, but the training was recreational & difficult, so one expects some difference).

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.
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