One thing I did do was piggyback on my Noopept self-experiment: I blinded & randomized the Noopept for a real experiment, but simply made sure to vary the Magtein without worrying about blinding or randomizing it. (The powder is quite bulky.) The correlation the experiment turned in was a odds-ratio of 1.9; interesting and in the right direction (higher is better), but since the magnesium part wasn’t random or blind, not a causal result.
Any consideration of the future of nootropics is directly tied into the future of humanity. As long as work productivity demands continue to soar, there will like be a affiliated rise in the desire to increase brain power. As Vice discusses in a thoughtful article providing several insights into why nootropics are popular, it is not surprising that smart drugs and the nootropic industry are ever-expanding. Vice points out that sci-fi writers once warned of people being overtaken by machines, but instead, human beings are becoming machines, taking on unrealistic work levels.[15] Taking nootropic drugs is akin to loading up on premium fuel in an effort to go faster and do better.
At small effects like d=0.07, a nontrivial chance of negative effects, and an unknown level of placebo effects (this was non-blinded, which could account for any residual effects), this strongly implies that LLLT is not doing anything for me worth bothering with. I was pretty skeptical of LLLT in the first place, and if 167 days can’t turn up anything noticeable, I don’t think I’ll be continuing with LLLT usage and will be giving away my LED set. (Should any experimental studies of LLLT for cognitive enhancement in healthy people surface with large quantitative effects - as opposed to a handful of qualitative case studies about brain-damaged people - and I decide to give LLLT another try, I can always just buy another set of LEDs: it’s only ~$15, after all.)
A big part is that we are finally starting to apply complex systems science to psycho-neuro-pharmacology and a nootropic approach. The neural system is awesomely complex and old-fashioned reductionist science has a really hard time with complexity. Big companies spends hundreds of millions of dollars trying to separate the effects of just a single molecule from placebo – and nootropics invariably show up as “stacks” of many different ingredients (ours, Qualia , currently has 42 separate synergistic nootropics ingredients from alpha GPC to bacopa monnieri and L-theanine). That kind of complex, multi pathway input requires a different methodology to understand well that goes beyond simply what’s put in capsules.
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 third category was cognitive control - how effectively you can check yourself in circumstances where the most natural response is the wrong one. A classic test is the Stroop Task, in which people are shown the name of a colour (let's say orange) written in a different colour (let's say purple). They're asked to read the word (which is easy, because our habitual response to a word is to read it) or to name the ink colour (which is harder, because our first impulse is to say "orange"). These studies presented a more mixed picture, but overall they showed some benefit "for most normal healthy subjects" - especially for people who had inherently poorer cognitive control.
First half at 6 AM; second half at noon. Wrote a short essay I’d been putting off and napped for 1:40 from 9 AM to 10:40. This approach seems to work a little better as far as the aboulia goes. (I also bother to smell my urine this time around - there’s a definite off smell to it.) Nights: 10:02; 8:50; 10:40; 7:38 (2 bad nights of nasal infections); 8:28; 8:20; 8:43 (▆▃█▁▂▂▃).
So with these 8 results in hand, what do I think? Roughly, I was right 5 of the days and wrong 3 of them. If not for the sleep effect on #4, which is - in a way - cheating (one hopes to detect modafinil due to good effects), the ratio would be 5:4 which is awfully close to a coin-flip. Indeed, a scoring rule ranks my performance at almost identical to a coin flip: -5.49 vs -5.5420. (The bright side is that I didn’t do worse than a coin flip: I was at least calibrated.)
We felt that True Focus offered a good product but the price was slightly high compared to others. Their website doesn’t show a clear money-back guarantee though, which definitely reduced their rating. We found that their customer reviews were mixed and saw that some consumers did not mind paying a little more for a product that is more consumer friendly.

It would be like saying: 'No, you can't use a cell phone. It might increase productivity!'" If we eventually decide that neuroenhancers work, and are basically safe, will we one day enforce their use? Lawmakers might compel certain workers - A&E doctors, air-traffic controllers - to take them. (Indeed, the US Air Force already makes modafinil available to pilots embarking on long missions.) For the rest of us, the pressure will be subtler - that queasy feeling I get when I remember that my younger colleague is taking Provigil to meet deadlines. All this may be leading to a kind of society I'm not sure I want to live in: a society where we're even more overworked and driven by technology than we already are, and where we have to take drugs to keep up; a society where we give children academic steroids along with their daily vitamins.
Powders are good for experimenting with (easy to vary doses and mix), but not so good for regular taking. I use OO gel capsules with a Capsule Machine: it’s hard to beat $20, it works, it’s not that messy after practice, and it’s not too bad to do 100 pills. However, I once did 3kg of piracetam + my other powders, and doing that nearly burned me out on ever using capsules again. If you’re going to do that much, something more automated is a serious question! (What actually wound up infuriating me the most was when capsules would stick in either the bottom or top try - requiring you to very gingerly pull and twist them out, lest the two halves slip and spill powder - or when the two halves wouldn’t lock and you had to join them by hand. In contrast: loading the gel caps could be done automatically without looking, after some experience.)
True Focus offers several very positive elements. The ingredients are excellent quality and all natural and without side effects. We like the fact they offer a product that is both vegan and vegetarian friendly, as well as being gluten, soy and dairy free. This allows many consumers to experience the benefits of this product. The fact they do not offer a clear money-back guarantee, we felt, placed them in a weaker position. Moreover, the lack of multi-purchase price deals left us feeling that this was slightly expensive, as with no options to reduce the cost per bottle, consumers will be stuck paying slightly more for each bottle.
After I ran out of creatine, I noticed the increased difficulty, and resolved to buy it again at some point; many months later, there was a Smart Powders sale so bought it in my batch order, $12 for 1000g. As before, it made Taekwondo classes a bit easier. I paid closer attention this second time around and noticed that as one would expect, it only helped with muscular fatigue and did nothing for my aerobic issues. (I hate aerobic exercise, so it’s always been a weak point.) I eventually capped it as part of a sulbutiamine-DMAE-creatine-theanine mix. This ran out 1 May 2013. In March 2014, I spent $19 for 1kg of micronized creatine monohydrate to resume creatine use and also to use it as a placebo in a honey-sleep experiment testing Seth Roberts’s claim that a few grams of honey before bedtime would improve sleep quality: my usual flour placebo being unusable because the mechanism might be through simple sugars, which flour would digest into. (I did not do the experiment: it was going to be a fair amount of messy work capping the honey and creatine, and I didn’t believe Roberts’s claims for a second - my only reason to do it would be to prove the claim wrong but he’d just ignore me and no one else cares.) I didn’t try measuring out exact doses but just put a spoonful in my tea each morning (creatine is tasteless). The 1kg lasted from 25 March to 18 September or 178 days, so ~5.6g & $0.11 per day.
It's been widely reported that Silicon Valley entrepreneurs and college students turn to Adderall (without a prescription) to work late through the night. In fact, a 2012 study published in the Journal of American College Health, showed that roughly two-thirds of undergraduate students were offered prescription stimulants for non-medical purposes by senior year.
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.)
As discussed in my iodine essay (FDA adverse events), iodine is a powerful health intervention as it eliminates cretinism and improves average IQ by a shocking magnitude. If this effect were possible for non-fetuses in general, it would be the best nootropic ever discovered, and so I looked at it very closely. Unfortunately, after going through ~20 experiments looking for ones which intervened with iodine post-birth and took measures of cognitive function, my meta-analysis concludes that: the effect is small and driven mostly by one outlier study. Once you are born, it’s too late. But the results could be wrong, and iodine might be cheap enough to take anyway, or take for non-IQ reasons. (This possibility was further weakened for me by an August 2013 blood test of TSH which put me at 3.71 uIU/ml, comfortably within the reference range of 0.27-4.20.)

The AC-11 that Marcus mentioned for health is an extract from the Amazon jungle vine una de gato, and has been shown in laboratory and clinical trials to encourage DNA repair. The Mucuna pruriens he named for motivation is a legume that's a concentrated source of L-Dopa, which the body converts to the neurotransmitter dopamine. The Huperzia serrata Marcus selected for hunting is the same substance that induces lucid dreaming. This seems appropriate. While I felt the Alpha Brain helped my hunting, maybe I was dreaming. Or maybe a dream state of mind is good for hunting.
Seltzer's decision to take piracetam was based on his own online reading, which included medical-journal abstracts. He hadn't consulted a doctor. Since settling on a daily regime of supplements, he had sensed an improvement in his intellectual work and his ability to engage in stimulating conversation. He continued: "I feel I'm better able to articulate my thoughts. I'm sure you've been in the zone - you're having a really exciting debate with somebody, your brain feels alive. I feel that more. But I don't want to say that it's this profound change."

Your brain loves omega-3 fatty acids, which are thought to play an important role in cognitive function. According to the New York Times describing research in the journal Neurology, low levels of these unsaturated fats in the blood are linked with smaller brain volume and worse performance on certain tests of mental function. Omega-3s, which are found in salmon and other cold-water fish like tuna, may improve the retention of brain cells and also bolster the brainpower of younger adults. According to University of Pittsburgh research published last year, adults under age 25 who increased their omega-3 intake over six months improved their scores on tests measuring working memory.
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.
Mosconi gets the anthropology right. Her foundation is based on two empirical findings. The first one is her studying of the “Blue Zones” or the five areas in the World associated with the greatest proportion of centenarians. And, her second one is her experience as a neuroscientist. She has seen thousands of brain MRIs while knowing what diet her patients ate. She uncovered a link between brain health and diet. The ones who ate a Mediterranean diet had far healthier brains (per MRIs) than the ones on an American diet. She also observed that 2 out of the 5 Blue Zones eat a Mediterranean diets. And, the three other ones have major overlapping components with a Mediterranean diet including complex carbohydrates (fresh produce) that have a lot of fiber, starches (sweet potatoes), nuts, fish, and not much meat and animal protein.

Nootropics—the name given to a broad class of so-called "cognitive-enhancing" drugs—are all the rage in Silicon Valley these days. Programmers like nootropics because they’re said to increase productivity and sharpen focus without the intensity or side effects of a prescription drug like Adderall or modafinil. Some users mix their own nootropics using big bins of powders, purchased off the Internet or in supplement stores. And some take pre-made "stacks" that are designed to produce specific effects.
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.

But what does this all have to do with food? Our gut helps keep our body’s immune responses and inflammation under control. Additionally, gut hormones that enter the brain or are produced in the brain influence cognitive ability, like understanding and processing new information, staying focused on the task at hand and recognizing when we’re full. (3)

One curious thing that leaps out looking at the graphs is that the estimated underlying standard deviations differ: the nicotine days have a strikingly large standard deviation, indicating greater variability in scores - both higher and lower, since the means weren’t very different. The difference in standard deviations is just 6.6% below 0, so the difference almost reaches our usual frequentist levels of confidence too, which we can verify by testing:
After informally testing various formulas of Qualia OS on themselves and friends, Collective founders did an unblinded pilot study with nine volunteers that Dr. Stickler says showed significant benefits in cognitive function and stress response in eight of the subjects. Still, he admits this isn’t airtight scientific proof that the product works. He says the Collective is hoping to do a placebo-controlled study, but in the meantime, he’s confident the stack works because of the results he’s seen in patients.
The Nootroo arrives in a shiny gold envelope with the words “proprietary blend” and “intended for use only in neuroscience research” written on the tin. It has been designed, says Matzner, for “hours of enhanced learning and memory”. The capsules contain either Phenylpiracetam or Noopept (a peptide with similar effects and similarly uncategorised) and are distinguished by real flakes of either edible silver or gold. They are to be alternated between daily, allowing about two weeks for the full effect to be felt. Also in the capsules are L-Theanine, a form of choline, and a types of caffeine which it is claimed has longer lasting effects.
Eugeroics (armodafinil and modafinil) – are classified as "wakefulness promoting" agents; modafinil increased alertness, particularly in sleep deprived individuals, and was noted to facilitate reasoning and problem solving in non-ADHD youth.[23] In a systematic review of small, preliminary studies where the effects of modafinil were examined, when simple psychometric assessments were considered, modafinil intake appeared to enhance executive function.[27] Modafinil does not produce improvements in mood or motivation in sleep deprived or non-sleep deprived individuals.[28]
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