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.

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.
These pills don’t work. The reality is that MOST of these products don’t work effectively. Maybe we’re cynical, but if you simply review the published studies on memory pills, you can quickly eliminate many of the products that don’t have “the right stuff.” The active ingredients in brain and memory health pills are expensive and most companies sell a watered down version that is not effective for memory and focus. The more brands we reviewed, the more we realized that many of these marketers are slapping slick labels on low-grade ingredients.
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.
Herbs and plants have been used for cognitive enhancement for at least 5,000 years in Indian and Chinese medicine, long before the first synthetic nootropic was created. The practice of Indian Ayurvedic medicine includes the use of a group of nootropic plants known as Medhya Rasayana, the four primary plants of which are Mandukaparni, Yastimadhu, Duduchi and Shankhapushpi, though other lesser known plants are also used. One of the most common supplements in Ayurvedic medicine is Brahmi, known scientifically as “Bacopa monnieri” or “B. monnieri “ and more commonly as water hyssop, Thyme-leaved Gratiola, herb of grace or Indian pennywort. It is named after Lord Brahma, the creator God and originator of Ayurveda, and has been used for centuries to treat disorders ranging from pain and epilepsy to inflammation and memory dysfunction. The exact mechanism behind its action is not fully understood, but it is believed to promote antioxidant activity as well as protect neurons in the prefrontal cortex, hippocampus and corpus striatum against cytotoxicity and DNA damage associated with Alzheimer’s. The prefrontal cortex is critical in rational, social and personality behavior, the hippocampus is believed to be the seat of memory and the autonomic nervous system and the striatum play a role in the reward system of action, so the protection Brahmi provides is extremely helpful in preventing the degeneration of many important cognitive faculties. An effective dose ranges from 300 to 450 mg per day. Winter cherry (ashwagandha) is another well-known Ayurvedic supplement that can promote improved cognitive development, memory and intelligence and reduce the effects of neurodegenerative diseases such as Parkinson’s, Huntington’s and Alzheimer’s. The optimal dose is 6,000 mg per day divided into three 2,000 mg doses. Aloeweed (shankhpushpi) is also used in Ayurvedic medicine to improve memory and intellect as well as treat hypertension, epilepsy and diabetes. Effective doses for most neuroenhancing benefits range as high as 40 g per day.
Avocados are almost as good as blueberries in promoting brain health, Dr. Pratt told These buttery fruits are rich in monounsaturated fat, which contributes to healthy blood flow in the brain, according to Ann Kulze, MD, author of Dr. Ann’s 10-Step Diet: A Simple Plan for Permanent Weight Loss & Lifelong Vitality. This helps every organ in your body—particularly the brain and heart. Avocados also lower blood pressure, thanks to their potassium. Because high blood pressure can impair cognitive abilities, lower blood pressure helps to keep the brain in top form and reduce your risks for hypertension or a stroke. The fiber in avocados also reduces the risk of heart disease and bad cholesterol.  These foods are good for your brain later in life.
Piracetam is used to increase memory, learning, and concentration. It is not reported to be toxic even at high doses, but healthy people are reported to not get that much of a boost from it, and it is understood to be most effective for older people. It’s been found to reduce the chances of a breath-holding spell in children, enhance cellular membrane fluidity, and prevent blood clotting on par with aspirin.
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.
So I eventually got around to ordering another thing of nicotine gum, Habitrol Nicotine Gum, 4mg MINT flavor COATED gum. 96 pieces per box. Gum should be easier to double-blind myself with than nicotine patches - just buy some mint gum. If 4mg is too much, cut the gum in half or whatever. When it arrived, my hopes were borne out: the gum was rectangular and soft, which made it easy to cut into fourths.

Choosing to take smart drugs is not an effective or long term solution. Smart drugs may help you study faster or keep you awake longer, but they are not your best option. Most of the ADHD medications are based on an amphetamine structure and they are not healthy for your heart or your liver. Also, by taking smart drugs, you are putting yourself at considerable risk for addiction to these substances.

So the chi-squared believes there is a statistically-significant difference, the two-sample test disagrees, and the binomial also disagrees. Since I regarded it as a dubious theory, can’t see a difference, and the binomial seems like the most appropriate test, I conclude that several months of 1mg iodine did not change my eye color. (As a final test, when I posted the results on the Longecity forum where people were claiming the eye color change, I swapped the labels on the photos to see if anyone would claim something along the lines when I look at the photos, I can see a difference!. I thought someone might do that, which would be a damning demonstration of their biases & wishful thinking, but no one did.)

B vitamins are also sold with claims of enhancing memory, usually rationalized by their reduction of homocysteine, a chemical in the blood that may affect circulation in the brain. No benefits from B vitamin intake have been demonstrated when it comes to memory or cognitive function except in the case of people who have high homocysteine levels due to a diet that is very low in B vitamins. There is some concern that folic acid, one of the B vitamins, may spur the growth of polyps in the colon at doses greater than 800 micrograms a day. Phosphatidyl serine is a natural component of nerve cell membranes and its promoters argue that a deficiency leads to impaired communication between nerve cells which in turn impairs cognitive function. Sounds reasonable, except that proper controlled trials have come up empty. The same goes for vinpocetine, a compound originally isolated from the lesser periwinkle plant by Hungarian chemist Csaba Szantay in 1975. It is widely used in Europe to treat strokes and memory problems with claims of increased circulation to the brain. It does indeed increase circulation, much like ginkgo, but there is no compelling evidence for memory improvement.
The bitter reality of life is that there’s no organ of our body, which can defy the effects of aging with success. At least not entirely on its own. That’s why we need supplements in the first place. Remember? That’s only the beginning of the bad news for your brain. Certain sections of our brain, especially prefrontal cortex and hippocampus, can be seriously reduced in size as you are getting older. In addition, the number of capillaries in your head reduces, as well. Let’s not forget the arteries that become narrower and therefore limit the blood flow.
Another prescription stimulant medication, modafinil (known by the brand name Provigil), is usually prescribed to patients suffering from narcolepsy and shift-work sleep disorder, but it might turn out to have broader applications. “We have conducted at the University of Cambridge double-blind, placebo-controlled studies in healthy people using modafinil and have found improvements in cognition, including in working memory,” Sahakian says. However, she doesn’t think everyone should start using the drug off-label. “There are no long-term safety and efficacy studies of modafinil in healthy people, and so it is unclear what the risks might be.”

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.
Turns out, when compared with smokers who drank coffee regularly, non-coffee drinkers had twice as much of the cell damage associated with tobacco use. In addition, the smokers who didn’t consume coffee were up to seven times more likely to be affected by the same cancer as nonsmokers. Regular smokers who drank coffee fewer than two times each week had double the chances of developing cancer compared to those who drank coffee frequently. So ultimately, coffee-drinking cigarette-puffers have some kind of health advantage over their smoking counterparts who don’t drink coffee.
“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.”
To our partners, community supporters, and funders: The Brainfood journey has taken us many places, and at each fork in the road we discovered an amazing network of youth advocates ready to help lift our work to the next level. Whether you donated pro-bono consulting hours, connected us to allies in the city, or came in to meet our students and see a class, you helped us build something really special. Thanks for believing in us.

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Another prescription stimulant medication, modafinil (known by the brand name Provigil), is usually prescribed to patients suffering from narcolepsy and shift-work sleep disorder, but it might turn out to have broader applications. “We have conducted at the University of Cambridge double-blind, placebo-controlled studies in healthy people using modafinil and have found improvements in cognition, including in working memory,” Sahakian says. However, she doesn’t think everyone should start using the drug off-label. “There are no long-term safety and efficacy studies of modafinil in healthy people, and so it is unclear what the risks might be.”

Nootropics. You might have heard of them. The “limitless pill” that keeps Billionaires rich. The ‘smart drugs’ that students are taking to help boost their hyperfocus. The cognitive enhancers that give corporate executives an advantage. All very exciting. But as always, the media are way behind the curve. Yes, for the past few decades, cognitive enhancers were largely sketchy substances that people used to grasp at a short term edge at the expense of their health and wellbeing. But the days of taking prescription pills to pull an all-nighter are so 2010. The better, safer path isn’t with these stimulants but with nootropics. Nootropics consist of supplements and substances which enhance your cognition, in particular when it comes to motivation, creativity, memory, and other executive functions.