The task of building a better mousetrap just got a lot harder. Scientists at Princeton University recently created a strain of smarter mice by inserting a gene that boosts the activity of brain cells. The mice can learn to navigate mazes and find or recognize objects faster than run-of-the-mill rodents. The news, announced in the Sept. 2, 1999 issue of the journal Nature, raises the possibility that genetic engineers may someday be able to help humans learn and remember faster, too.
One thing I notice looking at the data is that the red magnesium-free days seem to dominate the upper ranks towards the end, and blues appear mostly at the bottom, although this is a little hard to see because good days in general start to become sparse towards the end. Now, why would days start to be worse towards the end, and magnesium-dose days in particular? The grim surmise is: an accumulating overdose - no immediate acute effect, but the magnesium builds up, dragging down all days, but especially magnesium-dose days. The generally recognized symptoms of hypermagnesemia don’t include effect on mood or cognition, aside from muscle weakness, confusion, and decreased reflexes…poor appetite that does not improve, but it seems plausible that below medically-recognizable levels of distress like hypermagnesemia might still cause mental changes, and I wouldn’t expect any psychological research to have been done on this topic.
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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.

Tyrosine (Examine.com) is an amino acid; people on the Imminst.org forums (as well as Wikipedia) suggest that it helps with energy and coping with stress. I ordered 4oz (bought from Smart Powders) to try it out, and I began taking 1g with my usual caffeine+piracetam+choline mix. It does not dissolve easily in hot water, and is very chalky and not especially tasty. I have not noticed any particular effects from it.
Tyrosine (Examine.com) is an amino acid; people on the Imminst.org forums (as well as Wikipedia) suggest that it helps with energy and coping with stress. I ordered 4oz (bought from Smart Powders) to try it out, and I began taking 1g with my usual caffeine+piracetam+choline mix. It does not dissolve easily in hot water, and is very chalky and not especially tasty. I have not noticed any particular effects from it.

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.)
(People aged <=18 shouldn’t be using any of this except harmless stuff - where one may have nutritional deficits - like fish oil & vitamin D; melatonin may be especially useful, thanks to the effects of screwed-up school schedules & electronics use on teenagers’ sleep. Changes in effects with age are real - amphetamines’ stimulant effects and modafinil’s histamine-like side-effects come to mind as examples.)
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.)

In my SkepDoc column in Skeptic magazine (text available online) I reviewed the video series “Awakening from Alzheimer’s,” in which a journalist interviews numerous “experts” and claims that Alzheimer’s is for the most part preventable and can be reversed in 9 out of 10 patients! The recommendations of those “experts” are all over the map. There is nothing even remotely approaching a scientific consensus. They claim the main cause of Alzheimer’s is everything from gluten to obesity to lack of sleep to chronic Lyme disease to toxins spewed by “leaky gut” syndrome. They claim to have reversed Alzheimer’s with a wide variety of treatments: everything from coconut oil to a ketogenic diet to probiotics to strenuous exercise to various long lists of dietary supplements to psychological interventions that are considered successful if they make patients cry. There is no satisfactory evidence to support any of their claims.
The next cheap proposition to test is that the 2ml dose is so large that the sedation/depressive effect of nicotine has begun to kick in. This is easy to test: take much less, like half a ml. I do so two or three times over the next day, and subjectively the feeling seems to be the same - which seems to support that proposition (although perhaps I’ve been placebo effecting myself this whole time, in which case the exact amount doesn’t matter). If this theory is true, my previous sleep results don’t show anything; one would expect nicotine-as-sedative to not hurt sleep or improve it. I skip the day (no cravings or addiction noticed), and take half a ml right before bed at 11:30; I fall asleep in 12 minutes and have a ZQ of ~105. The next few days I try putting one or two drops into the tea kettle, which seems to work as well (or poorly) as before. At that point, I was warned that there were some results that nicotine withdrawal can kick in with delays as long as a week, so I shouldn’t be confident that a few days off proved an absence of addiction; I immediately quit to see what the week would bring. 4 or 7 days in, I didn’t notice anything. I’m still using it, but I’m definitely a little nonplussed and disgruntled - I need some independent source of nicotine to compare with!
…The Fate of Nicotine in the Body also describes Battelle’s animal work on nicotine absorption. Using C14-labeled nicotine in rabbits, the Battelle scientists compared gastric absorption with pulmonary absorption. Gastric absorption was slow, and first pass removal of nicotine by the liver (which transforms nicotine into inactive metabolites) was demonstrated following gastric administration, with consequently low systemic nicotine levels. In contrast, absorption from the lungs was rapid and led to widespread distribution. These results show that nicotine absorbed from the stomach is largely metabolized by the liver before it has a chance to get to the brain. That is why tobacco products have to be puffed, smoked or sucked on, or absorbed directly into the bloodstream (i.e., via a nicotine patch). A nicotine pill would not work because the nicotine would be inactivated before it reached the brain.
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.
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:
Subjects with a history or presence of clinically important cardiac, renal, hepatic, endocrine (including diabetes mellitus), pulmonary, biliary, gastrointestinal, pancreatic, or neurologic disorders that, in the judgment of the Investigator, would interfere with the subject's ability to provide informed consent, comply with the study protocol (which might confound the interpretation of the study results), or put the subject at undue risk.
Traditional Chinese medicine also has a long, well-established relationship with nootropic herbs and plants. One of the most popular and well-known is ginkgo biloba, derived from the Chinese maidenhair tree, a relic of the ancient world. The maidenhair tree is the last living species of the division Ginkgophyta>. Some believe that the name ginkgo is a misspelling of the original Japanese gin kyo, meaning “silver apricot”. It’s seen as a symbol of longevity and vitality and is known to be effective at stimulating the growth of new neurons. Researchers have demonstrated that ginkgo flavonoids, the main constituents in ginkgo extract, provide potent anti-Alzheimer’s effects via antioxidant activity in the brains of mice and also stabilize and improve the cognitive performance of Alzheimer patients for 6 months to 1 year. Effective doses range from 120 to 240 mg one to four hours before performance, and for older adults, doses range from 40 to 120 mg three times a day.
Like caffeine, nicotine tolerates rapidly and addiction can develop, after which the apparent performance boosts may only represent a return to baseline after withdrawal; so nicotine as a stimulant should be used judiciously, perhaps roughly as frequent as modafinil. Another problem is that nicotine has a half-life of merely 1-2 hours, making regular dosing a requirement. There is also some elevated heart-rate/blood-pressure often associated with nicotine, which may be a concern. (Possible alternatives to nicotine include cytisine, 2’-methylnicotine, GTS-21, galantamine, Varenicline, WAY-317,538, EVP-6124, and Wellbutrin, but none have emerged as clearly superior.)
Chocolate or cocoa powder (Examine.com), contains the stimulants caffeine and the caffeine metabolite theobromine, so it’s not necessarily surprising if cocoa powder was a weak stimulant. It’s also a witch’s brew of chemicals such as polyphenols and flavonoids some of which have been fingered as helpful10, which all adds up to an unclear impact on health (once you control for eating a lot of sugar).

I have been taking these supplements for almost three weeks now. What I have noticed is there is a marked difference in the decrease of my daily brain fog. This was huge for me! However, I gave the product 4 stars because of my concern about the high count of vitamin B6. I think this should have been addressed in a disclaimer for concerned consumers
Since each 400mg pill takes up 2 00 pills, that’s 4 gel caps a day to reach 800mg magnesium citrate (ie. 136mg elemental magnesium), or 224 gel caps (2x120) for the first batch of Solgar magnesium pills. Turning the Solgar tablets into gel capsules was difficult enough that I switched to NOW Food’s 227g magnesium citrate powder for the second batch.
“Most people assume that because it’s a supplement, it can’t be bad for you because it’s natural,” says Louis Kraus, M.D., a psychiatrist with Rush University Medical Center in Chicago. In 2016, he chaired a committee that investigated nootropics for the American Medical Association. After reviewing the science, the committee found little to no evidence to support the efficacy or safety of nootropics.
I asked him if piracetam made him feel smarter, or just more alert and confident - a little better equipped to marshal the resources he naturally had. "Maybe," he said. "I'm not sure what being smarter means, entirely. It's a difficult quality to measure. It's the Gestalt factor, all these qualities coming together - not only your ability to crunch some numbers, or remember some figures or a sequence of numbers, but also your ability to maintain a certain emotional state that is conducive to productive intellectual work. I do feel I'm more intelligent with the drugs, but I can't give you a number of IQ points."

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.


-Raw cacao is rich in theobromine, a powerful antioxidant known to support cellular aging and reduce the risk of heart disease. Its effects are similar to those of caffeine, as they both are vasodilators and improve blood flow to the brain [except cacao won’t give you jitters]...You can use raw cacao to make cacao tea, or in your smoothies. Dark chocolate with cocoa content of 80% or higher is also rich in theobromine and natural antioxidants. Besides, chocolate makes you happy. I have a small piece of high-quality dark chocolate, like 85% or 90% dark, every day.
On the other hand, Phillips said, Provigil's effects "have attenuated over time. The body is an amazing adjusting machine, and there's no upside that I've been able to see to just taking more." A few years ago Phillips tired of poker and started playing competitive Scrabble. He was good, but not that good. He was older than many of his rivals and he needed to undertake a lot of rote memorisation, which didn't come as easily as it once had. "I stopped short of memorising the entire dictionary, and to be really good you have to get up to eight- and nine-letter words," he told me. "But I did learn every word up to five letters, plus maybe 10,000 seven- and eight-letter words." Provigil, he said, helped with the memorisation process but, "it's not going to make you smarter. It's going to make you better able to use the tools you have for a sustained period."
The ingredients in her recipes are representative of her thinking. Local raw honey. Organic everything. Free-range eggs. Organic, grass-fed whole milk (I assume she means feeding grass to the cows, not feeding it to the milk). Filtered water. Goji berries. Açai berry powder. Ginseng extract with royal jelly and bee pollen. Organic spirulina powder. Even Himalayan pink sea salt, for heaven’s sake! Good grief!!

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. 

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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 (▆▃█▁▂▂▃).
The powder totals 227g of magnesium citrate, hence there is ~0.945g per magnesium citrate pill. The nutritional information states that it contains 119 servings of 0.315g magnesium elemental = 37.485g elemental, as expected, and so likewise there is 0.156g elemental magnesium per pill. This is the same dosage as the second half of the first magnesium citrate experiment (249 gel capsules there, 240 here), where the overdose effect seemed to also happen; so to avoid the overdosage, I will take one pill every other day to halve the dose to an average of ~0.078g/78mg elemental per day (piggybacking on the morning-caffeine experiment to make compliance easier).
According to Dr. Lisa, "neuro-nutrition is how our internal work translates to the external, for instance how we perform, behave, and use our strength, as opposed to 'dieting' which has an external (aesthetic) goal." An important portion of her research and theories on this matter root from her Mediterranean upbringing. She recalls immediately noticing how drastically different was the Western's culture in regards to food upon her arrival to the U.S. Interestingly enough, a recent study published in the British Medical Journal showed just how stark the difference between these lifestyles are and concluded that the Western lifestyle usually leads to "accelerated aging and increased risk of future dementia." 
While the mechanism is largely unknown, one commonly mechanism possibility is that light of the relevant wavelengths is preferentially absorbed by the protein cytochrome c oxidase, which is a key protein in mitochondrial metabolism and production of ATP, substantially increasing output, and this extra output presumably can be useful for cellular activities like healing or higher performance.

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.
These days, nootropics are beginning to take their rightful place as a particularly powerful tool in the Neurohacker’s toolbox. After all, biochemistry is deeply foundational to neural function. Whether you are trying to fix the damage that is done to your nervous system by a stressful and toxic environment or support and enhance your neural functioning, getting the chemistry right is table-stakes. And we are starting to get good at getting it right. What’s changed?
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