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!
Nootropics can also show signs of neuro-preservation and neuro-protection. These compounds directly affect the levels of brain chemicals associated with slowing down the aging process. Some nootropics could in an increase in the production of Nerve Growth Factor and Brain-Derived Neurotrophic Factor to stimulate the growth of neurons and neurites while slowing down the rate of damage as well.
Research does not support that drugs like Ritalin help students do well in school. Studies show that prescription stimulants do not help to improve learning or thinking in those who do not actually have ADHD. Further, research reveals that students who abuse prescription stimulants have lower GPAs than students who do not abuse the drugs.[14] Although Ritalin improves concentration, this effect is largely misunderstood among non-prescribed users. These illicit users mistakenly believe that they can use a drug out of its prescribed context, thinking they can reap the benefits intended for legitimate users.

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.
…Four subjects correctly stated when they received nicotine, five subjects were unsure, and the remaining two stated incorrectly which treatment they received on each occasion of testing. These numbers are sufficiently close to chance expectation that even the four subjects whose statements corresponded to the treatments received may have been guessing.
In fact, many nerve gas agents act similarly to Huperzia serrata by blocking the enzyme that breaks down acetylcholine. But research has shown that in smaller doses, Huperzine A, the extract of Huperzia serrata used in nootropics, would likely offer some protection against damage from nerve agents. That the same substance can act as a nerve agent, protect against nerve agents, and give you crazy dreams, underscores how important it is to stay within the recommended doses.
The nootropics I’m taking are called RISE, and they're made by a company called Nootrobox, which was started by Geoffrey Woo, a young Stanford computer science graduate. There's no one common ingredient in nootropics; what unites them is the intent to improve brain performance. The RISE stack, which costs $29 plus shipping for 30 pills, contains 350 mg of bacopa monnieri powder (an herb that is commonly used medicinally in South Asia), 100 mg of L-theanine (an amino acid found in green tea), and 50 mg of caffeine (about the amount in a can of Diet Coke). Like most nootropics, the RISE stack itself isn't FDA-approved for use as a cognitive enhancer, but Nootrobox says that the compounds within it are approved as dietary supplements. "We use the precise ingredients at the right dosages and the right ratios as supported by double-blind, peer-reviewed clinicals," Nootrobox's site claims.
Potassium citrate powder is neither expensive nor cheap: I purchased 453g for $21. The powder is crystalline white, dissolves instantly in water, and largely tasteless (sort of saline & slightly unpleasant). The powder is 37% potassium by weight (the formula is C6H5K3O7) so 453g is actually 167g of potassium, so 80-160 days’ worth depending on dose.

Choline works best when stacked with nootropics. Stacking choline with a nootropic can also help prevent or reduce side effects. Often, people find that they get headaches when they take nootropics by themselves and that stacking them with choline helps reduce this problem. It is usually suggested to stack nootropics with a choline source, especially if you do not get enough from your diet.
Last spring, 100 people showed up at a Peak Performance event where psychedelic psychologist James Fadiman said the key to unleashing the cognition-enhancing effects of LSD — which he listed as less anxiety, better focus, improved sleep, greater creativity — was all in the dosage. He recommended a tenth of a “party dose” — enough to give you “the glow” and enhance your cognitive powers without “the trip.”
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)
I have no particularly compelling story for why this might be a correlation and not causation. It could be placebo, but I wasn’t expecting that. It could be selection effect (days on which I bothered to use the annoying LED set are better days) but then I’d expect the off-days to be below-average and compared to the 2 years of trendline before, there doesn’t seem like much of a fall.
The desire to improve cognitive functioning has probably existed since the dawn of human consciousness. Throughout our evolution, increased mental agility has been associated with fitness and improved odds of survival and success. Although concoctions to stimulate brainpower have existed in Chinese and Indian medicine for hundreds of years, Western nootropics were not developed until 1964.
As with any thesis, there are exceptions to this general practice. For example, theanine for dogs is sold under the brand Anxitane is sold at almost a dollar a pill, and apparently a month’s supply costs $50+ vs $13 for human-branded theanine; on the other hand, this thesis predicts downgrading if the market priced pet versions higher than human versions, and that Reddit poster appears to be doing just that with her dog.↩
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Caffeine + L-Theanine: Since caffeine can produce unwanted side effects in high amounts (such as jitteriness and headaches), most people, and especially “slow caffeine oxidizers” find that by adding L-Theanine to a caffeine source such as coffee, any negative side effects of caffeine can be controlled. Caffeine and L-Theanine in combination have been researched and proven to boost concentration, attention, and energy while reducing anxiety. For this stack, use a ratio of four parts L-Theanine to one part caffeine, such as 400 milligrams of L-Theanine along with 100 milligrams of caffeine. You may want to start out with a smaller dose such as 200 milligrams of L-Theanine and 50 milligrams of caffeine and work your way up to find the best dose for you (the average cup of coffee has about 100mg of caffeine).
Vitamin C has long been thought to have the power to increase mental agility, and some research suggests that a deficiency may be a risk factor for age-related brain degeneration including dementia and Alzheimer's.  Furthermore, interesting studies demonstrate that vitamin C may be useful in managing anxiety and stress. One of the best sources of this vital vitamin are blackcurrants. Others include red peppers, citrus fruits such as oranges and broccoli.
A Romanian psychologist and chemist named Corneliu Giurgea started using the word nootropic in the 1970s to refer to substances that improve brain function, but humans have always gravitated toward foods and chemicals that make us feel sharper, quicker, happier, and more content. Our brains use about 20 percent of our energy when our bodies are at rest (compared with 8 percent for apes), according to National Geographic, so our thinking ability is directly affected by the calories we’re taking in as well as by the nutrients in the foods we eat. Here are the nootropics we don’t even realize we’re using, and an expert take on how they work.
Back home, I contacted Aubrey Marcus, whose company Onnit Labs produces Alpha Brain. He attributed my lucid dreaming to increased levels of the neurotransmitter acetylcholine, which enhances REM dreaming. Alpha Brain has two ingredients that boost acetylcholine levels: GPC choline, which the body converts to acetylcholine, and Huperzine A, an alkaloid derived from Chinese club moss, also known as Huperzia serrata. "Huperzine A disarms the enzyme that naturally breaks down acetylcholine," Marcus said. "So while the GPC choline is being converted to acetylcholine, the Huperzine A is keeping it from disappearing. It's like plugging the drain and turning on the faucet."
Finding a usable product on Amazon caused me some difficulties. I wanted a 500mg magnesium-citrate-only product at <$20 for 120 doses, but I discovered most of the selection for magnesium citrate had sub-500mg doses, involved calcium citrate or other substances like zinc (not necessarily a bad thing, but would confound an experiment), were mostly magnesium oxide rather than citrate, or some still other problem. Ultimately I settled on Solgar’s $13 120x400mg magnesium citrate as acceptable. (To compare with the bulkiness of the LEF vitamin D+l-threonate powder, the Office of Dietary Supplements says magnesium citrate is 16% magnesium, so to get 400mg of magnesium as claimed, would take 2.5g of material, rather than 7g for 200mg; even if l-threonate is absorbed 100% and citrate 50%, the citrate is ahead. The pills turn out to be wider and longer than my 00 pills; if I want to get them into my gel capsules, I have to crush them into fine powder. The powder from one pill turns out to take up 2 00 pills.)

Woo understands that when selling brain drugs, skepticism comes with the territory. "The typical first reaction is, this is bullshit, you guys are snake-oil salesmen," he says. "We're not medical doctors nor biochemistry experts, but we are experts in building teams and building products. Like how Elon Musk attacks rockets and electric cars from 'first principles,' we see ourselves as applying Silicon Valley aesthetics and operational know-how to the murky world of nootropics."

I have elsewhere remarked on the apparent lack of benefit to taking multivitamins and the possible harm; so one might well wonder about a specific vitamin like vitamin D. However, a multivitamin is not vitamin D, so it’s no surprise that they might do different things. If a multivitamin had no vitamin D in it, or if it had vitamin D in different doses, or if it had substances which interacted with vitamin D (such as calcium), or if it had substances which had negative effects which outweigh the positive (such as vitamin A?), we could well expect differing results. In this case, all of those are true to varying extents. Some multivitamins I’ve had contained no vitamin D. The last multivitamin I was taking both contains vitamins used in the negative trials and also some calcium; the listed vitamin D dosage was a trivial ~400IU, while I take >10x as much now (5000IU).
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:
As far as anxiety goes, psychiatrist Emily Deans has an overview of why the Kiecolt-Glaser et al 2011 study is nice; she also discusses why fish oil seems like a good idea from an evolutionary perspective. There was also a weaker earlier 2005 study also using healthy young people, which showed reduced anger/anxiety/depression plus slightly faster reactions. The anti-stress/anxiolytic may be related to the possible cardiovascular benefits (Carter et al 2013).
The biohacking movement is trying to overcome its “N=1” problem (in which a sample size includes only the person doing the experimenting) by sharing experiences online or via meetups. But a biohacking group, like any community organized around a common interest, can easily become an echo chamber. James Alcock, Ph.D., a professor of social psychology at York University in Canada and the author of the book Belief: What It Means to Believe and Why Our Convictions Are So Compelling, says biohackers may be unwittingly painting one another an unreasonably rosy picture of how well nootropics work—even when they don’t.
What worries me about amphetamine is its addictive potential, and the fact that it can cause stress and anxiety. Research says it’s only slightly likely to cause addiction in people with ADHD, [7] but we don’t know much about its addictive potential in healthy adults. We all know the addictive potential of methamphetamine, and amphetamine is closely related enough to make me nervous about so many people giving it to their children. Amphetamines cause withdrawal symptoms, so the potential for addiction is there.
Related to the famous -racetams but reportedly better (and much less bulky), Noopept is one of the many obscure Russian nootropics. (Further reading: Google Scholar, Examine.com, Reddit, Longecity, Bluelight.ru.) Its advantages seem to be that it’s far more compact than piracetam and doesn’t taste awful so it’s easier to store and consume; doesn’t have the cloud hanging over it that piracetam does due to the FDA letters, so it’s easy to purchase through normal channels; is cheap on a per-dose basis; and it has fans claiming it is better than piracetam.
2ml is supposed to translate to 24mg, which is a big dose. I do not believe any of the commercial patches go much past that. I asked Wedrifid, whose notes inspired my initial interest, and he was taking perhaps 2-4mg, and expressed astonishment that I might be taking 24mg. (2mg is in line with what I am told by another person - that 2mg was so much that they actually felt a little sick. On the other hand, in one study, the subjects could not reliably distinguish between 1mg and placebo25.) 24mg is particularly troubling in that I weigh ~68kg, and nicotine poisoning and the nicotine LD50 start, for me, at around 68mg of nicotine. (I reflected that the entire jar could be a useful murder weapon, although nicotine presumably would be caught in an autopsy’s toxicology screen; I later learned nicotine was an infamous weapon in the 1800s before any test was developed. It doesn’t seem used anymore, but there are still fatal accidents due to dissolved nicotine.) The upper end of the range, 10mg/kg or 680mg for me, is calculated based on experienced smokers. Something is wrong here - I can’t see why I would have nicotine tolerance comparable to a hardened smoker, inasmuch as my maximum prior exposure was second-hand smoke once in a blue moon. More likely is that either the syringe is misleading me or the seller NicVape sold me something more dilute than 12mg/ml. (I am sure that it’s not simply plain water; when I mix the drops with regular water, I can feel the propylene glycol burning as it goes down.) I would rather not accuse an established and apparently well-liked supplier of fraud, nor would I like to simply shrug and say I have a mysterious tolerance and must experiment with doses closer to the LD50, so the most likely problem is a problem with the syringe. The next day I altered the procedure to sucking up 8ml, squirting out enough fluid to move the meniscus down to 7ml, and then ejecting the rest back into the container. The result was another mild clean stimulation comparable to the previous 1ml days. The next step is to try a completely different measuring device, which doesn’t change either.
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.)
All clear? Try one (not dozens) of nootropics for a few weeks and keep track of how you feel, Kerl suggests. It’s also important to begin with as low a dose as possible; when Cyr didn’t ease into his nootropic regimen, his digestion took the blow, he admits. If you don’t notice improvements, consider nixing the product altogether and focusing on what is known to boost cognitive function – eating a healthy diet, getting enough sleep regularly and exercising. "Some of those lifestyle modifications," Kerl says, "may improve memory over a supplement."

When it comes to brain power, greens should be on your plate (and cover a lot of that plate) every meal. “Leafy greens are a great base. You swap out a lot of the empty carbohydrates you get from things like pastas or breads, and you can use some leafy greens,” says Psychiatrist Drew Ramsey, MD, author of The Happiness Diet and Eat Complete: The 21 Nutrients That Fuel Brainpower, Boost Weight Loss, and Transform Your Health. “Again, just lots of nutrient density.”

Took full pill at 10:21 PM when I started feeling a bit tired. Around 11:30, I noticed my head feeling fuzzy but my reading seemed to still be up to snuff. I would eventually finish the science book around 9 AM the next day, taking some very long breaks to walk the dog, write some poems, write a program, do Mnemosyne review (memory performance: subjectively below average, but not as bad as I would have expected from staying up all night), and some other things. Around 4 AM, I reflected that I felt much as I had during my nightwatch job at the same hour of the day - except I had switched sleep schedules for the job. The tiredness continued to build and my willpower weakened so the morning wasn’t as productive as it could have been - but my actual performance when I could be bothered was still pretty normal. That struck me as kind of interesting that I can feel very tired and not act tired, in line with the anecdotes.
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I tried taking whole pills at 1 and 3 AM. I felt kind of bushed at 9 AM after all the reading, and the 50 minute nap didn’t help much - I was sleep only around 10 minutes and spent most of it thinking or meditation. Just as well the 3D driver is still broken; I doubt the scores would be reasonable. Began to perk up again past 10 AM, then felt more bushed at 1 PM, and so on throughout the day; kind of gave up and began watching & finishing anime (Amagami and Voices of a Distant Star) for the rest of the day with occasional reading breaks (eg. to start James C. Scotts Seeing Like A State, which is as described so far). As expected from the low quality of the day, the recovery sleep was bigger than before: a full 10 hours rather than 9:40; the next day, I slept a normal 8:50, and the following day ~8:20 (woken up early); 10:20 (slept in); 8:44; 8:18 (▁▇▁▁). It will be interesting to see whether my excess sleep remains in the hour range for ’good modafinil nights and two hours for bad modafinil nights.
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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