People with failing memory and worried about Alzheimer’s disease are sometimes seduced by advertisements for Huperzine A, extracted from a type of moss. Some studies have shown that it increases levels of acetylcholine in the brain, a chemical that is in short supply in Alzheimer’s. But despite increasing acetylcholine, aside from a few questionable studies in China, there is no evidence that it improves memory. Unfortunately when it comes to memory pills, they are best forgotten. There is, however, hope that a nasal spray containing insulin can increase the absorption of glucose into brain cells and improve cognitive function. But in the meantime, the best bet to maintain good brain function is to monitor blood glucose and blood pressure, eat a diet rich in fruits, vegetables and whole grains, and low in simple carbs and saturated fat. And don’t forget that physical exercise also exercises your brain.
If you are a slow caffeine metabolizer and consume too much caffeine, you run the risk of mild to severe complications, such as cardiovascular disease. There’s also the sleep disruption problem of having too much caffeine left in your bloodstream late in the day as a result of a longer caffeine half-life, a problem not faced by fast caffeine metabolizers (it’s so unfair if you love your cup of joe, right?). In addition, fast caffeine metabolizers actually run a reduced risk of cardiovascular complications if they consume at least one cup of coffee per day. While anyone can be a slow caffeine metabolizer, there are certain ethnic backgrounds that are indeed associated with slower and faster caffeine metabolisms. For example, it’s known that people with Asian and African ethnic backgrounds generally have slower rates of caffeine metabolism. To find out if you’re a fast or slow caffeine metabolizer, you can have a relatively inexpensive salivary genetic test performed by a company like 23andme and then use the online dashboard to jump straight to your CYP1A2 gene. When you’re there, you type into the search bar “rs762551”. If your rs762551 SNP variant is AA, then you’re a fast caffeine metabolizer, but if your variant is AC or CC, you’re a slow caffeine metabolizer. Fortunately, many genetic testing companies will now simply report directly on your results whether you’re a slow or fast metabolizer, without you needing to go through the SNP searching trouble.
You’ve no doubt heard that we’re now entering a new golden age of psychedelics, and microdosing with LSD, psilocybin, ketamine and other compounds previously placed in the realm of party animals and rave enthusiasts is now commonplace for CEO’s, the Navy SEALs, famous authors and beyond. You no longer have to be a tree-hugging, anti-war rebel to achieve the many positive health benefits of psychedelics. My own personal experience with these compounds has spanned several years of quarterly heavy psilocybin and DMT dosages for personal self-discovery, weekly LSD microdoses for creativity and productivity, and iboga microdosing for a pre-workout boost.
I’ve spent over a million dollars hacking my own biology. The lion’s share has gone to making my brain produce as much energy as it can. I even wrote a book, Head Strong, about neurofeedback, oxygen deprivation, supplements, deeper sleep, meditation, cold exposure, and about a dozen other brain hacks, and how you can use them to make your brain stronger than you thought possible.
Some nootropics users are hopeful that the drugs could be permanently “neuroprotective”—in other words, that the compounds could slow down the neuronal aging process, and help avoid cognitive deterioration later in life. (For what it's worth, most of the users I spoke to said that didn't matter much to them. “I doubt anything I’ve tried has made me smarter in a long-term way,” Baker says. “That’s still science fiction.”)
I do recommend a few things, like modafinil or melatonin, to many adults, albeit with misgivings about any attempt to generalize like that. (It’s also often a good idea to get powders, see the appendix.) Some of those people are helped; some have told me that they tried and the suggestion did little or nothing. I view nootropics as akin to a biological lottery; one good discovery pays for all. I forge on in the hopes of further striking gold in my particular biology. Your mileage will vary. All you have to do, all you can do is to just try it. Most of my experiences were in my 20s as a right-handed 5’11 white male weighing 190-220lbs, fitness varying over time from not-so-fit to fairly fit. In rough order of personal effectiveness weighted by costs+side-effects, I rank them as follows:
Nootropics – sometimes called smart drugs – are compounds that enhance brain function. They’re becoming a popular way to give your mind an extra boost. According to one Telegraph report, up to 25% of students at leading UK universities have taken the prescription smart drug modafinil [1], and California tech startup employees are trying everything from Adderall to LSD to push their brains into a higher gear [2].
An unusual intervention is infrared/near-infrared light of particular wavelengths (LLLT), theorized to assist mitochondrial respiration and yielding a variety of therapeutic benefits. Some have suggested it may have cognitive benefits. LLLT sounds strange but it’s simple, easy, cheap, and just plausible enough it might work. I tried out LLLT treatment on a sporadic basis 2013-2014, and statistically, usage correlated strongly & statistically-significantly with increases in my daily self-ratings, and not with any sleep disturbances. Excited by that result, I did a randomized self-experiment 2014-2015 with the same procedure, only to find that the causal effect was weak or non-existent. I have stopped using LLLT as likely not worth the inconvenience.
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Still, putting unregulated brain drugs into my system feels significantly scarier than downing a latte or a Red Bull—not least because the scientific research on nootropics’ long-term effects is still so thin. One 2014 study found that Ritalin, modafinil, ampakines, and other similar stimulants could eventually reduce the “plasticity” of some of the brain’s neural networks by providing them with too much dopamine, glutamate and norepinephrine, and potentially cause long-term harm in young people whose brains were still developing. (In fact, in young people, the researchers wrote, these stimulants could actually have the opposite effect the makers intended: “Healthy individuals run the risk of pushing themselves beyond optimal levels into hyperdopaminergic and hypernoradrenergic states, thus vitiating the very behaviors they are striving to improve.”) But the researchers found no evidence that normal doses of these drugs were harmful when taken by adults.
Adaptogens are also known to participate in regulating homeostasis through helping to beneficially regulate the mechanisms of action associated with the HPA-axis (think back to the importance of proper HPA-axis function which you learned about in my last article on breathwork), including cortisol regulation and nitric oxide regulation. Through these mechanisms, they can protect against chronic inflammation, atherosclerosis, neurodegenerative cognitive impairment, metabolic disorders, cancer and other aging-related diseases. There are plenty of adaptogens with potent benefits, but the ones you learn about in this article are an excellent start to begin building or expanding your stress-adaptation toolbox.
By the way, since I’ll throw around the term a few more times in this article, I should probably clarify what an adaptogen actually is. The actual name adaptogen gives some hint as to what these fascinating compounds do: they help you to adapt, specifically by stimulating a physiological adaptive response to some mild, hormesis-like stressor. A process known as general adaptation syndrome (GAS) was first described by the 20th-century physician and organic chemist Hans Selye, who defined GAS as the body’s response to the demands placed upon it. When these demands are excessive and consistent, it can result in the common deleterious symptoms now associated with long-term exposure to chronic stress. GAS is comprised of an alarm stage (characterized by a burst of energy), a resistance stage (characterized by resistance or adaptation to the stressor), and – in the case of excessive and chronic stress – an exhaustion stage (characterized by energy depletion). Adaptogens are plant-derived compounds capable of modulating these phases of GAS by either downregulating stress reactions in the alarm phase or inhibiting the onset of the exhaustion phase, thus providing some degree of protection against damage from stress.

Took pill 1:27 PM. At 2 my hunger gets the best of me (despite my usual tea drinking and caffeine+piracetam pills) and I eat a large lunch. This makes me suspicious it was placebo - on the previous days I had noted a considerable appetite-suppressant effect. 5:25 PM: I don’t feel unusually tired, but nothing special about my productivity. 8 PM; no longer so sure. Read and excerpted a fair bit of research I had been putting off since the morning. After putting away all the laundry at 10, still feeling active, I check. It was Adderall. I can’t claim this one either way. By 9 or 10 I had begun to wonder whether it was really Adderall, but I didn’t feel confident saying it was; my feeling could be fairly described as 50%.
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.
The evidence? A 2012 study in Greece found it can boost cognitive function in adults with mild cognitive impairment (MCI), a type of disorder marked by forgetfulness and problems with language, judgement, or planning that are more severe than average “senior moments,” but are not serious enough to be diagnosed as dementia. In some people, MCI will progress into dementia.
“It is surprising and encouraging that it may be possible to predict the magnitude of a placebo effect before treatment,” says Tor Wager, a neuroscientist at the University of Colorado Boulder, who was not involved in the research. More work is needed to see how the predictive features hold up in other populations and for different pain conditions, he says.

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."


However, normally when you hear the term nootropic kicked around, people really mean a “cognitive enhancer” — something that does benefit thinking in some way (improved memory, faster speed-of-processing, increased concentration, or a combination of these, etc.), but might not meet the more rigorous definition above.  “Smart drugs” is another largely-interchangeable term.
In avoiding experimenting with more Russian Noopept pills and using instead the easily-purchased powder form of Noopept, there are two opposing considerations: Russian Noopept is reportedly the best, so we might expect anything I buy online to be weaker or impure or inferior somehow and the effect size smaller than in the pilot experiment; but by buying my own supply & using powder I can double or triple the dose to 20mg or 30mg (to compensate for the original under-dosing of 10mg) and so the effect size larger than in the pilot experiment.
Some people are concerned that when they discontinue the use of nootropics, they will experience cognitive functioning below that of their normal level; however, this is usually not the case, especially regarding nootropics in the racetam class. Discontinuing nootropics will cause a person to lose any benefits experienced on these drugs. In other words, nootropics do not appear to build up the brain in any long-lasting way; their benefits are directly tied to their use. There is no evidence that nootropics erode one’s natural level of cognitive functioning.
In my last post, I talked about the idea that there is a resource that is necessary for self-control…I want to talk a little bit about the candidate for this resource, glucose. Could willpower fail because the brain is low on sugar? Let’s look at the numbers. A well-known statistic is that the brain, while only 2% of body weight, consumes 20% of the body’s energy. That sounds like the brain consumes a lot of calories, but if we assume a 2,400 calorie/day diet - only to make the division really easy - that’s 100 calories per hour on average, 20 of which, then, are being used by the brain. Every three minutes, then, the brain - which includes memory systems, the visual system, working memory, then emotion systems, and so on - consumes one (1) calorie. One. Yes, the brain is a greedy organ, but it’s important to keep its greediness in perspective… Suppose, for instance, that a brain in a person exerting their willpower - resisting eating brownies or what have you - used twice as many calories as a person not exerting willpower. That person would need an extra one third of a calorie per minute to make up the difference compared to someone not exerting willpower. Does exerting self control burn more calories?
Our #5 pick is BriteSmart which has a long list of ingredients, which look good on the bottle, but when we actually visited each one, we were left wondering about why some of them had been included. We did like the fact that it contained Vinpocetine and Huperzine A. We felt that this was a good product, but missing some key ingredients such as a supportive vitamin blend.
But while some studies have found short-term benefits, Doraiswamy says there is no evidence that what are commonly known as smart drugs — of any type — improve thinking or productivity over the long run. “There’s a sizable demand, but the hype around efficacy far exceeds available evidence,” notes Doraiswamy, adding that, for healthy young people such as Silicon Valley go-getters, “it’s a zero-sum game. That’s because when you up one circuit in the brain, you’re probably impairing another system.”
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."
Some suggested that the lithium would turn me into a zombie, recalling the complaints of psychiatric patients. But at 5mg elemental lithium x 200 pills, I’d have to eat 20 to get up to a single clinical dose (a psychiatric dose might be 500mg of lithium carbonate, which translates to ~100mg elemental), so I’m not worried about overdosing. To test this, I took on day 1 & 2 no less than 4 pills/20mg as an attack dose; I didn’t notice any large change in emotional affect or energy levels. And it may’ve helped my motivation (though I am also trying out the tyrosine).
A randomized non-blind self-experiment of LLLT 2014-2015 yields a causal effect which is several times smaller than a correlative analysis and non-statistically-significant/very weak Bayesian evidence for a positive effect. This suggests that the earlier result had been driven primarily by reverse causation, and that my LLLT usage has little or no benefits.
Alex was eager to dispel the notion that students who took Adderall were "academic automatons who are using it in order to be first in their class". In fact, he said, "it's often people" - mainly guys - "who are looking in some way to compensate for activities that are detrimental to their performance". He explained, "At Harvard, at the most basic level, they aim to do better than they would have otherwise. Everyone is aware that if you were up at 3am writing this paper it isn't going to be as good as it could have been. The fact that you were partying all weekend, or spent the last week being high, watching Lost - that's going to take a toll."
Although research linking diet and dementia is still in its infancy, there are a few important relationships between nutrients and brain health that are worth exploring. Having a nourishing, well rounded diet gives our brain the best chance of avoiding disease. If your diet is unbalanced for whatever reason, you may want to consider a multivitamin and mineral complex and an omega-3 fatty acid supplement to help make up a few of the essentials. If you are considering taking a supplement it is best to discuss this with your GP or qualified healthcare professional.
My impression after the first two days (2 doses of 400mg each, one with breakfast & then lunch) was positive. I did not have the rumored digestion problems, and the first day went excellently: I was up until 1:30AM working and even then didn’t feel like going to bed - and I probably should have since I then slept abominably, which made the second day merely a good day. The third day I took none and it was an ordinary day. This is consistent with what I expected from the LEF l-threonate & TruBrain glycinate/lycinate, and so it is worth investigating with a self-experiment.

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".
As professionals and aging baby boomers alike become more interested in enhancing their own brain power (either to achieve more in a workday or to stave off cognitive decline), a huge market has sprung up for nonprescription nootropic supplements. These products don’t convince Sahakian: “As a clinician scientist, I am interested in evidence-based cognitive enhancement,” she says. “Many companies produce supplements, but few, if any, have double-blind, placebo-controlled studies to show that these supplements are cognitive enhancers.” Plus, supplements aren’t regulated by the U.S. Food and Drug Administration (FDA), so consumers don’t have that assurance as to exactly what they are getting. Check out these 15 memory exercises proven to keep your brain sharp.
This research is in contrast to the other substances I like, such as piracetam or fish oil. I knew about withdrawal of course, but it was not so bad when I was drinking only tea. And the side-effects like jitteriness are worse on caffeine without tea; I chalk this up to the lack of theanine. (My later experiences with theanine seems to confirm this.) These negative effects mean that caffeine doesn’t satisfy the strictest definition of nootropic (having no negative effects), but is merely a cognitive enhancer (with both benefits & costs). One might wonder why I use caffeine anyway if I am so concerned with mental ability.
Spinach is rich in the antioxidant lutein, which is thought to help protect against cognitive decline, according to researchers from Tufts University. And a longitudinal study at Harvard Medical School found that women who reported eating the most leafy green and cruciferous vegetables had a markedly lower rate of cognitive decline, compared to those who ate the least.
We can read off the results from the table or graph: the nicotine days average 1.1% higher, for an effect size of 0.24; however, the 95% credible interval (equivalent of confidence interval) goes all the way from 0.93 to -0.44, so we cannot exclude 0 effect and certainly not claim confidence the effect size must be >0.1. Specifically, the analysis gives a 66% chance that the effect size is >0.1. (One might wonder if any increase is due purely to a training effect - getting better at DNB. Probably not26.)
We all wish success came in a pill form. That was the premise of the hour and half Adderall commercial/ thriller film ‘Limitless’ starring Bradley Cooper. In the film he popped a transparent round pill and instantly his brain power skyrocketed- anything became possible. Most of us wished that pill existed- and now it does. Donepezil is a drug that is used to treat Alzheimers, but it’s effects on normal people make Adderall and Vyvanse look like a cup of coffee.
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.
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.
Or in other words, since the standard deviation of my previous self-ratings is 0.75 (see the Weather and my productivity data), a mean rating increase of >0.39 on the self-rating. This is, unfortunately, implying an extreme shift in my self-assessments (for example, 3s are ~50% of the self-ratings and 4s ~25%; to cause an increase of 0.25 while leaving 2s alone in a sample of 23 days, one would have to push 3s down to ~25% and 4s up to ~47%). So in advance, we can see that the weak plausible effects for Noopept are not going to be detected here at our usual statistical levels with just the sample I have (a more plausible experiment might use 178 pairs over a year, detecting down to d>=0.18). But if the sign is right, it might make Noopept worthwhile to investigate further. And the hardest part of this was just making the pills, so it’s not a waste of effort.

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.
Results: Women with high caffeine intakes had significantly higher rates of bone loss at the spine than did those with low intakes (−1.90 ± 0.97% compared with 1.19 ± 1.08%; P = 0.038). When the data were analyzed according to VDR genotype and caffeine intake, women with the tt genotype had significantly (P = 0.054) higher rates of bone loss at the spine (−8.14 ± 2.62%) than did women with the TT genotype (−0.34 ± 1.42%) when their caffeine intake was >300 mg/d…In 1994, Morrison et al (22) first reported an association between vitamin D receptor gene (VDR) polymorphism and BMD of the spine and hip in adults. After this initial report, the relation between VDR polymorphism and BMD, bone turnover, and bone loss has been extensively evaluated. The results of some studies support an association between VDR polymorphism and BMD (23-,25), whereas other studies showed no evidence for this association (26,27)…At baseline, no significant differences existed in serum parathyroid hormone, serum 25-hydroxyvitamin D, serum osteocalcin, and urinary N-telopeptide between the low- and high-caffeine groups (Table 1⇑). In the longitudinal study, the percentage of change in serum parathyroid hormone concentrations was significantly lower in the high-caffeine group than in the low-caffeine group (Table 2⇑). However, no significant differences existed in the percentage of change in serum 25-hydroxyvitamin D
I started with the 10g of Vitality Enhanced Blend, a sort of tan dust. Used 2 little-spoonfuls (dust tastes a fair bit like green/oolong tea dust) into the tea mug and then some boiling water. A minute of steeping and… bleh. Tastes sort of musty and sour. (I see why people recommended sweetening it with honey.) The effects? While I might’ve been more motivated - I hadn’t had caffeine that day and was a tad under the weather, a feeling which seemed to go away perhaps half an hour after starting - I can’t say I experienced any nausea or very noticeable effects. (At least the flavor is no longer quite so offensive.)

At this point, I discovered I had run out of magnesium pills and had forgotten to order the magnesium citrate powder I’d intended to. I still had a lot of Noopept pills for the concurrently running second Noopept self-experiment, but since I wanted to wrap up some other experiments with a big analysis at the end of the year, I decided to halt and resume in January 2014.


Took pill 1:27 PM. At 2 my hunger gets the best of me (despite my usual tea drinking and caffeine+piracetam pills) and I eat a large lunch. This makes me suspicious it was placebo - on the previous days I had noted a considerable appetite-suppressant effect. 5:25 PM: I don’t feel unusually tired, but nothing special about my productivity. 8 PM; no longer so sure. Read and excerpted a fair bit of research I had been putting off since the morning. After putting away all the laundry at 10, still feeling active, I check. It was Adderall. I can’t claim this one either way. By 9 or 10 I had begun to wonder whether it was really Adderall, but I didn’t feel confident saying it was; my feeling could be fairly described as 50%.
Jump up ^ Weyandt LL, Oster DR, Marraccini ME, Gudmundsdottir BG, Munro BA, Zavras BM, Kuhar B (September 2014). "Pharmacological interventions for adolescents and adults with ADHD: stimulant and nonstimulant medications and misuse of prescription stimulants". Psychol. Res. Behav. Manag. 7: 223–249. doi:10.2147/PRBM.S47013. PMC 4164338. PMID 25228824.
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