I’ve been actively benefitting from nootropics since 1997, when I was struggling with cognitive performance and ordered almost $1000 worth of smart drugs from Europe (the only place where you could get them at the time). I remember opening the unmarked brown package and wondering whether the pharmaceuticals and natural substances would really enhance my brain.

Barbara Sahakian, a neuroscientist at Cambridge University, doesn’t dismiss the possibility of nootropics to enhance cognitive function in healthy people. She would like to see society think about what might be considered acceptable use and where it draws the line – for example, young people whose brains are still developing. But she also points out a big problem: long-term safety studies in healthy people have never been done. Most efficacy studies have only been short-term. “Proving safety and efficacy is needed,” she says.
It all comes down to my personal investigation and exploration into how one can use a variety of compounds to enhance the mind, all while combining ancestral wisdom and herbs such as bacopa and gingko with modern science and tactics such as LSD and racetams. The fact is, I’ve taken a deep dive in the wonderful world of smart drugs, nootropics and psychedelics, and have had the opportunity to interview some of the brightest minds in this unique field of brain enhancement on my podcast. So in this article, I’ll spill the beans on it all, including how to navigate the oft-confusing world of smart drugs and nootropics, the best brain supplement stacks I’ve discovered and experimented with, how to procure and microdose psychedelics and much more.
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.”
As a result of her years of research in this area, Dr. Lisa proposes a variety of foods that lead to better cognitive functioning and those which, in contrast, minimize cognitive functioning. "The best four foods one can consume to boost brain power are fish, dark leafy green veggies, berries, and water," she explains. And the worst? "Fast food, processed foods and poor quality meat." 
Similarly, we could try applying Nick Bostrom’s reversal test and ask ourselves, how would we react to a virus which had no effect but to eliminate sleep from alternating nights and double sleep in the intervening nights? We would probably grouch about it for a while and then adapt to our new hedonistic lifestyle of partying or working hard. On the other hand, imagine the virus had the effect of eliminating normal sleep but instead, every 2 minutes, a person would fall asleep for a minute. This would be disastrous! Besides the most immediate problems like safely driving vehicles, how would anything get done? You would hold a meeting and at any point, a third of the participants would be asleep. If the virus made it instead 2 hours on, one hour off, that would be better but still problematic: there would be constant interruptions. And so on, until we reach our present state of 16 hours on, 8 hours off. Given that we rejected all the earlier buffer sizes, one wonders if 16:8 can be defended as uniquely suited to circumstances. Is that optimal? It may be, given the synchronization with the night-day cycle, but I wonder; rush hour alone stands as an argument against synchronized sleep - wouldn’t our infrastructure would be much cheaper if it only had to handle the average daily load rather than cope with the projected peak loads? Might not a longer cycle be better? The longer the day, the less we are interrupted by sleep; it’s a hoary cliche about programmers that they prefer to work in long sustained marathons during long nights rather than sprint occasionally during a distraction-filled day, to the point where some famously adopt a 28 hour day (which evenly divides a week into 6 days). Are there other occupations which would benefit from a 20 hour waking period? Or 24 hour waking period? We might not know because without chemical assistance, circadian rhythms would overpower anyone attempting such schedules. It certainly would be nice if one had long time chunks in which could read a challenging book in one sitting, without heroic arrangements.↩

The Blood Brain Barrier (BBB) is similar in structure to the intestinal barrier (6) and is usually highly selective, allowing certain required metabolic products such as short chain fatty acids and amino acids to pass into the brain from our wider circulation but protecting the brain from potentially damaging components. When the BBB is compromised, unwanted translocation may occur such as allowing a bacterial invasion, which can alter the function of immune cells that are responsible for regulating inflammation. Chronic inflammation is associated with many mental and physical health problems, so it is therefore suggested that poor gut health can have a direct correlation to poor mental wellbeing, as a result of a compromised intestinal barrier and the negative impact this has on our brain’s own structural barrier (BBB) and resulting inflammation.

Such competitive anxieties are already being felt in the workplace. Recently an advice column in Wired featured a question from a reader worried about "a rising star at the firm" who was "using unprescribed modafinil to work crazy hours. Our boss has started getting on my case for not being as productive." And on internet forums such as ImmInst (Immortality Institute), whose members share a nerdy passion for tweaking their cognitive function through drugs and supplements, people trade advice about dosages and "stacks" - improvised combinations - of neuroenhancers ("Cut a tablet into fourths and took 25mg every four hours, four times today, and had a great and productive day - with no side-effects"). In one recent post a 52-year-old - who was working full time, studying for an advanced degree at night and "married, etc" - wrote that after experimenting with modafinil he had settled on two daily doses of 100mg each. He believed that he was "performing a little better", adding: "I also feel slightly more animated when in discussion."
For starters, it’s one of the highest antioxidant-rich foods known to man, including vitamin C and vitamin K and fiber. Because of their high levels of gallic acid, blueberries are especially good at protecting our brains from degeneration and stress. Get your daily dose of brain berries in an Omega Blueberry Smoothie, Pumpkin Blueberry Pancakes or in a Healthy Blueberry Cobbler.

This is absolutely fantastic work - Dr. Mosconi's clear, concise prose readily breaks down the science of how we can protect our beloved brains from the horrors of dementia and keep our minds humming beautifully for years. Her mastery of the various key subjects - neurobiology, nutrition, biochemistry - is incredible and her ability to decode complex scientific findings into digestible, easy-to-use advice for the layperson is second to none. This is easily one of the best popular science books I've ever come across and by far the best read on nutrition I know of.


(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.)
It’s not easy to make it in the modern world, which asks you to be focused and sharp all the time. You have to be creative and learn the new skills all the time. That’s a heavy burden for your brain cells. One day, sooner or later, you have to accept the fact that your brain power and effectiveness are no longer as impressive and reliable as once they were. Brain Pill can help. You don’t have to force yourself to accept your new reality of limited focus and weak ability to learn new things. Brain Pill can refresh your mental clarity and improve your problem-solving and decision-making skills.
One should note the serious caveats here: it is a small in vitro study of a single category of human cells with an effect size that is not clear on a protein which feeds into who-knows-what pathways. It is not a result in a whole organism on any clinically meaningful endpoint, even if we take it at face-value (many results never replicate). A look at followup work citing Rapuri et al 2007 is not encouraging: Google Scholar lists no human studies of any kind, much less high-quality studies like RCTs; just some rat followups on the calcium effect. This is not to say Rapuri et al 2007 is a bad study, just that it doesn’t bear the weight people are putting on it: if you enjoy caffeine, this is close to zero evidence that you should reduce or drop caffeine consumption; if you’re taking too much caffeine, you already have plenty of reasons to reduce; if you’re drinking lots of coffee, you already have plenty of reasons to switch to tea; etc.

Since the discovery of the effect of nootropics on memory and focus, the number of products on the market has increased exponentially. The ingredients used in a supplement can tell you about the effectiveness of the product. Brain enhancement pills that produce the greatest benefit are formulated with natural vitamins and substances, rather than caffeine and synthetic ingredients. In addition to better results, natural supplements are less likely to produce side effects, compared with drugs formulated with chemical ingredients.
Take quarter at midnight, another quarter at 2 AM. Night runs reasonably well once I remember to eat a lot of food (I finish a big editing task I had put off for weeks), but the apathy kicks in early around 4 AM so I gave up and watched Scott Pilgrim vs. the World, finishing around 6 AM. I then read until it’s time to go to a big shotgun club function, which occupies the rest of the morning and afternoon; I had nothing to do much of the time and napped very poorly on occasion. By the time we got back at 4 PM, the apathy was completely gone and I started some modafinil research with gusto (interrupted by going to see Puss in Boots). That night: Zeo recorded 8:30 of sleep, gap of about 1:50 in the recording, figure 10:10 total sleep; following night, 8:33; third night, 8:47; fourth, 8:20 (▇▁▁▁).
Noopept is a Russian stimulant sometimes suggested for nootropics use as it may be more effective than piracetam or other -racetams, and its smaller doses make it more convenient & possibly safer. Following up on a pilot study, I ran a well-powered blind randomized self-experiment between September 2013 and August 2014 using doses of 12-60mg Noopept & pairs of 3-day blocks to investigate the impact of Noopept on self-ratings of daily functioning in addition to my existing supplementation regimen involving small-to-moderate doses of piracetam. A linear regression, which included other concurrent experiments as covariates & used multiple imputation for missing data, indicates a small benefit to the lower dose levels and harm from the highest 60mg dose level, but no dose nor Noopept as a whole was statistically-significant. It seems Noopept’s effects are too subtle to easily notice if they exist, but if one uses it, one should probably avoid 60mg+.
Some nootropics are more commonly used than others. These include nutrients like Alpha GPC, huperzine A, L-Theanine, bacopa monnieri, and vinpocetine. Other types of nootropics are still gaining traction. With all that in mind, to claim there is a “best” nootropic for everyone would be the wrong approach since every person is unique and looking for different benefits.
We did note a significant warning with this product, namely that the caffeine it contains may cause a negative impact, mainly that some users may experience the jitters. Their dosage suggests that one can take up to 6 pills a day, which we felt was too many. These issues made us a little wary of the product, even though they seem to know the right ingredients to include.
I took the pill at 11 PM the evening of (technically, the day before); that day was a little low on sleep than usual, since I had woken up an hour or half-hour early. I didn’t yawn at all during the movie (merely mediocre to my eyes with some questionable parts)23. It worked much the same as it did the previous time - as I walked around at 5 AM or so, I felt perfectly alert. I made good use of the hours and wrote up my memories of ICON 2011.

Brain enhancing drug – the steroids of the mental world, these are compounds that can be both artificial or natural that are not recommended for casual consumption. If taken over a long period of time, they can and will result in permanent and debilitating damage, and if taken wrongly, they can and will result in injury, illness, and death. So far from being the best brain pill that they loop around and punch the actual best brain pill in the face.

In this large population-based cohort, we saw consistent robust associations between cola consumption and low BMD in women. The consistency of pattern across cola types and after adjustment for potential confounding variables, including calcium intake, supports the likelihood that this is not due to displacement of milk or other healthy beverages in the diet. The major differences between cola and other carbonated beverages are caffeine, phosphoric acid, and cola extract. Although caffeine likely contributes to lower BMD, the result also observed for decaffeinated cola, the lack of difference in total caffeine intake across cola intake groups, and the lack of attenuation after adjustment for caffeine content suggest that caffeine does not explain these results. A deleterious effect of phosphoric acid has been proposed (26). Cola beverages contain phosphoric acid, whereas other carbonated soft drinks (with some exceptions) do not.

Maca root has been used by indigenous people groups in South America for thousands of years. It’s part of the mustard family found primarily in Andean regions and some of its primary uses include improving sexual function, memory and learning as well as reducing the effects of osteoporosis. The standard effective dose ranges from 1,500 to 3,000 mg.
Large scale studies have shown the association between chronic low-grade inflammation and depression (8). For example, in a study that examined data from 14,275 people who were interviewed between 2007 and 2012, they found that people who had depression had 46% higher levels of C-reactive protein (CRP), a marker of inflammatory disease, in their blood samples (9). Studies like these are paving the way towards a new understanding of the pathology of mental health conditions and how diet and stress can alter bodily systems, such as digestive function and consequently impact mental wellbeing. Measuring IgG antibodies in food intolerance tests has been implicated as a popular strategy to tackle symptoms related to sensitivities such as IBS, joint pain, fatigue, migraines, anxiety and depression. A recent survey on 708 people commissioned by Allergy UK, demonstrated how 81% of those with elevated IgG levels, as well as psychological symptoms, reported an improvement in their condition after following a food-specific IgG elimination diet (9). Taking this all into account, health professionals and those with poor mental health may want to consider the potential role of food intolerances in mental well-being and in managing common mood-related disorders, such as depression and anxiety.
One item always of interest to me is sleep; a stimulant is no good if it damages my sleep (unless that’s what it is supposed to do, like modafinil) - anecdotes and research suggest that it does. Over the past few days, my Zeo sleep scores continued to look normal. But that was while not taking nicotine much later than 5 PM. In lieu of a different ml measurer to test my theory that my syringe is misleading me, I decide to more directly test nicotine’s effect on sleep by taking 2ml at 10:30 PM, and go to bed at 12:20; I get a decent ZQ of 94 and I fall asleep in 16 minutes, a bit below my weekly average of 19 minutes. The next day, I take 1ml directly before going to sleep at 12:20; the ZQ is 95 and time to sleep is 14 minutes.

Pop this pill and improve your memory. Swallow that one and reduce your cognitive decline. We see ads for such products all the time and I suspect they will increase as the baby boomers reach senior citizenhood. The most popular brain boosting supplements are fish oil pills and they are also probably the best studied ones. The results are not encouraging.

The experiment then is straightforward: cut up a fresh piece of gum, randomly select from it and an equivalent dry piece of gum, and do 5 rounds of dual n-back to test attention/energy & WM. (If it turns out to be placebo, I’ll immediately use the remaining active dose: no sense in wasting gum, and this will test whether nigh-daily use renders nicotine gum useless, similar to how caffeine may be useless if taken daily. If there’s 3 pieces of active gum left, then I wrap it very tightly in Saran wrap which is sticky and air-tight.) The dose will be 1mg or 1/4 a gum. I cut up a dozen pieces into 4 pieces for 48 doses and set them out to dry. Per the previous power analyses, 48 groups of DNB rounds likely will be enough for detecting small-medium effects (partly since we will be only looking at one metric - average % right per 5 rounds - with no need for multiple correction). Analysis will be one-tailed, since we’re looking for whether there is a clear performance improvement and hence a reason to keep using nicotine gum (rather than whether nicotine gum might be harmful).


Even party drugs are going to work: Biohackers are taking recreational drugs like LSD, psilocybin mushrooms, and mescaline in microdoses—about a tenth of what constitutes a typical dose—with the goal of becoming more focused and creative. Many who’ve tried it report positive results, but real research on the practice—and its safety—is a long way off. “Whether microdosing with LSD improves creativity and cognition remains to be determined in an objective experiment using double-blind, placebo-controlled methodology,” Sahakian says.

Using the 21mg patches, I cut them into quarters. What I would do is I would cut out 1 quarter, and then seal the two edges with scotch tape, and put the Pac-Man back into its sleeve. Then the next time I would cut another quarter, seal the new edge, and so on. I thought that 5.25mg might be too much since I initially found 4mg gum to be too much, but it’s delivered over a long time and it wound up feeling much more like 1mg gum used regularly. I don’t know if the tape worked, but I did not notice any loss of potency. I didn’t like them as much as the gum because I would sometimes forget to take off a patch at the end of the day and it would interfere with sleep, and because the onset is much slower and I find I need stimulants more for getting started than for ongoing stimulation so it is better to have gum which can be taken precisely when needed and start acting quickly. (One case where the patches were definitely better than the gum was long car trips where slow onset is fine, since you’re most alert at the start.) When I finally ran out of patches in June 2016 (using them sparingly), I ordered gum instead.


Most people I talk to about modafinil seem to use it for daytime usage; for me that has not ever worked out well, but I had nothing in particular to show against it. So, as I was capping the last of my piracetam-caffeine mix and clearing off my desk, I put the 4 remaining Modalerts pills into capsules with the last of my creatine powder and then mixed them with 4 of the theanine-creatine pills. Like the previous Adderall trial, I will pick one pill blindly each day and guess at the end which it was. If it was active (modafinil-creatine), take a break the next day; if placebo (theanine-creatine), replace the placebo and try again the next day. We’ll see if I notice anything on DNB or possibly gwern.net edits.
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).
Because it’s so nutrient-dense — packing loads of vitamins, minerals and nutrients with very little calories — it’s a great snack option if you’re looking to shed pounds. And while we often eat celery stalks, don’t skip the seeds and leaves; both provide extra health benefits and taste great in things like stir fries and soups. Not sure where to begin with eating more celery? Try my easy Ants on a Log or refreshing Super Hydrator Juice recipes.

The nootropics community is surprisingly large and involved. When I wade into forums and the nootropics subreddit, I find members trading stack recipes and notifying each other of newly synthesized compounds. Some of these “psychonauts” seem like they’ve studied neuroscience; others appear to be novices dipping their toes into the world of cognitive enhancement. But all of them have the same goal: amplifying the brain’s existing capabilities without screwing anything up too badly. It’s the same impulse that grips bodybuilders—the feeling that with small chemical tweaks and some training, we can squeeze more utility out of the body parts we have. As Taylor Hatmaker of the Daily Dot recently wrote, “Together, these faceless armchair scientists seek a common truth—a clean, unharmful way to make their brains better—enforcing their own self-imposed safety parameters and painstakingly precise methods, all while publishing their knowledge for free, in plain text, to relatively crude, shared databases."
Qualia claims that its product stems from a new approach to science based on “principled meta-analysis and synthesis of existing research” to optimize “memory, focus, the speed of information processing, and pattern analysis.” The bottom line, however, is in its online medical disclaimer, which says: “These statements have not been evaluated by the Food and Drug Administration. . . . No claims are made about the safety of this product, nor are any medical or psychological benefits claimed.”
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."
[…] 2. Blueberries: Also called “brainberries” by Dr. Steven Platt, MD author of Superfoods Rx: Fourteen Foods Proven to Change Your Life, blueberries have one of the highest antioxidant capacities of all fruits and vegetables and are known to improve memory and cognitive function. They have memory-protecting properties and have even been associated with the prevention of Alzheimer’s disease. Add some blueberries to your breakfast and you may not need to check that to-do list several times throughout the day. Also Read The 7 Best Brain Boosting Supplements […]
When I worked on the Bulletproof Diet book, I wanted to verify that the effects I was getting from Bulletproof Coffee were not coming from modafinil, so I stopped using it and measured my cognitive performance while I was off of it. What I found was that on Bulletproof Coffee and the Bulletproof Diet, my mental performance was almost identical to my performance on modafinil. I still travel with modafinil, and I’ll take it on occasion, but while living a Bulletproof lifestyle I rarely feel the need.
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.
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