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.
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.
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.
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.
Hericium erinaceus (Examine.com) was recommended strongly by several on the ImmInst.org forums for its long-term benefits to learning, apparently linked to Nerve growth factor. Highly speculative stuff, and it’s unclear whether the mushroom powder I bought was the right form to take (ImmInst.org discussions seem to universally assume one is taking an alcohol or hotwater extract). It tasted nice, though, and I mixed it into my sleeping pills (which contain melatonin & tryptophan). I’ll probably never know whether the $30 for 0.5lb was well-spent or not.

The blood half-life is 12-36 hours; hence two or three days ought to be enough to build up and wash out. A week-long block is reasonable since that gives 5 days for effects to manifest, although month-long blocks would not be a bad choice either. (I prefer blocks which fit in round periods because it makes self-experiments easier to run if the blocks fit in normal time-cycles like day/week/month. The most useless self-experiment is the one abandoned halfway.)


If this is the case, this suggests some thoughtfulness about my use of nicotine: there are times when use of nicotine will not be helpful, but times where it will be helpful. I don’t know what makes the difference, but I can guess it relates to over-stimulation: on some nights during the experiment, I had difficult concentrating on n-backing because it was boring and I was thinking about the other things I was interested in or working on - in retrospect, I wonder if those instances were nicotine nights.

My predictions were substantially better than random chance7, so my default belief - that Adderall does affect me and (mostly) for the better - is borne out. I usually sleep very well and 3 separate incidents of horrible sleep in a few weeks seems rather unlikely (though I didn’t keep track of dates carefully enough to link the Zeo data with the Adderall data). Between the price and the sleep disturbances, I don’t think Adderall is personally worthwhile.
Provigil may well confer a temporary advantage on healthy people, but this doesn't mean that it's ready to replace your morning espresso. Anjan Chatterjee told me that there "just aren't enough studies of these drugs in normal people". One study, published recently in the Journal of the American Medical Association, suggests that Provigil can be habit-forming. A group led by Nora Volkow, the director of the National Institute on Drug Abuse, scanned the brains of 10 men after they had been given a placebo, and also after they had been given a dose of modafinil. The modafinil appeared to lead to an increase in the brain chemical dopamine. "Because drugs that increase dopamine have the potential for abuse," Volkow's report concluded, "these results suggest that risk for addiction in vulnerable persons merits heightened awareness." (Cephalon, in a response to the report, notes that Provigil's label urges physicians to monitor patients closely, especially those with a history of drug abuse.) On the website Erowid, where people vividly and anonymously report their experiences with legal and illegal drugs, some modafinil users have described a dependency on the drug. One man, who identified himself as a former biochemistry student, said that he had succeeded in kicking cocaine and opiate habits but couldn't stop using modafinil. Whenever he ran out of the drug, he said, "I start to freak out." After "four to five days" without it, "the head fog starts to come back".

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.
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Looking at the prices, the overwhelming expense is for modafinil. It’s a powerful stimulant - possibly the single most effective ingredient in the list - but dang expensive. Worse, there’s anecdotal evidence that one can develop tolerance to modafinil, so we might be wasting a great deal of money on it. (And for me, modafinil isn’t even very useful in the daytime: I can’t even notice it.) If we drop it, the cost drops by a full $800 from $1761 to $961 (almost halving) and to $0.96 per day. A remarkable difference, and if one were genetically insensitive to modafinil, one would definitely want to remove it.
If you’re a coffee or tea drinker, keep sipping: Caffeine may help protect against age-related cognitive decline. “Studies have indicated that caffeine—for example, roughly 500 milligrams daily, the equivalent of about five cups of coffee—may help stave off memory issues in humans,” says Bruce Citron, PhD, a neuroscientist at Bay Pines VA Healthcare System and the USF Morsani College of Medicine in Florida. (Experts warn against taking caffeine supplements, which flood your body with a lot of caffeine all at once.)

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."


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."

That study is also interesting for finding benefits to chronic piracetam+choline supplementation in the mice, which seems connected to a Russian study which reportedly found that piracetam (among other more obscure nootropics) increased secretion of BDNF in mice. See also Drug heuristics on a study involving choline supplementation in pregnant rats.↩
But how to blind myself? I used my pill maker to make 9 OO pills of piracetam mix, and then 9 OO pills of piracetam mix+the Adderall, then I put them in a baggy. The idea is that I can blind myself as to what pill I am taking that day since at the end of the day, I can just look in the baggy and see whether a placebo or Adderall pill is missing: the big capsules are transparent so I can see whether there is a crushed-up blue Adderall in the end or not. If there are fewer Adderall than placebo, I took an Adderall, and vice-versa. Now, since I am checking at the end of each day, I also need to remove or add the opposite pill to maintain the ratio and make it easy to check the next day; more importantly I need to replace or remove a pill, because otherwise the odds will be skewed and I will know how they are skewed. (Imagine I started with 4 Adderalls and 4 placebos, and then 3 days in a row I draw placebos but I don’t add or remove any pills; the next day, because most of the placebos have been used up, there’s only a small chance I will get a placebo…)
In August 2011, after winning the spaced repetition contest and finishing up the Adderall double-blind testing, I decided the time was right to try nicotine again. I had since learned that e-cigarettes use nicotine dissolved in water, and that nicotine-water was a vastly cheaper source of nicotine than either gum or patches. So I ordered 250ml of water at 12mg/ml (total cost: $18.20). A cigarette apparently delivers around 1mg of nicotine, so half a ml would be a solid dose of nicotine, making that ~500 doses. Plenty to experiment with. The question is, besides the stimulant effect, nicotine also causes habit formation; what habits should I reinforce with nicotine? Exercise, and spaced repetition seem like 2 good targets.

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Of course, as you can probably imagine, the antioxidant content of coffee (which you’ll learn how to maximize below) may not be the only smoking savior here. And no, it’s not the tobacco and nasty chemicals in a cigarette that’s working the magic: as other studies have gone on to prove, it’s the nicotine folks – and the nicotine is pretty powerful stuff, not only enhancing locomotor and cognitive performance when combined with coffee but also ramping up exercise performance by 18-21% all on its own!
(I was more than a little nonplussed when the mushroom seller included a little pamphlet educating one about how papaya leaves can cure cancer, and how I’m shortening my life by decades by not eating many raw fruits & vegetables. There were some studies cited, but usually for points disconnected from any actual curing or longevity-inducing results.)
After a month of testing nootropics, I’m not ready to commit to them permanently. They’re simply too untested, and while “move fast and break things” might be a good approach to building software, it’s not what I want for my brain. Still, I think we’ll likely hear more about nootropics, especially as recreational users of more powerful prescription drugs like Adderall and modafinil look for less harsh alternatives. Sometimes, when you’re working, you don’t want to put your brain on jet fuel—a little unleaded gas will do. And for those moments, nootropics could be a fertile testing ground for the intrepid body-hacker.

Similar delicacies from around the world include Mexican tacos de sesos.[1] The Anyang tribe of Cameroon practiced a tradition in which a new tribal chief would consume the brain of a hunted gorilla, while another senior member of the tribe would eat the heart.[2] Indonesian cuisine specialty in Minangkabau cuisine also served beef brain in a coconut-milk gravy named gulai otak (beef brain curry).[3][4] In Cuban cuisine, "brain fritters" are made by coating pieces of brain with bread crumbs and then frying them.[5]

“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.
-Phosphatidylserine, which occurs naturally in high concentrations in the brain and has been shown to lower stress, cortisol and physical fatigue, improve attention-deficit and forgetfulness and increase mental processing and memory. Research indicates an effective dose of 100 mg three times daily, but anything over that may lead to adverse side effects like insomnia.
Power times prior times benefit minus cost of experimentation: (0.20 \times 0.30 \times 540) - 41 = -9. So the VoI is negative: because my default is that fish oil works and I am taking it, weak information that it doesn’t work isn’t enough. If the power calculation were giving us 40% reliable information, then the chance of learning I should drop fish oil is improved enough to make the experiment worthwhile (going from 20% to 40% switches the value from -$9 to +$23.8).
Your brain is essentially a network of billions of neurons connected by synapses. These neurons communicate and work together through chemicals known as neurotransmitters. When neurotransmitters are able to send signals more efficiently, you experience improved concentration, better memory, mood elevation, increased processing ability for mental work, and longer attention spans.
Provigil may well confer a temporary advantage on healthy people, but this doesn't mean that it's ready to replace your morning espresso. Anjan Chatterjee told me that there "just aren't enough studies of these drugs in normal people". One study, published recently in the Journal of the American Medical Association, suggests that Provigil can be habit-forming. A group led by Nora Volkow, the director of the National Institute on Drug Abuse, scanned the brains of 10 men after they had been given a placebo, and also after they had been given a dose of modafinil. The modafinil appeared to lead to an increase in the brain chemical dopamine. "Because drugs that increase dopamine have the potential for abuse," Volkow's report concluded, "these results suggest that risk for addiction in vulnerable persons merits heightened awareness." (Cephalon, in a response to the report, notes that Provigil's label urges physicians to monitor patients closely, especially those with a history of drug abuse.) On the website Erowid, where people vividly and anonymously report their experiences with legal and illegal drugs, some modafinil users have described a dependency on the drug. One man, who identified himself as a former biochemistry student, said that he had succeeded in kicking cocaine and opiate habits but couldn't stop using modafinil. Whenever he ran out of the drug, he said, "I start to freak out." After "four to five days" without it, "the head fog starts to come back".

along with the previous bit of globalization is an important factor: shipping is ridiculously cheap. The most expensive S&H in my modafinil price table is ~$15 (and most are international). To put this in perspective, I remember in the 90s you could easily pay $15 for domestic S&H when you ordered online - but it’s 2013, and the dollar has lost at least half its value, so in real terms, ordering from abroad may be like a quarter of what it used to cost, which makes a big difference to people dipping their toes in and contemplating a small order to try out this ’nootropics thing they’ve heard about.

The placebos can be the usual pills filled with olive oil. The Nature’s Answer fish oil is lemon-flavored; it may be worth mixing in some lemon juice. In Kiecolt-Glaser et al 2011, anxiety was measured via the Beck Anxiety scale; the placebo mean was 1.2 on a standard deviation of 0.075, and the experimental mean was 0.93 on a standard deviation of 0.076. (These are all log-transformed covariates or something; I don’t know what that means, but if I naively plug those numbers into Cohen’s d, I get a very large effect: \frac{1.2 - 0.93}{0.076}=3.55.)


Ampakines are structurally derived from a popular nootropic called “aniracetam”. Their basic function is to activate AMPA glutamate receptors (AMPARs). Glutamate (a neurotransmitter) is the primary mediator of excitatory synaptic transmission in mammalian brains, which makes it crucial for synaptic plasticity (the adaptation of synapses, the space between neurons across which information is sent), learning and memory, so when you activate or stimulate glutamate receptors, you can trigger many of these functions. AMPARs are distributed across the central nervous system and are stimulated by incoming glutamate to begin the neuroenhancing benefits they’re often used for. But it is possible to have too much glutamate activity. When excess glutamate is produced, accumulates and binds to AMPARs, the result is excitotoxicity, which is a state of cell death (in the case of the central nervous system and your brain, neuron death) resulting from the toxic levels of excitatory amino acids. Excitotoxicity is believed to play a major role in the development of various degenerative neurological conditions such as schizophrenia, delirium and dementia.
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.
It can easily pass through the blood-brain barrier, and is known to protect the nerve tissues present in the brain. There is evidence that the acid plays an instrumental role in preventing strokes in adults by decreasing the number of free radicals in the body.  It increases the production of acetylcholine , a neurotransmitter that most Alzheimer’s patients are deficit in.
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.
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.
Get plenty of sleep.  It can be a real challenge to get seven to nine hours of restful sleep each night with a busy fulltime work schedule, but rest is essential to optimum brain functioning!  A healthy nootropic pill can help to clear up brain fog and sharpen your concentration, but it cannot work miracles.  If you are trying to power through on four to five hours of sleep each night, nothing is going to cut it.
Jump up ^ Sattler, Sebastian; Mehlkop, Guido; Graeff, Peter; Sauer, Carsten (February 1, 2014). "Evaluating the drivers of and obstacles to the willingness to use cognitive enhancement drugs: the influence of drug characteristics, social environment, and personal characteristics". Substance Abuse Treatment, Prevention, and Policy. BioMed Central Ltd. p. 8. doi:10.1186/1747-597X-9-8. ISSN 1747-597X. Retrieved April 5, 2014.
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