Conversely, you have to consider that the long term effects of Modafinil haven’t been studies very well. It significantly upsets sleep cycles, and 50% of Modafinil users report a number of short term side effects, such as mild to severe headaches, insomnia, nausea, anxiety, nervousness, hypertension, decreased appetite, and weight loss. PET scans show it affects the same areas of the brain that are stimulated by substance abuse.
As you may or may not know, curcumin has become a darling of the nutrition world in the last several years, thanks to a flurry of research that indicates the turmeric derivative can do everything from support the brain to reduce painful body-wide inflammation to even support positive mood. You can learn more about the research behind curcumin here:
The powder itself is quite bulky; the recommended dose to hit 200mg of absorbed magnesium leads to ~7g of powder (so capping will be difficult) and the container provides only 30 doses’ worth (or each dose costs $1!). It’s described as lemon-flavored, and it is, but it’s sickly-sweet unpleasant and since it’s so much powder, takes half a glass of water to dissolve it entirely and wash it down. Subjectively, I notice nothing after taking it for a week. I may try a simple A-B-A analysis of sleep or Mnemosyne, but I’m not optimistic. And given the large expense of LEF’s Magtein, it’s probably a non-starter even if there seems to be an effect. For sleep effects, I will have to look at more reasonably priced magnesium sources.
The effects of piracetam on healthy volunteers have been studied even less than those of Adderall or modafinil. Most peer-reviewed studies focus on its effects on dementia or on people who have suffered a seizure or a concussion. Many of the studies that look at other neurological effects were performed on rats and mice. Piracetam's mechanisms of action are not understood, though it may increase levels of the neurotransmitter acetylcholine. In 2008 a committee of the British Academy of Medical Sciences noted that many of the clinical trials of piracetam for dementia were methodologically flawed. Another published review of the available studies of the drug concluded that the evidence "does not support the use of piracetam in the treatment of people with dementia or cognitive impairment", but suggested that further investigation might be warranted. I asked Seltzer if he thought he should wait for scientific ratification of piracetam. He laughed. "I don't want to," he said. "Because it's working."
So where did the idea of Blue Monday come from? The concept of Blue Monday was originally coined by Dr Cliff Arnall in 2005 and distributed by the PR company Sky Travel. It has now become an annual event and can fall on either the third or the fourth Monday of January, using Dr Cliff Arnall’s original mathematical equation that measures a combination of factors such as weather, potential debt post-Christmas, the amount of time since Christmas, potential failure of New Year resolutions and motivation levels, that apparently conspire to make the date the gloomiest of the year.
I posted a link to the survey on my Google+ account, and inserted the link at the top of all gwern.net pages; 51 people completed all 11 binary choices (most of them coming from North America & Europe), which seems adequate since the 11 questions are all asking the same question, and 561 responses to one question is quite a few. A few different statistical tests seem applicable: a chi-squared test whether there’s a difference between all the answers, a two-sample test on the averages, and most meaningfully, summing up the responses as a single pair of numbers and doing a binomial test:

Our 2nd choice for a Brain and Memory supplement is Clari-T by Life Seasons. We were pleased to see that their formula included 3 of the 5 necessary ingredients Huperzine A, Phosphatidylserine and Bacopin. In addition, we liked that their product came in a vegetable capsule. The product contains silica and rice bran, though, which we are not sure is necessary.
Intrigued by old scientific results & many positive anecdotes since, I experimented with microdosing LSD - taking doses ~10μg, far below the level at which it causes its famous effects. At this level, the anecdotes claim the usual broad spectrum of positive effects on mood, depression, ability to do work, etc. After researching the matter a bit, I discovered that as far as I could tell, since the original experiment in the 1960s, no one had ever done a blind or even a randomized self-experiment on it.
l-theanine (Examine.com) is occasionally mentioned on Reddit or Imminst or LessWrong33 but is rarely a top-level post or article; this is probably because theanine was discovered a very long time ago (>61 years ago), and it’s a pretty straightforward substance. It’s a weak relaxant/anxiolytic (Google Scholar) which is possibly responsible for a few of the health benefits of tea, and which works synergistically with caffeine (and is probably why caffeine delivered through coffee feels different from the same amount consumed in tea - in one study, separate caffeine and theanine were a mixed bag, but the combination beat placebo on all measurements). The half-life in humans seems to be pretty short, with van der Pijl 2010 putting it ~60 minutes. This suggests to me that regular tea consumption over a day is best, or at least that one should lower caffeine use - combining caffeine and theanine into a single-dose pill has the problem of caffeine’s half-life being much longer so the caffeine will be acting after the theanine has been largely eliminated. The problem with getting it via tea is that teas can vary widely in their theanine levels and the variations don’t seem to be consistent either, nor is it clear how to estimate them. (If you take a large dose in theanine like 400mg in water, you can taste the sweetness, but it’s subtle enough I doubt anyone can actually distinguish the theanine levels of tea; incidentally, r-theanine - the useless racemic other version - anecdotally tastes weaker and less sweet than l-theanine.)
Another traditional Chinese brain booster is Danggui-Shaoyao-San (DSS). It has been suggested that DSS has potent beneficial angiogenesis and neurogenesis effects that may make it a potential treatment for ischemic stroke therapy. DSS is also known to beneficially impact free radical-mediated neurological diseases, exhibit anti-inflammatory and antioxidant activities and reduce cell death in the hippocampus, thereby promoting greater emotional, memory-related and autonomic nervous system function. Currently, there is limited research on proper dosage, but you can learn more about DSS in this fantastic summary article on it’s interplay with Alzheimer’s.
My first dose on 1 March 2017, at the recommended 0.5ml/1.5mg was miserable, as I felt like I had the flu and had to nap for several hours before I felt well again, requiring 6h to return to normal; after waiting a month, I tried again, but after a week of daily dosing in May, I noticed no benefits; I tried increasing to 3x1.5mg but this immediately caused another afternoon crash/nap on 18 May. So I scrapped my cytisine. Oh well.
We felt that the price for this product was OK but were concerned about how cheap it was on some websites. Our experience suggests that this could reflect the standard of the product, it could be that the quality of ingredients is poor and the dosage low so that they can price cut, however, this leaves consumers having to take more to reach the same level as other products. This can lead to all sorts of issues regarding overdosing, so for these reasons, until further testing can be carried out, we could not place this higher on our score board.
Price discrimination is aided by barriers such as ignorance and oligopolies. An example of the former would be when I went to a Food Lion grocery store in search of spices, and noticed that there was a second selection of spices in the Hispanic/Latino ethnic food aisle, with unit prices perhaps a fourth of the regular McCormick-brand spices; I rather doubt that regular cinnamon varies that much in quality. An example of the latter would be using veterinary drugs on humans - any doctor to do so would probably be guilty of medical malpractice even if the drugs were manufactured in the same factories (as well they might be, considering economies of scale). Similarly, we can predict that whenever there is a veterinary drug which is chemically identical to a human drug, the veterinary drug will be much cheaper, regardless of actual manufacturing cost, than the human drug because pet owners do not value their pets more than themselves. Human drugs are ostensibly held to a higher standard than veterinary drugs; so if veterinary prices are higher, then there will be an arbitrage incentive to simply buy the cheaper human version and downgrade them to veterinary drugs.
Safety Warning — Do not exceed recommended dose. Not intended for pregnant or nursing mothers or children under the age of 18. Individuals taking blood thinners, any other medications, or have any known medical conditions should consult a physician before using any herbal supplements. Discontinue use and consult your doctor if any adverse reactions occur. Not intended to medical conditions; consult a physician before beginning any weight loss program. KEEP OUT OF REACH OF CHILDREN. DO NOT USE IF SAFETY SEAL IS DAMAGED OR MISSING. KEEP BOTTLE CLOSED TIGHTLY AND STORE IN A COOL, DRY PLACE. These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease. Keep out of reach of children. Do not use if safety seal is damaged or missing. Store in a cool, dry place. CAUTION: Do not exceed recommended dose. St. John’s Wort may contribute to photosensitivity resulting in skin irritation and redness in persons exposed to strong sunlight or tanning booths. Avoid use in patients at risk of bleeding, taking anticoagulants, or with clotting disorders, based on case reports of bleeding. Discontinue use 2-3 weeks prior to some surgical and dental procedures due to increased risk of bleeding. Avoid use in couples who are trying to conceive, based on theoretical reduction of fertility. Pregnant or nursing mothers, children under 18, individuals with history of seizure, taking MAO inhibiting drugs, or with a known medical condition should consult a physician before using this or any dietary supplement. This product is manufactured and packaged in a facility which may also process milk, soy, wheat, egg, peanuts, tree nuts, fish and crustacean shellfish. This product is a dietary supplement. If you feel an adverse reaction, please contact our support staff immediately to notify us of the issue so that we can offer assistance. Please consult with a physician prior to beginning this supplement. This product has not been approved by the Food and Drug Administration. Always consult your physician or licensed qualified healthcare professional before using this product. If you begin to experience any side effects, consult your doctor, discontinue use and contact us for a full refund. Your doctor will have your extensive medical health history as well as knowledge of what other substances you are consuming, which is important when taking a supplement. We recommend that you do not rely solely on the information presented and that you always read labels, warnings, and directions before using or consuming a product. Do not use if seal around cap is broken or missing.
The word “nootropic” was coined in 1972 by a Romanian scientist, Corneliu Giurgea, who combined the Greek words for “mind” and “bending.” Caffeine and nicotine can be considered mild nootropics, while prescription Ritalin, Adderall and Provigil (modafinil, a drug for treating narcolepsy) lie at the far end of the spectrum when prescribed off-label as cognitive enhancers. Even microdosing of LSD is increasingly viewed as a means to greater productivity.

As you may or may not know, curcumin has become a darling of the nutrition world in the last several years, thanks to a flurry of research that indicates the turmeric derivative can do everything from support the brain to reduce painful body-wide inflammation to even support positive mood. You can learn more about the research behind curcumin here:
Participants (n=205) [young adults aged 18-30 years] were recruited between July 2010 and January 2011, and were randomized to receive either a daily 150 µg (0.15mg) iodine supplement or daily placebo supplement for 32 weeks…After adjusting for baseline cognitive test score, examiner, age, sex, income, and ethnicity, iodine supplementation did not significantly predict 32 week cognitive test scores for Block Design (p=0.385), Digit Span Backward (p=0.474), Matrix Reasoning (p=0.885), Symbol Search (p=0.844), Visual Puzzles (p=0.675), Coding (p=0.858), and Letter-Number Sequencing (p=0.408).
Running low on gum (even using it weekly or less, it still runs out), I decided to try patches. Reading through various discussions, I couldn’t find any clear verdict on what patch brands might be safer (in terms of nicotine evaporation through a cut or edge) than others, so I went with the cheapest Habitrol I could find as a first try of patches (Nicotine Transdermal System Patch, Stop Smoking Aid, 21 mg, Step 1, 14 patches) in May 2013. I am curious to what extent nicotine might improve a long time period like several hours or a whole day, compared to the shorter-acting nicotine gum which feels like it helps for an hour at most and then tapers off (which is very useful in its own right for kicking me into starting something I have been procrastinating on). I have not decided whether to try another self-experiment.
That left me with 329 days of data. The results are that (correcting for the magnesium citrate self-experiment I was running during the time period which did not turn out too great) days on which I happened to use my LED device for LLLT were much better than regular days. Below is a graph showing the entire MP dataseries with LOESS-smoothed lines showing LLLT vs non-LLLT days:
The available literature on cognitive enhancing practices at times appears to lump together nootropics and “smart drugs.” Smart drugs are not officially defined, but references to this group generally include Provigil (modafinil), Adderall and Ritalin. Any confusion about the addiction potential of different brain-enhancing drugs can spread misinformation about the individual drugs. There are many nootropics on the market, so the best practice is to focus on the addiction potential of each nootropic of interest or concern.

A third of participants in clinical trials on Modafinil have reported crippling headaches.  An additional 11% experienced nausea, while others reported an array of other side-effects ranging from nervousness to diarrhea.  Dizziness and insomnia may also result from Modafinil use.   I can attest that the side effects are very real.  In fact, I had to stop using Modafinil after 2 days when my headaches became so intense I ended up at the ER.
Evidence in support of the neuroprotective effects of flavonoids has increased significantly in recent years, although to date much of this evidence has emerged from animal rather than human studies. Nonetheless, with a view to making recommendations for future good practice, we review 15 existing human dietary intervention studies that have examined the effects of particular types of flavonoid on cognitive performance. The studies employed a total of 55 different cognitive tests covering a broad range of cognitive domains. Most studies incorporated at least one measure of executive function/working memory, with nine reporting significant improvements in performance as a function of flavonoid supplementation compared to a control group. However, some domains were overlooked completely (e.g. implicit memory, prospective memory), and for the most part there was little consistency in terms of the particular cognitive tests used making across study comparisons difficult. Furthermore, there was some confusion concerning what aspects of cognitive function particular tests were actually measuring. Overall, while initial results are encouraging, future studies need to pay careful attention when selecting cognitive measures, especially in terms of ensuring that tasks are actually sensitive enough to detect treatment effects.
Intrigued by old scientific results & many positive anecdotes since, I experimented with microdosing LSD - taking doses ~10μg, far below the level at which it causes its famous effects. At this level, the anecdotes claim the usual broad spectrum of positive effects on mood, depression, ability to do work, etc. After researching the matter a bit, I discovered that as far as I could tell, since the original experiment in the 1960s, no one had ever done a blind or even a randomized self-experiment on it.
The bitter reality of life is that there’s no organ of our body, which can defy the effects of aging with success. At least not entirely on its own. That’s why we need supplements in the first place. Remember? That’s only the beginning of the bad news for your brain. Certain sections of our brain, especially prefrontal cortex and hippocampus, can be seriously reduced in size as you are getting older. In addition, the number of capillaries in your head reduces, as well. Let’s not forget the arteries that become narrower and therefore limit the blood flow.
We hope you find our website to be a reliable and valuable resource in your search for the most effective brain enhancing supplements. In addition to product reviews, you will find information about how nootropics work to stimulate memory, focus, and increase concentration, as well as tips and techniques to help you experience the greatest benefit for your efforts.
I’ve been taking nootropics on and off for a month, and despite my spurts of productivity, I’m still not 100 percent sure that they’re working. I could well be placebo-ing myself into thinking I'm working harder and focusing better than I typically do. But apparently enough people are feeling some effect, placebo or not, because nootropics start-ups are thriving. There’s truBrain, Nootrobrain, Nootroo, and a host of others. Nootrobox, the company that makes my pills, says that it’s selling "five figures" worth of cognitive supplements monthly to customers that include top Silicon Valley executives and Hollywood moguls.
Gibson and Green (2002), talking about a possible link between glucose and cognition, wrote that research in the area …is based on the assumption that, since glucose is the major source of fuel for the brain, alterations in plasma levels of glucose will result in alterations in brain levels of glucose, and thus neuronal function. However, the strength of this notion lies in its common-sense plausibility, not in scientific evidence… (p. 185).
The single most reliable way to protect our brain cells as we age, most researchers agree, is to eat plenty of fruits and vegetables, which are chock-full of antioxidants and nutrients. In a study published in the October 1997 issue of the American Journal of Clinical Nutrition, researchers tested 260 people aged 65 to 90 with a series of mental exercises that involved memorizing words or doing mental arithmetic. The top performers were those who consumed the most fruits and vegetables and ate the least artery-clogging saturated fat.
Piracetam is well studied and is credited by its users with boosting their memory, sharpening their focus, heightening their immune system, even bettering their personalities. But it’s only one of many formulations in the racetam drug family. Newer ones include aniracetam, phenylpiracetam and oxiracetam. All are available online, where their efficacy and safety are debated and reviewed on message boards and in podcasts.

There are a variety of substances to get magnesium from. Considerable enthusiasm for the new compound magnesium l-threonate was stirred by 2 small animal rat studies finding that magnesium l-threonate was able to increase magnesium levels in the brain and improve learning/memory tasks. (There are no published human trials as of October 2015, and evidence of publication bias, which I take as evidence against there being large effects in humans.) Animal studies mean very little, of course (see the appendix), but I thought it’d be interesting to try using l-threonate, so I bought the $30 Life Extension Neuro-Mag Magnesium L-Threonate with Calcium and Vitamin D3 (205g), which according to the LEF product page works out to ~60g of Magtein™ magnesium L-threonate and ~4.31g elemental magnesium inasmuch as LEF claims 2000mg of threonate powder provides 144mg elemental magnesium or a 14:1 ratio. (I don’t need the calcium or vitamin D3, but this was the only magnesium l-threonate on Amazon.) Experiment-wise, I’ll probably look at sleep metrics and Mnemosyne performance; I put off designing a blind self-experiment until after trying some.
-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.
Cost-wise, the gum itself (~$5) is an irrelevant sunk cost and the DNB something I ought to be doing anyway. If the results are negative (which I’ll define as d<0.2), I may well drop nicotine entirely since I have no reason to expect other forms (patches) or higher doses (2mg+) to create new benefits. This would save me an annual expense of ~$40 with a net present value of <820 ($); even if we count the time-value of the 20 minutes for the 5 DNB rounds over 48 days (0.2 \times 48 \times 7.25 = 70), it’s still a clear profit to run a convincing experiment.
l-Theanine – A 2014 systematic review and meta-analysis found that concurrent caffeine and l-theanine use had synergistic psychoactive effects that promoted alertness, attention, and task switching;[29] these effects were most pronounced during the first hour post-dose.[29] However, the European Food Safety Authority reported that, when L-theanine is used by itself (i.e. without caffeine), there is insufficient information to determine if these effects exist.[34]
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