The research literature, while copious, is messy and varied: methodologies and devices vary substantially, sample sizes are tiny, the study designs vary from paper to paper, metrics are sometimes comically limited (one study measured speed of finishing a RAPM IQ test but not scores), blinding is rare and unclear how successful, etc. Relevant papers include Chung et al 2012, Rojas & Gonzalez-Lima 2013, & Gonzalez-Lima & Barrett 2014. Another Longecity user ran a self-experiment, with some design advice from me, where he performed a few cognitive tests over several periods of LLLT usage (the blocks turned out to be ABBA), using his father and towels to try to blind himself as to condition. I analyzed his data, and his scores did seem to improve, but his scores improved so much in the last part of the self-experiment I found myself dubious as to what was going on - possibly a failure of randomness given too few blocks and an temporal exogenous factor in the last quarter which was responsible for the improvement.
Tyrosine (Examine.com) is an amino acid; people on the Imminst.org forums (as well as Wikipedia) suggest that it helps with energy and coping with stress. I ordered 4oz (bought from Smart Powders) to try it out, and I began taking 1g with my usual caffeine+piracetam+choline mix. It does not dissolve easily in hot water, and is very chalky and not especially tasty. I have not noticed any particular effects from it.
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.
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.
Huperzine A: This compound is found in a firmoss plant called Huperzia serrata.  Studies conducted on Huperzine A so far have not used the best methodology, so scientists are still not sure how beneficial this compound is for preventing or treating Alzheimer’s disease.  But one review of studies on Huperzine A concluded that the compound “appears to have beneficial effects on improvement of cognitive function, daily living activity, and global clinical assessment in participants with Alzheimer’s disease.”
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.
Panax ginseng – A review by the Cochrane Collaboration concluded that "there is a lack of convincing evidence to show a cognitive enhancing effect of Panax ginseng in healthy participants and no high quality evidence about its efficacy in patients with dementia."[36] According to the National Center for Complementary and Integrative Health, "[a]lthough Asian ginseng has been widely studied for a variety of uses, research results to date do not conclusively support health claims associated with the herb."[37]

That’s why adults aren’t as crazy as teenagers, because adult brains aren’t as sensitive or reactive to external factors and experience teaches us to know better. That’s the potential danger with a drug like this. You return your brain to a state when you can learn a lot easier because you are ultra-sensitive to all stimuli in your environment, but it also makes it easier for that stimuli to affect you, for better or worse. The worst case scenario? You take this drug to be smarter but your personality can be destroyed by external stresses- it’s like being an emotional mess and losing yourself in high school again.
The original magnesium l-threonate caused me no apparent problems by the time I finished off the powder and usage correlated with better days, further supporting the hypothesis that magnesium helps it. But l-threonate would be difficult to cap (and hence blind self-experiment) and is ruinously expensive on a per-dose basis. So I looked around for alternatives for the followup; one of the most common compounds suggested was the citrate form because it is reasonably well-absorbed and causes fewer digestive problems, so I could just take that. Magnesium oxide is widely available it looks cheap, but the absorption/bioavailability problem makes it unattractive: at a 3:5 ratio, an estimate of 4% absorption, a ZMA formulation of an impressive-sounding 500mg would be 500 \times \frac{3}{5} \times 0.04 = 12mg or a small fraction of RDAs for male adults like 400mg elemental. (Calcium shouldn’t be a problem since I get 220mg of calcium from my multivitamin and I enjoy dairy products daily.)
Sure, you could certainly swallow too much St. John’s Wort and create the same type of serotonin or neurotransmitter issues you could create with a synthetic smart drug, but it’s far more difficult to harm yourself with a nootropic compared to a synthetic smart drug. Although synthetic, laboratory-designed nootropics do indeed exist, even those are not as harsh on the biology as a smart drug and have a mechanism of action that is a bit more natural. Let’s begin with the more natural nootropics.
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?
In addition to this, privilege also plays an important role in this epidemic. "Not everyone has access to eat healthily", she mentions. In fact, she recalls an anecdote in which a supermarket owner noticed how people living off food stamps rarely use them to buy fruits and vegetables. Curious about this trend, the owner approached someone with food stamps, to which she admitted she didn't buy them because she didn't know the price prior to weighing them and felt ashamed of asking. His solution? Pre-cutting and packaging fruits in order to make them more accessible to those with lower incomes. 
As far as anxiety goes, psychiatrist Emily Deans has an overview of why the Kiecolt-Glaser et al 2011 study is nice; she also discusses why fish oil seems like a good idea from an evolutionary perspective. There was also a weaker earlier 2005 study also using healthy young people, which showed reduced anger/anxiety/depression plus slightly faster reactions. The anti-stress/anxiolytic may be related to the possible cardiovascular benefits (Carter et al 2013).
2 commenters point out that my possible lack of result is due to my mistaken assumption that if nicotine is absorbable through skin, mouth, and lungs it ought to be perfectly fine to absorb it through my stomach by drinking it (rather than vaporizing it and breathing it with an e-cigarette machine) - it’s apparently known that absorption differs in the stomach.
"Over the years, I have learned so much from the work of Dr. Mosconi, whose accomplished credentials spanning both neuroscience and nutrition are wholly unique. This book represents the first time her studies on the interaction between food and long-term cognitive function reach a general audience. Dr. Mosconi always makes the point that we would eat differently and treat our brains better if only we could see what we are doing to them. From the lab to the kitchen, this is extremely valuable and urgent advice, complete with recommendations that any one of us can take."
Paul Phillips was unusual for a professional poker player. When he joined the circuit in the late 1990s he was already a millionaire: a twentysomething tech guy who helped found an internet portal called go2net and cashed in at the right moment. He was cerebral and at times brusque. On the international poker scene Phillips cultivated a geeky New Wave style. He wore vintage shirts in wild geometric patterns; his hair was dyed orange or silver one week, shaved off the next. Most unusual of all, Phillips talked freely about taking prescription drugs - Adderall and, especially, Provigil - in order to play better cards.
(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.)

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.


Tuesday: I went to bed at 1am, and first woke up at 6am, and I wrote down a dream; the lucid dreaming book I was reading advised that waking up in the morning and then going back for a short nap often causes lucid dreams, so I tried that - and wound up waking up at 10am with no dreams at all. Oops. I take a pill, but the whole day I don’t feel so hot, although my conversation and arguments seem as cogent as ever. I’m also having a terrible time focusing on any actual work. At 8 I take another; I’m behind on too many things, and it looks like I need an all-nighter to catch up. The dose is no good; at 11, I still feel like at 8, possibly worse, and I take another along with the choline+piracetam (which makes a total of 600mg for the day). Come 12:30, and I disconsolately note that I don’t seem any better, although I still seem to understand the IQ essays I am reading. I wonder if this is tolerance to modafinil, or perhaps sleep catching up to me? Possibly it’s just that I don’t remember what the quasi-light-headedness of modafinil felt like. I feel this sort of zombie-like state without change to 4am, so it must be doing something, when I give up and go to bed, getting up at 7:30 without too much trouble. Some N-backing at 9am gives me some low scores but also some pretty high scores (38/43/66/40/24/67/60/71/54 or ▂▂▆▂▁▆▅▇▄), which suggests I can perform normally if I concentrate. I take another pill and am fine the rest of the day, going to bed at 1am as usual.
Alpha GPC + AC-11 + Bacopa Monniera + Huperzine: This combination is found in the supplement Alpha Brain, created by the company Onnit. According to a clinical trial that was conducted by the Boston Center for Memory, this combination has demonstrated a notable increase in cognitive performance for healthy individuals and shows particular potential to boost the memory and learning capacity of users. AC-11 is derived from a rainforest herb, and studies have found that it may be able to help people in a variety of ways such as slowing the growth of cancer due to its DNA repairing antioxidant properties. This stack seems to work best if you take it daily for at about two weeks. After that, effects become more pronounced over time, so, similar to the Gingko, Bacopa, Lion’s Mane stack above you need to allow this blend to build up in your system before you judge its overall effectiveness.
Another factor to consider is whether the nootropic is natural or synthetic. Natural nootropics generally have effects which are a bit more subtle, while synthetic nootropics can have more pronounced effects. It’s also important to note that there are natural and synthetic nootropics. Some natural nootropics include Ginkgo biloba and ginseng. One benefit to using natural nootropics is they boost brain function and support brain health. They do this by increasing blood flow and oxygen delivery to the arteries and veins in the brain.

With so many different ones to choose from, choosing the best nootropics for you can be overwhelming at times. As usual, a decision this important will require research. Study up on the top nootropics which catch your eye the most. The nootropics you take will depend on what you want the enhancement for. The ingredients within each nootropic determine its specific function. For example, some nootropics contain ginkgo biloba, which can help memory, thinking speed, and increase attention span. Check the nootropic ingredients as you determine what end results you want to see.


Starting from the studies in my meta-analysis, we can try to estimate an upper bound on how big any effect would be, if it actually existed. One of the most promising null results, Southon et al 1994, turns out to be not very informative: if we punch in the number of kids, we find that they needed a large effect size (d=0.81) before they could see anything:


“By drawing on more than fifteen years of scientific research and experience, Dr. Mosconi provides expert advice to prevent medical decline and sharpen memory. Her brain healthy recipes will help you maintain peak cognitive performance well into old age and therefore delay and may even prevent the appearance of debilitating diseases like Alzheimer’s.”
With subtle effects, we need a lot of data, so we want at least half a year (6 blocks) or better yet, a year (12 blocks); this requires 180 actives and 180 placebos. This is easily covered by $11 for Doctor’s Best Best Lithium Orotate (5mg), 200-Count (more precisely, Lithium 5mg (from 125mg of lithium orotate)) and $14 for 1000x1g empty capsules (purchased February 2012). For convenience I settled on 168 lithium & 168 placebos (7 pill-machine batches, 14 batches total); I can use them in 24 paired blocks of 7-days/1-week each (48 total blocks/48 weeks). The lithium expiration date is October 2014, so that is not a problem
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.
The different ADHD medications like Adderall and Ritalin are classified as stimulants, and deal with these symptoms by increasing the neurotransmitters known as dopamine and norepinephrine, which are associated with pleasure, movement, and attention. They have a calming and focusing effect on people affected with ADHD, and are helpful for the inattentiveness, poor memory, impulsiveness, and mood swings experienced by those people.
"They're not regulated by the FDA like other drugs, so safety testing isn't required," Kerl says. What's more, you can't always be sure that what's on the ingredient label is actually in the product. Keep in mind, too, that those that contain water-soluble vitamins like B and C, she adds, aren't going to help you if you're already getting enough of those vitamins through diet. "If your body is getting more than you need, you're just going to pee out the excess," she says. "You're paying a lot of money for these supplements; maybe just have orange juice."
Exercise is also important, says Lebowitz. Studies have shown it sharpens focus, elevates your mood and improves concentration. Likewise, maintaining a healthy social life and getting enough sleep are vital, too. Studies have consistently shown that regularly skipping out on the recommended eight hours can drastically impair critical thinking skills and attention.
Dr. Lisa Mosconi, PhD, INHC, is the associate director of the Alzheimer's Prevention Clinic at Weill Cornell Medical College (WCMC)/NewYork-Presbyterian Hospital, where she was recruited as an associate professor of Neuroscience in Neurology. She also is an adjunct faculty member in the Department of Psychiatry at NYU School of Medicine, in the Department of Nutrition at NYU Steinhardt School of Nutrition and Public Health, and in the Departments of Neurology and Nuclear Medicine at the University of Florence (Italy). Formerly, Dr. Mosconi founded and was the director of the Nutrition & Brain Fitness Lab at New York University School of Medicine (NYU), and an assistant professor in the NYU Department of Psychiatry, where she served as the director of the Family History of Alzheimer's disease research program. Dr. Mosconi holds a dual PhD degree in Neuroscience and Nuclear Medicine from the University of Florence, Italy, and is a board certified integrative nutritionist and holistic healthcare practitioner. She is well known for her research on the early detection of Alzheimer's disease and is passionately interested in the mitigation and prevention of memory loss through lifestyle modifications including diet, nutrition, and physical and intellectual fitness.
With so many different ones to choose from, choosing the best nootropics for you can be overwhelming at times. As usual, a decision this important will require research. Study up on the top nootropics which catch your eye the most. The nootropics you take will depend on what you want the enhancement for. The ingredients within each nootropic determine its specific function. For example, some nootropics contain ginkgo biloba, which can help memory, thinking speed, and increase attention span. Check the nootropic ingredients as you determine what end results you want to see.
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