The Lynches said that Provigil was a classic example of a related phenomenon: mission creep. In 1998, Cephalon, the pharmaceutical company that manufactures it, received US government approval to market the drug but only for "excessive daytime sleepiness" due to narcolepsy; by 2004, Cephalon had obtained permission to expand the labelling so that it included sleep apnoea and "shift-work sleep disorder". Net sales of Provigil climbed from $196m in 2002 to $988m in 2008.
Working memory has been likened to a mental scratch pad: you use it to keep relevant data in mind while you're completing a task. (Imagine a cross-examination, in which a lawyer has to keep track of the answers a witness has given and formulate new questions based on them.) In one common test subjects are shown a series of items - usually letters or numbers - and then presented with challenges: was this number or letter in the series? Was this one? In the working-memory tests, subjects performed better on neuroenhancers, though several of the studies suggested that the effect depended on how good a subject's working memory was to begin with: the better it was, the less benefit the drugs provided.
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My answer is that this is not a lot of research or very good research (not nearly as good as the research on nicotine, eg.), and assuming it’s true, I don’t value long-term memory that much because LTM is something that is easily assisted or replaced (personal archives, and spaced repetition). For me, my problems tend to be more about akrasia and energy and not getting things done, so even if a stimulant comes with a little cost to long-term memory, it’s still useful for me. I’m going continue to use the caffeine. It’s not so bad in conjunction with tea, is very cheap, and I’m already addicted, so why not? Caffeine is extremely cheap, addictive, has minimal effects on health (and may be beneficial, from the various epidemiological associations with tea/coffee/chocolate & longevity), and costs extra to remove from drinks popular regardless of their caffeine content (coffee and tea again). What would be the point of carefully investigating it? Suppose there was conclusive evidence on the topic, the value of this evidence to me would be roughly $0 or since ignorance is bliss, negative money - because unless the negative effects were drastic (which current studies rule out, although tea has other issues like fluoride or metal contents), I would not change anything about my life. Why? I enjoy my tea too much. My usual tea seller doesn’t even have decaffeinated oolong in general, much less various varieties I might want to drink, apparently because de-caffeinating is so expensive it’s not worthwhile. What am I supposed to do, give up my tea and caffeine just to save on the cost of caffeine? Buy de-caffeinating machines (which I couldn’t even find any prices for, googling)? This also holds true for people who drink coffee or caffeinated soda. (As opposed to a drug like modafinil which is expensive, and so the value of a definitive answer is substantial and would justify some more extensive calculating of cost-benefit.)
I have a needle phobia, so injections are right out; but from the images I have found, it looks like testosterone enanthate gels using DMSO resemble other gels like Vaseline. This suggests an easy experimental procedure: spoon an appropriate dose of testosterone gel into one opaque jar, spoon some Vaseline gel into another, and pick one randomly to apply while not looking. If one gel evaporates but the other doesn’t, or they have some other difference in behavior, the procedure can be expanded to something like and then half an hour later, take a shower to remove all visible traces of the gel. Testosterone itself has a fairly short half-life of 2-4 hours, but the gel or effects might linger. (Injections apparently operate on a time-scale of weeks; I’m not clear on whether this is because the oil takes that long to be absorbed by surrounding materials or something else.) Experimental design will depend on the specifics of the obtained substance. As a controlled substance (Schedule III in the US), supplies will be hard to obtain; I may have to resort to the Silk Road.
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.
But when aficionados talk about nootropics, they usually refer to substances that have supposedly few side effects and low toxicity. Most often they mean piracetam, which Giurgea first synthesized in 1964 and which is approved for therapeutic use in dozens of countries for use in adults and the elderly. Not so in the United States, however, where officially it can be sold only for research purposes.
Maybe you are you new to nootropics? The word, “Nootropic” is a very broad term describing a supplement or drug that increases mental performance. There are several different groups of nootropics including herbal supplements and a class of research chemicals known as racetams. Below are some of the many common benefits that may potentially be experienced with nootropic supplements.
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.)
When you drink tea, you’re getting some caffeine (less than the amount in coffee), plus an amino acid called L-theanine that has been shown in studies to increase activity in the brain’s alpha frequency band, which can lead to relaxation without drowsiness. These calming-but-stimulating effects might contribute to tea’s status as the most popular beverage aside from water. People have been drinking it for more than 4,000 years, after all, but modern brain hackers try to distill and enhance the benefits by taking just L-theanine as a nootropic supplement. Unfortunately, that means they’re missing out on the other health effects that tea offers. It’s packed with flavonoids, which are associated with longevity, reduced inflammation, weight loss, cardiovascular health, and cancer prevention.
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:
70 pairs is 140 blocks; we can drop to 36 pairs or 72 blocks if we accept a power of 0.5/50% chance of reaching significance. (Or we could economize by hoping that the effect size is not 3.5 but maybe twice the pessimistic guess; a d=0.5 at 50% power requires only 12 pairs of 24 blocks.) 70 pairs of blocks of 2 weeks, with 2 pills a day requires (70 \times 2) \times (2 \times 7) \times 2 = 3920 pills. I don’t even have that many empty pills! I have <500; 500 would supply 250 days, which would yield 18 2-week blocks which could give 9 pairs. 9 pairs would give me a power of:
Long story short, aging is your brain’s worst enemy. The same applies to all organs of our body, but the brain suffers the most. Both neurotransmitters and neurons are taking the blow too. As a result, the neuron communication is affected. Now, this may seem like the rocket science to you, but it’s enough to say, serotonin and dopamine are the most important neurotransmitters. Without these components, you can forget about good mood. Serotonin and dopamine levels drop at a rate of approximately 10% for every decade you add to your age.
A key ingredient of Noehr’s chemical “stack” is a stronger racetam called Phenylpiracetam. He adds a handful of other compounds considered to be mild cognitive enhancers. One supplement, L-theanine, a natural constituent in green tea, is claimed to neutralise the jittery side-effects of caffeine. Another supplement, choline, is said to be important for experiencing the full effects of racetams. Each nootropic is distinct and there can be a lot of variation in effect from person to person, says Lawler. Users semi-annonymously compare stacks and get advice from forums on sites such as Reddit. Noehr, who buys his powder in bulk and makes his own capsules, has been tweaking chemicals and quantities for about five years accumulating more than two dozens of jars of substances along the way. He says he meticulously researches anything he tries, buys only from trusted suppliers and even blind-tests the effects (he gets his fiancée to hand him either a real or inactive capsule).
L-Alpha glycerylphosphorylcholine or choline alfoscerate, also known as Alpha GPC is a natural nootropic which works both on its own and also in combination with other nootropics. It can be found in the human body naturally in small amounts. It’s also present in some dairy products, wheat germ, and in organic meats. However, these dietary sources contain small amounts of GPC, which is why people prefer taking it through supplements.
Oxidative stress refers to a biochemical process that occurs as a result of an accumulative everyday exposure to toxic burdens such as chemicals in cosmetics, furniture, paints, cars, and pollution. Our body has its own way of armouring itself from the damage that exposure to toxins can create through its production of endogenous antioxidants, which is nature’s way of neutralising oxidative stress. Although we have our own production of these wonder molecules, when we are continuously overloaded with toxins in our environment and have problems detoxifying, the liver can become overwhelmed. Research shows that over time oxidative stress can lead to an increase in inflammatory molecules such as cytokines, which have been shown to correlate with depression (5).This is why it is important to have a high intake of nutrients that support the liver in metabolising and removing toxins from the body, as well as regulating the inflammatory response. There are a few things we can change in our diet to support this area, for example eating foods such as the cruciferous family of vegetables which includes kale, cauliflower, broccoli and cabbage. These are particularly effective at supporting the liver in ushering out toxins as they all share an antioxidant compound called indole-3 Carbinol, which plays an important role in liver health (6). In addition, bitter greens such as collard greens, rocket, chicory and swiss chard are also great for supporting the liver’s own antioxidant defence system.
Alex's sense of who uses stimulants for so-called "non-medical" purposes is borne out by two dozen or so scientific studies. In 2005 a team led by Sean Esteban McCabe, a professor at the University of Michigan, reported that in the previous year 4.1% of American undergraduates had taken prescription stimulants for off-label use - at one school the figure was 25%, while a 2002 study at a small college found that more than 35% of the students had used prescription stimulants non-medically in the previous year.
…Four subjects correctly stated when they received nicotine, five subjects were unsure, and the remaining two stated incorrectly which treatment they received on each occasion of testing. These numbers are sufficiently close to chance expectation that even the four subjects whose statements corresponded to the treatments received may have been guessing.
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.
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.
However, they fell short in several categories. The key issue with their product is that it does not contain DHA Omega 3 and the other essential vitamins and nutrients needed to support the absorption of Huperzine A and Phosphatidylserine. Without having DHA Omega 3 it will not have an essential piece to maximum effectiveness. This means that you would need to take a separate pill of DHA Omega 3 and several other essential vitamins to ensure you are able to reach optimal memory support. They also are still far less effective than our #1 pick’s complete array of the 3 essential brain supporting ingredients and over 30 supporting nutrients, making their product less effective.
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.↩
Over the years, science has looked into the validity of this date being the most blue of all dates, however there is little evidence to prove this. There is some research that suggests how weekends are a time when people generally feel happier and less anxious, mostly for those that work full-time Monday-Friday, however there is little difference with subjective mood for other days of the week. Some charities such as MIND, have even said that Blue Monday, which is used mainly as a marketing tool to sell products and stories, can also be dangerously misleading and have even set up the hashtag #BlueAnyDay to help dispel the myth of this date.The idea that as a population we are more likely to feel down on the third of fourth Monday of the year can not only trivialise depression as a medical illness that can be life threatening but can also affect those that live with depression and know too well that feelings associated to this illness are not dictated by a single date in the diary.
Cacao contains powerful flavonols, compounds that act as antioxidants and help preserve the brain’s stem cells. “Stem cells produce new brain cells,” says Dennis Steindler, PhD, director of the Neuroscience and Aging Lab at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, “and chronic inflammation or the beginnings of disease can damage these reparative cells and the other at-risk brain cells used for standard operating procedures, like memory and thinking.” Flavonols have also been shown to support the hippocampus, a part of the brain involved in memory and mood, notes Steindler. Stick to a square or two of dark chocolate daily.
I tried taking whole pills at 1 and 3 AM. I felt kind of bushed at 9 AM after all the reading, and the 50 minute nap didn’t help much - I was sleep only around 10 minutes and spent most of it thinking or meditation. Just as well the 3D driver is still broken; I doubt the scores would be reasonable. Began to perk up again past 10 AM, then felt more bushed at 1 PM, and so on throughout the day; kind of gave up and began watching & finishing anime (Amagami and Voices of a Distant Star) for the rest of the day with occasional reading breaks (eg. to start James C. Scotts Seeing Like A State, which is as described so far). As expected from the low quality of the day, the recovery sleep was bigger than before: a full 10 hours rather than 9:40; the next day, I slept a normal 8:50, and the following day ~8:20 (woken up early); 10:20 (slept in); 8:44; 8:18 (▁▇▁▁). It will be interesting to see whether my excess sleep remains in the hour range for ’good modafinil nights and two hours for bad modafinil nights.
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Bacopa Monnieri: Also known as “waterhyssop,” this herb grows in wetlands around the world. It has a long history of use in Ayurvedic medicine. It is a powerful antioxidant which had demonstrated protective effects on cells. It also has anti-inflammatory properties. Inflammation is believed to play a major role in the development of dementia. Additionally, this herb boosts blood flow to the brain and activates choline acetyltransferase, a key enzyme which is necessary to synthesize the neurotransmitter cetylcholine.
Broccoli is great source of vitamin K, which is known to enhance cognitive function and improve brainpower. Researchers have reported that because broccoli is high in compounds called glucosinolates, it can slow the breakdown of the neurotransmitter, acetylcholine, which we need for the central nervous system to perform properly and to keep our brains and our memories sharp. Low levels of acetylcholine are associated with Alzheimer's.
B vitamins are also sold with claims of enhancing memory, usually rationalized by their reduction of homocysteine, a chemical in the blood that may affect circulation in the brain. No benefits from B vitamin intake have been demonstrated when it comes to memory or cognitive function except in the case of people who have high homocysteine levels due to a diet that is very low in B vitamins. There is some concern that folic acid, one of the B vitamins, may spur the growth of polyps in the colon at doses greater than 800 micrograms a day. Phosphatidyl serine is a natural component of nerve cell membranes and its promoters argue that a deficiency leads to impaired communication between nerve cells which in turn impairs cognitive function. Sounds reasonable, except that proper controlled trials have come up empty. The same goes for vinpocetine, a compound originally isolated from the lesser periwinkle plant by Hungarian chemist Csaba Szantay in 1975. It is widely used in Europe to treat strokes and memory problems with claims of increased circulation to the brain. It does indeed increase circulation, much like ginkgo, but there is no compelling evidence for memory improvement.
Too much caffeine may be bad for bone health because it can deplete calcium. Overdoing the caffeine also may affect the vitamin D in your body, which plays a critical role in your body’s bone metabolism. However, the roles of vitamin D as well as caffeine in the development of osteoporosis continue to be a source of debate. Significance: Caffeine may interfere with your body’s metabolism of vitamin D, according to a 2007 Journal of Steroid Biochemistry & Molecular Biology study. You have vitamin D receptors, or VDRs, in your osteoblast cells. These large cells are responsible for the mineralization and synthesis of bone in your body. They create a sheet on the surface of your bones. The D receptors are nuclear hormone receptors that control the action of vitamin D-3 by controlling hormone-sensitive gene expression. These receptors are critical to good bone health. For example, a vitamin D metabolism disorder in which these receptors don’t work properly causes rickets.
The magnesium was neither randomized nor blinded and included mostly as a covariate to avoid confounding (the Noopept coefficient & t-value increase somewhat without the Magtein variable), so an OR of 1.9 is likely too high; in any case, this experiment was too small to reliably detect any effect (~26% power, see bootstrap power simulation in the magnesium section) so we can’t say too much.
Mosconi gets the anthropology right. Her foundation is based on two empirical findings. The first one is her studying of the “Blue Zones” or the five areas in the World associated with the greatest proportion of centenarians. And, her second one is her experience as a neuroscientist. She has seen thousands of brain MRIs while knowing what diet her patients ate. She uncovered a link between brain health and diet. The ones who ate a Mediterranean diet had far healthier brains (per MRIs) than the ones on an American diet. She also observed that 2 out of the 5 Blue Zones eat a Mediterranean diets. And, the three other ones have major overlapping components with a Mediterranean diet including complex carbohydrates (fresh produce) that have a lot of fiber, starches (sweet potatoes), nuts, fish, and not much meat and animal protein.
I was contacted by the Longecity user lostfalco, and read through some of his writings on the topic. I had never heard of LLLT before, but the mitochondria mechanism didn’t sound impossible (although I wondered whether it made sense at a quantity level14151617), and there was at least some research backing it; more importantly, lostfalco had discovered that devices for LLLT could be obtained as cheap as $15. (Clearly no one will be getting rich off LLLT or affiliate revenue any time soon.) Nor could I think of any way the LLLT could be easily harmful: there were no drugs involved, physical contact was unnecessary, power output was too low to directly damage through heating, and if it had no LLLT-style effect but some sort of circadian effect through hitting photoreceptors, using it in the morning wouldn’t seem to interfere with sleep.
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.
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.
He recommends a 10mg dose, but sublingually. He mentions COLURACETAM’s taste is more akin to that of PRAMIRACETAM than OXIRACETAM, in that it tastes absolutely vile (not a surprise), so it is impossible to double-blind a sublingual administration - even if I knew of an inactive equally-vile-tasting substitute, I’m not sure I would subject myself to it. To compensate for ingesting the coluracetam, it would make sense to double the dose to 20mg (turning the 2g into <100 doses). Whether the effects persist over multiple days is not clear; I’ll assume it does not until someone says it does, since this makes things much easier.
Blinding stymied me for a few months since the nasty taste was unmistakable and I couldn’t think of any gums with a similar flavor to serve as placebo. (The nasty taste does not seem to be due to the nicotine despite what one might expect; Vaniver plausibly suggested the bad taste might be intended to prevent over-consumption, but nothing in the Habitrol ingredient list seemed to be noted for its bad taste, and a number of ingredients were sweetening sugars of various sorts. So I couldn’t simply flavor some gum.)
An important dietary step to avoid heavy metal toxicity is choosing seafood and fish that has reduced levels of exposure. The Seafood Watch web page is a fantastic resource that has an extensive list of fish, seafood and sushi products that are safe, as well as those that are best to stay away from. For example, choosing wild pacific caught salmon is safer than Atlantic caught salmon.
Modafinil, also known as Provigil, Modalert, and Alertec, was originally made and marketed for sleep disorders, and has been prescribed in the US for this reason since 1998. It was found only by chance to help with focus and concentration, and it is only approved for the treatment of narcolepsy, shift work sleep disorder, and obstructive sleep apnea.
When comparing supplements, consider products with a score above 90% to get the greatest benefit from smart pills to improve memory. Additionally, we consider the reviews that users send to us when scoring supplements, so you can determine how well products work for others and use this information to make an informed decision. Every month, our editor puts her name on that month’s best smart bill, in terms of results and value offered to users.
There are many studies that suggest that Creatine helps in treating cognitive decline in individuals when combined with other therapies. It also helps people suffering from Parkinsons and Huntingtons disease. Though there are minimal side effects associated with creatine, pretty much like any nootropic, it is not absolutely free of side-effects. An overdose of creatine can lead to gastrointestinal issues, weight gain, stress and anxiety.
Apkarian and colleagues imaged the brains of 68 participants and gave them personality tests. The researchers then randomly assigned the participants to groups that either received no treatment, sugar pills or a pain-killing drug. Those given pills were not told if they received a placebo or an active drug. Participants took the treatment for two weeks, stopped for one week and then repeated this cycle.
I noticed what may have been an effect on my dual n-back scores; the difference is not large (▃▆▃▃▂▂▂▂▄▅▂▄▂▃▅▃▄ vs ▃▄▂▂▃▅▂▂▄▁▄▃▅▂▃▂▄▂▁▇▃▂▂▄▄▃▃▂▃▂▂▂▃▄▄▃▆▄▄▂▃▄▃▁▂▂▂▃▂▄▂▁▁▂▄▁▃▂▄) and appears mostly in the averages - Toomim’s quick two-sample t-test gave p=0.23, although a another analysis gives p=0.138112. One issue with this before-after quasi-experiment is that one would expect my scores to slowly rise over time and hence a fish oil after would yield a score increase - the 3.2 point difference could be attributable to that, placebo effect, or random variation etc. But an accidentally noticed effect (d=0.28) is a promising start. An experiment may be worth doing given that fish oil does cost a fair bit each year: randomized blocks permitting an fish-oil-then-placebo comparison would take care of the first issue, and then blinding (olive oil capsules versus fish oil capsules?) would take care of the placebo worry.
Mosconi does not make a persuasive argument that the brain requires anything unique, anything more than the same good nutrition that benefits the entire body. Her Brain Food plan provides much good advice about healthy lifestyle and diet, but the good advice is mixed with unsupported claims, speculations, extrapolations that go far beyond the evidence, and some very questionable ideas. (Himalayan pink sea salt? Water that doesn’t hydrate?) Her plan might reduce the risk of Alzheimer’s; it might not. Is it any better than any of the many other plans recommended in the “Awakening from Alzheimer’s” videos? The only way to tell would be to do controlled studies, which have not been done or even contemplated, as far as I could see. It might not be any better than the general health advice provided by science-based conventional medical practitioners. There may be no difference between eating for your brain and eating for your entire organism.
Or in other words, since the standard deviation of my previous self-ratings is 0.75 (see the Weather and my productivity data), a mean rating increase of >0.39 on the self-rating. This is, unfortunately, implying an extreme shift in my self-assessments (for example, 3s are ~50% of the self-ratings and 4s ~25%; to cause an increase of 0.25 while leaving 2s alone in a sample of 23 days, one would have to push 3s down to ~25% and 4s up to ~47%). So in advance, we can see that the weak plausible effects for Noopept are not going to be detected here at our usual statistical levels with just the sample I have (a more plausible experiment might use 178 pairs over a year, detecting down to d>=0.18). But if the sign is right, it might make Noopept worthwhile to investigate further. And the hardest part of this was just making the pills, so it’s not a waste of effort.
"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."
Omega-3 fatty acids: DHA and EPA – two Cochrane Collaboration reviews on the use of supplemental omega-3 fatty acids for ADHD and learning disorders conclude that there is limited evidence of treatment benefits for either disorder. Two other systematic reviews noted no cognition-enhancing effects in the general population or middle-aged and older adults.