Compared with those reporting no use, subjects drinking >4 cups/day of decaffeinated coffee were at increased risk of RA [rheumatoid arthritis] (RR 2.58, 95% CI 1.63-4.06). In contrast, women consuming >3 cups/day of tea displayed a decreased risk of RA (RR 0.39, 95% CI 0.16-0.97) compared with women who never drank tea. Caffeinated coffee and daily caffeine intake were not associated with the development of RA.
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.
Nootroo and Nootrobox are two San Francisco nootropics startups that launched last year. Their founders come from the tech scene and their products are squarely aimed at the tech crowd seeking the convenience of not having to build their own combinations. Each claims big-name Silicon Valley entrepreneurs and investors among their users, though neither will name them.
2ml is supposed to translate to 24mg, which is a big dose. I do not believe any of the commercial patches go much past that. I asked Wedrifid, whose notes inspired my initial interest, and he was taking perhaps 2-4mg, and expressed astonishment that I might be taking 24mg. (2mg is in line with what I am told by another person - that 2mg was so much that they actually felt a little sick. On the other hand, in one study, the subjects could not reliably distinguish between 1mg and placebo25.) 24mg is particularly troubling in that I weigh ~68kg, and nicotine poisoning and the nicotine LD50 start, for me, at around 68mg of nicotine. (I reflected that the entire jar could be a useful murder weapon, although nicotine presumably would be caught in an autopsy’s toxicology screen; I later learned nicotine was an infamous weapon in the 1800s before any test was developed. It doesn’t seem used anymore, but there are still fatal accidents due to dissolved nicotine.) The upper end of the range, 10mg/kg or 680mg for me, is calculated based on experienced smokers. Something is wrong here - I can’t see why I would have nicotine tolerance comparable to a hardened smoker, inasmuch as my maximum prior exposure was second-hand smoke once in a blue moon. More likely is that either the syringe is misleading me or the seller NicVape sold me something more dilute than 12mg/ml. (I am sure that it’s not simply plain water; when I mix the drops with regular water, I can feel the propylene glycol burning as it goes down.) I would rather not accuse an established and apparently well-liked supplier of fraud, nor would I like to simply shrug and say I have a mysterious tolerance and must experiment with doses closer to the LD50, so the most likely problem is a problem with the syringe. The next day I altered the procedure to sucking up 8ml, squirting out enough fluid to move the meniscus down to 7ml, and then ejecting the rest back into the container. The result was another mild clean stimulation comparable to the previous 1ml days. The next step is to try a completely different measuring device, which doesn’t change either.
This is not something you notice when you talk to Seltzer. And though our memory is probably at its peak in our early 20s, few 30-year-olds are aware of a deficit. But Seltzer considers himself a transhumanist, in the mould of the Oxford philosopher Nick Bostrom and the futuristic writer and inventor Ray Kurzweil. Transhumanists are interested in robots, cryogenics and living a really, really long time; they consider biological limitations that the rest of us might accept, or even appreciate, as creaky obstacles to be aggressively surmounted. On the ImmInst (Immortality Institute) forums, Seltzer and other members discuss life-extension strategies and the potential benefits of cognitive enhancers. Some members, Seltzer among them, use a drug called piracetam, which was first marketed by a Belgian pharmaceutical company in 1972 and in recent years has become available in the US from retailers that sell supplements. Although not approved for any use by the FDA, piracetam has been used experimentally on stroke patients - to little effect - and on patients with a rare neurological condition called progressive myoclonus epilepsy, for whom it proved helpful in alleviating muscle spasms. Data on piracetam's benefits for healthy people is virtually nonexistent, but many users believe that the drug increases blood flow to the brain.

One claim was partially verified in passing by Eliezer Yudkowsky (Supplementing potassium (citrate) hasn’t helped me much, but works dramatically for Anna, Kevin, and Vassar…About the same as drinking a cup of coffee - i.e., it works as a perker-upper, somehow. I’m not sure, since it doesn’t do anything for me except possibly mitigate foot cramps.)
Took pill around 6 PM; I had a very long drive to and from an airport ahead of me, ideal for Adderall. In case it was Adderall, I chewed up the pill - by making it absorb faster, more of the effect would be there when I needed it, during driving, and not lingering in my system past midnight. Was it? I didn’t notice any change in my pulse, I yawned several times on the way back, my conversation was not more voluminous than usual. I did stay up later than usual, but that’s fully explained by walking to get ice cream. All in all, my best guess was that the pill was placebo, and I feel fairly confident but not hugely confident that it was placebo. I’d give it ~70%. And checking the next morning… I was right! Finally.
Chocolate or cocoa powder (Examine.com), contains the stimulants caffeine and the caffeine metabolite theobromine, so it’s not necessarily surprising if cocoa powder was a weak stimulant. It’s also a witch’s brew of chemicals such as polyphenols and flavonoids some of which have been fingered as helpful10, which all adds up to an unclear impact on health (once you control for eating a lot of sugar).
Because modafinil works in a manner similar to methylphenidate, it also bears similar risks. The improper dosage or abuse of modafinil may lead to the disrupted development of executive controls like decision-making and working memory. Modafinil’s effects may also depend upon the IQ of the taker. Two university studies determined that in a test of sustained attention, modafinil only improved cognition in the group with “lower” IQs. Although safer than other stimulants due to its milder effect on neurotransmitter levels, there are still risks associated with any kind of drug that affects dopaminergic neurotransmission, mostly because this can lead to addiction and, similar to a pornography user who needs increasingly fringe porn to achieve the same effect, can produce a resistance or lowered sensitivity to dopamine.

A study published in the Journal of Environmental Healths Perspective stated that "researchers, physicians, and others poked around in the dark crevices of the gene, (are) trying to untangle the clues that suggested gene function could be altered by more than just changes in sequence." This ties in perfectly with what Dr. Lisa mentions about how our lifestyles play a crucial role in how/if we manifest a certain cognitive disfunction. Which brings us to our next question: What kind of "brain diet" can help support this lifestyle?
The problems with our mental functions begin if the blood flow to the brain cells is disrupted regardless of the reasons. There are countless capillaries in the head, which supply the brain with essential nutrients and oxygen. If the blood doesn’t get to these capillaries, your optimal mental performance is compromised. Here’s a term worth remembering – hypoperfusion. If you’re suffering from hypoperfusion, then this means you are having problems with the blood flow to your brain. Here’s a quick overview of the factors that most commonly cause hypoperfusion:

We reached out to several raw material manufacturers and learned that Phosphatidylserine and Huperzine A are in short supply. We also learned that these ingredients can be pricey, incentivizing many companies to cut corners.  A company has to have the correct ingredients in the correct proportions in order for a brain health formula to be effective. We learned that not just having the two critical ingredients was important – but, also that having the correct supporting ingredients was essential in order to be effective.
[…] The 7 Best Brain Boosting Supplements | Live in the Now … – … much research has indicated that certain supplements can help sustain and promote excellent brain function as we age. The supplements recommended by the Alzheimer’s Prevention and … Take adequate supplements for brain and help your kids to perform well in their tests by enhancing … […]

Pop this pill and improve your memory. Swallow that one and reduce your cognitive decline. We see ads for such products all the time and I suspect they will increase as the baby boomers reach senior citizenhood. The most popular brain boosting supplements are fish oil pills and they are also probably the best studied ones. The results are not encouraging.
Breathing carefully, I clutched the Costco special edition family size 1.5-liter glass bottle of vodka and carefully extracted 10 milliliters with a miniature glass pipette, which I then transferred into a small amber glass bottle. Then, with my nine-year-old son’s tiny set of school scissors, I snipped exactly 1/10 of LSD from the blotter square I’d ordered from a psychedelic research chemical supplier website the week prior, with a cloaked browser, of course, so the feds didn’t come knocking at my door. I dropped the LSD into the bottle, gave it a thirty-second shake, then placed the bottle in the pantry, next to my protein powder and creatine. I smiled. Within 24 hours, I’d be ready to sample my first homemade, volumetric “microdose” of a drug reported to increase lateral thinking patterns, improve creativity, massively boost productivity and much, much more.

We can read off the results from the table or graph: the nicotine days average 1.1% higher, for an effect size of 0.24; however, the 95% credible interval (equivalent of confidence interval) goes all the way from 0.93 to -0.44, so we cannot exclude 0 effect and certainly not claim confidence the effect size must be >0.1. Specifically, the analysis gives a 66% chance that the effect size is >0.1. (One might wonder if any increase is due purely to a training effect - getting better at DNB. Probably not26.)
L-Glutamine- One Of The 13 Essential Ingredients In Brain Fuel Plus… Perhaps the best fitting ingredient in our product’s name, L-Glutamine is the only compound besides blood sugar that can both cross the blood brain barrier AND be used by the brain for energy, which is why it is commonly called “brain fuel.” In fact L-Glutamine is involved in more metabolic processes than any other amino acid in the entire body. It is shown to promote mental alertness, improve mood and memory, and help with depression and irritability. It has even been shown to improve IQ.
Nootropics—the name given to a broad class of so-called "cognitive-enhancing" drugs—are all the rage in Silicon Valley these days. Programmers like nootropics because they’re said to increase productivity and sharpen focus without the intensity or side effects of a prescription drug like Adderall or modafinil. Some users mix their own nootropics using big bins of powders, purchased off the Internet or in supplement stores. And some take pre-made "stacks" that are designed to produce specific effects.
Clarke and Sokoloff (1998) remarked that although [a] common view equates concentrated mental effort with mental work…there appears to be no increased energy utilization by the brain during such processes (p. 664), and …the areas that participate in the processes of such reasoning represent too small a fraction of the brain for changes in their functional and metabolic activities to be reflected in the energy metabolism of the brain… (p. 675).
Taking the tryptophan is fairly difficult. The powder as supplied by Bulk Nutrition is extraordinarily dry and fine; it seems to be positively hydrophobic. The first time I tried to swallow a teaspoon, I nearly coughed it out - the power had seemed to explode in my mouth and go down my lungs. Thenceforth I made sure to have a mouth of water first. After a while, I took a different tack: I mixed in as much Hericium as would fit in the container. The mushroom powder is wetter and chunkier than the tryptophan, and seems to reduce the problem. Combining the mix with chunks of melatonin inside a pill works even better.
I took the first pill at 12:48 pm. 1:18, still nothing really - head is a little foggy if anything. later noticed a steady sort of mental energy lasting for hours (got a good deal of reading and programming done) until my midnight walk, when I still felt alert, and had trouble sleeping. (Zeo reported a ZQ of 100, but a full 18 minutes awake, 2 or 3 times the usual amount.)
Since coffee drinking may lead to a worsening of calcium balance in humans, we studied the serial changes of serum calcium, PTH, 1,25-dihydroxyvitamin D (1,25(OH)2D) vitamin D and calcium balance in young and adult rats after daily administration of caffeine for 4 weeks. In the young rats, there was an increase in urinary calcium and endogenous fecal calcium excretion after four days of caffeine administration that persisted for the duration of the experiment. Serum calcium decreased on the fourth day of caffeine administration and then returned to control levels. In contrast, the serum PTH and 1,25(OH)2D remained unchanged initially, but increased after 2 weeks of caffeine administration…In the adult rat group, an increase in the urinary calcium and endogenous fecal calcium excretion and serum levels of PTH was found after caffeine administration. However, the serum 1,25(OH)2D levels and intestinal absorption coefficient of calcium remained the same as in the adult control group.
I can’t try either of the products myself – I am pregnant and my doctor doesn’t recommend it – but my husband agrees to. He describes the effect of the Nootrobox product as like having a cup of coffee but not feeling as jittery. “I had a very productive day, but I don’t know if that was why,” he says. His Nootroo experience ends after one capsule. He gets a headache, which he is convinced is related, and refuses to take more. “It is just not a beginner friendly cocktail,” offers Noehr.
Factor analysis. The strategy: read in the data, drop unnecessary data, impute missing variables (data is too heterogeneous and collected starting at varying intervals to be clean), estimate how many factors would fit best, factor analyze, pick the ones which look like they match best my ideas of what productive is, extract per-day estimates, and finally regress LLLT usage on the selected factors to look for increases.

In 2011, as part of the Silk Road research, I ordered 10x100mg Modalert (5btc) from a seller. I also asked him about his sourcing, since if it was bad, it’d be valuable to me to know whether it was sourced from one of the vendors listed in my table. He replied, more or less, I get them from a large Far Eastern pharmaceuticals wholesaler. I think they’re probably the supplier for a number of the online pharmacies. 100mg seems likely to be too low, so I treated this shipment as 5 doses:
Awesome list. You are what you eat both mentally and physically. Studies have shown that food therapy can alleviate depression, anxiety and stress, as well as reduce chances of developing Alzheimer’s later on in life. Here’s an additional list of brain food recipes that can improve your clarity of thinking. http://www.brainieryou.com/product-descriptions/top-brain-food-recipe-ideas-for-2017
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We’d want 53 pairs, but Fitzgerald 2012’s experimental design called for 32 weeks of supplementation for a single pair of before-after tests - so that’d be 1664 weeks or ~54 months or ~4.5 years! We can try to adjust it downwards with shorter blocks allowing more frequent testing; but problematically, iodine is stored in the thyroid and can apparently linger elsewhere - many of the cited studies used intramuscular injections of iodized oil (as opposed to iodized salt or kelp supplements) because this ensured an adequate supply for months or years with no further compliance by the subjects. If the effects are that long-lasting, it may be worthless to try shorter blocks than ~32 weeks.
Piracetam is used to increase memory, learning, and concentration. It is not reported to be toxic even at high doses, but healthy people are reported to not get that much of a boost from it, and it is understood to be most effective for older people. It’s been found to reduce the chances of a breath-holding spell in children, enhance cellular membrane fluidity, and prevent blood clotting on par with aspirin.
Regardless, while in the absence of piracetam, I did notice some stimulant effects (somewhat negative - more aggressive than usual while driving) and similar effects to piracetam, I did not notice any mental performance beyond piracetam when using them both. The most I can say is that on some nights, I seemed to be less easily tired when writing or editing or n-backing (and I felt less tired than ICON 2011 than ICON 2010), but those were also often nights I was also trying out all the other things I had gotten in that order from Smart Powders, and I am still dis-entangling what was responsible. (Probably the l-theanine or sulbutiamine.)
One idea I’ve been musing about is the connections between IQ, Conscientiousness, and testosterone. IQ and Conscientiousness do not correlate to a remarkable degree - even though one would expect IQ to at least somewhat enable a long-term perspective, self-discipline, metacognition, etc! There are indications in studies of gifted youth that they have lower testosterone levels. The studies I’ve read on testosterone indicate no improvements to raw ability. So, could there be a self-sabotaging aspect to human intelligence whereby greater intelligence depends on lack of testosterone, but this same lack also holds back Conscientiousness (despite one’s expectation that intelligence would produce greater self-discipline and planning), undermining the utility of greater intelligence? Could cases of high IQ types who suddenly stop slacking and accomplish great things sometimes be due to changes in testosterone? Studies on the correlations between IQ, testosterone, Conscientiousness, and various measures of accomplishment are confusing and don’t always support this theory, but it’s an idea to keep in mind.
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.

The fact is, many of these compounds in small amounts and less frequent use can be relatively safe, but as you’re probably not surprised to hear, I’m not 100% convinced of the overall long-term safety or efficacy of most smart drugs used frequently or in moderate to high dosages for the reasons stated above. It is true that some are slightly less risky than others and are increasing in popularity among biohackers and medical professionals. They’re also becoming used with high frequency by students, athletes and e-gamers, three populations for which smart drug “doping control” is becoming more frequently banned and considered to be illegal use of performance-enhancing drugs. Yes, “brain doping” and “brain PED’s” (brain Performance Enhancing Drugs) are now a thing. But I’d consider carefully the use of smart drugs as daily go-to brain enhancing supplements, especially in light of the safer alternative you’re about to discover: the entire category of natural and synthetic nootropic compounds.
See Melatonin for information on effects & cost; I regularly use melatonin to sleep (more to induce sleep than prolong or deepen it), and investigating with my Zeo, it does seem to improve & shorten my sleep. Some research suggests that higher doses are not necessarily better and may be overkill, so each time I’ve run out, I’ve been steadily decreasing the dose from 3mg to 1.5mg to 1mg, without apparently compromising the usefulness.
At SelfHacked, it’s our goal to offer our readers all the tools possible to get optimally healthy. When I was struggling with chronic health issues I felt stuck because I didn’t have any tools to help me get better. I had to spend literally thousands of hours trying to read through studies on pubmed to figure out how the body worked and how to fix it.
These brain enhancers allow users to go without sleep for extended periods of time. But in the long-term, insomnia is a hazardous side effect, not a so-called benefit. Lack of sleep is extremely detrimental to your brain health and function. It’s during sleep that your brain consolidates memories, cleans away toxins, repairs itself, and creates new brain cells. (52, 53, 54, 55)
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.

Research in animals shows that blueberries may help protect the brain from the damage caused by free radicals and may reduce the effects of age-related conditions such as Alzheimer's disease or dementia. Studies also show that diets rich in blueberries improved both the learning and muscle function of aging rats, making them mentally equal to much younger rats.

Analgesics Anesthetics General Local Anorectics Anti-ADHD agents Antiaddictives Anticonvulsants Antidementia agents Antidepressants Antimigraine agents Antiparkinson agents Antipsychotics Anxiolytics Depressants Entactogens Entheogens Euphoriants Hallucinogens Psychedelics Dissociatives Deliriants Hypnotics/Sedatives Mood Stabilizers Neuroprotectives Nootropics Neurotoxins Orexigenics Serenics Stimulants Wakefulness-promoting agents
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