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.)
Similarly, we could try applying Nick Bostrom’s reversal test and ask ourselves, how would we react to a virus which had no effect but to eliminate sleep from alternating nights and double sleep in the intervening nights? We would probably grouch about it for a while and then adapt to our new hedonistic lifestyle of partying or working hard. On the other hand, imagine the virus had the effect of eliminating normal sleep but instead, every 2 minutes, a person would fall asleep for a minute. This would be disastrous! Besides the most immediate problems like safely driving vehicles, how would anything get done? You would hold a meeting and at any point, a third of the participants would be asleep. If the virus made it instead 2 hours on, one hour off, that would be better but still problematic: there would be constant interruptions. And so on, until we reach our present state of 16 hours on, 8 hours off. Given that we rejected all the earlier buffer sizes, one wonders if 16:8 can be defended as uniquely suited to circumstances. Is that optimal? It may be, given the synchronization with the night-day cycle, but I wonder; rush hour alone stands as an argument against synchronized sleep - wouldn’t our infrastructure would be much cheaper if it only had to handle the average daily load rather than cope with the projected peak loads? Might not a longer cycle be better? The longer the day, the less we are interrupted by sleep; it’s a hoary cliche about programmers that they prefer to work in long sustained marathons during long nights rather than sprint occasionally during a distraction-filled day, to the point where some famously adopt a 28 hour day (which evenly divides a week into 6 days). Are there other occupations which would benefit from a 20 hour waking period? Or 24 hour waking period? We might not know because without chemical assistance, circadian rhythms would overpower anyone attempting such schedules. It certainly would be nice if one had long time chunks in which could read a challenging book in one sitting, without heroic arrangements.↩
A randomized non-blind self-experiment of LLLT 2014-2015 yields a causal effect which is several times smaller than a correlative analysis and non-statistically-significant/very weak Bayesian evidence for a positive effect. This suggests that the earlier result had been driven primarily by reverse causation, and that my LLLT usage has little or no benefits.
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]
Because it’s so nutrient-dense — packing loads of vitamins, minerals and nutrients with very little calories — it’s a great snack option if you’re looking to shed pounds. And while we often eat celery stalks, don’t skip the seeds and leaves; both provide extra health benefits and taste great in things like stir fries and soups. Not sure where to begin with eating more celery? Try my easy Ants on a Log or refreshing Super Hydrator Juice recipes.
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. 
Though coffee gives instant alertness and many cups of the beverage are downed throughout the day, the effect lasts only for a short while. People who drink coffee every day may develop caffeine tolerance; this is the reason why it is still important to control your daily intake. It is advisable that an individual should not consume more than 300mg of coffee a day. Caffeine, the world’s favourite nootropic has very less side effects but if consumed abnormally high can result in nausea, restlessness, nervousness and hyperactivity. This is the reason why people who need increased sharpness would rather induce L-theanine, or some other Nootropic, along with caffeine. Today, you can find various smart drugs that contain caffeine in them. OptiMind , one of the best and most sought-after nootropic in the U.S, containing caffeine, is considered more effective and efficient when compared to other focus drugs present in the market today.
Ampakines are structurally derived from a popular nootropic called “aniracetam”. Their basic function is to activate AMPA glutamate receptors (AMPARs). Glutamate (a neurotransmitter) is the primary mediator of excitatory synaptic transmission in mammalian brains, which makes it crucial for synaptic plasticity (the adaptation of synapses, the space between neurons across which information is sent), learning and memory, so when you activate or stimulate glutamate receptors, you can trigger many of these functions. AMPARs are distributed across the central nervous system and are stimulated by incoming glutamate to begin the neuroenhancing benefits they’re often used for. But it is possible to have too much glutamate activity. When excess glutamate is produced, accumulates and binds to AMPARs, the result is excitotoxicity, which is a state of cell death (in the case of the central nervous system and your brain, neuron death) resulting from the toxic levels of excitatory amino acids. Excitotoxicity is believed to play a major role in the development of various degenerative neurological conditions such as schizophrenia, delirium and dementia.

I'm not mad, I'm disappointed. This product did not work at all. It didn't even feel like it was just a caffeine pill (usually what supplements that don't work are actually made of). It literally does nothing. In hindsight, I feel like I did when I was a kid and ordered $4.50 X-ray sunglasses from the back of a comic book. Deep down knew it was too good to be true, but secretly I hoped it would work. Shame on me for getting sucked into a bunch of hype.
After many years recruiting teens from across the city to join us for a year of culinary adventures, we’re relying on the city’s network of talented youth service providers to fill the gap and cultivate the next generation of smart, resilient youth leaders. While this isn’t where we wanted to be, we’re reaching for gratitude and sharing KUDOS one last time.
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?

Smart drugs offer significant memory enhancing benefits. Clinical studies of the best memory pills have shown gains to focus and memory. Individuals seek the best quality supplements to perform better for higher grades in college courses or become more efficient, productive, and focused at work for career advancement. It is important to choose a high quality supplement to get the results you want.
One item always of interest to me is sleep; a stimulant is no good if it damages my sleep (unless that’s what it is supposed to do, like modafinil) - anecdotes and research suggest that it does. Over the past few days, my Zeo sleep scores continued to look normal. But that was while not taking nicotine much later than 5 PM. In lieu of a different ml measurer to test my theory that my syringe is misleading me, I decide to more directly test nicotine’s effect on sleep by taking 2ml at 10:30 PM, and go to bed at 12:20; I get a decent ZQ of 94 and I fall asleep in 16 minutes, a bit below my weekly average of 19 minutes. The next day, I take 1ml directly before going to sleep at 12:20; the ZQ is 95 and time to sleep is 14 minutes.
She provides many examples of observational studies where lower intakes of a certain nutrient were correlated with cognitive impairment. Obviously, if someone is deficient in a vitamin or other nutrient, the deficiency should be corrected. But she doesn’t have any evidence from prospective interventional studies showing that, in practice, altering diet significantly improves cognition for people who are deficient, much less in people who are not deficient.
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 treat obesity; 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. 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. 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. Keep out of reach of children. Do not use if safety seal is damaged or missing. Store at a room temperature. Avoid 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. Use cautiously in patients with history of seizure, based on reports of seizure due to Ginkgo seed ingestion. Not intended for children under 18 years of age. Avoid use in couples who are trying to conceive, based on theoretical reduction of fertility. Pregnant or nursing mothers, children under 18, individuals making MAO inhibiting Drugs, or with a known medical condition should consult a physician before using this or any dietary supplement.
And without those precious nutrients, your brain will start to wither. In a recent Bulletproof Radio podcast episode [iTunes], I talked with neuroscientist Dale Bredesen about why neurodegeneration happens. One of the three most common causes of brain aging is a lack of specific brain nutrients (check out the episode to hear about the other two main causes of brain aging, and what you can do about them).
Though coffee gives instant alertness and many cups of the beverage are downed throughout the day, the effect lasts only for a short while. People who drink coffee every day may develop caffeine tolerance; this is the reason why it is still important to control your daily intake. It is advisable that an individual should not consume more than 300mg of coffee a day. Caffeine, the world’s favourite nootropic has very less side effects but if consumed abnormally high can result in nausea, restlessness, nervousness and hyperactivity. This is the reason why people who need increased sharpness would rather induce L-theanine, or some other Nootropic, along with caffeine. Today, you can find various smart drugs that contain caffeine in them. OptiMind , one of the best and most sought-after nootropic in the U.S, containing caffeine, is considered more effective and efficient when compared to other focus drugs present in the market today.

When you start taking legit nootropics, you get to leave all of that behind you.  You may never achieve perfect concentration (most of us never will), but you should find you are able to concentrate on the task at hand for much longer than you do now.  You will end up taking fewer breaks, and you might start finishing up your work on time each day again—or even early!

1 PM; overall this was a pretty productive day, but I can’t say it was very productive. I would almost say even odds, but for some reason I feel a little more inclined towards modafinil. Say 55%. That night’s sleep was vile: the Zeo says it took me 40 minutes to fall asleep, I only slept 7:37 total, and I woke up 7 times. I’m comfortable taking this as evidence of modafinil (half-life 10 hours, 1 PM to midnight is only 1 full halving), bumping my prediction to 75%. I check, and sure enough - modafinil.
“We stumbled upon fasting as a way to optimize cognition and make yourself into a more efficient human being,” says Manuel Lam, an internal medicine physician who advises Nootrobox on clinical issues. He and members of the company’s executive team have implanted glucose monitors in their arms — not because they fear diabetes but because they wish to track the real-time effect of the foods they eat.
By the way, before we move on, allow me to clarify what I mean by “slow caffeine metabolizer”. Ever wondered why your co-worker can slam four giant mugs of coffee during a brief morning of work, while one shot of espresso leaves you jittery and irritated? Turns out that not everyone metabolizes caffeine the same. Generally speaking, in healthy adults, caffeine has a half-life that ranges from about 3 to 7 hours. For example, if the half-life of caffeine in your blood is 5 hours, that means that it takes 5 hours for caffeine levels to be reduced by 50%. Then it takes another 5 hours for that amount to be reduced by 50%. While caffeine metabolism time also depends upon age and environmental factors, a big influence on varying caffeine half-life times is your genetic makeup.

On 8 April 2011, I purchased from Smart Powders (20g for $8); as before, some light searching seemed to turn up SP as the best seller given shipping overhead; it was on sale and I planned to cap it so I got 80g. This may seem like a lot, but I was highly confident that theanine and I would get along since I already drink so much tea and was a tad annoyed at the edge I got with straight caffeine. So far I’m pretty happy with it. My goal was to eliminate the physical & mental twitchiness of caffeine, which subjectively it seems to do.
She repeats the oft-refuted advice to drink at least 8 glasses of water a day. She claims that drinking water improves cognitive performance. Her citation for that claim is a small study in which participants were instructed to fast overnight and not eat or drink anything after 9 pm, so they were presumably somewhat dehydrated. There is no evidence that people who are not dehydrated benefit from increasing water intake.
Vitamin D is probably the most important supplement you can take, and one of the best brain food. It acts on more than over 1,000 different genes and is a substrate for testosterone, progesterone, estradiol, and other  hormones.[1] It also influences inflammation and brain calcium absorption.[2] No surprise that optimal vitamin D levels are linked to stronger cognitive function and slower brain aging.[3][4]

NeuroFuse was almost there with a top quality product but we felt that there were several key elements missing. It does contain a lot of the top natural ingredients for cognitive energy enhancement. However, the fact that their money-back guarantee is not apparent and that they are baiting customers in using a 14-day free trial offer, made us slightly wary. If they addressed these issues, we felt that this could have been a winner!
Nootropic (new-tro-pik) is the term for supplements, also known as smart drugs, that improve brain function. They can be food substances like phenethylamine and L-Theanine, found in chocolate and green tea, respectively. Nootropics also include extracted and purified components of medicinal plants, as well as substances synthesized from chemical precursors, such as piracetam, the world's first official nootropic (piracetam was created in 1964 in Belgium by a team of scientists whose leader, Dr. Corneliu E. Giurgea, coined the term). Since then piracetam has been widely used as a cognitive enhancer and to treat neurological diseases like Alzheimer's.
Caffeine keeps you awake, which keeps you coding. It may also be a nootropic, increasing brain-power. Both desirable results. However, it also inhibits vitamin D receptors, and as such decreases the body’s uptake of this-much-needed-vitamin. OK, that’s not so bad, you’re not getting the maximum dose of vitamin D. So what? Well, by itself caffeine may not cause you any problems, but combined with cutting off a major source of the vitamin - the production via sunlight - you’re leaving yourself open to deficiency in double-quick time.
Can the Folic Acid in this Supplement be Taken by Men? Folic acid is most well-known for its use in prenatal vitamins during pregnancy and breastfeeding. However, it is an important nutrient for the bodies of both men and women. The level of folic acid in Cognizance is nowhere near as high as the levels found in prenatal vitamins taken during pregnancy, making it safe for use by both genders. Is it Safe? All of the ingredients in Cognizance have been tested individually for their safety of use. They have also been monitored in use together, to ensure there are no side effects from the combination of ingredients.1 Though Cognizance is safe, you should still speak to your doctor if you are under the age of 18, have a pre-existing medical condition, or are a woman who is pregnant or nursing.
Caffeine (Examine.com; FDA adverse events) is of course the most famous stimulant around. But consuming 200mg or more a day, I have discovered the downside: it is addictive and has a nasty withdrawal - headaches, decreased motivation, apathy, and general unhappiness. (It’s a little amusing to read academic descriptions of caffeine addiction9; if caffeine were a new drug, I wonder what Schedule it would be in and if people might be even more leery of it than modafinil.) Further, in some ways, aside from the ubiquitous placebo effect, caffeine combines a mix of weak performance benefits (Lorist & Snel 2008, Nehlig 2010) with some possible decrements, anecdotally and scientifically:

I have no particularly compelling story for why this might be a correlation and not causation. It could be placebo, but I wasn’t expecting that. It could be selection effect (days on which I bothered to use the annoying LED set are better days) but then I’d expect the off-days to be below-average and compared to the 2 years of trendline before, there doesn’t seem like much of a fall.

Brain Pill™ combines the most powerful, clinically proven ingredients on the forefront of brain productivity and memory research. Each of our carefully selected ingredients is potent and effective on its own, but together, our research goal was to create far and away the ultimate synergistic combination for enhancing mental clarity, alertness and overall brain function.
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.
Microdosing With Psilocybin: Psilocybin, AKA “magic mushrooms”, are naturally occurring fungi, with over 180 different species and research from archaeologist evidence has shown that humans have been using psilocybin mushrooms for over 7,000 years. I’ve personally found microdoses of psilocybin, AKA “magic mushrooms”, to be best for nature immersions, hiking, journaling or self-discovery.  Psilocybin primarily interacts with the serotonin receptors in the brain and has been used in therapeutic settings to treat disorders such as headaches, anxiety, depression, addiction, and obsessive-compulsive disorders (See additional studies here, here, here and here). There is limited data to show any adverse drug interactions with the use of psilocybin, and liver function, blood sugar, and hormonal regulation all appear to be unaffected during consumption (although it is best to avoid alcohol and any serotonin-based antidepressants while taking any psychedelics) (See studies here, here and here). A microdose of psilocybin is generally between 0.2 grams and .5 grams, and I’d highly recommend you start on the low end of the dosage range with these or any of the psychedelics mentioned here.
But there’s a surprising lack of skepticism in the room. That’s because this is a weekly meetup of amateur biohackers. In fact, positivity is one of their ground rules. Members share experiences with ketogenic diets, biofeedback apps, sensory-deprivation tanks, and, lately, a class of smart drugs known as “nootropics.” Their primary obsession is brain enhancement.

Took full pill at 10:21 PM when I started feeling a bit tired. Around 11:30, I noticed my head feeling fuzzy but my reading seemed to still be up to snuff. I would eventually finish the science book around 9 AM the next day, taking some very long breaks to walk the dog, write some poems, write a program, do Mnemosyne review (memory performance: subjectively below average, but not as bad as I would have expected from staying up all night), and some other things. Around 4 AM, I reflected that I felt much as I had during my nightwatch job at the same hour of the day - except I had switched sleep schedules for the job. The tiredness continued to build and my willpower weakened so the morning wasn’t as productive as it could have been - but my actual performance when I could be bothered was still pretty normal. That struck me as kind of interesting that I can feel very tired and not act tired, in line with the anecdotes.
Specifically, the film is completely unintelligible if you had not read the book. The best I can say for it is that it delivers the action and events one expects in the right order and with basic competence, but its artistic merits are few. It seems generally devoid of the imagination and visual flights of fancy that animated movies 1 and 3 especially (although Mike Darwin disagrees), copping out on standard imagery like a Star Wars-style force field over Hogwarts Castle, or luminescent white fog when Harry was dead and in his head; I was deeply disappointed to not see any sights that struck me as novel and new. (For example, the aforementioned dead scene could have been done in so many interesting ways, like why not show Harry & Dumbledore in a bustling King’s Cross shot in bright sharp detail, but with not a single person in sight and all the luggage and equipment animatedly moving purposefully on their own?) The ending in particular boggles me. I actually turned to the person next to me and asked them whether that really was the climax and Voldemort was dead, his death was so little dwelt upon or laden with significance (despite a musical score that beat you over the head about everything else). In the book, I remember it feeling like a climactic scene, with everyone watching and little speeches explaining why Voldemort was about to be defeated, and a suitable victory celebration; I read in the paper the next day a quote from the director or screenwriter who said one scene was cut because Voldemort would not talk but simply try to efficiently kill Harry. (This is presumably the explanation for the incredible anti-climax. Hopefully.) I was dumbfounded by the depths of dishonesty or delusion or disregard: Voldemort not only does that in Deathly Hallows multiple times, he does it every time he deals with Harry, exactly as the classic villains (he is numbered among) always do! How was it possible for this man to read the books many times, as he must have, and still say such a thing?↩
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Apart from the risks that accompany drugs with dopaminergic effects, amphetamines, even when used to treat neurological disorders like ADHD, have been known to frequently and predictably cause anorexia, weight loss and insomnia. High doses can cause psychotic behavior, and even normal doses have been known to produce psychosis that ranged from the loss of short-term memory to horrific visual and auditory hallucinations. Are you getting the impression that using synthetic stimulants to flood your brain short-term with excessive or unnaturally high levels of hormones and neurotransmitters may not be a good idea, especially when done frequently or in excess?

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.
50 pairs of active/placebos or 100 days. With 120 tablets and 4 tablets used up, that leaves me 58 doses. That might seem adequate except the paired t-test approximation is overly-optimistic, and I also expect the non-randomized non-blinded correlation is too high which means that is overly-optimistic as well. The power would be lower than I’d prefer. I decided to simply order another bottle of Solgar’s & double the sample size to be safe.
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.

Traditional Chinese medicine also has a long, well-established relationship with nootropic herbs and plants. One of the most popular and well-known is ginkgo biloba, derived from the Chinese maidenhair tree, a relic of the ancient world. The maidenhair tree is the last living species of the division Ginkgophyta>. Some believe that the name ginkgo is a misspelling of the original Japanese gin kyo, meaning “silver apricot”. It’s seen as a symbol of longevity and vitality and is known to be effective at stimulating the growth of new neurons. Researchers have demonstrated that ginkgo flavonoids, the main constituents in ginkgo extract, provide potent anti-Alzheimer’s effects via antioxidant activity in the brains of mice and also stabilize and improve the cognitive performance of Alzheimer patients for 6 months to 1 year. Effective doses range from 120 to 240 mg one to four hours before performance, and for older adults, doses range from 40 to 120 mg three times a day.
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.)

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.
She reveals where she went astray. In a lecture she gave, she lamented the failure of science to offer a cure for Alzheimer’s or even an effective treatment. Someone in the audience asked, “How about olive oil?” She realized she didn’t know anything about the effects of nutrition on Alzheimer’s. She seems to have assumed that diet must be crucially important, and for some reason instead of studying conventional nutrition science, she got a degree in Holistic Nutrition. She bills herself as a certified Integrative Nutritionist and holistic healthcare practitioner. I couldn’t find where she studied, but Stephen Barrett has criticized the Institute for Integrative Nutrition on Quackwatch. Its training is not based on scientific nutrition. It seems most programs in Integrative Nutrition are 6- to 8-month correspondence courses with no prerequisites. I wonder what she was taught.
I took the pill at 11 PM the evening of (technically, the day before); that day was a little low on sleep than usual, since I had woken up an hour or half-hour early. I didn’t yawn at all during the movie (merely mediocre to my eyes with some questionable parts)23. It worked much the same as it did the previous time - as I walked around at 5 AM or so, I felt perfectly alert. I made good use of the hours and wrote up my memories of ICON 2011.
If you are in or are able to come to London, you may be interested in also coming to a one day workshop we are hosting with Patrick Holford, our founder and one the UK’s leading nutritional therapists. We are excited to be running this workshop, which enables our supporters to access Patrick’s wealth of knowledge on nutrition and mental health. More details can be found below. If you are outside of the UK and are interested in this workshop or learning more about nutrition and mental health, please sign up for news on our Seminar series here. 
“In an era of confusion about what we should eat, Brain Food is a shining light. This is the straight story about ‘neuro-nutrition’ firmly rooted in research by a neuroscientist who has a deep understanding of how food affects our cognitive health. Dr. Mosconi gives us advice we can easily implement into our lives and a story about the science behind it that is both delightful and accessible. A must read!”
“Who doesn’t want to maximize their cognitive ability? Who doesn’t want to maximize their muscle mass?” asks Murali Doraiswamy, who has led several trials of cognitive enhancers at Duke University Health System and has been an adviser to pharmaceutical and supplement manufacturers as well as the Food and Drug Administration. He attributes the demand to an increasingly knowledge-based society that values mental quickness and agility above all else.
Armodafinil is sort of a purified modafinil which Cephalon sells under the brand-name Nuvigil (and Sun under Waklert21). Armodafinil acts much the same way (see the ADS Drug Profile) but the modafinil variant filtered out are the faster-acting molecules22. Hence, it is supposed to last longer. as studies like Pharmacodynamic effects on alertness of single doses of armodafinil in healthy subjects during a nocturnal period of acute sleep loss seem to bear out; anecdotally, it’s also more powerful, with Cephalon offering pills with doses as low as 50mg. (To be technical, modafinil is racemic: it comes in two forms which are rotations, mirror-images of each other. The rotation usually doesn’t matter, but sometimes it matters tremendously - for example, one form of thalidomide stops morning sickness, and the other rotation causes hideous birth defects.)
Vinpocetine: This chemical is a semi-synthetic derivative of an extract from periwinkle.  It acts as a potent anti-inflammatory agent, and has also received some testing as a supplement for memory enhancement.  While research results are inconclusive right now, this chemical has been shown to increase blood circulation and metabolism in the brain and may slow down neuron loss.  Some tests have also shown that it can improve concentration and attention.

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.
Pre and Post-Natal Depression are both complex conditions that can have multifactorial underlying drivers, including genetic and environmental influences. These are currently poorly investigated and the gold standard of treatment is often medication to help stabilise mood. Whilst SSRIs and other types of antidepressants have proven to be helpful for many, they do not address potential causes or drivers of poor mental health and can often mask symptoms. Antidepressants are also not regularly recommended during pregnancy, which is why being more mindful of nutrition and lifestyle habits can be a safer option for you and your baby. There are some natural, evidence-based steps you can take to help support optimal mental wellbeing:
Beans. Beans are "under-recognized" and "economical," says Kulze. They also stabilize glucose (blood sugar) levels. The brain is dependent on glucose for fuel, Kulze explains, and since it can't store the glucose, it relies on a steady stream of energy -- which beans can provide. Any beans will do, says Kulze, but she is especially partial to lentils and black beans and recommends 1/2 cup every day.
Cephalon executives have repeatedly said that they do not condone off-label use of Provigil, but in 2002 the company was reprimanded by the FDA for distributing marketing materials that presented the drug as a remedy for tiredness, "decreased activity" and other supposed ailments. And in 2008 Cephalon paid $425m and pleaded guilty to a federal criminal charge relating to its promotion of off-label uses for Provigil and two other drugs. Later this year, Cephalon plans to introduce Nuvigil, a longer-lasting variant of Provigil. Candace Steele, a spokesperson, said: "We're exploring its possibilities to treat excessive sleepiness associated with schizophrenia, bipolar depression, traumatic injury and jet lag." Though she emphasised that Cephalon was not developing Nuvigil as a neuroenhancer, she noted: "As part of the preparation for some of these diseases, we're looking to see if there's improvement in cognition."
Modafinil is not addictive but there may be chances of drug abuse and memory impairment.  This can manifest in people who consume it to stay up for way too long, as a result, this would probably make them sick. Long-term use of Modafinil may reduce plasticity and can have an adverse effect on the memory of some individuals. Hence it is sold only on prescription by a qualified physician.
To understand further about how food intolerances can impact our mental health, it is important to explain the relationship between our gut microbiome, the immune system and our brain in a little more detail. The walls of our digestive tract provide a barrier between what we eat and the rest of our body and an unhealthy gut microbiome can lead to increased levels of inflammation, leaving the walls vulnerable to structural damage (4). Our intestinal wall is composed of cell junctions that prevent bacteria and large food molecules from entering the bloodstream, however, if these become damaged, proteins from foods that should not be circulating in our bloodstream can enter and an immune response is mounted as a reaction. This response is mediated by IgG, an antibody, that helps to protect against bacterial and viral infections as well as food antigens and is the most abundant immune cell in the body. Whilst food antigens are usually quickly cleared by an intelligent system called the reticuloendothelial system, with structural damage and a poor gut microbiome, this immune response can keep reoccurring. It is suggested that a chronic immune response such as this can have a negative impact on the brain, damaging its own structural barrier, called the Blood Brain Barrier (5).

The acid is also known to restore the vitamin C and E levels in the body. Alpha Lipoic Acid’s efficient antioxidant property protects brain cells from damage during any injury. This helps in making sure that your brain functions normally even if there is any external or internal brain injury. OptiMind, one of the best nootropic supplements that you can find today contains Alpha Lipoic Acid that can help in enhancing your brain’s capabilities.
Choline is a nootropic: it enhances your ability to pay attention and learn efficiently,[18] probably because you use a lot of acetylcholine during mentally-demanding tasks, and choline helps you synthesize enough to work harder and go longer.[19] Choline also links to decreased brain inflammation in a dose-dependent manner — the more choline you eat, the less inflamed your brain tends to be.[20]
Flaxseed oil is, ounce for ounce, about as expensive as fish oil, and also must be refrigerated and goes bad within months anyway. Flax seeds on the other hand, do not go bad within months, and cost dollars per pound. Various resources I found online estimated that the ALA component of human-edible flaxseed to be around 20% So Amazon’s 6lbs for $14 is ~1.2lbs of ALA, compared to 16fl-oz of fish oil weighing ~1lb and costing ~$17, while also keeping better and being a calorically useful part of my diet. The flaxseeds can be ground in an ordinary food processor or coffee grinder. It’s not a hugely impressive cost-savings, but I think it’s worth trying when I run out of fish oil.
Dr Hart explained how communication between the gut and the brain is controlled via our immune system, our endocrine system (hormones) and our central nervous system, which are all under the influence of the bacteria in our gut. The types and amount of these bacteria, known as our gut microbiome, can be directly impacted by factors such as diet, stress, pollution and medications (2) and the composition of the microbiome is also understood to affect one’s susceptibility to food sensitivities and intolerances (3).  
“We didn’t see significant long-term effects from the dosage used,” said Wen-Jun Gao, a professor of neurobiology at the Drexel University College of Medicine, and one of the authors of the study. He added that the brain doesn’t fully stop developing until age 25 or 30, making cognitive enhancement potentially risky even for users who are well into adulthood.
At small effects like d=0.07, a nontrivial chance of negative effects, and an unknown level of placebo effects (this was non-blinded, which could account for any residual effects), this strongly implies that LLLT is not doing anything for me worth bothering with. I was pretty skeptical of LLLT in the first place, and if 167 days can’t turn up anything noticeable, I don’t think I’ll be continuing with LLLT usage and will be giving away my LED set. (Should any experimental studies of LLLT for cognitive enhancement in healthy people surface with large quantitative effects - as opposed to a handful of qualitative case studies about brain-damaged people - and I decide to give LLLT another try, I can always just buy another set of LEDs: it’s only ~$15, after all.)
I have personally found that with respect to the NOOTROPIC effect(s) of all the RACETAMS, whilst I have experienced improvements in concentration and working capacity / productivity, I have never experienced a noticeable ongoing improvement in memory. COLURACETAM is the only RACETAM that I have taken wherein I noticed an improvement in MEMORY, both with regards to SHORT-TERM and MEDIUM-TERM MEMORY. To put matters into perspective, the memory improvement has been mild, yet still significant; whereas I have experienced no such improvement at all with the other RACETAMS.
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.)
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 treat obesity; 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. 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. 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. Keep out of reach of children. Do not use if safety seal is damaged or missing. Store at a room temperature. Avoid 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. Use cautiously in patients with history of seizure, based on reports of seizure due to Ginkgo seed ingestion. Not intended for children under 18 years of age. Avoid use in couples who are trying to conceive, based on theoretical reduction of fertility. Pregnant or nursing mothers, children under 18, individuals making MAO inhibiting Drugs, or with a known medical condition should consult a physician before using this or any dietary supplement.
Past noon, I began to feel better, but since I would be driving to errands around 4 PM, I decided to not risk it and take an hour-long nap, which went well, as did the driving. The evening was normal enough that I forgot I had stayed up the previous night, and indeed, I didn’t much feel like going to bed until past midnight. I then slept well, the Zeo giving me a 108 ZQ (not an all-time record, but still unusual).

I find this very troubling. The magnesium supplementation was harmful enough to do a lot of cumulative damage over the months involved (I could have done a lot of writing September 2013 - June 2014), but not so blatantly harmful enough as to be noticeable without a randomized blind self-experiment or at least systematic data collection - neither of which are common among people who would be supplementing magnesium I would much prefer it if my magnesium overdose had come with visible harm (such as waking up in the middle of the night after a nightmare soaked in sweat), since then I’d know quickly and surely, as would anyone else taking magnesium. But the harm I observed in my data? For all I know, that could be affecting every user of magnesium supplements! How would we know otherwise?


-Water [is also important]. Over 80% of the brain’s content is water. Every chemical reaction that takes place in the brain needs water, especially energy production. The brain is so sensitive to dehydration that even a minimal loss of water can cause symptoms like brain fog, fatigue, dizziness, confusion and, more importantly, brain shrinkage. The longevity and well-being of your brain are critically dependent upon consuming hard water. This refers to plain water that is high in minerals and natural electrolytes. Most people don’t realize that the water they’re drinking is not actually “water”.
Traditional Chinese medicine also has a long, well-established relationship with nootropic herbs and plants. One of the most popular and well-known is ginkgo biloba, derived from the Chinese maidenhair tree, a relic of the ancient world. The maidenhair tree is the last living species of the division Ginkgophyta>. Some believe that the name ginkgo is a misspelling of the original Japanese gin kyo, meaning “silver apricot”. It’s seen as a symbol of longevity and vitality and is known to be effective at stimulating the growth of new neurons. Researchers have demonstrated that ginkgo flavonoids, the main constituents in ginkgo extract, provide potent anti-Alzheimer’s effects via antioxidant activity in the brains of mice and also stabilize and improve the cognitive performance of Alzheimer patients for 6 months to 1 year. Effective doses range from 120 to 240 mg one to four hours before performance, and for older adults, doses range from 40 to 120 mg three times a day.
Here’s a thing or two you should know about your brain, so you can have a better understanding of natural brain supplements. This is the most important organ in our body that controls every single action we take. On the other hand, this importance comes at the huge price for our body’s energy levels. Our brain usually requires up to 20% of the body’s energy to function properly. The energy consumption can easily rise above 60%, if your brain engages in a series of intense mental activities.

Take quarter at midnight, another quarter at 2 AM. Night runs reasonably well once I remember to eat a lot of food (I finish a big editing task I had put off for weeks), but the apathy kicks in early around 4 AM so I gave up and watched Scott Pilgrim vs. the World, finishing around 6 AM. I then read until it’s time to go to a big shotgun club function, which occupies the rest of the morning and afternoon; I had nothing to do much of the time and napped very poorly on occasion. By the time we got back at 4 PM, the apathy was completely gone and I started some modafinil research with gusto (interrupted by going to see Puss in Boots). That night: Zeo recorded 8:30 of sleep, gap of about 1:50 in the recording, figure 10:10 total sleep; following night, 8:33; third night, 8:47; fourth, 8:20 (▇▁▁▁).
At this point, I discovered I had run out of magnesium pills and had forgotten to order the magnesium citrate powder I’d intended to. I still had a lot of Noopept pills for the concurrently running second Noopept self-experiment, but since I wanted to wrap up some other experiments with a big analysis at the end of the year, I decided to halt and resume in January 2014.

For this batch, I tried out NOW Foods Magnesium Citrate Powder ($7 for 227g); the powder was still a bit sticky but much easier to work with than the Solgar pills, and the 227g made 249 gel capsule pills. The package estimates 119 serving of 315mg elemental magnesium, so a ratio of 0.315g magnesium for 1.9g magnesium citrate, implying that each gel cap pill then contains 0.152g magnesium (\frac{(119\times315)}{249}=150) and since I want a total dose of 0.8g, I need 5 of the gel cap pills a day or 35 per block.


The evidence? In small studies, healthy people taking modafinil showed improved planning and working memory, and better reaction time, spatial planning, and visual pattern recognition. A 2015 meta-analysis claimed that “when more complex assessments are used, modafinil appears to consistently engender enhancement of attention, executive functions, and learning” without affecting a user’s mood. In a study from earlier this year involving 39 male chess players, subjects taking modafinil were found to perform better in chess games played against a computer.
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.
Board-certified neuropsychologist Brian Lebowitz, PhD and associate clinical professor of neurology at Stony Brook University, explains to MensHealth.com that the term "encompasses so many things," including prescription medications. Brain enhancers fall into two different categories: naturally occurring substances like Ginkgo biloba, creatine and phenibut; and manmade prescription drugs, like Adderall, and over-the-counter supplements such as Noopept.
If all of this sounds great to you, get ready to level up your brain to game like a god with GodMode. Unless, you know, you're under 18, pregnant, potentially have any pre-existing medical conditions, are taking any prescription medications, are otherwise ingesting caffeine or taking other stimulants, or you don't want to drop $60 on gamer pills. Then, you know, don't.
Since the discovery of the effect of nootropics on memory and focus, the number of products on the market has increased exponentially. The ingredients used in a supplement can tell you about the effectiveness of the product. Brain enhancement pills that produce the greatest benefit are formulated with natural vitamins and substances, rather than caffeine and synthetic ingredients. In addition to better results, natural supplements are less likely to produce side effects, compared with drugs formulated with chemical ingredients.
The task of building a better mousetrap just got a lot harder. Scientists at Princeton University recently created a strain of smarter mice by inserting a gene that boosts the activity of brain cells. The mice can learn to navigate mazes and find or recognize objects faster than run-of-the-mill rodents. The news, announced in the Sept. 2, 1999 issue of the journal Nature, raises the possibility that genetic engineers may someday be able to help humans learn and remember faster, too.
The low-carb & high-fat diet (includes keto-diet) are not good for you because the brain needs glucose for fuel. It can burn fat. But, the brain’s preferred energy source is glucose. The key is to provide the brain with glucose without raising glucose/serum blood level. You do that by avoiding sugar and eating complex carbohydrates (fresh produce) that convert into glucose.

Dr Hart talked through food intolerance tests that are available through a number of well known companies, including York Test for whom she is Scientific Director. A possible strategy could be to use such testing to identify intolerances, follow an elimination protocol, temporarily removing on foods triggering an IgG response; and then work to improve your gut health to support longer term well-being. Foods that are rich in collagen and its amino acids, like glycine and proline, are great for healing connective tissue, which is what the intestines are made up of. A traditional food, rich in these amino acids, that has made its way into our kitchens again after rediscovering its therapeutic properties is bone broth. Another example of a group of traditional foods that can be used therapeutically in building digestive health, are fermented foods such as kefir, sauerkraut and kimchi. These are abundant in probiotics, which are the ‘good’ bacteria our digestive system needs to help keep a good balance and protect the intestinal barrier from pathogens, toxins and parasites. Once these foods have been introduced on an everyday basis along with eating a healthy nutrient-dense diet and the possible use of supplements to help restore balance, you may be able to reintroduce foods that were previously triggering an IgG response carefully, one at a time, whilst monitoring symptoms.
Celastrus paniculatus, also known as the Intellect Tree, is perhaps one of the more interesting Ayurvedic medicinal plants that has been used for thousands of years, and one that I personally use quite frequently as part of the supplement “Qualia Mind”. In the Ayurvedic tradition, oil derived from C. paniculatus (Malkanguni oil) is used to enhance memory and intellectual capacity, as well as to improve dream recall and induce lucid dreams. In a study performed on healthy rats, the oil was shown to improve 24-hour memory retention after a single dose, an effect accompanied by a reduction in monoamines like norepinephrine, dopamine and serotonin, indicating a decreased turnover of these neurotransmitters which, in turn, may aid in reducing conditions like depression. In another study with rats, C. paniculatus oil administered for 14 days reversed stress-induced spatial learning and memory impairment and restored working memory. In mice with scopolamine-induced memory deficits, the oil has been shown to improve both spatial and fear memory (a type of fear conditioning through which an organism learns to avoid detrimental situations or events). Traditionally, is taken in seed form, starting with 10 seeds and working up to 15 and finally 20 seeds.
Along with a great formula, Brainol offers real value in their package deals. Brainol extends discounts of $280 if you order 6 bottles, this is an incredible, sensible, cost saving option. Positive customer feedback and testimonials demonstrate the huge numbers of satisfied customers. Consumers can feel very confident in this brain boosting product as it offers a 100% money-back guarantee. Brainol is formulated in a laboratory that is GMP certified. This means that the company is held to very strict standards and high-quality assurance.
The fact of the matter is, though, that the phrase ‘best brain pill’ doesn’t cover any of the bases you’d want an informative article to cover. The human brain is a large and complex thing, and there are many different kinds of pills, supplements, and medications that you can take to improve or affect different areas and functions. Many more of those pills, supplements and medications you take when it breaks down or glitches, to help control harmful or disorienting symptoms of various mental diseases.
Take the synthetic nootropic piracetam, for example. Since piracetam has been shown to improve cell membrane function and cause a host of neuroprotective effects, when combined with other cell membrane stabilizing supplements such as choline and DHA, the brain cells on piracetam can better signal and relay messages to each other for a longer period of time, which improves cognition and brain activity and decreases risk of a crash. So one example of an intelligent “stack” is piracetam taken with choline and DHA.

This product has very nice labeling - very easy to understand and the directions for taking it are immediately at the top of the label in the back. You only have to take or or two tablets a day (preferably with meals) so I 've been taking one a day with my noon meal. I'm a bit surprised that it seems already (after two weeks) that I'm remembering things better (my husband even remarked on it!). Normally, I rely on him for my memory about most things (that, and post-it notes) but I seem to be doing better since taking this supplement. My husband also noticed that I'm in a better mood (more playful and wanting to do things). It has definitely altered my mood - it is winter now where I live and because you don't get as much sunshine and every spare moment is taken up by shoveling, you can get a bit more down in the dumps, which I normally do every year.. It hasn't been like that this year and I feel this supplement has a lot to do with that. Thanks #Vitacern!!!!

After informally testing various formulas of Qualia OS on themselves and friends, Collective founders did an unblinded pilot study with nine volunteers that Dr. Stickler says showed significant benefits in cognitive function and stress response in eight of the subjects. Still, he admits this isn’t airtight scientific proof that the product works. He says the Collective is hoping to do a placebo-controlled study, but in the meantime, he’s confident the stack works because of the results he’s seen in patients.

Absorption of nicotine across biological membranes depends on pH. Nicotine is a weak base with a pKa of 8.0 (Fowler, 1954). In its ionized state, such as in acidic environments, nicotine does not rapidly cross membranes…About 80 to 90% of inhaled nicotine is absorbed during smoking as assessed using C14-nicotine (Armitage et al., 1975). The efficacy of absorption of nicotine from environmental smoke in nonsmoking women has been measured to be 60 to 80% (Iwase et al., 1991)…The various formulations of nicotine replacement therapy (NRT), such as nicotine gum, transdermal patch, nasal spray, inhaler, sublingual tablets, and lozenges, are buffered to alkaline pH to facilitate the absorption of nicotine through cell membranes. Absorption of nicotine from all NRTs is slower and the increase in nicotine blood levels more gradual than from smoking (Table 1). This slow increase in blood and especially brain levels results in low abuse liability of NRTs (Henningfield and Keenan, 1993; West et al., 2000). Only nasal spray provides a rapid delivery of nicotine that is closer to the rate of nicotine delivery achieved with smoking (Sutherland et al., 1992; Gourlay and Benowitz, 1997; Guthrie et al., 1999). The absolute dose of nicotine absorbed systemically from nicotine gum is much less than the nicotine content of the gum, in part, because considerable nicotine is swallowed with subsequent first-pass metabolism (Benowitz et al., 1987). Some nicotine is also retained in chewed gum. A portion of the nicotine dose is swallowed and subjected to first-pass metabolism when using other NRTs, inhaler, sublingual tablets, nasal spray, and lozenges (Johansson et al., 1991; Bergstrom et al., 1995; Lunell et al., 1996; Molander and Lunell, 2001; Choi et al., 2003). Bioavailability for these products with absorption mainly through the mucosa of the oral cavity and a considerable swallowed portion is about 50 to 80% (Table 1)…Nicotine is poorly absorbed from the stomach because it is protonated (ionized) in the acidic gastric fluid, but is well absorbed in the small intestine, which has a more alkaline pH and a large surface area. Following the administration of nicotine capsules or nicotine in solution, peak concentrations are reached in about 1 h (Benowitz et al., 1991; Zins et al., 1997; Dempsey et al., 2004). The oral bioavailability of nicotine is about 20 to 45% (Benowitz et al., 1991; Compton et al., 1997; Zins et al., 1997). Oral bioavailability is incomplete because of the hepatic first-pass metabolism. Also the bioavailability after colonic (enema) administration of nicotine (examined as a potential therapy for ulcerative colitis) is low, around 15 to 25%, presumably due to hepatic first-pass metabolism (Zins et al., 1997). Cotinine is much more polar than nicotine, is metabolized more slowly, and undergoes little, if any, first-pass metabolism after oral dosing (Benowitz et al., 1983b; De Schepper et al., 1987; Zevin et al., 1997).
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