Some supplement blends, meanwhile, claim to work by combining ingredients – bacopa, cat's claw, huperzia serrata and oat straw in the case of Alpha Brain, for example – that have some support for boosting cognition and other areas of nervous system health. One 2014 study in Frontiers in Aging Neuroscience, suggested that huperzia serrata, which is used in China to fight Alzheimer's disease, may help slow cell death and protect against (or slow the progression of) neurodegenerative diseases. The Alpha Brain product itself has also been studied in a company-funded small randomized controlled trial, which found Alpha Brain significantly improved verbal memory when compared to adults who took a placebo.
Nootropics may seem attractive to anyone who wants to try to improve their cognitive function and is willing to purchase powders, pills and other forms of these natural and synthetic supplements. Nootropic users have their own terminology, referring to measured combinations of nootropics and vitamins and minerals as “stacks.” For instance, Danger and Play, a site for active people, features a stack for beginners. The recipe includes 1600 mg of the piracetam along with recommended dosages of supplements such as ALCAR, rhodiola and magnesium. There are recipes for morning, afternoon and night, thus providing daylong guidance on how to most effectively stack for more energy, greater concentration, and improved information retention. The stack tip specifically states that the ingredients are not addictive, especially if taken in strict accordance with the recipe.
Related to the famous -racetams but reportedly better (and much less bulky), Noopept is one of the many obscure Russian nootropics. (Further reading: Google Scholar, Examine.com, Reddit, Longecity, Bluelight.ru.) Its advantages seem to be that it’s far more compact than piracetam and doesn’t taste awful so it’s easier to store and consume; doesn’t have the cloud hanging over it that piracetam does due to the FDA letters, so it’s easy to purchase through normal channels; is cheap on a per-dose basis; and it has fans claiming it is better than piracetam.
If you want to try a nootropic in supplement form, check the label to weed out products you may be allergic to and vet the company as best you can by scouring its website and research basis, and talking to other customers, Kerl recommends. "Find one that isn't just giving you some temporary mental boost or some quick fix – that’s not what a nootropic is intended to do," Cyr says.
Caffeine dose dependently decreased the 1,25(OH)(2)D(3) induced VDR expression and at concentrations of 1 and 10mM, VDR expression was decreased by about 50-70%, respectively. In addition, the 1,25(OH)(2)D(3) induced alkaline phosphatase activity was also reduced at similar doses thus affecting the osteoblastic function. The basal ALP activity was not affected with increasing doses of caffeine. Overall, our results suggest that caffeine affects 1,25(OH)(2)D(3) stimulated VDR protein expression and 1,25(OH)(2)D(3) mediated actions in human osteoblast cells.
The methodology would be essentially the same as the vitamin D in the morning experiment: put a multiple of 7 placebos in one container, the same number of actives in another identical container, hide & randomly pick one of them, use container for 7 days then the other for 7 days, look inside them for the label to determine which period was active and which was placebo, refill them, and start again.
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.
Nootropics are classically defined as something that a) improves brain health, and b) does no harm. So, while many treatments being advertised online and on TV can be classified as nootropics, some of them don’t fit the bill because of the dangerous and damaging side effects they also confer upon the unwary consumer. In fact, most of the results you might get from searching ‘best brain pills’ are similarly not that great, let alone the best.
Finally, it’s not clear that caffeine results in performance gains after long-term use; homeostasis/tolerance is a concern for all stimulants, but especially for caffeine. It is plausible that all caffeine consumption does for the long-term chronic user is restore performance to baseline. (Imagine someone waking up and drinking coffee, and their performance improves - well, so would the performance of a non-addict who is also slowly waking up!) See for example, James & Rogers 2005, Sigmon et al 2009, and Rogers et al 2010. A cross-section of thousands of participants in the Cambridge brain-training study found caffeine intake showed negligible effect sizes for mean and component scores (participants were not told to use caffeine, but the training was recreational & difficult, so one expects some difference).
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Our current natural brain health formula contains Cordyceps-Sinensis Extract as well as the complete balance of brain health supporting nutrients that work perfectly together to help your body elevate essential acetylcholine levels while increasing the neurological components (neurotransmitters) needed to help you stay alert, focused, mentally driven and calm.
Caffeine, the mild stimulant found in coffee, improves mental acuity, though the drink's enthusiasts -- who guzzle 120,000 tons of the stuff each year -- likely already know that. Aside from caffeine's brain boosting effects, coffee's antioxidant richness helps maintain brain health. And some research suggests that drinking coffee can actually stave off depression in women.
DNB-wise, eyeballing my stats file seems to indicate a small increase: when I compare peak scores D4B scores, I see mostly 50s and a few 60s before piracetam, and after starting piracetam, a few 70s mixed into the 50s and 60s. Natural increase from training? Dunno - I’ve been stuck on D4B since June, so 5 or 10% in a week or 3 seems a little suspicious. A graph of the score series27:
Our 2nd choice for a Brain and Memory supplement is Clari-T by Life Seasons. We were pleased to see that their formula included 3 of the 5 necessary ingredients Huperzine A, Phosphatidylserine and Bacopin. In addition, we liked that their product came in a vegetable capsule. The product contains silica and rice bran, though, which we are not sure is necessary.
While it’s no miracle pill, it can certainly give you the edge when it comes to enhanced mental and cognitive processing, as well as boosting your focus and memory retention. So, if you’re the kind of person who’s looking to optimize your performance and get the best results possible, then using an effective nootropic like the Brain Pill is a smart decision that will quickly pay dividends when it’s used in the appropriate way.
When I worked on the Bulletproof Diet book, I wanted to verify that the effects I was getting from Bulletproof Coffee were not coming from modafinil, so I stopped using it and measured my cognitive performance while I was off of it. What I found was that on Bulletproof Coffee and the Bulletproof Diet, my mental performance was almost identical to my performance on modafinil. I still travel with modafinil, and I’ll take it on occasion, but while living a Bulletproof lifestyle I rarely feel the need.
Stayed up with the purpose of finishing my work for a contest. This time, instead of taking the pill as a single large dose (I feel that after 3 times, I understand what it’s like), I will take 4 doses over the new day. I took the first quarter at 1 AM, when I was starting to feel a little foggy but not majorly impaired. Second dose, 5:30 AM; feeling a little impaired. 8:20 AM, third dose; as usual, I feel physically a bit off and mentally tired - but still mentally sharp when I actually do something. Early on, my heart rate seemed a bit high and my limbs trembling, but it’s pretty clear now that that was the caffeine or piracetam. It may be that the other day, it was the caffeine’s fault as I suspected. The final dose was around noon. The afternoon crash wasn’t so pronounced this time, although motivation remains a problem. I put everything into finishing up the spaced repetition literature review, and didn’t do any n-backing until 11:30 PM: 32/34/31/54/40%.
There are a number of smart drugs on the market, the most well-known of which are probably Adderall and Ritalin. Both are technically known as psychostimulants, which means that they stimulate increased activity of the central nervous system: the brain and spinal cord. There are also two other common smart drugs, specifically Modafinil and a class of something called “ampakines”. You’re about to learn how each of them works and the benefits and potential risks therein.
The above are all reasons to expect that even if I do excellent single-subject design self-experiments, there will still be the old problem of internal validity versus external validity: an experiment may be wrong or erroneous or unlucky in some way (lack of internal validity) or be right but not matter to anyone else (lack of external validity). For example, alcohol makes me sad & depressed; I could run the perfect blind randomized experiment for hundreds of trials and be extremely sure that alcohol makes me less happy, but would that prove that alcohol makes everyone sad or unhappy? Of course not, and as far as I know, for a lot of people alcohol has the opposite effect. So my hypothetical alcohol experiment might have tremendous internal validity (it does prove that I am sadder after inebriating), and zero external validity (someone who has never tried alcohol learns nothing about whether they will be depressed after imbibing). Keep this in mind if you are minded to take the experiments too seriously.
Nootropics That is offered through an email showing Ben Carson and Bill O Reily talking about it and they offer a deal the more you buy the cheaper it is with free bottles is a scam. I ordered 3 bottles with 2 free and free shipping which should have been 120.00. They had a offer for 59.99 for cleansing product and I didn’t order it. My total came out to 189.94. I called them and they removed it and then the 5 bottles was still going to be 189.99. I told them about the offer and they would not honor it. I ended up canceling the order. This is a scam!!
I posted a link to the survey on my Google+ account, and inserted the link at the top of all gwern.net pages; 51 people completed all 11 binary choices (most of them coming from North America & Europe), which seems adequate since the 11 questions are all asking the same question, and 561 responses to one question is quite a few. A few different statistical tests seem applicable: a chi-squared test whether there’s a difference between all the answers, a two-sample test on the averages, and most meaningfully, summing up the responses as a single pair of numbers and doing a binomial test:
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Reason: Acetyl-L-carnitine can protect the brain from neurotoxicity. It can also ward off oxygen deprivation. Acetyl-L-carnitine can even preserve cells energy-producing mitochondria. Plus, it can rejuvenate mental and physical function. Dosages for studies have been in the 1,500 – 4,000 mg range. These are divided into two or three doses. However, we recommend no more than 1,000 mg of acetyl-L-carnitine a day without medical supervision.
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.
To make things more interesting, I think I would like to try randomizing different dosages as well: 12mg, 24mg, and 36mg (1-3 pills); on 5 May 2014, because I wanted to finish up the experiment earlier, I decided to add 2 larger doses of 48 & 60mg (4-5 pills) as options. Then I can include the previous pilot study as 10mg doses, and regress over dose amount.
All of the coefficients are positive, as one would hope, and one specific factor (MR7) squeaks in at d=0.34 (p=0.05). The graph is much less impressive than the graph for just MP, suggesting that the correlation may be spread out over a lot of factors, the current dataset isn’t doing a good job of capturing the effect compared to the MP self-rating, or it really was a placebo effect:
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Amphetamines are synthetic stimulants and were first created in 1887. These are among the most powerful stimulant-based smart drugs in use and work primarily by targeting dopamine, serotonin and noradrenaline/norepinephrine. Given what you’ve already learned about the dopaminergic effects of modafinil and methylphenidate, you should already be wary of amphetamines’ targeting of dopamine. Hormones and neurotransmitters such as dopamine, serotonin, norepinephrine and histamine are known as monoamines, and amphetamines block their uptake by being taken up instead themselves by monoamine transporters. This leads to higher levels of monoamines in synapses, and consequently to the psychostimulant effects characteristic of drugs like Adderall.
The AC-11 that Marcus mentioned for health is an extract from the Amazon jungle vine una de gato, and has been shown in laboratory and clinical trials to encourage DNA repair. The Mucuna pruriens he named for motivation is a legume that's a concentrated source of L-Dopa, which the body converts to the neurotransmitter dopamine. The Huperzia serrata Marcus selected for hunting is the same substance that induces lucid dreaming. This seems appropriate. While I felt the Alpha Brain helped my hunting, maybe I was dreaming. Or maybe a dream state of mind is good for hunting.
The Nootroo arrives in a shiny gold envelope with the words “proprietary blend” and “intended for use only in neuroscience research” written on the tin. It has been designed, says Matzner, for “hours of enhanced learning and memory”. The capsules contain either Phenylpiracetam or Noopept (a peptide with similar effects and similarly uncategorised) and are distinguished by real flakes of either edible silver or gold. They are to be alternated between daily, allowing about two weeks for the full effect to be felt. Also in the capsules are L-Theanine, a form of choline, and a types of caffeine which it is claimed has longer lasting effects.
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.↩
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:
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The fish oil can be considered a free sunk cost: I would take it in the absence of an experiment. The empty pill capsules could be used for something else, so we’ll put the 500 at $5. Filling 500 capsules with fish and olive oil will be messy and take an hour. Taking them regularly can be added to my habitual morning routine for vitamin D and the lithium experiment, so that is close to free but we’ll call it an hour over the 250 days. Recording mood/productivity is also free a sunk cost as it’s necessary for the other experiments; but recording dual n-back scores is more expensive: each round is ~2 minutes and one wants >=5, so each block will cost >10 minutes, so 18 tests will be >180 minutes or >3 hours. So >5 hours. Total: 5 + (>5 \times 7.25) = >41.
The makeup of the brain is about 29% fat, most of which is located in myelin (which itself is 70–80% fat). Specific fatty acid ratios will depend in part on the diet of the animal it is harvested from. The brain is also very high in cholesterol. For example, a single 140 g (5 oz) serving of "pork brains in milk gravy" can contain 3500 mg of cholesterol (1170% of the USRDA).
Systematic reviews and meta-analyses of clinical human research using low doses of certain central nervous system stimulants found enhanced cognition in healthy people. In particular, the classes of stimulants that demonstrate cognition-enhancing effects in humans act as direct agonists or indirect agonists of dopamine receptor D1, adrenoceptor A2, or both types of receptor in the prefrontal cortex. Relatively high doses of stimulants cause cognitive deficits.