In that year, Dr. Corneliu Giurgea, a Romanian scientist, synthesized piracetam for the first time. Piracetam is classified as a nootropic, although the term nootropic was not used until 1972.[2] Dr. Giurgea coined the term “nootropic” by combining the Greek words for mind (nous) and bend (trepein).  Nootropic literally translates into the phrase “mind bender.”
Dr. Mosconi: I love apples. When I’m at the office though, I’ll bring homemade trail mix [made with] higher quality dried fruit, nuts and seeds. [It's] packed with brain-essential nutrients that come from goji berries, Brazil nuts, walnuts, cacao nibs, pistachios, hemp hearts and  more. Plus, I drink plenty of rose water throughout the day, which is very anti-inflammatory.
We felt that the price for this product was OK but were concerned about how cheap it was on some websites. Our experience suggests that this could reflect the standard of the product, it could be that the quality of ingredients is poor and the dosage low so that they can price cut, however, this leaves consumers having to take more to reach the same level as other products. This can lead to all sorts of issues regarding overdosing, so for these reasons, until further testing can be carried out, we could not place this higher on our score board.
Some nootropics are more commonly used than others. These include nutrients like Alpha GPC, huperzine A, L-Theanine, bacopa monnieri, and vinpocetine. Other types of nootropics are still gaining traction. With all that in mind, to claim there is a “best” nootropic for everyone would be the wrong approach since every person is unique and looking for different benefits.
One curious thing that leaps out looking at the graphs is that the estimated underlying standard deviations differ: the nicotine days have a strikingly large standard deviation, indicating greater variability in scores - both higher and lower, since the means weren’t very different. The difference in standard deviations is just 6.6% below 0, so the difference almost reaches our usual frequentist levels of confidence too, which we can verify by testing:
And in his followup work, An opportunity cost model of subjective effort and task performance (discussion). Kurzban seems to have successfully refuted the blood-glucose theory, with few dissenters from commenting researchers. The more recent opinion seems to be that the sugar interventions serve more as a reward-signal indicating more effort is a good idea, not refueling the engine of the brain (which would seem to fit well with research on procrastination).↩

Took pill #6 at 12:35 PM. Hard to be sure. I ultimately decided that it was Adderall because I didn’t have as much trouble as I normally would in focusing on reading and then finishing my novel (Surface Detail) despite my family watching a movie, though I didn’t notice any lack of appetite. Call this one 60-70% Adderall. I check the next evening and it was Adderall.


The soft gels are very small; one needs to be a bit careful - Vitamin D is fat-soluble and overdose starts in the range of 70,000 IU36, so it would take at least 14 pills, and it’s unclear where problems start with chronic use. Vitamin D, like many supplements, follows a U-shaped response curve (see also Melamed et al 2008 and Durup et al 2012) - too much can be quite as bad as too little. Too little, though, is likely very bad. The previously cited studies with high acute doses worked out to <1,000 IU a day, so they may reassure us about the risks of a large acute dose but not tell us much about smaller chronic doses; the mortality increases due to too-high blood levels begin at ~140nmol/l and reading anecdotes online suggest that 5k IU daily doses tend to put people well below that (around 70-100nmol/l). I probably should get a blood test to be sure, but I have something of a needle phobia.

Because smart drugs like modafinil, nicotine, and Adderall come with drawbacks, I developed my own line of nootropics, including Forbose and SmartMode, that’s safe, widely available, and doesn’t require a prescription. Forskolin, found in Forbose, has been a part of Indian Ayurvedic medicine for thousands of years. In addition to being fun to say, forskolin increases cyclic adenosine monophosphate (cAMP), a molecule essential to learning and memory formation. [8]


But when aficionados talk about nootropics, they usually refer to substances that have supposedly few side effects and low toxicity. Most often they mean piracetam, which Giurgea first synthesized in 1964 and which is approved for therapeutic use in dozens of countries for use in adults and the elderly. Not so in the United States, however, where officially it can be sold only for research purposes.
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.

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. 
Encouraged by TruBrain’s magnesium & my magnesium l-threonate use, I design and run a blind random self-experiment to see whether magnesium citrate supplementation would improve my mood or productivity. I collected ~200 days of data at two dose levels. The analysis finds that the net effect was negative, but a more detailed look shows time-varying effects with a large initial benefit negated by an increasingly-negative effect. Combined with my expectations, the long half-life, and the higher-than-intended dosage, I infer that I overdosed on the magnesium. To verify this, I will be running a followup experiment with a much smaller dose.
You have probably heard and you already love the term “soul food.” You should know that there’s “brain food” too. Natural supplements are the best way to express your gratitude for all the hard work your brain does for you around the clock. These products aren’t reserved only for the elderly users. On the contrary, if you start using them while you’re still young and sharp, you can ensure the proper protection against all those age-related mental deterioration processes.
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.[5] 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.
The beauty of this stack is that nature has already given us a perfectly packaged combination of caffeine and theanine in the form of green tea, whether a cup of green tea, a bowl of matcha tea, or even a green tea extract supplement as a substitute for a cup of coffee. This is an especially convenient stack to use during a time when you don’t want the excess stimulation of coffee or caffeine in isolation, such as during an evening dinner at a restaurant or in the latter stages of a workday when a cup of coffee might keep you awake too late into the night.
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.
One of the most obscure -racetams around, coluracetam (Smarter Nootropics, Ceretropic, Isochroma) acts in a different way from piracetam - piracetam apparently attacks the breakdown of acetylcholine while coluracetam instead increases how much choline can be turned into useful acetylcholine. This apparently is a unique mechanism. A crazy Longecity user, ScienceGuy ponied up $16,000 (!) for a custom synthesis of 500g; he was experimenting with 10-80mg sublingual doses (the ranges in the original anti-depressive trials) and reported a laundry list of effects (as does Isochroma): primarily that it was anxiolytic and increased work stamina. Unfortunately for my stack, he claims it combines poorly with piracetam. He offered free 2g samples for regulars to test his claims. I asked & received some.
Some nootropics users are hopeful that the drugs could be permanently “neuroprotective”—in other words, that the compounds could slow down the neuronal aging process, and help avoid cognitive deterioration later in life. (For what it's worth, most of the users I spoke to said that didn't matter much to them. “I doubt anything I’ve tried has made me smarter in a long-term way,” Baker says. “That’s still science fiction.”)
But Baldino may have been overly modest. In 2002, researchers at Cambridge University gave 60 healthy young male volunteers a battery of standard cognitive tests. One group received modafinil, the other a placebo. The modafinil group performed better on several tasks, such as the "digit span" test, in which subjects are asked to repeat increasingly longer strings of numbers forwards, then backwards. They also did better in recognising repeated visual patterns and at a spatial-planning challenge known as the Tower of London task. (It's not nearly as fun as it sounds.) Writing in the journal Psychopharmacology, the study's authors said the results suggested that "modafinil offers significant potential as a cognitive enhancer".
But he has also seen patients whose propensity for self-experimentation to improve cognition got out of hand. One chief executive he treated, Ngo said, developed an unhealthy predilection for albuterol, because he felt the asthma inhaler medicine kept him alert and productive long after others had quit working. Unfortunately, the drug ended up severely imbalancing his electrolytes, which can lead to dehydration, headaches, vision and cardiac problems, muscle contractions and, in extreme cases, seizures.
But like any other supplement, there are some safety concerns negative studies like Fish oil fails to hold off heart arrhythmia or other reports cast doubt on a protective effect against dementia or Fish Oil Use in Pregnancy Didn’t Make Babies Smart (WSJ) (an early promise but one that faded a bit later) or …Supplementation with DHA compared with placebo did not slow the rate of cognitive and functional decline in patients with mild to moderate Alzheimer disease..
At this point I began to get bored with it and the lack of apparent effects, so I began a pilot trial: I’d use the LED set for 10 minutes every few days before 2PM, record, and in a few months look for a correlation with my daily self-ratings of mood/productivity (for 2.5 years I’ve asked myself at the end of each day whether I did more, the usual, or less work done that day than average, so 2=below-average, 3=average, 4=above-average; it’s ad hoc, but in some factor analyses I’ve been playing with, it seems to load on a lot of other variables I’ve measured, so I think it’s meaningful).

At dose #9, I’ve decided to give up on kratom. It is possible that it is helping me in some way that careful testing (eg. dual n-back over weeks) would reveal, but I don’t have a strong belief that kratom would help me (I seem to benefit more from stimulants, and I’m not clear on how an opiate-bearer like kratom could stimulate me). So I have no reason to do careful testing. Oh well.
For more in-depth personalised support, some people find nutritional therapy hugely beneficial. To find a suitable therapist, please head to BANT (British Association of Applied Nutrition and Nutritional Therapy) or contact our not-for-profit clinic, the Brain Bio Centre (www.brainbiocentre.com), which offers expertise in nutritional therapy for mental health conditions including depression, on 0208 332 9600 or info@brainbiocentre.com. If you feel you need more immediate help, for whatever it is that you’re going through, theSamaritans helpline offer support 24 hours a day, 365 days a year and can point you in the right direction of getting further help.

Consider something as simple as a phone call. You hear the phone ring – your auditory capacity kicks in. Next, you decide whether to answer – decision-making comes into play. You reach for the phone – calling your motor skills to work. You answer – using your voice – all controlled by your brain, all done in mere moments, without conscious thought. Your brain works non-stop, consuming mental energy and physical resources.
Caffeine metabolism is primarily determined by the cytochrome enzyme P-450 1A2 (CYP1A2), and studies have shown that different ethnic populations exhibit widely varying expressions of the gene responsible for CYP1A2. Evidence suggests that a particular CYP1A2 impacts caffeine consumption by modifying the risks of certain diseases that are associated with caffeine consumption. It has also been shown that variations in the expression of genes that code for adenosine and dopamine receptors play a role in mediating your response to caffeine. For example, in Caucasians, the presence of certain genetic expressions for both adenosine and dopamine receptors is associated with caffeine-induced anxiety. Variations in CYP1A2 are also responsible for the speed at which different people metabolize caffeine.
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:
Consider something as simple as a phone call. You hear the phone ring – your auditory capacity kicks in. Next, you decide whether to answer – decision-making comes into play. You reach for the phone – calling your motor skills to work. You answer – using your voice – all controlled by your brain, all done in mere moments, without conscious thought. Your brain works non-stop, consuming mental energy and physical resources.
But before you dismiss the diet-brain connection as mere conjecture, keep in mind that study after study has found a relationship between what we put in our mouths and how well we can perform important thinking and memory tasks. While certain nutrients may specifically assist brain function, there is also the totality of our diets to consider. One recent U.K. study found that a diet high in saturated fat actually caused damage to neurons that control energy and appetite in mice. And several well-regarded studies have shown that meal timing is an important predictor of performance. For example, research shows that eating breakfast can improve the memory and acquisition skills of schoolchildren.
But it's not the mind-expanding 1960s any more. Every era, it seems, has its own defining drug. Neuroenhancers are perfectly suited to the anxiety of white-collar competition in a floundering economy. And they have a synergistic relationship with our multiplying digital technologies: the more gadgets we own, the more distracted we become and the more we need help in order to focus. The experience that neuroenhancement offers is not, for the most part, about opening the doors of perception, or about breaking the bonds of the self, or about experiencing a surge of genius. It's about squeezing out an extra few hours to finish those sales figures when you'd really rather collapse into bed; getting a B instead of a B-minus on the final exam in a lecture class where you spent half your time texting; cramming for the GREs (postgraduate entrance exams) at night, because the information-industry job you got after college turned out to be deadening. Neuroenhancers don't offer freedom. Rather, they facilitate a pinched, unromantic, grindingly efficient form of productivity.
According to the US Food and Drug Administration, "Piracetam is not a vitamin, mineral, amino acid, herb or other botanical, or dietary substance for use by man to supplement the diet by increasing the total dietary intake. Further, piracetam is not a concentrate, metabolite, constituent, extract or combination of any such dietary ingredient. [...] Accordingly, these products are drugs, under section 201(g)(1)(C) of the Act, 21 U.S.C. § 321(g)(1)(C), because they are not foods and they are intended to affect the structure or any function of the body. Moreover, these products are new drugs as defined by section 201(p) of the Act, 21 U.S.C. § 321(p), because they are not generally recognized as safe and effective for use under the conditions prescribed, recommended, or suggested in their labeling."[33]
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