As it happens, these are areas I am distinctly lacking in. When I first began reading about testosterone I had no particular reason to think it might be an issue for me, but it increasingly sounded plausible, an aunt independently suggested I might be deficient, a biological uncle turned out to be severely deficient with levels around 90 ng/dl (where the normal range for 20-49yo males is 249-839), and finally my blood test in August 2013 revealed that my actual level was 305 ng/dl; inasmuch as I was 25 and not 49, this is a tad low.
Null results are generally less likely to be published. Consistent with the operation of such a bias in the present literature, the null results found in our survey were invariably included in articles reporting the results of multiple tasks or multiple measures of a single task; published single-task studies with exclusively behavioral measures all found enhancement. This suggests that some single-task studies with null results have gone unreported. The present mixed results are consistent with those of other recent reviews that included data from normal subjects, using more limited sets of tasks or medications (Advokat, 2010; Chamberlain et al., 2010; Repantis, Schlattmann, Laisney, & Heuser, 2010).
They can cause severe side effects, and their long-term effects aren’t well-researched. They’re also illegal to sell, so they must be made outside of the UK and imported. That means their manufacture isn’t regulated, and they could contain anything. And, as 'smart drugs' in 2018 are still illegal, you might run into legal issues from possessing some ‘smart drugs’ without a prescription.
The absence of a suitable home for this needed research on the current research funding landscape exemplifies a more general problem emerging now, as applications of neuroscience begin to reach out of the clinical setting and into classrooms, offices, courtrooms, nurseries, marketplaces, and battlefields (Farah, 2011). Most of the longstanding sources of public support for neuroscience research are dedicated to basic research or medical applications. As neuroscience is increasingly applied to solving problems outside the medical realm, it loses access to public funding. The result is products and systems reaching the public with less than adequate information about effectiveness and/or safety. Examples include cognitive enhancement with prescription stimulants, event-related potential and fMRI-based lie detection, neuroscience-based educational software, and anti-brain-aging computer programs. Research and development in nonmedical neuroscience are now primarily the responsibility of private corporations, which have an interest in promoting their products. Greater public support of nonmedical neuroscience research, including methods of cognitive enhancement, will encourage greater knowledge and transparency concerning the efficacy and safety of these products and will encourage the development of products based on social value rather than profit value.
“My husband and I (Ryan Cedermark) are so impressed with the research Cavin did when writing this book. If you, a family member or friend has suffered a TBI, concussion or are just looking to be nicer to your brain, then we highly recommend this book! Your brain is only as good as the body’s internal environment and Cavin has done an amazing job on providing the information needed to obtain such!”
Manually mixing powders is too annoying, and pre-mixed pills are expensive in bulk. So if I’m not actively experimenting with something, and not yet rich, the best thing is to make my own pills, and if I’m making my own pills, I might as well make a custom formulation using the ones I’ve found personally effective. And since making pills is tedious, I want to not have to do it again for years. 3 years seems like a good interval - 1095 days. Since one is often busy and mayn’t take that day’s pills (there are enough ingredients it has to be multiple pills), it’s safe to round it down to a nice even 1000 days. What sort of hypothetical stack could I make? What do the prices come out to be, and what might we omit in the interests of protecting our pocketbook?
The stimulant now most popular in news articles as a legitimate “smart drug” is Modafinil, which came to market as an anti-narcolepsy drug, but gained a following within the military, doctors on long shifts, and college students pulling all-nighters who needed a drug to improve alertness without the “wired” feeling associated with caffeine. Modafinil is a relatively new smart drug, having gained widespread use only in the past 15 years. More research is needed before scientists understand this drug’s function within the brain – but the increase in alertness it provides is uncontested.
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:
Second, users are concerned with the possibility of withdrawal if they stop taking the nootropics. They worry that if they stop taking nootropics they won’t be as smart as when they were taking nootropics, and will need to continue taking them to function. Some users report feeling a slight brain fog when discontinuing nootropics, but that isn’t a sign of regression.
A fundamental aspect of human evolution has been the drive to augment our capabilities. The neocortex is the neural seat of abstract and higher order cognitive processes. As it grew, so did our ability to create. The invention of tools and weapons, writing, the steam engine, and the computer have exponentially increased our capacity to influence and understand the world around us. These advances are being driven by improved higher-order cognitive processing.1Fascinatingly, the practice of modulating our biology through naturally occurring flora predated all of the above discoveries. Indeed, Sumerian clay slabs as old as 5000 BC detail medicinal recipes which include over 250 plants2. The enhancement of human cognition through natural compounds followed, as people discovered plants containing caffeine, theanine, and other cognition-enhancing, or nootropic, agents.
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.

COGNITUNE is for informational purposes only, and should not be considered medical advice, diagnosis or treatment recommendations. Always consult with your doctor or primary care physician before using any nutraceuticals, dietary supplements, or prescription medications. Seeking a proper diagnosis from a certified medical professional is vital for your health.


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“Cavin’s enthusiasm and drive to help those who need it is unparalleled! He delivers the information in an easy to read manner, no PhD required from the reader. 🙂 Having lived through such trauma himself he has real empathy for other survivors and it shows in the writing. This is a great read for anyone who wants to increase the health of their brain, injury or otherwise! Read it!!!”
The chemicals he takes, dubbed nootropics from the Greek “noos” for “mind”, are intended to safely improve cognitive functioning. They must not be harmful, have significant side-effects or be addictive. That means well-known “smart drugs” such as the prescription-only stimulants Adderall and Ritalin, popular with swotting university students, are out. What’s left under the nootropic umbrella is a dizzying array of over-the-counter supplements, prescription drugs and unclassified research chemicals, some of which are being trialled in older people with fading cognition.
Companies already know a great deal about how their employees live their lives. With the help of wearable technologies and health screenings, companies can now analyze the relation between bodily activities — exercise, sleep, nutrition, etc. — and work performance. With the justification that healthy employees perform better, some companies have made exercise mandatory by using sanctions against those who refuse to perform. And according to The Kaiser Family Foundation, of the large U.S. companies that offer health screenings, nearly half of them use financial incentives to persuade employees to participate.
I took 1.5mg of melatonin, and went to bed at ~1:30AM; I woke up around 6:30, took a modafinil pill/200mg, and felt pretty reasonable. By noon my mind started to feel a bit fuzzy, and lunch didn’t make much of it go away. I’ve been looking at studies, and users seem to degrade after 30 hours; I started on mid-Thursday, so call that 10 hours, then 24 (Friday), 24 (Saturday), and 14 (Sunday), totaling 72hrs with <20hrs sleep; this might be equivalent to 52hrs with no sleep, and Wikipedia writes:

Research on animals has shown that intermittent fasting — limiting caloric intake at least two days a week — can help improve neural connections in the hippocampus and protect against the accumulation of plaque, a protein prevalent in the brains of people with Alzheimer’s disease. Research has also shown that intermittent fasting helped reduce anxiety in mice.
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:
2 commenters point out that my possible lack of result is due to my mistaken assumption that if nicotine is absorbable through skin, mouth, and lungs it ought to be perfectly fine to absorb it through my stomach by drinking it (rather than vaporizing it and breathing it with an e-cigarette machine) - it’s apparently known that absorption differs in the stomach.
One might suggest just going to the gym or doing other activities which may increase endogenous testosterone secretion. This would be unsatisfying to me as it introduces confounds: the exercise may be doing all the work in any observed effect, and certainly can’t be blinded. And blinding is especially important because the 2011 review discusses how some studies report that the famed influence of testosterone on aggression (eg. Wedrifid’s anecdote above) is a placebo effect caused by the folk wisdom that testosterone causes aggression & rage!
The prefrontal cortex at the front of the brain is the zone that produces such representations, and it is the focus of Arnsten’s work. “The way the prefrontal cortex creates these representations is by having pyramidal cells – they’re actually shaped like little pyramids – exciting each other. They keep each other firing, even when there’s no information coming in from the environment to stimulate the circuits,” she explains.
Gamma-aminobutyric acid, also known as GABA, naturally produced in the brain from glutamate, is a neurotransmitter that helps in the communication between the nervous system and brain. The primary function of this GABA Nootropic is to reduce the additional activity of the nerve cells and helps calm the mind. Thus, it helps to improve various conditions, like stress, anxiety, and depression by decreasing the beta brain waves and increasing the alpha brain waves. It is one of the best nootropic for anxiety that you can find in the market today.  As a result, cognitive abilities like memory power, attention, and alertness also improve. GABA helps drug addicts recover from addiction by normalizing the brain’s GABA receptors which reduce anxiety and craving levels in the absence of addictive substances.

The FDA has approved the first smart pill for use in the United States. Called Abilify MyCite, the pill contains a drug and an ingestible sensor that is activated when it comes into contact with stomach fluid to detect when the pill has been taken. The pill then transmits this data to a wearable patch that subsequently transfers the information to an app on a paired smartphone. From that point, with a patient's consent, the data can be accessed by the patient's doctors or caregivers via a web portal.
AMP and MPH increase catecholamine activity in different ways. MPH primarily inhibits the reuptake of dopamine by pre-synaptic neurons, thus leaving more dopamine in the synapse and available for interacting with the receptors of the postsynaptic neuron. AMP also affects reuptake, as well as increasing the rate at which neurotransmitter is released from presynaptic neurons (Wilens, 2006). These effects are manifest in the attention systems of the brain, as already mentioned, and in a variety of other systems that depend on catecholaminergic transmission as well, giving rise to other physical and psychological effects. Physical effects include activation of the sympathetic nervous system (i.e., a fight-or-flight response), producing increased heart rate and blood pressure. Psychological effects are mediated by activation of the nucleus accumbens, ventral striatum, and other parts of the brain’s reward system, producing feelings of pleasure and the potential for dependence.
Powders are good for experimenting with (easy to vary doses and mix), but not so good for regular taking. I use OO gel capsules with a Capsule Machine: it’s hard to beat $20, it works, it’s not that messy after practice, and it’s not too bad to do 100 pills. However, I once did 3kg of piracetam + my other powders, and doing that nearly burned me out on ever using capsules again. If you’re going to do that much, something more automated is a serious question! (What actually wound up infuriating me the most was when capsules would stick in either the bottom or top try - requiring you to very gingerly pull and twist them out, lest the two halves slip and spill powder - or when the two halves wouldn’t lock and you had to join them by hand. In contrast: loading the gel caps could be done automatically without looking, after some experience.)
The truth is that, almost 20 years ago when my brain was failing and I was fat and tired, I did not know to follow this advice. I bought $1000 worth of smart drugs from Europe, took them all at once out of desperation, and got enough cognitive function to save my career and tackle my metabolic problems. With the information we have now, you don’t need to do that. Please learn from my mistakes!

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Long-term use is different, and research-backed efficacy is another question altogether. The nootropic market is not regulated, so a company can make claims without getting in trouble for making those claims because they’re not technically selling a drug. This is why it’s important to look for well-known brands and standardized nootropic herbs where it’s easier to calculate the suggested dose and be fairly confident about what you’re taking.
Some of the newest substances being used as ‘smart drugs’ are medically prescribed for other conditions. For example, methylphenidate, commonly known as Ritalin, is used to treat attention deficit hyperactivity disorder (ADHD). So is Adderall, a combination drug containing two forms of amphetamine. These are among a suite of pharmaceuticals now being used by healthy people, particularly university students, to enhance their capabilities for learning or working. 
Evidence in support of the neuroprotective effects of flavonoids has increased significantly in recent years, although to date much of this evidence has emerged from animal rather than human studies. Nonetheless, with a view to making recommendations for future good practice, we review 15 existing human dietary intervention studies that have examined the effects of particular types of flavonoid on cognitive performance. The studies employed a total of 55 different cognitive tests covering a broad range of cognitive domains. Most studies incorporated at least one measure of executive function/working memory, with nine reporting significant improvements in performance as a function of flavonoid supplementation compared to a control group. However, some domains were overlooked completely (e.g. implicit memory, prospective memory), and for the most part there was little consistency in terms of the particular cognitive tests used making across study comparisons difficult. Furthermore, there was some confusion concerning what aspects of cognitive function particular tests were actually measuring. Overall, while initial results are encouraging, future studies need to pay careful attention when selecting cognitive measures, especially in terms of ensuring that tasks are actually sensitive enough to detect treatment effects.
Taurine (Examine.com) was another gamble on my part, based mostly on its inclusion in energy drinks. I didn’t do as much research as I should have: it came as a shock to me when I read in Wikipedia that taurine has been shown to prevent oxidative stress induced by exercise and was an antioxidant - oxidative stress is a key part of how exercise creates health benefits and antioxidants inhibit those benefits.
“I bought this book because I didn’t want a weightloss diet, but I wanted the most optimal gut/brain food I could find to help with an autoimmune. I subscribe to Cavin’s podcast and another newsletter for gut health which also recommended this book. Also, he’s a personal friend of mine who’s recovery I have witnessed firsthand. Thank you so much for all of the research and your continued dedication to not only help yourself, but for also helping others!”
Government restrictions and difficulty getting approval for various medical devices is expected to impede market growth. The stringency of approval by regulatory authorities is accompanied by the high cost of smart pills to challenge the growth of the smart pills market. However, the demand for speedy diagnosis, and improving reimbursement policies are likely to reveal market opportunities.
Blinding stymied me for a few months since the nasty taste was unmistakable and I couldn’t think of any gums with a similar flavor to serve as placebo. (The nasty taste does not seem to be due to the nicotine despite what one might expect; Vaniver plausibly suggested the bad taste might be intended to prevent over-consumption, but nothing in the Habitrol ingredient list seemed to be noted for its bad taste, and a number of ingredients were sweetening sugars of various sorts. So I couldn’t simply flavor some gum.)
One might suggest just going to the gym or doing other activities which may increase endogenous testosterone secretion. This would be unsatisfying to me as it introduces confounds: the exercise may be doing all the work in any observed effect, and certainly can’t be blinded. And blinding is especially important because the 2011 review discusses how some studies report that the famed influence of testosterone on aggression (eg. Wedrifid’s anecdote above) is a placebo effect caused by the folk wisdom that testosterone causes aggression & rage!
Methylphenidate – a benzylpiperidine that had cognitive effects (e.g., working memory, episodic memory, and inhibitory control, aspects of attention, and planning latency) in healthy people.[21][22][23] It also may improve task saliency and performance on tedious tasks.[25] At above optimal doses, methylphenidate had off–target effects that decreased learning.[26]
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