(On a side note, I think I understand now why modafinil doesn’t lead to a Beggars in Spain scenario; BiS includes massive IQ and motivation boosts as part of the Sleepless modification. Just adding 8 hours a day doesn’t do the world-changing trick, no more than some researchers living to 90 and others to 60 has lead to the former taking over. If everyone were suddenly granted the ability to never need sleep, many of them would have no idea what to do with the extra 8 or 9 hours and might well be destroyed by the gift; it takes a lot of motivation to make good use of the time, and if one cannot, then it is a curse akin to the stories of immortals who yearn for death - they yearn because life is not a blessing to them, though that is a fact more about them than life.)
The blood half-life is 12-36 hours; hence two or three days ought to be enough to build up and wash out. A week-long block is reasonable since that gives 5 days for effects to manifest, although month-long blocks would not be a bad choice either. (I prefer blocks which fit in round periods because it makes self-experiments easier to run if the blocks fit in normal time-cycles like day/week/month. The most useless self-experiment is the one abandoned halfway.)
Use of prescription stimulants by normal healthy individuals to enhance cognition is said to be on the rise. Who is using these medications for cognitive enhancement, and how prevalent is this practice? Do prescription stimulants in fact enhance cognition for normal healthy people? We review the epidemiological and cognitive neuroscience literatures in search of answers to these questions. Epidemiological issues addressed include the prevalence of nonmedical stimulant use, user demographics, methods by which users obtain prescription stimulants, and motivations for use. Cognitive neuroscience issues addressed include the effects of prescription stimulants on learning and executive function, as well as the task and individual variables associated with these effects. Little is known about the prevalence of prescription stimulant use for cognitive enhancement outside of student populations. Among college students, estimates of use vary widely but, taken together, suggest that the practice is commonplace. The cognitive effects of stimulants on normal healthy people cannot yet be characterized definitively, despite the volume of research that has been carried out on these issues. Published evidence suggests that declarative memory can be improved by stimulants, with some evidence consistent with enhanced consolidation of memories. Effects on the executive functions of working memory and cognitive control are less reliable but have been found for at least some individuals on some tasks. In closing, we enumerate the many outstanding questions that remain to be addressed by future research and also identify obstacles facing this research.
It may also be necessary to ask not just whether a drug enhances cognition, but in whom. Researchers at the University of Sussex have found that nicotine improved performance on memory tests in young adults who carried one variant of a particular gene but not in those with a different version. In addition, there are already hints that the smarter you are, the less smart drugs will do for you. One study found that modafinil improved performance in a group of students whose mean IQ was 106, but not in a group with an average of 115.
“In 183 pages, Cavin Balaster’s new book, How to Feed A Brain provides an outline and plan for how to maximize one’s brain performance. The “Citation Notes” provide all the scientific and academic documentation for further understanding. The “Additional Resources and Tips” listing takes you to Cavin’s website for more detail than could be covered in 183 pages. Cavin came to this knowledge through the need to recover from a severe traumatic brain injury and he did not keep his lessons learned to himself. This book is enlightening for anyone with a brain. We all want to function optimally, even to take exams, stay dynamic, and make positive contributions to our communities. Bravo Cavin for sharing your lessons learned!”
A 2015 review of various nutrients and dietary supplements found no convincing evidence of improvements in cognitive performance. While there are “plausible mechanisms” linking these and other food-sourced nutrients to better brain function, “supplements cannot replicate the complexity of natural food and provide all its potential benefits,” says Dr. David Hogan, author of that review and a professor of medicine at the University of Calgary in Canada.
The evidence? Ritalin is FDA-approved to treat ADHD. It has also been shown to help patients with traumatic brain injury concentrate for longer periods, but does not improve memory in those patients, according to a 2016 meta-analysis of several trials. A study published in 2012 found that low doses of methylphenidate improved cognitive performance, including working memory, in healthy adult volunteers, but high doses impaired cognitive performance and a person’s ability to focus. (Since the brains of teens have been found to be more sensitive to the drug’s effect, it’s possible that methylphenidate in lower doses could have adverse effects on working memory and cognitive functions.)
As discussed in my iodine essay (FDA adverse events), iodine is a powerful health intervention as it eliminates cretinism and improves average IQ by a shocking magnitude. If this effect were possible for non-fetuses in general, it would be the best nootropic ever discovered, and so I looked at it very closely. Unfortunately, after going through ~20 experiments looking for ones which intervened with iodine post-birth and took measures of cognitive function, my meta-analysis concludes that: the effect is small and driven mostly by one outlier study. Once you are born, it’s too late. But the results could be wrong, and iodine might be cheap enough to take anyway, or take for non-IQ reasons. (This possibility was further weakened for me by an August 2013 blood test of TSH which put me at 3.71 uIU/ml, comfortably within the reference range of 0.27-4.20.)
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.
Serotonin, or 5-hydroxytryptamine (5-HTP), is another primary neurotransmitter and controls major features of the mental landscape including mood, sleep and appetite. Serotonin is produced within the body by exposure, which is one reason that the folk-remedy of “getting some sun” to fight depression is scientifically credible. Many foods contain natural serotonergic (serotonin-promoting or releasing) compounds, including the well-known chemical L-Tryptophan found in turkey, which can promote sleep after big Thanksgiving dinners.
A rough translation for the word “nootropic” comes from the Greek for “to bend or shape the mind.” And already, there are dozens of over-the-counter (OTC) products—many of which are sold widely online or in stores—that claim to boost creativity, memory, decision-making or other high-level brain functions. Some of the most popular supplements are a mixture of food-derived vitamins, lipids, phytochemicals and antioxidants that studies have linked to healthy brain function. One popular pick on Amazon, for example, is an encapsulated cocktail of omega-3s, B vitamins and plant-derived compounds that its maker claims can improve memory, concentration and focus.
A total of 330 randomly selected Saudi adolescents were included. Anthropometrics were recorded and fasting blood samples were analyzed for routine analysis of fasting glucose, lipid levels, calcium, albumin and phosphorous. Frequency of coffee and tea intake was noted. 25-hydroxyvitamin D levels were measured using enzyme-linked immunosorbent assays…Vitamin D levels were significantly highest among those consuming 9-12 cups of tea/week in all subjects (p-value 0.009) independent of age, gender, BMI, physical activity and sun exposure.
Chocolate or cocoa powder (Examine.com), contains the stimulants caffeine and the caffeine metabolite theobromine, so it’s not necessarily surprising if cocoa powder was a weak stimulant. It’s also a witch’s brew of chemicals such as polyphenols and flavonoids some of which have been fingered as helpful10, which all adds up to an unclear impact on health (once you control for eating a lot of sugar).
An entirely different set of questions concerns cognitive enhancement in younger students, including elementary school and even preschool children. Some children can function adequately in school without stimulants but perform better with them; medicating such children could be considered a form of cognitive enhancement. How often does this occur? What are the roles and motives of parents, teachers, and pediatricians in these cases? These questions have been discussed elsewhere and deserve continued attention (Diller, 1996; Singh & Keller, 2010).
Does little alone, but absolutely necessary in conjunction with piracetam. (Bought from Smart Powders.) When turning my 3kg of piracetam into pills, I decided to avoid the fishy-smelling choline and go with 500g of DMAE (Examine.com); it seemed to work well when I used it before with oxiracetam & piracetam, since I had no piracetam headaches, and be considerably less bulky.
I split the 2 pills into 4 doses for each hour from midnight to 4 AM. 3D driver issues in Debian unstable prevented me from using Brain Workshop, so I don’t have any DNB scores to compare with the armodafinil DNB scores. I had the subjective impression that I was worse off with the Modalert, although I still managed to get a fair bit done so the deficits couldn’t’ve been too bad. The apathy during the morning felt worse than armodafinil, but that could have been caused by or exacerbated by an unexpected and very stressful 2 hour drive through rush hour and multiple accidents; the quick hour-long nap at 10 AM was half-waking half-light-sleep according to the Zeo, but seemed to help a bit. As before, I began to feel better in the afternoon and by evening felt normal, doing my usual reading. That night, the Zeo recorded my sleep as lasting ~9:40, when it was usually more like 8:40-9:00 (although I am not sure that this was due to the modafinil inasmuch as once a week or so I tend to sleep in that long, as I did a few days later without any influence from the modafinil); assuming the worse, the nap and extra sleep cost me 2 hours for a net profit of ~7 hours. While it’s not clear how modafinil affects recovery sleep (see the footnote in the essay), it’s still interesting to ponder the benefits of merely being able to delay sleep18.
A provisional conclusion about the effects of stimulants on learning is that they do help with the consolidation of declarative learning, with effect sizes varying widely from small to large depending on the task and individual study. Indeed, as a practical matter, stimulants may be more helpful than many of the laboratory tasks indicate, given the apparent dependence of enhancement on length of delay before testing. Although, as a matter of convenience, experimenters tend to test memory for learned material soon after the learning, this method has not generally demonstrated stimulant-enhanced learning. However, when longer periods intervene between learning and test, a more robust enhancement effect can be seen. Note that the persistence of the enhancement effect well past the time of drug action implies that state-dependent learning is not responsible. In general, long-term effects on learning are of greater practical value to people. Even students cramming for exams need to retain information for more than an hour or two. We therefore conclude that stimulant medication does enhance learning in ways that may be useful in the real world.
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:
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.
Harrisburg, NC -- (SBWIRE) -- 02/18/2019 -- Global Smart Pills Technology Market - Segmented by Technology, Disease Indication, and Geography - Growth, Trends, and Forecast (2019 - 2023) The smart pill is a wireless capsule that can be swallowed, and with the help of a receiver (worn by patients) and software that analyzes the pictures captured by the smart pill, the physician is effectively able to examine the gastrointestinal tract. Gastrointestinal disorders have become very common, but recently, there has been increasing incidence of colorectal cancer, inflammatory bowel disease, and Crohns disease as well.
One fairly powerful nootropic substance that, appropriately, has fallen out of favor is nicotine. It’s the chemical that gives tobacco products their stimulating kick. It isn’t what makes them so deadly, but it does make smoking very addictive. When Europeans learned about tobacco’s use from indigenous tribes they encountered in the Americas in the 15th and 16th centuries, they got hooked on its mood-altering effects right away and even believed it could cure joint pain, epilepsy, and the plague. Recently, researchers have been testing the effects of nicotine that’s been removed from tobacco, and they believe that it might help treat neurological disorders including Parkinson’s disease and schizophrenia; it may also improve attention and focus. But, please, don’t start smoking or vaping. Check out these 14 weird brain exercises that make you smarter.
Even the best of today’s nootropics only just barely scratch the surface. You might say that we are in the “Nokia 1100” phase of taking nootropics, and as better tools and more data come along, the leading thinkers in the space see a powerful future. For example, they are already beginning to look past biochemistry to the epigenome. Not only is the epigenome the code that runs much of your native biochemistry, we now know that experiences in life can be recorded in your epigenome and then passed onto future generations. There is every reason to believe that you are currently running epigenetic code that you inherited from your great-grandmother’s life experiences. And there is every reason to believe that the epigenome can be hacked – that the nootropics of the future can not only support and enhance our biochemistry, but can permanently change the epigenetic code that drives that biochemistry and that we pass onto our children. This is why many healthy individuals use nootropics. They have great benefits and can promote brain function and reduce oxidative stress. They can also improve sleep quality.
Next, if these theorized safe and effective pills don't just get you through a test or the day's daily brain task but also make you smarter, whatever smarter means, then what? Where's the boundary between genius and madness? If Einstein had taken such drugs, would he have created a better theory of gravity? Or would he have become delusional, chasing quantum ghosts with no practical application, or worse yet, string theory. (Please use "string theory" in your subject line for easy sorting of hate mail.)
It is a known fact that cognitive decline is often linked to aging. It may not be as visible as skin aging, but the brain does in fact age. Often, cognitive decline is not noticeable because it could be as mild as forgetting names of people. However, research has shown that even in healthy adults, cognitive decline can start as early as in the late twenties or early thirties.
Fortunately for me, the FDA decided Smart Powder’s advertising was too explicit and ordered its piracetam sales stopped; I was equivocal at the previous price point, but then I saw that between the bulk discount and the fire-sale coupon, 3kg was only $99.99 (shipping was amortized over that, the choline, caffeine, and tryptophan). So I ordered in September 2010. As well, I had decided to cap my own pills, eliminating the inconvenience and bad taste. 3kg goes a very long way so I am nowhere close to running out of my pills; there is nothing to report since, as the pills are simply part of my daily routine.
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.
Most diehard nootropic users have considered using racetams for enhancing brain function. Racetams are synthetic nootropic substances first developed in Russia. These smart drugs vary in potency, but they are not stimulants. They are unlike traditional ADHD medications (Adderall, Ritalin, Vyvanse, etc.). Instead, racetams boost cognition by enhancing the cholinergic system.
The greatly increased variance, but only somewhat increased mean, is consistent with nicotine operating on me with an inverted U-curve for dosage/performance (or the Yerkes-Dodson law): on good days, 1mg nicotine is too much and degrades performance (perhaps I am overstimulated and find it hard to focus on something as boring as n-back) while on bad days, nicotine is just right and improves n-back performance.
Herbal supplements have been used for centuries to treat a wide range of medical conditions. Studies have shown that certain herbs may improve memory and cognition, and they can be used to help fight the effects of dementia and Alzheimer's disease. These herbs are considered safe when taken in normal doses, but care should be taken as they may interfere with other medications.
Sleep itself is an underrated cognition enhancer. It is involved in enhancing long-term memories as well as creativity. For instance, it is well established that during sleep memories are consolidated-a process that "fixes" newly formed memories and determines how they are shaped. Indeed, not only does lack of sleep make most of us moody and low on energy, cutting back on those precious hours also greatly impairs cognitive performance. Exercise and eating well also enhance aspects of cognition. It turns out that both drugs and "natural" enhancers produce similar physiological changes in the brain, including increased blood flow and neuronal growth in structures such as the hippocampus. Thus, cognition enhancers should be welcomed but not at the expense of our health and well being.
A poster or two on Longecity claimed that iodine supplementation had changed their eye color, suggesting a connection to the yellow-reddish element bromine - bromides being displaced by their chemical cousin, iodine. I was skeptical this was a real effect since I don’t know why visible amounts of either iodine or bromine would be in the eye, and the photographs produced were less than convincing. But it’s an easy thing to test, so why not?
Most research on these nootropics suggest they have some benefits, sure, but as Barbara Sahakian and Sharon Morein-Zamir explain in the journal Nature, nobody knows their long-term effects. And we don’t know how extended use might change your brain chemistry in the long run. Researchers are getting closer to what makes these substances do what they do, but very little is certain right now. If you’re looking to live out your own Limitless fantasy, do your research first, and proceed with caution.
In my last post, I talked about the idea that there is a resource that is necessary for self-control…I want to talk a little bit about the candidate for this resource, glucose. Could willpower fail because the brain is low on sugar? Let’s look at the numbers. A well-known statistic is that the brain, while only 2% of body weight, consumes 20% of the body’s energy. That sounds like the brain consumes a lot of calories, but if we assume a 2,400 calorie/day diet - only to make the division really easy - that’s 100 calories per hour on average, 20 of which, then, are being used by the brain. Every three minutes, then, the brain - which includes memory systems, the visual system, working memory, then emotion systems, and so on - consumes one (1) calorie. One. Yes, the brain is a greedy organ, but it’s important to keep its greediness in perspective… Suppose, for instance, that a brain in a person exerting their willpower - resisting eating brownies or what have you - used twice as many calories as a person not exerting willpower. That person would need an extra one third of a calorie per minute to make up the difference compared to someone not exerting willpower. Does exerting self control burn more calories?
Another study on the olfactory impact of essential oils like lavender and rosemary revealed that they produced positive effects on cognitive performance and mood.16 And in another study on the inhalation of essential oils like grapefruit, fennel, Estragon, and black pepper essential oil, inhalation of the oils resulted in modulation of sympathetic activity in adults.17,18
One symptom of Alzheimer's disease is a reduced brain level of the neurotransmitter called acetylcholine. It is thought that an effective treatment for Alzheimer's disease might be to increase brain levels of acetylcholine. Another possible treatment would be to slow the death of neurons that contain acetylcholine. Two drugs, Tacrine and Donepezil, are both inhibitors of the enzyme (acetylcholinesterase) that breaks down acetylcholine. These drugs are approved in the US for treatment of Alzheimer's disease.
One possibility is that when an individual takes a drug like noopept, they experience greater alertness and mental clarity. So, while the objective ability to see may not actually improve, the ability to process visual stimuli increases, resulting in the perception of improved vision. This allows individuals to process visual cues more quickly, take in scenes more easily, and allows for the increased perception of smaller details.
The use of prescription stimulants is especially prevalent among students. Surveys suggest that 0.7–4.5% of German students have used cognitive enhancers in their lifetimes. Stimulants such as dimethylamylamine and methylphenidate are used on college campuses and by younger groups. Based upon studies of self-reported illicit stimulant use, 5–35% of college students use diverted ADHD stimulants, which are primarily used for enhancement of academic performance rather than as recreational drugs. Several factors positively and negatively influence an individual's willingness to use a drug for the purpose of enhancing cognitive performance. Among them are personal characteristics, drug characteristics, and characteristics of the social context.