l-Theanine – A 2014 systematic review and meta-analysis found that concurrent caffeine and l-theanine use had synergistic psychoactive effects that promoted alertness, attention, and task switching; these effects were most pronounced during the first hour post-dose. However, the European Food Safety Authority reported that, when L-theanine is used by itself (i.e. without caffeine), there is insufficient information to determine if these effects exist.
This looks interesting: the Noopept effect is positive for all the dose levels, but it looks like a U-curve - low at 10mg, high at 15mg, lower at 20mg, and even lower at 30mg 48mg and 60mg aren’t estimated because they are hit by the missingness problem: the magnesium citrate variable is unavailable for the days the higher doses were taken on, and so their days are omitted and those levels of the factor are not estimated. One way to fix this is to drop magnesium from the model entirely, at the cost of fitting the data much more poorly and losing a lot of R2:
Some people consider stimulants to be a form of nootropic, while others distinguish them from the likes of caffeine, and Adderall -- of which there's currently a nationwide shortage. Most legal users of this attention-deficit hyperactivity disorder (ADHD) drug are children; it's prescribed sparingly in adults for fear of abuse. The FDA caused the shortage by halting delivery to drug manufacturers of the drug's active ingredient, an amphetamine, for months, arguing that enough Adderall had already been produced to satisfy all legal demand. The agency argued that abusers of Adderall are responsible for the shortage. That's a group that includes students and professionals using Adderall to help boost productivity during stressful times.
Qualia claims that its product stems from a new approach to science based on “principled meta-analysis and synthesis of existing research” to optimize “memory, focus, the speed of information processing, and pattern analysis.” The bottom line, however, is in its online medical disclaimer, which says: “These statements have not been evaluated by the Food and Drug Administration. . . . No claims are made about the safety of this product, nor are any medical or psychological benefits claimed.”
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.
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.
As professionals and aging baby boomers alike become more interested in enhancing their own brain power (either to achieve more in a workday or to stave off cognitive decline), a huge market has sprung up for nonprescription nootropic supplements. These products don’t convince Sahakian: “As a clinician scientist, I am interested in evidence-based cognitive enhancement,” she says. “Many companies produce supplements, but few, if any, have double-blind, placebo-controlled studies to show that these supplements are cognitive enhancers.” Plus, supplements aren’t regulated by the U.S. Food and Drug Administration (FDA), so consumers don’t have that assurance as to exactly what they are getting. Check out these 15 memory exercises proven to keep your brain sharp.
Spinach is rich in the antioxidant lutein, which is thought to help protect against cognitive decline, according to researchers from Tufts University. And a longitudinal study at Harvard Medical School found that women who reported eating the most leafy green and cruciferous vegetables had a markedly lower rate of cognitive decline, compared to those who ate the least.
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.
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.
The basic idea is to remedy a deficiency (not look for acute stimulant effects) and magnesium has a slow excretion rate18, so week-long blocks seem appropriate. I can reuse the same methodology as the lithium self-experiment. The response variables will be the usual mood/productivity self-rating and, since I was originally interested in magnesium for possible sleep quality improvements, a standardized score of sleep latency + # of awakenings + time spent awake (the same variable as my potassium sleep experiment).
For now, instead of reaching for a designer supplement, you're better off taking a multivitamin, according to some experts. It's well known that antioxidants like vitamins C and E protect cells from damage by disarming free radicals. Brain cells are especially vulnerable to these troublemakers because the brain generates more free radicals per gram of tissue than any other organ. Antioxidants also protect neurons by keeping blood vessels supple and open, ensuring the flow of nutrients to the brain.
Mosconi uses a pragmatic approach to improve your diet for brain health. The book is divided in three parts. The first one provides information regarding the brain nutritional requirement. The second one teaches you how to eat better. And, the third part tests you to find out where you are in terms of feeding yourself well. This includes an 80 question test that grades you as either Beginner/Intermediate/Advanced. “Beginner” entails you have little food awareness. You eat a lot of processed food. “Advanced” entails you eat very healthily, mainly organic foods. And, “Intermediate” falls in between.
Barbara Sahakian, a neuroscientist at Cambridge University, doesn’t dismiss the possibility of nootropics to enhance cognitive function in healthy people. She would like to see society think about what might be considered acceptable use and where it draws the line – for example, young people whose brains are still developing. But she also points out a big problem: long-term safety studies in healthy people have never been done. Most efficacy studies have only been short-term. “Proving safety and efficacy is needed,” she says.
Nor am I sure how important the results are - partway through, I haven’t noticed anything bad, at least, from taking Noopept. And any effect is going to be subtle: people seem to think that 10mg is too small for an ingested rather than sublingual dose and I should be taking twice as much, and Noopept’s claimed to be a chronic gradual sort of thing, with less of an acute effect. If the effect size is positive, regardless of statistical-significance, I’ll probably think about doing a bigger real self-experiment (more days blocked into weeks or months & 20mg dose)
Somewhat ironically given the stereotypes, while I was in college I dabbled very little in nootropics, sticking to melatonin and tea. Since then I have come to find nootropics useful, and intellectually interesting: they shed light on issues in philosophy of biology & evolution, argue against naive psychological dualism and for materialism, offer cases in point on the history of technology & civilization or recent psychology theories about addiction & willpower, challenge our understanding of the validity of statistics and psychology - where they don’t offer nifty little problems in statistics and economics themselves, and are excellent fodder for the young Quantified Self movement4; modafinil itself demonstrates the little-known fact that sleep has no accepted evolutionary explanation. (The hard drugs also have more ramifications than one might expect: how can one understand the history of Southeast Asia and the Vietnamese War without reference to heroin, or more contemporaneously, how can one understand the lasting appeal of the Taliban in Afghanistan and the unpopularity & corruption of the central government without reference to the Taliban’s frequent anti-drug campaigns or the drug-funded warlords of the Northern Alliance?)
The effects of piracetam on healthy volunteers have been studied even less than those of Adderall or modafinil. Most peer-reviewed studies focus on its effects on dementia or on people who have suffered a seizure or a concussion. Many of the studies that look at other neurological effects were performed on rats and mice. Piracetam's mechanisms of action are not understood, though it may increase levels of the neurotransmitter acetylcholine. In 2008 a committee of the British Academy of Medical Sciences noted that many of the clinical trials of piracetam for dementia were methodologically flawed. Another published review of the available studies of the drug concluded that the evidence "does not support the use of piracetam in the treatment of people with dementia or cognitive impairment", but suggested that further investigation might be warranted. I asked Seltzer if he thought he should wait for scientific ratification of piracetam. He laughed. "I don't want to," he said. "Because it's working."
It doesn't take a neuroscientist with a degree in nutrition to get that diet can affect the brain. It does take a neuroscientist with a degree in nutrition to provide such a smart research-driven analysis of how and to what extent. Brain Food is based on the work of literally hundreds of scientists and provides a dietary roadmap to enhanced cognitive power. That Dr. Mosconi's book is also fully accessible to a layperson makes this a true must read. (Bonus: Chapter 16 is a mini-cookbook with "brain boosting" recipes including several that are kid-friendly.)
One reason I like modafinil is that it enhances dopamine release, but it binds to your dopamine receptors differently than addictive substances like cocaine and amphetamines do, which may be part of the reason modafinil shares many of the benefits of other stimulants but doesn’t cause addiction or withdrawal symptoms.   It does increase focus, problem-solving abilities, and wakefulness, but it is not in the same class of drugs as Adderall, and it is not a classical stimulant. Modafinil is off of patent, so you can get it generically, or order it from India. It’s a prescription drug, so you need to talk to a physician.
When it comes to brain power, greens should be on your plate (and cover a lot of that plate) every meal. “Leafy greens are a great base. You swap out a lot of the empty carbohydrates you get from things like pastas or breads, and you can use some leafy greens,” says Psychiatrist Drew Ramsey, MD, author of The Happiness Diet and Eat Complete: The 21 Nutrients That Fuel Brainpower, Boost Weight Loss, and Transform Your Health. “Again, just lots of nutrient density.”
Since coffee drinking may lead to a worsening of calcium balance in humans, we studied the serial changes of serum calcium, PTH, 1,25-dihydroxyvitamin D (1,25(OH)2D) vitamin D and calcium balance in young and adult rats after daily administration of caffeine for 4 weeks. In the young rats, there was an increase in urinary calcium and endogenous fecal calcium excretion after four days of caffeine administration that persisted for the duration of the experiment. Serum calcium decreased on the fourth day of caffeine administration and then returned to control levels. In contrast, the serum PTH and 1,25(OH)2D remained unchanged initially, but increased after 2 weeks of caffeine administration…In the adult rat group, an increase in the urinary calcium and endogenous fecal calcium excretion and serum levels of PTH was found after caffeine administration. However, the serum 1,25(OH)2D levels and intestinal absorption coefficient of calcium remained the same as in the adult control group.
Difficulty concentrating. As mentioned previously, this may not be a direct result of age—though it can be a common side-effect of struggling with fatigue and brain fog. When it takes more mental energy to think, it is harder to stay with it for a long time. Many of us also are surrounded by distractions clambering for our limited attention. Modern life is fast-paced, stressful, and overcrowded.
If you’re a coffee or tea drinker, keep sipping: Caffeine may help protect against age-related cognitive decline. “Studies have indicated that caffeine—for example, roughly 500 milligrams daily, the equivalent of about five cups of coffee—may help stave off memory issues in humans,” says Bruce Citron, PhD, a neuroscientist at Bay Pines VA Healthcare System and the USF Morsani College of Medicine in Florida. (Experts warn against taking caffeine supplements, which flood your body with a lot of caffeine all at once.)
along with the previous bit of globalization is an important factor: shipping is ridiculously cheap. The most expensive S&H in my modafinil price table is ~$15 (and most are international). To put this in perspective, I remember in the 90s you could easily pay $15 for domestic S&H when you ordered online - but it’s 2013, and the dollar has lost at least half its value, so in real terms, ordering from abroad may be like a quarter of what it used to cost, which makes a big difference to people dipping their toes in and contemplating a small order to try out this ’nootropics thing they’ve heard about.
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 lifetime. 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 intended for performance enhancement 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.