“Who doesn’t want to maximize their cognitive ability? Who doesn’t want to maximize their muscle mass?” asks Murali Doraiswamy, who has led several trials of cognitive enhancers at Duke University Health System and has been an adviser to pharmaceutical and supplement manufacturers as well as the Food and Drug Administration. He attributes the demand to an increasingly knowledge-based society that values mental quickness and agility above all else.
We felt that True Focus offered a good product but the price was slightly high compared to others. Their website doesn’t show a clear money-back guarantee though, which definitely reduced their rating. We found that their customer reviews were mixed and saw that some consumers did not mind paying a little more for a product that is more consumer friendly.
This tendency is exacerbated by general inefficiencies in the nootropics market - they are manufactured for vastly less than they sell for, although the margins aren’t as high as they are in other supplement markets, and not nearly as comical as illegal recreational drugs. (Global Price Fixing: Our Customers are the Enemy (Connor 2001) briefly covers the vitamin cartel that operated for most of the 20th century, forcing food-grade vitamins prices up to well over 100x the manufacturing cost.) For example, the notorious Timothy Ferriss (of The Four-hour Work Week) advises imitators to find a niche market with very high margins which they can insert themselves into as middlemen and reap the profits; one of his first businesses specialized in… nootropics & bodybuilding. Or, when Smart Powders - usually one of the cheapest suppliers - was dumping its piracetam in a fire sale of half-off after the FDA warning, its owner mentioned on forums that the piracetam was still profitable (and that he didn’t really care because selling to bodybuilders was so lucrative); this was because while SP was selling 2kg of piracetam for ~$90, Chinese suppliers were offering piracetam on AliBaba for $30 a kilogram or a third of that in bulk. (Of course, you need to order in quantities like 30kg - this is more or less the only problem the middlemen retailers solve.) It goes without saying that premixed pills or products are even more expensive than the powders.
These days, nootropics are beginning to take their rightful place as a particularly powerful tool in the Neurohacker’s toolbox. After all, biochemistry is deeply foundational to neural function. Whether you are trying to fix the damage that is done to your nervous system by a stressful and toxic environment or support and enhance your neural functioning, getting the chemistry right is table-stakes. And we are starting to get good at getting it right. What’s changed?
A pastor named John Piper said it well, “If hearing about God’s judgment makes it harder for us to love God, then probably the God we love is a figment of our imagination and not the real and true God. If we would love the true God, we must know the true God. There is something wrong with our faith if we cannot sing praises to God not only as our loving Father but also as the righteous Judge of all the earth.”
Cacao contains powerful flavonols, compounds that act as antioxidants and help preserve the brain’s stem cells. “Stem cells produce new brain cells,” says Dennis Steindler, PhD, director of the Neuroscience and Aging Lab at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, “and chronic inflammation or the beginnings of disease can damage these reparative cells and the other at-risk brain cells used for standard operating procedures, like memory and thinking.” Flavonols have also been shown to support the hippocampus, a part of the brain involved in memory and mood, notes Steindler. Stick to a square or two of dark chocolate daily.
Brain enhancing drug – the steroids of the mental world, these are compounds that can be both artificial or natural that are not recommended for casual consumption. If taken over a long period of time, they can and will result in permanent and debilitating damage, and if taken wrongly, they can and will result in injury, illness, and death. So far from being the best brain pill that they loop around and punch the actual best brain pill in the face.
Celastrus paniculatus, also known as the Intellect Tree, is perhaps one of the more interesting Ayurvedic medicinal plants that has been used for thousands of years, and one that I personally use quite frequently as part of the supplement “Qualia Mind”. In the Ayurvedic tradition, oil derived from C. paniculatus (Malkanguni oil) is used to enhance memory and intellectual capacity, as well as to improve dream recall and induce lucid dreams. In a study performed on healthy rats, the oil was shown to improve 24-hour memory retention after a single dose, an effect accompanied by a reduction in monoamines like norepinephrine, dopamine and serotonin, indicating a decreased turnover of these neurotransmitters which, in turn, may aid in reducing conditions like depression. In another study with rats, C. paniculatus oil administered for 14 days reversed stress-induced spatial learning and memory impairment and restored working memory. In mice with scopolamine-induced memory deficits, the oil has been shown to improve both spatial and fear memory (a type of fear conditioning through which an organism learns to avoid detrimental situations or events). Traditionally, is taken in seed form, starting with 10 seeds and working up to 15 and finally 20 seeds.
The peculiar tired-sharp feeling was there as usual, and the DNB scores continue to suggest this is not an illusion, as they remain in the same 30-50% band as my normal performance. I did not notice the previous aboulia feeling; instead, around noon, I was filled with a nervous energy and a disturbingly rapid pulse which meditation & deep breathing did little to help with, and which didn’t go away for an hour or so. Fortunately, this was primarily at church, so while I felt irritable, I didn’t actually interact with anyone or snap at them, and was able to keep a lid on it. I have no idea what that was about. I wondered if it might’ve been a serotonin storm since amphetamines are some of the drugs that can trigger storms but the Adderall had been at 10:50 AM the previous day, or >25 hours (the half-lives of the ingredients being around 13 hours). An hour or two previously I had taken my usual caffeine-piracetam pill with my morning tea - could that have interacted with the armodafinil and the residual Adderall? Or was it caffeine+modafinil? Speculation, perhaps. A house-mate was ill for a few hours the previous day, so maybe the truth is as prosaic as me catching whatever he had.
The abuse liability of caffeine has been evaluated.147,148 Tolerance development to the subjective effects of caffeine was shown in a study in which caffeine was administered at 300 mg twice each day for 18 days.148 Tolerance to the daytime alerting effects of caffeine, as measured by the MSLT, was shown over 2 days on which 250 g of caffeine was given twice each day48 and to the sleep-disruptive effects (but not REM percentage) over 7 days of 400 mg of caffeine given 3 times each day.7 In humans, placebo-controlled caffeine-discontinuation studies have shown physical dependence on caffeine, as evidenced by a withdrawal syndrome.147 The most frequently observed withdrawal symptom is headache, but daytime sleepiness and fatigue are also often reported. The withdrawal-syndrome severity is a function of the dose and duration of prior caffeine use…At higher doses, negative effects such as dysphoria, anxiety, and nervousness are experienced. The subjective-effect profile of caffeine is similar to that of amphetamine,147 with the exception that dysphoria/anxiety is more likely to occur with higher caffeine doses than with higher amphetamine doses. Caffeine can be discriminated from placebo by the majority of participants, and correct caffeine identification increases with dose.147 Caffeine is self-administered by about 50% of normal subjects who report moderate to heavy caffeine use. In post-hoc analyses of the subjective effects reported by caffeine choosers versus nonchoosers, the choosers report positive effects and the nonchoosers report negative effects. Interestingly, choosers also report negative effects such as headache and fatigue with placebo, and this suggests that caffeine-withdrawal syndrome, secondary to placebo choice, contributes to the likelihood of caffeine self-administration. This implies that physical dependence potentiates behavioral dependence to caffeine.
Some people warn of the dangers of modafinil. There are anecdotal personal accounts online of people becoming dependent on this drug. Modafinil is the generic of the brand Provigil, a nootropic. Provigil is FDA-approved to stimulate wakefulness in people suffering from sleep disorders, such as narcolepsy and sleep apnea. Initially, Provigil was thought to have a benign, non-addiction-forming profile. As such, the Drug Enforcement Administration classifies Provigil as a Schedule IV drug, a category reserved for drugs with low abuse potential; however, recent research conducted by the National Institute on Drug Abuse (NIDA) has found that Provigil may in fact be addictive.
The advantage of adrafinil is that it is legal & over-the-counter in the USA, so one removes the small legal risk of ordering & possessing modafinil without a prescription, and the retailers may be more reliable because they are not operating in a niche of dubious legality. Based on comments from others, the liver problem may have been overblown, and modafinil vendors post-2012 seem to have become more unstable, so I may give adrafinil (from another source than Antiaging Central) a shot when my modafinil/armodafinil run out.
Finding a usable product on Amazon caused me some difficulties. I wanted a 500mg magnesium-citrate-only product at <$20 for 120 doses, but I discovered most of the selection for magnesium citrate had sub-500mg doses, involved calcium citrate or other substances like zinc (not necessarily a bad thing, but would confound an experiment), were mostly magnesium oxide rather than citrate, or some still other problem. Ultimately I settled on Solgar’s $13 120x400mg magnesium citrate as acceptable. (To compare with the bulkiness of the LEF vitamin D+l-threonate powder, the Office of Dietary Supplements says magnesium citrate is 16% magnesium, so to get 400mg of magnesium as claimed, would take 2.5g of material, rather than 7g for 200mg; even if l-threonate is absorbed 100% and citrate 50%, the citrate is ahead. The pills turn out to be wider and longer than my 00 pills; if I want to get them into my gel capsules, I have to crush them into fine powder. The powder from one pill turns out to take up 2 00 pills.)
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.
The chemical Huperzine-A (Examine.com) is extracted from a moss. It is an acetylcholinesterase inhibitor (instead of forcing out more acetylcholine like the -racetams, it prevents acetylcholine from breaking down). My experience report: One for the null hypothesis files - Huperzine-A did nothing for me. Unlike piracetam or fish oil, after a full bottle (Source Naturals, 120 pills at 200μg each), I noticed no side-effects, no mental improvements of any kind, and no changes in DNB scores from straight Huperzine-A.
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.
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.
A record of nootropics I have tried, with thoughts about which ones worked and did not work for me. These anecdotes should be considered only as anecdotes, and one’s efforts with nootropics a hobby to put only limited amounts of time into due to the inherent limits of drugs as a force-multiplier compared to other things like programming1; for an ironic counterpoint, I suggest the reader listen to a video of Jonathan Coulton’s I Feel Fantastic while reading.
“Brain-berries” is what Steven Pratt, MD, author of SuperFoods Rx: Fourteen Foods That Will Change Your Life, calls these antioxidant-packed fruits on WebMD.com. This tiny but powerful berry helps protect the brain from oxidative stress and may reduce the effects of age-related conditions such as Alzheimer’s disease or dementia. In a recent study, researchers gave a group of adults with mild cognitive impairment, a risk condition for Alzheimer’s, freeze-dried blueberry powder daily, while another group took a placebo. After 16 weeks, those who ate the blueberry powder (the equivalent of one cup of berries) had improved memory, better cognitive performance, and increased brain activity. Your everyday habits may also reduce your risk of Alzheimer’s.
The body has its own inherent detoxification pathways that are responsible for packaging and removing heavy metals safely from the system. For example, glutathione is known as the body’s ‘master antioxidant’ and aside from playing an important role in preventing free radicals from causing damage to the body’s cells, it also helps to bind to heavy metals and remove them from the body. Research shows that glutathione levels are lower than normal in those on the autism spectrum, so enhancing levels through the diet may be an effective way to prevent the accumulation of heavy metals. Consuming sulfur-rich foods such as broccoli, cabbage, onions, garlic, kale and cauliflower can boost glutathione levels, as well as milk thistle, which has unique flavonoids that also support glutathione production.
Nootropics. You might have heard of them. The “limitless pill” that keeps Billionaires rich. The ‘smart drugs’ that students are taking to help boost their hyperfocus. The cognitive enhancers that give corporate executives an advantage. All very exciting. But as always, the media are way behind the curve. Yes, for the past few decades, cognitive enhancers were largely sketchy substances that people used to grasp at a short term edge at the expense of their health and wellbeing. But the days of taking prescription pills to pull an all-nighter are so 2010. The better, safer path isn’t with these stimulants but with nootropics. Nootropics consist of supplements and substances which enhance your cognition, in particular when it comes to motivation, creativity, memory, and other executive functions.