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.
Methylphenidate was accepted into medical practice in 1960 as a way to treat narcolepsy and ADHD. It works by inhibiting the reuptake of dopamine and norepinephrine into the nervous system, causing a flooding of dopamine and norepinephrine in the synapse between the nerves, which in turn leads to amplified signaling between neurons. It’s been said that these effects are basically the same as those of amphetamines (see more details below), which are synthetic, addictive, mood-altering drugs, used illegally in sports as a stimulant and also legally as a prescription drug – like Ritalin – to treat children with ADD and adults with narcolepsy.
It’s a frosty Monday evening in March, but in the back of Idea Coffee, a dingy café near the Empire State Building, things are heating up. A group huddles around a small black box—the $160 ApeX Type A brain stimulator, with its retro-looking meter and dial and two electrodes. It’s supposed to bolster learning by delivering a mild electric current to the brain. The guy who’s been experimenting with it for a week notes that the only thing he’s noticed so far is a metallic taste in his mouth.
Woo understands that when selling brain drugs, skepticism comes with the territory. "The typical first reaction is, this is bullshit, you guys are snake-oil salesmen," he says. "We're not medical doctors nor biochemistry experts, but we are experts in building teams and building products. Like how Elon Musk attacks rockets and electric cars from 'first principles,' we see ourselves as applying Silicon Valley aesthetics and operational know-how to the murky world of nootropics."
And yet when enthusiasts share their vision of our neuroenhanced future it can sound dystopian. Zack Lynch, of NeuroInsights, gave me a rationale for smart pills that I found particularly grim. "If you're a 55-year-old in Boston, you have to compete with a 26-year-old from Mumbai now, and those kinds of pressures are only going to grow," he began. Countries other than the US might tend to be a little looser with their regulations and offer approval of new cognitive enhancers first. "And if you're a company that's got 47 offices worldwide, and all of a sudden your Singapore office is using cognitive enablers, and you're saying to Congress: 'I'm moving all my financial operations to Singapore and Taiwan, because it's legal to use those there', you bet that Congress is going to say: 'Well, OK.' It will be a moot question then.
These brain enhancers allow users to go without sleep for extended periods of time. But in the long-term, insomnia is a hazardous side effect, not a so-called benefit. Lack of sleep is extremely detrimental to your brain health and function. It’s during sleep that your brain consolidates memories, cleans away toxins, repairs itself, and creates new brain cells. (52, 53, 54, 55)
Adderall, a stimulant composed of mixed amphetamine salts, is commonly prescribed for children and adults who have been given a diagnosis of attention-deficit hyperactivity disorder (ADHD). But in recent years Adderall and Ritalin, another stimulant, have been adopted as cognitive enhancers: drugs that high-functioning, overcommitted people take to become higher-functioning and more overcommitted. (Such use is "off label", meaning that it does not have the approval of either the drug's manufacturer or the FDA, America's Food and Drug Administration.) College campuses have become laboratories for experimentation with neuroenhancement, and Alex was an ingenious experimenter. His brother had received a diagnosis of ADHD, and in his first year as an undergraduate Alex obtained an Adderall prescription for himself by describing to a doctor symptoms that he knew were typical of the disorder. During his college years, Alex took 15mg of Adderall most evenings, usually after dinner, guaranteeing that he would maintain intense focus while losing "any ability to sleep for approximately eight to 10 hours". In his second year, he persuaded the doctor to add a 30mg "extended-release" capsule to his daily regime.
A picture is worth a thousand words, particularly in this case where there seems to be temporal effects, different trends for the conditions, and general confusion. So, I drag up 2.5 years of MP data (for context), plot all the data, color by magnesium/non-magnesium, and fit different LOESS lines to each as a sort of smoothed average (since categorical data is hard to interpret as a bunch of dots), which yields:
Nootropics include natural and manmade chemicals that produce cognitive benefits. These substances are used to make smart pills that deliver results for enhancing memory and learning ability, improving brain function, enhancing the firing control mechanisms in neurons, and providing protection for the brain. College students, adult professionals, and elderly people are turning to supplements to get the advantages of nootropic substances for memory, focus, and concentration.
On the other metric, suppose we removed the creatine? Dropping 4 grams of material means we only need to consume 5.75 grams a day, covered by 8 pills (compared to 13 pills). We save 5,000 pills, which would have cost $45 and also don’t spend the $68 for the creatine; assuming a modafinil formulation, that drops our $1761 down to $1648 or $1.65 a day. Or we could remove both the creatine and modafinil, for a grand total of $848 or $0.85 a day, which is pretty reasonable.
Zack explained that he didn't really like the term enhancement: "We're not talking about superhuman intelligence. No one's saying we're coming out with a pill that's going to make you smarter than Einstein! What we're really talking about is enabling people." He sketched a bell curve on the back of a napkin. "Almost every drug in development is something that will take someone who's working at, like, 40% or 50%, and take them up to 80," he said.
I don’t believe there’s any need to control for training with repeated within-subject sampling, since there will be as many samples on both control and active days drawn from the later trained period as with the initial untrained period. But yes, my D5B scores seem to have plateaued pretty much and only very slowly increase; you can look at the stats file yourself.
Back home, I contacted Aubrey Marcus, whose company Onnit Labs produces Alpha Brain. He attributed my lucid dreaming to increased levels of the neurotransmitter acetylcholine, which enhances REM dreaming. Alpha Brain has two ingredients that boost acetylcholine levels: GPC choline, which the body converts to acetylcholine, and Huperzine A, an alkaloid derived from Chinese club moss, also known as Huperzia serrata. "Huperzine A disarms the enzyme that naturally breaks down acetylcholine," Marcus said. "So while the GPC choline is being converted to acetylcholine, the Huperzine A is keeping it from disappearing. It's like plugging the drain and turning on the faucet."
Research in animals shows that blueberries may help protect the brain from the damage caused by free radicals and may reduce the effects of age-related conditions such as Alzheimer's disease or dementia. Studies also show that diets rich in blueberries improved both the learning and muscle function of aging rats, making them mentally equal to much younger rats.
2 break days later, I took the quarter-pill at 11:22 PM. I had discovered I had for years physically possessed a very long interview not available online, and transcribing that seemed like a good way to use up a few hours. I did some reading, some Mnemosyne, and started it around midnight, finishing around 2:30 AM. There seemed a mental dip around 30 minutes after the armodafinil, but then things really picked up and I made very good progress transcribing the final draft of 9000 words in that period. (In comparison, The Conscience of the Otaking parts 2 & 4 were much easier to read than the tiny font of the RahXephon booklet, took perhaps 3 hours, and totaled only 6500 words. The nicotine is probably also to thank.) By 3:40 AM, my writing seems to be clumsier and my mind fogged. Began DNB at 3:50: 61/53/44. Went to bed at 4:05, fell asleep in 16 minutes, slept for 3:56. Waking up was easier and I felt better, so the extra hour seemed to help.
Analyzing the results is a little tricky because I was simultaneously running the first magnesium citrate self-experiment, which turned out to cause a quite complex result which looks like a gradually-accumulating overdose negating an initial benefit for net harm, and also toying with LLLT, which turned out to have a strong correlation with benefits. So for the potential small Noopept effect to not be swamped, I need to include those in the analysis. I designed the experiment to try to find the best dose level, so I want to look at an average Noopept effect but also the estimated effect at each dose size in case some are negative (especially in the case of 5-pills/60mg); I included the pilot experiment data as 10mg doses since they were also blind & randomized. Finally, missingness affects analysis: because not every variable is recorded for each date (what was the value of the variable for the blind randomized magnesium citrate before and after I finished that experiment? what value do you assign the Magtein variable before I bought it and after I used it all up?), just running a linear regression may not work exactly as one expects as various days get omitted because part of the data was missing.
Blueberries. "Brainberries" is what Steven Pratt, MD, author of Superfoods Rx: Fourteen Foods Proven to Change Your Life, calls these tasty fruits. Pratt, who is also on staff at Scripps Memorial Hospital in La Jolla, Calif., says that in animal studies researchers have found that blueberries help protect the brain from oxidative stress and may reduce the effects of age-related conditions such as Alzheimer's disease or dementia. Studies have also shown that diets rich in blueberries significantly improved both the learning capacity and motor skills of aging rats, making them mentally equivalent to much younger rats. Ann Kulze, MD, author of Dr. Ann's 10-Step Diet: A Simple Plan for Permanent Weight Loss & Lifelong Vitality, recommends adding at least 1 cup of blueberries a day in any form -- fresh, frozen, or freeze-dried.
I take my piracetam in the form of capped pills consisting (in descending order) of piracetam, choline bitartrate, anhydrous caffeine, and l-tyrosine. On 8 December 2012, I happened to run out of them and couldn’t fetch more from my stock until 27 December. This forms a sort of (non-randomized, non-blind) short natural experiment: did my daily 1-5 mood/productivity ratings fall during 8-27 December compared to November 2012 & January 2013? The graphed data29 suggests to me a decline:
I have personally found that with respect to the NOOTROPIC effect(s) of all the RACETAMS, whilst I have experienced improvements in concentration and working capacity / productivity, I have never experienced a noticeable ongoing improvement in memory. COLURACETAM is the only RACETAM that I have taken wherein I noticed an improvement in MEMORY, both with regards to SHORT-TERM and MEDIUM-TERM MEMORY. To put matters into perspective, the memory improvement has been mild, yet still significant; whereas I have experienced no such improvement at all with the other RACETAMS.
Take at 10 AM; seem a bit more active but that could just be the pressure of the holiday season combined with my nice clean desk. I do the chores without too much issue and make progress on other things, but nothing major; I survive going to The Sitter without too much tiredness, so ultimately I decide to give the palm to it being active, but only with 60% confidence. I check the next day, and it was placebo. Oops.
Caffeine, Tulsi and Astragalus: Tulsi is one of the greatest calming adaptogens that exists, trusted and revered for centuries in Ayurvedic medicine and culture. Tulsi has been researched and shown to uplift mood, support digestion, and promote balanced energy. Because it’s also an anxiolytic (causes anti-anxiety effects) tulsi, similar to coffee with L-theanine, does a good job balancing out any over-stimulating effects of the caffeine in coffee. But you can also take things one step further and blend in astragalus, which, in Chinese medicine, is considered a “strong” Ki invigorating herb that provides a stable source of non-crashing energy. Astragalus also contains an enormous variety of saponins, flavonoids, and polysaccharides, and is considered to be a “longevity adaptogen”. Pairing with antioxidant-rich coffee and tulsi produces a match made in longevity heaven. For this blend, which I often use if drinking coffee in the afternoon, I’m a fan of the Four Sigmatic Adaptogen Blend, which contains coffee, astragalus, tulsi and cinnamon.
Looking at the prices, the overwhelming expense is for modafinil. It’s a powerful stimulant - possibly the single most effective ingredient in the list - but dang expensive. Worse, there’s anecdotal evidence that one can develop tolerance to modafinil, so we might be wasting a great deal of money on it. (And for me, modafinil isn’t even very useful in the daytime: I can’t even notice it.) If we drop it, the cost drops by a full $800 from $1761 to $961 (almost halving) and to $0.96 per day. A remarkable difference, and if one were genetically insensitive to modafinil, one would definitely want to remove it.
More than once I have seen results indicating that high-IQ types benefit the least from random nootropics; nutritional deficits are the premier example, because high-IQ types almost by definition suffer from no major deficiencies like iodine. But a stimulant modafinil may be another such nootropic (see Cognitive effects of modafinil in student volunteers may depend on IQ, Randall et al 2005), which mentions:
It is incredibly easy to abuse and become addicted to methylphenidate, and misuse is shockingly prevalent, even among so-called “non-affected” users: with students, biohackers, soccer moms and busy executives popping it – and many of the other smart drugs below – like candy. It’s also not all it’s cracked up to be. Side effects include insomnia, stomach ache, headache and anorexia. Overdoses (which may occur easily as it can be difficult to estimate and regulate dosage) can lead to agitation, hallucinations, psychosis, lethargy, seizures, tachycardia (rapid heart rate), dysrhythmia (irregular heart rhythms), hypertension and hyperthermia. Methylphenidate is particularly hazardous to developing brains, especially those of younger students who are frequently prescribed the drug or who – often in high school and college – use it without a prescription. The prefrontal cortex, located behind the forehead, is responsible for cognition, personality-expression and decision-making, and develops well into the mid-20s, at which point it takes over as the “rational” part of the brain. In the central nervous system, and particularly in the prefrontal cortex, dopamine levels must have a natural rise and fall in order for healthy rational processes (executive control) to develop. By influencing dopamine levels, methylphenidate can negatively impact this healthy cognitive development, especially when it is abused or used too frequently.
Directions As a dietary supplement take two(2) veggie capsules once a day. For best results take 20-30 min before a meal with an 8oz. glass of water or as directed by your healthcare professional. as a dietary supplement take 2 veggie capsules once a day . For best results take 20-30 min before a meal with an 8oz. Glass of water or as directed by your healthcare professional. — — Suggested Use: As a dietary supplement, adults take one (1) capsule per day. Do not exceed 2 capsules per day. Take 1 capsule at a time with or after a meal. No more than 2 capsules a day.
L-Alpha glycerylphosphorylcholine or choline alfoscerate, also known as Alpha GPC is a natural nootropic which works both on its own and also in combination with other nootropics. It can be found in the human body naturally in small amounts. It’s also present in some dairy products, wheat germ, and in organic meats. However, these dietary sources contain small amounts of GPC, which is why people prefer taking it through supplements.
-Water [is also important]. Over 80% of the brain’s content is water. Every chemical reaction that takes place in the brain needs water, especially energy production. The brain is so sensitive to dehydration that even a minimal loss of water can cause symptoms like brain fog, fatigue, dizziness, confusion and, more importantly, brain shrinkage. The longevity and well-being of your brain are critically dependent upon consuming hard water. This refers to plain water that is high in minerals and natural electrolytes. Most people don’t realize that the water they’re drinking is not actually “water”.
Regardless, while in the absence of piracetam, I did notice some stimulant effects (somewhat negative - more aggressive than usual while driving) and similar effects to piracetam, I did not notice any mental performance beyond piracetam when using them both. The most I can say is that on some nights, I seemed to be less easily tired when writing or editing or n-backing (and I felt less tired than ICON 2011 than ICON 2010), but those were also often nights I was also trying out all the other things I had gotten in that order from Smart Powders, and I am still dis-entangling what was responsible. (Probably the l-theanine or sulbutiamine.)
Most of the most solid fish oil results seem to meliorate the effects of age; in my 20s, I’m not sure they are worth the cost. But I would probably resume fish oil in my 30s or 40s when aging really becomes a concern. So the experiment at most will result in discontinuing for a decade. At $X a year, that’s a net present value of sum $ map (\n -> 70 / (1 + 0.05)^n) [1..10] = $540.5.
It goes without saying that ensuring your brain performs at its top capacity levels is every person’s priority. However, the trouble is this is something easier said than done. We live in the extremely competitive and demanding modern world. That’s a fact. We aren’t getting any younger. That’s also a fact. The inevitable aging process takes a toll on our mental capacity and brain itself, as well. So, what can you do about it? Natural supplements can boost your brain power in an efficient and harmless way. This is how one of these supplements named Brain Pill caught our attention.
The powder itself is quite bulky; the recommended dose to hit 200mg of absorbed magnesium leads to ~7g of powder (so capping will be difficult) and the container provides only 30 doses’ worth (or each dose costs $1!). It’s described as lemon-flavored, and it is, but it’s sickly-sweet unpleasant and since it’s so much powder, takes half a glass of water to dissolve it entirely and wash it down. Subjectively, I notice nothing after taking it for a week. I may try a simple A-B-A analysis of sleep or Mnemosyne, but I’m not optimistic. And given the large expense of LEF’s Magtein, it’s probably a non-starter even if there seems to be an effect. For sleep effects, I will have to look at more reasonably priced magnesium sources.
A big part is that we are finally starting to apply complex systems science to psycho-neuro-pharmacology and a nootropic approach. The neural system is awesomely complex and old-fashioned reductionist science has a really hard time with complexity. Big companies spends hundreds of millions of dollars trying to separate the effects of just a single molecule from placebo – and nootropics invariably show up as “stacks” of many different ingredients (ours, Qualia , currently has 42 separate synergistic nootropics ingredients from alpha GPC to bacopa monnieri and L-theanine). That kind of complex, multi pathway input requires a different methodology to understand well that goes beyond simply what’s put in capsules.