On the other end of the spectrum is the nootropic stack, a practice where individuals create a cocktail or mixture of different smart drugs for daily intake. The mixture and its variety actually depend on the goals of the user. Many users have said that nootropic stacking is more effective for delivering improved cognitive function in comparison to single nootropics.
l-theanine (Examine.com) is occasionally mentioned on Reddit or Imminst or LessWrong32 but is rarely a top-level post or article; this is probably because theanine was discovered a very long time ago (>61 years ago), and it’s a pretty straightforward substance. It’s a weak relaxant/anxiolytic (Google Scholar) which is possibly responsible for a few of the health benefits of tea, and which works synergistically with caffeine (and is probably why caffeine delivered through coffee feels different from the same amount consumed in tea - in one study, separate caffeine and theanine were a mixed bag, but the combination beat placebo on all measurements). The half-life in humans seems to be pretty short, with van der Pijl 2010 putting it ~60 minutes. This suggests to me that regular tea consumption over a day is best, or at least that one should lower caffeine use - combining caffeine and theanine into a single-dose pill has the problem of caffeine’s half-life being much longer so the caffeine will be acting after the theanine has been largely eliminated. The problem with getting it via tea is that teas can vary widely in their theanine levels and the variations don’t seem to be consistent either, nor is it clear how to estimate them. (If you take a large dose in theanine like 400mg in water, you can taste the sweetness, but it’s subtle enough I doubt anyone can actually distinguish the theanine levels of tea; incidentally, r-theanine - the useless racemic other version - anecdotally tastes weaker and less sweet than l-theanine.)
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).
One claim was partially verified in passing by Eliezer Yudkowsky (Supplementing potassium (citrate) hasn’t helped me much, but works dramatically for Anna, Kevin, and Vassar…About the same as drinking a cup of coffee - i.e., it works as a perker-upper, somehow. I’m not sure, since it doesn’t do anything for me except possibly mitigate foot cramps.)
One of the most widely known classes of smart drugs on the market, Racetams, have a long history of use and a lot of evidence of their effectiveness. They hasten the chemical exchange between brain cells, directly benefiting our mental clarity and learning process. They are generally not controlled substances and can be purchased without a prescription in a lot of locations globally.
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.
I noticed what may have been an effect on my dual n-back scores; the difference is not large (▃▆▃▃▂▂▂▂▄▅▂▄▂▃▅▃▄ vs ▃▄▂▂▃▅▂▂▄▁▄▃▅▂▃▂▄▂▁▇▃▂▂▄▄▃▃▂▃▂▂▂▃▄▄▃▆▄▄▂▃▄▃▁▂▂▂▃▂▄▂▁▁▂▄▁▃▂▄) and appears mostly in the averages - Toomim’s quick two-sample t-test gave p=0.23, although a another analysis gives p=0.138112. One issue with this before-after quasi-experiment is that one would expect my scores to slowly rise over time and hence a fish oil after would yield a score increase - the 3.2 point difference could be attributable to that, placebo effect, or random variation etc. But an accidentally noticed effect (d=0.28) is a promising start. An experiment may be worth doing given that fish oil does cost a fair bit each year: randomized blocks permitting an fish-oil-then-placebo comparison would take care of the first issue, and then blinding (olive oil capsules versus fish oil capsules?) would take care of the placebo worry.
Tyrosine (Examine.com) is an amino acid; people on the Imminst.org forums (as well as Wikipedia) suggest that it helps with energy and coping with stress. I ordered 4oz (bought from Smart Powders) to try it out, and I began taking 1g with my usual caffeine+piracetam+choline mix. It does not dissolve easily in hot water, and is very chalky and not especially tasty. I have not noticed any particular effects from it.
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Intrigued by old scientific results & many positive anecdotes since, I experimented with microdosing LSD - taking doses ~10μg, far below the level at which it causes its famous effects. At this level, the anecdotes claim the usual broad spectrum of positive effects on mood, depression, ability to do work, etc. After researching the matter a bit, I discovered that as far as I could tell, since the original experiment in the 1960s, no one had ever done a blind or even a randomized self-experiment on it.
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.)
Other drugs, like cocaine, are used by bankers to manage their 18-hour workdays . Unlike nootropics, dependency is very likely and not only mentally but also physically. Bankers and other professionals who take drugs to improve their productivity will become dependent. Almost always, the negative consequences outweigh any positive outcomes from using drugs.
When comparing supplements, consider products with a score above 90% to get the greatest benefit from smart pills to improve memory. Additionally, we consider the reviews that users send to us when scoring supplements, so you can determine how well products work for others and use this information to make an informed decision. Every month, our editor puts her name on that month’s best smart bill, in terms of results and value offered to users.
I’ve been actively benefitting from nootropics since 1997, when I was struggling with cognitive performance and ordered almost $1000 worth of smart drugs from Europe (the only place where you could get them at the time). I remember opening the unmarked brown package and wondering whether the pharmaceuticals and natural substances would really enhance my brain.
With so many different ones to choose from, choosing the best nootropics for you can be overwhelming at times. As usual, a decision this important will require research. Study up on the top nootropics which catch your eye the most. The nootropics you take will depend on what you want the enhancement for. The ingredients within each nootropic determine its specific function. For example, some nootropics contain ginkgo biloba, which can help memory, thinking speed, and increase attention span. Check the nootropic ingredients as you determine what end results you want to see. Some nootropics supplements can increase brain chemicals such as dopamine and serotonin. An increase in dopamine levels can be very useful for memory, alertness, reward and more. Many healthy adults, as well as college students take nootropics. This really supports the central nervous system and the brain.
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.
Fortunately, there are some performance-enhancing habits that have held up under rigorous scientific scrutiny. They are free, and easy to pronounce. Unfortunately, they are also the habits you were perhaps hoping to forego by using nootropics instead. “Of all the things that are supposed to be ‘good for the brain,’” says Stanford neurology professor Sharon Sha, “there is more evidence for exercise than anything else.” Next time you’re facing a long day, you could take a pill and see what happens.
In addition, while the laboratory research reviewed here is of interest concerning the effects of stimulant drugs on specific cognitive processes, it does not tell us about the effects on cognition in the real world. How do these drugs affect academic performance when used by students? How do they affect the total knowledge and understanding that students take with them from a course? How do they affect various aspects of occupational performance? Similar questions have been addressed in relation to students and workers with ADHD (Barbaresi, Katusic, Colligan, Weaver, & Jacobsen, 2007; Halmøy, Fasmer, Gillberg, & Haavik, 2009; see also Advokat, 2010) but have yet to be addressed in the context of cognitive enhancement of normal individuals.
Adderall is an amphetamine, used as a drug to help focus and concentration in people with ADHD, and promote wakefulness for sufferers of narcolepsy. Adderall increases levels of dopamine and norepinephrine in the brain, along with a few other chemicals and neurotransmitters. It’s used off-label as a study drug, because, as mentioned, it is believed to increase focus and concentration, improve cognition and help users stay awake. Please note: Side Effects Possible.
Stayed up with the purpose of finishing my work for a contest. This time, instead of taking the pill as a single large dose (I feel that after 3 times, I understand what it’s like), I will take 4 doses over the new day. I took the first quarter at 1 AM, when I was starting to feel a little foggy but not majorly impaired. Second dose, 5:30 AM; feeling a little impaired. 8:20 AM, third dose; as usual, I feel physically a bit off and mentally tired - but still mentally sharp when I actually do something. Early on, my heart rate seemed a bit high and my limbs trembling, but it’s pretty clear now that that was the caffeine or piracetam. It may be that the other day, it was the caffeine’s fault as I suspected. The final dose was around noon. The afternoon crash wasn’t so pronounced this time, although motivation remains a problem. I put everything into finishing up the spaced repetition literature review, and didn’t do any n-backing until 11:30 PM: 32/34/31/54/40%.
Smart pills have revolutionized the diagnosis of gastrointestinal disorders and could replace conventional diagnostic techniques such as endoscopy. Traditionally, an endoscopy probe is inserted into a patient’s esophagus, and subsequently the upper and lower gastrointestinal tract, for diagnostic purposes. There is a risk of perforation or tearing of the esophageal lining, and the patient faces discomfort during and after the procedure. A smart pill or wireless capsule endoscopy (WCE), however, can easily be swallowed and maneuvered to capture images, and requires minimal patient preparation, such as sedation. The built-in sensors allow the measurement of all fluids and gases in the gut, giving the physician a multidimensional picture of the human body.
Nootropics are a broad classification of cognition-enhancing compounds that produce minimal side effects and are suitable for long-term use. These compounds include those occurring in nature or already produced by the human body (such as neurotransmitters), and their synthetic analogs. We already regularly consume some of these chemicals: B vitamins, caffeine, and L-theanine, in our daily diets.
The main area of the brain effected by smart pills is the prefrontal cortex, where representations of our goals for the future are created. Namely, the prefrontal cortex consists of pyramidal cells that keep each other firing. However in some instances they can become disconnected due to chemical imbalances, or due to being tired, stressed, and overworked.
As expected since most of the data overlaps with the previous LLLT analysis, the LLLT variable correlates strongly; the individual magnesium variables may look a little more questionable but were justified in the magnesium citrate analysis. The Noopept result looks a little surprising - almost zero effect? Let’s split by dose (which was the point of the whole rigmarole of changing dose levels):
Historically used to help people with epilepsy, piracetam is used in some cases of myoclonus, or muscle twitching. Its actual mechanism of action is unclear: It doesn’t act exactly as a sedative or stimulant, but still influences cognitive function, and is believed to act on receptors for acetylcholine in the brain. Piracetam is used off-label as a 'smart drug' to help focus and concentration or sometimes as a way to allegedly boost your mood. Again, piracetam is a prescription-only drug - any supply to people without a prescription is illegal, and supplying it may result in a fine or prison sentence.
Deficiencies in B vitamins can cause memory problems, mood disorders, and cognitive impairment. B vitamins will not make you smarter on their own. Still, they support a wide array of cognitive functions. Most of the B complex assists in some fashion with brain activity. Vitamin B12 (Methylcobalamin) is the most critical B vitamin for mental health.
Many of these supplements include exotic-sounding ingredients. Ginseng root and an herb called bacopa are two that have shown some promising memory and attention benefits, says Dr. Guillaume Fond, a psychiatrist with France’s Aix-Marseille University Medical School who has studied smart drugs and cognitive enhancement. “However, data are still lacking to definitely confirm their efficacy,” he adds.
(People aged <=18 shouldn’t be using any of this except harmless stuff - where one may have nutritional deficits - like fish oil & vitamin D; melatonin may be especially useful, thanks to the effects of screwed-up school schedules & electronics use on teenagers’ sleep. Changes in effects with age are real - amphetamines’ stimulant effects and modafinil’s histamine-like side-effects come to mind as examples.)
If this is the case, this suggests some thoughtfulness about my use of nicotine: there are times when use of nicotine will not be helpful, but times where it will be helpful. I don’t know what makes the difference, but I can guess it relates to over-stimulation: on some nights during the experiment, I had difficult concentrating on n-backing because it was boring and I was thinking about the other things I was interested in or working on - in retrospect, I wonder if those instances were nicotine nights.
Flow diagram of cognitive neuroscience literature search completed July 2, 2010. Search terms were dextroamphetamine, Aderrall, methylphenidate, or Ritalin, and cognitive, cognition, learning, memory, or executive function, and healthy or normal. Stages of subsequent review used the information contained in the titles, abstracts, and articles to determine whether articles reported studies meeting the inclusion criteria stated in the text.
Over the last few months, as part of a new research project, I have talked with five people who regularly use drugs at work. They are all successful in their jobs, financially secure, in stable relationships, and generally content with their lives. None of them have plans to stop using the drugs, and so far they have kept the secret from their employers. But as their colleagues become more likely to start using the same drugs (people talk, after all), will they continue to do so?
Nondrug cognitive-enhancement methods include the high tech and the low. An example of the former is transcranial magnetic stimulation (TMS), whereby weak currents are induced in specific brain areas by magnetic fields generated outside the head. TMS is currently being explored as a therapeutic modality for neuropsychiatric conditions as diverse as depression and ADHD and is capable of enhancing the cognition of normal healthy people (e.g., Kirschen, Davis-Ratner, Jerde, Schraedley-Desmond, & Desmond, 2006). An older technique, transcranial direct current stimulation (tDCS), has become the subject of renewed research interest and has proven capable of enhancing the cognitive performance of normal healthy individuals in a variety of tasks. For example, Flöel, Rösser, Michka, Knecht, and Breitenstein (2008) reported enhancement of learning and Dockery, Hueckel-Weng, Birbaumer, and Plewnia (2009) reported enhancement of planning with tDCS.
So is there a future in smart drugs? Some scientists are more optimistic than others. Gary Lynch, a professor in the School of Medicine at the University of California, Irvine argues that recent advances in neuroscience have opened the way for the smart design of drugs, configured for specific biological targets in the brain. “Memory enhancement is not very far off,” he says, although the prospects for other kinds of mental enhancement are “very difficult to know… To me, there’s an inevitability to the thing, but a timeline is difficult.”
It is not because of the few thousand francs which would have to be spent to put a roof [!] over the third-class carriages or to upholster the third-class seats that some company or other has open carriages with wooden benches. What the company is trying to do is to prevent the passengers who can pay the second class fare from traveling third class; it hits the poor, not because it wants to hurt them, but to frighten the rich. And it is again for the same reason that the companies, having proved almost cruel to the third-class passengers and mean to the second-class ones, become lavish in dealing with first-class passengers. Having refused the poor what is necessary, they give the rich what is superfluous.
Cognition is a suite of mental phenomena that includes memory, attention and executive functions, and any drug would have to enhance executive functions to be considered truly ‘smart’. Executive functions occupy the higher levels of thought: reasoning, planning, directing attention to information that is relevant (and away from stimuli that aren’t), and thinking about what to do rather than acting on impulse or instinct. You activate executive functions when you tell yourself to count to 10 instead of saying something you may regret. They are what we use to make our actions moral and what we think of when we think about what makes us human.
3 days later, I’m fairly miserable (slept poorly, had a hair-raising incident, and a big project was not received as well as I had hoped), so well before dinner (and after a nap) I brew up 2 wooden-spoons of Malaysia Green (olive-color dust). I drank it down; tasted slightly better than the first. I was feeling better after the nap, and the kratom didn’t seem to change that.
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.
Even party drugs are going to work: Biohackers are taking recreational drugs like LSD, psilocybin mushrooms, and mescaline in microdoses—about a tenth of what constitutes a typical dose—with the goal of becoming more focused and creative. Many who’ve tried it report positive results, but real research on the practice—and its safety—is a long way off. “Whether microdosing with LSD improves creativity and cognition remains to be determined in an objective experiment using double-blind, placebo-controlled methodology,” Sahakian says.
Ginsenoside Rg1, a molecule found in the plant genus panax (ginseng), is being increasingly researched as an effect nootropic. Its cognitive benefits including increasing learning ability and memory acquisition, and accelerating neural development. It targets mainly the NMDA receptors and nitric oxide synthase, which both play important roles in personal and emotional intelligence. The authors of the study cited above, say that their research findings thus far have boosted their confidence in a "bright future of cognitive drug development."
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.
Some cognitive enhancers, such as donepezil and galantamine, are prescribed for elderly patients with impaired reasoning and memory deficits caused by various forms of dementia, including Alzheimer disease, Parkinson disease with dementia, dementia with Lewy bodies, and vascular dementia. Children and young adults with attention-deficit/hyperactivity disorder (ADHD) are often treated with the cognitive enhancers Ritalin (methylphenidate) or Adderall (mixed amphetamine salts). Persons diagnosed with narcolepsy find relief from sudden attacks of sleep through wake-promoting agents such as Provigil (modafinil). Generally speaking, cognitive enhancers improve working and episodic (event-specific) memory, attention, vigilance, and overall wakefulness but act through different brain systems and neurotransmitters to exert their enhancing effects.
But, thanks to the efforts of a number of remarkable scientists, researchers and plain-old neurohackers, we are beginning to put together a “whole systems” model of how all the different parts of the human brain work together and how they mesh with the complex regulatory structures of the body. It’s going to take a lot more data and collaboration to dial this model in, but already we are empowered to design stacks that can meaningfully deliver on the promise of nootropics “to enhance the quality of subjective experience and promote cognitive health, while having extremely low toxicity and possessing very few side effects.” It’s a type of brain hacking that is intended to produce noticeable cognitive benefits.