Nootroo and Nootrobox are two San Francisco nootropics startups that launched last year. Their founders come from the tech scene and their products are squarely aimed at the tech crowd seeking the convenience of not having to build their own combinations. Each claims big-name Silicon Valley entrepreneurs and investors among their users, though neither will name them.
Most people would describe school as a place where they go to learn, so learning is an especially relevant cognitive process for students to enhance. Even outside of school, however, learning plays a role in most activities, and the ability to enhance the retention of information would be of value in many different occupational and recreational contexts.
Stimulants are drugs that accelerate the central nervous system (CNS) activity. They have the power to make us feel more awake, alert and focused, providing us with a needed energy boost. Unfortunately, this class encompasses a wide range of drugs, some which are known solely for their side-effects and addictive properties. This is the reason why many steer away from any stimulants, when in fact some greatly benefit our cognitive functioning and can help treat some brain-related impairments and health issues.
Two increasingly popular options are amphetamines and methylphenidate, which are prescription drugs sold under the brand names Adderall and Ritalin. In the United States, both are approved as treatments for people with ADHD, a behavioural disorder which makes it hard to sit still or concentrate. Now they’re also widely abused by people in highly competitive environments, looking for a way to remain focused on specific tasks.
There are also premade ‘stacks’ (or formulas) of cognitive enhancing superfoods, herbals or proteins, which pre-package several beneficial extracts for a greater impact. These types of cognitive enhancers are more ‘subtle’ than the pharmaceutical alternative with regards to effects, but they work all the same. In fact, for many people, they work better than smart drugs as they are gentler on the brain and produce fewer side-effects.
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In addition, large national surveys, including the NSDUH, have generally classified prescription stimulants with other stimulants including street drugs such as methamphetamine. For example, since 1975, the National Institute on Drug Abuse–sponsored Monitoring the Future (MTF) survey has gathered data on drug use by young people in the United States (Johnston, O’Malley, Bachman, & Schulenberg, 2009a, 2009b). Originally, MTF grouped prescription stimulants under a broader class of stimulants so that respondents were asked specifically about MPH only after they had indicated use of some drug in the category of AMPs. As rates of MPH prescriptions increased and anecdotal reports of nonmedical use grew, the 2001 version of the survey was changed to include a separate standalone question about MPH use. This resulted in more than a doubling of estimated annual use among 12th graders, from 2.4% to 5.1%. More recent data from the MTF suggests Ritalin use has declined (3.4% in 2008). However, this may still underestimate use of MPH, as the question refers specifically to Ritalin and does not include other brand names such as Concerta (an extended release formulation of MPH).
The smart pill that FDA approved is called Abilify MyCite. This tiny pill has a drug and an ingestible sensor. The sensor gets activated when it comes into contact with stomach fluid to detect when the pill has been taken. The data is then transmitted to a wearable patch that eventually conveys the information to a paired smartphone app. Doctors and caregivers, with the patient’s consent, can then access the data via a web portal.
Amphetamines have a long track record as smart drugs, from the workaholic mathematician Paul Erdös, who relied on them to get through 19-hour maths binges, to the writer Graham Greene, who used them to write two books at once. More recently, there are plenty of anecdotal accounts in magazines about their widespread use in certain industries, such as journalism, the arts and finance.
The resurgent popularity of nootropics—an umbrella term for supplements that purport to boost creativity, memory, and cognitive ability—has more than a little to do with the recent Silicon Valley-induced obsession with disrupting literally everything, up to and including our own brains. But most of the appeal of smart drugs lies in the simplicity of their age-old premise: Take the right pill and you can become a better, smarter, as-yet-unrealized version of yourself—a person that you know exists, if only the less capable you could get out of your own way.
Nature magazine conducted a poll asking its readers about their cognitive-enhancement practices and their attitudes toward cognitive enhancement. Hundreds of college faculty and other professionals responded, and approximately one fifth reported using drugs for cognitive enhancement, with Ritalin being the most frequently named (Maher, 2008). However, the nature of the sample—readers choosing to answer a poll on cognitive enhancement—is not representative of the academic or general population, making the results of the poll difficult to interpret. By analogy, a poll on Vermont vacations, asking whether people vacation in Vermont, what they think about Vermont, and what they do if and when they visit, would undoubtedly not yield an accurate estimate of the fraction of the population that takes its vacations in Vermont.
Cytisine is not known as a stimulant and I’m not addicted to nicotine, so why give it a try? Nicotine is one of the more effective stimulants available, and it’s odd how few nicotine analogues or nicotinic agonists there are available; nicotine has a few flaws like short half-life and increasing blood pressure, so I would be interested in a replacement. The nicotine metabolite cotinine, in the human studies available, looks intriguing and potentially better, but I have been unable to find a source for it. One of the few relevant drugs which I can obtain is cytisine, from Ceretropic, at 2x1.5mg doses. There are not many anecdotal reports on cytisine, but at least a few suggest somewhat comparable effects with nicotine, so I gave it a try.
Adderall increases dopamine and noradrenaline availability within the prefrontal cortex, an area in which our memory and attention are controlled. As such, this smart pill improves our mood, makes us feel more awake and attentive. It is also known for its lasting effect – depending on the dose, it can last up to 12 hours. However, note that it is crucial to get confirmation from your doctor on the exact dose you should take.
This research is in contrast to the other substances I like, such as piracetam or fish oil. I knew about withdrawal of course, but it was not so bad when I was drinking only tea. And the side-effects like jitteriness are worse on caffeine without tea; I chalk this up to the lack of theanine. (My later experiences with theanine seems to confirm this.) These negative effects mean that caffeine doesn’t satisfy the strictest definition of nootropic (having no negative effects), but is merely a cognitive enhancer (with both benefits & costs). One might wonder why I use caffeine anyway if I am so concerned with mental ability.
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.
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.
Neuroprime – Mind Nutrition’s offering to the nootropic industry. Mind Nutrition is one of the most interesting nootropics we’ve found on the industry. It brings a formula that is their solution for the market, as a fundamental combination of vitamins and nootropics, or at least they call it. Neuroprime brings that to the table, as well as the fact that Neuroprime is also one of the most transparent companies that we’ve seen. Their online site is detailed, yet clean, without making any outrageous claims or statements. However, we here at Top10BrainPills.com… Learn More...
“One of my favorites is 1, 3, 7-trimethylxanthine,” says Dr. Mark Moyad, director of preventive and alternative medicine at the University of Michigan. He says this chemical boosts many aspects of cognition by improving alertness. It’s also associated with some memory benefits. “Of course,” Moyad says, “1, 3, 7-trimethylxanthine goes by another name—caffeine.”
However, they fell short in several categories. The key issue with their product is that it does not contain DHA Omega 3 and the other essential vitamins and nutrients needed to support the absorption of Huperzine A and Phosphatidylserine. Without having DHA Omega 3 it will not have an essential piece to maximum effectiveness. This means that you would need to take a separate pill of DHA Omega 3 and several other essential vitamins to ensure you are able to reach optimal memory support. They also are still far less effective than our #1 pick’s complete array of the 3 essential brain supporting ingredients and over 30 supporting nutrients, making their product less effective.
Board-certified neuropsychologist Brian Lebowitz, PhD and associate clinical professor of neurology at Stony Brook University, explains to MensHealth.com that the term "encompasses so many things," including prescription medications. Brain enhancers fall into two different categories: naturally occurring substances like Ginkgo biloba, creatine and phenibut; and manmade prescription drugs, like Adderall, and over-the-counter supplements such as Noopept.
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.
Our 2nd choice for a Brain and Memory supplement is Clari-T by Life Seasons. We were pleased to see that their formula included 3 of the 5 necessary ingredients Huperzine A, Phosphatidylserine and Bacopin. In addition, we liked that their product came in a vegetable capsule. The product contains silica and rice bran, though, which we are not sure is necessary.
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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?)
From the standpoint of absorption, the drinking of tobacco juice and the interaction of the infusion or concoction with the small intestine is a highly effective method of gastrointestinal nicotine administration. The epithelial area of the intestines is incomparably larger than the mucosa of the upper tract including the stomach, and the small intestine represents the area with the greatest capacity for absorption (Levine 1983:81-83). As practiced by most of the sixty-four tribes documented here, intoxicated states are achieved by drinking tobacco juice through the mouth and/or nose…The large intestine, although functionally little equipped for absorption, nevertheless absorbs nicotine that may have passed through the small intestine.
Iluminal is an example of an over-the-counter serotonergic drug used by people looking for performance enhancement, memory improvements, and mood-brightening. Also noteworthy, a wide class of prescription anti-depression drugs are based on serotonin reuptake inhibitors that slow the absorption of serotonin by the presynaptic cell, increasing the effect of the neurotransmitter on the receptor neuron – essentially facilitating the free flow of serotonin throughout the brain.
Exercise and nutrition also play an important role in neuroplasticity. Many vitamins and ingredients found naturally in food products have been shown to have cognitive enhancing effects. Some of these include vitamins B6 and B12, caffeine, phenethylamine found in chocolate and l-theanine, found in green tea, whose combined effects with caffeine are more extensively researched.
…It is without activity in man! Certainly not for the lack of trying, as some of the dosage trials that are tucked away in the literature (as abstracted in the Qualitative Comments given above) are pretty heavy duty. Actually, I truly doubt that all of the experimenters used exactly that phrase, No effects, but it is patently obvious that no effects were found. It happened to be the phrase I had used in my own notes.
Two additional studies assessed the effects of d-AMP on visual–motor sequence learning, a form of nondeclarative, procedural learning, and found no effect (Kumari et al., 1997; Makris, Rush, Frederich, Taylor, & Kelly, 2007). In a related experimental paradigm, Ward, Kelly, Foltin, and Fischman (1997) assessed the effect of d-AMP on the learning of motor sequences from immediate feedback and also failed to find an effect.
We included studies of the effects of these drugs on cognitive processes including learning, memory, and a variety of executive functions, including working memory and cognitive control. These studies are listed in Table 2, along with each study’s sample size, gender, age and tasks administered. Given our focus on cognition enhancement, we excluded studies whose measures were confined to perceptual or motor abilities. Studies of attention are included when the term attention refers to an executive function but not when it refers to the kind of perceptual process taxed by, for example, visual search or dichotic listening or when it refers to a simple vigilance task. Vigilance may affect cognitive performance, especially under conditions of fatigue or boredom, but a more vigilant person is not generally thought of as a smarter person, and therefore, vigilance is outside of the focus of the present review. The search and selection process is summarized in Figure 2.
So what about the flip side: a drug to erase bad memories? It may have failed Jim Carrey in Eternal Sunshine of the Spotless Mind, but neuroscientists have now discovered an amnesia drug that can dull the pain of traumatic events. The drug, propranolol, was originally used to treat high blood pressure and heart disease. Doctors noticed that patients given the drug suffered fewer signs of stress when recalling a trauma.
It's been widely reported that Silicon Valley entrepreneurs and college students turn to Adderall (without a prescription) to work late through the night. In fact, a 2012 study published in the Journal of American College Health, showed that roughly two-thirds of undergraduate students were offered prescription stimulants for non-medical purposes by senior year.
In 3, you’re considering adding a new supplement, not stopping a supplement you already use. The I don’t try Adderall case has value $0, the Adderall fails case is worth -$40 (assuming you only bought 10 pills, and this number should be increased by your analysis time and a weighted cost for potential permanent side effects), and the Adderall succeeds case is worth $X-40-4099, where $X is the discounted lifetime value of the increased productivity due to Adderall, minus any discounted long-term side effect costs. If you estimate Adderall will work with p=.5, then you should try out Adderall if you estimate that 0.5 \times (X-4179) > 0 ~> $X>4179$. (Adderall working or not isn’t binary, and so you might be more comfortable breaking down the various how effective Adderall is cases when eliciting X, by coming up with different levels it could work at, their values, and then using a weighted sum to get X. This can also give you a better target with your experiment- this needs to show a benefit of at least Y from Adderall for it to be worth the cost, and I’ve designed it so it has a reasonable chance of showing that.)
Frustrated by the lack of results, pharmaceutical companies have been shutting down their psychiatric drug research programmes. Traditional methods, such as synthesising new molecules and seeing what effect they have on symptoms, seem to have run their course. A shift of strategy is looming, towards research that focuses on genes and brain circuitry rather than chemicals. The shift will prolong the wait for new blockbuster drugs further, as the new systems are developed, and offers no guarantees of results.
So it's no surprise that as soon as medical science develops a treatment for a disease, we often ask if it couldn't perhaps make a healthy person even healthier. Take Viagra, for example: developed to help men who couldn't get erections, it's now used by many who function perfectly well without a pill but who hope it will make them exceptionally virile.
I am not alone in thinking of the potential benefits of smart drugs in the military. In their popular novel Ghost Fleet: A Novel of the Next World War, P.W. Singer and August Cole tell the story of a future war using drug-like nootropic implants and pills, such as Modafinil. DARPA is also experimenting with neurological technology and enhancements such as the smart drugs discussed here. As demonstrated in the following brain initiatives: Targeted Neuroplasticity Training (TNT), Augmented Cognition, and High-quality Interface Systems such as their Next-Generational Nonsurgical Neurotechnology (N3).
And in his followup work, An opportunity cost model of subjective effort and task performance (discussion). Kurzban seems to have successfully refuted the blood-glucose theory, with few dissenters from commenting researchers. The more recent opinion seems to be that the sugar interventions serve more as a reward-signal indicating more effort is a good idea, not refueling the engine of the brain (which would seem to fit well with research on procrastination).↩
If I stop tonight and do nothing Monday (and I sleep the normal eight hours and do not pay any penalty), then that’ll be 4 out of 5 days on modafinil, each saving 3 or 4 hours. Each day took one pill which cost me $1.20, but each pill saved let’s call it 3.5 hours; if I value my time at minimum wage, or 7.25/hr (federal minimum wage), then that 3.5 hours is worth $25.37, which is much more than $1.20, ~21x more.
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:
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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.
Noopept shows a much greater affinity for certain receptor sites in the brain than racetams, allowing doses as small as 10-30mg to provide increased focus, improved logical thinking function, enhanced short and long-term memory functions, and increased learning ability including improved recall. In addition, users have reported a subtle psychostimulatory effect.
Competitors of importance in the smart pills market have been recorded and analyzed in MRFR's report. These market players include RF Co., Ltd., CapsoVision, Inc., JINSHAN Science & Technology, BDD Limited, MEDTRONIC, Check-Cap, PENTAX Medical, INTROMEDIC, Olympus Corporation, FUJIFILM Holdings Corporation, MEDISAFE, and Proteus Digital Health, Inc.
Recent developments include biosensor-equipped smart pills that sense the appropriate environment and location to release pharmacological agents. Medimetrics (Eindhoven, Netherlands) has developed a pill called IntelliCap with drug reservoir, pH and temperature sensors that release drugs to a defined region of the gastrointestinal tract. This device is CE marked and is in early stages of clinical trials for FDA approval. Recently, Google announced its intent to invest and innovate in this space.
Some suggested that the lithium would turn me into a zombie, recalling the complaints of psychiatric patients. But at 5mg elemental lithium x 200 pills, I’d have to eat 20 to get up to a single clinical dose (a psychiatric dose might be 500mg of lithium carbonate, which translates to ~100mg elemental), so I’m not worried about overdosing. To test this, I took on day 1 & 2 no less than 4 pills/20mg as an attack dose; I didn’t notice any large change in emotional affect or energy levels. And it may’ve helped my motivation (though I am also trying out the tyrosine).
Omega-3 fatty acids: DHA and EPA – two Cochrane Collaboration reviews on the use of supplemental omega-3 fatty acids for ADHD and learning disorders conclude that there is limited evidence of treatment benefits for either disorder. Two other systematic reviews noted no cognition-enhancing effects in the general population or middle-aged and older adults.