Table 1 shows all of the studies of middle school, secondary school, and college students that we identified. As indicated in the table, the studies are heterogeneous, with varying populations sampled, sample sizes, and year of data collection, and they focused on different subsets of the epidemiological questions addressed here, including prevalence and frequency of use, motivations for use, and method of obtaining the medication.
A synthetic derivative of Piracetam, aniracetam is believed to be the second most widely used nootropic in the Racetam family, popular for its stimulatory effects because it enters the bloodstream quickly. Initially developed for memory and learning, many anecdotal reports also claim that it increases creativity. However, clinical studies show no effect on the cognitive functioning of healthy adult mice.
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SOURCES: Marvin Hausman, MD, CEO, Axonyx Inc. Axel Unterbeck, PhD, president, chief scientific officer, Memory Pharmaceuticals. Martha Farah, PhD, professor, department of psychiatry, University of Pennsylvania. Howard Gardner, PhD, Hobbs Professor of Education and Cognition, Harvard Graduate School of Education. Nature Reviews Neuroscience, May 2004. Neurology, July 2002. Alzheimer's Association.
The next morning, four giant pills’ worth of the popular piracetam-and-choline stack made me... a smidge more alert, maybe? (Or maybe that was just the fact that I had slept pretty well the night before. It was hard to tell.) Modafinil, which many militaries use as their “fatigue management” pill of choice, boasts glowing reviews from satisfied users. But in the United States, civilians need a prescription to get it; without one, they are stuck using adrafinil, a precursor substance that the body metabolizes into modafinil after ingestion. Taking adrafinil in lieu of coffee just made me keenly aware that I hadn’t had coffee.
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.
Unfortunately, cognitive enhancement falls between the stools of research funding, which makes it unlikely that such research programs will be carried out. Disease-oriented funders will, by definition, not support research on normal healthy individuals. The topic intersects with drug abuse research only in the assessment of risk, leaving out the study of potential benefits, as well as the comparative benefits of other enhancement methods. As a fundamentally applied research question, it will not qualify for support by funders of basic science. The pharmaceutical industry would be expected to support such research only if cognitive enhancement were to be considered a legitimate indication by the FDA, which we hope would happen only after considerably more research has illuminated its risks, benefits, and societal impact. Even then, industry would have little incentive to delve into all of the issues raised here, including the comparison of drug effects to nonpharmaceutical means of enhancing cognition.
Another well-known smart drug classed as a cholinergic is Sulbutiamine, a synthetic derivative of thiamine which crosses the blood-brain barrier and has been shown to improve memory while reducing psycho-behavioral inhibition. While Sulbutiamine has been shown to exhibit cholinergic regulation within the hippocampus, the reasons for the drug’s discernable effects on the brain remain unclear. This smart drug, available over the counter as a nutritional supplement, has a long history of use, and appears to have no serious side effects at therapeutic levels.
"A system that will monitor their behavior and send signals out of their body and notify their doctor? You would think that, whether in psychiatry or general medicine, drugs for almost any other condition would be a better place to start than a drug for schizophrenia," says Paul Appelbaum, director of Columbia University's psychiatry department in an interview with the New York Times.
Some supplement blends, meanwhile, claim to work by combining ingredients – bacopa, cat's claw, huperzia serrata and oat straw in the case of Alpha Brain, for example – that have some support for boosting cognition and other areas of nervous system health. One 2014 study in Frontiers in Aging Neuroscience, suggested that huperzia serrata, which is used in China to fight Alzheimer's disease, may help slow cell death and protect against (or slow the progression of) neurodegenerative diseases. The Alpha Brain product itself has also been studied in a company-funded small randomized controlled trial, which found Alpha Brain significantly improved verbal memory when compared to adults who took a placebo.
I had tried 8 randomized days like the Adderall experiment to see whether I was one of the people whom modafinil energizes during the day. (The other way to use it is to skip sleep, which is my preferred use.) I rarely use it during the day since my initial uses did not impress me subjectively. The experiment was not my best - while it was double-blind randomized, the measurements were subjective, and not a good measure of mental functioning like dual n-back (DNB) scores which I could statistically compare from day to day or against my many previous days of dual n-back scores. Between my high expectation of finding the null result, the poor experiment quality, and the minimal effect it had (eliminating an already rare use), the value of this information was very small.
Some smart drugs can be found in health food stores; others are imported or are drugs that are intended for other disorders such as Alzheimer's disease and Parkinson's disease. There are many Internet web sites, books, magazines and newspaper articles detailing the supposed effects of smart drugs. There are also plenty of advertisements and mail-order businesses that try to sell "smart drugs" to the public. However, rarely do these businesses or the popular press report results that show the failure of smart drugs to improve memory or learning. Rather, they try to show that their products have miraculous effects on the brain and can improve mental functioning. Wouldn't it be easy to learn something by "popping a pill" or drinking a soda laced with a smart drug? This would be much easier than taking the time to study. Feeling dull? Take your brain in for a mental tune up by popping a pill!
Studies show that B vitamin supplements can protect the brain from cognitive decline. These natural nootropics can also reduce the likelihood of developing neurodegenerative diseases. The prevention of Alzheimer’s and even dementia are among the many benefits. Due to their effects on mental health, B vitamins make an excellent addition to any smart drug stack.
The power calculation indicates a 20% chance of getting useful information. My quasi-experiment has <70% chance of being right, and I preserve a general skepticism about any experiment, even one as well done as the medical student one seems to be, and give that one a <80% chance of being right; so let’s call it 70% the effect exists, or 30% it doesn’t exist (which is the case in which I save money by dropping fish oil for 10 years).
But perhaps the biggest difference between Modafinil and other nootropics like Piracetam, according to Patel, is that Modafinil studies show more efficacy in young, healthy people, not just the elderly or those with cognitive deficits. That’s why it’s great for (and often prescribed to) military members who are on an intense tour, or for those who can’t get enough sleep for physiological reasons. One study, by researchers at Imperial College London, and published in Annals of Surgery, even showed that Modafinil helped sleep-deprived surgeons become better at planning, redirecting their attention, and being less impulsive when making decisions.
Several new medications are on the market and in development for Alzheimer's disease, a progressive neurological disease leading to memory loss, language deterioration, and confusion that afflicts about 4.5 million Americans and is expected to strike millions more as the baby boom generation ages. Yet the burning question for those who aren't staring directly into the face of Alzheimer's is whether these medications might make us smarter.
Amongst the brain focus supplements that are currently available in the nootropic drug market, Modafinil is probably the most common focus drug or one of the best focus pills used by people, and it’s praised to be the best nootropic available today. It is a powerful cognitive enhancer that is great for boosting your overall alertness with least side effects. However, to get your hands on this drug, you would require a prescription.
I can test fish oil for mood, since the other claimed benefits like anti-schizophrenia are too hard to test. The medical student trial (Kiecolt-Glaser et al 2011) did not see changes until visit 3, after 3 weeks of supplementation. (Visit 1, 3 weeks, visit 2, supplementation started for 3 weeks, visit 3, supplementation continued 3 weeks, visit 4 etc.) There were no tests in between the test starting week 1 and starting week 3, so I can’t pin it down any further. This suggests randomizing in 2 or 3 week blocks. (For an explanation of blocking, see the footnote in the Zeo page.)
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So what’s the catch? Well, it’s potentially addictive for one. Anything that messes with your dopamine levels can be. And Patel says there are few long-term studies on it yet, so we don’t know how it will affect your brain chemistry down the road, or after prolonged, regular use. Also, you can’t get it very easily, or legally for that matter, if you live in the U.S. It’s classified as a schedule IV controlled substance. That’s where Adrafinil comes in.
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 quantities of GPC, which is why people prefer taking it through supplements.
In 2011, as part of the Silk Road research, I ordered 10x100mg Modalert (5btc) from a seller. I also asked him about his sourcing, since if it was bad, it’d be valuable to me to know whether it was sourced from one of the vendors listed in my table. He replied, more or less, I get them from a large Far Eastern pharmaceuticals wholesaler. I think they’re probably the supplier for a number of the online pharmacies. 100mg seems likely to be too low, so I treated this shipment as 5 doses:
None of that has kept entrepreneurs and their customers from experimenting and buying into the business of magic pills, however. In 2015 alone, the nootropics business raked in over $1 billion dollars, and web sites like the nootropics subreddit, the Bluelight forums, and Bulletproof Exec are popular and packed with people looking for easy ways to boost their mental performance. Still, this bizarre, Philip K. Dick-esque world of smart drugs is a tough pill to swallow. To dive into the topic and explain, I spoke to Kamal Patel, Director of evidence-based medical database Examine.com, and even tried a few commercially-available nootropics myself.
Adrafinil is a prodrug for Modafinil, which means it can be metabolized into Modafinil to give you a similar effect. And you can buy it legally just about anywhere. But there are a few downsides. Patel explains that you have to take a lot more to achieve a similar effect as Modafinil, wait longer for it to kick in (45-60 minutes), there are more potential side effects, and there aren’t any other benefits to taking it.