For illustration, consider amphetamines, Ritalin, and modafinil, all of which have been proposed as cognitive enhancers of attention. These drugs exhibit some positive effects on cognition, especially among individuals with lower baseline abilities. However, individuals of normal or above-average cognitive ability often show negligible improvements or even decrements in performance following drug treatment (for details, see de Jongh, Bolt, Schermer, & Olivier, 2008). For instance, Randall, Shneerson, and File (2005) found that modafinil improved performance only among individuals with lower IQ, not among those with higher IQ. [See also Finke et al 2010 on visual attention.] Farah, Haimm, Sankoorikal, & Chatterjee 2009 found a similar nonlinear relationship of dose to response for amphetamines in a remote-associates task, with low-performing individuals showing enhanced performance but high-performing individuals showing reduced performance. Such ∩-shaped dose-response curves are quite common (see Cools & Robbins, 2004)
Nootropics are becoming increasingly popular as a tool for improving memory, information recall, and focus. Though research has not yet determined the mechanism for how nootropics work, it is clear that they provide significant cognitive benefits. Additionally, through a variety of hypothesized biological mechanisms, these compounds are thought to have the potential to improve vision.
It is known that American college students have embraced cognitive enhancement, and some information exists about the demographics of the students most likely to practice cognitive enhancement with prescription stimulants. Outside of this narrow segment of the population, very little is known. What happens when students graduate and enter the world of work? Do they continue using prescription stimulants for cognitive enhancement in their first jobs and beyond? How might the answer to this question depend on occupation? For those who stay on campus to pursue graduate or professional education, what happens to patterns of use? To what extent do college graduates who did not use stimulants as students begin to use them for cognitive enhancement later in their careers? To what extent do workers without college degrees use stimulants to enhance job performance? How do the answers to these questions differ for countries outside of North America, where the studies of Table 1 were carried out?
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Swanson J, Arnold LE, Kraemer H, Hechtman L, Molina B, Hinshaw S, Wigal T. Evidence, interpretation and qualification from multiple reports of long-term outcomes in the Multimodal Treatment Study of Children With ADHD (MTA): Part II. Supporting details. Journal of Attention Disorders. 2008;12:15–43. doi: 10.1177/1087054708319525. [PubMed] [CrossRef]
Medication can be ineffective if the drug payload is not delivered at its intended place and time. Since an oral medication travels through a broad pH spectrum, the pill encapsulation could dissolve at the wrong time. However, a smart pill with environmental sensors, a feedback algorithm and a drug release mechanism can give rise to smart drug delivery systems. This can ensure optimal drug delivery and prevent accidental overdose.
Table 5 lists the results of 16 tasks from 13 articles on the effects of d-AMP or MPH on cognitive control. One of the simplest tasks used to study cognitive control is the go/no-go task. Subjects are instructed to press a button as quickly as possible for one stimulus or class of stimuli (go) and to refrain from pressing for another stimulus or class of stimuli (no go). De Wit et al. (2002) used a version of this task to measure the effects of d-AMP on subjects’ ability to inhibit a response and found enhancement in the form of decreased false alarms (responses to no-go stimuli) and increased speed of correct go responses. They also found that subjects who made the most errors on placebo experienced the greatest enhancement from the drug.
Do you start your day with a cup (or two, or three) of coffee? It tastes delicious, but it’s also jump-starting your brain because of its caffeine content. Caffeine is definitely a nootropic substance—it’s a mild stimulant that can alleviate fatigue and improve concentration, according to the Mayo Clinic. Current research shows that coffee drinkers don’t suffer any ill effects from drinking up to about four cups of coffee per day. Caffeine is also found in tea, soda, and energy drinks. Not too surprisingly, it’s also in many of the nootropic supplements that are being marketed to people looking for a mental boost. Take a look at these 7 genius brain boosters to try in the morning.
First half at 6 AM; second half at noon. Wrote a short essay I’d been putting off and napped for 1:40 from 9 AM to 10:40. This approach seems to work a little better as far as the aboulia goes. (I also bother to smell my urine this time around - there’s a definite off smell to it.) Nights: 10:02; 8:50; 10:40; 7:38 (2 bad nights of nasal infections); 8:28; 8:20; 8:43 (▆▃█▁▂▂▃).
Nootrobox co-founder Geoffrey Woo declines a caffeinated drink in favour of a capsule of his newest product when I meet him in a San Francisco coffee shop. The entire industry has a “wild west” aura about it, he tells me, and Nootrobox wants to fix it by pushing for “smarter regulation” so safe and effective drugs that are currently unclassified can be brought into the fold. Predictably, both companies stress the higher goal of pushing forward human cognition. “I am trying to make a smarter, better populace to solve all the problems we have created,” says Nootroo founder Eric Matzner.
But there would also be significant downsides. Amphetamines are structurally similar to crystal meth – a potent, highly addictive recreational drug which has ruined countless lives and can be fatal. Both Adderall and Ritalin are known to be addictive, and there are already numerous reports of workers who struggled to give them up. There are also side effects, such as nervousness, anxiety, insomnia, stomach pains, and even hair loss, among others.
The stimulant now most popular in news articles as a legitimate “smart drug” is Modafinil, which came to market as an anti-narcolepsy drug, but gained a following within the military, doctors on long shifts, and college students pulling all-nighters who needed a drug to improve alertness without the “wired” feeling associated with caffeine. Modafinil is a relatively new smart drug, having gained widespread use only in the past 15 years. More research is needed before scientists understand this drug’s function within the brain – but the increase in alertness it provides is uncontested.
Creatine is a substance that’s produced in the human body. It is initially produced in the kidneys, and the process is completed in the liver. It is then stored in the brain tissues and muscles, to support the energy demands of a human body. Athletes and bodybuilders use creatine supplements to relieve fatigue and increase the recovery of the muscle tissues affected by vigorous physical activities. Apart from helping the tissues to recover faster, creatine also helps in enhancing the mental functions in sleep-deprived adults, and it also improves the performance of difficult cognitive tasks.
By the end of 2009, at least 25 studies reported surveys of college students’ rates of nonmedical stimulant use. Of the studies using relatively smaller samples, prevalence was, in chronological order, 16.6% (lifetime; Babcock & Byrne, 2000), 35.3% (past year; Low & Gendaszek, 2002), 13.7% (lifetime; Hall, Irwin, Bowman, Frankenberger, & Jewett, 2005), 9.2% (lifetime; Carroll, McLaughlin, & Blake, 2006), and 55% (lifetime, fraternity students only; DeSantis, Noar, & Web, 2009). Of the studies using samples of more than a thousand students, somewhat lower rates of nonmedical stimulant use were found, although the range extends into the same high rates as the small studies: 2.5% (past year, Ritalin only; Teter, McCabe, Boyd, & Guthrie, 2003), 5.4% (past year; McCabe & Boyd, 2005), 4.1% (past year; McCabe, Knight, Teter, & Wechsler, 2005), 11.2% (past year; Shillington, Reed, Lange, Clapp, & Henry, 2006), 5.9% (past year; Teter, McCabe, LaGrange, Cranford, & Boyd, 2006), 16.2% (lifetime; White, Becker-Blease, & Grace-Bishop, 2006), 1.7% (past month; Kaloyanides, McCabe, Cranford, & Teter, 2007), 10.8% (past year; Arria, O’Grady, Caldeira, Vincent, & Wish, 2008); 5.3% (MPH only, lifetime; Du-Pont, Coleman, Bucher, & Wilford, 2008); 34% (lifetime; DeSantis, Webb, & Noar, 2008), 8.9% (lifetime; Rabiner et al., 2009), and 7.5% (past month; Weyandt et al., 2009).
One often-cited study published in the British Journal of Pharmacology looked at cognitive function in the elderly and showed that racetam helped to improve their brain function.19 Another study, which was published in Psychopharmacology, looked at adult volunteers (including those who are generally healthy) and found that piracetam helped improve their memory.20
When Giurgea coined the word nootropic (combining the Greek words for mind and bending) in the 1970s, he was focused on a drug he had synthesized called piracetam. Although it is approved in many countries, it isn’t categorized as a prescription drug in the United States. That means it can be purchased online, along with a number of newer formulations in the same drug family (including aniracetam, phenylpiracetam, and oxiracetam). Some studies have shown beneficial effects, including one in the 1990s that indicated possible improvement in the hippocampal membranes in Alzheimer’s patients. But long-term studies haven’t yet borne out the hype.
Today piracetam is a favourite with students and young professionals looking for a way to boost their performance, though decades after Giurgea’s discovery, there still isn’t much evidence that it can improve the mental abilities of healthy people. It’s a prescription drug in the UK, though it’s not approved for medical use by the US Food and Drug Administration and can’t be sold as a dietary supplement either.
Though their product includes several vitamins including Bacopa, it seems to be missing the remaining four of the essential ingredients: DHA Omega 3, Huperzine A, Phosphatidylserine and N-Acetyl L-Tyrosine. It missed too many of our key criteria and so we could not endorse this product of theirs. Simply, if you don’t mind an insufficient amount of essential ingredients for improved brain and memory function and an inclusion of unwanted ingredients – then this could be a good fit for you.
10:30 AM; no major effect that I notice throughout the day - it’s neither good nor bad. This smells like placebo (and part of my mind is going how unlikely is it to get placebo 3 times in a row!, which is just the Gambler’s fallacy talking inasmuch as this is sampling with replacement). I give it 60% placebo; I check the next day right before taking, and it is. Man!
Barbara Sahakian, a neuroscientist at Cambridge University, doesn’t dismiss the possibility of nootropics to enhance cognitive function in healthy people. She would like to see society think about what might be considered acceptable use and where it draws the line – for example, young people whose brains are still developing. But she also points out a big problem: long-term safety studies in healthy people have never been done. Most efficacy studies have only been short-term. “Proving safety and efficacy is needed,” she says.
Critics will often highlight ethical issues and the lack of scientific evidence for these drugs. Ethical arguments typically take the form of “tampering with nature.” Alena Buyx discusses this argument in a neuroethics project called Smart Drugs: Ethical Issues. She says that critics typically ask if it is ethically superior to accept what is “given” instead of striving for what is “made”. My response to this is simple. Just because it is natural does not mean it is superior.
One of the other suggested benefits is for boosting serotonin levels; low levels of serotonin are implicated in a number of issues like depression. I’m not yet sure whether tryptophan has helped with motivation or happiness. Trial and error has taught me that it’s a bad idea to take tryptophan in the morning or afternoon, however, even smaller quantities like 0.25g. Like melatonin, the dose-response curve is a U: ~1g is great and induces multiple vivid dreams for me, but ~1.5g leads to an awful night and a headache the next day that was worse, if anything, than melatonin. (One morning I woke up with traces of at least 7 dreams, although I managed to write down only 2. No lucid dreams, though.)
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.
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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Piracetam boosts acetylcholine function, a neurotransmitter responsible for memory consolidation. Consequently, it improves memory in people who suffer from age-related dementia, which is why it is commonly prescribed to Alzheimer’s patients and people struggling with pre-dementia symptoms. When it comes to healthy adults, it is believed to improve focus and memory, enhancing the learning process altogether.
Caffeine keeps you awake, which keeps you coding. It may also be a nootropic, increasing brain-power. Both desirable results. However, it also inhibits vitamin D receptors, and as such decreases the body’s uptake of this-much-needed-vitamin. OK, that’s not so bad, you’re not getting the maximum dose of vitamin D. So what? Well, by itself caffeine may not cause you any problems, but combined with cutting off a major source of the vitamin - the production via sunlight - you’re leaving yourself open to deficiency in double-quick time.
Before taking any supplement or chemical, people want to know if there will be long term effects or consequences, When Dr. Corneliu Giurgea first authored the term “nootropics” in 1972, he also outlined the characteristics that define nootropics. Besides the ability to benefit memory and support the cognitive processes, Dr. Giurgea believed that nootropics should be safe and non-toxic.
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.
In contrast to the types of memory discussed in the previous section, which are long-lasting and formed as a result of learning, working memory is a temporary store of information. Working memory has been studied extensively by cognitive psychologists and cognitive neuroscientists because of its role in executive function. It has been likened to an internal scratch pad; by holding information in working memory, one keeps it available to consult and manipulate in the service of performing tasks as diverse as parsing a sentence and planning a route through the environment. Presumably for this reason, working memory ability correlates with measures of general intelligence (Friedman et al., 2006). The possibility of enhancing working memory ability is therefore of potential real-world interest.
Take at 11 AM; distractions ensue and the Christmas tree-cutting also takes up much of the day. By 7 PM, I am exhausted and in a bad mood. While I don’t expect day-time modafinil to buoy me up, I do expect it to at least buffer me against being tired, and so I conclude placebo this time, and with more confidence than yesterday (65%). I check before bed, and it was placebo.
A fancier method of imputation would be multiple imputation using, for example, the R library mice (Multivariate Imputation by Chained Equations) (guide), which will try to impute all missing values in a way which mimicks the internal structure of the data and provide several possible datasets to give us an idea of what the underlying data might have looked like, so we can see how our estimates improve with no missingness & how much of the estimate is now due to the imputation:
Many laboratory tasks have been developed to study working memory, each of which taxes to varying degrees aspects such as the overall capacity of working memory, its persistence over time, and its resistance to interference either from task-irrelevant stimuli or among the items to be retained in working memory (i.e., cross-talk). Tasks also vary in the types of information to be retained in working memory, for example, verbal or spatial information. The question of which of these task differences correspond to differences between distinct working memory systems and which correspond to different ways of using a single underlying system is a matter of debate (e.g., D’Esposito, Postle, & Rypma, 2000; Owen, 2000). For the present purpose, we ignore this question and simply ask, Do MPH and d-AMP affect performance in the wide array of tasks that have been taken to operationalize working memory? If the literature does not yield a unanimous answer to this question, then what factors might be critical in determining whether stimulant effects are manifest?
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