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.
If you’re concerned with using either supplement, speak to your doctor. Others will replace these supplements with something like Phenylpiracetam or Pramiracetam. Both of these racetams provide increased energy levels, yielding less side-effects. If you do plan on taking Modafinil or Adrafinil, it’s best to use them on occasion or cycle your doses.

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.
Natural and herbal nootropics are by far the safest and best smart drugs to ingest. For this reason, they’re worth covering first. Our recommendation is always to stick with natural brain fog cures. Herbal remedies for enhancing mental cognition are often side-effect free. These substances are superior for both long-term safety and effectiveness. They are also well-studied and have deep roots in traditional medicine.
Turning to analyses related specifically to the drugs that are the subject of this article, reanalysis of the 2002 NSDUH data by Kroutil and colleagues (2006) found past-year nonmedical use of stimulants other than methamphetamine by 2% of individuals between the ages of 18 and 25 and by 0.3% of individuals 26 years of age and older. For ADHD medications in particular, these rates were 1.3% and 0.1%, respectively. Finally, Novak, Kroutil, Williams, and Van Brunt (2007) surveyed a sample of over four thousand individuals from the Harris Poll Online Panel and found that 4.3% of those surveyed between the ages of 18 and 25 had used prescription stimulants nonmedically in the past year, compared with only 1.3% between the ages of 26 and 49.
If you’re considering taking pharmaceutical nootropics, then it’s important that you learn as much as you can about how they work and that you seek professional advice before taking them. Be sure to read the side effects and contraindications of the nootropic that you are considering taking, and do not use it if you have any pre-existing medical conditions or allergies. If you’re taking other medications, then discuss your plans with a doctor or pharmacist to make sure that your nootropic is safe for you to use.
In addition, the cognitive enhancing effects of stimulant drugs often depend on baseline performance. So whilst stimulants enhance performance in people with low baseline cognitive abilities, they often impair performance in those who are already at optimum. Indeed, in a study by Randall et al., modafinil only enhanced cognitive performance in subjects with a lower (although still above-average) IQ.
How exactly – and if – nootropics work varies widely. Some may work, for example, by strengthening certain brain pathways for neurotransmitters like dopamine, which is involved in motivation, Barbour says. Others aim to boost blood flow – and therefore funnel nutrients – to the brain to support cell growth and regeneration. Others protect brain cells and connections from inflammation, which is believed to be a factor in conditions like Alzheimer's, Barbour explains. Still others boost metabolism or pack in vitamins that may help protect the brain and the rest of the nervous system, explains Dr. Anna Hohler, an associate professor of neurology at Boston University School of Medicine and a fellow of the American Academy of Neurology.
I posted a link to the survey on my Google+ account, and inserted the link at the top of all gwern.net pages; 51 people completed all 11 binary choices (most of them coming from North America & Europe), which seems adequate since the 11 questions are all asking the same question, and 561 responses to one question is quite a few. A few different statistical tests seem applicable: a chi-squared test whether there’s a difference between all the answers, a two-sample test on the averages, and most meaningfully, summing up the responses as a single pair of numbers and doing a binomial test:
Some critics argue that Modafinil is an expression of that, a symptom of a new 24/7 work routine. But what if the opposite is true? Let’s say you could perform a task in significantly less time than usual. You could then use the rest of your time differently, spending it with family, volunteering, or taking part in a leisure activity. And imagine that a drug helped you focus on clearing your desk and inbox before leaving work. Wouldn’t that help you relax once you get home?
A number of different laboratory studies have assessed the acute effect of prescription stimulants on the cognition of normal adults. In the next four sections, we review this literature, with the goal of answering the following questions: First, do MPH (e.g., Ritalin) and d-AMP (by itself or as the main ingredient in Adderall) improve cognitive performance relative to placebo in normal healthy adults? Second, which cognitive systems are affected by these drugs? Third, how do the effects of the drugs depend on the individual using them?
As far as anxiety goes, psychiatrist Emily Deans has an overview of why the Kiecolt-Glaser et al 2011 study is nice; she also discusses why fish oil seems like a good idea from an evolutionary perspective. There was also a weaker earlier 2005 study also using healthy young people, which showed reduced anger/anxiety/depression plus slightly faster reactions. The anti-stress/anxiolytic may be related to the possible cardiovascular benefits (Carter et al 2013).
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.
I have also tried to get in contact with senior executives who have experience with these drugs (either themselves or in their firms), but without success. I have to wonder: Are they completely unaware of the drugs’ existence? Or are they actively suppressing the issue? For now, companies can ignore the use of smart drugs. And executives can pretend as if these drugs don’t exist in their workplaces. But they can’t do it forever.
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.

All clear? Try one (not dozens) of nootropics for a few weeks and keep track of how you feel, Kerl suggests. It’s also important to begin with as low a dose as possible; when Cyr didn’t ease into his nootropic regimen, his digestion took the blow, he admits. If you don’t notice improvements, consider nixing the product altogether and focusing on what is known to boost cognitive function – eating a healthy diet, getting enough sleep regularly and exercising. "Some of those lifestyle modifications," Kerl says, "may improve memory over a supplement."

These days, nootropics are beginning to take their rightful place as a particularly powerful tool in the Neurohacker’s toolbox. After all, biochemistry is deeply foundational to neural function. Whether you are trying to fix the damage that is done to your nervous system by a stressful and toxic environment or support and enhance your neural functioning, getting the chemistry right is table-stakes. And we are starting to get good at getting it right. What’s changed?
Gibson and Green (2002), talking about a possible link between glucose and cognition, wrote that research in the area …is based on the assumption that, since glucose is the major source of fuel for the brain, alterations in plasma levels of glucose will result in alterations in brain levels of glucose, and thus neuronal function. However, the strength of this notion lies in its common-sense plausibility, not in scientific evidence… (p. 185).

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.

CDP-Choline is also known as Citicoline or Cytidine Diphosphocholine. It has been enhanced to allow improved crossing of the blood-brain barrier. Your body converts it to Choline and Cytidine. The second then gets converted to Uridine (which crosses the blood-brain barrier). CDP-Choline is found in meats (liver), eggs (yolk), fish, and vegetables (broccoli, Brussels sprout).
But though it’s relatively new on the scene with ambitious young professionals, creatine has a long history with bodybuilders, who have been taking it for decades to improve their muscle #gains. In the US, sports supplements are a multibillion-dollar industry – and the majority contain creatine. According to a survey conducted by Ipsos Public Affairs last year, 22% of adults said they had taken a sports supplement in the last year. If creatine was going to have a major impact in the workplace, surely we would have seen some signs of this already.

“Cavin, you are phemomenal! An incredulous journey of a near death accident scripted by an incredible man who chose to share his knowledge of healing his own broken brain. I requested our public library purchase your book because everyone, those with and without brain injuries, should have access to YOUR brain and this book. Thank you for your legacy to mankind!”
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Evidence in support of the neuroprotective effects of flavonoids has increased significantly in recent years, although to date much of this evidence has emerged from animal rather than human studies. Nonetheless, with a view to making recommendations for future good practice, we review 15 existing human dietary intervention studies that have examined the effects of particular types of flavonoid on cognitive performance. The studies employed a total of 55 different cognitive tests covering a broad range of cognitive domains. Most studies incorporated at least one measure of executive function/working memory, with nine reporting significant improvements in performance as a function of flavonoid supplementation compared to a control group. However, some domains were overlooked completely (e.g. implicit memory, prospective memory), and for the most part there was little consistency in terms of the particular cognitive tests used making across study comparisons difficult. Furthermore, there was some confusion concerning what aspects of cognitive function particular tests were actually measuring. Overall, while initial results are encouraging, future studies need to pay careful attention when selecting cognitive measures, especially in terms of ensuring that tasks are actually sensitive enough to detect treatment effects.
(On a side note, I think I understand now why modafinil doesn’t lead to a Beggars in Spain scenario; BiS includes massive IQ and motivation boosts as part of the Sleepless modification. Just adding 8 hours a day doesn’t do the world-changing trick, no more than some researchers living to 90 and others to 60 has lead to the former taking over. If everyone were suddenly granted the ability to never need sleep, many of them would have no idea what to do with the extra 8 or 9 hours and might well be destroyed by the gift; it takes a lot of motivation to make good use of the time, and if one cannot, then it is a curse akin to the stories of immortals who yearn for death - they yearn because life is not a blessing to them, though that is a fact more about them than life.)
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.
We started hearing the buzz when Daytime TV Doctors, started touting these new pills that improve concentration, memory recall, focus, mental clarity and energy. And though we love the good Doctor and his purple gloves, we don’t love the droves of hucksters who prey on his loyal viewers trying to make a quick buck, often selling low-grade versions of his medical discoveries.
Alpha Lipoic Acid is a vitamin-like chemical filled with antioxidant properties, that naturally occur in broccoli, spinach, yeast, kidney, liver, and potatoes. The compound is generally prescribed to patients suffering from nerve-related symptoms of diabetes because it helps in preventing damage to the nerve cells and improves the functioning of neurons. It can be termed as one of the best memory boosting supplements.
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.
Kratom (Erowid, Reddit) is a tree leaf from Southeast Asia; it’s addictive to some degree (like caffeine and nicotine), and so it is regulated/banned in Thailand, Malaysia, Myanmar, and Bhutan among others - but not the USA. (One might think that kratom’s common use there indicates how very addictive it must be, except it literally grows on trees so it can’t be too hard to get.) Kratom is not particularly well-studied (and what has been studied is not necessarily relevant - I’m not addicted to any opiates!), and it suffers the usual herbal problem of being an endlessly variable food product and not a specific chemical with the fun risks of perhaps being poisonous, but in my reading it doesn’t seem to be particularly dangerous or have serious side-effects.
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:
Brain-imaging studies are consistent with the existence of small effects that are not reliably captured by the behavioral paradigms of the literature reviewed here. Typically with executive function tasks, reduced activation of task-relevant areas is associated with better performance and is interpreted as an indication of higher neural efficiency (e.g., Haier, Siegel, Tang, Abel, & Buchsbaum, 1992). Several imaging studies showed effects of stimulants on task-related activation while failing to find effects on cognitive performance. Although changes in brain activation do not necessarily imply functional cognitive changes, they are certainly suggestive and may well be more sensitive than behavioral measures. Evidence of this comes from a study of COMT variation and executive function. Egan and colleagues (2001) found a genetic effect on executive function in an fMRI study with sample sizes as small as 11 but did not find behavioral effects in these samples. The genetic effect on behavior was demonstrated in a separate study with over a hundred participants. In sum, d-AMP and MPH measurably affect the activation of task-relevant brain regions when participants’ task performance does not differ. This is consistent with the hypothesis (although by no means positive proof) that stimulants exert a true cognitive-enhancing effect that is simply too small to be detected in many studies.

20 March, 2x 13mg; first time, took around 11:30AM, half-life 3 hours, so halved by 2:30PM. Initial reaction: within 20 minutes, started to feel light-headed, experienced a bit of physical clumsiness while baking bread (dropped things or poured too much thrice); that began to pass in an hour, leaving what felt like a cheerier mood and less anxiety. Seems like it mostly wore off by 6PM. Redosed at 8PM TODO: maybe take a look at the HRV data? looks interestingly like HRV increased thanks to the tianeptine 21 March, 2x17mg; seemed to buffer effects of FBI visit 22 March, 2x 23 March, 2x 24 March, 2x 25 March, 2x 26 March, 2x 27 March, 2x 28 March, 2x 7 April, 2x 8 April, 2x 9 April, 2x 10 April, 2x 11 April, 2x 12 April, 2x 23 April, 2x 24 April, 2x 25 April, 2x 26 April, 2x 27 April, 2x 28 April, 2x 29 April, 2x 7 May, 2x 8 May, 2x 9 May, 2x 10 May, 2x 3 June, 2x 4 June, 2x 5 June, 2x 30 June, 2x 30 July, 1x 31 July, 1x 1 August, 2x 2 August, 2x 3 August, 2x 5 August, 2x 6 August, 2x 8 August, 2x 10 August, 2x 12 August: 2x 14 August: 2x 15 August: 2x 16 August: 1x 18 August: 2x 19 August: 2x 21 August: 2x 23 August: 1x 24 August: 1x 25 August: 1x 26 August: 2x 27 August: 1x 29 August: 2x 30 August: 1x 02 September: 1x 04 September: 1x 07 September: 2x 20 September: 1x 21 September: 2x 24 September: 2x 25 September: 2x 26 September: 2x 28 September: 2x 29 September: 2x 5 October: 2x 6 October: 1x 19 October: 1x 20 October: 1x 27 October: 1x 4 November: 1x 5 November: 1x 8 November: 1x 9 November: 2x 10 November: 1x 11 November: 1x 12 November: 1x 25 November: 1x 26 November: 1x 27 November: 1x 4 December: 2x 27 December: 1x 28 December: 1x 2017 7 January: 1x 8 January: 2x 10 January: 1x 16 January: 1x 17 January: 1x 20 January: 1x 24 January: 1x 25 January: 2x 27 January: 2x 28 January: 2x 1 February: 2x 3 February: 2x 8 February: 1x 16 February: 2x 17 February: 2x 18 February: 1x 22 February: 1x 27 February: 2x 14 March: 1x 15 March: 1x 16 March: 2x 17 March: 2x 18 March: 2x 19 March: 2x 20 March: 2x 21 March: 2x 22 March: 2x 23 March: 1x 24 March: 2x 25 March: 2x 26 March: 2x 27 March: 2x 28 March: 2x 29 March: 2x 30 March: 2x 31 March: 2x 01 April: 2x 02 April: 1x 03 April: 2x 04 April: 2x 05 April: 2x 06 April: 2x 07 April: 2x 08 April: 2x 09 April: 2x 10 April: 2x 11 April: 2x 20 April: 1x 21 April: 1x 22 April: 1x 23 April: 1x 24 April: 1x 25 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July: 2x 01 August: 2x 02 August: 2x 03 August: 2x 04 August: 2x 05 August: 2x 06 August: 2x 07 August: 2x 08 August: 2x 09 August: 2x 10 August: 2x 11 August: 2x 12 August: 2x 13 August: 2x 14 August: 2x 15 August: 2x 16 August: 2x 17 August: 2x 18 August: 2x 19 August: 2x 20 August: 2x 21 August: 2x 22 August: 2x 23 August: 2x 24 August: 2x 25 August: 2x 26 August: 1x 27 August: 2x 28 August: 2x 29 August: 2x 30 August: 2x 31 August: 2x 01 September: 2x 02 September: 2x 03 September: 2x 04 September: 2x 05 September: 2x 06 September: 2x 07 September: 2x 08 September: 2x 09 September: 2x 10 September: 2x 11 September: 2x 12 September: 2x 13 September: 2x 14 September: 2x 15 September: 2x 16 September: 2x 17 September: 2x 18 September: 2x 19 September: 2x 20 September: 2x 21 September: 2x 22 September: 2x 23 September: 2x 24 September: 2x 25 September: 2x 26 September: 2x 27 September: 2x 28 September: 2x 29 September: 2x 30 September: 2x October 01 October: 2x 02 October: 2x 03 October: 2x 04 October: 2x 05 October: 2x 06 October: 2x 07 October: 2x 08 October: 2x 09 October: 2x 10 October: 2x 11 October: 2x 12 October: 2x 13 October: 2x 14 October: 2x 15 October: 2x 16 October: 2x 17 October: 2x 18 October: 2x 20 October: 2x 21 October: 2x 22 October: 2x 23 October: 2x 24 October: 2x 25 October: 2x 26 October: 2x 27 October: 2x 28 October: 2x 29 October: 2x 30 October: 2x 31 October: 2x 01 November: 2x 02 November: 2x 03 November: 2x 04 November: 2x 05 November: 2x 06 November: 2x 07 November: 2x 08 November: 2x 09 November: 2x 10 November: 2x 11 November: 2x 12 November: 2x 13 November: 2x 14 November: 2x 15 November: 2x 16 November: 2x 17 November: 2x 18 November: 2x 19 November: 2x 20 November: 2x 21 November: 2x 22 November: 2x 23 November: 2x 24 November: 2x 25 November: 2x 26 November: 2x 27 November: 2x 28 November: 2x 29 November: 2x 30 November: 2x 01 December: 2x 02 December: 2x 03 December: 2x 04 December: 2x 05 December: 2x 06 December: 2x 07 December: 2x 08 December: 2x 09 December: 2x 10 December: 2x 11 December: 2x 12 December: 2x 13 December: 2x 14 December: 2x 15 December: 2x 16 December: 2x 17 December: 2x 18 December: 2x 19 December: 2x 20 December: 2x 21 December: 2x 22 December: 2x 23 December: 2x 24 December: 2x 25 December: 2x ran out, last day: 25 December 2017 –>
“How to Feed a Brain is an important book. It’s the book I’ve been looking for since sustaining multiple concussions in the fall of 2013. I’ve dabbled in and out of gluten, dairy, and (processed) sugar free diets the past few years, but I have never eaten enough nutritious foods. This book has a simple-to-follow guide on daily consumption of produce, meat, and water.
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%.
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.
Next, if these theorized safe and effective pills don't just get you through a test or the day's daily brain task but also make you smarter, whatever smarter means, then what? Where's the boundary between genius and madness? If Einstein had taken such drugs, would he have created a better theory of gravity? Or would he have become delusional, chasing quantum ghosts with no practical application, or worse yet, string theory. (Please use "string theory" in your subject line for easy sorting of hate mail.)
ADHD medication sales are growing rapidly, with annual revenues of $12.9 billion in 2015. These drugs can be obtained legally by those who have a prescription, which also includes those who have deliberately faked the symptoms in order to acquire the desired medication. (According to an experiment published in 2010, it is difficult for medical practitioners to separate those who feign the symptoms from those who actually have them.) That said, faking might not be necessary if a doctor deems your desired productivity level or your stress around a big project as reason enough to prescribe medication.

Many of the food-derived ingredients that are often included in nootropics—omega-3s in particular, but also flavonoids—do seem to improve brain health and function. But while eating fatty fish, berries and other healthy foods that are high in these nutrients appears to be good for your brain, the evidence backing the cognitive benefits of OTC supplements that contain these and other nutrients is weak.
Despite some positive findings, a lot of studies find no effects of enhancers in healthy subjects. For instance, although some studies suggest moderate enhancing effects in well-rested subjects, modafinil mostly shows enhancing effects in cases of sleep deprivation. A recent study by Martha Farah and colleagues found that Adderall (mixed amphetamine salts) had only small effects on cognition but users believed that their performance was enhanced when compared to placebo.

If you could take a drug to boost your brainpower, would you? This question, faced by Bradley Cooper’s character in the big-budget movie Limitless, is now facing students who are frantically revising for exams. Although they are nowhere near the strength of the drug shown in the film, mind-enhancing drugs are already on the pharmacy shelves, and many people are finding the promise of sharper thinking through chemistry highly seductive.

As I am not any of the latter, I didn’t really expect a mental benefit. As it happens, I observed nothing. What surprised me was something I had forgotten about: its physical benefits. My performance in Taekwondo classes suddenly improved - specifically, my endurance increased substantially. Before, classes had left me nearly prostrate at the end, but after, I was weary yet fairly alert and happy. (I have done Taekwondo since I was 7, and I have a pretty good sense of what is and is not normal performance for my body. This was not anything as simple as failing to notice increasing fitness or something.) This was driven home to me one day when in a flurry before class, I prepared my customary tea with piracetam, choline & creatine; by the middle of the class, I was feeling faint & tired, had to take a break, and suddenly, thunderstruck, realized that I had absentmindedly forgot to actually drink it! This made me a believer.
Similarly, we could try applying Nick Bostrom’s reversal test and ask ourselves, how would we react to a virus which had no effect but to eliminate sleep from alternating nights and double sleep in the intervening nights? We would probably grouch about it for a while and then adapt to our new hedonistic lifestyle of partying or working hard. On the other hand, imagine the virus had the effect of eliminating normal sleep but instead, every 2 minutes, a person would fall asleep for a minute. This would be disastrous! Besides the most immediate problems like safely driving vehicles, how would anything get done? You would hold a meeting and at any point, a third of the participants would be asleep. If the virus made it instead 2 hours on, one hour off, that would be better but still problematic: there would be constant interruptions. And so on, until we reach our present state of 16 hours on, 8 hours off. Given that we rejected all the earlier buffer sizes, one wonders if 16:8 can be defended as uniquely suited to circumstances. Is that optimal? It may be, given the synchronization with the night-day cycle, but I wonder; rush hour alone stands as an argument against synchronized sleep - wouldn’t our infrastructure would be much cheaper if it only had to handle the average daily load rather than cope with the projected peak loads? Might not a longer cycle be better? The longer the day, the less we are interrupted by sleep; it’s a hoary cliche about programmers that they prefer to work in long sustained marathons during long nights rather than sprint occasionally during a distraction-filled day, to the point where some famously adopt a 28 hour day (which evenly divides a week into 6 days). Are there other occupations which would benefit from a 20 hour waking period? Or 24 hour waking period? We might not know because without chemical assistance, circadian rhythms would overpower anyone attempting such schedules. It certainly would be nice if one had long time chunks in which could read a challenging book in one sitting, without heroic arrangements.↩
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.
The infinite promise of stacking is why, whatever weight you attribute to the evidence of their efficacy, nootropics will never go away: With millions of potential iterations of brain-enhancing regimens out there, there is always the tantalizing possibility that seekers haven’t found the elusive optimal combination of pills and powders for them—yet. Each “failure” is but another step in the process-of-elimination journey to biological self-actualization, which may be just a few hundred dollars and a few more weeks of amateur alchemy away.
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.

Perceptual–motor congruency was the basis of a study by Fitzpatrick et al. (1988) in which subjects had to press buttons to indicate the location of a target stimulus in a display. In the simple condition, the left-to-right positions of the buttons are used to indicate the left-to-right positions of the stimuli, a natural mapping that requires little cognitive control. In the rotation condition, the mapping between buttons and stimulus positions is shifted to the right by one and wrapped around, such that the left-most button is used to indicate the right-most position. Cognitive control is needed to resist responding with the other, more natural mapping. MPH was found to speed responses in this task, and the speeding was disproportionate for the rotation condition, consistent with enhancement of cognitive control.
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So, I thought I might as well experiment since I have it. I put the 23 remaining pills into gel capsules with brown rice as filling, made ~30 placebo capsules, and will use the one-bag blinding/randomization method. I don’t want to spend the time it would take to n-back every day, so I will simply look for an effect on my daily mood/productivity self-rating; hopefully Noopept will add a little on average above and beyond my existing practices like caffeine+piracetam (yes, Noopept may be as good as piracetam, but since I still have a ton of piracetam from my 3kg order, I am primarily interested in whether Noopept adds onto piracetam rather than replaces). 10mg doses seem to be on the low side for Noopept users, weakening the effect, but on the other hand, if I were to take 2 capsules at a time, then I’d halve the sample size; it’s not clear what is the optimal tradeoff between dose and n for statistical power.

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).↩
The effect? 3 or 4 weeks later, I’m not sure. When I began putting all of my nootropic powders into pill-form, I put half a lithium pill in each, and nevertheless ran out of lithium fairly quickly (3kg of piracetam makes for >4000 OO-size pills); those capsules were buried at the bottom of the bucket under lithium-less pills. So I suddenly went cold-turkey on lithium. Reflecting on the past 2 weeks, I seem to have been less optimistic and productive, with items now lingering on my To-Do list which I didn’t expect to. An effect? Possibly.

Companies already know a great deal about how their employees live their lives. With the help of wearable technologies and health screenings, companies can now analyze the relation between bodily activities — exercise, sleep, nutrition, etc. — and work performance. With the justification that healthy employees perform better, some companies have made exercise mandatory by using sanctions against those who refuse to perform. And according to The Kaiser Family Foundation, of the large U.S. companies that offer health screenings, nearly half of them use financial incentives to persuade employees to participate.

The goal of this article has been to synthesize what is known about the use of prescription stimulants for cognitive enhancement and what is known about the cognitive effects of these drugs. We have eschewed discussion of ethical issues in favor of simply trying to get the facts straight. Although ethical issues cannot be decided on the basis of facts alone, neither can they be decided without relevant facts. Personal and societal values will dictate whether success through sheer effort is as good as success with pharmacologic help, whether the freedom to alter one’s own brain chemistry is more important than the right to compete on a level playing field at school and work, and how much risk of dependence is too much risk. Yet these positions cannot be translated into ethical decisions in the real world without considerable empirical knowledge. Do the drugs actually improve cognition? Under what circumstances and for whom? Who will be using them and for what purposes? What are the mental and physical health risks for frequent cognitive-enhancement users? For occasional users?
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]
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.

And the drugs are not terribly difficult to get, depending on where you’re located. Modafinil has an annual global share of $700 million, with high estimated off-label use. Although these drugs can be purchased over the internet, their legal status varies between countries. For example, it is legal to possess and use Modafinil in the United Kingdom without a prescription, but not in United States.
The infinite promise of stacking is why, whatever weight you attribute to the evidence of their efficacy, nootropics will never go away: With millions of potential iterations of brain-enhancing regimens out there, there is always the tantalizing possibility that seekers haven’t found the elusive optimal combination of pills and powders for them—yet. Each “failure” is but another step in the process-of-elimination journey to biological self-actualization, which may be just a few hundred dollars and a few more weeks of amateur alchemy away.
There is evidence to suggest that modafinil, methylphenidate, and amphetamine enhance cognitive processes such as learning and working memory...at least on certain laboratory tasks. One study found that modafinil improved cognitive task performance in sleep-deprived doctors. Even in non-sleep deprived healthy volunteers, modafinil improved planning and accuracy on certain cognitive tasks. Similarly, methylphenidate and amphetamine also enhanced performance of healthy subjects in certain cognitive tasks.

One fairly powerful nootropic substance that, appropriately, has fallen out of favor is nicotine. It’s the chemical that gives tobacco products their stimulating kick. It isn’t what makes them so deadly, but it does make smoking very addictive. When Europeans learned about tobacco’s use from indigenous tribes they encountered in the Americas in the 15th and 16th centuries, they got hooked on its mood-altering effects right away and even believed it could cure joint pain, epilepsy, and the plague. Recently, researchers have been testing the effects of nicotine that’s been removed from tobacco, and they believe that it might help treat neurological disorders including Parkinson’s disease and schizophrenia; it may also improve attention and focus. But, please, don’t start smoking or vaping. Check out these 14 weird brain exercises that make you smarter.

In the largest nationwide study, McCabe et al. (2005) sampled 10,904 students at 119 public and private colleges and universities across the United States, providing the best estimate of prevalence among American college students in 2001, when the data were collected. This survey found 6.9% lifetime, 4.1% past-year, and 2.1% past-month nonmedical use of a prescription stimulant. It also found that prevalence depended strongly on student and school characteristics, consistent with the variability noted among the results of single-school studies. The strongest predictors of past-year nonmedical stimulant use by college students were admissions criteria (competitive and most competitive more likely than less competitive), fraternity/sorority membership (members more likely than nonmembers), and gender (males more likely than females).

As Sulbutiamine crosses the blood-brain barrier very easily, it has a positive effect on the cholinergic and the glutamatergic receptors that are responsible for essential activities impacting memory, concentration, and mood. The compound is also fat-soluble, which means it circulates rapidly and widely throughout the body and the brain, ensuring positive results. Thus, patients with schizophrenia and Parkinson’s disease will find the drug to be very effective.

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.
One idea I’ve been musing about is the connections between IQ, Conscientiousness, and testosterone. IQ and Conscientiousness do not correlate to a remarkable degree - even though one would expect IQ to at least somewhat enable a long-term perspective, self-discipline, metacognition, etc! There are indications in studies of gifted youth that they have lower testosterone levels. The studies I’ve read on testosterone indicate no improvements to raw ability. So, could there be a self-sabotaging aspect to human intelligence whereby greater intelligence depends on lack of testosterone, but this same lack also holds back Conscientiousness (despite one’s expectation that intelligence would produce greater self-discipline and planning), undermining the utility of greater intelligence? Could cases of high IQ types who suddenly stop slacking and accomplish great things sometimes be due to changes in testosterone? Studies on the correlations between IQ, testosterone, Conscientiousness, and various measures of accomplishment are confusing and don’t always support this theory, but it’s an idea to keep in mind.

Rabiner et al. (2009) 2007 One public and one private university undergraduates (N = 3,390) 8.9% (while in college), 5.4% (past 6 months) Most common reasons endorsed: to concentrate better while studying, to be able to study longer, to feel less restless while studying 48%: from a friend with a prescription; 19%: purchased it from a friend with a prescription; 6%: purchased it from a friend without a prescription
“The author’s story alone is a remarkable account of not just survival, but transcendence of a near-death experience. Cavin went on to become an advocate for survival and survivors of traumatic brain injuries, discovering along the way the key role played by nutrition. But this book is not just for injury survivors. It is for anyone who wants to live (and eat) well.”
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.
Many of the positive effects of cognitive enhancers have been seen in experiments using rats. For example, scientists can train rats on a specific test, such as maze running, and then see if the "smart drug" can improve the rats' performance. It is difficult to see how many of these data can be applied to human learning and memory. For example, what if the "smart drug" made the rat hungry? Wouldn't a hungry rat run faster in the maze to receive a food reward than a non-hungry rat? Maybe the rat did not get any "smarter" and did not have any improved memory. Perhaps the rat ran faster simply because it was hungrier. Therefore, it was the rat's motivation to run the maze, not its increased cognitive ability that affected the performance. Thus, it is important to be very careful when interpreting changes observed in these types of animal learning and memory experiments.
It looks like the overall picture is that nicotine is absorbed well in the intestines and the colon, but not so well in the stomach; this might be the explanation for the lack of effect, except on the other hand, the specific estimates I see are that 10-20% of the nicotine will be bioavailable in the stomach (as compared to 50%+ for mouth or lungs)… so any of my doses of >5ml should have overcome the poorer bioavailability! But on the gripping hand, these papers are mentioning something about the liver metabolizing nicotine when absorbed through the stomach, so…

With regards to your mental well-being, nootropics are not antidepressants and mental care is important. They are not a replacement for other ways of treating mental difficulties. That being said, they can help boost your happiness. For instance by helping you sleep better. Melatonin is a synthetic version of a naturally occurring neurotransmitter and could help you sleep better.

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.

"Where can you draw the line between Red Bull, six cups of coffee and a prescription drug that keeps you more alert," says Michael Schrage of the MIT Center for Digital Business, who has studied the phenomenon. "You can't draw the line meaningfully - some organizations have cultures where it is expected that employees go the extra mile to finish an all-nighter. "
Chocolate or cocoa powder (Examine.com), contains the stimulants caffeine and the caffeine metabolite theobromine, so it’s not necessarily surprising if cocoa powder was a weak stimulant. It’s also a witch’s brew of chemicals such as polyphenols and flavonoids some of which have been fingered as helpful10, which all adds up to an unclear impact on health (once you control for eating a lot of sugar).
Neuroplasticity, or the brain's ability to change and reorganize itself in response to intrinsic and extrinsic factors, indicates great potential for us to enhance brain function by medical or other interventions. Psychotherapy has been shown to induce structural changes in the brain. Other interventions that positively influence neuroplasticity include meditation, mindfulness , and compassion.
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:
Popular smart drugs on the market include methylphenidate (commonly known as Ritalin) and amphetamine (Adderall), stimulants normally used to treat attention deficit hyperactivity disorder or ADHD. In recent years, another drug called modafinil has emerged as the new favourite amongst college students. Primarily used to treat excessive sleepiness associated with the sleep disorder narcolepsy, modafinil increases alertness and energy.
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):
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.

The concept of neuroenhancement and the use of substances to improve cognitive functioning in healthy individuals, is certainly not a new one. In fact, one of the first cognitive enhancement drugs, Piracetam, was developed over fifty years ago by psychologist and chemist C.C. Giurgea. Although he did not know the exact mechanism, Giurgia believed the drug boosted brain power and so began his exploration into "smart pills", or nootropics, a term he coined from the Greek nous, meaning "mind," and trepein, meaning "to bend.  

Phenotropil is an over-the-counter supplement similar in structure to Piracetam (and Noopept). This synthetic smart drug has been used to treat stroke, epilepsy and trauma recovery. A 2005 research paper also demonstrated that patients diagnosed with natural lesions or brain tumours see improvements in cognition. Phenylpiracetam intake can also result in minimised feelings of anxiety and depression. This is one of the more powerful unscheduled Nootropics available.
If you haven’t seen the movie, imagine unfathomable brain power in capsule form. Picture a drug from another universe. It can transform an unsuccessful couch potato into a millionaire financial mogul. Ingesting the powerful smart pill boosts intelligence and turns you into a prodigy. Its results are instant. Sounds great, right? If only it were real.
There is no shortage of nootropics available for purchase online that can be shipped to you nearly anywhere in the world. Yet, many of these supplements and drugs have very little studies, particularly human studies, confirming their results. While this lack of research may not scare away more adventurous neurohackers, many people would prefer to […]