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 evidence? In small studies, healthy people taking modafinil showed improved planning and working memory, and better reaction time, spatial planning, and visual pattern recognition. A 2015 meta-analysis claimed that “when more complex assessments are used, modafinil appears to consistently engender enhancement of attention, executive functions, and learning” without affecting a user’s mood. In a study from earlier this year involving 39 male chess players, subjects taking modafinil were found to perform better in chess games played against a computer.

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.

Jesper Noehr, 30, reels off the ingredients in the chemical cocktail he’s been taking every day before work for the past six months. It’s a mixture of exotic dietary supplements and research chemicals that he says gives him an edge in his job without ill effects: better memory, more clarity and focus and enhanced problem-solving abilities. “I can keep a lot of things on my mind at once,” says Noehr, who is chief technology officer for a San Francisco startup.


Both nootropics startups provide me with samples to try. In the case of Nootrobox, it is capsules called Sprint designed for a short boost of cognitive enhancement. They contain caffeine – the equivalent of about a cup of coffee, and L-theanine – about 10 times what is in a cup of green tea, in a ratio that is supposed to have a synergistic effect (all the ingredients Nootrobox uses are either regulated as supplements or have a “generally regarded as safe” designation by US authorities)

The prefrontal cortex at the front of the brain is the zone that produces such representations, and it is the focus of Arnsten’s work. “The way the prefrontal cortex creates these representations is by having pyramidal cells – they’re actually shaped like little pyramids – exciting each other. They keep each other firing, even when there’s no information coming in from the environment to stimulate the circuits,” she explains.
Kennedy et al. (1990) administered what they termed a grammatical reasoning task to subjects, in which a sentence describing the order of two letters, A and B, is presented along with the letter pair, and subjects must determine whether or not the sentence correctly describes the letter pair. They found no effect of d-AMP on performance of this task.
Smart pills have revolutionized the diagnosis of gastrointestinal disorders and could replace conventional diagnostic techniques such as endoscopy. Traditionally, an endoscopy probe is inserted into a patient’s esophagus, and subsequently the upper and lower gastrointestinal tract, for diagnostic purposes. There is a risk of perforation or tearing of the esophageal lining, and the patient faces discomfort during and after the procedure. A smart pill or wireless capsule endoscopy (WCE), however, can easily be swallowed and maneuvered to capture images, and requires minimal patient preparation, such as sedation. The built-in sensors allow the measurement of all fluids and gases in the gut, giving the physician a multidimensional picture of the human body.

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).
Armodafinil is sort of a purified modafinil which Cephalon sells under the brand-name Nuvigil (and Sun under Waklert20). Armodafinil acts much the same way (see the ADS Drug Profile) but the modafinil variant filtered out are the faster-acting molecules21. Hence, it is supposed to last longer. as studies like Pharmacodynamic effects on alertness of single doses of armodafinil in healthy subjects during a nocturnal period of acute sleep loss seem to bear out; anecdotally, it’s also more powerful, with Cephalon offering pills with doses as low as 50mg. (To be technical, modafinil is racemic: it comes in two forms which are rotations, mirror-images of each other. The rotation usually doesn’t matter, but sometimes it matters tremendously - for example, one form of thalidomide stops morning sickness, and the other rotation causes hideous birth defects.)
That doesn’t necessarily mean all smart drugs – now and in the future – will be harmless, however. The brain is complicated. In trying to upgrade it, you risk upsetting its intricate balance. “It’s not just about more, it’s about having to be exquisitely and exactly right. And that’s very hard to do,” says Arnstein. “What’s good for one system may be bad for another system,” adds Trevor Robbins, Professor of Cognitive Neuroscience at the University of Cambridge. “It’s clear from the experimental literature that you can affect memory with pharmacological agents, but the problem is keeping them safe.”
On the other metric, suppose we removed the creatine? Dropping 4 grams of material means we only need to consume 5.75 grams a day, covered by 8 pills (compared to 13 pills). We save 5,000 pills, which would have cost $45 and also don’t spend the $68 for the creatine; assuming a modafinil formulation, that drops our $1761 down to $1648 or $1.65 a day. Or we could remove both the creatine and modafinil, for a grand total of $848 or $0.85 a day, which is pretty reasonable.
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.
Several studies have assessed the effect of MPH and d-AMP on tasks tapping various other aspects of spatial working memory. Three used the spatial working memory task from the CANTAB battery of neuropsychological tests (Sahakian & Owen, 1992). In this task, subjects search for a target at different locations on a screen. Subjects are told that locations containing a target in previous trials will not contain a target in future trials. Efficient performance therefore requires remembering and avoiding these locations in addition to remembering and avoiding locations already searched within a trial. Mehta et al. (2000) found evidence of greater accuracy with MPH, and Elliott et al. (1997) found a trend for the same. In Mehta et al.’s study, this effect depended on subjects’ working memory ability: the lower a subject’s score on placebo, the greater the improvement on MPH. In Elliott et al.’s study, MPH enhanced performance for the group of subjects who received the placebo first and made little difference for the other group. The reason for this difference is unclear, but as mentioned above, this may reflect ability differences between the groups. More recently, Clatworthy et al. (2009) undertook a positron emission tomography (PET) study of MPH effects on two tasks, one of which was the CANTAB spatial working memory task. They failed to find consistent effects of MPH on working memory performance but did find a systematic relation between the performance effect of the drug in each individual and its effect on individuals’ dopamine activity in the ventral striatum.
However, normally when you hear the term nootropic kicked around, people really mean a “cognitive enhancer” — something that does benefit thinking in some way (improved memory, faster speed-of-processing, increased concentration, or a combination of these, etc.), but might not meet the more rigorous definition above.  “Smart drugs” is another largely-interchangeable term.
For 2 weeks, upon awakening I took close-up photographs of my right eye. Then I ordered two jars of Life-Extension Sea-Iodine (60x1mg) (1mg being an apparently safe dose), and when it arrived on 10 September 2012, I stopped the photography and began taking 1 iodine pill every other day. I noticed no ill effects (or benefits) after a few weeks and upped the dose to 1 pill daily. After the first jar of 60 pills was used up, I switched to the second jar, and began photography as before for 2 weeks. The photographs were uploaded, cropped by hand in Gimp, and shrunk to more reasonable dimensions; both sets are available in a Zip file.

Another important epidemiological question about the use of prescription stimulants for cognitive enhancement concerns the risk of dependence. MPH and d-AMP both have high potential for abuse and addiction related to their effects on brain systems involved in motivation. On the basis of their reanalysis of NSDUH data sets from 2000 to 2002, Kroutil and colleagues (2006) estimated that almost one in 20 nonmedical users of prescription ADHD medications meets criteria for dependence or abuse. This sobering estimate is based on a survey of all nonmedical users. The immediate and long-term risks to individuals seeking cognitive enhancement remain unknown.


The surveys just reviewed indicate that many healthy, normal students use prescription stimulants to enhance their cognitive performance, based in part on the belief that stimulants enhance cognitive abilities such as attention and memorization. Of course, it is possible that these users are mistaken. One possibility is that the perceived cognitive benefits are placebo effects. Another is that the drugs alter students’ perceptions of the amount or quality of work accomplished, rather than affecting the work itself (Hurst, Weidner, & Radlow, 1967). A third possibility is that stimulants enhance energy, wakefulness, or motivation, which improves the quality and quantity of work that students can produce with a given, unchanged, level of cognitive ability. To determine whether these drugs enhance cognition in normal individuals, their effects on cognitive task performance must be assessed in relation to placebo in a masked study design.
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.
Sometimes called smart drugs, brain boosters, or memory-enhancing drugs, the term "nootropics" was coined by scientist Dr. Corneliu E. Giurgea, who developed the compound piracetam as a brain enhancer, according to The Atlantic. The word is derived from the Greek noo, meaning mind, and trope, which means "change" in French. In essence, all nootropics aim to change your mind by enhancing functions like memory or attention.
By which I mean that simple potassium is probably the most positively mind altering supplement I’ve ever tried…About 15 minutes after consumption, it manifests as a kind of pressure in the head or temples or eyes, a clearing up of brain fog, increased focus, and the kind of energy that is not jittery but the kind that makes you feel like exercising would be the reasonable and prudent thing to do. I have done no tests, but feel smarter from this in a way that seems much stronger than piracetam or any of the conventional weak nootropics. It is not just me – I have been introducing this around my inner social circle and I’m at 7/10 people felt immediately noticeable effects. The 3 that didn’t notice much were vegetarians and less likely to have been deficient. Now that I’m not deficient, it is of course not noticeable as mind altering, but still serves to be energizing, particularly for sustained mental energy as the night goes on…Potassium chloride initially, but since bought some potassium gluconate pills… research indicates you don’t want to consume large amounts of chloride (just moderate amounts).
Most people I talk to about modafinil seem to use it for daytime usage; for me that has not ever worked out well, but I had nothing in particular to show against it. So, as I was capping the last of my piracetam-caffeine mix and clearing off my desk, I put the 4 remaining Modalerts pills into capsules with the last of my creatine powder and then mixed them with 4 of the theanine-creatine pills. Like the previous Adderall trial, I will pick one pill blindly each day and guess at the end which it was. If it was active (modafinil-creatine), take a break the next day; if placebo (theanine-creatine), replace the placebo and try again the next day. We’ll see if I notice anything on DNB or possibly gwern.net edits.

Participants (n=205) [young adults aged 18-30 years] were recruited between July 2010 and January 2011, and were randomized to receive either a daily 150 µg (0.15mg) iodine supplement or daily placebo supplement for 32 weeks…After adjusting for baseline cognitive test score, examiner, age, sex, income, and ethnicity, iodine supplementation did not significantly predict 32 week cognitive test scores for Block Design (p=0.385), Digit Span Backward (p=0.474), Matrix Reasoning (p=0.885), Symbol Search (p=0.844), Visual Puzzles (p=0.675), Coding (p=0.858), and Letter-Number Sequencing (p=0.408).


A similar pill from HQ Inc. (Palmetto, Fla.) called the CorTemp Ingestible Core Body Temperature Sensor transmits real-time body temperature. Firefighters, football players, soldiers and astronauts use it to ensure that they do not overheat in high temperatures. HQ Inc. is working on a consumer version, to be available in 2018, that would wirelessly communicate to a smartphone app.

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.


However, history has shown that genies don’t stay in bottles. All ethics aside, there is ample proof that use of smart drugs can profoundly improve human cognition, and where there is an advantage to be gained – even where risks are involved – some people will leap at the chance to capitalize. At Smart Drug Smarts, we anticipate the social tide will continue to turn in favor of elective neural enhancers, and that the beneficial effects to users who choose to make the most of their brains will inevitably outweigh the costs.
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.

The Stroop task tests the ability to inhibit the overlearned process of reading by presenting color names in colored ink and instructing subjects to either read the word (low need for cognitive control because this is the habitual response to printed words) or name the ink color (high need for cognitive control). Barch and Carter (2005) administered this task to normal control subjects on placebo and d-AMP and found speeding of responses with the drug. However, the speeding was roughly equivalent for the conditions with low and high cognitive control demands, suggesting that the observed facilitation may not have been specific to cognitive control.
Nootropics are a specific group of smart drugs. But nootropics aren’t the only drugs out there that promise you some extra productivity. More students and office workers are using drugs to increase their productivity than ever before [79]. But unlike with nootropics, many have side-effects. And that is precisely what is different between nootropics and other enhancing drugs, nootropics have little to no negative side-effects.

Two additional studies used other spatial working memory tasks. Barch and Carter (2005) required subjects to maintain one of 18 locations on the perimeter of a circle in working memory and then report the name of the letter that appeared there in a similarly arranged circle of letters. d-AMP caused a speeding of responses but no change in accuracy. Fleming et al. (1995) referred to a spatial delay response task, with no further description or citation. They reported no effect of d-AMP in the task except in the zero-delay condition (which presumably places minimal demand on working memory).

The choline-based class of smart drugs play important cognitive roles in memory, attention, and mood regulation. Acetylcholine (ACh) is one of the brain’s primary neurotransmitters, and also vital in the proper functioning of the peripheral nervous system. Studies with rats have shown that certain forms of learning and neural plasticity seem to be impossible in acetylcholine-depleted areas of the brain. This is particularly worth mentioning because (as noted above under the Racetams section), the Racetam class of smart drugs tends to deplete cholines from the brain, so one of the classic “supplement stacks” – chemical supplements that are used together – are Piracetam and Choline Bitartrate. Cholines can also be found in normal food sources, like egg yolks and soybeans.
You have the highest density of mitochondria in your brain’s prefrontal cortex, which helps to explain why I feel Unfair Advantage in my head first. You have the second highest density in your heart, which is probably why I feel it in the center of my chest next. Mitochondrial energizers can have profound nootropic effects! At higher doses mitochondrial energizers also make for an excellent pre-workout supplements.
×