But while some studies have found short-term benefits, Doraiswamy says there is no evidence that what are commonly known as smart drugs — of any type — improve thinking or productivity over the long run. “There’s a sizable demand, but the hype around efficacy far exceeds available evidence,” notes Doraiswamy, adding that, for healthy young people such as Silicon Valley go-getters, “it’s a zero-sum game. That’s because when you up one circuit in the brain, you’re probably impairing another system.”
It's been widely reported that Silicon Valley entrepreneurs and college students turn to Adderall (without a prescription) to work late through the night. In fact, a 2012 study published in the Journal of American College Health, showed that roughly two-thirds of undergraduate students were offered prescription stimulants for non-medical purposes by senior year.
The research literature, while copious, is messy and varied: methodologies and devices vary substantially, sample sizes are tiny, the study designs vary from paper to paper, metrics are sometimes comically limited (one study measured speed of finishing a RAPM IQ test but not scores), blinding is rare and unclear how successful, etc. Relevant papers include Chung et al 2012, Rojas & Gonzalez-Lima 2013, & Gonzalez-Lima & Barrett 2014. Another Longecity user ran a self-experiment, with some design advice from me, where he performed a few cognitive tests over several periods of LLLT usage (the blocks turned out to be ABBA), using his father and towels to try to blind himself as to condition. I analyzed his data, and his scores did seem to improve, but his scores improved so much in the last part of the self-experiment I found myself dubious as to what was going on - possibly a failure of randomness given too few blocks and an temporal exogenous factor in the last quarter which was responsible for the improvement.
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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.
Analgesics Anesthetics General Local Anorectics Anti-ADHD agents Antiaddictives Anticonvulsants Antidementia agents Antidepressants Antimigraine agents Antiparkinson agents Antipsychotics Anxiolytics Depressants Entactogens Entheogens Euphoriants Hallucinogens Psychedelics Dissociatives Deliriants Hypnotics/Sedatives Mood Stabilizers Neuroprotectives Nootropics Neurotoxins Orexigenics Serenics Stimulants Wakefulness-promoting agents
The Trail Making Test is a paper-and-pencil neuropsychological test with two parts, one of which requires shifting between stimulus categories. Part A simply requires the subject to connect circled numbers in ascending order. Part B requires the subject to connect circled numbers and letters in an interleaved ascending order (1, A, 2, B, 3, C….), a task that places heavier demands on cognitive control. Silber et al. (2006) analyzed the effect of d-AMP on Trails A and B and failed to find an effect.

The amphetamine mix branded Adderall is terribly expensive to obtain even compared to modafinil, due to its tight regulation (a lower schedule than modafinil), popularity in college as a study drug, and reportedly moves by its manufacture to exploit its privileged position as a licensed amphetamine maker to extract more consumer surplus. I paid roughly $4 a pill but could have paid up to $10. Good stimulant hygiene involves recovery periods to avoid one’s body adapting to eliminate the stimulating effects, so even if Adderall was the answer to all my woes, I would not be using it more than 2 or 3 times a week. Assuming 50 uses a year (for specific projects, let’s say, and not ordinary aimless usage), that’s a cool $200 a year. My general belief was that Adderall would be too much of a stimulant for me, as I am amphetamine-naive and Adderall has a bad reputation for letting one waste time on unimportant things. We could say my prediction was 50% that Adderall would be useful and worth investigating further. The experiment was pretty simple: blind randomized pills, 10 placebo & 10 active. I took notes on how productive I was and the next day guessed whether it was placebo or Adderall before breaking the seal and finding out. I didn’t do any formal statistics for it, much less a power calculation, so let’s try to be conservative by penalizing the information quality heavily and assume it had 25%. So \frac{200 - 0}{\ln 1.05} \times 0.50 \times 0.25 = 512! The experiment probably used up no more than an hour or two total.


If the entire workforce were to start doping with prescription stimulants, it seems likely that they would have two major effects. Firstly, people would stop avoiding unpleasant tasks, and weary office workers who had perfected the art of not-working-at-work would start tackling the office filing system, keeping spreadsheets up to date, and enthusiastically attending dull meetings.
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.
If smart drugs are the synthetic cognitive enhancers, sleep, nutrition and exercise are the "natural" ones. But the appeal of drugs like Ritalin and modafinil lies in their purported ability to enhance brain function beyond the norm. Indeed, at school or in the workplace, a pill that enhanced the ability to acquire and retain information would be particularly useful when it came to revising and learning lecture material. But despite their increasing popularity, do prescription stimulants actually enhance cognition in healthy users?
All of the coefficients are positive, as one would hope, and one specific factor (MR7) squeaks in at d=0.34 (p=0.05). The graph is much less impressive than the graph for just MP, suggesting that the correlation may be spread out over a lot of factors, the current dataset isn’t doing a good job of capturing the effect compared to the MP self-rating, or it really was a placebo effect:

Modafinil is a prescription smart drug most commonly given to narcolepsy patients, as it promotes wakefulness. In addition, users indicate that this smart pill helps them concentrate and boosts their motivation. Owing to Modafinil, the feeling of fatigue is reduced, and people report that their everyday functions improve because they can manage their time and resources better, as a result reaching their goals easier.
“As a physical therapist with 30+ years of experience in treating neurological disorders such as traumatic brain injury, I simply could not believe it when Cavin told me the extent of his injuries. His story opened a new door to my awareness of the incredible benefits of proper nutrition, the power of attitude and community to heal anything we have arise in our lives Cavin is an inspiration and a true way-shower for anyone looking to invest in their health and well-being. No matter the state your brain is in, you will benefit from this cutting-edge information and be very glad (and entertained) that you read this fine work.”

Not included in the list below are prescription psychostimulants such as Adderall and Ritalin. Non-medical, illicit use of these drugs for the purpose of cognitive enhancement in healthy individuals comes with a high cost, including addiction and other adverse effects. Although these drugs are prescribed for those with attention deficit hyperactivity disorder (ADHD) to help with focus, attention and other cognitive functions, they have been shown to in fact impair these same functions when used for non-medical purposes. More alarming, when taken in high doses, they have the potential to induce psychosis.

For instance, they point to the U.S. Army's use of stimulants for soldiers to stave off sleep and to stay sharp. But the Army cares little about the long-term health effects of soldiers, who come home scarred physically or mentally, if they come home at all. It's a risk-benefit decision for the Army, and in a life-or-death situation, stimulants help.


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).
The chemicals he takes, dubbed nootropics from the Greek “noos” for “mind”, are intended to safely improve cognitive functioning. They must not be harmful, have significant side-effects or be addictive. That means well-known “smart drugs” such as the prescription-only stimulants Adderall and Ritalin, popular with swotting university students, are out. What’s left under the nootropic umbrella is a dizzying array of over-the-counter supplements, prescription drugs and unclassified research chemicals, some of which are being trialled in older people with fading cognition.
The term “smart pills” refers to miniature electronic devices that are shaped and designed in the mold of pharmaceutical capsules but perform highly advanced functions such as sensing, imaging and drug delivery. They may include biosensors or image, pH or chemical sensors. Once they are swallowed, they travel along the gastrointestinal tract to capture information that is otherwise difficult to obtain, and then are easily eliminated from the system. Their classification as ingestible sensors makes them distinct from implantable or wearable sensors.
You may have come across this age-old adage, “Work smarter, not harder.” So, why not extend the same philosophy in other aspects of your life? Are you in a situation wherein no matter how much you exercise, eat healthy, and sleep well, you still struggle to focus and motivate yourself? If yes, you need a smart solution minus the adverse health effects. Try ‘Smart Drugs,’ that could help you out of your situation by enhancing your thought process, boosting your memory, and making you more creative and productive.
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):
11:30 AM. By 2:30 PM, my hunger is quite strong and I don’t feel especially focused - it’s difficult to get through the tab-explosion of the morning, although one particularly stupid poster on the DNB ML makes me feel irritated like I might on Adderall. I initially figure the probability at perhaps 60% for Adderall, but when I wake up at 2 AM and am completely unable to get back to sleep, eventually racking up a Zeo score of 73 (compared to the usual 100s), there’s no doubt in my mind (95%) that the pill was Adderall. And it was the last Adderall pill indeed.

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.
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.
It is a known fact that cognitive decline is often linked to aging. It may not be as visible as skin aging, but the brain does in fact age. Often, cognitive decline is not noticeable because it could be as mild as forgetting names of people. However, research has shown that even in healthy adults, cognitive decline can start as early as in the late twenties or early thirties.

Sulbutiamine, mentioned earlier as a cholinergic smart drug, can also be classed a dopaminergic, although its mechanism is counterintuitive: by reducing the release of dopamine in the brain’s prefrontal cortex, the density of dopamine receptors actually increase after continued Sulbutiamine exposure, through a compensatory mechanism. (This provides an interesting example of how dividing smart drugs into sensible “classes” is a matter of taste as well as science, especially since many of them create their discernable neural effects through still undefined mechanisms.)
The data from 2-back and 3-back tasks are more complex. Three studies examined performance in these more challenging tasks and found no effect of d-AMP on average performance (Mattay et al., 2000, 2003; Mintzer & Griffiths, 2007). However, in at least two of the studies, the overall null result reflected a mixture of reliably enhancing and impairing effects. Mattay et al. (2000) examined the performance of subjects with better and worse working memory capacity separately and found that subjects whose performance on placebo was low performed better on d-AMP, whereas subjects whose performance on placebo was high were unaffected by d-AMP on the 2-back and impaired on the 3-back tasks. Mattay et al. (2003) replicated this general pattern of data with subjects divided according to genotype. The specific gene of interest codes for the production of Catechol-O-methyltransferase (COMT), an enzyme that breaks down dopamine and norepinephrine. A common polymorphism determines the activity of the enzyme, with a substitution of methionine for valine at Codon 158 resulting in a less active form of COMT. The met allele is thus associated with less breakdown of dopamine and hence higher levels of synaptic dopamine than the val allele. Mattay et al. (2003) found that subjects who were homozygous for the val allele were able to perform the n-back faster with d-AMP; those homozygous for met were not helped by the drug and became significantly less accurate in the 3-back condition with d-AMP. In the case of the third study finding no overall effect, analyses of individual differences were not reported (Mintzer & Griffiths, 2007).
The use of prescription stimulants is especially prevalent among students.[9] Surveys suggest that 0.7–4.5% of German students have used cognitive enhancers in their lifetimes.[10][11][12] Stimulants such as dimethylamylamine and methylphenidate are used on college campuses and by younger groups.[13] Based upon studies of self-reported illicit stimulant use, 5–35% of college students use diverted ADHD stimulants, which are primarily used for enhancement of academic performance rather than as recreational drugs.[14][15][16] Several factors positively and negatively influence an individual's willingness to use a drug for the purpose of enhancing cognitive performance. Among them are personal characteristics, drug characteristics, and characteristics of the social context.[10][11][17][18]
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