Many of the most popular “smart drugs” (Piracetam, Sulbutiamine, Ginkgo Biloba, etc.) have been around for decades or even millenia but are still known only in medical circles or among esoteric practicioners of herbal medicine. Why is this? If these compounds have proven cognitive benefits, why are they not ubiquitous? How come every grade-school child gets fluoride for the development of their teeth (despite fluoride’s being a known neurotoxin) but not, say, Piracetam for the development of their brains? Why does the nightly news slant stories to appeal more to a fear-of-change than the promise of a richer cognitive future?
When I spoke with Jesse Lawler, who hosts the podcast Smart Drugs Smarts, about breakthroughs in brain health and neuroscience, he was unsurprised to hear of my disappointing experience. Many nootropics are supposed to take time to build up in the body before users begin to feel their impact. But even then, says Barry Gordon, a neurology professor at the Johns Hopkins Medical Center, positive results wouldn’t necessarily constitute evidence of a pharmacological benefit.
COGNITUNE is for informational purposes only, and should not be considered medical advice, diagnosis or treatment recommendations. Always consult with your doctor or primary care physician before using any nutraceuticals, dietary supplements, or prescription medications. Seeking a proper diagnosis from a certified medical professional is vital for your health.
First off, overwhelming evidence suggests that smart drugs actually work. A meta-analysis by researchers at Harvard Medical School and Oxford showed that Modafinil has significant cognitive benefits for those who do not suffer from sleep deprivation. The drug improves their ability to plan and make decisions and has a positive effect on learning and creativity. Another study, by researchers at Imperial College London, showed that Modafinil helped sleep-deprived surgeons become better at planning, redirecting their attention, and being less impulsive when making decisions.
One curious thing that leaps out looking at the graphs is that the estimated underlying standard deviations differ: the nicotine days have a strikingly large standard deviation, indicating greater variability in scores - both higher and lower, since the means weren’t very different. The difference in standard deviations is just 6.6% below 0, so the difference almost reaches our usual frequentist levels of confidence too, which we can verify by testing:

Blinding stymied me for a few months since the nasty taste was unmistakable and I couldn’t think of any gums with a similar flavor to serve as placebo. (The nasty taste does not seem to be due to the nicotine despite what one might expect; Vaniver plausibly suggested the bad taste might be intended to prevent over-consumption, but nothing in the Habitrol ingredient list seemed to be noted for its bad taste, and a number of ingredients were sweetening sugars of various sorts. So I couldn’t simply flavor some gum.)

In general, I feel a little bit less alert, but still close to normal. By 6PM, I have a mild headache, but I try out 30 rounds of gbrainy (haven’t played it in months) and am surprised to find that I reach an all-time high; no idea whether this is due to DNB or not, since Gbrainy is very heavily crystallized (half the challenge disappears as you learn how the problems work), but it does indicate I’m not deluding myself about mental ability. (To give a figure: my last score well before I did any DNB was 64, and I was doing well that day; on modafinil, I had a 77.) I figure the headache might be food related, eat, and by 7:30 the headache is pretty much gone and I’m fine up to midnight.

The easiest way to use 2mg was to use half a gum; I tried not chewing it but just holding it in my cheek. The first night I tried, this seemed to work well for motivation; I knocked off a few long-standing to-do items. Subsequently, I began using it for writing, where it has been similarly useful. One difficult night, I wound up using the other half (for a total of 4mg over ~5 hours), and it worked but gave me a fairly mild headache and a faint sensation of nausea; these may have been due to forgetting to eat dinner, but this still indicates 3mg should probably be my personal ceiling until and unless tolerance to lower doses sets in.

Fitzgerald 2012 and the general absence of successful experiments suggests not, as does the general historic failure of scores of IQ-related interventions in healthy young adults. Of the 10 studies listed in the original section dealing with iodine in children or adults, only 2 show any benefit; in lieu of a meta-analysis, a rule of thumb would be 20%, but both those studies used a package of dozens of nutrients - and not just iodine - so if the responsible substance were randomly picked, that suggests we ought to give it a chance of 20% \times \frac{1}{\text{dozens}} of being iodine! I may be unduly optimistic if I give this as much as 10%.
Natural nootropic supplements derive from various nutritional studies. Research shows the health benefits of isolated vitamins, nutrients, and herbs. By increasing your intake of certain herbal substances, you can enhance brain function. Below is a list of the top categories of natural and herbal nootropics. These supplements are mainstays in many of today’s best smart pills.
Stimulants are drugs that accelerate the central nervous system (CNS) activity. They have the power to make us feel more awake, alert and focused, providing us with a needed energy boost. Unfortunately, this class encompasses a wide range of drugs, some which are known solely for their side-effects and addictive properties. This is the reason why many steer away from any stimulants, when in fact some greatly benefit our cognitive functioning and can help treat some brain-related impairments and health issues.
Expect to experience an increase in focus and a drastic reduction in reaction time [11][12][13][14][15][16]. You’ll have an easier time quickly switching between different mental tasks, and will experience an increase in general cognitive ability [17][18]. Queal Flow also improves cognition and motivation, by means of reducing anxiety and stress [19][20][21][22][23]. If you’re using Flow regularly for a longer period of time, it’s also very likely to improve your mental health in the long term (reducing cognitive decline), and might even improve your memory [24][25].
Fortunately, there are some performance-enhancing habits that have held up under rigorous scientific scrutiny. They are free, and easy to pronounce. Unfortunately, they are also the habits you were perhaps hoping to forego by using nootropics instead. “Of all the things that are supposed to be ‘good for the brain,’” says Stanford neurology professor Sharon Sha, “there is more evidence for exercise than anything else.” Next time you’re facing a long day, you could take a pill and see what happens.
So is there a future in smart drugs? Some scientists are more optimistic than others. Gary Lynch, a professor in the School of Medicine at the University of California, Irvine argues that recent advances in neuroscience have opened the way for the smart design of drugs, configured for specific biological targets in the brain. “Memory enhancement is not very far off,” he says, although the prospects for other kinds of mental enhancement are “very difficult to know… To me, there’s an inevitability to the thing, but a timeline is difficult.”
…Phenethylamine is intrinsically a stimulant, although it doesn’t last long enough to express this property. In other words, it is rapidly and completely destroyed in the human body. It is only when a number of substituent groups are placed here or there on the molecule that this metabolic fate is avoided and pharmacological activity becomes apparent.
I have no particularly compelling story for why this might be a correlation and not causation. It could be placebo, but I wasn’t expecting that. It could be selection effect (days on which I bothered to use the annoying LED set are better days) but then I’d expect the off-days to be below-average and compared to the 2 years of trendline before, there doesn’t seem like much of a fall.

Modafinil is not addictive, but there may be chances of drug abuse and memory impairment. This can manifest in people who consume it to stay up for way too long; as a result, this would probably make them ill. Long-term use of Modafinil may reduce plasticity and may harm the memory of some individuals. Hence, it is sold only on prescription by a qualified physician.
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.
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).

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 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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 –>


I have no particularly compelling story for why this might be a correlation and not causation. It could be placebo, but I wasn’t expecting that. It could be selection effect (days on which I bothered to use the annoying LED set are better days) but then I’d expect the off-days to be below-average and compared to the 2 years of trendline before, there doesn’t seem like much of a fall.

The pill delivers an intestinal injection without exposing the drug to digestive enzymes. The patient takes what seems to be an ordinary capsule, but the “robotic” pill is a sophisticated device which incorporates a number of innovations, enabling it to navigate through the stomach and enter the small intestine. The Rani Pill™ goes through a transformation and positions itself to inject the drug into the intestinal wall.
At small effects like d=0.07, a nontrivial chance of negative effects, and an unknown level of placebo effects (this was non-blinded, which could account for any residual effects), this strongly implies that LLLT is not doing anything for me worth bothering with. I was pretty skeptical of LLLT in the first place, and if 167 days can’t turn up anything noticeable, I don’t think I’ll be continuing with LLLT usage and will be giving away my LED set. (Should any experimental studies of LLLT for cognitive enhancement in healthy people surface with large quantitative effects - as opposed to a handful of qualitative case studies about brain-damaged people - and I decide to give LLLT another try, I can always just buy another set of LEDs: it’s only ~$15, after all.)

As it happened, Health Supplement Wholesalers (since renamed Powder City) offered me a sample of their products, including their 5g Noopept powder ($13). I’d never used HSW before & they had some issues in the past; but I haven’t seen any recent complaints, so I was willing to try them. My 5g from batch #130830 arrived quickly (photos: packaging, powder contents). I tried some (tastes just slightly unpleasant, like an ultra-weak piracetam), and I set about capping the fluffy white flour-like powder with the hilariously tiny scoop they provide.
Ashwagandha has been shown to improve cognition and motivation, by means of reducing anxiety [46]. It has been shown to significantly reduce stress and anxiety. As measured by cortisol levels, anxiety symptoms were reduced by around 30% compared to a placebo-controlled (double-blind) group [47]. And it may have neuroprotective effects and improve sleep, but these claims are still being researched.
Vinh Ngo, a San Francisco family practice doctor who specializes in hormone therapy, has become familiar with piracetam and other nootropics through a changing patient base. His office is located in the heart of the city’s tech boom and he is increasingly sought out by young, male tech workers who tell him they are interested in cognitive enhancement.
Methylphenidate – a benzylpiperidine that had cognitive effects (e.g., working memory, episodic memory, and inhibitory control, aspects of attention, and planning latency) in healthy people.[21][22][23] It also may improve task saliency and performance on tedious tasks.[25] At above optimal doses, methylphenidate had off–target effects that decreased learning.[26]
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