A rough translation for the word “nootropic” comes from the Greek for “to bend or shape the mind.” And already, there are dozens of over-the-counter (OTC) products—many of which are sold widely online or in stores—that claim to boost creativity, memory, decision-making or other high-level brain functions. Some of the most popular supplements are a mixture of food-derived vitamins, lipids, phytochemicals and antioxidants that studies have linked to healthy brain function. One popular pick on Amazon, for example, is an encapsulated cocktail of omega-3s, B vitamins and plant-derived compounds that its maker claims can improve memory, concentration and focus.
For obvious reasons, it’s difficult for researchers to know just how common the “smart drug” or “neuro-enhancing” lifestyle is. However, a few recent studies suggest cognition hacking is appealing to a growing number of people. A survey conducted in 2016 found that 15% of University of Oxford students were popping pills to stay competitive, a rate that mirrored findings from other national surveys of UK university students. In the US, a 2014 study found that 18% of sophomores, juniors, and seniors at Ivy League colleges had knowingly used a stimulant at least once during their academic career, and among those who had ever used uppers, 24% said they had popped a little helper on eight or more occasions. Anecdotal evidence suggests that pharmacological enhancement is also on the rise within the workplace, where modafinil, which treats sleep disorders, has become particularly popular.
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.
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Using the 21mg patches, I cut them into quarters. What I would do is I would cut out 1 quarter, and then seal the two edges with scotch tape, and put the Pac-Man back into its sleeve. Then the next time I would cut another quarter, seal the new edge, and so on. I thought that 5.25mg might be too much since I initially found 4mg gum to be too much, but it’s delivered over a long time and it wound up feeling much more like 1mg gum used regularly. I don’t know if the tape worked, but I did not notice any loss of potency. I didn’t like them as much as the gum because I would sometimes forget to take off a patch at the end of the day and it would interfere with sleep, and because the onset is much slower and I find I need stimulants more for getting started than for ongoing stimulation so it is better to have gum which can be taken precisely when needed and start acting quickly. (One case where the patches were definitely better than the gum was long car trips where slow onset is fine, since you’re most alert at the start.) When I finally ran out of patches in June 2016 (using them sparingly), I ordered gum instead.
American employers are already squeezing more productivity out of fewer workers, so one wonders whether we might feel pressure to enhance our brainpower pharmaceutically, should the state of the art develop so far. Already, workers may be tempted to seek prescriptions for Provigil, a drug that treats daytime sleepiness. Provigil was originally approved as a treatment for narcolepsy and was subsequently approved for use by people who work swing shifts and suffer from excessive daytime sleepiness.
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.)
Before taking any supplement or chemical, people want to know if there will be long term effects or consequences, When Dr. Corneliu Giurgea first authored the term “nootropics” in 1972, he also outlined the characteristics that define nootropics. Besides the ability to benefit memory and support the cognitive processes, Dr. Giurgea believed that nootropics should be safe and non-toxic.
This research is in contrast to the other substances I like, such as piracetam or fish oil. I knew about withdrawal of course, but it was not so bad when I was drinking only tea. And the side-effects like jitteriness are worse on caffeine without tea; I chalk this up to the lack of theanine. (My later experiences with theanine seems to confirm this.) These negative effects mean that caffeine doesn’t satisfy the strictest definition of nootropic (having no negative effects), but is merely a cognitive enhancer (with both benefits & costs). One might wonder why I use caffeine anyway if I am so concerned with mental ability.
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:
It isn’t unlikely to hear someone from Silicon Valley say the following: “I’ve just cycled off a stack of Piracetam and CDP-Choline because I didn’t get the mental acuity I was expecting. I will try a blend of Noopept and Huperzine A for the next two weeks and see if I can increase my output by 10%. We don’t have immortality yet and I would really like to join the three comma club before it’s all over.”
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?
The absence of a suitable home for this needed research on the current research funding landscape exemplifies a more general problem emerging now, as applications of neuroscience begin to reach out of the clinical setting and into classrooms, offices, courtrooms, nurseries, marketplaces, and battlefields (Farah, 2011). Most of the longstanding sources of public support for neuroscience research are dedicated to basic research or medical applications. As neuroscience is increasingly applied to solving problems outside the medical realm, it loses access to public funding. The result is products and systems reaching the public with less than adequate information about effectiveness and/or safety. Examples include cognitive enhancement with prescription stimulants, event-related potential and fMRI-based lie detection, neuroscience-based educational software, and anti-brain-aging computer programs. Research and development in nonmedical neuroscience are now primarily the responsibility of private corporations, which have an interest in promoting their products. Greater public support of nonmedical neuroscience research, including methods of cognitive enhancement, will encourage greater knowledge and transparency concerning the efficacy and safety of these products and will encourage the development of products based on social value rather than profit value.
This is a small water plant native to India. Bacopa is an adaptogen – it helps your body adapt to stress. It also improves memory in healthy adults and enhances attention and mood in people over 65.  Scientists still don’t fully understand how Bacopa works, but they do know it takes time to work; study participants didn’t feel its memory-enhancing effects until they’d been supplementing with it daily for 4 weeks, so if you try Bacopa, stick with it for a month before you give up on it.
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.
On the other hand, sometimes you’ll feel a great cognitive boost as soon as you take a pill. That can be a good thing or a bad thing. I find, for example, that modafinil makes you more of what you already are. That means if you are already kind of a dick and you take modafinil, you might act like a really big dick and regret it. It certainly happened to me! I like to think that I’ve done enough hacking of my brain that I’ve gotten over that programming… and that when I use nootropics they help me help people.
Most research on these nootropics suggest they have some benefits, sure, but as Barbara Sahakian and Sharon Morein-Zamir explain in the journal Nature, nobody knows their long-term effects. And we don’t know how extended use might change your brain chemistry in the long run. Researchers are getting closer to what makes these substances do what they do, but very little is certain right now. If you’re looking to live out your own Limitless fantasy, do your research first, and proceed with caution.
Despite decades of study, a full picture has yet to emerge of the cognitive effects of the classic psychostimulants and modafinil. Part of the problem is that getting rats, or indeed students, to do puzzles in laboratories may not be a reliable guide to the drugs’ effects in the wider world. Drugs have complicated effects on individuals living complicated lives. Determining that methylphenidate enhances cognition in rats by acting on their prefrontal cortex doesn’t tell you the potential impact that its effects on mood or motivation may have on human cognition.
The question of how much nonmedical use of stimulants occurs on college campuses is only partly answered by the proportion of students using the drugs in this way. The other part of the answer is how frequently they are used by those students. Three studies addressed this issue. Low and Gendaszek (2002) found a high past-year rate of 35.3%, but only 10% and 8% of this population used monthly and weekly, respectively. White et al. (2006) found a larger percentage used frequently: 15.5% using two to three times per week and 33.9% using two to three times per month. Teter et al. (2006) found that most nonmedical users take prescription stimulants sporadically, with well over half using five or fewer times and nearly 40% using only once or twice in their lives. DeSantis et al. (2008) offered qualitative evidence on the issue, reporting that students often turned to stimulants at exam time only, particularly when under pressure to study for multiple exams at the same time. Thus, there appears to be wide variation in the regularity of stimulant use, with the most common pattern appearing to be infrequent use.
Fatty acids are well-studied natural smart drugs that support many cognitive abilities. They play an essential role in providing structural support to cell membranes. Fatty acids also contribute to the growth and repair of neurons. Both functions are crucial for maintaining peak mental acuity as you age. Among the most prestigious fatty acids known to support cognitive health are:
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.
“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.”
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:
Cytisine is not known as a stimulant and I’m not addicted to nicotine, so why give it a try? Nicotine is one of the more effective stimulants available, and it’s odd how few nicotine analogues or nicotinic agonists there are available; nicotine has a few flaws like short half-life and increasing blood pressure, so I would be interested in a replacement. The nicotine metabolite cotinine, in the human studies available, looks intriguing and potentially better, but I have been unable to find a source for it. One of the few relevant drugs which I can obtain is cytisine, from Ceretropic, at 2x1.5mg doses. There are not many anecdotal reports on cytisine, but at least a few suggest somewhat comparable effects with nicotine, so I gave it a try.
Minnesota-based Medtronic offers a U.S. Food and Drug Administration (FDA)-cleared smart pill called PillCam COLON, which provides clear visualization of the colon and is complementary to colonoscopy. It is an alternative for patients who refuse invasive colon exams, have bleeding or sedation risks or inflammatory bowel disease, or have had a previous incomplete colonoscopy. PillCam COLON allows more people to get screened for colorectal cancer with a minimally invasive, radiation-free option. The research focus for WCEs is on effective localization, steering and control of capsules. Device development relies on leveraging applied science and technologies for better system performance, rather than completely reengineering the pill.
Racetams are often used as a smart drug by finance workers, students, and individuals in high-pressure jobs as a way to help them get into a mental flow state and work for long periods of time. Additionally, the habits and skills that an individual acquires while using a racetam can still be accessed when someone is not taking racetams because it becomes a habit.
(As I was doing this, I reflected how modafinil is such a pure example of the money-time tradeoff. It’s not that you pay someone else to do something for you, which necessarily they will do in a way different from you; nor is it that you have exchanged money to free yourself of a burden of some future time-investment; nor have you paid money for a speculative return of time later in life like with many medical expenses or supplements. Rather, you have paid for 8 hours today of your own time.)
As discussed in my iodine essay (FDA adverse events), iodine is a powerful health intervention as it eliminates cretinism and improves average IQ by a shocking magnitude. If this effect were possible for non-fetuses in general, it would be the best nootropic ever discovered, and so I looked at it very closely. Unfortunately, after going through ~20 experiments looking for ones which intervened with iodine post-birth and took measures of cognitive function, my meta-analysis concludes that: the effect is small and driven mostly by one outlier study. Once you are born, it’s too late. But the results could be wrong, and iodine might be cheap enough to take anyway, or take for non-IQ reasons. (This possibility was further weakened for me by an August 2013 blood test of TSH which put me at 3.71 uIU/ml, comfortably within the reference range of 0.27-4.20.)
As shown in Table 6, two of these are fluency tasks, which require the generation of as large a set of unique responses as possible that meet the criteria given in the instructions. Fluency tasks are often considered tests of executive function because they require flexibility and the avoidance of perseveration and because they are often impaired along with other executive functions after prefrontal damage. In verbal fluency, subjects are asked to generate as many words that begin with a specific letter as possible. Neither Fleming et al. (1995), who administered d-AMP, nor Elliott et al. (1997), who administered MPH, found enhancement of verbal fluency. However, Elliott et al. found enhancement on a more complex nonverbal fluency task, the sequence generation task. Subjects were able to touch four squares in more unique orders with MPH than with placebo.
In 3, you’re considering adding a new supplement, not stopping a supplement you already use. The I don’t try Adderall case has value $0, the Adderall fails case is worth -$40 (assuming you only bought 10 pills, and this number should be increased by your analysis time and a weighted cost for potential permanent side effects), and the Adderall succeeds case is worth $X-40-4099, where $X is the discounted lifetime value of the increased productivity due to Adderall, minus any discounted long-term side effect costs. If you estimate Adderall will work with p=.5, then you should try out Adderall if you estimate that 0.5 \times (X-4179) > 0 ~> $X>4179$. (Adderall working or not isn’t binary, and so you might be more comfortable breaking down the various how effective Adderall is cases when eliciting X, by coming up with different levels it could work at, their values, and then using a weighted sum to get X. This can also give you a better target with your experiment- this needs to show a benefit of at least Y from Adderall for it to be worth the cost, and I’ve designed it so it has a reasonable chance of showing that.)
My general impression is positive; it does seem to help with endurance and extended the effect of piracetam+choline, but is not as effective as that combo. At $20 for 30g (bought from Smart Powders), I’m not sure it’s worthwhile, but I think at $10-15 it would probably be worthwhile. Sulbutiamine seems to affect my sleep negatively, like caffeine. I bought 2 or 3 canisters for my third batch of pills along with the theanine. For a few nights in a row, I slept terribly and stayed awake thinking until the wee hours of the morning; eventually I realized it was because I was taking the theanine pills along with the sleep-mix pills, and the only ingredient that was a stimulant in the batch was - sulbutiamine. I cut out the theanine pills at night, and my sleep went back to normal. (While very annoying, this, like the creatine & taekwondo example, does tend to prove to me that sulbutiamine was doing something and it is not pure placebo effect.)
In sum, the evidence concerning stimulant effects of working memory is mixed, with some findings of enhancement and some null results, although no findings of overall performance impairment. A few studies showed greater enhancement for less able participants, including two studies reporting overall null results. When significant effects have been found, their sizes vary from small to large, as shown in Table 4. Taken together, these results suggest that stimulants probably do enhance working memory, at least for some individuals in some task contexts, although the effects are not so large or reliable as to be observable in all or even most working memory studies.
My answer is that this is not a lot of research or very good research (not nearly as good as the research on nicotine, eg.), and assuming it’s true, I don’t value long-term memory that much because LTM is something that is easily assisted or replaced (personal archives, and spaced repetition). For me, my problems tend to be more about akrasia and energy and not getting things done, so even if a stimulant comes with a little cost to long-term memory, it’s still useful for me. I’m going continue to use the caffeine. It’s not so bad in conjunction with tea, is very cheap, and I’m already addicted, so why not? Caffeine is extremely cheap, addictive, has minimal effects on health (and may be beneficial, from the various epidemiological associations with tea/coffee/chocolate & longevity), and costs extra to remove from drinks popular regardless of their caffeine content (coffee and tea again). What would be the point of carefully investigating it? Suppose there was conclusive evidence on the topic, the value of this evidence to me would be roughly $0 or since ignorance is bliss, negative money - because unless the negative effects were drastic (which current studies rule out, although tea has other issues like fluoride or metal contents), I would not change anything about my life. Why? I enjoy my tea too much. My usual tea seller doesn’t even have decaffeinated oolong in general, much less various varieties I might want to drink, apparently because de-caffeinating is so expensive it’s not worthwhile. What am I supposed to do, give up my tea and caffeine just to save on the cost of caffeine? Buy de-caffeinating machines (which I couldn’t even find any prices for, googling)? This also holds true for people who drink coffee or caffeinated soda. (As opposed to a drug like modafinil which is expensive, and so the value of a definitive answer is substantial and would justify some more extensive calculating of cost-benefit.)
Taken together, the available results are mixed, with slightly more null results than overall positive findings of enhancement and evidence of impairment in one reversal learning task. As the effect sizes listed in Table 5 show, the effects when found are generally substantial. When drug effects were assessed as a function of placebo performance, genotype, or self-reported impulsivity, enhancement was found to be greatest for participants who performed most poorly on placebo, had a COMT genotype associated with poorer executive function, or reported being impulsive in their everyday lives. In sum, the effects of stimulants on cognitive control are not robust, but MPH and d-AMP appear to enhance cognitive control in some tasks for some people, especially those less likely to perform well on cognitive control tasks.
I don’t believe there’s any need to control for training with repeated within-subject sampling, since there will be as many samples on both control and active days drawn from the later trained period as with the initial untrained period. But yes, my D5B scores seem to have plateaued pretty much and only very slowly increase; you can look at the stats file yourself.
Two studies investigated the effects of MPH on reversal learning in simple two-choice tasks (Clatworthy et al., 2009; Dodds et al., 2008). In these tasks, participants begin by choosing one of two stimuli and, after repeated trials with these stimuli, learn that one is usually rewarded and the other is usually not. The rewarded and nonrewarded stimuli are then reversed, and participants must then learn to choose the new rewarded stimulus. Although each of these studies found functional neuroimaging correlates of the effects of MPH on task-related brain activity (increased blood oxygenation level-dependent signal in frontal and striatal regions associated with task performance found by Dodds et al., 2008, using fMRI and increased dopamine release in the striatum as measured by increased raclopride displacement by Clatworthy et al., 2009, using PET), neither found reliable effects on behavioral performance in these tasks. The one significant result concerning purely behavioral measures was Clatworthy et al.’s (2009) finding that participants who scored higher on a self-report personality measure of impulsivity showed more performance enhancement with MPH. MPH’s effect on performance in individuals was also related to its effects on individuals’ dopamine activity in specific regions of the caudate nucleus.
The greatly increased variance, but only somewhat increased mean, is consistent with nicotine operating on me with an inverted U-curve for dosage/performance (or the Yerkes-Dodson law): on good days, 1mg nicotine is too much and degrades performance (perhaps I am overstimulated and find it hard to focus on something as boring as n-back) while on bad days, nicotine is just right and improves n-back performance.
Discussions of PEA mention that it’s almost useless without a MAOI to pave the way; hence, when I decided to get deprenyl and noticed that deprenyl is a MAOI, I decided to also give PEA a second chance in conjunction with deprenyl. Unfortunately, in part due to my own shenanigans, Nubrain canceled the deprenyl order and so I have 20g of PEA sitting around. Well, it’ll keep until such time as I do get a MAOI.
When I worked on the Bulletproof Diet book, I wanted to verify that the effects I was getting from Bulletproof Coffee were not coming from modafinil, so I stopped using it and measured my cognitive performance while I was off of it. What I found was that on Bulletproof Coffee and the Bulletproof Diet, my mental performance was almost identical to my performance on modafinil. I still travel with modafinil, and I’ll take it on occasion, but while living a Bulletproof lifestyle I rarely feel the need.