Dosage is apparently 5-10mg a day. (Prices can be better elsewhere; selegiline is popular for treating dogs with senile dementia, where those 60x5mg will cost $2 rather than $3531. One needs a veterinarian’s prescription to purchase from pet-oriented online pharmacies, though.) I ordered it & modafinil from Nubrain.com at $35 for 60x5mg; Nubrain delayed and eventually canceled my order - and my enthusiasm. Between that and realizing how much of a premium I was paying for Nubrain’s deprenyl, I’m tabling deprenyl along with nicotine & modafinil for now. Which is too bad, because I had even ordered 20g of PEA from Smart Powders to try out with the deprenyl. (My later attempt to order some off the Silk Road also failed when the seller canceled the order.)
The search to find more effective drugs to increase mental ability and intelligence capacity with neither toxicity nor serious side effects continues. But there are limitations. Although the ingredients may be separately known to have cognition-enhancing effects, randomized controlled trials of the combined effects of cognitive enhancement compounds are sparse.
Adrafinil is Modafinil’s predecessor, because the scientists tested it as a potential narcolepsy drug. It was first produced in 1974 and immediately showed potential as a wakefulness-promoting compound. Further research showed that Adrafinil is metabolized into its component parts in the liver, that is into inactive modafinil acid. Ultimately, Modafinil has been proclaimed the primary active compound in Adrafinil.
Table 4 lists the results of 27 tasks from 23 articles on the effects of d-AMP or MPH on working memory. The oldest and most commonly used type of working memory task in this literature is the Sternberg short-term memory scanning paradigm (Sternberg, 1966), in which subjects hold a set of items (typically letters or numbers) in working memory and are then presented with probe items, to which they must respond “yes” (in the set) or “no” (not in the set). The size of the set, and hence the working memory demand, is sometimes varied, and the set itself may be varied from trial to trial to maximize working memory demands or may remain fixed over a block of trials. Taken together, the studies that have used a version of this task to test the effects of MPH and d-AMP on working memory have found mixed and somewhat ambiguous results. No pattern is apparent concerning the specific version of the task or the specific drug. Four studies found no effect (Callaway, 1983; Kennedy, Odenheimer, Baltzley, Dunlap, & Wood, 1990; Mintzer & Griffiths, 2007; Tipper et al., 2005), three found faster responses with the drugs (Fitzpatrick, Klorman, Brumaghim, & Keefover, 1988; Ward et al., 1997; D. E. Wilson et al., 1971), and one found higher accuracy in some testing sessions at some dosages, but no main effect of drug (Makris et al., 2007). The meaningfulness of the increased speed of responding is uncertain, given that it could reflect speeding of general response processes rather than working memory–related processes. Aspects of the results of two studies suggest that the effects are likely due to processes other than working memory: D. E. Wilson et al. (1971) reported comparable speeding in a simple task without working memory demands, and Tipper et al. (2005) reported comparable speeding across set sizes.
And as before, around 9 AM I began to feel the peculiar feeling that I was mentally able and apathetic (in a sort of aboulia way); so I decided to try what helped last time, a short nap. But this time, though I took a full hour, I slept not a wink and my Zeo recorded only 2 transient episodes of light sleep! A back-handed sort of proof of alertness, I suppose. I didn’t bother trying again. The rest of the day was mediocre, and I wound up spending much of it on chores and whatnot out of my control. Mentally, I felt better past 3 PM.
Another common working memory task is the n-back task, which requires the subject to view a series of items (usually letters) and decide whether the current item is identical to the one presented n items back. This task taxes working memory because the previous items must be held in working memory to be compared with the current item. The easiest version of this is a 1-back task, which is also called a double continuous performance task (CPT) because the subject is continuously monitoring for a repeat or double. Three studies examined the effects of MPH on working memory ability as measured by the 1-back task, and all found enhancement of performance in the form of reduced errors of omission (Cooper et al., 2005; Klorman et al., 1984; Strauss et al., 1984). Fleming et al. (1995) tested the effects of d-AMP on a 5-min CPT and found a decrease in reaction time, but did not specify which version of the CPT was used.
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
I’m wary of others, though. The trouble with using a blanket term like “nootropics” is that you lump all kinds of substances in together. Technically, you could argue that caffeine and cocaine are both nootropics, but they’re hardly equal. With so many ways to enhance your brain function, many of which have significant risks, it’s most valuable to look at nootropics on a case-by-case basis. Here’s a list of 9 nootropics, along with my thoughts on each.
There’s been a lot of talk about the ketogenic diet recently—proponents say that minimizing the carbohydrates you eat and ingesting lots of fat can train your body to burn fat more effectively. It’s meant to help you both lose weight and keep your energy levels constant. The diet was first studied and used in patients with epilepsy, who suffered fewer seizures when their bodies were in a state of ketosis. Because seizures originate in the brain, this discovery showed researchers that a ketogenic diet can definitely affect the way the brain works. Brain hackers naturally started experimenting with diets to enhance their cognitive abilities, and now a company called HVMN even sells ketone esters in a bottle; to achieve these compounds naturally, you’d have to avoid bread and cake. Here are 6 ways exercise makes your brain better.
The one indisputable finding from the literature so far is that many people are seeking cognitive enhancement. Beyond that, the literature yields only partial and tentative answers to the questions just raised. Given the potential impact of cognitive enhancement on society, more research is needed. For research on the epidemiology of cognitive enhancement, studies focused on the cognitive-enhancement practices and experiences of students and nonstudent workers are needed. For research on the cognitive effects of prescription stimulants, larger samples are needed. Only with substantially larger samples will it be possible to assess small but potentially important benefits, as well as risks, and to distinguish individual differences in drug response. Large samples would also be required to compare these effects to the cognitive effects of improved sleep, exercise, nutrition, and stress management. To include more ecologically valid measures of cognition in academic and work environments would in addition require the equivalent of a large clinical trial.
Similar to the way in which some athletes used anabolic steroids (muscle-building hormones) to artificially enhance their physique, some students turned to smart drugs, particularly Ritalin and Adderall, to heighten their intellectual abilities. A 2005 study reported that, at some universities in the United States, as many as 7 percent of respondents had used smart drugs at least once in their lifetime and 2.1 percent had used smart drugs in the past month. Modafinil was used increasingly by persons who sought to recover quickly from jet lag and who were under heavy work demands. Military personnel were given the same drug when sent on missions with extended flight times.
The magnesium was neither randomized nor blinded and included mostly as a covariate to avoid confounding (the Noopept coefficient & t-value increase somewhat without the Magtein variable), so an OR of 1.9 is likely too high; in any case, this experiment was too small to reliably detect any effect (~26% power, see bootstrap power simulation in the magnesium section) so we can’t say too much.
Another class of substances with the potential to enhance cognition in normal healthy individuals is the class of prescription stimulants used to treat attention-deficit/hyperactivity disorder (ADHD). These include methylphenidate (MPH), best known as Ritalin or Concerta, and amphetamine (AMP), most widely prescribed as mixed AMP salts consisting primarily of dextroamphetamine (d-AMP), known by the trade name Adderall. These medications have become familiar to the general public because of the growing rates of diagnosis of ADHD children and adults (Froehlich et al., 2007; Sankaranarayanan, Puumala, & Kratochvil, 2006) and the recognition that these medications are effective for treating ADHD (MTA Cooperative Group, 1999; Swanson et al., 2008).
Nootropics are a great way to boost your productivity. Nootropics have been around for more than 40 years and today they are entering the mainstream. If you want to become the best you, nootropics are a way to level up your life. Nootropics are always personal and what works for others might not work for you. But no matter the individual outcomes, nootropics are here to make an impact!
Take quarter at midnight, another quarter at 2 AM. Night runs reasonably well once I remember to eat a lot of food (I finish a big editing task I had put off for weeks), but the apathy kicks in early around 4 AM so I gave up and watched Scott Pilgrim vs. the World, finishing around 6 AM. I then read until it’s time to go to a big shotgun club function, which occupies the rest of the morning and afternoon; I had nothing to do much of the time and napped very poorly on occasion. By the time we got back at 4 PM, the apathy was completely gone and I started some modafinil research with gusto (interrupted by going to see Puss in Boots). That night: Zeo recorded 8:30 of sleep, gap of about 1:50 in the recording, figure 10:10 total sleep; following night, 8:33; third night, 8:47; fourth, 8:20 (▇▁▁▁).
Brain focus pills mostly contain chemical components like L-theanine which is naturally found in green and black tea. It’s associated with enhancing alertness, cognition, relaxation, arousal, and reducing anxiety to a large extent. Theanine is an amino and glutamic acid that has been proven to be a safe psychoactive substance. Some studies suggest that this compound influences, the expression in the genes present in the brain which is responsible for aggression, fear, and memory. This, in turn, helps in balancing the behavioral responses to stress and also helps in improving specific conditions, like Post Traumatic Stress Disorder (PTSD).
(I was more than a little nonplussed when the mushroom seller included a little pamphlet educating one about how papaya leaves can cure cancer, and how I’m shortening my life by decades by not eating many raw fruits & vegetables. There were some studies cited, but usually for points disconnected from any actual curing or longevity-inducing results.)
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.↩
Finally, it’s not clear that caffeine results in performance gains after long-term use; homeostasis/tolerance is a concern for all stimulants, but especially for caffeine. It is plausible that all caffeine consumption does for the long-term chronic user is restore performance to baseline. (Imagine someone waking up and drinking coffee, and their performance improves - well, so would the performance of a non-addict who is also slowly waking up!) See for example, James & Rogers 2005, Sigmon et al 2009, and Rogers et al 2010. A cross-section of thousands of participants in the Cambridge brain-training study found caffeine intake showed negligible effect sizes for mean and component scores (participants were not told to use caffeine, but the training was recreational & difficult, so one expects some difference).
Results: Women with high caffeine intakes had significantly higher rates of bone loss at the spine than did those with low intakes (−1.90 ± 0.97% compared with 1.19 ± 1.08%; P = 0.038). When the data were analyzed according to VDR genotype and caffeine intake, women with the tt genotype had significantly (P = 0.054) higher rates of bone loss at the spine (−8.14 ± 2.62%) than did women with the TT genotype (−0.34 ± 1.42%) when their caffeine intake was >300 mg/d…In 1994, Morrison et al (22) first reported an association between vitamin D receptor gene (VDR) polymorphism and BMD of the spine and hip in adults. After this initial report, the relation between VDR polymorphism and BMD, bone turnover, and bone loss has been extensively evaluated. The results of some studies support an association between VDR polymorphism and BMD (23-,25), whereas other studies showed no evidence for this association (26,27)…At baseline, no significant differences existed in serum parathyroid hormone, serum 25-hydroxyvitamin D, serum osteocalcin, and urinary N-telopeptide between the low- and high-caffeine groups (Table 1⇑). In the longitudinal study, the percentage of change in serum parathyroid hormone concentrations was significantly lower in the high-caffeine group than in the low-caffeine group (Table 2⇑). However, no significant differences existed in the percentage of change in serum 25-hydroxyvitamin D
“Cavin’s enthusiasm and drive to help those who need it is unparalleled! He delivers the information in an easy to read manner, no PhD required from the reader. 🙂 Having lived through such trauma himself he has real empathy for other survivors and it shows in the writing. This is a great read for anyone who wants to increase the health of their brain, injury or otherwise! Read it!!!”
Some work has been done on estimating the value of IQ, both as net benefits to the possessor (including all zero-sum or negative-sum aspects) and as net positive externalities to the rest of society. The estimates are substantial: in the thousands of dollars per IQ point. But since increasing IQ post-childhood is almost impossible barring disease or similar deficits, and even increasing childhood IQs is very challenging, much of these estimates are merely correlations or regressions, and the experimental childhood estimates must be weakened considerably for any adult - since so much time and so many opportunities have been lost. A wild guess: $1000 net present value per IQ point. The range for severely deficient children was 10-15 points, so any normal (somewhat deficient) adult gain must be much smaller and consistent with Fitzgerald 2012’s ceiling on possible effect sizes (small).
There is no clear answer to this question. Many of the smart drugs have decades of medical research and widespread use behind them, as well as only minor, manageable, or nonexistent side effects, but are still used primarily as a crutch for people already experiencing cognitive decline, rather than as a booster-rocket for people with healthy brains. Unfortunately, there is a bias in Western medicine in favor of prescribing drugs once something bad has already begun, rather than for up-front prevention. There’s also the principle of “leave well enough alone” – in this case, extended to mean, don’t add unnecessary or unnatural drugs to the human body in place of a normal diet. [Smart Drug Smarts would argue that the average human diet has strayed so far from what is physiologically “normal” that leaving well enough alone is already a failed proposition.]
“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.”
Another classic approach to the assessment of working memory is the span task, in which a series of items is presented to the subject for repetition, transcription, or recognition. The longest series that can be reproduced accurately is called the forward span and is a measure of working memory capacity. The ability to reproduce the series in reverse order is tested in backward span tasks and is a more stringent test of working memory capacity and perhaps other working memory functions as well. The digit span task from the Wechsler (1981) IQ test was used in four studies of stimulant effects on working memory. One study showed that d-AMP increased digit span (de Wit et al., 2002), and three found no effects of d-AMP or MPH (Oken, Kishiyama, & Salinsky, 1995; Schmedtje, Oman, Letz, & Baker, 1988; Silber, Croft, Papafotiou, & Stough, 2006). A spatial span task, in which subjects must retain and reproduce the order in which boxes in a scattered spatial arrangement change color, was used by Elliott et al. (1997) to assess the effects of MPH on working memory. For subjects in the group receiving placebo first, MPH increased spatial span. However, for the subjects who received MPH first, there was a nonsignificant opposite trend. The group difference in drug effect is not easily explained. The authors noted that the subjects in the first group performed at an overall lower level, and so, this may be another manifestation of the trend for a larger enhancement effect for less able subjects.
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.
Taurine (Examine.com) was another gamble on my part, based mostly on its inclusion in energy drinks. I didn’t do as much research as I should have: it came as a shock to me when I read in Wikipedia that taurine has been shown to prevent oxidative stress induced by exercise and was an antioxidant - oxidative stress is a key part of how exercise creates health benefits and antioxidants inhibit those benefits.
Sure, those with a mental illness may very well need a little more monitoring to make sure they take their medications, but will those suffering from a condition with hallmark symptoms of paranoia and anxiety be helped by consuming a technology that quite literally puts a tracking device inside their body? For patients hearing voices telling them that they're being watched, a monitoring device may be a hard pill to swallow.
One of the most popular legal stimulants in the world, nicotine is often conflated with the harmful effects of tobacco; considered on its own, it has performance & possibly health benefits. Nicotine is widely available at moderate prices as long-acting nicotine patches, gums, lozenges, and suspended in water for vaping. While intended for smoking cessation, there is no reason one cannot use a nicotine patch or nicotine gum for its stimulant effects.
Some cognitive enhancers, such as donepezil and galantamine, are prescribed for elderly patients with impaired reasoning and memory deficits caused by various forms of dementia, including Alzheimer disease, Parkinson disease with dementia, dementia with Lewy bodies, and vascular dementia. Children and young adults with attention-deficit/hyperactivity disorder (ADHD) are often treated with the cognitive enhancers Ritalin (methylphenidate) or Adderall (mixed amphetamine salts). Persons diagnosed with narcolepsy find relief from sudden attacks of sleep through wake-promoting agents such as Provigil (modafinil). Generally speaking, cognitive enhancers improve working and episodic (event-specific) memory, attention, vigilance, and overall wakefulness but act through different brain systems and neurotransmitters to exert their enhancing effects.
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.
One reason I like modafinil is that it enhances dopamine release, but it binds to your dopamine receptors differently than addictive substances like cocaine and amphetamines do, which may be part of the reason modafinil shares many of the benefits of other stimulants but doesn’t cause addiction or withdrawal symptoms.   It does increase focus, problem-solving abilities, and wakefulness, but it is not in the same class of drugs as Adderall, and it is not a classical stimulant. Modafinil is off of patent, so you can get it generically, or order it from India. It’s a prescription drug, so you need to talk to a physician.