At this point, I discovered I had run out of magnesium pills and had forgotten to order the magnesium citrate powder I’d intended to. I still had a lot of Noopept pills for the concurrently running second Noopept self-experiment, but since I wanted to wrap up some other experiments with a big analysis at the end of the year, I decided to halt and resume in January 2014.
I eventually met Seltzer in an underground food court not far from the Pentagon. He's slim, with a shaved head, and he spoke precisely, rarely stumbling over his words. I asked him if he had any ethical worries about smart drugs. After a pause, he said that he might have a concern if somebody popped a neuroenhancer before taking a licensing exam that certified him as, say, a brain surgeon, and then stopped using the drug. Other than that he couldn't see a problem. He said that he was a firm believer in the idea that "we should have a fair degree of liberty to do with our bodies and our minds as we see fit, so long as it doesn't impinge on the basic rights, liberty and safety of others". He argued: "Why would you want an upward limit on the intellectual capabilities of a human being? And, if you have a very nationalist viewpoint, why wouldn't you want our country to have the advantage over other countries, particularly in what some people call a knowledge-based economy?" He went on: "Think about the complexity of the intellectual tasks that people need to accomplish today. Just trying to understand what Congress is doing is not a simple thing! The complexity of understanding the gamut of scientific and technical and social issues is difficult. If we had a tool that enabled more people to understand the world at a greater level of sophistication, how can we prejudice ourselves against the notion simply because we don't like athletes to do it? To me it doesn't seem like the same question. And it deserves its own debate."
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):
The evidence? Ritalin is FDA-approved to treat ADHD. It has also been shown to help patients with traumatic brain injury concentrate for longer periods, but does not improve memory in those patients, according to a 2016 meta-analysis of several trials. A study published in 2012 found that low doses of methylphenidate improved cognitive performance, including working memory, in healthy adult volunteers, but high doses impaired cognitive performance and a person’s ability to focus. (Since the brains of teens have been found to be more sensitive to the drug’s effect, it’s possible that methylphenidate in lower doses could have adverse effects on working memory and cognitive functions.)
The task of building a better mousetrap just got a lot harder. Scientists at Princeton University recently created a strain of smarter mice by inserting a gene that boosts the activity of brain cells. The mice can learn to navigate mazes and find or recognize objects faster than run-of-the-mill rodents. The news, announced in the Sept. 2, 1999 issue of the journal Nature, raises the possibility that genetic engineers may someday be able to help humans learn and remember faster, too.
A new all-in-one nootropic mix/company run by some people active on /r/nootropics; they offered me a month’s supply for free to try & review for them. At ~$100 a month (it depends on how many months one buys), it is not cheap (John Backus estimates one could buy the raw ingredients for $25/month) but it provides convenience & is aimed at people uninterested in spending a great deal of time reviewing research papers & anecdotes or capping their own pills (ie. people with lives) and it’s unlikely I could spare the money to subscribe if TruBrain worked well for me - but certainly there was no harm in trying it out.
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.
When many of us think of memory enhancers, we think of ginkgo biloba, the herb that now generates more than $240 million in sales a year worldwide. The October 22-29, 1997 issue of the Journal of the American Medical Association reported that Alzheimer's patients who took 120 mg of ginkgo showed small improvements in tests designed to measure mental performance.
Is 200 enough? There are no canned power functions for the ordinal logistic regression I would be using, so the standard advice is to estimate power by simulation: generating thousands of new datasets where we know by construction that the binary magnesium variable increases MP by 0.27 (such as by bootstrapping the original Noopept experiment’s data), and seeing how often in this collection the cutoff of statistical-significance is passed when the usual analysis is done (background: CrossValidated or Power Analysis and Sample Size Estimation using Bootstrap). In this case, we leave alpha at 0.05, reuse the Noopept experiment’s data with its Magtein correlation, and ask for the power when n=200
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Although piracetam has a history of “relatively few side effects,” it has fallen far short of its initial promise for treating any of the illnesses associated with cognitive decline, according to Lon Schneider, a professor of psychiatry and behavioral sciences at the Keck School of Medicine at the University of Southern California. “We don’t use it at all and never have.”
Theanine can also be combined with caffeine as both of them work in synergy to increase memory, reaction time, mental endurance, and memory. The best part about Theanine is that it free of side effects and is easily available in the form of capsules. A natural option would be to use a good green tea brand which constitutes of tea grown in the shade, because then Theanine would be abundantly present in it.
The drug methylphenidate is marketed as the brand Ritalin and used to treat children and adults with ADHD. As of 2011, according to the U.S. Centers for Disease Control and Prevention, 11 percent of Americans aged 4-17 were diagnosed with ADHD. The high number of people diagnosed with ADHD means that there is a vast amount of prescription drugs to treat this condition in medicine cabinets across the US. Ultimately, some of these drugs get diverted into the hands of non-prescribed users, such as college students who believe they may be able to improve their studying and performance on exams by taking these drugs.
There are plenty of brain supplements on the market, but none with the same combinations of potent and promising ingredients. If you want to maximize your ability to excel – at everything you do – your brain must be firing on all cylinders – all day, every day. You must protect and preserve your brain function, as it will diminish – it’s the reality of being human.
Last April the scientific journal Nature published the results of an informal online poll asking whether readers attempted to sharpen "their focus, concentration, or memory" by taking drugs such as Ritalin and Provigil, a newer kind of stimulant, known generically as modafinil, which was developed to treat narcolepsy. One in five respondents said they did. A majority of the 1,400 readers who responded said that healthy adults should be permitted to take brain boosters for non-medical reasons, and 69% said that mild side-effects were an acceptable risk. Though a majority said that such drugs should not be made available to children who had no diagnosed medical condition, a third admitted that they would feel pressure to give "smart drugs" to their kids if they learned that other parents were doing so.
Lebowitz says that if you're purchasing supplements to improve your brain power, you're probably wasting your money. "There is nothing you can buy at your local health food store that will improve your thinking skills," Lebowitz says. So that turmeric latte you've been drinking everyday has no additional brain benefits compared to a regular cup of java.
These actually work! I purchased these because of some focus and clarity issues. I like that there are two formulas, one for morning and one for night, and that they both help with the appropriate things at the appropriate times. The pills are easy to take, and not too large, which I have found to be an issue with some other supplements. They are capsules with what appears to be powder in them and appear to be well-made. There is no funky after taste or after effects. When several other natural approaches have not worked, these did, and the wait to see a difference was not long at all! The increase in focus and clarity and even some energy was evident within 2 days. They also come in 60 count bottles, so if you only take 1 per day, they will last 2 months!! I am incredibly impressed with these supplements and will likely be ordering them again.
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.
"Herbs will have several different compounds in them, as opposed to, let's say, a drug like amphetamine, which is basically one compound, one molecule," Sahelian says. "Herbs will have a set of several or several dozen compounds in them. It's difficult to pinpoint which one of them is the most active or whether it's the combination of many of them that are producing the result."
A recent study at the University of Innsbruck in Austria found that participants that drank two cups of coffee per day improved memory, reaction time, and neuron signaling, more than the control. More notably, the 676 daily coffee drinker participants experienced less mental decline than nondrinkers over a ten-year period. In other words, bottoms up on your cup of Joe!
The principal metric would be mood, however defined. Zeo’s web interface & data export includes a field for Day Feel, which is a rating 1-5 of general mood & quality of day. I can record a similar metric at the end of each day. 1-5 might be a little crude even with a year of data, so a more sophisticated measure might be in order. The first mood study is paywalled so I’m not sure what they used, but Shiotsuki 2008 used State-Trait of Anxiety Inventory (STAI) and Profiles of Mood States Test (POMS). The full POMS sounds too long to use daily, but the Brief POMS might work. In the original 1987 paper A brief POMS measure of distress for cancer patients, patients answering this questionnaire had a mean total mean of 10.43 (standard deviation 8.87). Is this the best way to measure mood? I’ve asked Seth Roberts; he suggested using a 0-100 scale, but personally, there’s no way I can assess my mood on 0-100. My mood is sufficiently stable (to me) that 0-5 is asking a bit much, even.
Manually mixing powders is too annoying, and pre-mixed pills are expensive in bulk. So if I’m not actively experimenting with something, and not yet rich, the best thing is to make my own pills, and if I’m making my own pills, I might as well make a custom formulation using the ones I’ve found personally effective. And since making pills is tedious, I want to not have to do it again for years. 3 years seems like a good interval - 1095 days. Since one is often busy and mayn’t take that day’s pills (there are enough ingredients it has to be multiple pills), it’s safe to round it down to a nice even 1000 days. What sort of hypothetical stack could I make? What do the prices come out to be, and what might we omit in the interests of protecting our pocketbook?
Zack explained that he didn't really like the term enhancement: "We're not talking about superhuman intelligence. No one's saying we're coming out with a pill that's going to make you smarter than Einstein! What we're really talking about is enabling people." He sketched a bell curve on the back of a napkin. "Almost every drug in development is something that will take someone who's working at, like, 40% or 50%, and take them up to 80," he said.
DAY B-1 1.5 mg B-2 1.7 mg Niacin 30 mg B-6 40 mg Folic Acid 400 mcg B-12 500 mcg Biotin 100 mcg Pantothenic Acid 10 mg Magnesium 100 mg Spirulina Algae Powder 5 mg Tongkat Ali Root 5 mg Panax ginseng 5 mg American Ginseng 5 mg Rhodiola rosea 5 mg Maca Root 5 mg L-Taurine 100 mg Acai Fruit 100 mg Caffeine Anhydrous 100 mg NIGHT Ginkgo biloba 50 mg Phosphatidylserine 125 mg N-Acetyl L-Carnitine HCl 50 mg St. John's Wort 250 mg L-Glutamine 50 mg Bacopa 100 mg Vinpocetine 2 mg Huperzine-A 10 mcg
Mosconi clarifies a few concepts. Other authors have advanced that the brain needs fat, including saturated fat, and cholesterol to function properly. Not so, Mosconi indicates that the fats we eat (saturated fat from animal protein) and cholesterol can’t even cross the blood-brain barrier. The brain needs a completely different type of fat: essential Polyunsaturated Fatty Acids (PUFAs). They include Omega-3s and Omega-6s fatty acids. Good sources of Omega-3s include fish, oils, eggs.
My worry about the MP variable is that, plausible or not, it does seem relatively weak against manipulation; other variables I could look at, like arbtt window-tracking of how I spend my computer time, # or size of edits to my files, or spaced repetition performance, would be harder to manipulate. If it’s all due to MP, then if I remove the MP and LLLT variables, and summarize all the other variables with factor analysis into 2 or 3 variables, then I should see no increases in them when I put LLLT back in and look for a correlation between the factors & LLLT with a multivariate regression.
Alex recalled one week during his junior year when he had four term papers due. Minutes after waking on Monday, around 7.30am, he swallowed some "immediate-release" Adderall. The drug, along with a steady stream of caffeine, helped him to concentrate during classes and meetings, but he noticed some odd effects; at a morning tutorial, he explained to me in an email, "I alternated between speaking too quickly and thoroughly on some subjects and feeling awkwardly quiet during other points of the discussion." Lunch was a blur: "It's always hard to eat much when on Adderall." That afternoon he went to the library, where he spent "too much time researching a paper rather than actually writing it - a problem that is common to all intellectually curious students on stimulants". At eight he attended a two-hour meeting "with a group focused on student mental health issues". Alex then "took an extended-release Adderall" and worked productively on the paper all night. At eight the next morning he attended a meeting of his student organisation; he felt like "a zombie" and went back to his room. He fell asleep until noon, waking "in time to polish my first paper and hand it in".
Dr. Lisa Mosconi, whose research spans an extraordinary range of specialties including brain science, the microbiome, and nutritional genomics, notes that the dietary needs of the brain are substantially different from those of the other organs, yet few of us have any idea what they might be. Her innovative approach to cognitive health incorporates concepts that most doctors have yet to learn. Busting through advice based on pseudoscience, Dr. Mosconi provides recommendations for a complete food plan, while calling out noteworthy surprises, including why that paleo diet you are following may not be ideal, why avoiding gluten may be a terrible mistake, and how simply getting enough water can dramatically improve alertness.
Another promising "smart pill" is phosphatidylserine, or PS, a natural substance that helps cell walls stay pliable and is thought to boost the effectiveness of neurotransmitters, which relay brain signals. In a May 1991 study published in Neurology, neuroscientist Thomas Crook found that patients with age-associated memory impairment improved their scores on key performance tests after 12 weeks on PS. Yet more research is needed before doctors can know that the supplement is safe and effective.
Artichoke + Forskolin: There is plenty of evidence that suggests artichoke extract supplements (made from the leaves of artichokes) offer strong neural antioxidant properties. Additionally, Forskolin (Coleus forskohlii) is one of the few studied compounds known to naturally boost cAMP (Cyclic Adenosine Monophosphate) in your brain and is also important for neural signaling within brain cells (291m 292). I’ve experienced noticeably enhanced memory and word recall when consuming this combo. Tim Ferriss talked about this one a bit in my podcast with him, particularly referencing its presence in the somewhat popular cognition supplement “CILTEP”. Made primarily from artichoke extracts and forskolin, CILTEP is a stack that also contains vitamin B6, L-phenylalanine and acetyl-L-carnitine. It is recommended to take two to three capsules at the beginning of each day and to skip dosage one or two days per week to achieve optimal results.
Powders are good for experimenting with (easy to vary doses and mix), but not so good for regular taking. I use OO gel capsules with a Capsule Machine: it’s hard to beat $20, it works, it’s not that messy after practice, and it’s not too bad to do 100 pills. However, I once did 3kg of piracetam + my other powders, and doing that nearly burned me out on ever using capsules again. If you’re going to do that much, something more automated is a serious question! (What actually wound up infuriating me the most was when capsules would stick in either the bottom or top try - requiring you to very gingerly pull and twist them out, lest the two halves slip and spill powder - or when the two halves wouldn’t lock and you had to join them by hand. In contrast: loading the gel caps could be done automatically without looking, after some experience.)
And without those precious nutrients, your brain will start to wither. In a recent Bulletproof Radio podcast episode [iTunes], I talked with neuroscientist Dale Bredesen about why neurodegeneration happens. One of the three most common causes of brain aging is a lack of specific brain nutrients (check out the episode to hear about the other two main causes of brain aging, and what you can do about them).
as scientific papers become much more accessible online due to Open Access, digitization by publishers, and cheap hosting for pirates, the available knowledge about nootropics increases drastically. This reduces the perceived risk by users, and enables them to educate themselves and make much more sophisticated estimates of risk and side-effects and benefits. (Take my modafinil page: in 1997, how could an average person get their hands on any of the papers available up to that point? Or get detailed info like the FDA’s prescribing guide? Even assuming they had a computer & Internet?)
So I eventually got around to ordering another thing of nicotine gum, Habitrol Nicotine Gum, 4mg MINT flavor COATED gum. 96 pieces per box. Gum should be easier to double-blind myself with than nicotine patches - just buy some mint gum. If 4mg is too much, cut the gum in half or whatever. When it arrived, my hopes were borne out: the gum was rectangular and soft, which made it easy to cut into fourths.
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:
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. It also may improve task saliency and performance on tedious tasks. At above optimal doses, methylphenidate had off–target effects that decreased learning.