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.)
Tyrosine (Examine.com) is an amino acid; people on the Imminst.org forums (as well as Wikipedia) suggest that it helps with energy and coping with stress. I ordered 4oz (bought from Smart Powders) to try it out, and I began taking 1g with my usual caffeine+piracetam+choline mix. It does not dissolve easily in hot water, and is very chalky and not especially tasty. I have not noticed any particular effects from it.
And if you obtain your vitamin C from a multivitamin, you receive other key nutrients that many studies over the years have linked to healthy brain function, including beta carotene, iron, zinc, B12 and folic acid. In the June 1999 issue of the Journal of Biology and Psychiatry, for instance, researchers at Sweden's Gotenborg University reported that older people were more likely to score poorly on word memory tests if they had low levels of folic acid.
One thing I did do was piggyback on my Noopept self-experiment: I blinded & randomized the Noopept for a real experiment, but simply made sure to vary the Magtein without worrying about blinding or randomizing it. (The powder is quite bulky.) The correlation the experiment turned in was a odds-ratio of 1.9; interesting and in the right direction (higher is better), but since the magnesium part wasn’t random or blind, not a causal result.
Fortunately for me, the FDA decided Smart Powder’s advertising was too explicit and ordered its piracetam sales stopped; I was equivocal at the previous price point, but then I saw that between the bulk discount and the fire-sale coupon, 3kg was only $99.99 (shipping was amortized over that, the choline, caffeine, and tryptophan). So I ordered in September 2010. As well, I had decided to cap my own pills, eliminating the inconvenience and bad taste. 3kg goes a very long way so I am nowhere close to running out of my pills; there is nothing to report since, as the pills are simply part of my daily routine.
My first impression of ~1g around 12:30PM was that while I do not feel like running around, within an hour I did feel like the brain fog was lighter than before. The effect wasn’t dramatic, so I can’t be very confident. Operationalizing brain fog for an experiment might be hard: it doesn’t necessarily feel like I would do better on dual n-back. I took 2 smaller doses 3 and 6 hours later, to no further effect. Over the following weeks and months, I continued to randomly alternate between potassium & non-potassium days. I noticed no effects other than sleep problems.
Large scale studies have shown the association between chronic low-grade inflammation and depression (8). For example, in a study that examined data from 14,275 people who were interviewed between 2007 and 2012, they found that people who had depression had 46% higher levels of C-reactive protein (CRP), a marker of inflammatory disease, in their blood samples (9). Studies like these are paving the way towards a new understanding of the pathology of mental health conditions and how diet and stress can alter bodily systems, such as digestive function and consequently impact mental wellbeing. Measuring IgG antibodies in food intolerance tests has been implicated as a popular strategy to tackle symptoms related to sensitivities such as IBS, joint pain, fatigue, migraines, anxiety and depression. A recent survey on 708 people commissioned by Allergy UK, demonstrated how 81% of those with elevated IgG levels, as well as psychological symptoms, reported an improvement in their condition after following a food-specific IgG elimination diet (9). Taking this all into account, health professionals and those with poor mental health may want to consider the potential role of food intolerances in mental well-being and in managing common mood-related disorders, such as depression and anxiety.
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 fish oil can be considered a free sunk cost: I would take it in the absence of an experiment. The empty pill capsules could be used for something else, so we’ll put the 500 at $5. Filling 500 capsules with fish and olive oil will be messy and take an hour. Taking them regularly can be added to my habitual morning routine for vitamin D and the lithium experiment, so that is close to free but we’ll call it an hour over the 250 days. Recording mood/productivity is also free a sunk cost as it’s necessary for the other experiments; but recording dual n-back scores is more expensive: each round is ~2 minutes and one wants >=5, so each block will cost >10 minutes, so 18 tests will be >180 minutes or >3 hours. So >5 hours. Total: 5 + (>5 \times 7.25) = >41.
Taking these drugs without a doctor’s supervision can be dangerous. There are interactions and contraindications that can cause serious problems. These drugs should not be used if you drink alcohol or take an antidepressant. (50) The possibility of adverse drug reactions should not be taken lightly. By some calculations, adverse drug reactions are now the fourth leading cause of death in the US. (51)
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.
The Nootroo arrives in a shiny gold envelope with the words “proprietary blend” and “intended for use only in neuroscience research” written on the tin. It has been designed, says Matzner, for “hours of enhanced learning and memory”. The capsules contain either Phenylpiracetam or Noopept (a peptide with similar effects and similarly uncategorised) and are distinguished by real flakes of either edible silver or gold. They are to be alternated between daily, allowing about two weeks for the full effect to be felt. Also in the capsules are L-Theanine, a form of choline, and a types of caffeine which it is claimed has longer lasting effects.
Does absolutely nothing it says it does....taking the pill is jus no effects at all, good or bad. its not a limitless effect its a pointless effect and a waste of money.I very rarely give an review and if i do its more likely a good one but this one i jus felt the need to let people know they're wasting their money buying these supplements. Im jus tired of these supplement companies getting rich of fraudulent advertisement. Its 2015 if your product is good people will continue to buy if its not don't go the fraud way about you'll have a very short good run before word gets out and people are not coming back for more compared to the run it could have had if it really does what it says it does. waste of time with this s*** people TRUST ME.
L-Alpha glycerylphosphorylcholine or choline alfoscerate, also known as Alpha GPC is a natural nootropic which works both on its own and also in combination with other nootropics. It can be found in the human body naturally in small amounts. It’s also present in some dairy products, wheat germ, and in organic meats. However, these dietary sources contain small amounts of GPC, which is why people prefer taking it through supplements.
That study is also interesting for finding benefits to chronic piracetam+choline supplementation in the mice, which seems connected to a Russian study which reportedly found that piracetam (among other more obscure nootropics) increased secretion of BDNF in mice. See also Drug heuristics on a study involving choline supplementation in pregnant rats.↩
This doesn’t fit the U-curve so well: while 60mg is substantially negative as one would extrapolate from 30mg being ~0, 48mg is actually better than 15mg. But we bought the estimates of 48mg/60mg at a steep price - we ignore the influence of magnesium which we know influences the data a great deal. And the higher doses were added towards the end, so may be influenced by the magnesium starting/stopping. Another fix for the missingness is to impute the missing data. In this case, we might argue that the placebo days of the magnesium experiment were identical to taking no magnesium at all and so we can classify each NA as a placebo day, and rerun the desired analysis:
Interesting. On days ranked 2 (below-average mood/productivity), nicotine seems to have boosted scores; on days ranked 3, nicotine hurts scores; there aren’t enough 4’s to tell, but even ’5 days seem to see a boost from nicotine, which is not predicted by the theory. But I don’t think much of a conclusion can be drawn: not enough data to make out any simple relationship. Some modeling suggests no relationship in this data either (although also no difference in standard deviations, leading me to wonder if I screwed up the data recording - not all of the DNB scores seem to match the input data in the previous analysis). So although the 2 days in the graph are striking, the theory may not be right.
Barbara Sahakian, a neuroscientist at Cambridge University, doesn’t dismiss the possibility of nootropics to enhance cognitive function in healthy people. She would like to see society think about what might be considered acceptable use and where it draws the line – for example, young people whose brains are still developing. But she also points out a big problem: long-term safety studies in healthy people have never been done. Most efficacy studies have only been short-term. “Proving safety and efficacy is needed,” she says.
Nootropics may seem attractive to anyone who wants to try to improve their cognitive function and is willing to purchase powders, pills and other forms of these natural and synthetic supplements. Nootropic users have their own terminology, referring to measured combinations of nootropics and vitamins and minerals as “stacks.” For instance, Danger and Play, a site for active people, features a stack for beginners. The recipe includes 1600 mg of the piracetam along with recommended dosages of supplements such as ALCAR, rhodiola and magnesium. There are recipes for morning, afternoon and night, thus providing daylong guidance on how to most effectively stack for more energy, greater concentration, and improved information retention. The stack tip specifically states that the ingredients are not addictive, especially if taken in strict accordance with the recipe.
Following up on the promising but unrandomized pilot, I began randomizing my LLLT usage since I worried that more productive days were causing use rather than vice-versa. I began on 2 August 2014, and the last day was 3 March 2015 (n=167); this was twice the sample size I thought I needed, and I stopped, as before, as part of cleaning up (I wanted to know whether to get rid of it or not). The procedure was simple: by noon, I flipped a bit and either did or did not use my LED device; if I was distracted or didn’t get around to randomization by noon, I skipped the day. This was an unblinded experiment because finding a randomized on/off switch is tricky/expensive and it was easier to just start the experiment already. The question is simple too: controlling for the simultaneous blind magnesium experiment & my rare nicotine use (I did not use modafinil during this period or anything else I expect to have major influence), is the pilot correlation of d=0.455 on my daily self-ratings borne out by the experiment?
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.)
That’s why adults aren’t as crazy as teenagers, because adult brains aren’t as sensitive or reactive to external factors and experience teaches us to know better. That’s the potential danger with a drug like this. You return your brain to a state when you can learn a lot easier because you are ultra-sensitive to all stimuli in your environment, but it also makes it easier for that stimuli to affect you, for better or worse. The worst case scenario? You take this drug to be smarter but your personality can be destroyed by external stresses- it’s like being an emotional mess and losing yourself in high school again.
The BoredAt websites - which allow college students to chat idly while they're ostensibly studying - are filled with messages about Adderall. Posts like these, from the BoredAtPenn site, are typical: "I have some Adderall - I'm sitting by room 101.10 in a grey shirt and headphones"; "I have Adderall for sale 20mg for $15"; "I took Adderall at 8pm, it's 6:30am and I've barely blinked." On the Columbia site one poster complains that her friends take Adderall "like candy", adding: "I don't want to be at a disadvantage to everyone else. Is it really that dangerous? My grades weren't that great this year and I could do with a bump." A Columbia student responds: "It's probably not a good idea if you're not prescribed", but offers practical advice anyway: "Keep the dose normal and don't grind them up or snort them." Occasional dissenters ("I think there should be random drug testing at every exam") are drowned out by testimonials like this one, from the BoredAtHarvard site: "I don't want to be a pusher or start people on something bad, but Adderall is amazing."
The ingredients in her recipes are representative of her thinking. Local raw honey. Organic everything. Free-range eggs. Organic, grass-fed whole milk (I assume she means feeding grass to the cows, not feeding it to the milk). Filtered water. Goji berries. Açai berry powder. Ginseng extract with royal jelly and bee pollen. Organic spirulina powder. Even Himalayan pink sea salt, for heaven’s sake! Good grief!!
He recommends a 10mg dose, but sublingually. He mentions COLURACETAM’s taste is more akin to that of PRAMIRACETAM than OXIRACETAM, in that it tastes absolutely vile (not a surprise), so it is impossible to double-blind a sublingual administration - even if I knew of an inactive equally-vile-tasting substitute, I’m not sure I would subject myself to it. To compensate for ingesting the coluracetam, it would make sense to double the dose to 20mg (turning the 2g into <100 doses). Whether the effects persist over multiple days is not clear; I’ll assume it does not until someone says it does, since this makes things much easier.
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.
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
Nicotine’s stimulant effects are general and do not come with the same tweakiness and aggression associated with the amphetamines, and subjectively are much cleaner with less of a crash. I would say that its stimulant effects are fairly strong, around that of modafinil. Another advantage is that nicotine operates through nicotinic receptors and so doesn’t cross-tolerate with dopaminergic stimulants (hence one could hypothetically cycle through nicotine, modafinil, amphetamines, and caffeine, hitting different receptors each time).
Clinical psychiatrist Emily Deans has a private practice in Massachusetts and teaches at Harvard Medical School. She told me by phone that, in principle, there's "probably nothing dangerous" about the occasional course of nootropics for a hunting trip, finals week, or some big project. Beyond that, she suggests considering that it's possible to build up a tolerance to many neuroactive products if you use them often enough.
Nootropics—the name given to a broad class of so-called "cognitive-enhancing" drugs—are all the rage in Silicon Valley these days. Programmers like nootropics because they’re said to increase productivity and sharpen focus without the intensity or side effects of a prescription drug like Adderall or modafinil. Some users mix their own nootropics using big bins of powders, purchased off the Internet or in supplement stores. And some take pre-made "stacks" that are designed to produce specific effects.
Like everything else in your body, the brain cannot work without energy. The ability to concentrate and focus comes from an adequate, steady supply of energy - in the form of glucose in our blood to the brain. Achieve this by choosing wholegrains with a low-GI, which release glucose slowly into the bloodstream, keeping you mentally alert throughout the day. Opt for 'brown' wholegrain cereals, granary bread, rice and pasta.
We all wish success came in a pill form. That was the premise of the hour and half Adderall commercial/ thriller film ‘Limitless’ starring Bradley Cooper. In the film he popped a transparent round pill and instantly his brain power skyrocketed- anything became possible. Most of us wished that pill existed- and now it does. Donepezil is a drug that is used to treat Alzheimers, but it’s effects on normal people make Adderall and Vyvanse look like a cup of coffee.
I take my piracetam in the form of capped pills consisting (in descending order) of piracetam, choline bitartrate, anhydrous caffeine, and l-tyrosine. On 8 December 2012, I happened to run out of them and couldn’t fetch more from my stock until 27 December. This forms a sort of (non-randomized, non-blind) short natural experiment: did my daily 1-5 mood/productivity ratings fall during 8-27 December compared to November 2012 & January 2013? The graphed data29 suggests to me a decline:
The Neurohacker Collective is a group of scientists, academics, and creatives who, among other things, sell nootropics. One of its premier products is Qualia Original Stack (OS), which has 41 ingredients. The large print says it improves focus, mood, and energy within 30 minutes and “supports long-term brain health.” A 22-dose supply costs $129. Such stacks operate on the idea that synergies among ingredients yield additional benefits.
One might suggest just going to the gym or doing other activities which may increase endogenous testosterone secretion. This would be unsatisfying to me as it introduces confounds: the exercise may be doing all the work in any observed effect, and certainly can’t be blinded. And blinding is especially important because the 2011 review discusses how some studies report that the famed influence of testosterone on aggression (eg. Wedrifid’s anecdote above) is a placebo effect caused by the folk wisdom that testosterone causes aggression & rage!
In the study, which evaluated the eating habits and mental ability of more than 950 older adults for an average of five years, those adults who ate a serving of leafy green veggies once or twice a day experienced slower mental deterioration than those who ate no vegetables, even when factors like age, education and family history of dementia were factored in.
For starters, it’s one of the highest antioxidant-rich foods known to man, including vitamin C and vitamin K and fiber. Because of their high levels of gallic acid, blueberries are especially good at protecting our brains from degeneration and stress. Get your daily dose of brain berries in an Omega Blueberry Smoothie, Pumpkin Blueberry Pancakes or in a Healthy Blueberry Cobbler.
And many people swear by them. Neal Thakkar, for example, is an entrepreneur from Marlboro, New Jersey, who claims nootropics improved his life so profoundly that he can’t imagine living without them. His first breakthrough came about five years ago, when he tried a piracetam/choline combination, or “stack,” and was amazed by his increased verbal fluency. (Piracetam is a cognitive-enhancement drug permitted for sale in the U. S. as a dietary supplement; choline is a natural substance.)
One of the most obscure -racetams around, coluracetam (Smarter Nootropics, Ceretropic, Isochroma) acts in a different way from piracetam - piracetam apparently attacks the breakdown of acetylcholine while coluracetam instead increases how much choline can be turned into useful acetylcholine. This apparently is a unique mechanism. A crazy Longecity user, ScienceGuy ponied up $16,000 (!) for a custom synthesis of 500g; he was experimenting with 10-80mg sublingual doses (the ranges in the original anti-depressive trials) and reported a laundry list of effects (as does Isochroma): primarily that it was anxiolytic and increased work stamina. Unfortunately for my stack, he claims it combines poorly with piracetam. He offered free 2g samples for regulars to test his claims. I asked & received some.
A big part is that we are finally starting to apply complex systems science to psycho-neuro-pharmacology and a nootropic approach. The neural system is awesomely complex and old-fashioned reductionist science has a really hard time with complexity. Big companies spends hundreds of millions of dollars trying to separate the effects of just a single molecule from placebo – and nootropics invariably show up as “stacks” of many different ingredients (ours, Qualia , currently has 42 separate synergistic nootropics ingredients from alpha GPC to bacopa monnieri and L-theanine). That kind of complex, multi pathway input requires a different methodology to understand well that goes beyond simply what’s put in capsules.