I almost resigned myself to buying patches to cut (and let the nicotine evaporate) and hope they would still stick on well enough afterwards to be indistinguishable from a fresh patch, when late one sleepless night I realized that a piece of nicotine gum hanging around on my desktop for a week proved useless when I tried it, and that was the answer: if nicotine evaporates from patches, then it must evaporate from gum as well, and if gum does evaporate, then to make a perfect placebo all I had to do was cut some gum into proper sizes and let the pieces sit out for a while. (A while later, I lost a piece of gum overnight and consumed the full 4mg to no subjective effect.) Google searches led to nothing indicating I might be fooling myself, and suggested that evaporation started within minutes in patches and a patch was useless within a day. Just a day is pushing it (who knows how much is left in a useless patch?), so I decided to build in a very large safety factor and let the gum sit for around a month rather than a single day.
After 7 days, I ordered a kg of choline bitartrate from Bulk Powders. Choline is standard among piracetam-users because it is pretty universally supported by anecdotes about piracetam headaches, has support in rat/mice experiments28, and also some human-related research. So I figured I couldn’t fairly test piracetam without some regular choline - the eggs might not be enough, might be the wrong kind, etc. It has a quite distinctly fishy smell, but the actual taste is more citrus-y, and it seems to neutralize the piracetam taste in tea (which makes things much easier for me).
The effects of piracetam on healthy volunteers have been studied even less than those of Adderall or modafinil. Most peer-reviewed studies focus on its effects on dementia or on people who have suffered a seizure or a concussion. Many of the studies that look at other neurological effects were performed on rats and mice. Piracetam's mechanisms of action are not understood, though it may increase levels of the neurotransmitter acetylcholine. In 2008 a committee of the British Academy of Medical Sciences noted that many of the clinical trials of piracetam for dementia were methodologically flawed. Another published review of the available studies of the drug concluded that the evidence "does not support the use of piracetam in the treatment of people with dementia or cognitive impairment", but suggested that further investigation might be warranted. I asked Seltzer if he thought he should wait for scientific ratification of piracetam. He laughed. "I don't want to," he said. "Because it's working."
From the standpoint of absorption, the drinking of tobacco juice and the interaction of the infusion or concoction with the small intestine is a highly effective method of gastrointestinal nicotine administration. The epithelial area of the intestines is incomparably larger than the mucosa of the upper tract including the stomach, and the small intestine represents the area with the greatest capacity for absorption (Levine 1983:81-83). As practiced by most of the sixty-four tribes documented here, intoxicated states are achieved by drinking tobacco juice through the mouth and/or nose…The large intestine, although functionally little equipped for absorption, nevertheless absorbs nicotine that may have passed through the small intestine.
Caffeine metabolism is primarily determined by the cytochrome enzyme P-450 1A2 (CYP1A2), and studies have shown that different ethnic populations exhibit widely varying expressions of the gene responsible for CYP1A2. Evidence suggests that a particular CYP1A2 impacts caffeine consumption by modifying the risks of certain diseases that are associated with caffeine consumption. It has also been shown that variations in the expression of genes that code for adenosine and dopamine receptors play a role in mediating your response to caffeine. For example, in Caucasians, the presence of certain genetic expressions for both adenosine and dopamine receptors is associated with caffeine-induced anxiety. Variations in CYP1A2 are also responsible for the speed at which different people metabolize caffeine.
Dallas Michael Cyr, a 41-year-old life coach and business mentor in San Diego, California, also says he experienced a mental improvement when he regularly took another product called Qualia Mind, which its makers say enhances focus, energy, mental clarity, memory and even creativity and mood. "One of the biggest things I noticed was it was much more difficult to be distracted," says Cyr, who took the supplements for about six months but felt their effects last longer. While he's naturally great at starting projects and tasks, the product allowed him to be a "great finisher" too, he says.
I am sort of a health nut. I only use natural medicines- never prescriptions. Lately I have been experiencing some brain fog in spite of my detoxing, so I tried this product. I LOVE IT! I really can tell a difference. I have tried many memory and brain support supplements before, but this one seems quite different. I love the daytime and separate night time formulas. I have never slept so soundly in my life. In fact, I've always had a lot of trouble sleeping, but I sleep like a baby and wake feeling refreshed and full of energy.
The soft gels are very small; one needs to be a bit careful - Vitamin D is fat-soluble and overdose starts in the range of 70,000 IU36, so it would take at least 14 pills, and it’s unclear where problems start with chronic use. Vitamin D, like many supplements, follows a U-shaped response curve (see also Melamed et al 2008 and Durup et al 2012) - too much can be quite as bad as too little. Too little, though, is likely very bad. The previously cited studies with high acute doses worked out to <1,000 IU a day, so they may reassure us about the risks of a large acute dose but not tell us much about smaller chronic doses; the mortality increases due to too-high blood levels begin at ~140nmol/l and reading anecdotes online suggest that 5k IU daily doses tend to put people well below that (around 70-100nmol/l). I probably should get a blood test to be sure, but I have something of a needle phobia.
Nootropics still exist largely in an unregulated gray area, which makes users somewhat hesitant to discuss their regimens. But I did speak to several people who told tales of increased productivity and sharpened focus. Bob Carter, a financial analyst for a start-up called LendingHome, says that nootropics have replaced his other morning stimulant. “I basically think of it as a substitute for coffee,” he says. “I think the problem with a cappuccino from Starbucks is that it gives you the feeling of being jittery. Whereas with this particular supplement, I feel more calm.”
To understand further about how food intolerances can impact our mental health, it is important to explain the relationship between our gut microbiome, the immune system and our brain in a little more detail. The walls of our digestive tract provide a barrier between what we eat and the rest of our body and an unhealthy gut microbiome can lead to increased levels of inflammation, leaving the walls vulnerable to structural damage (4). Our intestinal wall is composed of cell junctions that prevent bacteria and large food molecules from entering the bloodstream, however, if these become damaged, proteins from foods that should not be circulating in our bloodstream can enter and an immune response is mounted as a reaction. This response is mediated by IgG, an antibody, that helps to protect against bacterial and viral infections as well as food antigens and is the most abundant immune cell in the body. Whilst food antigens are usually quickly cleared by an intelligent system called the reticuloendothelial system, with structural damage and a poor gut microbiome, this immune response can keep reoccurring. It is suggested that a chronic immune response such as this can have a negative impact on the brain, damaging its own structural barrier, called the Blood Brain Barrier (5).
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.
Choline is a nootropic: it enhances your ability to pay attention and learn efficiently, probably because you use a lot of acetylcholine during mentally-demanding tasks, and choline helps you synthesize enough to work harder and go longer. Choline also links to decreased brain inflammation in a dose-dependent manner — the more choline you eat, the less inflamed your brain tends to be.
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):
One study of helicopter pilots suggested that 600 mg of modafinil given in three doses can be used to keep pilots alert and maintain their accuracy at pre-deprivation levels for 40 hours without sleep. However, significant levels of nausea and vertigo were observed. Another study of fighter pilots showed that modafinil given in three divided 100 mg doses sustained the flight control accuracy of sleep-deprived F-117 pilots to within about 27% of baseline levels for 37 hours, without any considerable side effects. In an 88-hour sleep loss study of simulated military grounds operations, 400 mg/day doses were mildly helpful at maintaining alertness and performance of subjects compared to placebo, but the researchers concluded that this dose was not high enough to compensate for most of the effects of complete sleep loss.
It is at the top of the supplement snake oil list thanks to tons of correlations; for a review, see Luchtman & Song 2013 but some specifics include Teenage Boys Who Eat Fish At Least Once A Week Achieve Higher Intelligence Scores, anti-inflammatory properties (see Fish Oil: What the Prescriber Needs to Know on arthritis), and others - Fish oil can head off first psychotic episodes (study; Seth Roberts commentary), Fish Oil May Fight Breast Cancer, Fatty Fish May Cut Prostate Cancer Risk & Walnuts slow prostate cancer, Benefits of omega-3 fatty acids tally up, Serum Phospholipid Docosahexaenonic Acid Is Associated with Cognitive Functioning during Middle Adulthood endless anecdotes.
Power times prior times benefit minus cost of experimentation: (0.20 \times 0.30 \times 540) - 41 = -9. So the VoI is negative: because my default is that fish oil works and I am taking it, weak information that it doesn’t work isn’t enough. If the power calculation were giving us 40% reliable information, then the chance of learning I should drop fish oil is improved enough to make the experiment worthwhile (going from 20% to 40% switches the value from -$9 to +$23.8).
I asked him if piracetam made him feel smarter, or just more alert and confident - a little better equipped to marshal the resources he naturally had. "Maybe," he said. "I'm not sure what being smarter means, entirely. It's a difficult quality to measure. It's the Gestalt factor, all these qualities coming together - not only your ability to crunch some numbers, or remember some figures or a sequence of numbers, but also your ability to maintain a certain emotional state that is conducive to productive intellectual work. I do feel I'm more intelligent with the drugs, but I can't give you a number of IQ points."
28,61,36,25,61,57,39,56,23,37,24,50,54,32,50,33,16,42,41,40,34,33,31,65,23,36,29,51,46,31,45,52,30, 50,29,36,57,60,34,48,32,41,48,34,51,40,53,73,56,53,53,57,46,50,35,50,60,62,30,60,48,46,52,60,60,48, 47,34,50,51,45,54,70,48,61,43,53,60,44,57,50,50,52,37,55,40,53,48,50,52,44,50,50,38,43,66,40,24,67, 60,71,54,51,60,41,58,20,28,42,53,59,42,31,60,42,58,36,48,53,46,25,53,57,60,35,46,32,26,68,45,20,51, 56,48,25,62,50,54,47,42,55,39,60,44,32,50,34,60,47,70,68,38,47,48,70,51,42,41,35,36,39,23,50,46,44,56,50,39
(People aged <=18 shouldn’t be using any of this except harmless stuff - where one may have nutritional deficits - like fish oil & vitamin D; melatonin may be especially useful, thanks to the effects of screwed-up school schedules & electronics use on teenagers’ sleep. Changes in effects with age are real - amphetamines’ stimulant effects and modafinil’s histamine-like side-effects come to mind as examples.)
According to Dr Vivette Glover, Director of the Foetal and Neonatal Stress and Research Centre, at any one time during pregnancy, one in every ten women will be depressed and around one in every thirty will be depressed both during pregnancy and the postnatal period (1). It is not yet understood exactly what causes the symptoms associated to depression during and after pregnancy. However, factors such as the large changes that the body undergoes due to the demands of the growing foetus, as well as breastfeeding and potential sleep deprivation, can all play a significant role in how the body deals with stress. It is during this period of time that our bodies require more nourishment from food than ever and it can also be at exactly this time when we perhaps struggle to prioritise nutrition due to lack of energy, loss of appetite or sickness.
This looks interesting: the Noopept effect is positive for all the dose levels, but it looks like a U-curve - low at 10mg, high at 15mg, lower at 20mg, and even lower at 30mg 48mg and 60mg aren’t estimated because they are hit by the missingness problem: the magnesium citrate variable is unavailable for the days the higher doses were taken on, and so their days are omitted and those levels of the factor are not estimated. One way to fix this is to drop magnesium from the model entirely, at the cost of fitting the data much more poorly and losing a lot of R2:
These little chemicals prompt the immune system to kick in and fight back against the stress through inflammation, as though stress is an infection. While inflammation helps protect us against illnesses and repairs the body when you do something like cut yourself, chronic inflammation is a different animal. It’s been linked to autoimmune diseases like multiple sclerosis, anxiety, high blood pressure and more. (2)
When I spoke with Sahakian she had just flown from England to Scottsdale, Arizona, to attend a conference, and she was tired. "We may be healthy and high-functioning, and think of ourselves that way," she told me, "but it's very rare that we are actually functioning at our optimal level. Take me. I'm over here and I've got jet lag and I've got to give a talk tonight and perform well in what will be the middle of the night, UK time." She mentioned businessmen who have to fly back and forth across the Atlantic: "The difference between making a deal and not is huge, and they sometimes only have one meeting to try and do it." She added: "We are a society that so wants a quick fix that many people are happy to take drugs."
Nor am I sure how important the results are - partway through, I haven’t noticed anything bad, at least, from taking Noopept. And any effect is going to be subtle: people seem to think that 10mg is too small for an ingested rather than sublingual dose and I should be taking twice as much, and Noopept’s claimed to be a chronic gradual sort of thing, with less of an acute effect. If the effect size is positive, regardless of statistical-significance, I’ll probably think about doing a bigger real self-experiment (more days blocked into weeks or months & 20mg dose)
Hericium erinaceus (Examine.com) was recommended strongly by several on the ImmInst.org forums for its long-term benefits to learning, apparently linked to Nerve growth factor. Highly speculative stuff, and it’s unclear whether the mushroom powder I bought was the right form to take (ImmInst.org discussions seem to universally assume one is taking an alcohol or hotwater extract). It tasted nice, though, and I mixed it into my sleeping pills (which contain melatonin & tryptophan). I’ll probably never know whether the $30 for 0.5lb was well-spent or not.
B vitamins are also sold with claims of enhancing memory, usually rationalized by their reduction of homocysteine, a chemical in the blood that may affect circulation in the brain. No benefits from B vitamin intake have been demonstrated when it comes to memory or cognitive function except in the case of people who have high homocysteine levels due to a diet that is very low in B vitamins. There is some concern that folic acid, one of the B vitamins, may spur the growth of polyps in the colon at doses greater than 800 micrograms a day. Phosphatidyl serine is a natural component of nerve cell membranes and its promoters argue that a deficiency leads to impaired communication between nerve cells which in turn impairs cognitive function. Sounds reasonable, except that proper controlled trials have come up empty. The same goes for vinpocetine, a compound originally isolated from the lesser periwinkle plant by Hungarian chemist Csaba Szantay in 1975. It is widely used in Europe to treat strokes and memory problems with claims of increased circulation to the brain. It does indeed increase circulation, much like ginkgo, but there is no compelling evidence for memory improvement.
After trying out 2 6lb packs between 12 September & 25 November 2012, and 20 March & 20 August 2013, I have given up on flaxseed meal. They did not seem to go bad in the refrigerator or freezer, and tasted OK, but I had difficulty working them into my usual recipes: it doesn’t combine well with hot or cold oatmeal, and when I tried using flaxseed meal in soups I learned flaxseed is a thickener which can give soup the consistency of snot. It’s easier to use fish oil on a daily basis.
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.