Compared with those reporting no use, subjects drinking >4 cups/day of decaffeinated coffee were at increased risk of RA [rheumatoid arthritis] (RR 2.58, 95% CI 1.63-4.06). In contrast, women consuming >3 cups/day of tea displayed a decreased risk of RA (RR 0.39, 95% CI 0.16-0.97) compared with women who never drank tea. Caffeinated coffee and daily caffeine intake were not associated with the development of RA.

How exactly – and if – nootropics work varies widely. Some may work, for example, by strengthening certain brain pathways for neurotransmitters like dopamine, which is involved in motivation, Barbour says. Others aim to boost blood flow – and therefore funnel nutrients – to the brain to support cell growth and regeneration. Others protect brain cells and connections from inflammation, which is believed to be a factor in conditions like Alzheimer's, Barbour explains. Still others boost metabolism or pack in vitamins that may help protect the brain and the rest of the nervous system, explains Dr. Anna Hohler, an associate professor of neurology at Boston University School of Medicine and a fellow of the American Academy of Neurology.
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.
But like any other supplement, there are some safety concerns negative studies like Fish oil fails to hold off heart arrhythmia or other reports cast doubt on a protective effect against dementia or Fish Oil Use in Pregnancy Didn’t Make Babies Smart (WSJ) (an early promise but one that faded a bit later) or …Supplementation with DHA compared with placebo did not slow the rate of cognitive and functional decline in patients with mild to moderate Alzheimer disease..
The NIDA research study focused on 10 healthy male participants. The men were subjected to two rounds of PET brain scans after consuming either Provigil (200 mg or 400 mg) or a placebo. The scans demonstrated that the Provigil users had an increase in the amount of dopamine in the brain. Dopamine is a key neurological messenger in the brain’s reward system. Cocaine and methamphetamine have a similar effect on the brain, but they are more potent and faster-acting than Provigil. As cocaine and amphetamines are addiction-forming, the reasoning here is that Provigil may also be addictive.
But, thanks to the efforts of a number of remarkable scientists, researchers and plain-old neurohackers, we are beginning to put together a “whole systems” model of how all the different parts of the human brain work together and how they mesh with the complex regulatory structures of the body. It’s going to take a lot more data and collaboration to dial this model in, but already we are empowered to design stacks that can meaningfully deliver on the promise of nootropics “to enhance the quality of subjective experience and promote cognitive health, while having extremely low toxicity and possessing very few side effects.” It’s a type of brain hacking that is intended to produce noticeable cognitive benefits.
Today, extraordinary research is showing that bacopa has the remarkable ability to increase levels of BDNF, a protein responsible for the growth, maintenance and survival of neurons, and the creation of new neural connections in the brain. It also has been shown to help promote the growth of new neurons and neural pathways, which helps to explain why it’s such a powerful memory and concentration booster.
Cost-wise, the gum itself (~$5) is an irrelevant sunk cost and the DNB something I ought to be doing anyway. If the results are negative (which I’ll define as d<0.2), I may well drop nicotine entirely since I have no reason to expect other forms (patches) or higher doses (2mg+) to create new benefits. This would save me an annual expense of ~$40 with a net present value of <820 ($); even if we count the time-value of the 20 minutes for the 5 DNB rounds over 48 days (0.2 \times 48 \times 7.25 = 70), it’s still a clear profit to run a convincing experiment.
The evidence? Found helpful in reducing bodily twitching in myoclonus epilepsy, a rare disorder, but otherwise little studied. Mixed evidence from a study published in 1991 suggests it may improve memory in subjects with cognitive impairment. A meta-analysis published in 2010 that reviewed studies of piracetam and other racetam drugs found that piracetam was somewhat helpful in improving cognition in people who had suffered a stroke or brain injury; the drugs’ effectiveness in treating depression and reducing anxiety was more significant.
NeuroFuse was almost there with a top quality product but we felt that there were several key elements missing. It does contain a lot of the top natural ingredients for cognitive energy enhancement. However, the fact that their money-back guarantee is not apparent and that they are baiting customers in using a 14-day free trial offer, made us slightly wary. If they addressed these issues, we felt that this could have been a winner!

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.


Since my experiment had a number of flaws (non-blind, varying doses at varying times of day), I wound up doing a second better experiment using blind standardized smaller doses in the morning. The negative effect was much smaller, but there was still no mood/productivity benefit. Having used up my first batch of potassium citrate in these 2 experiments, I will not be ordering again since it clearly doesn’t work for me.
The above are all reasons to expect that even if I do excellent single-subject design self-experiments, there will still be the old problem of internal validity versus external validity: an experiment may be wrong or erroneous or unlucky in some way (lack of internal validity) or be right but not matter to anyone else (lack of external validity). For example, alcohol makes me sad & depressed; I could run the perfect blind randomized experiment for hundreds of trials and be extremely sure that alcohol makes me less happy, but would that prove that alcohol makes everyone sad or unhappy? Of course not, and as far as I know, for a lot of people alcohol has the opposite effect. So my hypothetical alcohol experiment might have tremendous internal validity (it does prove that I am sadder after inebriating), and zero external validity (someone who has never tried alcohol learns nothing about whether they will be depressed after imbibing). Keep this in mind if you are minded to take the experiments too seriously.
A key area that has been widely researched is the link between the microbiome (bacteria) in the gut and the brain. The hypothesis is that alterations in bacteria due to changes in our environment such as increased hygiene, increased exposure to antibiotics, refined and processed foods and stress have led to disturbances in short-chain fatty acids (SFCAs), which are byproducts of fermentation in the gut when bacteria come into contact with indigestible fibre found in food.

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.
The abuse liability of caffeine has been evaluated.147,148 Tolerance development to the subjective effects of caffeine was shown in a study in which caffeine was administered at 300 mg twice each day for 18 days.148 Tolerance to the daytime alerting effects of caffeine, as measured by the MSLT, was shown over 2 days on which 250 g of caffeine was given twice each day48 and to the sleep-disruptive effects (but not REM percentage) over 7 days of 400 mg of caffeine given 3 times each day.7 In humans, placebo-controlled caffeine-discontinuation studies have shown physical dependence on caffeine, as evidenced by a withdrawal syndrome.147 The most frequently observed withdrawal symptom is headache, but daytime sleepiness and fatigue are also often reported. The withdrawal-syndrome severity is a function of the dose and duration of prior caffeine use…At higher doses, negative effects such as dysphoria, anxiety, and nervousness are experienced. The subjective-effect profile of caffeine is similar to that of amphetamine,147 with the exception that dysphoria/anxiety is more likely to occur with higher caffeine doses than with higher amphetamine doses. Caffeine can be discriminated from placebo by the majority of participants, and correct caffeine identification increases with dose.147 Caffeine is self-administered by about 50% of normal subjects who report moderate to heavy caffeine use. In post-hoc analyses of the subjective effects reported by caffeine choosers versus nonchoosers, the choosers report positive effects and the nonchoosers report negative effects. Interestingly, choosers also report negative effects such as headache and fatigue with placebo, and this suggests that caffeine-withdrawal syndrome, secondary to placebo choice, contributes to the likelihood of caffeine self-administration. This implies that physical dependence potentiates behavioral dependence to caffeine.
That it is somewhat valuable is clear if we consider it under another guise. Imagine you received the same salary you do, but paid every day. Accounting systems would incur considerable costs handling daily payments, since they would be making so many more and so much smaller payments, and they would have to know instantly whether you showed up to work that day and all sorts of other details, and the recipients themselves would waste time dealing with all these checks or looking through all the deposits to their account, and any errors would be that much harder to track down. (And conversely, expensive payday loans are strong evidence that for poor people, a bi-weekly payment is much too infrequent.) One might draw a comparison to batching or buffers in computers: by letting data pile up in buffers, the computer can then deal with them in one batch, amortizing overhead over many items rather than incurring the overhead again and again. The downside, of course, is that latency will suffer and performance may drop based on that or the items becoming outdated & useless. The right trade-off will depend on the specifics; one would not expect random buffer-sizes to be optimal, but one would have to test and see what works best.

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:
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.
Chocolate or cocoa powder (Examine.com), contains the stimulants caffeine and the caffeine metabolite theobromine, so it’s not necessarily surprising if cocoa powder was a weak stimulant. It’s also a witch’s brew of chemicals such as polyphenols and flavonoids some of which have been fingered as helpful10, which all adds up to an unclear impact on health (once you control for eating a lot of sugar).
One of the other suggested benefits is for boosting serotonin levels; low levels of serotonin are implicated in a number of issues like depression. I’m not yet sure whether tryptophan has helped with motivation or happiness. Trial and error has taught me that it’s a bad idea to take tryptophan in the morning or afternoon, however, even smaller quantities like 0.25g. Like melatonin, the dose-response curve is a U: ~1g is great and induces multiple vivid dreams for me, but ~1.5g leads to an awful night and a headache the next day that was worse, if anything, than melatonin. (One morning I woke up with traces of at least 7 dreams, although I managed to write down only 2. No lucid dreams, though.)
The evidence? In small studies, healthy people taking modafinil showed improved planning and working memory, and better reaction time, spatial planning, and visual pattern recognition. A 2015 meta-analysis claimed that “when more complex assessments are used, modafinil appears to consistently engender enhancement of attention, executive functions, and learning” without affecting a user’s mood. In a study from earlier this year involving 39 male chess players, subjects taking modafinil were found to perform better in chess games played against a computer.

Omega-3 fatty acids: DHA and EPA – two Cochrane Collaboration reviews on the use of supplemental omega-3 fatty acids for ADHD and learning disorders conclude that there is limited evidence of treatment benefits for either disorder.[42][43] Two other systematic reviews noted no cognition-enhancing effects in the general population or middle-aged and older adults.[44][45]
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