The Blood Brain Barrier (BBB) is similar in structure to the intestinal barrier (6) and is usually highly selective, allowing certain required metabolic products such as short chain fatty acids and amino acids to pass into the brain from our wider circulation but protecting the brain from potentially damaging components. When the BBB is compromised, unwanted translocation may occur such as allowing a bacterial invasion, which can alter the function of immune cells that are responsible for regulating inflammation. Chronic inflammation is associated with many mental and physical health problems, so it is therefore suggested that poor gut health can have a direct correlation to poor mental wellbeing, as a result of a compromised intestinal barrier and the negative impact this has on our brain’s own structural barrier (BBB) and resulting inflammation.

People with failing memory and worried about Alzheimer’s disease are sometimes seduced by advertisements for Huperzine A, extracted from a type of moss. Some studies have shown that it increases levels of acetylcholine in the brain, a chemical that is in short supply in Alzheimer’s. But despite increasing acetylcholine, aside from a few questionable studies in China, there is no evidence that it improves memory. Unfortunately when it comes to memory pills, they are best forgotten. There is, however, hope that a nasal spray containing insulin can increase the absorption of glucose into brain cells and improve cognitive function. But in the meantime, the best bet to maintain good brain function is to monitor blood glucose and blood pressure, eat a diet rich in fruits, vegetables and whole grains, and low in simple carbs and saturated fat. And don’t forget that physical exercise also exercises your brain.
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.
Huperzine A: This compound is found in a firmoss plant called Huperzia serrata.  Studies conducted on Huperzine A so far have not used the best methodology, so scientists are still not sure how beneficial this compound is for preventing or treating Alzheimer’s disease.  But one review of studies on Huperzine A concluded that the compound “appears to have beneficial effects on improvement of cognitive function, daily living activity, and global clinical assessment in participants with Alzheimer’s disease.”
In her new book, Brain Food: The Surprising Science of Eating for Cognitive Power (Avery/ Penguin Random House), Dr. Lisa Mosconi, PhD, INHC, Associate Director of the Alzheimer’s Prevention Clinic at Weill Cornell Medical College, highlights the connection between diet and brain function and shares approachable, actionable tips to put that research into practice.
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.
“It is surprising and encouraging that it may be possible to predict the magnitude of a placebo effect before treatment,” says Tor Wager, a neuroscientist at the University of Colorado Boulder, who was not involved in the research. More work is needed to see how the predictive features hold up in other populations and for different pain conditions, he says.
Caffeine (; FDA adverse events) is of course the most famous stimulant around. But consuming 200mg or more a day, I have discovered the downside: it is addictive and has a nasty withdrawal - headaches, decreased motivation, apathy, and general unhappiness. (It’s a little amusing to read academic descriptions of caffeine addiction9; if caffeine were a new drug, I wonder what Schedule it would be in and if people might be even more leery of it than modafinil.) Further, in some ways, aside from the ubiquitous placebo effect, caffeine combines a mix of weak performance benefits (Lorist & Snel 2008, Nehlig 2010) with some possible decrements, anecdotally and scientifically:
The use of prescription stimulants is especially prevalent among students.[9] Surveys suggest that 0.7–4.5% of German students have used cognitive enhancers in their lifetime.[10][11][12] Stimulants such as dimethylamylamine and methylphenidate are used on college campuses and by younger groups.[13] Based upon studies of self-reported illicit stimulant use, 5–35% of college students use diverted ADHD stimulants, which are primarily intended for performance enhancement rather than as recreational drugs.[14][15][16] Several factors positively and negatively influence an individual's willingness to use a drug for the purpose of enhancing cognitive performance. Among them are personal characteristics, drug characteristics, and characteristics of the social context.[10][11][17][18]