Some nootropics users are hopeful that the drugs could be permanently “neuroprotective”—in other words, that the compounds could slow down the neuronal aging process, and help avoid cognitive deterioration later in life. (For what it's worth, most of the users I spoke to said that didn't matter much to them. “I doubt anything I’ve tried has made me smarter in a long-term way,” Baker says. “That’s still science fiction.”)
One of the most popular legal stimulants in the world, nicotine is often conflated with the harmful effects of tobacco; considered on its own, it has performance & possibly health benefits. Nicotine is widely available at moderate prices as long-acting nicotine patches, gums, lozenges, and suspended in water for vaping. While intended for smoking cessation, there is no reason one cannot use a nicotine patch or nicotine gum for its stimulant effects.
So how do I pull off this stack? It’s quite simple, really. I order 1-milligram nicotine toothpicks on Amazon that I suck on when I’m downing a cup of coffee (the cinnamon flavor blends quite nicely with a cup o’ joe) and I also keep a dispenser of 1.5-milligram nicotine mints in my office. Warning: nicotine can be addictive. I recommend limiting yourself to no more than 1-2 toothpicks and 1-2 mints per day, and only using on more cognitively demanding days. As a bonus, both caffeine and nicotine are potent ergogenic, physical performance-enhancing aids (albeit in higher amounts, closer to 100+ milligrams for caffeine and 2.5+ milligrams for nicotine).
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.
While the mechanism is largely unknown, one commonly mechanism possibility is that light of the relevant wavelengths is preferentially absorbed by the protein cytochrome c oxidase, which is a key protein in mitochondrial metabolism and production of ATP, substantially increasing output, and this extra output presumably can be useful for cellular activities like healing or higher performance.
Be patient.  Even though you may notice some improvements right away (sometimes within the first day), you should give your brain supplement at least several months to work.  The positive effects are cumulative, and most people do not max out their brain potential on a supplement until they have used it for at least 90 days.  That is when the really dramatic effects start kicking in!
On the other hand, other SCFAs such as butyrate are well known for having health-promoting properties, such as producing anti-inflammatory effects by being able to regulate T-cells (immune cells) in the colon, as well as helping to maintain a healthy gut barrier function. In order to increase the favourable, health-promoting SCFAs, such as butyrate, it’s important to increase the intake of vegetables, fruits and good fats such as grass-fed butter, coconut oil, nuts and seeds, olive oil and avocado. These provide the bacteria with prebiotics, which is in other words, food for gut bacteria to feed on. Foods such as those listed above contain the right nourishment for gut bacteria to produce SCFAs that support health. Eating traditional foods such as fermented cabbage and other vegetables, as well as bone broth, are also rich in prebiotics and nutrients that support a healthy microbiome and digestive system.
One idea I’ve been musing about is the connections between IQ, Conscientiousness, and testosterone. IQ and Conscientiousness do not correlate to a remarkable degree - even though one would expect IQ to at least somewhat enable a long-term perspective, self-discipline, metacognition, etc! There are indications in studies of gifted youth that they have lower testosterone levels. The studies I’ve read on testosterone indicate no improvements to raw ability. So, could there be a self-sabotaging aspect to human intelligence whereby greater intelligence depends on lack of testosterone, but this same lack also holds back Conscientiousness (despite one’s expectation that intelligence would produce greater self-discipline and planning), undermining the utility of greater intelligence? Could cases of high IQ types who suddenly stop slacking and accomplish great things sometimes be due to changes in testosterone? Studies on the correlations between IQ, testosterone, Conscientiousness, and various measures of accomplishment are confusing and don’t always support this theory, but it’s an idea to keep in mind.
Taurine ( was another gamble on my part, based mostly on its inclusion in energy drinks. I didn’t do as much research as I should have: it came as a shock to me when I read in Wikipedia that taurine has been shown to prevent oxidative stress induced by exercise and was an antioxidant - oxidative stress is a key part of how exercise creates health benefits and antioxidants inhibit those benefits.
Research on animals has shown that intermittent fasting — limiting caloric intake at least two days a week — can help improve neural connections in the hippocampus and protect against the accumulation of plaque, a protein prevalent in the brains of people with Alzheimer’s disease. Research has also shown that intermittent fasting helped reduce anxiety in mice.
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.
Mercury exposure is among several other heavy metals, such as lead, aluminium and cadmium, that have been implicated in the aetiology of ADHD. Childhood exposure to mercury is predominantly through the consumption of seafood, dental amalgams and vaccines containing thimerosal. The reason why mercury can be so problematic, as well as other metals, is that it is capable of breaching the blood brain barrier. This is the brain’s ‘high fortress’, an intelligent gateway system that filters through molecules that are needed in the brain such as cells, nutrients and signalling molecules, and filters out pathogens and toxins.
Provigil may well confer a temporary advantage on healthy people, but this doesn't mean that it's ready to replace your morning espresso. Anjan Chatterjee told me that there "just aren't enough studies of these drugs in normal people". One study, published recently in the Journal of the American Medical Association, suggests that Provigil can be habit-forming. A group led by Nora Volkow, the director of the National Institute on Drug Abuse, scanned the brains of 10 men after they had been given a placebo, and also after they had been given a dose of modafinil. The modafinil appeared to lead to an increase in the brain chemical dopamine. "Because drugs that increase dopamine have the potential for abuse," Volkow's report concluded, "these results suggest that risk for addiction in vulnerable persons merits heightened awareness." (Cephalon, in a response to the report, notes that Provigil's label urges physicians to monitor patients closely, especially those with a history of drug abuse.) On the website Erowid, where people vividly and anonymously report their experiences with legal and illegal drugs, some modafinil users have described a dependency on the drug. One man, who identified himself as a former biochemistry student, said that he had succeeded in kicking cocaine and opiate habits but couldn't stop using modafinil. Whenever he ran out of the drug, he said, "I start to freak out." After "four to five days" without it, "the head fog starts to come back".
As a general class, nootropics are not usually addiction-forming.[6] Two of the strongest hallmarks of addiction-forming drugs is that they cause users to develop dependency and experience withdrawal when the drug use is eliminated or reduced. While there are some reports of nootropic users experiencing brain fog after use is discontinued, these side effects are not considered to be akin to withdrawal effects of addiction-forming drugs.[7]

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.[21][22][23] It also may improve task saliency and performance on tedious tasks.[25] At above optimal doses, methylphenidate had off–target effects that decreased learning.[26]