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.
12:18 PM. (There are/were just 2 Adderall left now.) I manage to spend almost the entire afternoon single-mindedly concentrating on transcribing two parts of a 1996 Toshio Okada interview (it was very long, and the formatting more challenging than expected), which is strong evidence for Adderall, although I did feel fairly hungry while doing it. I don’t go to bed until midnight and & sleep very poorly - despite taking triple my usual melatonin! Inasmuch as I’m already fairly sure that Adderall damages my sleep, this makes me even more confident (>80%). When I grumpily crawl out of bed and check: it’s Adderall. (One Adderall left.)
So, I thought I might as well experiment since I have it. I put the 23 remaining pills into gel capsules with brown rice as filling, made ~30 placebo capsules, and will use the one-bag blinding/randomization method. I don’t want to spend the time it would take to n-back every day, so I will simply look for an effect on my daily mood/productivity self-rating; hopefully Noopept will add a little on average above and beyond my existing practices like caffeine+piracetam (yes, Noopept may be as good as piracetam, but since I still have a ton of piracetam from my 3kg order, I am primarily interested in whether Noopept adds onto piracetam rather than replaces). 10mg doses seem to be on the low side for Noopept users, weakening the effect, but on the other hand, if I were to take 2 capsules at a time, then I’d halve the sample size; it’s not clear what is the optimal tradeoff between dose and n for statistical power.
Get plenty of sleep. It can be a real challenge to get seven to nine hours of restful sleep each night with a busy fulltime work schedule, but rest is essential to optimum brain functioning! A healthy nootropic pill can help to clear up brain fog and sharpen your concentration, but it cannot work miracles. If you are trying to power through on four to five hours of sleep each night, nothing is going to cut it.
Of course the idea behind mind hacking isn't exactly new. Sir Francis Bacon consumed everything from tobacco to saffron in the hope of goosing his brain. Balzac reputedly fuelled 16-hour bouts of writing with copious servings of coffee, which, he wrote, "chases away sleep and gives us the capacity to engage a little longer in the exercise of our intellects". Sartre dosed himself with speed in order to finish Critique of Dialectical Reason. Seltzer and his interlocutors on the ImmInst forum are just the latest members of a seasoned cohort, even if they have more complex pharmaceuticals at their disposal.
For example, prenatal exposure to pthalates, which are chemical compounds that are commonly added to plastics to increase their durability and flexibility, have been linked tobehavioural abnormalities characterised by shortened attention span and impaired social interaction. Pthalates are an extensive group of chemicals, and whilst not all of them have been studied, several have shown to have negative health impacts. This class of chemicals is found abundantly and can find they can find their way into food packaging, cosmetics and household cleaners - making them virtually impossible to avoid. However, a growing awareness about the potential negative impact on health has led to the production of pthalate-free cosmetic and personal care products, as well as cleaning products. It may, therefore, be a significant step to try to avoid these chemicals by choosing products wisely, as well as trying to buy vegetables, fruit etc that haven’t been wrapped in plastic.
Mosconi clarifies a few concepts. Other authors have advanced that the brain needs fat, including saturated fat, and cholesterol to function properly. Not so, Mosconi indicates that the fats we eat (saturated fat from animal protein) and cholesterol can’t even cross the blood-brain barrier. The brain needs a completely different type of fat: essential Polyunsaturated Fatty Acids (PUFAs). They include Omega-3s and Omega-6s fatty acids. Good sources of Omega-3s include fish, oils, eggs.
The blood half-life is 12-36 hours; hence two or three days ought to be enough to build up and wash out. A week-long block is reasonable since that gives 5 days for effects to manifest, although month-long blocks would not be a bad choice either. (I prefer blocks which fit in round periods because it makes self-experiments easier to run if the blocks fit in normal time-cycles like day/week/month. The most useless self-experiment is the one abandoned halfway.)
In this large population-based cohort, we saw consistent robust associations between cola consumption and low BMD in women. The consistency of pattern across cola types and after adjustment for potential confounding variables, including calcium intake, supports the likelihood that this is not due to displacement of milk or other healthy beverages in the diet. The major differences between cola and other carbonated beverages are caffeine, phosphoric acid, and cola extract. Although caffeine likely contributes to lower BMD, the result also observed for decaffeinated cola, the lack of difference in total caffeine intake across cola intake groups, and the lack of attenuation after adjustment for caffeine content suggest that caffeine does not explain these results. A deleterious effect of phosphoric acid has been proposed (26). Cola beverages contain phosphoric acid, whereas other carbonated soft drinks (with some exceptions) do not.
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The evidence? Ritalin is FDA-approved to treat ADHD. It has also been shown to help patients with traumatic brain injury concentrate for longer periods, but does not improve memory in those patients, according to a 2016 meta-analysis of several trials. A study published in 2012 found that low doses of methylphenidate improved cognitive performance, including working memory, in healthy adult volunteers, but high doses impaired cognitive performance and a person’s ability to focus. (Since the brains of teens have been found to be more sensitive to the drug’s effect, it’s possible that methylphenidate in lower doses could have adverse effects on working memory and cognitive functions.)
There are over a thousand websites and hundreds of reference guides chock full of complicated methods for combining many of the compounds you’ve just discovered. There’s a reason for this: the practice of “stacking” nootropics and smart drugs into specific combinations can be far more powerful and efficacious than consuming a single, lonely compound in isolation. For example, dosing choline sources with your morning coffee can make your brain feel fresh for hours or mixing curcumin with black pepper can dramatically amp up the neural anti-inflammatory effects of both compounds. Ultimately, a teaspoon of lion’s mane extract just isn’t as titillating as lion’s mane blended with caffeine, theanine, nicotine and a touch of vinpocetine.
A randomized non-blind self-experiment of LLLT 2014-2015 yields a causal effect which is several times smaller than a correlative analysis and non-statistically-significant/very weak Bayesian evidence for a positive effect. This suggests that the earlier result had been driven primarily by reverse causation, and that my LLLT usage has little or no benefits.
To thwart the rise of non-prescription nootropics, opponents may rally for increased regulation; however, at present, there is insufficient research available to support that non-prescription nootropics pose a danger to public health. Prescription nootropics, such as Ritalin, are already regulated. Further, these drugs have a proven beneficial treatment purpose for intended users.
Using neuroenhancers, Seltzer said, "is like customising yourself - customising your brain". For some people, he added, it was important to enhance their mood, so they took antidepressants; but for people like him it was more important "to increase mental horsepower". He said: "It's fundamentally a choice you're making about how you want to experience consciousness." Whereas the 1990s had been about "the personalisation of technology", this decade was about the personalisation of the brain - what some enthusiasts have begun to call "mind hacking".
As you are no doubt well aware, coffee and cigarettes have long been a popular combination. Ah, nostalgia. Just think back to the 1950’s and the man in the suit perfectly pairing his black brew with a cigarette hanging out the corner of his mouth as he enjoyed the Sunday paper or rocked on a lazy afternoon out on the family patio. Heck, there’s even a movie called “Coffee and Cigarettes” and a song called “Cigarettes & Coffee” (in the former, you can see Bill Murray, Tom Waits, Steve Buscemi and Cate Blanchett partaking in their fair share of smoking and sipping).
Nootrobox co-founder Geoffrey Woo declines a caffeinated drink in favour of a capsule of his newest product when I meet him in a San Francisco coffee shop. The entire industry has a “wild west” aura about it, he tells me, and Nootrobox wants to fix it by pushing for “smarter regulation” so safe and effective drugs that are currently unclassified can be brought into the fold. Predictably, both companies stress the higher goal of pushing forward human cognition. “I am trying to make a smarter, better populace to solve all the problems we have created,” says Nootroo founder Eric Matzner.
My worry about the MP variable is that, plausible or not, it does seem relatively weak against manipulation; other variables I could look at, like arbtt window-tracking of how I spend my computer time, # or size of edits to my files, or spaced repetition performance, would be harder to manipulate. If it’s all due to MP, then if I remove the MP and LLLT variables, and summarize all the other variables with factor analysis into 2 or 3 variables, then I should see no increases in them when I put LLLT back in and look for a correlation between the factors & LLLT with a multivariate regression.
A picture is worth a thousand words, particularly in this case where there seems to be temporal effects, different trends for the conditions, and general confusion. So, I drag up 2.5 years of MP data (for context), plot all the data, color by magnesium/non-magnesium, and fit different LOESS lines to each as a sort of smoothed average (since categorical data is hard to interpret as a bunch of dots), which yields:
But how to blind myself? I used my pill maker to make 9 OO pills of piracetam mix, and then 9 OO pills of piracetam mix+the Adderall, then I put them in a baggy. The idea is that I can blind myself as to what pill I am taking that day since at the end of the day, I can just look in the baggy and see whether a placebo or Adderall pill is missing: the big capsules are transparent so I can see whether there is a crushed-up blue Adderall in the end or not. If there are fewer Adderall than placebo, I took an Adderall, and vice-versa. Now, since I am checking at the end of each day, I also need to remove or add the opposite pill to maintain the ratio and make it easy to check the next day; more importantly I need to replace or remove a pill, because otherwise the odds will be skewed and I will know how they are skewed. (Imagine I started with 4 Adderalls and 4 placebos, and then 3 days in a row I draw placebos but I don’t add or remove any pills; the next day, because most of the placebos have been used up, there’s only a small chance I will get a placebo…)
These brain enhancers allow users to go without sleep for extended periods of time. But in the long-term, insomnia is a hazardous side effect, not a so-called benefit. Lack of sleep is extremely detrimental to your brain health and function. It’s during sleep that your brain consolidates memories, cleans away toxins, repairs itself, and creates new brain cells. (52, 53, 54, 55)
Eliminating foggy-headedness seems to be the goal of many users of neuroenhancers. But can today's drugs actually accomplish this? I recently posed this question to Chatterjee's colleague Martha Farah, who is a psychologist at Penn and the director of its Center for Cognitive Neuroscience. She is deeply fascinated by, and mildly critical of, neuroenhancers, but basically in favour - with the important caveat that we need to know much more about how these drugs work. While Farah does not take neuroenhancers, she had just finished a paper in which she reviewed the evidence on prescription stimulants as neuroenhancers from 40 laboratory studies involving healthy subjects. Most of the studies looked at one of three types of cognition: learning, working memory, and cognitive control. A typical learning test asks subjects to memorise a list of paired words; an hour, a few days, or a week later, they are presented with the first words in the pairs and asked to come up with the second. Neuroenhancers did improve retention, especially where subjects had been asked to remember information for several days or longer.
Jump up ^ Weyandt LL, Oster DR, Marraccini ME, Gudmundsdottir BG, Munro BA, Zavras BM, Kuhar B (September 2014). "Pharmacological interventions for adolescents and adults with ADHD: stimulant and nonstimulant medications and misuse of prescription stimulants". Psychol. Res. Behav. Manag. 7: 223–249. doi:10.2147/PRBM.S47013. PMC 4164338. PMID 25228824.