Here’s how it works: Donepezil boosts serotonin and acetylcholine in the brain, chemicals that are usually found in high concentrations in the brains of young children which naturally decrease with age. As a cholinesterase inhibitor, Donezepil boosts brain function by increasing the amount of acetylcholine around nerve endings. In dementia and Alzheimer’s patients, the drug has been shown to improve memory function.
While you may not find yourself mixing an LSD homebrew in your kitchen anytime soon, a bit of better living through science may be exactly what you need to upgrade your productivity, creativity and overall cognitive performance. You’re now equipped with every shred of knowledge necessary to do so, whether you choose a risky smart drug approach, a natural nootropic approach, a synthetic nootropic approach, or a blend of all three.

It’s basic economics: the price of a good must be greater than cost of producing said good, but only under perfect competition will price = cost. Otherwise, the price is simply whatever maximizes profit for the seller. (Bottled water doesn’t really cost $2 to produce.) This can lead to apparently counter-intuitive consequences involving price discrimination & market segmentation - such as damaged goods which are the premium product which has been deliberately degraded and sold for less (some Intel CPUs, some headphones etc.). The most famous examples were railroads; one notable passage by French engineer-economist Jules Dupuit describes the motivation for the conditions in 1849:
The benefit of sequential analysis here is being able to stop early, conserving pills, and letting me test another dosage: if I see another pattern of initial benefits followed by decline, I can then try cutting the dose by taking one pill every 3 days; or, if there is a benefit and no decline, then I can try tweaking the dose up a bit (maybe 3 days out of 5?). Since I don’t have a good idea what dose I want and the optimal dose seems like it could be valuable (and the wrong dose harmful!), I can’t afford to spend a lot of time on a single definitive experiment.
We did note a significant warning with this product, namely that the caffeine it contains may cause a negative impact, mainly that some users may experience the jitters. Their dosage suggests that one can take up to 6 pills a day, which we felt was too many. These issues made us a little wary of the product, even though they seem to know the right ingredients to include.
My impression after the first two days (2 doses of 400mg each, one with breakfast & then lunch) was positive. I did not have the rumored digestion problems, and the first day went excellently: I was up until 1:30AM working and even then didn’t feel like going to bed - and I probably should have since I then slept abominably, which made the second day merely a good day. The third day I took none and it was an ordinary day. This is consistent with what I expected from the LEF l-threonate & TruBrain glycinate/lycinate, and so it is worth investigating with a self-experiment.
1 PM; overall this was a pretty productive day, but I can’t say it was very productive. I would almost say even odds, but for some reason I feel a little more inclined towards modafinil. Say 55%. That night’s sleep was vile: the Zeo says it took me 40 minutes to fall asleep, I only slept 7:37 total, and I woke up 7 times. I’m comfortable taking this as evidence of modafinil (half-life 10 hours, 1 PM to midnight is only 1 full halving), bumping my prediction to 75%. I check, and sure enough - modafinil.

A total of 330 randomly selected Saudi adolescents were included. Anthropometrics were recorded and fasting blood samples were analyzed for routine analysis of fasting glucose, lipid levels, calcium, albumin and phosphorous. Frequency of coffee and tea intake was noted. 25-hydroxyvitamin D levels were measured using enzyme-linked immunosorbent assays…Vitamin D levels were significantly highest among those consuming 9-12 cups of tea/week in all subjects (p-value 0.009) independent of age, gender, BMI, physical activity and sun exposure.
ave you heard of EHT for brain health, memory and focus?, a group out of Princeton, has some rather promising research for brain wellness. Their supplement, EHT, is newly available in the last month. It’s great for memory enhancement, brain health, focus, immune system support and more.

The Lynches said that Provigil was a classic example of a related phenomenon: mission creep. In 1998, Cephalon, the pharmaceutical company that manufactures it, received US government approval to market the drug but only for "excessive daytime sleepiness" due to narcolepsy; by 2004, Cephalon had obtained permission to expand the labelling so that it included sleep apnoea and "shift-work sleep disorder". Net sales of Provigil climbed from $196m in 2002 to $988m in 2008.
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.
70 pairs is 140 blocks; we can drop to 36 pairs or 72 blocks if we accept a power of 0.5/50% chance of reaching significance. (Or we could economize by hoping that the effect size is not 3.5 but maybe twice the pessimistic guess; a d=0.5 at 50% power requires only 12 pairs of 24 blocks.) 70 pairs of blocks of 2 weeks, with 2 pills a day requires (70 \times 2) \times (2 \times 7) \times 2 = 3920 pills. I don’t even have that many empty pills! I have <500; 500 would supply 250 days, which would yield 18 2-week blocks which could give 9 pairs. 9 pairs would give me a power of:
Still, even if you acknowledge that cosmetic neurology is here to stay, there is something dispiriting about the way the drugs are used - the kind of aspirations they open up, or don't. Jonathan Eisen, an evolutionary biologist at the University of California, Davis, is sceptical of what he mockingly calls "brain doping". During a recent conversation, he spoke about colleagues who take neuroenhancers in order to grind out grant proposals. "It's weird to me that people are taking these drugs to write grants," he said. "I mean, if you came up with some really interesting paper that was spurred by taking some really interesting drug - magic mushrooms or something - that would make more sense to me. In the end you're only as good as the ideas you've come up with."

Pop this pill and improve your memory. Swallow that one and reduce your cognitive decline. We see ads for such products all the time and I suspect they will increase as the baby boomers reach senior citizenhood. The most popular brain boosting supplements are fish oil pills and they are also probably the best studied ones. The results are not encouraging. When all the studies are pooled, we are left with the possibility of a barely significant improvement in recalling lists of words soon after they have been learned, but the effect does not last. Extracts of the ginkgo biloba tree are also popular, and here the prospects are even dimmer. There is no impact on memory, despite claims of increased circulation in the brain. And ginkgo can interfere with the action of anticoagulants and has also been shown to be an animal carcinogen.
The powder itself is quite bulky; the recommended dose to hit 200mg of absorbed magnesium leads to ~7g of powder (so capping will be difficult) and the container provides only 30 doses’ worth (or each dose costs $1!). It’s described as lemon-flavored, and it is, but it’s sickly-sweet unpleasant and since it’s so much powder, takes half a glass of water to dissolve it entirely and wash it down. Subjectively, I notice nothing after taking it for a week. I may try a simple A-B-A analysis of sleep or Mnemosyne, but I’m not optimistic. And given the large expense of LEF’s Magtein, it’s probably a non-starter even if there seems to be an effect. For sleep effects, I will have to look at more reasonably priced magnesium sources.
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The fact is, many of these compounds in small amounts and less frequent use can be relatively safe, but as you’re probably not surprised to hear, I’m not 100% convinced of the overall long-term safety or efficacy of most smart drugs used frequently or in moderate to high dosages for the reasons stated above. It is true that some are slightly less risky than others and are increasing in popularity among biohackers and medical professionals. They’re also becoming used with high frequency by students, athletes and e-gamers, three populations for which smart drug “doping control” is becoming more frequently banned and considered to be illegal use of performance-enhancing drugs. Yes, “brain doping” and “brain PED’s” (brain Performance Enhancing Drugs) are now a thing. But I’d consider carefully the use of smart drugs as daily go-to brain enhancing supplements, especially in light of the safer alternative you’re about to discover: the entire category of natural and synthetic nootropic compounds.
Systematic reviews and meta-analyses of clinical human research using low doses of certain central nervous system stimulants found enhanced cognition in healthy people.[21][22][23] In particular, the classes of stimulants that demonstrate cognition-enhancing effects in humans act as direct agonists or indirect agonists of dopamine receptor D1, adrenoceptor A2, or both types of receptor in the prefrontal cortex.[21][22][24][25] Relatively high doses of stimulants cause cognitive deficits.[24][25]