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.
Somewhat ironically given the stereotypes, while I was in college I dabbled very little in nootropics, sticking to melatonin and tea. Since then I have come to find nootropics useful, and intellectually interesting: they shed light on issues in philosophy of biology & evolution, argue against naive psychological dualism and for materialism, offer cases in point on the history of technology & civilization or recent psychology theories about addiction & willpower, challenge our understanding of the validity of statistics and psychology - where they don’t offer nifty little problems in statistics and economics themselves, and are excellent fodder for the young Quantified Self movement4; modafinil itself demonstrates the little-known fact that sleep has no accepted evolutionary explanation. (The hard drugs also have more ramifications than one might expect: how can one understand the history of Southeast Asia and the Vietnamese War without reference to heroin, or more contemporaneously, how can one understand the lasting appeal of the Taliban in Afghanistan and the unpopularity & corruption of the central government without reference to the Taliban’s frequent anti-drug campaigns or the drug-funded warlords of the Northern Alliance?)
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.
There are a number of treatments for the last. I already use melatonin. I sort of have light therapy from a full-spectrum fluorescent desk lamp. But I get very little sunlight; the surprising thing would be if I didn’t have a vitamin D deficiency. And vitamin D deficiencies have been linked with all sorts of interesting things like near-sightedness, with time outdoors inversely correlating with myopia and not reading or near-work time. (It has been claimed that caffeine interferes with vitamin D absorption and so people like me especially need to take vitamin D, on top of the deficits caused by our vampiric habits, but I don’t think this is true35.) Unfortunately, there’s not very good evidence that vitamin D supplementation helps with mood/SAD/depression: there’s ~6 small RCTs with some findings of benefits, with their respective meta-analysis turning in a positive but currently non-statistically-significant result. Better confirmed is reducing all-cause mortality in elderly people (see, in order of increasing comprehensiveness: Evidence Syntheses 2013, Chung et al 2009, Autier & Gandini 2007, Bolland et al 2014).
I follow Jesus and use nootropics to help me glorify God with my mind. Many conservative Christians would say that micro-dosing on LSD is a sin because it is somewhat mind altering and we are called to be sober-minded (1 Peter 5:8). I am just curious. I have a follow Christian brother who uses cannabis as a supplement to help him do work on a daily basis..yet I worry about him sometimes because his tolerance is so high. It’s a grey area for sure because the Bible isn’t explicit about the topic.

Even the best of today’s nootropics only just barely scratch the surface. You might say that we are in the “Nokia 1100” phase of taking nootropics, and as better tools and more data come along, the leading thinkers in the space see a powerful future. For example, they are already beginning to look past biochemistry to the epigenome. Not only is the epigenome the code that runs much of your native biochemistry, we now know that experiences in life can be recorded in your epigenome and then passed onto future generations. There is every reason to believe that you are currently running epigenetic code that you inherited from your great-grandmother’s life experiences. And there is every reason to believe that the epigenome can be hacked – that the nootropics of the future can not only support and enhance our biochemistry, but can permanently change the epigenetic code that drives that biochemistry and that we pass onto our children.
(As I was doing this, I reflected how modafinil is such a pure example of the money-time tradeoff. It’s not that you pay someone else to do something for you, which necessarily they will do in a way different from you; nor is it that you have exchanged money to free yourself of a burden of some future time-investment; nor have you paid money for a speculative return of time later in life like with many medical expenses or supplements. Rather, you have paid for 8 hours today of your own time.)
Sun: This is a day I devote to spiritual disciplines and deep personal exploration, along with a hefty dose of neurogenesis, and for a day such as this, I’ll use a more potent neuron sprouting and ego-dissolving mix – most notably a blend of psilocybin microdose with Lion’s Mane extract and niacin (if the skin flush and increased blood flow from niacin tends to be too much for you, you can also use “nicotinamide riboside”, a form of vitamin B3 that has similar effects without the flushing).
One thing I notice looking at the data is that the red magnesium-free days seem to dominate the upper ranks towards the end, and blues appear mostly at the bottom, although this is a little hard to see because good days in general start to become sparse towards the end. Now, why would days start to be worse towards the end, and magnesium-dose days in particular? The grim surmise is: an accumulating overdose - no immediate acute effect, but the magnesium builds up, dragging down all days, but especially magnesium-dose days. The generally recognized symptoms of hypermagnesemia don’t include effect on mood or cognition, aside from muscle weakness, confusion, and decreased reflexes…poor appetite that does not improve, but it seems plausible that below medically-recognizable levels of distress like hypermagnesemia might still cause mental changes, and I wouldn’t expect any psychological research to have been done on this topic.
At dose #9, I’ve decided to give up on kratom. It is possible that it is helping me in some way that careful testing (eg. dual n-back over weeks) would reveal, but I don’t have a strong belief that kratom would help me (I seem to benefit more from stimulants, and I’m not clear on how an opiate-bearer like kratom could stimulate me). So I have no reason to do careful testing. Oh well.

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.
[…] 2. Blueberries: Also called “brainberries” by Dr. Steven Platt, MD author of Superfoods Rx: Fourteen Foods Proven to Change Your Life, blueberries have one of the highest antioxidant capacities of all fruits and vegetables and are known to improve memory and cognitive function. They have memory-protecting properties and have even been associated with the prevention of Alzheimer’s disease. Add some blueberries to your breakfast and you may not need to check that to-do list several times throughout the day. Also Read The 7 Best Brain Boosting Supplements […]
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).
By the way, since I’ll throw around the term a few more times in this article, I should probably clarify what an adaptogen actually is. The actual name adaptogen gives some hint as to what these fascinating compounds do: they help you to adapt, specifically by stimulating a physiological adaptive response to some mild, hormesis-like stressor. A process known as general adaptation syndrome (GAS) was first described by the 20th-century physician and organic chemist Hans Selye, who defined GAS as the body’s response to the demands placed upon it. When these demands are excessive and consistent, it can result in the common deleterious symptoms now associated with long-term exposure to chronic stress. GAS is comprised of an alarm stage (characterized by a burst of energy), a resistance stage (characterized by resistance or adaptation to the stressor), and – in the case of excessive and chronic stress – an exhaustion stage (characterized by energy depletion). Adaptogens are plant-derived compounds capable of modulating these phases of GAS by either downregulating stress reactions in the alarm phase or inhibiting the onset of the exhaustion phase, thus providing some degree of protection against damage from stress.
However, normally when you hear the term nootropic kicked around, people really mean a “cognitive enhancer” — something that does benefit thinking in some way (improved memory, faster speed-of-processing, increased concentration, or a combination of these, etc.), but might not meet the more rigorous definition above.  “Smart drugs” is another largely-interchangeable term.
Forums including reddit.com/r/Nootropics/ have more than 140,000 subscribers discussing products with names like Orange Brainwash and GodMode. Nootropics are blends of ingredients touted as a low-risk way to enhance learning, memory, motivation, and even serenity. These ingredients range from herbs such as water hyssop (Bacopa monnieri) and arctic root to chemicals such as vinpocetine.
She reveals where she went astray. In a lecture she gave, she lamented the failure of science to offer a cure for Alzheimer’s or even an effective treatment. Someone in the audience asked, “How about olive oil?” She realized she didn’t know anything about the effects of nutrition on Alzheimer’s. She seems to have assumed that diet must be crucially important, and for some reason instead of studying conventional nutrition science, she got a degree in Holistic Nutrition. She bills herself as a certified Integrative Nutritionist and holistic healthcare practitioner. I couldn’t find where she studied, but Stephen Barrett has criticized the Institute for Integrative Nutrition on Quackwatch. Its training is not based on scientific nutrition. It seems most programs in Integrative Nutrition are 6- to 8-month correspondence courses with no prerequisites. I wonder what she was taught.
But what does this all have to do with food? Our gut helps keep our body’s immune responses and inflammation under control. Additionally, gut hormones that enter the brain or are produced in the brain influence cognitive ability, like understanding and processing new information, staying focused on the task at hand and recognizing when we’re full. (3)
Gibson and Green (2002), talking about a possible link between glucose and cognition, wrote that research in the area …is based on the assumption that, since glucose is the major source of fuel for the brain, alterations in plasma levels of glucose will result in alterations in brain levels of glucose, and thus neuronal function. However, the strength of this notion lies in its common-sense plausibility, not in scientific evidence… (p. 185).
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.
After 7 days, I ordered a kg of choline bitartrate from Bulk Powders. Choline is standard among piracetam-users because it is pretty universally supported by anecdotes about piracetam headaches, has support in rat/mice experiments28, and also some human-related research. So I figured I couldn’t fairly test piracetam without some regular choline - the eggs might not be enough, might be the wrong kind, etc. It has a quite distinctly fishy smell, but the actual taste is more citrus-y, and it seems to neutralize the piracetam taste in tea (which makes things much easier for me).
Feeling behind, I resolved to take some armodafinil the next morning, which I did - but in my hurry I failed to recall that 200mg armodafinil was probably too much to take during the day, with its long half life. As a result, I felt irritated and not that great during the day (possibly aggravated by some caffeine - I wish some studies would be done on the possible interaction of modafinil and caffeine so I knew if I was imagining it or not). Certainly not what I had been hoping for. I went to bed after midnight (half an hour later than usual), and suffered severe insomnia. The time wasn’t entirely wasted as I wrote a short story and figured out how to make nicotine gum placebos during the hours in the dark, but I could have done without the experience. All metrics omitted because it was a day usage.
These days, young, ambitious professionals prefer prescription stimulants—including methylphenidate (usually sold as Ritalin) and Adderall—that are designed to treat people with attention deficit hyperactivity disorder (ADHD) and are more common and more acceptable than cocaine or nicotine (although there is a black market for these pills). ADHD makes people more likely to lose their focus on tasks and to feel restless and impulsive. Diagnoses of the disorder have been rising dramatically over the past few decades—and not just in kids: In 2012, about 16 million Adderall prescriptions were written for adults between the ages of 20 and 39, according to a report in the New York Times. Both methylphenidate and Adderall can improve sustained attention and concentration, says Barbara Sahakian, professor of clinical neuropsychology at the University of Cambridge and author of the 2013 book Bad Moves: How Decision Making Goes Wrong, and the Ethics of Smart Drugs. But the drugs do have side effects, including insomnia, lack of appetite, mood swings, and—in extreme cases—hallucinations, especially when taken in amounts the exceed standard doses. Take a look at these 10 foods that help you focus.
Began double-blind trial. Today I took one pill blindly at 1:53 PM. at the end of the day when I have written down my impressions and guess whether it was one of the Adderall pills, then I can look in the baggy and count and see whether it was. there are many other procedures one can take to blind oneself (have an accomplice mix up a sequence of pills and record what the sequence was; don’t count & see but blindly take a photograph of the pill each day, etc.) Around 3, I begin to wonder whether it was Adderall because I am arguing more than usual on IRC and my heart rate seems a bit high just sitting down. 6 PM: I’ve started to think it was a placebo. My heart rate is back to normal, I am having difficulty concentrating on long text, and my appetite has shown up for dinner (although I didn’t have lunch, I don’t think I had lunch yesterday and yesterday the hunger didn’t show up until past 7). Productivity wise, it has been a normal day. All in all, I’m not too sure, but I think I’d guess it was Adderall with 40% confidence (another way of saying placebo with 60% confidence). When I go to examine the baggie at 8:20 PM, I find out… it was an Adderall pill after all. Oh dear. One little strike against Adderall that I guessed wrong. It may be that the problem is that I am intrinsically a little worse today (normal variation? come down from Adderall?).
After 7 days, I ordered a kg of choline bitartrate from Bulk Powders. Choline is standard among piracetam-users because it is pretty universally supported by anecdotes about piracetam headaches, has support in rat/mice experiments28, and also some human-related research. So I figured I couldn’t fairly test piracetam without some regular choline - the eggs might not be enough, might be the wrong kind, etc. It has a quite distinctly fishy smell, but the actual taste is more citrus-y, and it seems to neutralize the piracetam taste in tea (which makes things much easier for me).
Reason: Vitamin B12 supports brain health in critical ways. The water-soluble B vitamin helps the body convert carbohydrates and fats into energy the brain needs to function properly. It also helps reduce the brain shrinkage often associated with cognitive disorders, supports healthy sleep-wake cycles (incredibly important, given what we now know about sleep and Alzheimer’s risk), and aids the proper “firing” of communications between neurons.
Creatine is a substance that’s produced in the human body. It is initially produced in the kidneys, and the process is completed in the liver. It is then stored in the brain tissues and muscles, to support the energy demands of a human body. Athletes and bodybuilders take creatine supplements for relieving fatigue and increasing the recovery of the muscle tissues that are affected by vigorous physical activities. Apart from helping the tissues to recover faster, creatine also helps in enhancing the mental functions in sleep-deprived adults and it also improves the performance of difficult cognitive tasks.
One curious thing that leaps out looking at the graphs is that the estimated underlying standard deviations differ: the nicotine days have a strikingly large standard deviation, indicating greater variability in scores - both higher and lower, since the means weren’t very different. The difference in standard deviations is just 6.6% below 0, so the difference almost reaches our usual frequentist levels of confidence too, which we can verify by testing:
A constituent of the turmeric spice, curcumin was first discovered for its brain health benefits when epidemiological studies revealed those in regions with a high consumption of the curry spice turmeric had fewer reported cases of cognitive diseases. It is theorized that the unmatched anti-inflammatory power of curcumin, in combination with its unique antioxidant make-up, inhibits the formation of amyloid build up in the brain.
I took the pill at 11 PM the evening of (technically, the day before); that day was a little low on sleep than usual, since I had woken up an hour or half-hour early. I didn’t yawn at all during the movie (merely mediocre to my eyes with some questionable parts)23. It worked much the same as it did the previous time - as I walked around at 5 AM or so, I felt perfectly alert. I made good use of the hours and wrote up my memories of ICON 2011.

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.
Dr Hart explained how communication between the gut and the brain is controlled via our immune system, our endocrine system (hormones) and our central nervous system, which are all under the influence of the bacteria in our gut. The types and amount of these bacteria, known as our gut microbiome, can be directly impacted by factors such as diet, stress, pollution and medications (2) and the composition of the microbiome is also understood to affect one’s susceptibility to food sensitivities and intolerances (3).  
Dr Hart talked through food intolerance tests that are available through a number of well known companies, including York Test for whom she is Scientific Director. A possible strategy could be to use such testing to identify intolerances, follow an elimination protocol, temporarily removing on foods triggering an IgG response; and then work to improve your gut health to support longer term well-being. Foods that are rich in collagen and its amino acids, like glycine and proline, are great for healing connective tissue, which is what the intestines are made up of. A traditional food, rich in these amino acids, that has made its way into our kitchens again after rediscovering its therapeutic properties is bone broth. Another example of a group of traditional foods that can be used therapeutically in building digestive health, are fermented foods such as kefir, sauerkraut and kimchi. These are abundant in probiotics, which are the ‘good’ bacteria our digestive system needs to help keep a good balance and protect the intestinal barrier from pathogens, toxins and parasites. Once these foods have been introduced on an everyday basis along with eating a healthy nutrient-dense diet and the possible use of supplements to help restore balance, you may be able to reintroduce foods that were previously triggering an IgG response carefully, one at a time, whilst monitoring symptoms.
I can test fish oil for mood, since the other claimed benefits like anti-schizophrenia are too hard to test. The medical student trial (Kiecolt-Glaser et al 2011) did not see changes until visit 3, after 3 weeks of supplementation. (Visit 1, 3 weeks, visit 2, supplementation started for 3 weeks, visit 3, supplementation continued 3 weeks, visit 4 etc.) There were no tests in between the test starting week 1 and starting week 3, so I can’t pin it down any further. This suggests randomizing in 2 or 3 week blocks. (For an explanation of blocking, see the footnote in the Zeo page.)
Oxiracetam is one of the 3 most popular -racetams; less popular than piracetam but seems to be more popular than aniracetam. Prices have come down substantially since the early 2000s, and stand at around 1.2g/$ or roughly 50 cents a dose, which was low enough to experiment with; key question, does it stack with piracetam or is it redundant for me? (Oxiracetam can’t compete on price with my piracetam pile stockpile: the latter is now a sunk cost and hence free.)
Legal Disclaimer Do Not exceed recommended dose for Colon Clean. Pregnant or nursing mothers, children under 18, and individuals with a known medical condition should consult a physician before using this or any dietary supplement. Be careful when using supplements with other supplements or prescription pharmaceuticals. This product is not intended to diagnose, treat, cure, or prevent any disease.

She speaks from professional and personal experience. When she first moved to the United States from Italy at age 24 she was struck by how shifting from the Mediterranean-style diet she grew up on to a standard American diet negatively impacted her physical health and work performance. The experience led her to more closely study nutrition and the link between diet and brain health. In this excerpt from a longer interview, she discusses the brain foods you should be eating.
Bacopa Monnieri is probably one of the safest and most effective memory and mood enhancer nootropic available today with the least side-effects. In some humans, a majorly extended use of Bacopa Monnieri can result in nausea. Amongst AlternaScript’s, primary products is Optimind, a nootropic supplement which largely constitutes of Bacopa Monnieri as one of the main ingredients.
Nuts and seeds are terrific sources of vitamin E, which, according to a 2014 study, can help prevent cognitive decline and Alzheimer’s disease as you age. Other vitamin E-rich foods include eggs and cooked veggies. And it’s not just your brain that benefits from nuts; your heart will be happier too. Almonds, walnuts, cashews, Brazil nuts, pistachios, and peanuts have been linked to a decreased risk of cardiovascular disease, according to a Harvard study. Try these other vitamin E-rich foods.

The use of cognition-enhancing drugs by healthy individuals in the absence of a medical indication spans numerous controversial issues, including the ethics and fairness of their use, concerns over adverse effects, and the diversion of prescription drugs for nonmedical uses, among others.[1][2] Nonetheless, the international sales of cognition-enhancing supplements exceeded US$1 billion in 2015 when global demand for these compounds grew.[3]

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