Caffeine dose dependently decreased the 1,25(OH)(2)D(3) induced VDR expression and at concentrations of 1 and 10mM, VDR expression was decreased by about 50-70%, respectively. In addition, the 1,25(OH)(2)D(3) induced alkaline phosphatase activity was also reduced at similar doses thus affecting the osteoblastic function. The basal ALP activity was not affected with increasing doses of caffeine. Overall, our results suggest that caffeine affects 1,25(OH)(2)D(3) stimulated VDR protein expression and 1,25(OH)(2)D(3) mediated actions in human osteoblast cells.

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.
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.
Professor David O Kennedy published a book in 2014 called Plants and the Human Brain. In his book he summarizes the last 15 years of research into cognitive nutrition, including the work he's done with colleagues at the Brain Performance Nutrition Research Center at Northumbria University. It's a great read and a good guide to what sorts of herbs and other plants to include in our weekly diet and it is all based on hard science rather than mere assertion or trendy but unsubstantiated beliefs.
Often her language is not that of a scientist. She uses buzzwords like detoxification and boosting the immune system. She avoids GMOs and things that she thinks are unnatural like “manufactured” minerals and salts. She says she takes royal jelly daily for its natural antibiotic effects; she says these effects are “known, but perhaps not scientifically confirmed.” If not scientifically confirmed, how are the effects “known”? She says plants produce phytonutrients to increase their life span, and then she leaps to the conclusion that humans will derive the same benefits from eating the plants.
If you’re a coffee or tea drinker, keep sipping: Caffeine may help protect against age-related cognitive decline. “Studies have indicated that caffeine—for example, roughly 500 milligrams daily, the equivalent of about five cups of coffee—may help stave off memory issues in humans,” says Bruce Citron, PhD, a neuroscientist at Bay Pines VA Healthcare System and the USF Morsani College of Medicine in Florida. (Experts warn against taking caffeine supplements, which flood your body with a lot of caffeine all at once.)
In avoiding experimenting with more Russian Noopept pills and using instead the easily-purchased powder form of Noopept, there are two opposing considerations: Russian Noopept is reportedly the best, so we might expect anything I buy online to be weaker or impure or inferior somehow and the effect size smaller than in the pilot experiment; but by buying my own supply & using powder I can double or triple the dose to 20mg or 30mg (to compensate for the original under-dosing of 10mg) and so the effect size larger than in the pilot experiment.
Flaxseed oil is, ounce for ounce, about as expensive as fish oil, and also must be refrigerated and goes bad within months anyway. Flax seeds on the other hand, do not go bad within months, and cost dollars per pound. Various resources I found online estimated that the ALA component of human-edible flaxseed to be around 20% So Amazon’s 6lbs for $14 is ~1.2lbs of ALA, compared to 16fl-oz of fish oil weighing ~1lb and costing ~$17, while also keeping better and being a calorically useful part of my diet. The flaxseeds can be ground in an ordinary food processor or coffee grinder. It’s not a hugely impressive cost-savings, but I think it’s worth trying when I run out of fish oil.
Blinding stymied me for a few months since the nasty taste was unmistakable and I couldn’t think of any gums with a similar flavor to serve as placebo. (The nasty taste does not seem to be due to the nicotine despite what one might expect; Vaniver plausibly suggested the bad taste might be intended to prevent over-consumption, but nothing in the Habitrol ingredient list seemed to be noted for its bad taste, and a number of ingredients were sweetening sugars of various sorts. So I couldn’t simply flavor some gum.)
Even party drugs are going to work: Biohackers are taking recreational drugs like LSD, psilocybin mushrooms, and mescaline in microdoses—about a tenth of what constitutes a typical dose—with the goal of becoming more focused and creative. Many who’ve tried it report positive results, but real research on the practice—and its safety—is a long way off. “Whether microdosing with LSD improves creativity and cognition remains to be determined in an objective experiment using double-blind, placebo-controlled methodology,” Sahakian says.
The effects of piracetam on healthy volunteers have been studied even less than those of Adderall or modafinil. Most peer-reviewed studies focus on its effects on dementia or on people who have suffered a seizure or a concussion. Many of the studies that look at other neurological effects were performed on rats and mice. Piracetam's mechanisms of action are not understood, though it may increase levels of the neurotransmitter acetylcholine. In 2008 a committee of the British Academy of Medical Sciences noted that many of the clinical trials of piracetam for dementia were methodologically flawed. Another published review of the available studies of the drug concluded that the evidence "does not support the use of piracetam in the treatment of people with dementia or cognitive impairment", but suggested that further investigation might be warranted. I asked Seltzer if he thought he should wait for scientific ratification of piracetam. He laughed. "I don't want to," he said. "Because it's working."
Microdosing with LSD: LSD (lysergic acid diethylamide) is derived from a chemical in rye fungus. It was originally synthesized in 1938 to aid in childbirth and is widely known for its powerful hallucinogenic effects, but less well known for what I personally use it for: inducing intense sparks of creativity when a merging of the left and right brain hemispheres is the desired goal, such as a day on which I need to do a great deal of creative writing or copywriting. It also works quite well for keeping you “chugging along” on a sleep deprived or jet-lagged day. Similar to psilocybin, LSD affects serotonin levels in the body. By deactivating serotonin mechanisms, brain levels of serotonin are dramatically increased after a dose of LSD, which also causes a “feel good” dopamine release. It is thought that LSD may reduce the blood flow to the control centers of the brain, which weaken their activity, allowing for a heightened brain connection. This enhancement in brain connectivity is most likely why users experience increased creativity and unique thought patterns. Therapeutic effects of LSD include treating addiction, depression, anxiety, obsessive-compulsive disorder, cluster headaches, end-of-life anxiety, resistant behavior change, and increase reaction time, concentration, balance, mood, and pain perception (See additional studies here, here, here, here, here, here, here and here). A typical microdose of LSD is between 5 and 20 micrograms. My own approach for using LSD is quite simple and is called the “volumetric dosing” method. I purchase a blotter paper of LSD or P-LSD, then cut out 100 micrograms with scissors and drop one square tab into a 10-milliliter dropper bottle of vodka. I then know that a single drop of the liquid contains a neat 10 micrograms of LSD, and don’t risk the inaccurate dosing so notoriously associated with simply cutting out and placing the blotter paper into the mouth. Interestingly, I’ve found that if you take slightly too much LSD, a small dose of CBD (e.g. 10-20 milligrams) seems to knock the edge off.

According to the official website, Cognizin is based on Citicoline, which is a highly beneficial nutrient that’s useful for assisting certain brain functions that are related to mental focus and cognitive processing. What’s more, it’s shown to improve your brain’s metabolism regarding the use of acetylcholine, which is an important neurotransmitter involved in the storage and processing of memory.

More than once I have seen results indicating that high-IQ types benefit the least from random nootropics; nutritional deficits are the premier example, because high-IQ types almost by definition suffer from no major deficiencies like iodine. But a stimulant modafinil may be another such nootropic (see Cognitive effects of modafinil in student volunteers may depend on IQ, Randall et al 2005), which mentions:
Too much caffeine may be bad for bone health because it can deplete calcium. Overdoing the caffeine also may affect the vitamin D in your body, which plays a critical role in your body’s bone metabolism. However, the roles of vitamin D as well as caffeine in the development of osteoporosis continue to be a source of debate. Significance: Caffeine may interfere with your body’s metabolism of vitamin D, according to a 2007 Journal of Steroid Biochemistry & Molecular Biology study. You have vitamin D receptors, or VDRs, in your osteoblast cells. These large cells are responsible for the mineralization and synthesis of bone in your body. They create a sheet on the surface of your bones. The D receptors are nuclear hormone receptors that control the action of vitamin D-3 by controlling hormone-sensitive gene expression. These receptors are critical to good bone health. For example, a vitamin D metabolism disorder in which these receptors don’t work properly causes rickets.
The first night I was eating some coconut oil, I did my n-backing past 11 PM; normally that damages my scores, but instead I got 66/66/75/88/77% (▁▁▂▇▃) on D4B and did not feel mentally exhausted by the end. The next day, I performed well on the Cambridge mental rotations test. An anecdote, of course, and it may be due to the vitamin D I simultaneously started. Or another day, I was slumped under apathy after a promising start to the day; a dose of fish & coconut oil, and 1 last vitamin D, and I was back to feeling chipper and optimist. Unfortunately I haven’t been testing out coconut oil & vitamin D separately, so who knows which is to thank. But still interesting.

A fancier method of imputation would be multiple imputation using, for example, the R library mice (Multivariate Imputation by Chained Equations) (guide), which will try to impute all missing values in a way which mimicks the internal structure of the data and provide several possible datasets to give us an idea of what the underlying data might have looked like, so we can see how our estimates improve with no missingness & how much of the estimate is now due to the imputation:


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.
While the primary effect of the drug is massive muscle growth the psychological side effects actually improved his sanity by an absurd degree. He went from barely functional to highly productive. When one observes that the decision to not attempt to fulfill one’s CEV at a given moment is a bad decision it follows that all else being equal improved motivation is improved sanity.
The body has its own inherent detoxification pathways that are responsible for packaging and removing heavy metals safely from the system. For example, glutathione is known as the body’s ‘master antioxidant’ and aside from playing an important role in preventing free radicals from causing damage to the body’s cells, it also helps to bind to heavy metals and remove them from the body. Research shows that glutathione levels are lower than normal in those on the autism spectrum, so enhancing levels through the diet may be an effective way to prevent the accumulation of heavy metals. Consuming sulfur-rich foods such as broccoli, cabbage, onions, garlic, kale and cauliflower can boost glutathione levels, as well as milk thistle, which has unique flavonoids that also support glutathione production.
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.
The evidence? In small studies, healthy people taking modafinil showed improved planning and working memory, and better reaction time, spatial planning, and visual pattern recognition. A 2015 meta-analysis claimed that “when more complex assessments are used, modafinil appears to consistently engender enhancement of attention, executive functions, and learning” without affecting a user’s mood. In a study from earlier this year involving 39 male chess players, subjects taking modafinil were found to perform better in chess games played against a computer.
Ginkgo Biloba, Bacopa Monnieri, and Lion’s Mane: This particular unique blend boosts mental focus, memory, learning, and cognitive performance while reducing anxiety and depression, and I’ve found that it can significantly boost mental alertness for around six hours at a time without any jitteriness or irritability – or any significant amounts of caffeine. It’s important to allow for a grace period of about 12 weeks before you feel the stack’s full potential, so don’t expect immediate results with this combination.
Because smart drugs like modafinil, nicotine, and Adderall come with drawbacks, I developed my own line of nootropics, including Forbose and SmartMode, that’s safe, widely available, and doesn’t require a prescription. Forskolin, found in Forbose, has been a part of Indian Ayurvedic medicine for thousands of years. In addition to being fun to say, forskolin increases cyclic adenosine monophosphate (cAMP), a molecule essential to learning and memory formation. [8]

(We already saw that too much iodine could poison both adults and children, and of course too little does not help much - iodine would seem to follow a U-curve like most supplements.) The listed doses at iherb.com often are ridiculously large: 10-50mg! These are doses that seems to actually be dangerous for long-term consumption, and I believe these are doses that are designed to completely suffocate the thyroid gland and prevent it from absorbing any more iodine - which is useful as a short-term radioactive fallout prophylactic, but quite useless from a supplementation standpoint. Fortunately, there are available doses at Fitzgerald 2012’s exact dose, which is roughly the daily RDA: 0.15mg. Even the contrarian materials seem to focus on a modest doubling or tripling of the existing RDA, so the range seems relatively narrow. I’m fairly confident I won’t overshoot if I go with 0.15-1mg, so let’s call this 90%.


…Phenethylamine is intrinsically a stimulant, although it doesn’t last long enough to express this property. In other words, it is rapidly and completely destroyed in the human body. It is only when a number of substituent groups are placed here or there on the molecule that this metabolic fate is avoided and pharmacological activity becomes apparent.
They’re also rich in vitamin B and vitamin C, which aren’t stored in your body and need to be replenished daily. Plus, they have the highest protein and lowest sugar content of any fruit. Not too shabby! Avocados’ creamy texture makes them a smart addition to smoothies and a replacement for fats in baked goods, or try these brain foods in one of these 50 amazing and easy avocado recipes.
Dallas Michael Cyr, a 41-year-old life coach and business mentor in San Diego, California, also says he experienced a mental improvement when he regularly took another product called Qualia Mind, which its makers say enhances focus, energy, mental clarity, memory and even creativity and mood. "One of the biggest things I noticed was it was much more difficult to be distracted," says Cyr, who took the supplements for about six months but felt their effects last longer. While he's naturally great at starting projects and tasks, the product allowed him to be a "great finisher" too, he says.
Choosing to take smart drugs is not an effective or long term solution. Smart drugs may help you study faster or keep you awake longer, but they are not your best option. Most of the ADHD medications are based on an amphetamine structure and they are not healthy for your heart or your liver. Also, by taking smart drugs, you are putting yourself at considerable risk for addiction to these substances.

It is incredibly easy to abuse and become addicted to methylphenidate, and misuse is shockingly prevalent, even among so-called “non-affected” users: with students, biohackers, soccer moms and busy executives popping it – and many of the other smart drugs below – like candy. It’s also not all it’s cracked up to be. Side effects include insomnia, stomach ache, headache and anorexia. Overdoses (which may occur easily as it can be difficult to estimate and regulate dosage) can lead to agitation, hallucinations, psychosis, lethargy, seizures, tachycardia (rapid heart rate), dysrhythmia (irregular heart rhythms), hypertension and hyperthermia. Methylphenidate is particularly hazardous to developing brains, especially those of younger students who are frequently prescribed the drug or who – often in high school and college – use it without a prescription. The prefrontal cortex, located behind the forehead, is responsible for cognition, personality-expression and decision-making, and develops well into the mid-20s, at which point it takes over as the “rational” part of the brain. In the central nervous system, and particularly in the prefrontal cortex, dopamine levels must have a natural rise and fall in order for healthy rational processes (executive control) to develop. By influencing dopamine levels, methylphenidate can negatively impact this healthy cognitive development, especially when it is abused or used too frequently.


To make things more interesting, I think I would like to try randomizing different dosages as well: 12mg, 24mg, and 36mg (1-3 pills); on 5 May 2014, because I wanted to finish up the experiment earlier, I decided to add 2 larger doses of 48 & 60mg (4-5 pills) as options. Then I can include the previous pilot study as 10mg doses, and regress over dose amount.
Similarly, Mehta et al 2000 noted that the positive effects of methylphenidate (40 mg) on spatial working memory performance were greatest in those volunteers with lower baseline working memory capacity. In a study of the effects of ginkgo biloba in healthy young adults, Stough et al 2001 found improved performance in the Trail-Making Test A only in the half with the lower verbal IQ.
2ml is supposed to translate to 24mg, which is a big dose. I do not believe any of the commercial patches go much past that. I asked Wedrifid, whose notes inspired my initial interest, and he was taking perhaps 2-4mg, and expressed astonishment that I might be taking 24mg. (2mg is in line with what I am told by another person - that 2mg was so much that they actually felt a little sick. On the other hand, in one study, the subjects could not reliably distinguish between 1mg and placebo25.) 24mg is particularly troubling in that I weigh ~68kg, and nicotine poisoning and the nicotine LD50 start, for me, at around 68mg of nicotine. (I reflected that the entire jar could be a useful murder weapon, although nicotine presumably would be caught in an autopsy’s toxicology screen; I later learned nicotine was an infamous weapon in the 1800s before any test was developed. It doesn’t seem used anymore, but there are still fatal accidents due to dissolved nicotine.) The upper end of the range, 10mg/kg or 680mg for me, is calculated based on experienced smokers. Something is wrong here - I can’t see why I would have nicotine tolerance comparable to a hardened smoker, inasmuch as my maximum prior exposure was second-hand smoke once in a blue moon. More likely is that either the syringe is misleading me or the seller NicVape sold me something more dilute than 12mg/ml. (I am sure that it’s not simply plain water; when I mix the drops with regular water, I can feel the propylene glycol burning as it goes down.) I would rather not accuse an established and apparently well-liked supplier of fraud, nor would I like to simply shrug and say I have a mysterious tolerance and must experiment with doses closer to the LD50, so the most likely problem is a problem with the syringe. The next day I altered the procedure to sucking up 8ml, squirting out enough fluid to move the meniscus down to 7ml, and then ejecting the rest back into the container. The result was another mild clean stimulation comparable to the previous 1ml days. The next step is to try a completely different measuring device, which doesn’t change either.
So with these 8 results in hand, what do I think? Roughly, I was right 5 of the days and wrong 3 of them. If not for the sleep effect on #4, which is - in a way - cheating (one hopes to detect modafinil due to good effects), the ratio would be 5:4 which is awfully close to a coin-flip. Indeed, a scoring rule ranks my performance at almost identical to a coin flip: -5.49 vs -5.5420. (The bright side is that I didn’t do worse than a coin flip: I was at least calibrated.)
First half at 6 AM; second half at noon. Wrote a short essay I’d been putting off and napped for 1:40 from 9 AM to 10:40. This approach seems to work a little better as far as the aboulia goes. (I also bother to smell my urine this time around - there’s a definite off smell to it.) Nights: 10:02; 8:50; 10:40; 7:38 (2 bad nights of nasal infections); 8:28; 8:20; 8:43 (▆▃█▁▂▂▃).
Smart drugs offer significant memory enhancing benefits. Clinical studies of the best memory pills have shown gains to focus and memory. Individuals seek the best quality supplements to perform better for higher grades in college courses or become more efficient, productive, and focused at work for career advancement. It is important to choose a high quality supplement to get the results you want.
One thing I did do was piggyback on my Noopept self-experiment: I blinded & randomized the Noopept for a real experiment, but simply made sure to vary the Magtein without worrying about blinding or randomizing it. (The powder is quite bulky.) The correlation the experiment turned in was a odds-ratio of 1.9; interesting and in the right direction (higher is better), but since the magnesium part wasn’t random or blind, not a causal result.
Barbara Sahakian, a neuroscientist at Cambridge University, doesn’t dismiss the possibility of nootropics to enhance cognitive function in healthy people. She would like to see society think about what might be considered acceptable use and where it draws the line – for example, young people whose brains are still developing. But she also points out a big problem: long-term safety studies in healthy people have never been done. Most efficacy studies have only been short-term. “Proving safety and efficacy is needed,” she says.
"More and more of our young people are using these drugs to help them work. They've got their laptop, their iPhone, and their Adderall. This rising generation of workers and leaders may have a subtly different style of thinking and working, because they're using these drugs or because they learned to work using these drugs, so that even if you take the drugs away they'll still have a certain approach. I'm a little concerned that we could be raising a generation of very focused accountants."
Cognizin– this is a derivative of citicoline. It increases* the levels of acetylcholine neurotransmitters, dopamine, and noradrenaline in the brain. These are neurotransmitters essential for brain functioning. Besides this, Cognizin maintains the functioning and stamina of neuronal cell membranes and enhance* energy production from the frontal cortex. With this, you will have increased mental reaction time, expanded focusing ability, improved* immediate and short-term verbal memory and augment the brain’s metabolism.

Beans. Beans are "under-recognized" and "economical," says Kulze. They also stabilize glucose (blood sugar) levels. The brain is dependent on glucose for fuel, Kulze explains, and since it can't store the glucose, it relies on a steady stream of energy -- which beans can provide. Any beans will do, says Kulze, but she is especially partial to lentils and black beans and recommends 1/2 cup every day.
Of course, as you can probably imagine, the antioxidant content of coffee (which you’ll learn how to maximize below) may not be the only smoking savior here. And no, it’s not the tobacco and nasty chemicals in a cigarette that’s working the magic: as other studies have gone on to prove, it’s the nicotine folks – and the nicotine is pretty powerful stuff, not only enhancing locomotor and cognitive performance when combined with coffee but also ramping up exercise performance by 18-21% all on its own!
Eugeroics (armodafinil and modafinil) – are classified as "wakefulness promoting" agents; modafinil increased alertness, particularly in sleep deprived individuals, and was noted to facilitate reasoning and problem solving in non-ADHD youth.[23] In a systematic review of small, preliminary studies where the effects of modafinil were examined, when simple psychometric assessments were considered, modafinil intake appeared to enhance executive function.[27] Modafinil does not produce improvements in mood or motivation in sleep deprived or non-sleep deprived individuals.[28]
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