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!
Breathing carefully, I clutched the Costco special edition family size 1.5-liter glass bottle of vodka and carefully extracted 10 milliliters with a miniature glass pipette, which I then transferred into a small amber glass bottle. Then, with my nine-year-old son’s tiny set of school scissors, I snipped exactly 1/10 of LSD from the blotter square I’d ordered from a psychedelic research chemical supplier website the week prior, with a cloaked browser, of course, so the feds didn’t come knocking at my door. I dropped the LSD into the bottle, gave it a thirty-second shake, then placed the bottle in the pantry, next to my protein powder and creatine. I smiled. Within 24 hours, I’d be ready to sample my first homemade, volumetric “microdose” of a drug reported to increase lateral thinking patterns, improve creativity, massively boost productivity and much, much more.
Reason: More than 50 percent of your brain is comprised of DHA! Among a big group of elderly Americans, those with the highest blood levels of DHA were about half as apt to develop dementia and 39% as apt to develop Alzheimer’s as those with lower blood levels of DHA over a nine-year period. The top 25% of those with the highest blood DHA got about 180 mg DHA a day or three servings of fish a week, researchers said. In this study, the other major fatty acid in fish oil. EPA had no effect.
The human drive to be smarter is a familiar theme on the big screen. In 2011, Oscar-nominated actor Bradley Cooper played struggling writer Eddie Morra in the sci-fi thriller Limitless. In the film, Morra acquires a (fictitious) nootropic NZT-48 that allows him to access 100 percent of his mind. Although he finds himself in lots of trouble, his use of the nootropic transforms him from a desperate writer to a multimillionaire who ultimately runs for the U.S. Senate. The film is a testament to a dream deeply entrenched in the American psyche – that an everyman can become superhuman and lead an extraordinary life.
This is not something you notice when you talk to Seltzer. And though our memory is probably at its peak in our early 20s, few 30-year-olds are aware of a deficit. But Seltzer considers himself a transhumanist, in the mould of the Oxford philosopher Nick Bostrom and the futuristic writer and inventor Ray Kurzweil. Transhumanists are interested in robots, cryogenics and living a really, really long time; they consider biological limitations that the rest of us might accept, or even appreciate, as creaky obstacles to be aggressively surmounted. On the ImmInst (Immortality Institute) forums, Seltzer and other members discuss life-extension strategies and the potential benefits of cognitive enhancers. Some members, Seltzer among them, use a drug called piracetam, which was first marketed by a Belgian pharmaceutical company in 1972 and in recent years has become available in the US from retailers that sell supplements. Although not approved for any use by the FDA, piracetam has been used experimentally on stroke patients - to little effect - and on patients with a rare neurological condition called progressive myoclonus epilepsy, for whom it proved helpful in alleviating muscle spasms. Data on piracetam's benefits for healthy people is virtually nonexistent, but many users believe that the drug increases blood flow to the brain.
When asked if there’s a discrepancy between Qualia’s claims and that disclaimer, Dr. Stickler points out that products such as OS aren’t promising to treat or cure any diseases. That’s the line these companies can’t cross. They can claim their product makes you smarter or more focused without data from clinical trials, but they can’t claim their pill treats traumatic brain injury, ADHD, or Alzheimer’s.
A study published in the Journal of Environmental Healths Perspective stated that "researchers, physicians, and others poked around in the dark crevices of the gene, (are) trying to untangle the clues that suggested gene function could be altered by more than just changes in sequence." This ties in perfectly with what Dr. Lisa mentions about how our lifestyles play a crucial role in how/if we manifest a certain cognitive disfunction. Which brings us to our next question: What kind of "brain diet" can help support this lifestyle?

Brain focus pills largely contain chemical components like L-theanine which is naturally found in green and black tea. It’s associated with enhancing alertness, cognition, relaxation, arousal, and reducing anxiety to a large extent.  Theanine is an amino and glutamic acid that has been proven to be a safe psychoactive substance. There are studies that suggest that this compound influences, the expression in the genes present in the brain which is responsible for aggression, fear and memory. This, in turn, helps in balancing the behavioural responses to stress and also helps in improving specific conditions, like Post Traumatic Stress Disorder (PTSD).
Tomatoes - does that include tinned? And what about passata? And while we are at it, are frozen veg as good [or very nearly] as fresh? I'm particularly thinking of green veg like peas, broad beans, green beans. Fresh peas are a seasonal rarity, so are broad beans and green beans in supermarkets are often rather tired after their long trip from Kenya.

The original magnesium l-threonate caused me no apparent problems by the time I finished off the powder and usage correlated with better days, further supporting the hypothesis that magnesium helps it. But l-threonate would be difficult to cap (and hence blind self-experiment) and is ruinously expensive on a per-dose basis. So I looked around for alternatives for the followup; one of the most common compounds suggested was the citrate form because it is reasonably well-absorbed and causes fewer digestive problems, so I could just take that. Magnesium oxide is widely available it looks cheap, but the absorption/bioavailability problem makes it unattractive: at a 3:5 ratio, an estimate of 4% absorption, a ZMA formulation of an impressive-sounding 500mg would be 500 \times \frac{3}{5} \times 0.04 = 12mg or a small fraction of RDAs for male adults like 400mg elemental. (Calcium shouldn’t be a problem since I get 220mg of calcium from my multivitamin and I enjoy dairy products daily.)
The compound has great nootropic properties that includes memory enhancement and protection against brain aging. There are studies that suggest that the compound is an effective treatment for disorders like vascular dementia, Alzheimer’s, brain stroke, anxiety and depression. However, there are some side effects associated with Alpha GPC, like headache, heartburn, dizziness, skin rashes, insomnia, and confusion.
Both nootropics startups provide me with samples to try. In the case of Nootrobox, it is capsules called Sprint designed for a short boost of cognitive enhancement. They contain caffeine – the equivalent of about a cup of coffee, and L-theanine – about 10 times what is in a cup of green tea, in a ratio that is supposed to have a synergistic effect (all the ingredients Nootrobox uses are either regulated as supplements or have a “generally regarded as safe” designation by US authorities)
Cacao contains powerful flavonols, compounds that act as antioxidants and help preserve the brain’s stem cells. “Stem cells produce new brain cells,” says Dennis Steindler, PhD, director of the Neuroscience and Aging Lab at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, “and chronic inflammation or the beginnings of disease can damage these reparative cells and the other at-risk brain cells used for standard operating procedures, like memory and thinking.” Flavonols have also been shown to support the hippocampus, a part of the brain involved in memory and mood, notes Steindler. Stick to a square or two of dark chocolate daily.
However, as a result of the efficacy of this type of stacking, the supplement world is saturated with brain-boosting blends, and it can be difficult to cut through the confusion and figure out what really works and what could be a waste of time and money, or downright dangerous. The fact is, when creating your own stack, you must carefully think about your specific needs and goals. For example, if you want to reduce anxiety and depression, but don’t necessarily care to enhance your cognitive performance or get through a day of work in a sleep-deprived state, you could just stick to a single nootropic that increases dopamine levels, such as Mucuna pruriens or tryptophan. Or if you wanted to reduce anxiety and depression while simultaneously improving your memory because you’re studying for a school or work exam, you could add Bacopa monnieri to the mucuna or tryptophan. Then, let’s say you want long-term cognitive performance to the mix that lasts an entire day: in this case, you’d add a racetam, and to avoid an end of day crash, a touch of choline or DHA. It’s a bit like cooking in the kitchen, isn’t it?
By analyzing the brain images, the team found that these patients, compared with people who weren’t susceptible to the placebo, had a difference in volume between the right and left sides of the limbic system in the brain, which is involved in instinct and mood. There were also differences in the number of nerve cell connections between the prefrontal cortex and other brain areas. Personality questionnaires revealed that these people had a higher self-awareness and openness than nonresponders.
In August 2011, after winning the spaced repetition contest and finishing up the Adderall double-blind testing, I decided the time was right to try nicotine again. I had since learned that e-cigarettes use nicotine dissolved in water, and that nicotine-water was a vastly cheaper source of nicotine than either gum or patches. So I ordered 250ml of water at 12mg/ml (total cost: $18.20). A cigarette apparently delivers around 1mg of nicotine, so half a ml would be a solid dose of nicotine, making that ~500 doses. Plenty to experiment with. The question is, besides the stimulant effect, nicotine also causes habit formation; what habits should I reinforce with nicotine? Exercise, and spaced repetition seem like 2 good targets.
Potassium citrate powder is neither expensive nor cheap: I purchased 453g for $21. The powder is crystalline white, dissolves instantly in water, and largely tasteless (sort of saline & slightly unpleasant). The powder is 37% potassium by weight (the formula is C6H5K3O7) so 453g is actually 167g of potassium, so 80-160 days’ worth depending on dose.
“Brain-berries” is what Steven Pratt, MD, author of SuperFoods Rx: Fourteen Foods That Will Change Your Life, calls these antioxidant-packed fruits on WebMD.com. This tiny but powerful berry helps protect the brain from oxidative stress and may reduce the effects of age-related conditions such as Alzheimer’s disease or dementia. In a recent study, researchers gave a group of adults with mild cognitive impairment, a risk condition for Alzheimer’s, freeze-dried blueberry powder daily, while another group took a placebo. After 16 weeks, those who ate the blueberry powder (the equivalent of one cup of berries) had improved memory, better cognitive performance, and increased brain activity. Your everyday habits may also reduce your risk of Alzheimer’s.
"Instead of messing it up, we should be appreciating something that nature has taken years to optimize," Dr. Lisa mentions. But, we aren't messing it up voluntarily or, at the very least, on any conscious or malicious level. She attributes our disregard for neuro-nutrition to a series of factors, which include the portion size of meals, how parents don't have the time to cook or teach children how to eat healthily, the big influence of cafeteria food, and our "always on the go" culture. According to her, this leads us to unconsciously choose meals which are poor quality and high in sugars, a deathly combination for our brains.
As Sulbutiamine crosses the blood-brain barrier very easily, it has a positive effect on the cholinergic and the glutamatergic receptors that are responsible for vital activities impacting memory, concentration, and mood. The compound is also fat soluble, which means it circulates rapidly and widely throughout the body and the brain, ensuring positive results. Thus, patients with schizophrenia and Parkinson’s disease will find the drug to be very effective.
Nootropics include natural and manmade chemicals that produce cognitive benefits. These substances are used to make smart pills that deliver results for enhancing memory and learning ability, improving brain function, enhancing the firing control mechanisms in neurons, and providing protection for the brain. College students, adult professionals, and elderly people are turning to supplements to get the advantages of nootropic substances for memory, focus, and concentration.

My general impression is positive; it does seem to help with endurance and extended the effect of piracetam+choline, but is not as effective as that combo. At $20 for 30g (bought from Smart Powders), I’m not sure it’s worthwhile, but I think at $10-15 it would probably be worthwhile. Sulbutiamine seems to affect my sleep negatively, like caffeine. I bought 2 or 3 canisters for my third batch of pills along with the theanine. For a few nights in a row, I slept terribly and stayed awake thinking until the wee hours of the morning; eventually I realized it was because I was taking the theanine pills along with the sleep-mix pills, and the only ingredient that was a stimulant in the batch was - sulbutiamine. I cut out the theanine pills at night, and my sleep went back to normal. (While very annoying, this, like the creatine & taekwondo example, does tend to prove to me that sulbutiamine was doing something and it is not pure placebo effect.)
Following up on the promising but unrandomized pilot, I began randomizing my LLLT usage since I worried that more productive days were causing use rather than vice-versa. I began on 2 August 2014, and the last day was 3 March 2015 (n=167); this was twice the sample size I thought I needed, and I stopped, as before, as part of cleaning up (I wanted to know whether to get rid of it or not). The procedure was simple: by noon, I flipped a bit and either did or did not use my LED device; if I was distracted or didn’t get around to randomization by noon, I skipped the day. This was an unblinded experiment because finding a randomized on/off switch is tricky/expensive and it was easier to just start the experiment already. The question is simple too: controlling for the simultaneous blind magnesium experiment & my rare nicotine use (I did not use modafinil during this period or anything else I expect to have major influence), is the pilot correlation of d=0.455 on my daily self-ratings borne out by the experiment?

Sure, you could certainly swallow too much St. John’s Wort and create the same type of serotonin or neurotransmitter issues you could create with a synthetic smart drug, but it’s far more difficult to harm yourself with a nootropic compared to a synthetic smart drug. Although synthetic, laboratory-designed nootropics do indeed exist, even those are not as harsh on the biology as a smart drug and have a mechanism of action that is a bit more natural. Let’s begin with the more natural nootropics.
Manually mixing powders is too annoying, and pre-mixed pills are expensive in bulk. So if I’m not actively experimenting with something, and not yet rich, the best thing is to make my own pills, and if I’m making my own pills, I might as well make a custom formulation using the ones I’ve found personally effective. And since making pills is tedious, I want to not have to do it again for years. 3 years seems like a good interval - 1095 days. Since one is often busy and mayn’t take that day’s pills (there are enough ingredients it has to be multiple pills), it’s safe to round it down to a nice even 1000 days. What sort of hypothetical stack could I make? What do the prices come out to be, and what might we omit in the interests of protecting our pocketbook?
The magnesium was neither randomized nor blinded and included mostly as a covariate to avoid confounding (the Noopept coefficient & t-value increase somewhat without the Magtein variable), so an OR of 1.9 is likely too high; in any case, this experiment was too small to reliably detect any effect (~26% power, see bootstrap power simulation in the magnesium section) so we can’t say too much.
For 2 weeks, upon awakening I took close-up photographs of my right eye. Then I ordered two jars of Life-Extension Sea-Iodine (60x1mg) (1mg being an apparently safe dose), and when it arrived on 10 September 2012, I stopped the photography and began taking 1 iodine pill every other day. I noticed no ill effects (or benefits) after a few weeks and upped the dose to 1 pill daily. After the first jar of 60 pills was used up, I switched to the second jar, and began photography as before for 2 weeks. The photographs were uploaded, cropped by hand in Gimp, and shrunk to more reasonable dimensions; both sets are available in a Zip file.
SOURCES: Ray Sahelian, MD. Psychopharmacology, September 2000. Human Psychopharmacology, July 2001; January 2002. Psychopharmacology Bulletin, Summer 2002. The Cochrane Database of Systematic Reviews, 2002. Archives of Neurology, November 1998. Zhongguo Yao Li Xue Bao, July 1999. Pharmacological Research, September 1999. International Clinical Psychopharmacology, March 2003. FDA web site.
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.)
Apart from the risks that accompany drugs with dopaminergic effects, amphetamines, even when used to treat neurological disorders like ADHD, have been known to frequently and predictably cause anorexia, weight loss and insomnia. High doses can cause psychotic behavior, and even normal doses have been known to produce psychosis that ranged from the loss of short-term memory to horrific visual and auditory hallucinations. Are you getting the impression that using synthetic stimulants to flood your brain short-term with excessive or unnaturally high levels of hormones and neurotransmitters may not be a good idea, especially when done frequently or in excess?
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.
I have lots of problems with procrastination and productivity, most likely due to a mild case of ADHD, and recently it's been getting worse and worse. I was a bit hesitant to take Addium at first because I, like most people, had heard about it as a tool for students to use for cramming and it's results sound a little bit like the results of taking Adderall recreationally, which isn't my cup of tea. I was also hesitant to try it because it's marketing just makes it seem like it's a scam pill, and I unfortunately take quality of advertising rather seriously. I changed my mind (after another particularly trying week at work) after a friend of mine actually recommended it for me and told me that she was having great results from it. In my mind, I figured that if a real person,someone I know and trust, tells me in real life that I should maybe try it...then I may as well give it a shot. I ordered the Addium and as soon as I got it, I started taking it immediately. The Addium actually works. I can't believe it. It's helped a lot with my productivity at work. I'm taking just one tablet per day and it seems to be doing the trick. I think the best part about it is that it's not something that you have to continuously take every day.
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Nootropics are classically defined as something that a) improves brain health, and b) does no harm. So, while many treatments being advertised online and on TV can be classified as nootropics, some of them don’t fit the bill because of the dangerous and damaging side effects they also confer upon the unwary consumer. In fact, most of the results you might get from searching ‘best brain pills’ are similarly not that great, let alone the best.

Oxidative stress refers to a biochemical process that occurs as a result of an accumulative everyday exposure to toxic burdens such as chemicals in cosmetics, furniture, paints, cars, and pollution. Our body has its own way of armouring itself from the damage that exposure to toxins can create through its production of endogenous antioxidants, which is nature’s way of neutralising oxidative stress. Although we have our own production of these wonder molecules, when we are continuously overloaded with toxins in our environment and have problems detoxifying, the liver can become overwhelmed. Research shows that over time oxidative stress can lead to an increase in inflammatory molecules such as cytokines, which have been shown to correlate with depression (5).This is why it is important to have a high intake of nutrients that support the liver in metabolising and removing toxins from the body, as well as regulating the inflammatory response. There are a few things we can change in our diet to support this area, for example eating foods such as the cruciferous family of vegetables which includes kale, cauliflower, broccoli and cabbage. These are particularly effective at supporting the liver in ushering out toxins as they all share an antioxidant compound called indole-3 Carbinol, which plays an important role in liver health (6). In addition, bitter greens such as collard greens, rocket, chicory and swiss chard are also great for supporting the liver’s own antioxidant defence system.
Bacopa is a supplement herb often used for memory or stress adaptation. Its chronic effects reportedly take many weeks to manifest, with no important acute effects. Out of curiosity, I bought 2 bottles of Bacognize Bacopa pills and ran a non-randomized non-blinded ABABA quasi-self-experiment from June 2014 to September 2015, measuring effects on my memory performance, sleep, and daily self-ratings of mood/productivity. Because of the very slow onset, small effective sample size, definite temporal trends probably unrelated to Bacopa, and noise in the variables, the results were as expected, ambiguous, and do not strongly support any correlation between Bacopa and memory/sleep/self-rating (+/-/- respectively).
Creatine is stored as phosphocreatine, which acts as a high-energy reserve. Phosphocreatine decreases rapidly during brain activity. Supplementing with creatine (2 grams per day for 1 month) increased average brain creatine by 9.7%. It acts as an energy source for the brain to focus on learning tasks, as well as an energy source for storing memories.
Took pill 12:11 PM. I am not certain. While I do get some things accomplished (a fair amount of work on the Silk Road article and its submission to places), I also have some difficulty reading through a fiction book (Sum) and I seem kind of twitchy and constantly shifting windows. I am weakly inclined to think this is Adderall (say, 60%). It’s not my normal feeling. Next morning - it was Adderall.

Another prescription stimulant medication, modafinil (known by the brand name Provigil), is usually prescribed to patients suffering from narcolepsy and shift-work sleep disorder, but it might turn out to have broader applications. “We have conducted at the University of Cambridge double-blind, placebo-controlled studies in healthy people using modafinil and have found improvements in cognition, including in working memory,” Sahakian says. However, she doesn’t think everyone should start using the drug off-label. “There are no long-term safety and efficacy studies of modafinil in healthy people, and so it is unclear what the risks might be.”
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.)
Is lifestyle truly important, though? According to Dr. Lisa, "genes load the gun, but lifestyle pulls the trigger." As someone who grew up very aware of my genetic predisposition (diabetes, cardiovascular diseases, breast cancer — you name it and someone in my family has it), I always thought that this weighed heavily on whether or not someone manifests an illness. But, groundbreaking research on epigenetics actually states the contrary. 
Lost confidence.  If you can’t find your keys, much less get through your workday in a timely fashion without a slew of mistakes, you are going to lose confidence in both your brain and yourself.  When you cannot remember where you put things and it takes an absurd amount of effort just to do a simple task, you might question your very sanity.  As your confidence continues to nose-dive, you just end up making more and more mistakes.  It turns into a vicious cycle.

These days, nootropics are beginning to take their rightful place as a particularly powerful tool in the Neurohacker’s toolbox. After all, biochemistry is deeply foundational to neural function. Whether you are trying to fix the damage that is done to your nervous system by a stressful and toxic environment or support and enhance your neural functioning, getting the chemistry right is table-stakes. And we are starting to get good at getting it right. What’s changed?
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