Another well-known smart drug classed as a cholinergic is Sulbutiamine, a synthetic derivative of thiamine which crosses the blood-brain barrier and has been shown to improve memory while reducing psycho-behavioral inhibition. While Sulbutiamine has been shown to exhibit cholinergic regulation within the hippocampus, the reasons for the drug’s discernable effects on the brain remain unclear. This smart drug, available over the counter as a nutritional supplement, has a long history of use, and appears to have no serious side effects at therapeutic levels.
Most diehard nootropic users have considered using racetams for enhancing brain function. Racetams are synthetic nootropic substances first developed in Russia. These smart drugs vary in potency, but they are not stimulants. They are unlike traditional ADHD medications (Adderall, Ritalin, Vyvanse, etc.). Instead, racetams boost cognition by enhancing the cholinergic system.
And there are other uses that may make us uncomfortable. The military is interested in modafinil as a drug to maintain combat alertness. A drug such as propranolol could be used to protect soldiers from the horrors of war. That could be considered a good thing – post-traumatic stress disorder is common in soldiers. But the notion of troops being unaffected by their experiences makes many feel uneasy.
We’ve talk about how caffeine affects the body in great detail, but the basic idea is that it can improve your motivation and focus by increasing catecholamine signaling. Its effects can be dampened over time, however, as you start to build a caffeine tolerance. Research on L-theanine, a common amino acid, suggests it promotes neuronal health and can decrease the incidence of cold and flu symptoms by strengthening the immune system. And one study, published in the journal Biological Psychology, found that L-theanine reduces psychological and physiological stress responses—which is why it’s often taken with caffeine. In fact, in a 2014 systematic review of 11 different studies, published in the journal Nutrition Review, researchers found that use of caffeine in combination with L-theanine promoted alertness, task switching, and attention. The reviewers note the effects are most pronounced during the first two hours post-dose, and they also point out that caffeine is the major player here, since larger caffeine doses were found to have more of an effect than larger doses of L-theanine.
Accordingly, we searched the literature for studies in which MPH or d-AMP was administered orally to nonelderly adults in a placebo-controlled design. Some of the studies compared the effects of multiple drugs, in which case we report only the results of stimulant–placebo comparisons; some of the studies compared the effects of stimulants on a patient group and on normal control subjects, in which case we report only the results for control subjects. The studies varied in many other ways, including the types of tasks used, the specific drug used, the way in which dosage was determined (fixed dose or weight-dependent dose), sample size, and subject characteristics (e.g., age, college sample or not, gender). Our approach to the classic splitting versus lumping dilemma has been to take a moderate lumping approach. We group studies according to the general type of cognitive process studied and, within that grouping, the type of task. The drug and dose are reported, as well as sample characteristics, but in the absence of pronounced effects of these factors, we do not attempt to make generalizations about them.
Starting from the studies in my meta-analysis, we can try to estimate an upper bound on how big any effect would be, if it actually existed. One of the most promising null results, Southon et al 1994, turns out to be not very informative: if we punch in the number of kids, we find that they needed a large effect size (d=0.81) before they could see anything:
One reason I like modafinil is that it enhances dopamine release, but it binds to your dopamine receptors differently than addictive substances like cocaine and amphetamines do, which may be part of the reason modafinil shares many of the benefits of other stimulants but doesn’t cause addiction or withdrawal symptoms.   It does increase focus, problem-solving abilities, and wakefulness, but it is not in the same class of drugs as Adderall, and it is not a classical stimulant. Modafinil is off of patent, so you can get it generically, or order it from India. It’s a prescription drug, so you need to talk to a physician.
(People aged <=18 shouldn’t be using any of this except harmless stuff - where one may have nutritional deficits - like fish oil & vitamin D; melatonin may be especially useful, thanks to the effects of screwed-up school schedules & electronics use on teenagers’ sleep. Changes in effects with age are real - amphetamines’ stimulant effects and modafinil’s histamine-like side-effects come to mind as examples.)
Most research on these nootropics suggest they have some benefits, sure, but as Barbara Sahakian and Sharon Morein-Zamir explain in the journal Nature, nobody knows their long-term effects. And we don’t know how extended use might change your brain chemistry in the long run. Researchers are getting closer to what makes these substances do what they do, but very little is certain right now. If you’re looking to live out your own Limitless fantasy, do your research first, and proceed with caution.
So, I thought I might as well experiment since I have it. I put the 23 remaining pills into gel capsules with brown rice as filling, made ~30 placebo capsules, and will use the one-bag blinding/randomization method. I don’t want to spend the time it would take to n-back every day, so I will simply look for an effect on my daily mood/productivity self-rating; hopefully Noopept will add a little on average above and beyond my existing practices like caffeine+piracetam (yes, Noopept may be as good as piracetam, but since I still have a ton of piracetam from my 3kg order, I am primarily interested in whether Noopept adds onto piracetam rather than replaces). 10mg doses seem to be on the low side for Noopept users, weakening the effect, but on the other hand, if I were to take 2 capsules at a time, then I’d halve the sample size; it’s not clear what is the optimal tradeoff between dose and n for statistical power.
In my last post, I talked about the idea that there is a resource that is necessary for self-control…I want to talk a little bit about the candidate for this resource, glucose. Could willpower fail because the brain is low on sugar? Let’s look at the numbers. A well-known statistic is that the brain, while only 2% of body weight, consumes 20% of the body’s energy. That sounds like the brain consumes a lot of calories, but if we assume a 2,400 calorie/day diet - only to make the division really easy - that’s 100 calories per hour on average, 20 of which, then, are being used by the brain. Every three minutes, then, the brain - which includes memory systems, the visual system, working memory, then emotion systems, and so on - consumes one (1) calorie. One. Yes, the brain is a greedy organ, but it’s important to keep its greediness in perspective… Suppose, for instance, that a brain in a person exerting their willpower - resisting eating brownies or what have you - used twice as many calories as a person not exerting willpower. That person would need an extra one third of a calorie per minute to make up the difference compared to someone not exerting willpower. Does exerting self control burn more calories?
“Who doesn’t want to maximize their cognitive ability? Who doesn’t want to maximize their muscle mass?” asks Murali Doraiswamy, who has led several trials of cognitive enhancers at Duke University Health System and has been an adviser to pharmaceutical and supplement manufacturers as well as the Food and Drug Administration. He attributes the demand to an increasingly knowledge-based society that values mental quickness and agility above all else.
Sounds too good to be true? Welcome to the world of ‘Nootropics’ popularly known as ‘Smart Drugs’ that can help boost your brain’s power. Do you recall the scene from the movie Limitless, where Bradley Cooper’s character uses a smart drug that makes him brilliant? Yes! The effect of Nootropics on your brain is such that the results come as a no-brainer.
If you want to make sure that whatever you’re taking is safe, search for nootropics that have been backed by clinical trials and that have been around long enough for any potential warning signs about that specific nootropic to begin surfacing. There are supplements and nootropics that have been tested in a clinical setting, so there are options out there.
Instead, I urge the military to examine the use of smart drugs and the potential benefits they bring to the military. If they are safe, and pride cognitive enhancement to servicemembers, then we should discuss their use in the military. Imagine the potential benefits on the battlefield. They could potentially lead to an increase in the speed and tempo of our individual and collective OODA loop. They could improve our ability to become aware and make observations. Improve the speed of orientation and decision-making. Lastly, smart drugs could improve our ability to act and adapt to rapidly changing situations.
By which I mean that simple potassium is probably the most positively mind altering supplement I’ve ever tried…About 15 minutes after consumption, it manifests as a kind of pressure in the head or temples or eyes, a clearing up of brain fog, increased focus, and the kind of energy that is not jittery but the kind that makes you feel like exercising would be the reasonable and prudent thing to do. I have done no tests, but feel smarter from this in a way that seems much stronger than piracetam or any of the conventional weak nootropics. It is not just me – I have been introducing this around my inner social circle and I’m at 7/10 people felt immediately noticeable effects. The 3 that didn’t notice much were vegetarians and less likely to have been deficient. Now that I’m not deficient, it is of course not noticeable as mind altering, but still serves to be energizing, particularly for sustained mental energy as the night goes on…Potassium chloride initially, but since bought some potassium gluconate pills… research indicates you don’t want to consume large amounts of chloride (just moderate amounts).
If you want to focus on boosting your brain power, Lebowitz says you should primarily focus on improving your cardiovascular health, which is "the key to good thinking." For example, high blood pressure and cholesterol, which raise the risk of heart disease, can cause arteries to harden, which can decrease blood flow to the brain. The brain relies on blood to function normally.
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But he has also seen patients whose propensity for self-experimentation to improve cognition got out of hand. One chief executive he treated, Ngo said, developed an unhealthy predilection for albuterol, because he felt the asthma inhaler medicine kept him alert and productive long after others had quit working. Unfortunately, the drug ended up severely imbalancing his electrolytes, which can lead to dehydration, headaches, vision and cardiac problems, muscle contractions and, in extreme cases, seizures.
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?
The principal metric would be mood, however defined. Zeo’s web interface & data export includes a field for Day Feel, which is a rating 1-5 of general mood & quality of day. I can record a similar metric at the end of each day. 1-5 might be a little crude even with a year of data, so a more sophisticated measure might be in order. The first mood study is paywalled so I’m not sure what they used, but Shiotsuki 2008 used State-Trait of Anxiety Inventory (STAI) and Profiles of Mood States Test (POMS). The full POMS sounds too long to use daily, but the Brief POMS might work. In the original 1987 paper A brief POMS measure of distress for cancer patients, patients answering this questionnaire had a mean total mean of 10.43 (standard deviation 8.87). Is this the best way to measure mood? I’ve asked Seth Roberts; he suggested using a 0-100 scale, but personally, there’s no way I can assess my mood on 0-100. My mood is sufficiently stable (to me) that 0-5 is asking a bit much, even.
Today piracetam is a favourite with students and young professionals looking for a way to boost their performance, though decades after Giurgea’s discovery, there still isn’t much evidence that it can improve the mental abilities of healthy people. It’s a prescription drug in the UK, though it’s not approved for medical use by the US Food and Drug Administration and can’t be sold as a dietary supplement either.
Since LLLT was so cheap, seemed safe, was interesting, just trying it would involve minimal effort, and it would be a favor to lostfalco, I decided to try it. I purchased off eBay a $13 48 LED illuminator light IR Infrared Night Vision+Power Supply For CCTV. Auto Power-On Sensor, only turn-on when the surrounding is dark. IR LED wavelength: 850nm. Powered by DC 12V 500mA adaptor. It arrived in 4 days, on 7 September 2013. It fits handily in my palm. My cellphone camera verified it worked and emitted infrared - important because there’s no visible light at all (except in complete darkness I can make out a faint red light), no noise, no apparent heat (it took about 30 minutes before the lens or body warmed up noticeably when I left it on a table). This was good since I worried that there would be heat or noise which made blinding impossible; all I had to do was figure out how to randomly turn the power on and I could run blinded self-experiments with it.
All clear? Try one (not dozens) of nootropics for a few weeks and keep track of how you feel, Kerl suggests. It’s also important to begin with as low a dose as possible; when Cyr didn’t ease into his nootropic regimen, his digestion took the blow, he admits. If you don’t notice improvements, consider nixing the product altogether and focusing on what is known to boost cognitive function – eating a healthy diet, getting enough sleep regularly and exercising. "Some of those lifestyle modifications," Kerl says, "may improve memory over a supplement."
Last spring, 100 people showed up at a Peak Performance event where psychedelic psychologist James Fadiman said the key to unleashing the cognition-enhancing effects of LSD — which he listed as less anxiety, better focus, improved sleep, greater creativity — was all in the dosage. He recommended a tenth of a “party dose” — enough to give you “the glow” and enhance your cognitive powers without “the trip.”
3 days later, I’m fairly miserable (slept poorly, had a hair-raising incident, and a big project was not received as well as I had hoped), so well before dinner (and after a nap) I brew up 2 wooden-spoons of Malaysia Green (olive-color dust). I drank it down; tasted slightly better than the first. I was feeling better after the nap, and the kratom didn’t seem to change that.
We included studies of the effects of these drugs on cognitive processes including learning, memory, and a variety of executive functions, including working memory and cognitive control. These studies are listed in Table 2, along with each study’s sample size, gender, age and tasks administered. Given our focus on cognition enhancement, we excluded studies whose measures were confined to perceptual or motor abilities. Studies of attention are included when the term attention refers to an executive function but not when it refers to the kind of perceptual process taxed by, for example, visual search or dichotic listening or when it refers to a simple vigilance task. Vigilance may affect cognitive performance, especially under conditions of fatigue or boredom, but a more vigilant person is not generally thought of as a smarter person, and therefore, vigilance is outside of the focus of the present review. The search and selection process is summarized in Figure 2.
Core body temperature, local pH and internal pressure are important indicators of patient well-being. While a thermometer can give an accurate reading during regular checkups, the monitoring of professionals in high-intensity situations requires a more accurate inner body temperature sensor. An ingestible chemical sensor can record acidity and pH levels along the gastrointestinal tract to screen for ulcers or tumors. Sensors also can be built into medications to track compliance.
Some critics argue that Modafinil is an expression of that, a symptom of a new 24/7 work routine. But what if the opposite is true? Let’s say you could perform a task in significantly less time than usual. You could then use the rest of your time differently, spending it with family, volunteering, or taking part in a leisure activity. And imagine that a drug helped you focus on clearing your desk and inbox before leaving work. Wouldn’t that help you relax once you get home?
Smart drugs act within the brain speeding up chemical transfers, acting as neurotransmitters, or otherwise altering the exchange of brain chemicals. There are typically very few side effects, and they are considered generally safe when used as indicated. Special care should be used by those who have underlying health conditions, are on other medications, pregnant women, and children, as there is no long-term data on the use and effects of nootropics in these groups.
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:
That doesn’t necessarily mean all smart drugs – now and in the future – will be harmless, however. The brain is complicated. In trying to upgrade it, you risk upsetting its intricate balance. “It’s not just about more, it’s about having to be exquisitely and exactly right. And that’s very hard to do,” says Arnstein. “What’s good for one system may be bad for another system,” adds Trevor Robbins, Professor of Cognitive Neuroscience at the University of Cambridge. “It’s clear from the experimental literature that you can affect memory with pharmacological agents, but the problem is keeping them safe.”
The truth is that, almost 20 years ago when my brain was failing and I was fat and tired, I did not know to follow this advice. I bought $1000 worth of smart drugs from Europe, took them all at once out of desperation, and got enough cognitive function to save my career and tackle my metabolic problems. With the information we have now, you don’t need to do that. Please learn from my mistakes!