Unlike many hypothetical scenarios that bioethicists worry about - human clones, "designer babies" - cognitive enhancement is already in full swing. But how much do they actually help? Are they potentially harmful or addictive? Then there's the question of what we mean by "smarter". Could enhancing one kind of thinking exact a toll on others? All these questions need proper scientific answers, but for now much of the discussion is taking place furtively, among the increasing number of people who are performing daily experiments on their own brains.
The abuse liability of caffeine has been evaluated.147,148 Tolerance development to the subjective effects of caffeine was shown in a study in which caffeine was administered at 300 mg twice each day for 18 days.148 Tolerance to the daytime alerting effects of caffeine, as measured by the MSLT, was shown over 2 days on which 250 g of caffeine was given twice each day48 and to the sleep-disruptive effects (but not REM percentage) over 7 days of 400 mg of caffeine given 3 times each day.7 In humans, placebo-controlled caffeine-discontinuation studies have shown physical dependence on caffeine, as evidenced by a withdrawal syndrome.147 The most frequently observed withdrawal symptom is headache, but daytime sleepiness and fatigue are also often reported. The withdrawal-syndrome severity is a function of the dose and duration of prior caffeine use…At higher doses, negative effects such as dysphoria, anxiety, and nervousness are experienced. The subjective-effect profile of caffeine is similar to that of amphetamine,147 with the exception that dysphoria/anxiety is more likely to occur with higher caffeine doses than with higher amphetamine doses. Caffeine can be discriminated from placebo by the majority of participants, and correct caffeine identification increases with dose.147 Caffeine is self-administered by about 50% of normal subjects who report moderate to heavy caffeine use. In post-hoc analyses of the subjective effects reported by caffeine choosers versus nonchoosers, the choosers report positive effects and the nonchoosers report negative effects. Interestingly, choosers also report negative effects such as headache and fatigue with placebo, and this suggests that caffeine-withdrawal syndrome, secondary to placebo choice, contributes to the likelihood of caffeine self-administration. This implies that physical dependence potentiates behavioral dependence to caffeine.
Dosage is apparently 5-10mg a day. (Prices can be better elsewhere; selegiline is popular for treating dogs with senile dementia, where those 60x5mg will cost $2 rather than $3532. One needs a veterinarian’s prescription to purchase from pet-oriented online pharmacies, though.) I ordered it & modafinil from Nubrain.com at $35 for 60x5mg; Nubrain delayed and eventually canceled my order - and my enthusiasm. Between that and realizing how much of a premium I was paying for Nubrain’s deprenyl, I’m tabling deprenyl along with nicotine & modafinil for now. Which is too bad, because I had even ordered 20g of PEA from Smart Powders to try out with the deprenyl. (My later attempt to order some off the Silk Road also failed when the seller canceled the order.)
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.
And as before, around 9 AM I began to feel the peculiar feeling that I was mentally able and apathetic (in a sort of aboulia way); so I decided to try what helped last time, a short nap. But this time, though I took a full hour, I slept not a wink and my Zeo recorded only 2 transient episodes of light sleep! A back-handed sort of proof of alertness, I suppose. I didn’t bother trying again. The rest of the day was mediocre, and I wound up spending much of it on chores and whatnot out of my control. Mentally, I felt better past 3 PM.
I take my piracetam in the form of capped pills consisting (in descending order) of piracetam, choline bitartrate, anhydrous caffeine, and l-tyrosine. On 8 December 2012, I happened to run out of them and couldn’t fetch more from my stock until 27 December. This forms a sort of (non-randomized, non-blind) short natural experiment: did my daily 1-5 mood/productivity ratings fall during 8-27 December compared to November 2012 & January 2013? The graphed data29 suggests to me a decline:
Adderall is a mix of 4 amphetamine salts (FDA adverse events), and not much better than the others (but perhaps less addictive); as such, like caffeine or methamphetamine, it is not strictly a nootropic but a cognitive enhancer and can be tricky to use right (for how one should use stimulants, see How To Take Ritalin Correctly). I ordered 10x10mg Adderall IR off Silk Road (Wikipedia). On the 4th day after confirmation from seller, the package arrived. It was a harmless looking little padded mailer. Adderall as promised: 10 blue pills with markings, in a double ziplock baggy (reasonable, it’s not cocaine or anything). They matched pretty much exactly the descriptions of the generic I had found online. (Surprisingly, apparently both the brand name and the generic are manufactured by the same pharmacorp.)
Our current natural brain health formula contains Cordyceps-Sinensis Extract as well as the complete balance of brain health supporting nutrients that work perfectly together to help your body elevate essential acetylcholine levels while increasing the neurological components (neurotransmitters) needed to help you stay alert, focused, mentally driven and calm.
"Over the years, I have learned so much from the work of Dr. Mosconi, whose accomplished credentials spanning both neuroscience and nutrition are wholly unique. This book represents the first time her studies on the interaction between food and long-term cognitive function reach a general audience. Dr. Mosconi always makes the point that we would eat differently and treat our brains better if only we could see what we are doing to them. From the lab to the kitchen, this is extremely valuable and urgent advice, complete with recommendations that any one of us can take."
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).
That left me with 329 days of data. The results are that (correcting for the magnesium citrate self-experiment I was running during the time period which did not turn out too great) days on which I happened to use my LED device for LLLT were much better than regular days. Below is a graph showing the entire MP dataseries with LOESS-smoothed lines showing LLLT vs non-LLLT days:
For starters, it’s one of the highest antioxidant-rich foods known to man, including vitamin C and vitamin K and fiber. Because of their high levels of gallic acid, blueberries are especially good at protecting our brains from degeneration and stress. Get your daily dose of brain berries in an Omega Blueberry Smoothie, Pumpkin Blueberry Pancakes or in a Healthy Blueberry Cobbler.
“We stumbled upon fasting as a way to optimize cognition and make yourself into a more efficient human being,” says Manuel Lam, an internal medicine physician who advises Nootrobox on clinical issues. He and members of the company’s executive team have implanted glucose monitors in their arms — not because they fear diabetes but because they wish to track the real-time effect of the foods they eat.
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 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.
I asked Marcus which nootropic he would want if he were stranded on a desert island. "I guess it would depend on the challenges I was facing on the island. If staying healthy was the biggest challenge, then I'd choose AC-11," he said. "If I needed to stay motivated to rebuild the village, I would choose Mucuna [pruriens]. If I was hunting, I'd choose Huperzia serrata, for mental acuity and speed."
The beauty of this stack is that nature has already given us a perfectly packaged combination of caffeine and theanine in the form of green tea, whether a cup of green tea, a bowl of matcha tea, or even a green tea extract supplement as a substitute for a cup of coffee. This is an especially convenient stack to use during a time when you don’t want the excess stimulation of coffee or caffeine in isolation, such as during an evening dinner at a restaurant or in the latter stages of a workday when a cup of coffee might keep you awake too late into the night.
Reason: Acetyl-L-carnitine can protect the brain from neurotoxicity. It can also ward off oxygen deprivation. Acetyl-L-carnitine can even preserve cells energy-producing mitochondria. Plus, it can rejuvenate mental and physical function. Dosages for studies have been in the 1,500 – 4,000 mg range. These are divided into two or three doses. However, we recommend no more than 1,000 mg of acetyl-L-carnitine a day without medical supervision.
Caffeine, Tulsi and Astragalus: Tulsi is one of the greatest calming adaptogens that exists, trusted and revered for centuries in Ayurvedic medicine and culture. Tulsi has been researched and shown to uplift mood, support digestion, and promote balanced energy. Because it’s also an anxiolytic (causes anti-anxiety effects) tulsi, similar to coffee with L-theanine, does a good job balancing out any over-stimulating effects of the caffeine in coffee. But you can also take things one step further and blend in astragalus, which, in Chinese medicine, is considered a “strong” Ki invigorating herb that provides a stable source of non-crashing energy. Astragalus also contains an enormous variety of saponins, flavonoids, and polysaccharides, and is considered to be a “longevity adaptogen”. Pairing with antioxidant-rich coffee and tulsi produces a match made in longevity heaven. For this blend, which I often use if drinking coffee in the afternoon, I’m a fan of the Four Sigmatic Adaptogen Blend, which contains coffee, astragalus, tulsi and cinnamon.
The price is not as good as multivitamins or melatonin. The studies showing effects generally use pretty high dosages, 1-4g daily. I took 4 capsules a day for roughly 4g of omega acids. The jar of 400 is 100 days’ worth, and costs ~$17, or around 17¢ a day. The general health benefits push me over the edge of favoring its indefinite use, but looking to economize. Usually, small amounts of packaged substances are more expensive than bulk unprocessed, so I looked at fish oil fluid products; and unsurprisingly, liquid is more cost-effective than pills (but like with the powders, straight fish oil isn’t very appetizing) in lieu of membership somewhere or some other price-break. I bought 4 bottles (16 fluid ounces each) for $53.31 total (thanks to coupons & sales), and each bottle lasts around a month and a half for perhaps half a year, or ~$100 for a year’s supply. (As it turned out, the 4 bottles lasted from 4 December 2010 to 17 June 2011, or 195 days.) My next batch lasted 19 August 2011-20 February 2012, and cost $58.27. Since I needed to buy empty 00 capsules (for my lithium experiment) and a book (Stanovich 2010, for SIAI work) from Amazon, I bought 4 more bottles of 16fl oz Nature’s Answer (lemon-lime) at $48.44, which I began using 27 February 2012. So call it ~$70 a year.
The evidence? Ritalin is FDA-approved to treat ADHD. It has also been shown to help patients with traumatic brain injury concentrate for longer periods, but does not improve memory in those patients, according to a 2016 meta-analysis of several trials. A study published in 2012 found that low doses of methylphenidate improved cognitive performance, including working memory, in healthy adult volunteers, but high doses impaired cognitive performance and a person’s ability to focus. (Since the brains of teens have been found to be more sensitive to the drug’s effect, it’s possible that methylphenidate in lower doses could have adverse effects on working memory and cognitive functions.)
Common environmental toxins – pesticides, for example – cause your brain to release glutamate (a neurotransmitter). Your brain needs glutamate to function, but when you create too much of it it becomes toxic and starts killing neurons. Oxaloacetate protects rodents from glutamate-induced brain damage. Of course, we need more research to determine whether or not oxaloacetate has the same effect on humans.
Eliminating foggy-headedness seems to be the goal of many users of neuroenhancers. But can today's drugs actually accomplish this? I recently posed this question to Chatterjee's colleague Martha Farah, who is a psychologist at Penn and the director of its Center for Cognitive Neuroscience. She is deeply fascinated by, and mildly critical of, neuroenhancers, but basically in favour - with the important caveat that we need to know much more about how these drugs work. While Farah does not take neuroenhancers, she had just finished a paper in which she reviewed the evidence on prescription stimulants as neuroenhancers from 40 laboratory studies involving healthy subjects. Most of the studies looked at one of three types of cognition: learning, working memory, and cognitive control. A typical learning test asks subjects to memorise a list of paired words; an hour, a few days, or a week later, they are presented with the first words in the pairs and asked to come up with the second. Neuroenhancers did improve retention, especially where subjects had been asked to remember information for several days or longer.
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).
For more in-depth personalised support, some people find nutritional therapy hugely beneficial. To find a suitable therapist, please head to BANT (British Association of Applied Nutrition and Nutritional Therapy) or contact our not-for-profit clinic, the Brain Bio Centre (www.brainbiocentre.com), which offers expertise in nutritional therapy for mental health conditions including depression, on 0208 332 9600 or firstname.lastname@example.org. If you feel you need more immediate help, for whatever it is that you’re going through, theSamaritans helpline offer support 24 hours a day, 365 days a year and can point you in the right direction of getting further help.
If you want to try a nootropic in supplement form, check the label to weed out products you may be allergic to and vet the company as best you can by scouring its website and research basis, and talking to other customers, Kerl recommends. "Find one that isn't just giving you some temporary mental boost or some quick fix – that’s not what a nootropic is intended to do," Cyr says.
Broccoli is great source of vitamin K, which is known to enhance cognitive function and improve brainpower. Researchers have reported that because broccoli is high in compounds called glucosinolates, it can slow the breakdown of the neurotransmitter, acetylcholine, which we need for the central nervous system to perform properly and to keep our brains and our memories sharp. Low levels of acetylcholine are associated with Alzheimer's.
If you are in or are able to come to London, you may be interested in also coming to a one day workshop we are hosting with Patrick Holford, our founder and one the UK’s leading nutritional therapists. We are excited to be running this workshop, which enables our supporters to access Patrick’s wealth of knowledge on nutrition and mental health. More details can be found below. If you are outside of the UK and are interested in this workshop or learning more about nutrition and mental health, please sign up for news on our Seminar series here.
Similarly, we could try applying Nick Bostrom’s reversal test and ask ourselves, how would we react to a virus which had no effect but to eliminate sleep from alternating nights and double sleep in the intervening nights? We would probably grouch about it for a while and then adapt to our new hedonistic lifestyle of partying or working hard. On the other hand, imagine the virus had the effect of eliminating normal sleep but instead, every 2 minutes, a person would fall asleep for a minute. This would be disastrous! Besides the most immediate problems like safely driving vehicles, how would anything get done? You would hold a meeting and at any point, a third of the participants would be asleep. If the virus made it instead 2 hours on, one hour off, that would be better but still problematic: there would be constant interruptions. And so on, until we reach our present state of 16 hours on, 8 hours off. Given that we rejected all the earlier buffer sizes, one wonders if 16:8 can be defended as uniquely suited to circumstances. Is that optimal? It may be, given the synchronization with the night-day cycle, but I wonder; rush hour alone stands as an argument against synchronized sleep - wouldn’t our infrastructure would be much cheaper if it only had to handle the average daily load rather than cope with the projected peak loads? Might not a longer cycle be better? The longer the day, the less we are interrupted by sleep; it’s a hoary cliche about programmers that they prefer to work in long sustained marathons during long nights rather than sprint occasionally during a distraction-filled day, to the point where some famously adopt a 28 hour day (which evenly divides a week into 6 days). Are there other occupations which would benefit from a 20 hour waking period? Or 24 hour waking period? We might not know because without chemical assistance, circadian rhythms would overpower anyone attempting such schedules. It certainly would be nice if one had long time chunks in which could read a challenging book in one sitting, without heroic arrangements.↩
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.
Caffeine + L-Theanine: Since caffeine can produce unwanted side effects in high amounts (such as jitteriness and headaches), most people, and especially “slow caffeine oxidizers” find that by adding L-Theanine to a caffeine source such as coffee, any negative side effects of caffeine can be controlled. Caffeine and L-Theanine in combination have been researched and proven to boost concentration, attention, and energy while reducing anxiety. For this stack, use a ratio of four parts L-Theanine to one part caffeine, such as 400 milligrams of L-Theanine along with 100 milligrams of caffeine. You may want to start out with a smaller dose such as 200 milligrams of L-Theanine and 50 milligrams of caffeine and work your way up to find the best dose for you (the average cup of coffee has about 100mg of caffeine).
Of course, before wrapping up this section on psychedelics, I’ll address the topics of where to actually buy the stuff. There are a variety of websites that sell psychedelics, but not all ingredient, chemical or quality sourcing is created equal, nor is there any guarantee that any substance you are purchasing is not laced with undesirable compounds. Heck, I get my psilocybin from a farmer in Wisconsin who is a personal friend, and other ingredients from close acquaintances who have their own sources. I know it may seem unfair, but sometimes sourcing comes down to “who ya know” and doing your own due diligence on that person’s source.
This doesn’t fit the U-curve so well: while 60mg is substantially negative as one would extrapolate from 30mg being ~0, 48mg is actually better than 15mg. But we bought the estimates of 48mg/60mg at a steep price - we ignore the influence of magnesium which we know influences the data a great deal. And the higher doses were added towards the end, so may be influenced by the magnesium starting/stopping. Another fix for the missingness is to impute the missing data. In this case, we might argue that the placebo days of the magnesium experiment were identical to taking no magnesium at all and so we can classify each NA as a placebo day, and rerun the desired analysis:
Choline is very important for cognitive function because it is a precursor to Acteylcholine. Your body needs enough choline to convert into Acteylcholine to keep your brain healthy. For this reason, choline supplements are often considered great nootropics, even by themselves. CDP-Choline and Alpha GPC are the best sources for supplemental Choline.
The evidence? Found helpful in reducing bodily twitching in myoclonus epilepsy, a rare disorder, but otherwise little studied. Mixed evidence from a study published in 1991 suggests it may improve memory in subjects with cognitive impairment. A meta-analysis published in 2010 that reviewed studies of piracetam and other racetam drugs found that piracetam was somewhat helpful in improving cognition in people who had suffered a stroke or brain injury; the drugs’ effectiveness in treating depression and reducing anxiety was more significant.
But, thanks to the efforts of a number of remarkable scientists, researchers and plain-old neurohackers, we are beginning to put together a “whole systems” model of how all the different parts of the human brain work together and how they mesh with the complex regulatory structures of the body. It’s going to take a lot more data and collaboration to dial this model in, but already we are empowered to design stacks that can meaningfully deliver on the promise of nootropics “to enhance the quality of subjective experience and promote cognitive health, while having extremely low toxicity and possessing very few side effects.” It’s a type of brain hacking that is intended to produce noticeable cognitive benefits.