One claim was partially verified in passing by Eliezer Yudkowsky (Supplementing potassium (citrate) hasn’t helped me much, but works dramatically for Anna, Kevin, and Vassar…About the same as drinking a cup of coffee - i.e., it works as a perker-upper, somehow. I’m not sure, since it doesn’t do anything for me except possibly mitigate foot cramps.)
As a student Seltzer used both Adderall and piracetam. Now, after a hiatus of several years, he has recently resumed taking neuroenhancers. In addition to piracetam, he took a stack of supplements that he thought helped his brain to function: fish oils, five antioxidants, a product called ChocoMind and a number of others, all available at the health-food store. He was thinking about adding modafinil, but hadn't yet. For breakfast every morning he concocted a slurry of oatmeal, berries, soy milk, pomegranate juice, flaxseed, almond meal, raw eggs and protein powder. The goal behind the recipe was efficiency: to rely on "one goop you could eat or drink that would have everything you need nutritionally for your brain and body. I wanted to be able to keep it down - that was it." (He told me this in the kitchen of his apartment; he lives with a roommate, who walked in while we were talking, listened perplexedly for a moment, then put a frozen pizza in the oven.)
There are over a thousand websites and hundreds of reference guides chock full of complicated methods for combining many of the compounds you’ve just discovered. There’s a reason for this: the practice of “stacking” nootropics and smart drugs into specific combinations can be far more powerful and efficacious than consuming a single, lonely compound in isolation. For example, dosing choline sources with your morning coffee can make your brain feel fresh for hours or mixing curcumin with black pepper can dramatically amp up the neural anti-inflammatory effects of both compounds. Ultimately, a teaspoon of lion’s mane extract just isn’t as titillating as lion’s mane blended with caffeine, theanine, nicotine and a touch of vinpocetine.
“It is surprising and encouraging that it may be possible to predict the magnitude of a placebo effect before treatment,” says Tor Wager, a neuroscientist at the University of Colorado Boulder, who was not involved in the research. More work is needed to see how the predictive features hold up in other populations and for different pain conditions, he says.
I bought 500g of piracetam (Examine.com; FDA adverse events) from Smart Powders (piracetam is one of the cheapest nootropics and SP was one of the cheapest suppliers; the others were much more expensive as of October 2010), and I’ve tried it out for several days (started on 7 September 2009, and used it steadily up to mid-December). I’ve varied my dose from 3 grams to 12 grams (at least, I think the little scoop measures in grams), taking them in my tea or bitter fruit juice. Cranberry worked the best, although orange juice masks the taste pretty well; I also accidentally learned that piracetam stings horribly when I got some on a cat scratch. 3 grams (alone) didn’t seem to do much of anything while 12 grams gave me a nasty headache. I also ate 2 or 3 eggs a day.
A young man I'll call Alex recently graduated from Harvard. As a history major, Alex wrote about a dozen papers a term. He also ran a student organisation, for which he often worked more than 40 hours a week; when he wasn't working, he had classes. Weeknights were devoted to all the schoolwork he couldn't finish during the day, and weekend nights were spent drinking with friends and going to parties. "Trite as it sounds," he told me, it seemed important to "maybe appreciate my own youth". Since, in essence, this life was impossible, Alex began taking Adderall to make it possible.
Thursday: 3g piracetam/4g choline bitartrate at 1; 1 200mg modafinil at 2:20; noticed a leveling of fatigue by 3:30; dry eyes? no bad after taste or anything. a little light-headed by 4:30, but mentally clear and focused. wonder if light-headedness is due simply to missing lunch and not modafinil. 5:43: noticed my foot jiggling - doesn’t usually jiggle while in piracetam/choline. 7:30: starting feeling a bit jittery & manic - not much or to a problematic level but definitely noticeable; but then, that often happens when I miss lunch & dinner. 12:30: bedtime. Can’t sleep even with 3mg of melatonin! Subjectively, I toss & turn (in part thanks to my cat) until 4:30, when I really wake up. I hang around bed for another hour & then give up & get up. After a shower, I feel fairly normal, strangely, though not as good as if I had truly slept 8 hours. The lesson here is to pay attention to wikipedia when it says the half-life is 12-15 hours! About 6AM I take 200mg; all the way up to 2pm I feel increasingly less energetic and unfocused, though when I do apply myself I think as well as ever. Not fixed by food or tea or piracetam/choline. I want to be up until midnight, so I take half a pill of 100mg and chew it (since I’m not planning on staying up all night and I want it to work relatively soon). From 4-12PM, I notice that today as well my heart rate is elevated; I measure it a few times and it seems to average to ~70BPM, which is higher than normal, but not high enough to concern me. I stay up to midnight fine, take 3mg of melatonin at 12:30, and have no trouble sleeping; I think I fall asleep around 1. Alarm goes off at 6, I get up at 7:15 and take the other 100mg. Only 100mg/half-a-pill because I don’t want to leave the half laying around in the open, and I’m curious whether 100mg + ~5 hours of sleep will be enough after the last 2 days. Maybe next weekend I’ll just go without sleep entirely to see what my limits are.
The realm of natural nootropics is also accompanied by a family of synthetic nootropics called racetams, most notably piracetam and aniracetam. Piracetam is known to directly enhance learning, memory and attention and, with no observed adverse side effects, can restore cognitive performance in patients who have suffered cranial trauma, inflammation, strokes and ischemic complications following coronary bypass surgery. It can also improve symptoms of delirium and reduce depression and anxiety. In adults, the standard dose of piracetam ranges from 1,200 to 4,800 mg, often broken up into three smaller doses throughout the day. Aniracetam has been shown to concentration-dependently counteract cell death induced by excitotoxicity caused by glutamate, resulting in an overall neuroprotective effect. While you may not be shoveling mouthfuls of glutamate down your hatch or eating cartonsful of MSG-containing Chinese food each night, the same mechanism of action can help protect your brain from excitotoxicity or inflammation caused by other central nervous system irritants, such as toxins, chemicals, herbicides, pesticides, rancid oils, etc. Effective doses of aniracetam range from a single 400 mg dose to two doses per day between 500 and 750 mg, taken with meals.
But Baldino may have been overly modest. In 2002, researchers at Cambridge University gave 60 healthy young male volunteers a battery of standard cognitive tests. One group received modafinil, the other a placebo. The modafinil group performed better on several tasks, such as the "digit span" test, in which subjects are asked to repeat increasingly longer strings of numbers forwards, then backwards. They also did better in recognising repeated visual patterns and at a spatial-planning challenge known as the Tower of London task. (It's not nearly as fun as it sounds.) Writing in the journal Psychopharmacology, the study's authors said the results suggested that "modafinil offers significant potential as a cognitive enhancer".
But while some studies have found short-term benefits, Doraiswamy says there is no evidence that what are commonly known as smart drugs — of any type — improve thinking or productivity over the long run. “There’s a sizable demand, but the hype around efficacy far exceeds available evidence,” notes Doraiswamy, adding that, for healthy young people such as Silicon Valley go-getters, “it’s a zero-sum game. That’s because when you up one circuit in the brain, you’re probably impairing another system.”
Pop this pill and improve your memory. Swallow that one and reduce your cognitive decline. We see ads for such products all the time and I suspect they will increase as the baby boomers reach senior citizenhood. The most popular brain boosting supplements are fish oil pills and they are also probably the best studied ones. The results are not encouraging.
She provides many examples of observational studies where lower intakes of a certain nutrient were correlated with cognitive impairment. Obviously, if someone is deficient in a vitamin or other nutrient, the deficiency should be corrected. But she doesn’t have any evidence from prospective interventional studies showing that, in practice, altering diet significantly improves cognition for people who are deficient, much less in people who are not deficient.
The main concern with pharmaceutical drugs is adverse effects, which also apply to nootropics with undefined effects. Long-term safety evidence is typically unavailable for nootropics. Racetams — piracetam and other compounds that are structurally related to piracetam — have few serious adverse effects and low toxicity, but there is little evidence that they enhance cognition in people having no cognitive impairments.