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deletedMay 18, 2022ยทedited May 18, 2022
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I wonder where Oroxylum extract would place if it were included.

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Thatโ€™s really interesting that Dexedrine lists at the top.

I wonder if it outperforms Ritalin due to the anti-anxiety component of Dexedrine. This would be similar to energy drink manufacturers including theanine in their beverages.

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Is Zembrin freely available.

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Is ayahuasca not a Nootropic? It's far more effective for me than anything on the list.

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I was impressed that weight lifting ranks a fair bit higher than cardio of either kind. My teenage son started into weight lifting about six months ago and he says it's made a huge difference in his mental state.

I'd love to see studies comparing weight lifting to cardio and I wonder whether there are sex differences with regard to the benefit from each of those or if there aren't.

If someone said to me I had to become a regular runner or do daily HIIT classes to get the mood benefit, I'd find that pretty hard to stay motivated to do, but if someone said take up weight lifting, I could do that. Maybe we ought to be saying that to more people?

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The issue with the survey (https://www.nootroflix.com) is that it doesn't attempt to specify *what* exactly is being rated 1 to 10.

Weightlifting, for example. It's very easy to note physical changes in muscular hypertrophy from a few months of weightlifting. But did you actually notice it improved your mental health? Your physical health? Your bone density?

On the other hand, creatine and omega-3. I've been taking these for over a decade, because I KNOW they work. But there's no way I could ever notice an objective difference versus not taking them.

And then, Modafinil. I mean, obviously it's going to be rated high, because it's a drug, not a nootropic. You *feel* the effects.

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This is cool. I like weightlifting the most in the moment of the exercise, but I think my mood is most improved after light cardio. I can actually feel pretty bad after heavy cardio, not emotionally, but in the amount of pain I feel. Weightlifting does seem to reduce aches and pains though, which is really good for day to day functioning. It's also a fairly short term goal setting system. Cardio, especially light cardio, requires a longer duration while weightlifting can be much faster for a similar effect. Finally, I wonder how much of the perceived positive effect is a kind of coping mechanism. You spend a lot of money on weights or a gym membership, so you think that the resulting effect of weight lifting is positive. I really like weight lifting, but I know some people, despite occasionally trying, can never actually establish it as a habit. In these cases, I wonder if they don't put down their effect of weight lifting at all, or they feel compelled to put a positive score because they feel like weightlifting is good for you. In my opinion, weightlifting would be much higher than the median score here.

I'm also curious about what 'trying to get more sleep' means. If I try to get more sleep, but someone is wrong on the internet and I stay up until 3AM arguing with them, do I still say that I'm trying to get more sleep? I'd guess that would make me feel subjectively bad.

I'm surprised meditation scores so low, comparable to a cup of coffee. I'd expect that to be very good for people's well being, but perhaps negative experiences during meditation are more common than I might think, or people just don't get the advertised effects.

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This is great stuff, but I still think there is a lot less homogeneity amongst people and the effect various substances or lifestyle interventions will have on them.

The idea of a singular bell curve or one split along neat and tidy lines such as race or sex seems like one of the biggest areas of research which is under explored and largely ignored.

Every study finds individuals for whom a drug works much better or much worse and somehow we just go with some average effect and ignore the variance as though it were not worth studying.

I think with certain categories of drugs the variance is rather small and fairly well understood to not be a factor and yet for psychoactive drugs we find a huge huge variance and for whatever reason pretend this is not important.

Meanwhile nearly every single patient with depression or anxiety or whatever is on some never ending journey of personal drug discovery to find out which anti-depressant is going to work well for them or not. This is a pie in the face level obvious event and it gets very little attention compared to drug vs drug average effect comparisons which are clinically meaningless as every psychiatrist jumps around from drug to drug seeking whatever is going to work for a given individual.

For an anti-depressant or nootropic to range from doing absolutely nothing for some people and being a literal life saver for other people seems like an area of research worth pursuing. Perhaps I'm just being ignorant and foolish to ignore the massive and huge research trend towards personalised medicine that has been all the rage for 15+ years? But it seems a bit isolated as a novelty while mainstream research continues on doing drug vs drug and drug vs placebo average effect size based methodologies.

I still think we might find multiple curves like a series of rolling hills if we could increase our granularity. My experiences and those of the people I've met over the years by far reflect this with some substances effecting people much more strongly than others. Even something as simple as the common mind altering drug ethanol are blatantly obvious and people have widely different tolerances, even within the same ethnic groups.

The focus on averages at all is seemingly absurd as essentially hardly anyone is going to have the average experience with any substance and very few drugs fall into an actual bell curve. If you map the effect size on a per individual basis you'll usually end up with a series of bell curves with some people getting a large effect and others a small effect. Certainly no curve is as 'smooth' as it appears and this visual statistical artefact is poisoning and limiting people's thinking.

These statistical summaries often hide information and this is done on purpose in many cases, the top multi-billion dollar criminal and civil cases have all been against large pharmaceutical companies using stats and other methods to hide or obscure data which led to tens of thousand of deaths.

As Scott has said many times...we need the raw data...but I think we also need charts which have the most raw version possible to present data as well as even something as simple as an 'average' or 'variance' or 'standard deviation' or 'regression curve' or 'best fit whatever' can hide important information.

Too often meaningless 'demographic' information is the search term used search for population variances when the answers are often in the raw data. We should be led by our observations, not by our statistics or baseless assumptions of artificial demographic categories.

If what I'm saying is wrong somehow...then why are so many of every psychiatrist's patients on a personal journey of trial and error? Often giving up before finding a solution, if there even is one for them amongst available drugs.

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Another thing that underperforms according to your model is trying to sleep less. It is hard to do. If the emphasis is on *trying*, that implies you don't have to wake up early in the morning for some other reason.

I am surprised it does so poorly. Makes me update against Guzey's position.

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If only Walter White had sampled his own product (yes I know meth isn't on there), perhaps he could have cured his cancer.

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They left out lithium, which has been life-changing for me at a 5mg otc microdose. It's very cheap and legal and available on Amazon.

It seems to improve both mood and cognition. I credit it with helping me get a perfect score on the SAT and perform really well at a programming job. The ideal dosing schedule is one with breakfast and one with dinner. That'd be 10mg/day of elemental lithium equivalent to 300mg/day [EDIT: 100mg] of lithium citrate which is about a third to a quarter [EDIT: 10%] of the long term maintenance dose for bipolar.

The recommendation engine wasn't too useful for me. Even though I told it every stimulant I ever took had to be stopped because of side effects, it still told me to take ALL the amphetamines and ALL the afinils. It's as if the population stats form priors that are too strong and it doesn't update enough on individual info.

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What I'd really like to know is *who* this stuff benefits. For example; Inositol seems to help with depression in people with PCOS. Taking it with whey (which has alpha lacatalbumin) improves absorption. Since absorption is such an issue with inositol, I've always wondered what it might do if injected.

In any case, the point is that Inositol helps a very narrow range of people, but probably wouldn't help the general person with depressive episodes. The big problem with nootropic research (and, to a lesser extent, antidepressants in general) seems to be figuring out who will benefit from what without resorting to trial and error.

Also, it's interesting that nobody included provigil/nuvigil. Do those not have nootropic effects?

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Interestingly the top 2 drugs (Dexedrine and Adderall) are (I think) poorly compatible with Weightlifting and HIIT, as amphetamine salts are well known to increase heart rate and blood pressure.

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Scott, FYI the Doctor's Best Zembrin linked from the lorien psych page is no longer available at amazon.

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May 18, 2022ยทedited May 18, 2022

I considered taking nootropics. But then I realized it would be like Bo Jackson taking steroids. What's the point?

Sorry. I've been dying to use that joke for a long long time.

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Zembrin is known for its SSRI action, which is relatively weak, but it's also a blood brain barrier crossing selective PDE4 inhibitor. Combined with forskolin, synergistically increases cAMP levels which may affect long term potentiation. Neat to see it relatively high.

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The red flag for me is Vegan rating higher than Vegetarian. I think you should expect that if Vegetarian diet is bad, Vegan diet should be worse. Perhaps people trying the Vegan diet were more ideological than the Vegetarians, leading them to be biased in rating it higher?

Not sure how this idea would map onto the Keto/Paleo/Carnivore set. Naively I'd expect Keto to be the least ideological, and Carnivore to be the most, but Paleo seems to do much better and Keto and Carnivore about the same.

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founding

Scott, I vaguely think you had something like "Will I keep taking Zembrin?" on one of your prediction posts? If so, that may have biased your results relative to Troof's.

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Curious, I've been doing hardcore weightlifting and I'd hardly place it above placebo.

Probably because I did not think at the time that it might have nootropic effects.

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SAMe has been shown to work in RCT after RCT for what, exactly? I can find some articles on depression but an antidepressant is different than a nootropic.

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I bought some Zembrin on the strength of your last post, and I don't know how to evaluate it.

I had been feeling sluggish because I'd had to give up caffeine because of my IBS; getting going in the morning suddenly got a lot harder and I was after a caffeine replacement. Zembrin in no way provided that kick, but with it I think I feel better, but that feels like a really poor measure.

The only data I really have is that at the end of the bottle I let it run out, and 2 days later patterned said "What's wrong? You look really miserable. Have I upset you?", so I got some more

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Sample size of one: I replaced my SSRI prescription with Zembrin after your survey, and it has very similar effects (including the same genital anethesia side effect, though less intense.)

I'm usually very inclined to blame things on the placebo effect, but 'impossible to feel pleasure on d*?&' isn't a plausible placebo effect for me. On top of that, years of trying different SSRIs and going on/off them makes me very clear on whether I'm on them.

I'm completely convinced that Zembrin is an over the counter SSRI. I suspect the difference in rating is a selection bias in the population answering the survey. SSRIs suck unless you need them, so if their survey had fewer anxiety/depression patients than yours it would make sense that they have less signal.

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Call me Mr. Natural, but it seems to me a pretty good RX for optimizing brain function is regular exercise, good sleep sleep and meditation, my big 3, along with the healthy plant-based diet my doc recommended. There was a time when I used to find a couple of lines of good coke to be bracing, but those days have come and gone, as Brer Rabbit was wont to say.

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Feels like we need a benchmark (or better, placebo control, but that's not realistic) for this kind of comparison. The ad-hoc Bayesian adjustment you did is a reasonable starting point. From there, seems like caffeine is a decent benchmark, just because it's available to anyone and a lot of people consume it without setting out to find nootropics. Then again, the sorts of people that take a nootropic survey might also consume caffeine in unusual ways. But 'things statistically better than caffeine after adjustments and controls' probably pins down a generally strong set of possibilities.

More dimensions would probably help too. 'Drug good VS drug bad' (yes, that's an over-simplification, and the justification for vagueness of question made sense for the first run at this) is a good starting point, but I'm sure there are several common nootropic dimensions that people are looking to improve from their subjective baselines. Energy/wakefulness? Mental clarity? Productiveness? Happiness/satisfaction with life? I'm sure there's a better taxonomy floating around.

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I donโ€™t see any SARMs but I skimmed it really fast.

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Where is beer (or any alcoholic beverage)? And where is cutting down on drinking? Am I on the wrong planet here?

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I don't know how to categorise "reall. There is scant experimental and a lot of anecdotal evidence that beer (or maybe just small amounts of alcohol), with its disinhibiting effect, has a potential to make people think outside their boxes. Of course, the addiction risk makes it a very questionable nootropic. My bet is, there shall be more data on newer nootropics after a few generations to come. For my lifetime, I work with what has stood the test of time so far.

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Had not thought of categories, esp ease of accessing. Well done, very useful.

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Dexedrine is definitely better than Adderall. I had to quit Adderall and switch to Dexedrine because the levoamphetamine is too anxiogenic. I canโ€™t take more than 5 mg of Adderall without getting paresthesias but I can take a huge dose of Dexedrine without that effect.

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In "Worth The candle" Kefir was described as weak alcoholic drink, in this survey it turns out nootropic. What other majestic qualities this liquid hides, I wonder. *drinks a glass of kefir*

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Have you considered doing a scatterplot that combines your survey with Troof's? e.g. a cross around every data point. Then you can add a diagonal line (y=x), in which crossing the axis means that the two surveys are in agreement. Ellipses are an alternative to crosses and perfectly justified for large sample sizes.

If you send me the two datasets, I'd be very happy to do this.

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> I think we have mostly gotten what we can get out of this methodology, without many big surprises

The methodology I hope might take us further is for individuals to conduct their own blinded experiments. I tried this last year, with Phenibut, Adrenafil, and Phenylpiracetam. I put three of each kind in identical bags, mixed them around, and then tried to guess two hours later which of the three I'd taken. In 12 trials I ran, I guessed which of the three I had taken on half the attempts. This suggested to me that the effects from these three are pretty indistinguishable from a placebo. In explaining how I formulated my guess (prior to checking the answer), I often struggled to find any words to subjectively describe what made me think it was one noontropic over another. Since I couldn't enumerate how my guesses came about, and since my ability to distinguish between them was only slightly higher than chance would predict, I eventually discontinued them.

More recently I've come into a script for Adderall, so I went to Amazon and ordered a bottle of placebo tablets that are the same dimensions as the Adderall. I'm in the process of 10 trials to see the extent to which I can differentiate between the stimulant and my placebo. If even 10 people were to double blind experiment on themselves and publish the results, I'd feel a lot more confident that we really understand the efficacy of any of these substances on performance.

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