Alexander 2022 Link Troof Nootropics

6/20/22, 9:46 PM Link: Troof On Nootropics - by Scott Alexander
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Troof On Nootropics
May 17 86 119
Should have signal-boosted this earlier, forgot, sorry.
The author of the blog Troof sort of replicated my 2020 nootropics survey. But instead of
another survey, they made a recommendation engine. You rated all the nootropics you’d taken,
and it compared you to other people and predicted what else you would like. The end result
was the same: lots of people providing data on which nootropics they liked. Troof got 1981
subjects - more than twice as many as I did - and here were their results:
https://astralcodexten.substack.com/p/link-troof-on-nootropics 1/30
This is hard to compare to my survey - it has some different chemicals, and includes a few
things that aren’t chemicals at all like meditation and exercise. But the things that both
surveys share are in a pretty similar order. I think we have mostly gotten what we can get out
of this methodology, without many big surprises.
Why do I say this in such a resigned-sounding tone, as opposed to a more triumphant “the
results have replicated, so we’re now sure they’re true”? The surveys show that:
Addictive or illegal things do better than safer ones

Difficult but popular lifestyle interventions do better than chemicals
Fancy high-tech chemicals do better than well-known normal ones
We should sort of expect all of these things to be true. People wouldn’t keep doing difficult
lifestyle interventions unless they worked; the truly useless ones have probably fallen into
obscurity. People wouldn’t risk addictive or illegal things unless they had impressive effects.
But it also seems kind of suspicious for placebo effects. People go through a lot of trouble to
do something and then figure it must work. If something’s too cheap or easy or boring, they
forget about it.
I’m especially concerned by psilocybin microdosing, which ranked 8th of almost 150
interventions. Several double-blind studies have now shown this doesn’t work (eg). Worse, in
unblinded studies, it seems to “work” best for the people who most strongly believe it will
work, and seems to have whatever effect these people believe it will have. This is most likely a
very exciting-sounding intervention that doesn’t work at all, and it was one of the very
highest-rated on this survey. Meanwhile, SAMe, which has been shown to work well in RCT
after RCT, is one of the lowest-rated.
To put this another way: if you made a model combining some measure of “how hard is this
chemical to obtain / how hard is this lifestyle intervention to practice?” and “how novel and
high-tech does it feel?”, plus one or two other things like “is this a stimulant?”, it feels like this
would predic the results almost perfectly. Does anything stand out as doing substantially worse
than the simple model would predict? It really doesn’t. Maybe theanine, a little? I’m grasping
at straws.
Finally, in my survey, I got impressive results for Zembrin, a certain extract of the kanna plant.
This survey fails to replicate that - Zembrin lands exactly where the “how hard is it to get?
how fancy is it?” model would predict, which is not very high. I’m not sure why my survey got
such strong results. I know I was personally excited about Zembrin, so there’s room for
experimenter bias, but I can’t think of how I would have added in the experimenter bias when
I was just collecting your ratings. Maybe I bungled the statistics somehow? In any case, it’s a
completely average anxiolytic in every way.
Thanks to Troof for doing this! They draw some different conclusions from me, which you can
read at the end of their post.
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Chronological
MAC May 17
I wonder where Oroxylum extract would place if it were included.
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Scott Alexander May 17 Author
I predict the phenylpiracetam/bupropion/methylliberine area of slightly novel mild
stimulants.
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Alec May 17
That’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.
I don't think Dexedrine has an anti-anxiety component, beyond the general tendency of
stimulants to be anxiolytic to people who really need them. I think amphetamines just work
better than Ritalin does.
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Alec May 17
That’s a good point. I hadn’t thought of that.
Could it also be that Dexedrine happens to fall more within the sweet spot of how long
people want to work?
Dexedrine IR, Adderall IR operates in 3-5 hour windows, Ritalin IR operates in 2-4 hour
windows.
3-5 hour range seems more in-line with the length of a single work bout.
Scott Alexander May 17 · edited May 17 Author
There are a bunch of different amphetamine and methylphenidate derivatives with
different half-lives (Vyvanse, Concerta, Metadate, etc) and on average people
pretty consistently find the amphetamines better than the methylphendiates
regardless of half-life (though a few people have the opposite experience).
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Error May 17
For what it's worth, I've been on all three, and the amphetamines worked
noticeably better than Ritalin for me.
The desired window length may vary by what you're using it for. I work in IT and
find I *want* 7-8 hours, and today I use Dexedrine XR for that purpose. Used to be
Adderall, but Adderall rendered me sleepless long after the intended effect had
worn off.
(I can only guess why Dexedrine doesn't do the same; my current guess is that, of
the three (?) additional salts in Adderall, one of them metabolizes extremely slowly
for for some reason.)
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Himaldr May 17 · edited May 18
My friend, you're trying to solve something that isn't a mystery in the first place:
these drugs have different actions and feel different, it's long been known that
amphetamine is generally preferred, and it's long been known that
dexamphetamine is preferred to Adderall's 3:1 d:l mix.
I'm truly not sure why one might start postulating something like "they must have
added an anti-anxiety component" or "people must like how long it lasts" — no,
it's just dexamphetamine there's no added anxiolytic, there are a dozen different
formulations that last different amounts of time, 3-5 hours is not the usual desired
length in any case, and *it feels different in the first place why would you try to find
other reasons everyone knows amphetamine is preferred am I going insane*
Anomaly May 17
IME Ritalin would cause extreme drops in mood and self loathing in addition to the focus
effect. I'm talking crying and cursing myself while simultaneously cleaning and reading text
books. Amphetamines never had that effect on me. No idea what chemistry was going on
there.
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Alec May 17 · edited May 17
I had a similar experience on Ritalin—mania, paranoia, and anxiety. Dexedrine just gives
me a bit of paranoia—barricading my door at night—it works well for me overall though.
magic9mushroom May 18
>That’s really interesting that Dexedrine lists at the top.
Amphetamine is addictive i.e. it makes you feel good. This is going to cause high ratings
regardless of whether it helps in other ways. Scott mentions that amphetamine always gets
stellar ratings (and methamphetamine higher ones) back in Know Your Amphetamines.
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6/20/22, 9:46 PM
py p Link: Troof On Nootropics - by Scott Alexander
Eugene Norman May 17

Is Zembrin freely available.
Yes, there are a lot of Zembrin products for sale on Amazon, I think Calm-Z is the big one.
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Jonathan Ray Writes Far-Tentacled Axons May 17
I tried Calm-Z from Amazon and the first pill had a large immediate effect but caused a
continuous headache for 2 days. I recommend starting with half or a third of a pill and
tapering up if it's well tolerated.
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James Miller May 17
Calm-Z worked for me. Amazon stopped selling it and an alternative Zembrin product I
bought didn't work. I now buy Calm-Z from https://drbvitamins.com/.
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Did you the zembrin from nutricost on amazon? Nutricost is usually good (and
cheap)
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James Miller May 18
It was "Nutricost Sceletium Tortuosum Made with Zembrin"
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Wow, you're right, they really did take it down, wonder why.
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Ron Barr May 17
Is ayahuasca not a Nootropic? It's far more effective for me than anything on the list.
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Technically nootropics are supposed to only be things that are safe, near side-effectless,
and affect cognition rather than emotions, etc. Nobody sticks to that definition faithfully any
more so sure whatever why not?
6/20/22, 9:46 PM
more, so sure, whatever, why not? Link: Troof On Nootropics - by Scott Alexander
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Schweinepriester May 18
Ok, that explains why alcohol and tobacco haven`t been listed. Concerning side
effects, there is some evidence in cultural integration. As a youth, I was daring, but now
I prefer substances with some generations of humans using them. Better the devil you
know...
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Radar May 17
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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Radar May 17
Also while I'm fantasizing about studies, I'd like to see Effexor up against weightlifting.
Effexor always struck me as the nuclear weapon of antidepressants (from personal
experience and seeing others taking it) and if weightlifting is more effective, wow, shouldn't
we prescribe that a lot more? Maybe we just need to medicalize exercise regimes a bit more
and people would stick to them? Like with follow-up visits the way we do med management
and providing some insurance-covered coaching.
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Liface May 17 · edited May 17
See my top-level comment. The survey does not ask if weightlifting was effective for
depression, it merely asks about a vague "net benefit"
(https://i.imgur.com/CvbGHrJ.png). People could (and probably are) rating
weightlifting's effect on their physical appearance, not their mental health.
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Anomaly May 17
Weight lifting greatly improved my overall mood and mental stability long before I
had visible gains.
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Radar May 17
I guess if the survey had been done in a men's lifestyle magazine, I would agree
with you. But this was a survey of nootropics, including mention of possible
placebo response in the choices. With that frame of that survey, it would surprise
me if many people rated weightlifting high because they liked how it made them
look apart from any mental state benefits.
I also personally know some folks who would describe their experience of weight-
lifting as life changing in terms of energy, focus, and mood -- so that predisposes
me to reading that survey result as "the nootropic benefit of weightlifting" and not
"the cosmetic benefit of weightlifting." Of course cosmetic benefits can also have
mood benefits, but I don't imagine that accounts for all of it just given what we
understand about the biological benefits of exercise generally.
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Radu Floricica May 18
Weightlifting has psychological effects you definitely don't expect. I remember
many years ago when I first started diet+exercise that the biggest impact was...
agency. I was young and so slightly lost, and it was something which was difficult,
but showed results in proportion with the effort I put in. In a chaotic world that was
pure gold.
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smocc May 18
And even better, it has numbers that go up!
RRob May 18
Agree on the agency part. I barely lift at all each morning but it definitely
makes my day better, and I try hard not to miss it on a work day. Long term
there was a good benefit from realizing I wasn't as weak as I had felt, and
seeing my capacity increase was sweet and proof I could change things. But I
was having better days long before that.
Lifting weights is also the only thing that's ever cured my headaches once
they start. As soon as my body reaches the "more oxygen needed!" phase I
feel my head open up and I start to feel better. The stronger I've become the
more reps it's taken. I suspect this is part of the same mechanism that makes
my day better - I'm taking my body beyond some "slacker mode" threshold
where it would otherwise linger.
Minor positive impact on my ability to fall asleep, just from imagining the next
thing I'll be doing is waking up and lifting weights. This might be about
distractions, since I noticed the same benefit from thinking about solving
programming problems (vs. thinking about work problems which keep me
awake).
Carl Pham May 18
I hate weight-lifting. I do it because I must, but I'd rather run 10 miles -- in the rain -- than
squat a 200 lb barbell even once.
Himaldr May 18
Complete opposite here. God I fucking hate cardio, but I love me some weights.
Eye Beams are cool May 18
Individual variation uber alles. Resistance training and HIIT are great for my mood. LISS
is just a big no thank you.
Why do you feel you "must" lift? For aesthetics, yeah, I think you are right. For health
and longevity, I think the latest Stronger by Science podcast makes a pretty good
argument (against interest) that you don't.
Carl Pham May 20 · edited May 20
I've tried it both ways. If I don't lift, my back starts hurting from sitting in a chair
too often (and getting old of course), and my posture goes to hell. If I do a regular
regimen of squats, deadlifts, and presses with a barbell, plus a little bit of
dumbbell work for the arms, then my back doesn't hurt, I can breathe easier, move
better, and any aerobic exercise I do get easier and more effective. It's 100% clear
that for me, at least, the two are complementary and I need both, the aerobic stuff
to keep the arteries flexible and the mind clear, and the shifting of dead iron
around to build strength, resilience, and balance.
I'm not entirely sure why I despise weights so much. It may just be that it has to be
done indoors in a smelly gym facing the wall, with dumfuk rap or some other
twentysomething tunes blasting my ear. When I run I go on trails and I breathe
clean air freshly synthesized an hour ago by trees, I watch small animals jump out
of the way startled, I splash through streams or balance on logs, and hear nothing
but the wind and water. I am alone with my thoughts and nature, and it feels
restorative. Weight lifting just feels like work. Going to the office to do what must
be done
6/20/22, 9:46 PM
be done. Link: Troof On Nootropics - by Scott Alexander

Xpym May 18
I did weightlifting for years without any noticeable effect on my mood or whatever, but I
never interacted with anyone at the gym beyond the occasional spotting. My guess that
there is a big effect for people who socialise there while lacking other venues for that.
It is perfectly possible to do both. And any weight lifter should do endurance stuff as any
runner should train strength. Of course, all should do some stretching routine, coordinative
stuff and meditating, before even considering having a beer.
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Falacer May 18
Weightlifting is a strange one to me, people often seem to ascribe to it near magical impacts
but I can't really tell. I wonder if it's because I've been doing it long enough that I just don't
remember, and my baseline would be worse if I didn't have the experience? It also seems
like the benefit is going to be more noticeable while in the numbers-go-up phase, and once
you've started to hit plateaus that require turning it into a full time job to progress it
becomes more tedious.
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NLeseul May 19
I would love to see someone do a study comparing video game speedrunning to various
forms of physical exercise, personally. How much of the mental benefit is just due to seeing
yourself improve on a challenging task using quantifiable metrics of progress?
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Osiris 👁 Writes Osiris Oko’s Newsletter May 17
I can confirm that weight lifting makes me feel like a genius
Liface May 17
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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Freedom May 18
"But there's no way I could ever notice an objective difference versus not taking them."
From a no-creatine base, try not lifting for 5 days while you creatine load, then go back to
lifting. Guaranteed you would notice the difference just in the amounts you could lift.
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Radu Floricica May 18
I rated modafinil a 10, and I take only doses where subjective effects are almost zero. It
could be that some people take if for whatever small high if offers, but I find that less
productive. I'm basically using it as better coffee.
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Max May 18
You should actually test effects of creatine. They are pretty visible .3-5pct boost is
noticeable if you keep detailed stats and you are on a performance plateau
Troof May 18
On the survey, I explicitely asked people: "For lifestyle interventions like diets, please only
rate direct cogntive improvement.". You're right though, it was in small font, and a lot of
people don't read instructions anyway. It could inflate the result a little bit, but given these
specific instructions, and the fact that the survey is explicitely about nootropics, I'm pretty
confident the a large majority of people actually rated the cognitive benefit.
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Steeven Writes Blue Pine May 17
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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Josh Berry May 17
I was having a debate about meditation in another forum recently. It seems perfectly
captured by how much investment folks have in it. Such that some folk are so invested in it
that I feel they will greatly overstate any effect it could have.
Steeven Writes Blue Pine May 17
Personal investment seems like a component with any of these interventions. Why
would meditation in particular have an exaggerated overstatement relative to these
other interventions? In particular, Peloton bikes are jokingly referred to as a cult and
their classes actually seem to produce that level of buy-in.
I've meditated for years, and I think I'm calmer, but that might just be because I was
more emotional when I was younger, and I would have calmed down anyway. As far as
the scientific benefits, they seem weak enough that they could still plausibly be
overturned. I would still recommend meditating for 10 minutes a day, especially for
people who need assistance with emotional regulation, which is most people. The
plausible upside seems worth it, and the downside will be nil for most people
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Josh Berry May 17
I don't think meditation is even more exaggerated than the others. I think it is as
exaggerated as the others. Especially by those for whom it works.
Cups and Mugs May 17
This is great stuff but I still think there is a lot less homogeneity amongst people and the effect
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.
Expand full comment
Everything you say is true, but you still have to start your journey of finding what's right for
you by trying some specific thing, and the thing that works for most other people is a better
starting point than the thing that almost never works for anyone else.
Nobody has ever been able to consistently figure out the factors that predict who different
drugs will work for even when there are multiple teams throwing millions of dollars at the
problem for eg SSRIs, they're not going to do it for nootropics and so this is the level we're
stuck at for now.
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Yeah, Heroin works for everyone but somehow the people consuming it seem to have
something better to do than post here. This is no forum of losers.
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Libero Jun 4
I think his argument fails to: A) recognize the Bayesian importance of having a prior; B)
formalize that the treatment effect can be better mapped to a multimodal distribution.
Incidentally it seems that the recommendation engine works showing the similarity to a
treatment cluster, thus acknowledging that individuals can have different responses.
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Sandi May 17
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.
Unsigned Integer May 17
Curiously, extended sleep deprivation is a highly effective treatment for depression for
reasons that remain unclear. The effect goes away when you start sleeping again, though,
and for obvious reasons its unsafe to do this for long periods of time.
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Vaclav May 18
Sometimes an inadequate night's sleep can give me a sort of 'adrenaline shot', which
feels like my body's way of getting me through the day. If sleep deprivation is bringing
depressed people significantly above their usual baseline, I wonder if the body tends to
take the message that long sleep = you are safe and secure, and can afford to relax;
short sleep = you may be in a dangerous environment, and need to be ready to fight or
flee as required. I can see how the latter would counteract some kinds of depression,
albeit not in a sustainable way.
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RRob May 18
In my experience the first level of sleep deprivation isn't very self-evident. I feel
tired but not so tired. It's not until I look at the quality of my work from such a day
compared to a day with good rest that I see just how significantly impaired I was.
I've stayed in that mode for extended periods without realizing it.
Ghillie Dhu May 18
Are the people trying to get less sleep sleeping more or less than the people trying to get
6/20/22, 9:46 PM
Are the people trying to get less sleep sleeping more or less than the people trying to get
Link: Troof On Nootropics - by Scott Alexander
more sleep? My prior is on levels, not differences, being salient predictors.

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Sandi May 18
It's a good point.
My assumption was that that particular option was referring to Guzey's thesis, since it
recently made the rounds in the community so I'd assume anyone talking about
restricting sleep was inspired by his post.
If that's the case, Guzey says ~6 hours per night, so people ticking that option would
be aiming for that. Rather than it being hypersomniacs trying to get from 10-12 hours to
8. But even then, it should have a positive effect.
The Nybbler May 17
If only Walter White had sampled his own product (yes I know meth isn't on there), perhaps he
could have cured his cancer.
Meth is FDA-approved as a treatment for obesity when diet and exercise have failed. So, if
you need to lose a few pounds and the diet isn't working out, there's a simple, evidence-
based, FDA-approved solution available!
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Xpym May 18
But you might want to check out Requiem for a Dream first.
Jonathan Ray Writes Far-Tentacled Axons May 17 · edited May 18
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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In what sense is 10 mg/day orotate = 300 mg/day of citrate? I'm not an expert on this but my
calculations are different by like an order of ten.
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The label says 5mg of elemental lithium (as orotate), not 5mg of lithium orotate.
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But also I was off by a factor of 3 because I forgot that the citrate ion has a charge
of -3. I'll show my work this time.
Google says Lithium citrate is Li3C6H5O7 with a mass of 209.923
Lithium has a mass of 6.941
209.923 / (3*6.941) = 10.08
So 10mg of lithium from amazon equals only 100mg of lithium citrate.
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3ueuT May 18
Hi, I'm extremely interested in the topic of Lithium low dosing. Would you mind writing a bit
about it here in reply to this comment ? Or at the least would you mind telling me :
1. how long it took to work
2. if you have any issue or difference when you are NOT taking them (and how quickly those
signs come)
3. if you have any side effect
4. if you ever suspected you to have "non standard" mood prior to taking lithium, OR have
any diagnostics in particular.
As some of those questions are deeply personnal, I totally understand if you want to answer
by PM instead :)
Thanks!
1. Very quickly (within 15 minutes)

2. Bad mood, low motivation
3. No side effects on me, probably. I have some psoriasis that is listed as a potential
side effect but it started before I started taking lithium.
4. Mild to moderate depression diagnosis and some social anxiety.
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Troof May 18
Yeah right now the recommender system only takes into account ratings, not issues you
had. Good idea to include Lithium.
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Ryan W. May 17 · edited May 17
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?
IIRC you can snort inositol; it's often used as a fake substitute for cocaine on movie sets.
Anyone want to do a clinical trial on nasal bioavailability?
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dogiv May 17
Provigil is on there under the generic name, modafinil
dogiv May 17
Do you have a link on inositol for depression in people with PCOS?
TheAnswerIsAWall May 18
I found this: https://www.mdpi.com/1420-3049/25/23/5566/htm

I'm curious as to how inositol compares to e.g., metformin or hormonal contraceptives.
Someone close to me has struggled with PCOS for years and I don't believe any of her
doctors ever mentioned this to her, that's despite getting little to no benefit from the
first-line treatments.
myst_05 Writes myst_05’s Newsletter May 17
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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Based on personal experience, caffeine raises my heart rate a lot more than Adderall, and I
don't think anyone says you can't have caffeine while doing weightlifting or HIIT.
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myst_05 Writes myst_05’s Newsletter May 17
Out of curiosity, what's your avg BPM while walking with and without Adderall?
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Unsigned Integer May 17 · edited May 17
> Addictive or illegal things do better than safer ones
I imagine that some number of people who gave answers for Dexedrine or Adderall were taking
them legally for ADHD; I wonder if they give it a higher or lower rating than people obtaining it
illegally, and if that skews the average.
As someone with ADHD: Adderall is 7/10, allows me to do laundry, stops me from constantly
fidgeting, helps me pretend to focus during Zoom meetings. Doesn't help with executive
dysfunction much, though. It somehow both makes me less anxious and makes it harder for me
to sleep. YMMV.
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John May 17
Scott, FYI the Doctor's Best Zembrin linked from the lorien psych page is no longer available at
amazon.
Matt S May 17 · edited May 17
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.
So maybe you should take the steroids, and Bo should take the nootropics. We'll see who's
ahead afterwards.
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Ryan May 17
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.
Andrew May 17
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.
Milo Minderbinder May 17
Vegan might be catching some people who were allergic or sensitive to dairy and didn’t
know it.
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Bubblegum Lich May 18
I'd agree with your ideology ranking of keto/paleo/carnivore, but paleo is the least restrictive
of the three diets in terms of food groups/macronutrient balance. Ketosis is pretty
unpleasant for most people, and only a paleo person could avoid it.
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Vaclav May 18
The results don't say vegetarian bad, vegan less bad; they say vegetarian somewhat good,
vegan a bit better. The rating system is explained as:
6/20/22, 9:46 PM
g gy p
Link: Troof On Nootropics - by Scott Alexander
> 0 means a substance was totally useless, or had so many side effects you couldn’t
continue taking it.
> 1 - 4 means subtle effects, maybe placebo but still useful.
> 5 - 9 means strong effects, definitely not placebo.
> 10 means life-changing.
You can also see on this chart that the vegan and vegetarian diets are both assigned >70%
probability of having a positive effect:
https://troof.blog/posts/nootropics/ratings_effective_full.jpeg
(Also, I haven't checked exactly what the error bars mean, but the thick ones for vegan and
vegetarian overlap, suggesting low confidence that vegan > vegetarian. And the probability
of positive effect is slightly higher for vegetarian than for vegan.)
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csf May 17
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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Emilio Bumachar May 23
Makes total sense. Scott fans learn that Scott takes Zembrin, decide to try it on the grounds
that Scott is disproportionally likely to choose good stuff, then tell Scott that they're taking
it.
Unsigned Integer May 17 · edited May 17
So: I've recently become interested in possible links between Phenibut and GHB.
Though mostly known as an illegal drug, GHB is actually produced endogenously, where it acts
on both the specific "GHB receptor" and to a lesser extent on GABA-B. A lot about the brain's
endogenous GHB system appears to be unknown. GHB is (of course) a potent anxiolytic, and
seems to particularly reduce social inhibitions (hence its use association with date rape).
Phenibut seems to have similar qualities in terms of reducing anxiety and social inhibitions. Like
GHB, Phenibut is also a GABA-B agonist, but AFAIK it doesn't have any known effect on the GHB
receptor.
I'm curious as to whether these two drugs share the same mechanism of action (by both acting
on GABA-B), or if there's something unique about GHB that causes it to have different effects
(because of its action on the GHB receptor). There seems to be some evidence that activating
the GHB receptor causes a stimulating effect, possibly counteracting the sedation caused by
GABA B agonism
GABA-B agonism.
One also wonders if the GHB system plays a role in mental illness, given that it seems to be
important in regulating anxiety (particularly social anxiety). See this abstract (sadly the original
paper is in French): https://pubmed.ncbi.nlm.nih.gov/15745703/
Also see here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174623/
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Troof May 18
Do you know if there's the same kind of addiction risk with GHB than with Phenibut?
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Yes, if anything GHB is worse. So I wouldn't try it, but I might be curious if anyone in
this thread has tried both and can compare them.
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Treedoe May 19 · edited May 19
As you mention GHB is addictive by many accounts. But having taken the
prescription formulation (as of many others), it doesn’t seem to be addictive taken
once- or twice-nightly at fairly high doses. Not that that’s any sort of suggestion
anyone takes it recreationally or without prescription.
As for the stimulating effect you mention, yes. It has that. There’s a titration
schedule when starting it, and counterintuitively that effect is felt more often at
lower doses and it’s very unpleasant, like a waking dream with nausea and
dizziness turned up to 9; you just have to ride it out. My guess is that at lower
doses the sedative effects aren’t strong enough to keep one asleep against the
stimulating effects.
CptDrMoreno May 17
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.
Edmund Nelson May 18
exercise has proven benefits (https://www.cdc.gov/physicalactivity/basics/pa-
health/index.htm) and so i'd expect it to do well just because of that.
Cardio vs Weightlifting could be just people who did weightlifting were more likely to
actually keep trying or something.

dogiv May 17
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.
Yes, but both SSRIs and bupropion are pretty high up on the list. I think everyone has
forgotten the definition of nootropic and is voting off "makes me feel better".
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dogiv May 17
People do seem to conflate cognitive and mood benefits a bit (which is reasonable,
since improved mood can make you more productive). But bupropion is also a mild
stimulant, and SSRIs rank quite a bit lower. The stuff at the top of the list, adderrall,
Ritalin, modafinil, are all stimulants not especially known for improving mood. I think low
ratings for SAMe probably just mean it has no noticeable nootropic/stimulant effect.
I know people who do say it has a stimulant effect, but you're right that this could
be much rarer than the study-proven antidepressant effect.
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Himaldr May 18
"Adderall is not especially known for improving mood" is not a statement I
thought I'd see Scott let pass.
I thought depression can cause worse cognition, so fixing the depression might
improve cognition. Like curing a nutritional deficiency.
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On the other hand, being happy makes people more stupid and best analytical
thinking is not done in relaxed mode.
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DannyK May 18
Any suggestions on why No Fap placed so high? If they could put it in a capsule, it would be
advertised on late night cable TV.
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Xpym May 18
Probably because it is attempted as a part of commitment to go out/socialize more.
Jack AC May 19
Could it not just be that it's actually effective?
Potamus May 22
The answer to this question is found in researching "semen retention benefits."
Ben Curthoys May 18
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
Byrel Mitchell May 18
Zembrin isn't a stimulant, so it's not really going to replace the coffee kick. Sounds like it
might be having the mood-stabilizing effect of an SSRI though?
Byrel Mitchell May 18
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.
Michael Romkey May 18
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.
Scott A May 18
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.
Scott May 18
I don’t see any SARMs but I skimmed it really fast.
Alex C. May 18
The late psychologist (and noted self-experimenter) Seth Roberts developed a simple, quick
reaction time test that could be used to measure your brain function. I briefly worked on this
project with him before his untimely death in 2014. I'd like to start working on this project again,
and I'm looking for collaborators. The reaction-time test would be perfect for screening various
nootropics -- and it wouldn't rely on subjective assessments of their effectiveness. If anyone is
interested in working together on this project, please contact me at alexc [at] aya [dot] yale [dot]
edu. Seth's blog posts are still online. One representative post is here:
https://sethroberts.net/2014/01/09/reaction-time-as-a-measure-of-health/
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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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DannyK May 18
What’s the argument for beer being a nootropic? What about “reall
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John Schilling May 20
About the same as the argument for Phenibut being a nootropic. Phenibut's use case in
the nootropic arena seems to be "reduce anxiety, particularly the sort that impedes
social interaction". In which case, yeah, that's what a lot of people use beer for.
Since human brains are meant for social interaction at least as much as they are for
deep rational sciencey thinking, that's plausibly within the realm of nootropics.
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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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Kgoth May 21
Had not thought of categories, esp ease of accessing. Well done, very useful.
Moon Diamond Writes The Majorana Theory of Fascism May 22
Dexedrine is definitely better than Adderall. I had to quit Adderall and switch to Dexedrine
because the levoamphetamine is too anxiogenic. I can’t take more than 5 mg of Adderall without
getting paresthesias but I can take a huge dose of Dexedrine without that effect.
sapient fungus May 22
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*
Gustavo Lacerda Writes Gustavo’s Newsletter May 25
Gustavo Lacerda Writes Gustavo s NewsletterLink:May
6/20/22, 9:46 PM
25
Troof On Nootropics - by Scott Alexander
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.
inedibill Jun 2
> 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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Should have signal-boosted this earlier, forgot, sorry.

Addictive or illegal things do better than safer ones

Fancy high-tech chemicals do better than well-known normal ones

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Eugene Norman May 17

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various substances or lifestyle interventions will have on them.

more sleep? My prior is on levels, not differences, being salient predictors.

1. Very quickly (within 15 minutes)

I found this: https://www.mdpi.com/1420-3049/25/23/5566/htm

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