Posted by julianh65 23 hours ago
Even Vyvanse vs Adderall XR are reported to have markedly different effects on the same person -- and after metabolic conversion, they're supposed to be the same active ingredient with fairly similar time release duration.
Good recent writing on the topic: https://dynomight.net/theanine-2/
Not sure why the nootropics people are always trying to come up with alternate theories for why something works when substances like caffeine are well studied and known to provide a mood boost.
That's... sad! I look forward to every day! I look forward to breathing when I wake up! I hope that changes for you soon.
It’s wild to me that the nootropics community evolved into a hybrid between the recreational drug community and supplement enthusiast communities while forgetting all of the lessons people learned in those communities long ago.
So much of the nootropics discourse is about compounds that have a moderate to high recreational value: The above post is talking about Kratom (an opioid) as if it was a nootropic, which would be unfathomable under the original description of nootropics.
The linked article also includes psilocybin, tianeptine (a compound that started out with some myths about serotonin but was later discovered to be an opioid), and phenibut (an extremely addictive substance, see /r/quittingphenibut )
The latter substance is known for temporarily reducing anxiety and giving a confidence boost, which is a common theme among substances cited as helpful. Something about calling them “nootropics” seems to reset people’s expectations and they forget that all recreational drugs make people feel some combination of euphoria, motivation, confidence boost, anxiety reduction, or stimulation at first, before tolerance takes in. People find themselves not only tolerant to these substances, but in withdrawal when they don’t take them (as mentioned above)
Phenibut is one of the most obvious recreational drugs that got pulled into the “nootropics” label for years. Nootropics Depot got caught importing large numbers of drums of this substance for resale. They deleted a lot of the discussion about their lawsuit on /r/nootropics (did you know they control the subreddit?) and have put forward a very selective version of the story that makes them look like the victims. Meanwhile it was one of the most common debilitating addiction stories coming out of supplement and nootropics communities until word spread that it was highly addictive and the withdrawals were very long.
Whatever meaning the word “nootropic” originally had is long lost. It’s now a blanket term for experimenting with powerful supplements or prescription drugs under a different name. I think that alternative name has left a lot of people blind to the reality of what they’re doing. They also frequently don’t realize that self-reported feelings of drug liking effect are not indicative of the drug’s objective positive effects.
Kraton I couldn't make the same argument and not familiar with tianeptine / gas station scag.
It doesn't help that I'm on Adderall, but if left to my own devices, would absolutely skip it. I'm assuming I benefit in the able to think way from it. Largely the only reason I know I missed a dose is if I find I lose my patience quickly with others.
That, historically, does not work well for neurochemistry. Large random trials are good for an average biological response of profitable chemicals, but it seems there are significant differences in neurochemistry, between people, that these don't capture. If you've ever had a prescription for most anything mental related, like ADHD, depression, etc, there's never just one drug, there's a panel that you just kinda go through until one works for your personal neurochemistry, with some having detrimental side effects for some people.
Unsurprisingly, it seems to be the same with many of these nootropics. I've had several very negative reactions to common nootropics at fractional doses, where others have positive experiences at many times the dose. A few resulted in migraines every day I took it, until I stopped, with one quickly resulting in depression and the only suicidal thoughts of my life, which went aways just as fast as I stopped. One hurt my short term memory so much I couldn't repeat a phone number (a very potent racetam like).
Some nootropics are precursors, which are mostly self regulating/supplements, but there are many out there that very actively poke low level neurochemicals, and your personal response will vary, just as is expected in the regulated drug world.
Min/maxing personal neurochemistry won't come from large random trials.
Controlled trials are actually very revealing of the placebo effect, which is a rampant confounded in nootropics communities. When people spend months reading about new nootropics, then a week waiting for it in the mail, then they take their first dose with excitement and anticipation they generally report feeling something.
The nice thing about trials is that they can start separating out this placebo effect.
Several people have done self-trials with different compounds with surprising results. Gwern is perhaps the most famous. Whenever people post about magnesium being a life altering substance or producing profound effects I also point them to his measured magnesium trials where the net effect over time was beginning to trend negative.
One of the myths in nootropics communities is that everything is a matter of neurochemistry and everyone is substantially different. In reality, RCTs are actually great at capturing enough people to see subgroups responding if you have enough people.
One thing most nootropics people don’t acknowledge enough is how often placebo effect appears in RCTs. Perform an RCT for depression and the placebo group will get better. It happens in every study. Give college students Adderall before an exam and they will report performing better, despite no statistical improvement in their grades. Now consider these facts in light of all of the scattered nootropics forum reports from people claiming different substances cured their depression or made them smarter. Not surprisingly, if you check their post history more recent comments will show them off on a new tangent trying a new substance, the old one long forgotten as a short trial that didn’t work out.
There is an argument that people should treat their own lives as an experiment. Where you track the things you do and see if you can find patterns on mood and productivity and such. If you want to know what generally works, though, there is no counter to effectiveness in RCTs, though?
Put differently, when has evidence ever gone counter to RCTs? Not just are there some questions that an RCT hasn't covered, but times it has been counter to the results?
That's a good example, because the statement "clearly effective" is absolutely false, as will be stated by a doctor when they prescribe it to you, and can be found in the documentation that comes with the medication. It is not appropriate or effective for some people, and is detrimental for others (accounts of both are found trivially online).
> "your unique biochemistry means we have no idea whether it will work for you" level of uncertainty.
If by "work" you mean feeling something happen after you pop some pills, then sure...it's amphetamine.
If by "work" you mean "improved outcome", again, refer to the drugs documentation or are pharmacist, and also observe the existence of ADHD drugs that are not Adderall. The person prescribing it to you will quite literally tell you that it doesn't work for everyone, and go down the list of available drugs until you find something that, in fact "works for you", all entirely based on your personal response to the drug. Those reasons range from ineffectiveness (too high dosage requirement), unacceptable personality changes, to, of course, the rare full psychosis.
Difference in amphetamine response is well documented [1]:
> The clinical effects of amphetamine are quite variable, from positive effects on mood and cognition in some individuals, to negative responses in others, perhaps related to individual variations in monaminergic function and monoamine system genes.
Ritalin is also ineffective for some, for unidentified reasons [2]:
> The response rates to MPH among adult ADHD patients range from 25 to 78 % in controlled trials (Wilens et al. 2011).
The difference is that you’ve taken it medicinally for years, whereas most nootropics users are early users who are experimenting with high placebo priming.
Stimulant prescriptions have a high churn rate because many people take their first few doses and feel euphoric, then think it’s going to be like that forever. Fast forward a couple years and the fun is long gone so it’s a different story.
Nootropics forums are dominated by posts from people saying “Just took my first dose of $substance and I feel amazing!” which is the least useful measure of how well it will treat someone long term.
That said, sounds like we are largely in agreement? I have gotten where I assume everything is dominated by noise.
Modafinil, Racetams, Noopept, Phenibut
Noopept seems to be curiously missing from this list?
Very fun substance also nasty as fuck and undoubtably bad for your brain. (I got weird neurological "withdrawal" symptoms after like 3 days of taking it)
Spent 8 continuous hours vomiting with the worst nausea I've ever felt in my life.
Lesson hard learned. I've been using Phenibut for nearly 10 years, I only take it on the weekends.
I quite enjoy high doses, feels much better than drinking without negative physical side effects. I don't drink alcohol in general, to be honest.
It’s impossible for anyone to say this convincingly about their own experience. If it were easy to tell whether an effect was due to placebo, we wouldn’t need blinded trials!
Like...nobody could ever take a macro dose of LSD or mushrooms and not know it.
But it is evidence. Think of this as more observational science rather than experimental science; we have to do some work to determine whether it is worth trying to do blinded experiments to validate an effective, and this is that work.