5 ms·

Pretty much accurate, this is also my perception. I think the whole "nootropics" and "biohacking" community would benefit from mandatory introductory reading t

Pretty much accurate, this is also my perception. I think the whole "nootropics" and "biohacking" community would benefit from mandatory introductory reading to understand that disrupting homeostasis in a durable and meaningful way is actually darn hard to do without serious side effects.

spondylosaurus 1y ago
https://www.thecut.com/article/supplements-made-me-lose-my-mind.html https://www.thecut.com/article/supplements-made-me-lose-my-m... A recent cautionary tale about someone who took St. John's Wort because they didn't want to take antidepressants, then quit the SJW too quickly... which functionally put them into (prolonged, agonizing) SSRI withdrawal.
- Aurornis 1y ago
  SJW inhibits serotonin uptake and also has numerous other targets. It’s a fundamental misunderstanding of the alternative medicine world to consider it safer or more gentle than SSRIs.
  - spondylosaurus 1y ago
    Yeah, I thought it was ironic (and a little funny) that people promote it as an SSRI alternative even though it's just a less precise, less regulated SSRI. It's like telling someone to skip their quinine pills and chug a bunch of tonic water instead!
    - girvo 1y ago
      To be fair, tonic water (with some gin in it) tastes a lot better than quinine pills!
Aurornis 1y ago
> understand that disrupting homeostasis in a durable and meaningful way is actually darn hard to do This is a huge problem in online ADHD communities, too. The ADHD subreddits are a constant stream of people having “Wow I feel amazing” reactions after taking their first stimulant dosage, followed a week later by complaints that it “stopped working”. It’s a constant cycle of informing people that the euphoria they experienced was a side effect, not how they’re going to feel for the rest of their life taking a stimulant.
- protocolture 1y ago
  Yeah I remember that high lasted for several weeks.
- landl0rd 1y ago
  Yeah there's functionally no good solution besides occasional stimulant use and staying off them the rest of the time. I vaguely recall some literature that claimed many patients had basically no benefit by some period (believe over a year) which matches friends' anecdotal experience. Exceptions exist; they aren't super common. Direct dopamine regulation is just a crappy target for this. TAAR1 agonism may be a better target. I've heard some sketchy reports that things in the class of bromantane might be good options, as it acts to epigenetically upregulate dopamine synthesis rather than altering clearance, but not super well-investigated and noot bros are a little weird here (initial research chose it for a balance between physical work capacity increase vs. cognitive benefits, whereas a cognition-focused analogue might perform better.) HDAC inhibition is vaguely interesting but much too large a target. There are some possibilities to work on, but basically this remains a very unsolved problem, and rhetoric around tolerance often reminds me of the oxycodone "pseudo-addiction" language as much as anything. "Your brain is dopamine-deficient!" No, homeostasis means this probably isn't the case. There may be deficits in signaling but it's not an issue with the concentration of a neurotransmitter.
  - Aurornis 1y ago
    > Yeah there's functionally no good solution besides occasional stimulant use and staying off them the rest of the time. This is literally the misunderstanding I was talking about. The startup euphoric effects are a side effect, not the main ADHD therapeutic function. This is the confusion that leads people off track, especially when they’re prescribed too high of a starting dose. Taking the stimulant every day and acknowledging that it’s not supposed to be euphoric is the only way to use them for actual ADHD treatment. The attention-enhancing effects largely remain. This is also where the “stimulant medications affect ADHD people differently” myth comes from. The real reason is that the ADHD patient has taken the med for years and doesn’t get a stimulant rush when taking it. The college student who borrows the fully-titrated dose from their friend is speeding around because they are stimulant naive. > Direct dopamine regulation is just a crappy target for this. TAAR1 agonism may be a better target. Amphetamine (Adderall) is a TAAR1 ligand. Guanfacine (non-stimulant ADHD medication) is as well. > I've heard some sketchy reports that things in the class of bromantane might be good options, as it acts to epigenetically upregulate dopamine synthesis rather than altering clearance, Bromantane is thought to upregulate expression of some genes related to dopamine, but it also might have some effects on the sigma receptor, act on a potassium channel, and it does have some dopamine reuptake inhibition though the exact amount is up for debate. Anyway, people often equate ADHD and dopamine, but norepinephrine is actually the common thread among all ADHD medications. Like you said, there’s a lot of “dopamine deficiency” broscience on the internet that doesn’t really match the science.
os2warpman 1y ago
The nootropics and biohacking community would benefit most of all by being told repeatedly every time they post online about their “stack” that a good night’s sleep and adequate water intake is more effective for cognitive function than every powder ever put into a pill.
- nradov 1y ago
  Frequent exercise is also far more effective for cognitive function than anything you can get in a pill. https://pmc.ncbi.nlm.nih.gov/articles/PMC5934999/ https://pmc.ncbi.nlm.nih.gov/articles/PMC5934999/
  - Earw0rm 1y ago
    Good sleep and frequent exercise are both amazing. That said, without a good to excellent diet or supplements, exercise can deplete things which in turn compromises sleep and recovery. How do I know? My sleep quality was shot to shit. Tried Mg supplements on a hunch, and got a massive improvement in sleep quality and exercise metrics (I put the latter down to better sleep, not anything in the supplements). I'd tried all the other sleep stuff, no caffeine after 3pm, various GABA modulators, found the somewhat improved sleep quality wasn't worth morning foggyness and lack of motivation, and I didn't like the fog they cause generally (you sleep, but, like alcohol or weed, it's not _clean_ sleep.)
- DontchaKnowit 1y ago
  I mean Ive been out of the loop for a while but that was always a huge disclaimer that was frequently repeated

spondylosaurus 1y ago

https://www.thecut.com/article/supplements-made-me-lose-my-mind.html https://www.thecut.com/article/supplements-made-me-lose-my-m... A recent cautionary tale about someone who took St. John's Wort because they didn't want to take antidepressants, then quit the SJW too quickly... which functionally put them into (prolonged, agonizing) SSRI withdrawal.

Aurornis 1y ago
SJW inhibits serotonin uptake and also has numerous other targets. It’s a fundamental misunderstanding of the alternative medicine world to consider it safer or more gentle than SSRIs.
- spondylosaurus 1y ago
  Yeah, I thought it was ironic (and a little funny) that people promote it as an SSRI alternative even though it's just a less precise, less regulated SSRI. It's like telling someone to skip their quinine pills and chug a bunch of tonic water instead!
  - girvo 1y ago
    To be fair, tonic water (with some gin in it) tastes a lot better than quinine pills!

Aurornis 1y ago

> understand that disrupting homeostasis in a durable and meaningful way is actually darn hard to do This is a huge problem in online ADHD communities, too. The ADHD subreddits are a constant stream of people having “Wow I feel amazing” reactions after taking their first stimulant dosage, followed a week later by complaints that it “stopped working”. It’s a constant cycle of informing people that the euphoria they experienced was a side effect, not how they’re going to feel for the rest of their life taking a stimulant.

protocolture 1y ago
Yeah I remember that high lasted for several weeks.
landl0rd 1y ago
Yeah there's functionally no good solution besides occasional stimulant use and staying off them the rest of the time. I vaguely recall some literature that claimed many patients had basically no benefit by some period (believe over a year) which matches friends' anecdotal experience. Exceptions exist; they aren't super common. Direct dopamine regulation is just a crappy target for this. TAAR1 agonism may be a better target. I've heard some sketchy reports that things in the class of bromantane might be good options, as it acts to epigenetically upregulate dopamine synthesis rather than altering clearance, but not super well-investigated and noot bros are a little weird here (initial research chose it for a balance between physical work capacity increase vs. cognitive benefits, whereas a cognition-focused analogue might perform better.) HDAC inhibition is vaguely interesting but much too large a target. There are some possibilities to work on, but basically this remains a very unsolved problem, and rhetoric around tolerance often reminds me of the oxycodone "pseudo-addiction" language as much as anything. "Your brain is dopamine-deficient!" No, homeostasis means this probably isn't the case. There may be deficits in signaling but it's not an issue with the concentration of a neurotransmitter.
- Aurornis 1y ago
  > Yeah there's functionally no good solution besides occasional stimulant use and staying off them the rest of the time. This is literally the misunderstanding I was talking about. The startup euphoric effects are a side effect, not the main ADHD therapeutic function. This is the confusion that leads people off track, especially when they’re prescribed too high of a starting dose. Taking the stimulant every day and acknowledging that it’s not supposed to be euphoric is the only way to use them for actual ADHD treatment. The attention-enhancing effects largely remain. This is also where the “stimulant medications affect ADHD people differently” myth comes from. The real reason is that the ADHD patient has taken the med for years and doesn’t get a stimulant rush when taking it. The college student who borrows the fully-titrated dose from their friend is speeding around because they are stimulant naive. > Direct dopamine regulation is just a crappy target for this. TAAR1 agonism may be a better target. Amphetamine (Adderall) is a TAAR1 ligand. Guanfacine (non-stimulant ADHD medication) is as well. > I've heard some sketchy reports that things in the class of bromantane might be good options, as it acts to epigenetically upregulate dopamine synthesis rather than altering clearance, Bromantane is thought to upregulate expression of some genes related to dopamine, but it also might have some effects on the sigma receptor, act on a potassium channel, and it does have some dopamine reuptake inhibition though the exact amount is up for debate. Anyway, people often equate ADHD and dopamine, but norepinephrine is actually the common thread among all ADHD medications. Like you said, there’s a lot of “dopamine deficiency” broscience on the internet that doesn’t really match the science.

os2warpman 1y ago

The nootropics and biohacking community would benefit most of all by being told repeatedly every time they post online about their “stack” that a good night’s sleep and adequate water intake is more effective for cognitive function than every powder ever put into a pill.

nradov 1y ago
Frequent exercise is also far more effective for cognitive function than anything you can get in a pill. https://pmc.ncbi.nlm.nih.gov/articles/PMC5934999/ https://pmc.ncbi.nlm.nih.gov/articles/PMC5934999/
- Earw0rm 1y ago
  Good sleep and frequent exercise are both amazing. That said, without a good to excellent diet or supplements, exercise can deplete things which in turn compromises sleep and recovery. How do I know? My sleep quality was shot to shit. Tried Mg supplements on a hunch, and got a massive improvement in sleep quality and exercise metrics (I put the latter down to better sleep, not anything in the supplements). I'd tried all the other sleep stuff, no caffeine after 3pm, various GABA modulators, found the somewhat improved sleep quality wasn't worth morning foggyness and lack of motivation, and I didn't like the fog they cause generally (you sleep, but, like alcohol or weed, it's not _clean_ sleep.)
DontchaKnowit 1y ago
I mean Ive been out of the loop for a while but that was always a huge disclaimer that was frequently repeated