6 ms·

ISRIB (the molecule discussed in the article) seems _very_ promising for brain health. But people who (recklessly?) self-experimented with it had strange cardia

by manmal 5y ago

ISRIB (the molecule discussed in the article) seems _very_ promising for brain health. But people who (recklessly?) self-experimented with it had strange cardiac issues. A study on dogs discovered heart anomalies. It’s nicely summarized here: https://forums.phoenixrising.me/threads/isrib-to-treat-me-cfs.82311/page-2#post-2322603 https://forums.phoenixrising.me/threads/isrib-to-treat-me-cf...

bpodgursky 5y ago
If we pair ISRIB with pig heart transplants it's a side-effect free way to boost cognitive function though.
- soco 5y ago
  There we have it, yet another way to get those prion diseases...
- manmal 5y ago
  Perhaps a similar molecule can be found instead which does not have this problem. Or another compound can be added to prevent heart damage.
  - bpodgursky 5y ago
    It's probably going to be interpreted as cynical b/c it's HN but I do honestly believe that solving heart function will be lot easier than solving cognitive decline, and a win on cognitive decline is huge news (hopefully not paired with not pig hearts, but it's a reasonable proof of concept).
- redisman 5y ago
  Sounds very cyber punk.
- sdenton4 5y ago
  Open heart surgery - let alone replacement - isn't likely to be side effect free in our lifetime. A detached sternum is also a side effect, after all, requiring a couple months to recover to basic function...
- jac241 5y ago
  Totally side effect free if we ignore the risk of stroke from cardiopulmonary bypass (at least 0.5%), infection of the chest cavity (0.5-3% incidence of mediastinitis after median sternotomy), anesthesia complications, post op pulmonary embolism, pneumonia, UTI, etc.
  - meowface 5y ago
    I think that's the joke.
- bostonsre 5y ago
  I guess it depends on how long the bad effects on the heart last after taking ISRIB. If it keeps lingering, you may need new pig hearts over time. Or.. Just keep taking ISRIB and just schedule a yearly pig heart transplant.
PragmaticPulp 5y ago
I was debating whether or not to post some of those self-experiments. I'm aware of a couple more forums where people tried ISRIB and still claim to have lasting problems from it. One group was led by professional chemists who seemed like they knew what they were doing when it comes to testing and validating the product was pure. It's amazing what people can access now, but self-experimentation with these compounds is a terrible idea.
- meowface 5y ago
  Reminds me a bit of cerebrolysin self-experiments I've read. It can either permanently make you smarter or permanently give you brain damage. Or both, perhaps. (For anyone unaware, it's a bunch of neuropeptides harvested from pig brains that you typically either inject or - fittingly, due to the source - snort directly into your brain through your nose.)
  - texasbigdata 5y ago
    "Smarter" do you mean neuroregenesis? As I understood it's used post stroke to try to reverse some of the damage.
- treeman79 5y ago
  Developed a weird dementia at 39. Doctors Spent 2 years trying every prescription drug they could think of. Almost everything made matters worse. In some cases drastically. Complete nightmare. Those are with approved ones. Scary to try experiential. Eventually learned it was a blood disorder and a simple blood thinner was the answer.
  - nefitty 5y ago
    Wow. It sounds like you're better and hope you're better! That's an incredible story. Good on you for not giving up. You just lit a fire under my butt.
  - cma 5y ago
    Which blood disorder?
meowface 5y ago
Wow, that sounds pretty incredible. Part of what makes it sound promising to me is the extent of the "no free lunch" aspect: anecdotal reports of not just cardiac issues in humans and dogs but increased brain fog (mitigated with feed consumption...?), blunted emotions, inability to get drunk (maybe a plus?), accelerated cell death, psychosis and hallucinations - in exchange for, allegedly, reversing Alzheimer's and repairing lifelong brain damage: >One report of a person who gave ISRIB to their grandmother who had terminal stage Alzheimer's. She began to remember everyone. But died after 4 months (this may have been from old age and her type 1 diabetes). >One anecdotal report of a short course of ISRIB permanently fixing some prefrontal cortex brain damage in a Russian guy, caused by a car crash when he was a child. The repair to the brain was confirmed by MRI scans taken before and after the ISRIB treatment. Plus a pretty clear mechanism of action. Definitely sounds like it's worth significant study.
- emptysongglass 5y ago
  I mentioned this in another thread [1] but this idea of "no free lunch" is nothing more than a human aberration. There are many things in life that are free lunches, including drugs you put in your body but we as humans have such an overriding need to balance the scales of life we conveniently overlook them. Pattern recognition is helpful to a certain extent in life but we should be careful applying it arbitrarily and try to be aware of when we are doing it. I took a host of weird nootropics when I was younger. The most experimental was NSI-189. My experience is plenty of these drugs were gratis lunches but I wasn't enrolled in a study and don't have hard numbers to show you. [1] https://news.ycombinator.com/item?id=29800869 https://news.ycombinator.com/item?id=29800869
  - pitched 5y ago
    The scariest (potential) downside to nootropics to me is an increased risk of cancer. Because if your normal cells are healthier, cancerous cells are also healthier. As a younger person, cancer is less of a risk so nootropics are less of a risk too. So I was curious, with that in mind, where the free lunch drugs are? As in, which ones did you enjoy most and why stop taking them?

by manmal 5y ago

bpodgursky 5y ago

If we pair ISRIB with pig heart transplants it's a side-effect free way to boost cognitive function though.

soco 5y ago
There we have it, yet another way to get those prion diseases...
manmal 5y ago
Perhaps a similar molecule can be found instead which does not have this problem. Or another compound can be added to prevent heart damage.
- bpodgursky 5y ago
  It's probably going to be interpreted as cynical b/c it's HN but I do honestly believe that solving heart function will be lot easier than solving cognitive decline, and a win on cognitive decline is huge news (hopefully not paired with not pig hearts, but it's a reasonable proof of concept).
redisman 5y ago
Sounds very cyber punk.
sdenton4 5y ago
Open heart surgery - let alone replacement - isn't likely to be side effect free in our lifetime. A detached sternum is also a side effect, after all, requiring a couple months to recover to basic function...
jac241 5y ago
Totally side effect free if we ignore the risk of stroke from cardiopulmonary bypass (at least 0.5%), infection of the chest cavity (0.5-3% incidence of mediastinitis after median sternotomy), anesthesia complications, post op pulmonary embolism, pneumonia, UTI, etc.
- meowface 5y ago
  I think that's the joke.
bostonsre 5y ago
I guess it depends on how long the bad effects on the heart last after taking ISRIB. If it keeps lingering, you may need new pig hearts over time. Or.. Just keep taking ISRIB and just schedule a yearly pig heart transplant.

PragmaticPulp 5y ago

I was debating whether or not to post some of those self-experiments. I'm aware of a couple more forums where people tried ISRIB and still claim to have lasting problems from it. One group was led by professional chemists who seemed like they knew what they were doing when it comes to testing and validating the product was pure. It's amazing what people can access now, but self-experimentation with these compounds is a terrible idea.

meowface 5y ago
Reminds me a bit of cerebrolysin self-experiments I've read. It can either permanently make you smarter or permanently give you brain damage. Or both, perhaps. (For anyone unaware, it's a bunch of neuropeptides harvested from pig brains that you typically either inject or - fittingly, due to the source - snort directly into your brain through your nose.)
- texasbigdata 5y ago
  "Smarter" do you mean neuroregenesis? As I understood it's used post stroke to try to reverse some of the damage.
treeman79 5y ago
Developed a weird dementia at 39. Doctors Spent 2 years trying every prescription drug they could think of. Almost everything made matters worse. In some cases drastically. Complete nightmare. Those are with approved ones. Scary to try experiential. Eventually learned it was a blood disorder and a simple blood thinner was the answer.
- nefitty 5y ago
  Wow. It sounds like you're better and hope you're better! That's an incredible story. Good on you for not giving up. You just lit a fire under my butt.
- cma 5y ago
  Which blood disorder?

meowface 5y ago

Wow, that sounds pretty incredible. Part of what makes it sound promising to me is the extent of the "no free lunch" aspect: anecdotal reports of not just cardiac issues in humans and dogs but increased brain fog (mitigated with feed consumption...?), blunted emotions, inability to get drunk (maybe a plus?), accelerated cell death, psychosis and hallucinations - in exchange for, allegedly, reversing Alzheimer's and repairing lifelong brain damage: >One report of a person who gave ISRIB to their grandmother who had terminal stage Alzheimer's. She began to remember everyone. But died after 4 months (this may have been from old age and her type 1 diabetes). >One anecdotal report of a short course of ISRIB permanently fixing some prefrontal cortex brain damage in a Russian guy, caused by a car crash when he was a child. The repair to the brain was confirmed by MRI scans taken before and after the ISRIB treatment. Plus a pretty clear mechanism of action. Definitely sounds like it's worth significant study.

emptysongglass 5y ago
I mentioned this in another thread [1] but this idea of "no free lunch" is nothing more than a human aberration. There are many things in life that are free lunches, including drugs you put in your body but we as humans have such an overriding need to balance the scales of life we conveniently overlook them. Pattern recognition is helpful to a certain extent in life but we should be careful applying it arbitrarily and try to be aware of when we are doing it. I took a host of weird nootropics when I was younger. The most experimental was NSI-189. My experience is plenty of these drugs were gratis lunches but I wasn't enrolled in a study and don't have hard numbers to show you. [1] https://news.ycombinator.com/item?id=29800869 https://news.ycombinator.com/item?id=29800869
- pitched 5y ago
  The scariest (potential) downside to nootropics to me is an increased risk of cancer. Because if your normal cells are healthier, cancerous cells are also healthier. As a younger person, cancer is less of a risk so nootropics are less of a risk too. So I was curious, with that in mind, where the free lunch drugs are? As in, which ones did you enjoy most and why stop taking them?