16 ms·

Serotonin booster leads to increased functional brain connectivity

seesawtron 3y ago
>This provides further evidence that prucalopride is having an effect in areas of the brain that improve cognitive function – both by increasing and reducing connectivity between specific brain regions as required.” Altering the functional connectivity of the circuits is not necessarily correlated to "boosting" the memory.
ljf 3y ago
About 2 years ago I wasn't in a good place. My wife had been ill for a year, I found the lockdown hard (though I agreed with them), and I was struggling at my job. I wasn't sleeping well and was settling into a funk. I started taking 5-htp [0] every evening before bed - and over about a month I felt like a changed man. It took about 6 months to fully sort my sleep out and get my head back to where I wanted it, and to be honest it's only been in the last 6 months that I feel like I'm totally firing on all cylinders. But I personally feel like 5-htp had a massive impact in that. I only took it daily for about 6 months, then more sporadically for another 6 months, and now don't take it at all (but focus on other boosters like walking, litter picking, swimming, seeing friends etc.) [0 https://en.m.wikipedia.org/wiki/5-Hydroxytryptophan https://en.m.wikipedia.org/wiki/5-Hydroxytryptophan ]
- mobiuscog 3y ago
  As with anything like this (especially anecdotal), how much did you take each day, and did you change anything else over the same period ?
  - bflesch 3y ago
    he changed season, sun exposure and lockdown :)
    - MavisBacon 3y ago
      Bingo. It can really be tough to determine where progress is coming from over that period of time
  - ljf 3y ago
    I was taking 200mg a day, about 45 mins before I'd go to sleep, with a piece of brown bread. (200mg is considered a high dose - but I hadn't done a lot of research, I was just looking for 'something' to help, and bought from the first shop I found had them. On one hand, very little else changed for me, I started taking it in late summer so as the days were getting shorter. As my wife was quite ill we still didn't see a lot of people or socialise much. But around when I'd finished my first box of tablets (180), my job started returning to the office - that could have helped (though at first I hated going back to the office and dreaded it), the spring time we also became more social again. Which is approx when I moved to taking it more irregularly. Aware my example is purely anecdotal, but before I started taking these I had tried cbd and melatonin tablets to try and help my sleep - my insomnia was terrible and neither had helped noticeably. I had also tried the 'Calm' and 'Headspace' apps and various meditation and breathing exercises and none seemed to help me. I didn't actually think I was depressed at the time, but looking back it is clear I was in a place I'd not been before. 5htp might not have helped at all, but I'd recommend trying it for someone in a similar position - as it felt so transformative for me. I equally didn't realised how long it can take to come out of feeling so down, and how much I can now control my mood through exercise and being outdoors. ---edit--- Also to add - this wasn't a magic cure - but I feel it gave me the boost and reset to my mood that I needed to make the changes in my life. My wife is still ill to some degree, my job is 'more stressful' in some ways, but I've taken care of myself and know what to look for.
- lynx23 3y ago
  [flagged]
  - darreninthenet 3y ago
    I'm ready to see, what was done with me?
  - ljf 3y ago
    My poor sleep and stresses started well before Covid, but definitely came to a head then, combined with my wife's illness from long covid. After seeing what covid did to my wife and others with long covid, plus friends who lost parents etc., I remain fully supportive of the lockdowns here in the UK - though as I've said here before: the lockdowns were not about saving the old, but about keeping as many of the infirm out of hospital as possible, so that people wouldn't die from broken arms or childbirth.
- alwayslikethis 3y ago
  One warning about 5-HTP here. It seems that it can be potentially cardiotoxic at higher doses, or so as I read.
  - ljf 3y ago
    Certainly and some people also get serotonin syndrome if they mix this with other antidepressant medications. Read up before taking but to me this just highlights the impacts it can have. If it were patentable it would have had far more research I'm sure.
    - freehorse 3y ago
      > to me this just highlights the impacts it can have. I believe it also highlights that the body cannot regulate its conversion to serotonin, as it does with L-tryptophan (which needs to be converted to 5HTP) for instance, which can result to these issues. Also, the body does not regulate where in the body the conversion happens, you _really_ do not want it do be converted to serotonin in peripheral tissue (as it can cause heart issues), you only want it in the brain. Heart palpitations is a very common side effect due to it. If it was patentable drug it would possibly have been banned/restricted as a drug like many other 5HT2b agonists (but it is not patentable as it is something that our own body makes), and research would have turned to something with less cardiotoxic effects.
      - noduerme 3y ago
        >> Heart palpitations is a very common side effect due to it. This is the first time I've heard that, but - at some point in my life I found a technique for triggering mass bursts of seratonin when I want them. It's not that complicated; when I'm depressed and really need it, I just focus on a time when I felt my brain flooded with it. I habitually live with very low happiness but I'm familiar with the feeling of overwhelming joy - and love of everything around me - and I can put myself there, at a cost. Usually measured in hours or minutes. I also have an arrhythmia. When I do this, I often get heart palpitations lasting from 10-15 minutes. (I'm aware that the process I'm describing is also totally undocumented, but I've been doing it for years).
mtlmtlmtlmtl 3y ago
Too bad it's also a laxative.
- cvccvroomvroom 3y ago
  Magnesium is too, to a degree. With age, this is often a good property. There are plenty of opioid analogues to decrease it safely.
  - StrangeATractor 3y ago
    Mag isn't too bad, I believe you also get acclimated to it (haven't taken it in a while). IME it's not much different from having a fiber-heavy diet.
  - tpm 3y ago
    With magnesium it's more the specific salts that are laxative. Like the oxide which is both a laxative and has a low bioavailability. Citrate in huge doses is used as a laxative too. On the other hand, I have good experience with the orotate. Lactate and gluconate should be good too.
    - scns 3y ago
      Bisglycinate is supposed to have the highest bioavailability.
      - carlmr 3y ago
        And IME zero laxative effects. Citrate in normal doses is also okay
    - TheSpiceIsLife 3y ago
      Magnesium amino acid chelate is best for most, especially magnesium di-glycinate.
  - freehorse 3y ago
    Magnesium supplements have laxative effects as long as they are not absorbed. More bioavailable forms of magnesium do not exhibit laxative effects in normal dosages.
cvccvroomvroom 3y ago
Don't get too excited. It's likely to also cause cardiac issues like cisapride. Arrhythmia and 5-HT2B agonism are the worries.
- freehorse 3y ago
  Neither of them are 5-HT2b agonists, the cardiac effects of cisapride are due to inhibition of the cardiac HERG K+ channel, but apparently this does not seem to be as of an issue with prucalopride [1]. [1] https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2012.05011.x https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2012...
- PragmaticPulp 3y ago
  No, Prucalopride was specifically studied for cardiac complications. Why is there so much rampant misinformation in this comment section when the facts are a simple Google search away?
phreeza 3y ago
A note for people not familiar with the terminology - "functional connectivity" is a specific technical term that really just means temporal correlation between brain areas, as opposed to "structural connectivity" which refers to the actual neural pathways that are formed between brain areas. If you rephrase the headline as "Serotonin booster leads to increased correlation between activity in different brain areas" it maybe doesn't sound as exciting.
- mtlmtlmtlmtl 3y ago
  The main reason it's not too exciting to me is much simpler. They tested it for 6 days. You can do all sorts of wonderful stuff with a drug for a few days. But for most drugs, the effects simply cease if you keep taking it due to tolerance. And there doesn't seem to be a huge amount of leeway to up the dose either because it's a laxative.
  - ddalex 3y ago
    > because it's a laxative Good news everybody, no more fiber intake required.
  - psychphysic 3y ago
    I think this is a overly pessimistic take. It would be nice to see a longer term study. And no people shouldn't be buying this in IndiaMart but critical analysis of studies isn't just about being as pessimistic as possible. It's overly pessimistic as it's not constructive. Instead of asking for longer term studies you declare the effect probably won't last. There are loads of criticisms one could make of the study and wider hypothesis. But as with all criticism it should be constructive where reasonable.
    - mtlmtlmtlmtl 3y ago
      I would think it's pretty clear that the implication is longer term studies are needed and that people reading can infer that on their own.
    - manmal 3y ago
DiscourseFan 3y ago
Something in our industrial processes must be screwing with people's serotonin levels because Psychedelics and other serotenergic drugs are becoming the defacto treatment method for a whole host of ailments. I personally suffer from IBS, migraines, sleeping problems, and mood swings, if I haven't taken a dose of psychedelics in the last 6 months. Now, getting regular exercise, eating well, staying hydrated, sleeping 8 hours a night, spending time with friends, sexual and emotional fulfillment, and performing fulfilling labor, that will get you 80% or even 100% towards fixing most, if not all your problems. But I think these Serotonergic drugs give people the extra push in the right direction, and immediately fixes a lot of the underlying problems that would normally take consistent, positive environmental changes to root out. I myself am biased towards psychedelics, but I understand they're not for everyone. But SSRIs tend to be overprescribed and because they are often taken for far longer than necessary they cause a lot of changes neurophysically that aren't necessarily positive (and the most common side-effect, the loss of sex-drive, often creates many more problems for the user in their personal life.) I honestly don't know what's best, but I think almost nobody will have a poor reaction to a <1g dose of Psilocybin mushrooms (or if we want to be more conservative, <.5g), and the benefits of even just one small dose far outweigh the risks, in my opinion.
- ben_w 3y ago
  100-150 years ago we were using heroin, cocaine, and morphine for such things as cough syrups, hay fever, cola. Ancient Romans used cannabis and opium for insomnia and earaches. Wild animals get drunk on rotten fruit, cats stone themselves on catnip. So you're not wrong to wonder why people take stuff, but none of that's new.
  - ZunarJ5 3y ago
    Just because it's one of my favourites, we even have evidence of it in rock art: https://www.atlasobscura.com/articles/psychedelic-mushroom-algeria https://www.atlasobscura.com/articles/psychedelic-mushroom-a...
    - 4gotunameagain 3y ago
Giorgi 3y ago
Plot hole: It's laxative.
- RadixDLT 3y ago
  make you loose weight
Havoc 3y ago
Maybe this is why exercise is beneficial
2c2c2c 3y ago
anyone want to hypothesize what happens when this is combined with mdma
- AlecSchueler 3y ago
  Serotonin syndrome. I believe that qualitative effects of the MDMA would also be significantly reduced.
  - meepmorp 3y ago
    It's a highly specific HT4 agonist, I'm not sure why you'd be more likely serotonin syndrome by combining it with MDMA vs MDMA alone - it doesn't affect release or transport, nor does it have have significant activity at other binding sites. Am I missing something?
    - AlecSchueler 3y ago
      No, I'm just parroting the common wisdom of the drug crowd. But looks like there might not be much to worry about indeed: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5931730/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5931730/
code51 3y ago
Could this potentially help schizophrenia, emotional regulation, impulsivity, reward processing, ADHD etc because of an improvement in functional connectivity?
- bbor 3y ago
  This comment sums up why I’m so sad to be living in what I feel will be looked back on as the dark ages of neuroscience - these very very smart people are limited to “more correlated brain activity might help with everything!” OTOH perhaps I don’t want to live in a world with happy pills… we should all be grateful
  - theaussiestew 3y ago
    Seems like psychiatry is throwing things at the wall and going with whatever sticks. That plus spurious statistical correlations supporting the use of certain medications.
- vanderZwan 3y ago
  I can't speak for any other illness mentioned, but from what I've been told as someone with ADHD a significant part of the "nature" side of it is caused by either reduced serotonin sensitivity, a faster-than-normal re-uptake of serotonin whenever it gets released (meaning it doesn't get to do its job), or some other disruption of how serotonin is supposed to function in the brain. So when it's caused by reduced sensitivity I would expect it to potentially be a treatment for that part of the illness, yes. I wouldn't be surprised if it eventually turns out that ADHD has multiple potential causes that all lead to the same symptomatic serotonin disruption though, and that only a limited number of people who have it get benefits from this treatment. And of course, that's just the "nature" side, as mentioned. There is also a "nurture" side of things where not getting the right help to deal with the consequences of ADHD leads to issues that need to be solved through therapy (although I suppose effective medication does make it easier to able to endure therapy).
  - dustingetz 3y ago
    do you mean dopamine?
lakomen 3y ago
So when you like something, you're learning it easier than when you don't. I always thought science is the art of putting what you already know into "words". Aka "No shit, sherlock" :) Or maybe I got it all wrong.
martopix 3y ago
I remember during my PhD, already 5 or more years ago, the term "functional connectivity" was frowned upon by the computational neuroscience community and the concept was considered out of date.
- coldtea 3y ago
  Perhaps "computational neuroscience" is not the be all end all of neuroscience though... (not that you said so, but someone might think that if comp. neurosc. dismisses it, then it's necessarily bogus)
  - martopix 3y ago
    But functional connectivity is a fundamentally computational concept
- FrustratedMonky 3y ago
  Curious, what were they calling whatever took its place? I didn't know things were moving so fast that this is already passé.
acumenical 3y ago
I wish we stopped treating serotonin as a button that automatically improves mood. It is bullshit. Let's recognize the complexity of neural signaling. Whenever people call serotonin the happiness hormone I want to throw up. Such people would probably never believe that if you inject serotonin, the result is extreme pain at the injection site.
- mmiliauskas 3y ago
  Anecdotal, but I had depression episodes on weekly basis for 4 years, then started to microdose mushrooms for completely different reasons, and it is almost 2 years now, when I barely had a single such episode.
- kderbyma 3y ago
  Agreed. Trying to fix depression with drugs is a bad move for most people. They usually cause long term problems with continuous use and lead to psychosis and suicidal ideation in a large!!! number of patients.
- PragmaticPulp 3y ago
  > I wish we stopped treating serotonin as a button that automatically improves mood. We don’t. Studies like this are specifically searching for mechanisms by which serotonin and mood are related. I think you’re projecting the pop-culture idea of serotonin on to the research.
pr0zac 3y ago
I’ll probably be downvoted for pointing this out but I feel like it’s important. 90% of the comments at the time of my posting this are great examples of the logical fallacy a lot of intelligent people fall into where they think their intelligence in one area means they’re qualified to make assessments or reach conclusions in fields outside of their own. This would be the same error in judgment that’s turned the nootropic and longevity industries into billion dollar ones. If you are reading these comments please try and be aware of this fact and the possibility that anyone, yourself included, could fall into this trap and remember to take all of the amazing possibilities being suggested and conclusions reached herein with a grain of salt.
- harha_ 3y ago
  Yeah I keep seeing this behavior here in the comments section. There are some real experts here for sure, but I think assuming you understand anything about something as complex as this without extensive prior studies about the subject is just stupid. I'm tired of reasonably intelligent people extrapolating new information about any possible subject based on their very limited basic level knowledge combined with some new cool research paper headlines.
  - bluecalm 3y ago
    On the other hand the opinions you get from medical professionals is garbage as well. Just try going to a few with the same problem and you will realize it. In my case I want to 5 doctors with my knee issue and got 5 different diagnosis/treatments. One wanted knee surgery. Another wanted hip (!?) surgery, one said it's about cartilage, another said it's muscle imbalance, another said it's my hip mobility (so surgery!). One did hyaluronic acid injections another recommended manual therapy done by his friend. The one who did the surgery I later learnt is not recommended anymore told me I will never be able to run/play sports anymore. I do 15 hours a week these days including running 100+km/month for almost 3 years (I switched to other sports now as I find them more fun). Another time I've done a routine blood test and PhD liver specialist with decades of experience thought my liver is damaged looking at the result. She didn't know that liver markers are elevated by strength training (which I mentioned to her) and the way to test for that is to test CK levels as well. She wanted to put me on meds as well. "Studies" mean very little. You can learn a lot from people who took time to read a literature and are good at critical thinking or you can easily be fooled by a confident educated moron with a PhD. I've learnt more about my issues from random internet forums than I've learnt from doctors and I really tried it with doctors.
scotty79 3y ago
Is this substance known in nootropic circles?
- joenot443 3y ago
  Big time, it's often included in the introductory "stacks" for new members. I haven't really dabbled with nootropics since college, but I do remember 5HTP being suggested. I'd link the reddit wiki where it's mentioned, but we're still mid protest it seems! :)
abdulmoez 3y ago
[dead]
qwerty456127 3y ago
Sadly prucalopride is prescription-only and, because of having no recreational abuse potential, absent from the black market.
Euphemistic 3y ago
"INCREASED FUNCTIONAL BRAIN CONNECTIVITY" sounds pretty neat. Instead of debating why the brain is or is not like a computer. Or why you or your sister-in-law's brain is addled by mental illness. Let's frame this optimistically, hopefully. Maybe there's a genius working that study or commenting here. Geniuses think different. 1. geniuses look at problems in many different ways. 2. geniuses make their thoughts visible. 3. geniuses produce. 4. geniuses force relationships. 5. geniuses think metaphorically. A logical fallacy is not necessarily wrong.
- grugagag 3y ago
  How do you know? Do you think you may be one yourself?
jksmith 3y ago
So the new office is the bathroom?
peet2521 3y ago
I came to the comment section to mention other seratonergic drugs that do something similar to what the study mentions. Psilocin is a serotonin 2A agonist, LSD is a 1A agonist (according to a quick google search), and this new drug works on "4" receptors. All of which seem to have similar beneficial therapeutic effects when used properly. In general, I'm very excited to see drugs like these being researched, including previously illegal "schedule 1" drugs that can (and probably should) be used in therapeutic settings. If you're looking for some good content to learn more about this, Andrew Huberman is currently doing a handful of podcasts on drugs like these, and it's really educational. (Assuming you can handle his long-form podcast style)
- James87211 3y ago
  "If you're looking for some good content to learn more about this" I can also recommend the book How To Change Your mind by Michael Pollan.
- PragmaticPulp 3y ago
  > I came to the comment section to mention other seratonergic drugs that do something similar to what the study mentions. Psilocin is a serotonin 2A agonist, LSD is a 1A agonist (according to a quick google search), and this new drug works on "4" receptors. All of which seem to have similar beneficial therapeutic effects when used properly. Serotonin receptors are not interchangeable at all. 5-HT2A and 5-HT4 receptors have completely different effects and functions. You can’t suggest that drugs that work on one are similar to the other. They are nothing alike.
belter 3y ago
I thought Prucalopride was a laxative...
idkyall 3y ago
Isn't there a theory that any nootropic substance needs to have a downside or we would have naturally evolved it by now? I am amused thinking of the idea that this drug being a laxative is that downside
- feoren 3y ago
  > Isn't there a theory that any nootropic substance needs to have a downside or we would have naturally evolved it by now? Couldn't that be applied to all modern technology? Humans obviously weren't meant to fly or we would have evolved flight; therefore airplanes bad. Why is this any different? Evolution is an extremely blunt force with only so many tools at its disposal. Besides, there would need to be selective pressure for being happy and content with life, even into late adulthood. Is there? That's not clear at all.
PragmaticPulp 3y ago
For anyone coming to this comment section in hopes of understanding this further: This comment section is full of misinformation and discourse about drugs that are completely unrelated to what’s discussed in the article. Serotonin isn’t a singular system in the brain. Psychedelics generally don’t interact with the receptor mentioned in this article (5-HT4) so all of the anecdotes talking about LSD or mushrooms do not apply to this story at all. Serotonin agonists are not interchangeable and have very different effects depending on their targets. The drug in this study (Prucalopride) has been noted to influence depression symptoms positively for some time. However, it has also been noted to be associated with suicidal ideation in some vulnerable populations. This is an emergent area of research and absolutely should not be taken as a suggestion for self-treatment. If that’s not enough to convince you to not self-experiment, you should know that Prucalopride is primarily used as a constipation treatment. If you take it, you’re going to have some dramatic bowel effects. Please understand that these articles are interesting, but HN comments about anything related to psychedelics, serotonin, or dopamine are often quite far from the mark (despite being very confident in their delivery).
- 93po 3y ago
  Is there any actionable take away from the information being discussed in the article or comments here?
dreampod 3y ago
[flagged]
RadixDLT 3y ago
I think you can get serotonin from saffron
kapindo 3y ago
As someone in the pharmacy field, I would advise anyone against messing with the serotonergic pathway without knowing what they're doing. Serotonin serotonin syndrome can wreck you and complete recovery can take. Especially taking high doses of serotonin booster while consuming foods high in tyramine. Avoid quack pseudo-health care advices and supplements.
itvision 3y ago
This link doesn't work for me, this one does: https://www.alphagalileo.org/en-gb/Item-Display/ItemId/234406 https://www.alphagalileo.org/en-gb/Item-Display/ItemId/23440...

>This provides further evidence that prucalopride is having an effect in areas of the brain that improve cognitive function – both by increasing and reducing connectivity between specific brain regions as required.” Altering the functional connectivity of the circuits is not necessarily correlated to "boosting" the memory.

ljf 3y ago

About 2 years ago I wasn't in a good place. My wife had been ill for a year, I found the lockdown hard (though I agreed with them), and I was struggling at my job. I wasn't sleeping well and was settling into a funk. I started taking 5-htp [0] every evening before bed - and over about a month I felt like a changed man. It took about 6 months to fully sort my sleep out and get my head back to where I wanted it, and to be honest it's only been in the last 6 months that I feel like I'm totally firing on all cylinders. But I personally feel like 5-htp had a massive impact in that. I only took it daily for about 6 months, then more sporadically for another 6 months, and now don't take it at all (but focus on other boosters like walking, litter picking, swimming, seeing friends etc.) [0 https://en.m.wikipedia.org/wiki/5-Hydroxytryptophan https://en.m.wikipedia.org/wiki/5-Hydroxytryptophan ]

mobiuscog 3y ago
As with anything like this (especially anecdotal), how much did you take each day, and did you change anything else over the same period ?
- bflesch 3y ago
  he changed season, sun exposure and lockdown :)
  - MavisBacon 3y ago
    Bingo. It can really be tough to determine where progress is coming from over that period of time
- ljf 3y ago
  I was taking 200mg a day, about 45 mins before I'd go to sleep, with a piece of brown bread. (200mg is considered a high dose - but I hadn't done a lot of research, I was just looking for 'something' to help, and bought from the first shop I found had them. On one hand, very little else changed for me, I started taking it in late summer so as the days were getting shorter. As my wife was quite ill we still didn't see a lot of people or socialise much. But around when I'd finished my first box of tablets (180), my job started returning to the office - that could have helped (though at first I hated going back to the office and dreaded it), the spring time we also became more social again. Which is approx when I moved to taking it more irregularly. Aware my example is purely anecdotal, but before I started taking these I had tried cbd and melatonin tablets to try and help my sleep - my insomnia was terrible and neither had helped noticeably. I had also tried the 'Calm' and 'Headspace' apps and various meditation and breathing exercises and none seemed to help me. I didn't actually think I was depressed at the time, but looking back it is clear I was in a place I'd not been before. 5htp might not have helped at all, but I'd recommend trying it for someone in a similar position - as it felt so transformative for me. I equally didn't realised how long it can take to come out of feeling so down, and how much I can now control my mood through exercise and being outdoors. ---edit--- Also to add - this wasn't a magic cure - but I feel it gave me the boost and reset to my mood that I needed to make the changes in my life. My wife is still ill to some degree, my job is 'more stressful' in some ways, but I've taken care of myself and know what to look for.
lynx23 3y ago
[flagged]
- darreninthenet 3y ago
  I'm ready to see, what was done with me?
- ljf 3y ago
  My poor sleep and stresses started well before Covid, but definitely came to a head then, combined with my wife's illness from long covid. After seeing what covid did to my wife and others with long covid, plus friends who lost parents etc., I remain fully supportive of the lockdowns here in the UK - though as I've said here before: the lockdowns were not about saving the old, but about keeping as many of the infirm out of hospital as possible, so that people wouldn't die from broken arms or childbirth.
alwayslikethis 3y ago
One warning about 5-HTP here. It seems that it can be potentially cardiotoxic at higher doses, or so as I read.
- ljf 3y ago
  Certainly and some people also get serotonin syndrome if they mix this with other antidepressant medications. Read up before taking but to me this just highlights the impacts it can have. If it were patentable it would have had far more research I'm sure.
  - freehorse 3y ago
    > to me this just highlights the impacts it can have. I believe it also highlights that the body cannot regulate its conversion to serotonin, as it does with L-tryptophan (which needs to be converted to 5HTP) for instance, which can result to these issues. Also, the body does not regulate where in the body the conversion happens, you _really_ do not want it do be converted to serotonin in peripheral tissue (as it can cause heart issues), you only want it in the brain. Heart palpitations is a very common side effect due to it. If it was patentable drug it would possibly have been banned/restricted as a drug like many other 5HT2b agonists (but it is not patentable as it is something that our own body makes), and research would have turned to something with less cardiotoxic effects.
    - noduerme 3y ago
      >> Heart palpitations is a very common side effect due to it. This is the first time I've heard that, but - at some point in my life I found a technique for triggering mass bursts of seratonin when I want them. It's not that complicated; when I'm depressed and really need it, I just focus on a time when I felt my brain flooded with it. I habitually live with very low happiness but I'm familiar with the feeling of overwhelming joy - and love of everything around me - and I can put myself there, at a cost. Usually measured in hours or minutes. I also have an arrhythmia. When I do this, I often get heart palpitations lasting from 10-15 minutes. (I'm aware that the process I'm describing is also totally undocumented, but I've been doing it for years).

mtlmtlmtlmtl 3y ago

Too bad it's also a laxative.

cvccvroomvroom 3y ago
Magnesium is too, to a degree. With age, this is often a good property. There are plenty of opioid analogues to decrease it safely.
- StrangeATractor 3y ago
  Mag isn't too bad, I believe you also get acclimated to it (haven't taken it in a while). IME it's not much different from having a fiber-heavy diet.
- tpm 3y ago
  With magnesium it's more the specific salts that are laxative. Like the oxide which is both a laxative and has a low bioavailability. Citrate in huge doses is used as a laxative too. On the other hand, I have good experience with the orotate. Lactate and gluconate should be good too.
  - scns 3y ago
    Bisglycinate is supposed to have the highest bioavailability.
    - carlmr 3y ago
      And IME zero laxative effects. Citrate in normal doses is also okay
  - TheSpiceIsLife 3y ago
    Magnesium amino acid chelate is best for most, especially magnesium di-glycinate.
- freehorse 3y ago
  Magnesium supplements have laxative effects as long as they are not absorbed. More bioavailable forms of magnesium do not exhibit laxative effects in normal dosages.

cvccvroomvroom 3y ago

Don't get too excited. It's likely to also cause cardiac issues like cisapride. Arrhythmia and 5-HT2B agonism are the worries.

freehorse 3y ago
Neither of them are 5-HT2b agonists, the cardiac effects of cisapride are due to inhibition of the cardiac HERG K+ channel, but apparently this does not seem to be as of an issue with prucalopride [1]. [1] https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2012.05011.x https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2036.2012...
PragmaticPulp 3y ago
No, Prucalopride was specifically studied for cardiac complications. Why is there so much rampant misinformation in this comment section when the facts are a simple Google search away?

phreeza 3y ago

A note for people not familiar with the terminology - "functional connectivity" is a specific technical term that really just means temporal correlation between brain areas, as opposed to "structural connectivity" which refers to the actual neural pathways that are formed between brain areas. If you rephrase the headline as "Serotonin booster leads to increased correlation between activity in different brain areas" it maybe doesn't sound as exciting.

mtlmtlmtlmtl 3y ago
The main reason it's not too exciting to me is much simpler. They tested it for 6 days. You can do all sorts of wonderful stuff with a drug for a few days. But for most drugs, the effects simply cease if you keep taking it due to tolerance. And there doesn't seem to be a huge amount of leeway to up the dose either because it's a laxative.
- ddalex 3y ago
  > because it's a laxative Good news everybody, no more fiber intake required.
- psychphysic 3y ago
  I think this is a overly pessimistic take. It would be nice to see a longer term study. And no people shouldn't be buying this in IndiaMart but critical analysis of studies isn't just about being as pessimistic as possible. It's overly pessimistic as it's not constructive. Instead of asking for longer term studies you declare the effect probably won't last. There are loads of criticisms one could make of the study and wider hypothesis. But as with all criticism it should be constructive where reasonable.
  - mtlmtlmtlmtl 3y ago
    I would think it's pretty clear that the implication is longer term studies are needed and that people reading can infer that on their own.
  - manmal 3y ago

DiscourseFan 3y ago

Something in our industrial processes must be screwing with people's serotonin levels because Psychedelics and other serotenergic drugs are becoming the defacto treatment method for a whole host of ailments. I personally suffer from IBS, migraines, sleeping problems, and mood swings, if I haven't taken a dose of psychedelics in the last 6 months. Now, getting regular exercise, eating well, staying hydrated, sleeping 8 hours a night, spending time with friends, sexual and emotional fulfillment, and performing fulfilling labor, that will get you 80% or even 100% towards fixing most, if not all your problems. But I think these Serotonergic drugs give people the extra push in the right direction, and immediately fixes a lot of the underlying problems that would normally take consistent, positive environmental changes to root out. I myself am biased towards psychedelics, but I understand they're not for everyone. But SSRIs tend to be overprescribed and because they are often taken for far longer than necessary they cause a lot of changes neurophysically that aren't necessarily positive (and the most common side-effect, the loss of sex-drive, often creates many more problems for the user in their personal life.) I honestly don't know what's best, but I think almost nobody will have a poor reaction to a <1g dose of Psilocybin mushrooms (or if we want to be more conservative, <.5g), and the benefits of even just one small dose far outweigh the risks, in my opinion.

ben_w 3y ago
100-150 years ago we were using heroin, cocaine, and morphine for such things as cough syrups, hay fever, cola. Ancient Romans used cannabis and opium for insomnia and earaches. Wild animals get drunk on rotten fruit, cats stone themselves on catnip. So you're not wrong to wonder why people take stuff, but none of that's new.
- ZunarJ5 3y ago
  Just because it's one of my favourites, we even have evidence of it in rock art: https://www.atlasobscura.com/articles/psychedelic-mushroom-algeria https://www.atlasobscura.com/articles/psychedelic-mushroom-a...
  - 4gotunameagain 3y ago

Giorgi 3y ago

Plot hole: It's laxative.

RadixDLT 3y ago
make you loose weight

Havoc 3y ago

Maybe this is why exercise is beneficial

2c2c2c 3y ago

anyone want to hypothesize what happens when this is combined with mdma

AlecSchueler 3y ago
Serotonin syndrome. I believe that qualitative effects of the MDMA would also be significantly reduced.
- meepmorp 3y ago
  It's a highly specific HT4 agonist, I'm not sure why you'd be more likely serotonin syndrome by combining it with MDMA vs MDMA alone - it doesn't affect release or transport, nor does it have have significant activity at other binding sites. Am I missing something?
  - AlecSchueler 3y ago
    No, I'm just parroting the common wisdom of the drug crowd. But looks like there might not be much to worry about indeed: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5931730/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5931730/

code51 3y ago

Could this potentially help schizophrenia, emotional regulation, impulsivity, reward processing, ADHD etc because of an improvement in functional connectivity?

bbor 3y ago
This comment sums up why I’m so sad to be living in what I feel will be looked back on as the dark ages of neuroscience - these very very smart people are limited to “more correlated brain activity might help with everything!” OTOH perhaps I don’t want to live in a world with happy pills… we should all be grateful
- theaussiestew 3y ago
  Seems like psychiatry is throwing things at the wall and going with whatever sticks. That plus spurious statistical correlations supporting the use of certain medications.
vanderZwan 3y ago
I can't speak for any other illness mentioned, but from what I've been told as someone with ADHD a significant part of the "nature" side of it is caused by either reduced serotonin sensitivity, a faster-than-normal re-uptake of serotonin whenever it gets released (meaning it doesn't get to do its job), or some other disruption of how serotonin is supposed to function in the brain. So when it's caused by reduced sensitivity I would expect it to potentially be a treatment for that part of the illness, yes. I wouldn't be surprised if it eventually turns out that ADHD has multiple potential causes that all lead to the same symptomatic serotonin disruption though, and that only a limited number of people who have it get benefits from this treatment. And of course, that's just the "nature" side, as mentioned. There is also a "nurture" side of things where not getting the right help to deal with the consequences of ADHD leads to issues that need to be solved through therapy (although I suppose effective medication does make it easier to able to endure therapy).
- dustingetz 3y ago
  do you mean dopamine?

lakomen 3y ago

So when you like something, you're learning it easier than when you don't. I always thought science is the art of putting what you already know into "words". Aka "No shit, sherlock" :) Or maybe I got it all wrong.

martopix 3y ago

I remember during my PhD, already 5 or more years ago, the term "functional connectivity" was frowned upon by the computational neuroscience community and the concept was considered out of date.

coldtea 3y ago
Perhaps "computational neuroscience" is not the be all end all of neuroscience though... (not that you said so, but someone might think that if comp. neurosc. dismisses it, then it's necessarily bogus)
- martopix 3y ago
  But functional connectivity is a fundamentally computational concept
FrustratedMonky 3y ago
Curious, what were they calling whatever took its place? I didn't know things were moving so fast that this is already passé.

acumenical 3y ago

I wish we stopped treating serotonin as a button that automatically improves mood. It is bullshit. Let's recognize the complexity of neural signaling. Whenever people call serotonin the happiness hormone I want to throw up. Such people would probably never believe that if you inject serotonin, the result is extreme pain at the injection site.

mmiliauskas 3y ago
Anecdotal, but I had depression episodes on weekly basis for 4 years, then started to microdose mushrooms for completely different reasons, and it is almost 2 years now, when I barely had a single such episode.
kderbyma 3y ago
Agreed. Trying to fix depression with drugs is a bad move for most people. They usually cause long term problems with continuous use and lead to psychosis and suicidal ideation in a large!!! number of patients.
PragmaticPulp 3y ago
> I wish we stopped treating serotonin as a button that automatically improves mood. We don’t. Studies like this are specifically searching for mechanisms by which serotonin and mood are related. I think you’re projecting the pop-culture idea of serotonin on to the research.

pr0zac 3y ago

I’ll probably be downvoted for pointing this out but I feel like it’s important. 90% of the comments at the time of my posting this are great examples of the logical fallacy a lot of intelligent people fall into where they think their intelligence in one area means they’re qualified to make assessments or reach conclusions in fields outside of their own. This would be the same error in judgment that’s turned the nootropic and longevity industries into billion dollar ones. If you are reading these comments please try and be aware of this fact and the possibility that anyone, yourself included, could fall into this trap and remember to take all of the amazing possibilities being suggested and conclusions reached herein with a grain of salt.

harha_ 3y ago
Yeah I keep seeing this behavior here in the comments section. There are some real experts here for sure, but I think assuming you understand anything about something as complex as this without extensive prior studies about the subject is just stupid. I'm tired of reasonably intelligent people extrapolating new information about any possible subject based on their very limited basic level knowledge combined with some new cool research paper headlines.
- bluecalm 3y ago
  On the other hand the opinions you get from medical professionals is garbage as well. Just try going to a few with the same problem and you will realize it. In my case I want to 5 doctors with my knee issue and got 5 different diagnosis/treatments. One wanted knee surgery. Another wanted hip (!?) surgery, one said it's about cartilage, another said it's muscle imbalance, another said it's my hip mobility (so surgery!). One did hyaluronic acid injections another recommended manual therapy done by his friend. The one who did the surgery I later learnt is not recommended anymore told me I will never be able to run/play sports anymore. I do 15 hours a week these days including running 100+km/month for almost 3 years (I switched to other sports now as I find them more fun). Another time I've done a routine blood test and PhD liver specialist with decades of experience thought my liver is damaged looking at the result. She didn't know that liver markers are elevated by strength training (which I mentioned to her) and the way to test for that is to test CK levels as well. She wanted to put me on meds as well. "Studies" mean very little. You can learn a lot from people who took time to read a literature and are good at critical thinking or you can easily be fooled by a confident educated moron with a PhD. I've learnt more about my issues from random internet forums than I've learnt from doctors and I really tried it with doctors.

scotty79 3y ago

Is this substance known in nootropic circles?

joenot443 3y ago
Big time, it's often included in the introductory "stacks" for new members. I haven't really dabbled with nootropics since college, but I do remember 5HTP being suggested. I'd link the reddit wiki where it's mentioned, but we're still mid protest it seems! :)

abdulmoez 3y ago

[dead]

qwerty456127 3y ago

Sadly prucalopride is prescription-only and, because of having no recreational abuse potential, absent from the black market.

Euphemistic 3y ago

"INCREASED FUNCTIONAL BRAIN CONNECTIVITY" sounds pretty neat. Instead of debating why the brain is or is not like a computer. Or why you or your sister-in-law's brain is addled by mental illness. Let's frame this optimistically, hopefully. Maybe there's a genius working that study or commenting here. Geniuses think different. 1. geniuses look at problems in many different ways. 2. geniuses make their thoughts visible. 3. geniuses produce. 4. geniuses force relationships. 5. geniuses think metaphorically. A logical fallacy is not necessarily wrong.

grugagag 3y ago
How do you know? Do you think you may be one yourself?

jksmith 3y ago

So the new office is the bathroom?

peet2521 3y ago

I came to the comment section to mention other seratonergic drugs that do something similar to what the study mentions. Psilocin is a serotonin 2A agonist, LSD is a 1A agonist (according to a quick google search), and this new drug works on "4" receptors. All of which seem to have similar beneficial therapeutic effects when used properly. In general, I'm very excited to see drugs like these being researched, including previously illegal "schedule 1" drugs that can (and probably should) be used in therapeutic settings. If you're looking for some good content to learn more about this, Andrew Huberman is currently doing a handful of podcasts on drugs like these, and it's really educational. (Assuming you can handle his long-form podcast style)

James87211 3y ago
"If you're looking for some good content to learn more about this" I can also recommend the book How To Change Your mind by Michael Pollan.
PragmaticPulp 3y ago
> I came to the comment section to mention other seratonergic drugs that do something similar to what the study mentions. Psilocin is a serotonin 2A agonist, LSD is a 1A agonist (according to a quick google search), and this new drug works on "4" receptors. All of which seem to have similar beneficial therapeutic effects when used properly. Serotonin receptors are not interchangeable at all. 5-HT2A and 5-HT4 receptors have completely different effects and functions. You can’t suggest that drugs that work on one are similar to the other. They are nothing alike.

belter 3y ago

I thought Prucalopride was a laxative...

idkyall 3y ago

Isn't there a theory that any nootropic substance needs to have a downside or we would have naturally evolved it by now? I am amused thinking of the idea that this drug being a laxative is that downside

feoren 3y ago
> Isn't there a theory that any nootropic substance needs to have a downside or we would have naturally evolved it by now? Couldn't that be applied to all modern technology? Humans obviously weren't meant to fly or we would have evolved flight; therefore airplanes bad. Why is this any different? Evolution is an extremely blunt force with only so many tools at its disposal. Besides, there would need to be selective pressure for being happy and content with life, even into late adulthood. Is there? That's not clear at all.

PragmaticPulp 3y ago

For anyone coming to this comment section in hopes of understanding this further: This comment section is full of misinformation and discourse about drugs that are completely unrelated to what’s discussed in the article. Serotonin isn’t a singular system in the brain. Psychedelics generally don’t interact with the receptor mentioned in this article (5-HT4) so all of the anecdotes talking about LSD or mushrooms do not apply to this story at all. Serotonin agonists are not interchangeable and have very different effects depending on their targets. The drug in this study (Prucalopride) has been noted to influence depression symptoms positively for some time. However, it has also been noted to be associated with suicidal ideation in some vulnerable populations. This is an emergent area of research and absolutely should not be taken as a suggestion for self-treatment. If that’s not enough to convince you to not self-experiment, you should know that Prucalopride is primarily used as a constipation treatment. If you take it, you’re going to have some dramatic bowel effects. Please understand that these articles are interesting, but HN comments about anything related to psychedelics, serotonin, or dopamine are often quite far from the mark (despite being very confident in their delivery).

93po 3y ago
Is there any actionable take away from the information being discussed in the article or comments here?

dreampod 3y ago

[flagged]

RadixDLT 3y ago

I think you can get serotonin from saffron

kapindo 3y ago

As someone in the pharmacy field, I would advise anyone against messing with the serotonergic pathway without knowing what they're doing. Serotonin serotonin syndrome can wreck you and complete recovery can take. Especially taking high doses of serotonin booster while consuming foods high in tyramine. Avoid quack pseudo-health care advices and supplements.

itvision 3y ago

This link doesn't work for me, this one does: https://www.alphagalileo.org/en-gb/Item-Display/ItemId/234406 https://www.alphagalileo.org/en-gb/Item-Display/ItemId/23440...