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Psychedelics and 5HT2B cardiotoxicity Options
 
oversoul1919
#1 Posted : 5/30/2015 8:52:33 PM

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OK, I'm not a doctor so I don't have a single clue about what is written here, but I'm worried because it says that there's a connection between serotoenergic drugs and heart valve disease.

http://www.ncbi.nlm.nih.gov/pubmed/19505264

How important is this? Should we be worried or not? Because DMT also falls under this category.
 

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Nathanial.Dread
#2 Posted : 5/30/2015 9:13:46 PM

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It's certainly not GOOD news by any rate. Here's a study examining 5-HT2BR mediated cardiac abnormalities in rats
http://www.ncbi.nlm.nih.gov/pubmed/18511249

And here's a study suggesting that regular exposure to psilocin can cause similar cardiac abnormalities in mice.
http://old.imp.lodz.pl/n.../Borowiak%20ABSTRACT.pdf

Personally, I'm not worried. If you're only occasionally using psychedelics, you're almost certainly fine, and even in cultures with comparatively regular use (such as members of the UDV), I haven't come across reports of major heart problems (although I haven't seen any studies specifically looking at this either). Many people take many psychedelics and live nice long lives.

If you're regularly microdosing (as I do), you might want to be careful, however, so long as you're keeping your heart healthy in other ways (eating right, lots of exercise, etc), you'll probably be fine.

Pretty much everything in our environment is toxic in some way, at some dose.

Blessings
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oversoul1919
#3 Posted : 5/30/2015 11:16:32 PM

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Nathanial.Dread wrote:
It's certainly not GOOD news by any rate. Here's a study examining 5-HT2BR mediated cardiac abnormalities in rats
http://www.ncbi.nlm.nih.gov/pubmed/18511249

And here's a study suggesting that regular exposure to psilocin can cause similar cardiac abnormalities in mice.
http://old.imp.lodz.pl/n.../Borowiak%20ABSTRACT.pdf

Personally, I'm not worried. If you're only occasionally using psychedelics, you're almost certainly fine, and even in cultures with comparatively regular use (such as members of the UDV), I haven't come across reports of major heart problems (although I haven't seen any studies specifically looking at this either). Many people take many psychedelics and live nice long lives.

If you're regularly microdosing (as I do), you might want to be careful, however, so long as you're keeping your heart healthy in other ways (eating right, lots of exercise, etc), you'll probably be fine.

Pretty much everything in our environment is toxic in some way, at some dose.

Blessings
~ND


Thanks. And you're right, everything is bad when taken to much. Even water.
 
1ce
#4 Posted : 5/31/2015 2:16:28 AM

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Maybe it does, but the OP raises a good question? Is it important? Too much water can lead to death, but is this really all that important?

Nicotine can cause death, yet it can also reverse brain damage and boost cognative memory.

2,4-dinitrophenol can cause liver failure, brain damage, cataracts, EXTREMELY excessive internal/external body temperature, and many equally horrible things. Yet it's showing potential to cure diabetes.

Unless the effects are very broad spectrum in dosage/administration I don't think there's much to worry about. Stress causes heart disease, too.
 
Ufostrahlen
#5 Posted : 5/31/2015 6:09:33 AM

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There's already a thread about this topic: https://www.dmt-nexus.me...spx?g=posts&m=578918

Binding of DMT for the 5HT2B is 550nM, as strong as MDMA, Fenfluramine is 4134nM:

http://pdsp.med.unc.edu/...amp;doQuery=Submit+Query
http://pdsp.med.unc.edu/...amp;doQuery=Submit+Query
http://pdsp.med.unc.edu/...lue+only&kiKey=27707

Quote:
3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”) Induces Fenfluramine-Like Proliferative Actions on Human Cardiac Valvular Interstitial Cells in Vitro

http://molpharm.aspetjou...6/1223/T1.expansion.html
http://molpharm.aspetjou...g/content/63/6/1223.long


Thus DMT binds stronger to the 5HT2B receptor than FENFL (lower ki value, stronger binding). Don't consume it daily, I guess.

LSD-25 is even stronger:

0.9-30nM

http://pdsp.med.unc.edu/...amp;doQuery=Submit+Query

Also, McKenna paper from '89 with 5HT2B binding affinities for various hallucinogens:

http://www.jneurosci.org/content/9/10/3482.long

Related:

Quote:
Comparisons of hallucinogenic phenylisopropylamine binding affinities at cloned human 5-HT2A, -HT(2B) and 5-HT2C receptors.

http://www.ncbi.nlm.nih.gov/pubmed/9933142
http://libgen.org/scimag...doi=10.1007%2Fpl00005315
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Cognitive Heart
#6 Posted : 5/31/2015 3:01:33 PM

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I think it's important to add that we now have supplements, plants-herbs available to us that show some success and validation for preventing, modulating and protecting our 5-HT receptors from (if any) damage that may occur resulting from excess use or large doses of psychedelics. So whether that 'damage' has already taken place or not, one can safely integrate preventative strategies for over-coming any conflicting health effects. Even exercise, proper sleep or meditation can help mitigate.
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The Traveler
#7 Posted : 5/31/2015 9:11:05 PM

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Cognitive Heart wrote:
I think it's important to add that we now have supplements, plants-herbs available to us that show some success and validation for preventing, modulating and protecting our 5-HT receptors from (if any) damage that may occur resulting from excess use or large doses of psychedelics.

Do we really know if these supplements (like PQQ) will help the way we hope? And how sure are we that they will not have certain side effects? And how about long term studies about the use of those supplements on humans?

I am a bit skeptical if these supplements are really that good without any repercussion and/or side effects.


Kind regards,

The Traveler
 
greenmoss
#8 Posted : 5/31/2015 9:45:36 PM

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oversoul1919 wrote:
OK, I'm not a doctor so I don't have a single clue about what is written here, but I'm worried because it says that there's a connection between serotoenergic drugs and heart valve disease.

http://www.ncbi.nlm.nih.gov/pubmed/19505264

How important is this? Should we be worried or not? Because DMT also falls under this category.


Its not important.

If you look the substance up, its just one of those drugs that can cause negative effects.

Don't let it give you any negative opinion of Psychedelics.
 
Ufostrahlen
#9 Posted : 5/31/2015 9:57:59 PM

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greenmoss wrote:
Its not important.

How is evaluating the literature not important?

Mescaline seems to have a great safety profile regarding the 5HT2BR with a ki > 20,000nM. See:

http://www.jneurosci.org/content/9/10/3482.long
http://pdsp.med.unc.edu/...amp;doQuery=Submit+Query

So if you want to microdose psychedelics, look into mescaline. And stay away from LSD, if you believe in the researcher's numbers and care for you heart valves.

Look up "Alexander Shulgin heart valve replacement surgery 2008".

Someone could change the subject of the thread into a meaningful one, like: "Psychedelics and 5HT2B cardiotoxicity"
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oversoul1919
#10 Posted : 5/31/2015 10:14:03 PM

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As I see, it is yet to be determined how much affinity DMT has for the 5HT2b. Maybe it doesn't have high affinity at all.

 
oversoul1919
#11 Posted : 5/31/2015 10:19:23 PM

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More exactly, 5HT2 B agonism has not yet been discovered.
 
Ufostrahlen
#12 Posted : 5/31/2015 10:21:47 PM

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oversoul1919 wrote:
As I see, it is yet to be determined how much affinity DMT has for the 5HT2b. Maybe it doesn't have high affinity at all.


UFO wrote:
Binding of DMT for the 5HT2B is 550nM, as strong as MDMA, Fenfluramine is 4134nM:

http://pdsp.med.unc.edu/...amp;doQuery=Submit+Query
http://pdsp.med.unc.edu/...amp;doQuery=Submit+Query
http://pdsp.med.unc.edu/...lue+only&kiKey=27707

Quote:
3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”) Induces Fenfluramine-Like Proliferative Actions on Human Cardiac Valvular Interstitial Cells in Vitro

http://molpharm.aspetjou...6/1223/T1.expansion.html
http://molpharm.aspetjou...g/content/63/6/1223.long


Thus DMT binds stronger to the 5HT2B receptor than FENFL (lower ki value, stronger binding). Don't consume it daily, I guess.
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Ufostrahlen
#13 Posted : 5/31/2015 10:26:09 PM

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oversoul1919 wrote:
More exactly, 5HT2 B agonism has not yet been discovered.

Wikipedia lists MDMA & DMT as non-selective agonists, psilocin as a selective agonist.
https://en.wikipedia.org/wiki/5-HT2B_receptor

But it's too late for me to look up more sources... maybe more tomorrow.
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Cognitive Heart
#14 Posted : 6/5/2015 7:25:25 PM

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The Traveler wrote:
Do we really know if these supplements (like PQQ) will help the way we hope? And how sure are we that they will not have certain side effects? And how about long term studies about the use of those supplements on humans?I am a bit skeptical if these supplements are really that good without any repercussion and/or side effects.


I don't condone everyone to take PQQ.. we all have different responses to different substances. Said folks can do their homework and come to their own conclusions based on health sciences or whatever it may be. PQQ has beneficial effects shown in vivo and in vitro and is not damaging to plants, animals, children or adults. The role of this flavin is diverse within plants, animals and us, humans. PQQ is merely and only for an increased support of what functions specifically in our bodies on a day to day basis. Side effects are known but are not severe in any sense. Other supplements will vary.

A large portion of supplements have many preventive and protection effects when taken correctly, but not all of them.. a large portion have no studies whatsoever or have shown lacking results. I was also skeptical of PQQ, and usually I am with all supplements before utilizing them, until I can validate it based on studies and real data. I didn't experience anything negative from PQQ itself ime, for about 2-3 months. Some noticeable and subtle positive effects.
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Ufostrahlen
#15 Posted : 6/5/2015 8:20:08 PM

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The Traveler wrote:
Do we really know if these supplements (like PQQ) will help the way we hope? And how sure are we that they will not have certain side effects? And how about long term studies about the use of those supplements on humans?

Regarding cardiac fibrosis and supplements - in this case Resveratrol - there are these studies:

Olson, ER; Naugle, JE; Zhang, X; Bomser, JA; Meszaros, JG (2005). "Inhibition of cardiac fibroblast proliferation and myofibroblast differentiation by resveratrol". American journal of physiology. Heart and circulatory physiology 288 (3): H1131–8. doi:10.1152/ajpheart.00763.2004. PMID 15498824.

Aubin, MC; Lajoie, C; Clément, R; Gosselin, H; Calderone, A; Perrault, LP (2008). "Female rats fed a high-fat diet were associated with vascular dysfunction and cardiac fibrosis in the absence of overt obesity and hyperlipidemia: Therapeutic potential of resveratrol". The Journal of Pharmacology and Experimental Therapeutics 325 (3): 961–8. doi:10.1124/jpet.107.135061. PMID 18356487.

Sutra, T; Oiry, C; Azay-Milhau, J; Youl, E; Magous, R; Teissèdre, PL; Cristol, JP; Cros, G (2008). "Preventive effects of nutritional doses of polyphenolic molecules on cardiac fibrosis associated with metabolic syndrome: Involvement of osteopontin and oxidative stress". Journal of Agricultural and Food Chemistry 56 (24): 11683–7. doi:10.1021/jf802357g. PMID 19049292.

Haven't read them, but maybe it's a good idea to supplement Resveratrol while/after tripping.

Addendum: Polyphenols in general seem to be beneficial to the heart and in preventing cardiac fibrosis. At least a Google Scholar search indicates this. But consider this statement a weak one - made after a hot summer day by a tired lay researcher. I hope other look into this as well.

https://scholar.google.c...iac+fibrosis+polyphenols
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Seeingisbelieving
#16 Posted : 5/13/2021 5:00:04 AM

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Went down this rabbit hole expecting it to be a myth that's been busted but found a bunch of info that warrants further investigation. Why is this getting swept under the rug? I feel this would merit a few animal studies! Heart health is very important . It's stuff like this that frustrates me to the ends of the earth.

https://psychedelicreview.com/th...rotonin-5-ht2b-receptor/
https://thethirdwave.co/psychedelics-heart-risk/


https://www.cell.com/cell/pdf/S0092-8674(16)31749-4.pdf
https://chacruna.net/why-chronic...-might-break-your-heart/
 
Bisy
#17 Posted : 5/13/2021 6:19:44 AM

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seeingisbelieving, youre a research-a-holic, and a very efficient one obviously. you have that edge, the ability to ask the right questions and to know where the best places to look for answers are..i find myself often in admiration and fascinated by it. you dont just ask questions and wait for someone to tell you where to look. questions are good, they indicate that someone is curious and wants to learn, but when you decide to post, you bring more to the table than good questions..i admire that.
Everything i say is fictional, I just wanna be cool and fit in.
 
 
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