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☠ WARNING ☠ heart valve issues with long term psilocybin/LSD use

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Idrk brotha. Considering its more common stereoisomer is a strong 2b agonist, I wouldn't be surprised if it was too. But I don't really see what this has to do with anything when LSA is by far the most common alkaloid in hbwr?
I think you have it backwards:

"Between the two, ergometrine is significantly more potent at the 5ht2b than isoergometrine."
 
I was referring to ergometrine, as in isoergometrine’s stereoisomer. I still don’t see how this is relevant at all
Why would I being using ergometrine nootropically if I am trying to avoid overstressing 5ht2b? That's the entire point of this thread.
 
Why would I being using ergometrine nootropically if I am trying to avoid overstressing 5ht2b? That's the entire point of this thread.
Im not suggesting at all you use ergometrine nootropically, don’t know where you got that idea. I’m wondering why you began talking about isoergometrine in the first place. If you are currently using HBWR nootropically like you said, you are most certainly activating 2b frequently. But I doubt it’s of any actual medical concern. I mean as far as I’m aware one of the only people to suffer valvulopathy from psychedelic use was Shulgin and that only manifested after like 40 years of constant use (although look at sansert, def caused valvulopathy for daily users). Still if you want to be cautious with the 2b stuff, don’t take hbwr for nootropic purposes.
 
man i would love to see someone post the linked study in redditt and watch them meltdown.

the my drugs are good your drugs are bad child hippies would lose their minds.
 
man i would love to see someone post the linked study in redditt and watch them meltdown.

the my drugs are good your drugs are bad child hippies would lose their minds.
all drugs at the right dose are great in the right situation of course.
then again it is so easy to make mistakes in almost anything...
 
all drugs at the right dose are great in the right situation of course.
then again it is so easy to make mistakes in almost anything...

“those aren’t drugs those are plants and fungi man”

zero side effects and zero chemicals just pure spirit earth magic healing
 

Microdosing psychedelics and the risk of cardiac fibrosis and valvulopathy: Comparison to known cardiotoxins​


'Other ergolines have also been associated with the development of heart problems'. Cabergoline and pergolide are given as an examples... but they aren't ergolines, they are dihydroergolines with totally diferent minimum-energy conformations.

Concluding that a scaffold confirs activity rather than the relative spatial relationships of key moieties demonstrates a profound lack of understanding of how ligands WORK.

We know from aminorex/4MAR and (S) fenfluramine that chronic consumption of ligands with significant peripheral 5HT2b activity are indeed cardiotoxic but how much is a 'microdose' of MDMA? Because I've always doubted microdosing simply because while affinity data make look impressive, EC50 is actually the more useful metric. I can point to examples where the most POTENT member of a class wasn't the one with the lowest Ki, it was the one with the lowest ED50.

The conclusion appears to be 'we don't know' which does look an awful lot like 'if we had the funding...' because Silicon Valley investors and their money is soon parted.

I will make it simple - it's impossble to PROVE a negative but when someone has no positive data and makes invalid assumptions, the simple GIGO metric holds true. But it's a good way to get funding - to present risk.

I've always been very careful to state when something is outside my knowledge domain but the three authors are all psychologists/psychiatrists so I wouldn't expect it to be within their knowledge domain but for the first person credited, this is their first published work, and a lot of politics goes on so on the off-chance they are RIGHT, those other names want to be on there for the theorectical 'glory'.
 
I used a lot of psychedelics between 2008 and 2024. I also just had my aortic valve replaced due to an aortic dissection I suffered on march 16 2026. I was also abusing cocaine for many years. I also had a bicuspid aortic valve. They found that out during my emergency surgery. Maybe psychedelics snd cocaine exacerbated my congenital heart defect? I no longer use any drugs or alcohol, and im lucky to be alive.
 
The question is whether the happiness you get from tripping is more beneficial to your heart than not tripping. Euphoria is very good for you. Misery is a leading cause of heart disease. I have no intention of sitting here fucking miserable in the hope of adding a few weeks to my life. And anyway it's those weeks at the end when you're being spoonfed in a hospital - "Open wide, here comes the choo-choo train"!!

Increase your aerobic exercise if it worries you.
 
Increase your aerobic exercise if it worries you.

The two drugs they flagged as being cardiotoxic actually produce pulmonary arterial hypertension when cosumed at a fully active dose in a chronic (daily) manner. At the time CT revealed heart-valve damage BUT to be clear - the vast majority of people prescribed those medications were NOT so harmed. So there is at least some genetic element also in play. The fact they didn't note that also strikes me as wanting desperately to have some sort of way of SUGGESTING possible harm.

With both aminorex and fenfluramine, the serious damage did seem to occur quite fast in those susceptable. I actually added 4MAR because in the 1990s a family was caught producing 4MAR in a barn on their land and all three had developed severe pulmonary arterial hypertension which isn't enough to conclude that is is a genetic-bias and/or that it is dose-related but I believe when questioned they did admit to consuming a LOT of their own product thus broke RULE 1.

But it doesn't mean more evidence isn't available - only that the researchers woozled their results. But drug-induced pulmonary arterial hypertension is recognized and isn't limited to just two or three compounds.


But it's always chronic use i.e. when a person is consuming a compound every day or even multiple times a day for a prolonged period. Note the paper even names the associated gene. So I'm somewhat surprised that it wasn't cited. That's what makes me think the paper was more part of the publish-or-perish culture and that presenting risk is a very good way to get funding. The correct conclusion should have been 'there is no evidence to suggest microdosing is associated with pulmonary arterial hypertension'. I do understand that a hypothesis that proves false is less likely to be published and that is a tragedy as a negative results are actually MORE valuable.

Last month I found a 2021 paper that makes 50+ years of papers utterly wrong since they used a false axiom.

But here no axioms are really presented or inferred. Explaining the details of vasular remodelleling seems oddly detailed given the paucity of data. I suppose if it isn't your field, knowing what is important is difficult. But it's already known so why would you expend space simply explaining it (badly) again? It also ignores that there is a second mode of toxicity (endothelial Injury) and quite amazing to me, totally avoids mentioning that a lot of far more commonly prescribed medications are also known to produce those same toxicities but to such a small extent that one has to look at vast samples to spot the slight increases.

But using two dihydroergolines as evidence that ergolines may be cardiotoxic - that SHOULD have been spotted by peer review. But since these are all psychologists/psychiatrists, one assumes peer-review simply did not include a medicinal chemist. I AM going to contact Retraction Watch as the paper is so deeply flawed, it's only going to cause harms.
 
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