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

Pure science papers to share and discuss.
A new paper about the risks that may be associated with the use of psychedelics for micro dosing.

At times this practice has been promoted by members of the nexus. I think it’s important that we consider that the promotion of the practice of micro dosing might not be a good idea. Especially when considering that the proposed benefits seem to be mostly placebo effects.




Abstract
Though microdosing psychedelics has become increasingly popular, its long-term effects on cardiac health remain unknown. Microdosing most commonly involves ingesting sub-threshold doses of lysergic acid diethylamide (LSD), psilocybin, or other psychedelic drugs 2–4 times a week for at least several weeks, but potentially months or years. Concerningly, both LSD and psilocybin share structural similarities with medications which raise the risk of cardiac fibrosis and valvulopathy when taken regularly, including methysergide, pergolide, and fenfluramine. 3,4-Methylenedioxymethamphetamine, which is also reportedly used for microdosing, is likewise associated with heart valve damage when taken chronically. In this review, we evaluate the evidence that microdosing LSD, psilocybin, and other psychedelics for several months or more could raise the risk of cardiac fibrosis. We discuss the relationship between drug-induced cardiac fibrosis and the 5-HT2B receptor, and we make recommendations for evaluating the safety of microdosing psychedelics in future studies.
 

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What would your opinion be on non constant use? What if one took DMT a few times a day a couple times a week intermittently? You know, non constant but still a fair amount.
 
The key phrase here is "may cause", this is very theoretical claim. Worth discussion nevertheless, however I would expect a epidemic of valve diseases and unexpected rise in data discussed in literature if this was the case. The amount of psychedelics certain populations use would definitely been known by now.







A quick poll could be conducted on Nexus about members with valve issues as a starting point for data collection but something tells me there may not be many with issues. Sugar and saturated fat comes to mind as a substances with much stronger data associated with cardiovascular disease but I don't think that'll be illegal anytine soon.
 
Not to make light of it, but “choose your poison” comes to mind.

Sure and it is an understandable thought, the thing is that the there’s now a suggestion that there is apparently an risk for some very serious side effects for a not so effective (placebo) practice. I’m not saying that it’s wrong to micro dose but I do think that promoting the practice should come with a warning about the risks and not so convincing effects.

What would your opinion be on non constant use? What if one took DMT a few times a day a couple times a week intermittently? You know, non constant but still a fair amount.

I don’t have an opinion on it, I think that most drug use has a positive and negative effects balance. And I think that dmt has a favorable balance. Also from the literature it is wel established that the use of classic psychedelics is wel tolerated when used with moderation and with ample time between trips, read months. Having said that I think dmt is a bit of different animal since the effects are so short lived compared to for example lsd. At this point it’s just unknown what the long term effects are for our little hobby, it might be benign or could be more serious at this time there’s just no way of knowing.
 
The key phrase here is "may cause", this is very theoretical claim. Worth discussion nevertheless, however I would expect a epidemic of valve diseases and unexpected rise in data discussed in literature if this was the case. The amount of psychedelics certain populations use would definitely been known by now.
Your absolutely right, may cause, is the key here. It’s just one studie pointing at a purposed side effect, of a relative new practice of micro dosing. I’m not so sure that the side effects micro dosing can be explained by looking at populations with more traditional use because the key is the continuous use of low doses over a longer period of time and that is not something that was not previously done at the scale we are seeing now.
 
It's worrisome. My daughter has no psychedelic experience nor desire. I have a bag of mushrooms right now and I was going to recommend micro dosing to her for frequent migraines. You can get relief from more occasional use of larger doses, but I don't think that's for her. At least not right now.

Triptans are related to DMT and the use of shrooms for migraines has a lot of support.


Triptans are a family of tryptamine-based drugs used as abortive medication in the treatment of migraines and cluster headaches.
 
Personally, I don’t believe those microdosing studies are credible, or that the effects of microdoses are nothing more than placebo. In my experience, 100-200mg of cubensis mushrooms has predictable, undeniable, distinct, and consistent physical and mental effects similar to the way caffeine and THC effect me in distinct and predictable ways. In other words, I don’t believe the effects of psilocybin on my mood are any more attributable to placebo than the effects of caffeine on my wakefulness or the effects of THC on my stress levels. YMMV
 
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Personally, I don’t believe those microdosing studies are credible, or that the effects of microdoses are nothing more than placebo. In my experience, 100-200mg of cubensis mushrooms has predictable, undeniable, distinct, and consistent physical and mental effects similar to the way caffeine and THC effect me in distinct and predictable ways. In other words, I don’t believe the effects of psilocybin on my mood are any more attributable to placebo than the effects of caffeine on my wakefulness or the effects of THC on my stress levels. YMMV

He Omani, the placebo effect can be very powerful and that’s why it’s so important to do double blind studies to see if the proposed effects are placebo effects or actual effects. Having said that, placebo effects are helpful and real in some scenarios but can have very detrimental consequences when they are for example used to treat serious illnesses like cancer.
I think that what you experience could feel very real but also that common described effects of micro dosing are wel within the range of possible placebo effects. The only way of knowing if it’s one or the other is to do research and see if said effects are there when the subject is given a placebo or the real deal, denialism is just not a valid method to understand these things.
 
He Omani, the placebo effect can be very powerful and that’s why it’s so important to do double blind studies to see if the proposed effects are placebo effects or actual effects. Having said that, placebo effects are helpful and real in some scenarios but can have very detrimental consequences when they are for example used to treat serious illnesses like cancer.
I think that what you experience could feel very real but also that common described effects of micro dosing are wel within the range of possible placebo effects. The only way of knowing if it’s one or the other is to do research and see if said effects are there when the subject is given a placebo or the real deal, denialism is just not a valid method to understand these things.
Yeah nah. That’s not what I’m talking about. What I’m saying is that psilocybin has distinct, physical and mental effects that are undeniable - whether you take 200 or 2000mg, those effects can be clearly felt. Double blind studies are irrelevant in this sense. We don’t need double blind studies to prove that weed gets you high or that Ayahuasca makes you purge - that’s just what happens - same thing with psilocybin having an elevating effect on the body and mind.
 
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Yeah nah. That’s not what I’m talking about. What I’m saying is that psilocybin has distinct, physical and mental effects that are undeniable - whether you take 200 or 2000mg, those effects can be clearly felt. Double blind studies are irrelevant in this sense. We don’t need double blind studies to prove that weed gets you high or that Ayahuasca makes you purge - that’s just what happens - same thing with psilocybin having an elevating effect on the body and mind.
I understand where you are coming from and we do have to have double blind tests, not only to make sure what the difference are compared to placebo, but also for dose-response studies, and remember that they can also use other active substances for the control group so that all people involved will think they have the real deal and "some effect" from their dose.

So the more substances we test, the better we can make a correctly comparable control group and see what the real differences are.


Kind regards,

The Traveler
 
A new paper about the risks that may be associated with the use of psychedelics for micro dosing.

At times this practice has been promoted by members of the nexus. I think it’s important that we consider that the promotion of the practice of micro dosing might not be a good idea. Especially when considering that the proposed benefits seem to be mostly placebo effects.
I think it never hurts to use best practices with harm reduction, so yes, this is an important paper.

Though in science: one paper is no paper, two papers isn't even half a paper, and three papers might be just a start of something interesting that needs more research.

So before we make this our standard advice, I think we need to have a lot more more data and science papers on microdosing, this is a promising start but not yet the end of it all.


Kind regards,

The Traveler
 
Again, that’s not what I’m talking about. Double blind studies are used to determine the efficacy of a medication to treat a particular disease, in comparison to a placebo. We don’t need double blind studies to determine that serotonergic psychedelics have uplifting physical and mental effects, even when taken in small doses. Double blind studies are irrelevant with regard to proving the existence of these effects, which are a given - they are needed to determine if said effects coincide with reducing the symptoms of various maladies, which is a separate topic.
 
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I think it never hurts to use best practices with harm reduction, so yes, this is an important paper.

Though in science: one paper is no paper, two papers isn't even half a paper, and three papers might be just a start of something interesting that needs more research.

So before we make this our standard advice, I think we need to have a lot more more data and science papers on microdosing, this is a promising start but not yet the end of it all.
Your absolutely right it’s a pointer at most and we are stil at the surface of understanding psycadelics, especially in the relative new practice of micro dosing. I think I might compile a topic on the current state of research in the future so we can discuss the broader topic and its implications. What I have read so far is not fortifying the positive outcomes of the practice and is more pointing towards self suggestion and now a possibility of having negative health outcomes aswel.


Take care
 
Yes, this new world of psychedelic medicine is truly exciting, but there are so many unknowns. I’m glad we have professional scientists doing research in this area! Otherwise, it would be like the blind leading the blind. Have you guys heard of the book, How to Change Your Mind by Michael Pollan? That’s where I first learned about psychedelics and have been looking for a safe way to do them, ever since. I applied to do one of the trials with Compass Pathways, but didn’t meet the selection criteria for bicep size. Maybe I’ll try to sign up for one of the MAPS trials. I’ve heard nothing but great things about that organization. They’re really on the cutting edge of psychedelic science! It’s high time that we separate psychedelics from things like herbalism, shamanism, mysticism, spirituality, or direct experience. We need to bring psychedelics into the 21st century. Evidence based clinical protocols are the name of the game, am I right?!
 
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Might be worth mentioning here, evidence indicates that harmine has a cardioprotectant effect:
 
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.

The Structure and Function of the Serotonin 5-HT2B Receptor
Psychedelics & Heart Risk: Can LSD Cause A Heart Attack?
https://www.cell.com/cell/pdf/S0092-8674(16)31749-4.pdf
Why Chronic Microdosing Might Break Your Heart
A related message from a older topic on related issues. Just putting it here for reference.
 
A related message from a older topic on related issues. Just putting it here for reference.
Thanks for the cross-reference; @Jagube's recent contribution to that thread deserves an explicit mention in this thread too:
A good overview here: Cardiovascular safety of psychedelic medicine: current status and future directions - Pharmacological Reports

Tldr: there is no data for psilocybin or LSD.
There is some for aya and a hint that harmine may be cardioprotective:
The only experimental studies that have included a histological evaluation of the heart have been conducted with ayahuasca – a hallucinogenic beverage containing the beta-carbolines (harmine, harmaline, and tetrahydroharmine) and N,N-dimethyltryptamine [93, 94].

In the first study, no abnormalities were evident in a histological examination of the cardiac tissues of Wistar rats carried out 14 days after the administration of ayahuasca at a dose 50 times higher than in religious ceremonies (15.1 mg/kg DMT) [93].

A second animal study, in which ayahuasca was administered daily for 28 days in doses that exceeded those typically used in religious ceremonies, also showed that there were no histopathological changes in the heart [94].

The results of these experimental studies must be treated with some caution because ayahuasca is a mixture of DMT and beta-carbolines, which have different effects on the cardiovascular system. Indeed, in cardiovascular research, harmine has been shown to reduce systemic arterial blood pressure and peripheral vascular resistance through the inhibition of L-type calcium voltage-dependent channels.

Finally, a recent study provided several lines of evidence for the anti-hypertrophic effects of harmine. Namely, in an animal model of spontaneous hypertension (SHR), harmine reduced myocardial hypertrophy. In addition, in vitro observations (of human embryonic stem cell-derived cardiomyocytes) showed that by inhibiting NF-κB phosphorylation and reducing inflammation, harmine inhibited the phenotypes of norepinephrine-induced hypertrophy and also downregulated the expression of hypertrophy-related genes [95]
 
Again, that’s not what I’m talking about. Double blind studies are used to determine the efficacy of a medication to treat a particular disease, in comparison to a placebo. We don’t need double blind studies to determine that serotonergic psychedelics have uplifting physical and mental effects, even when taken in small doses. Double blind studies are irrelevant with regard to proving the existence of these effects, which are a given - they are needed to determine if said effects coincide with reducing the symptoms of various maladies, which is a separate topic.

I think what's being questioned is if a microdose is an effective amount. While yes, there are psychedelic effects from these drugs, you have to take a certain amount of them first. Perhaps they are speculating that the amount of a microdose only provides benefits by way of placebo because the dose is too low to be effective. By definition, a microdose should be subperceptual, that is, barely noticing it if anything at all.

To the OP, I'd be curious about if these potential negative side-effects are less prevalent in people that have regular physical activity.

One love
 
I could only speculate on that, I think an active lifestyle is in general a good idea and might help with staying healthy in the long run.

I think that the question of whether micro dosing is healthy is still open, but there are pointers to adverse health effects. The preconceived ideas that psychedelics are physiology benign is based upon studies that see no adverse effects of using them sporadically and might therefore not apply to continuous daily use over longer periods of time.

In a way when you would compare it to smoking tabaco, if you would only smoke one sigaret a handful of times in a year I think you would have a hard time finding anything more than benign effects. Yet we all know how devastating the effects of smoking regularly are. With the current trend of using psychedelics continuously over longer periods we might find a whole new array of adverse effects. At this point in time we just don’t know, but I think we should be careful with promoting the practice.
 
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