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

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.

 

[Voidmatrix]

Everything comes with some price, right. This is interesting to me seeing as I low dose DMT often and I microdose.

Your analogy to cigarettes is fitting considering we used to think those were benign as well.

It would be interesting to study cardiac systems and processes of people in some cultures that "trip" often, such as ayahuasceros and curanderos.

One love

 

[Sabnock1990]

As far as Tobacco and it's harms go though, i've learned lately that apparently Tobacco smoking can reduce Folate levels in the body, and lack of Folate can cause a lot of the issues we see from Tobacco, so it makes me wonder are the two connected? probably, and so what if a lack of Folate is actually the main culprit and not the Tobacco smoking? but then they'd have to study that and may have to conclude that Tobacco may not be as "harmful" as the anti-smoking propagandists made it out to be. Just a thought, especially considering our only source of Folate really has been Folic Acid which has issues of it's own and doesn't seem to work as well as natural Folates (like Methylfolate for example) in replenishing Folate levels in the body, so we could be having a low-level Folate deficiency, and that combined with the Tobacco smoking can deplete people's Folate and lack of Folate can cause heart issues, strokes, cancers, breathing issues, etc, especially considering the lack of oxygenated cells.

 

[Varallo]

Smoking reduces and increases many things in the body, but as with most correlations in smoking it’s not as easy to say that by solving the deficiency the health risks can be mitigated. The only way to make a difference is to cut out the confounding factor which is the smoking of tobacco itself.

 

[Varallo]

Everything comes with some price, right. This is interesting to me seeing as I low dose DMT often and I microdose.

Your analogy to cigarettes is fitting considering we used to think those were benign as well.

It would be interesting to study cardiac systems and processes of people in some cultures that "trip" often, such as ayahuasceros and curanderos.

One love

For a long time i have thought that my use of dmt was of no harm and I do stil feel that way, but as years have passed I do try to limit my use. I’m not much a micro doser myself as i feel it has no benefits for me, and then when I move up dose to the point where I feel the effects it’s counterproductive in my life.

For more then 2 decades I have used more or less every two/tree weeks a psycadelic usually a mix of pharma or aya with vaped dmt on top. And then usually for three or four days building up to a higher dose, looking back I never thought it’d be at this long, usually my hobbies don’t grab me for more then a couple years. But this has turned into something like a religious ritual for me, next to this I don’t drink or smoke and really like to be sober.

On the research, I’ve have been reading in to the adverse health effects of my hobby and plan on compiling all the articles into a new topic in some time. Hopefully I can find the time to do this after the summer, so far I have not found to much worrying stuf.

Take care

 

[Voidmatrix]

I feel you. I think that I've always thought of the negatives of my DMT use to be mild and worth it in the end, but there's always some downside: nothing is all good and nothing is all bad. I consider DMT and harmalas my sacraments so comes with the territory.

Thank you for being willing to share your research with us.

One love

 

[ermit]

Very interesting article, thanks!

Here the study looked at LSD, Psilocin and MDMA, but not DMT, compared to known problematic Valvular Heart Disease (VHD) - inducing drugs. Comparison was done at structural level, affinity level and effect levels (functional pathways linking the 5HT-2B receptor to fibroblast production in heart valves)

- study showed that there is a high probability that typical MD dosages are susceptible to be problematic
- I have some concerns with psilocin, as it has a greater affinity to the incriminated 5HT-2B receptor than LSD (! conflicting data) and DMT.
- DMT has the least affinity to 5HT-2B (184 - Keiser et al., 2009) in comparison to LSD (conflicting data: 30.0 - Nichols et al., 2002 or 0.977 (!) - Knight et al., 2004) and psilocin (4.6 - NIMH Psychoactive Drug Screening Program). Greater affinity (i.e. lower Ki) is not a direct correlation to VHD but rather an hint.

As for the effectiveness of microdosing itself: it is considerably difficult to design a correct experiment to assess / prove it. However, there is a ton of field reports on its effectiveness (IMHO, enough to expect more than placebo). Anecdotally, I personally confirm it worked quite well on me (and I experimented enough on myself to rule out the placebo). FWIW, I can't "prove it" (scientifically) but I "saw it with enough hints/effects to rule out placebo".


(edit) Some relevant reddit links:
-

https://www.reddit.com/r/microdosing/comments/1bd4l4i/microdosing_psychedelics_and_the_risk_of_cardiac

-

https://www.reddit.com/r/microdosing/comments/wi0p56/feeling_discouraged_about_md_because_common_sense

 

[Voidmatrix]

Can you expand more on how you mitigated your anecdotal experiences to rule out placebo?

Do you think placebo is a bad thing? If so, have you heard shulgin's thoughts on placebo?

I feel similarly in that I've gotten amazing effects, but I don't know how I'd rule put placebo completely.

And i do recognize that you said you cant prove it lol.

One love

 

[Transform]

I'm all for placebo effects - they can be highly cost-effective.

Thanks to the power of the placebo effect, I can gain superpowers by blowing into this brown paper bag! <jumps out of window>

 

[ermit]

Can you expand more on how you mitigated your anecdotal experiences to rule out placebo?

I did a several months long of psilocybin MD (with some breaks, and/or periods when I didn't have the drive to it), later I also tried LSD (analogs).

During the early-phase (finding the right dosage - not easy!), I learnt to recognize the subtle (and sometimes – when too high dosage – less-subtle effects).

My criteria was: low enough to not feel anything if I don't focus my attention on them and high enough to borderline notice them if I focus (like very slight vision improvement, very slight colors deepening, and also more "subjective" ones, like mood enhancement). I guess it's quite personal and may depend on a ton of factors (genetics, my own brain wiring, metabolism, etc. etc.)

=> During the period I followed the schedule (1 day on, 2 days off), it happened a lot of time I forgot I took a microdose this day or the day prior. And sometimes, at the end of the day, when wondering why I was such in a good mood or handled a difficult situation, I then remembered about the microdose I took in the morning or the day before.
=> "The subtle but sensible effects if I focused on" were really consistent over time

Do you think placebo is a bad thing? If so, have you heard shulgin's thoughts on placebo?

No, Placebo-effect is absolutely fascinating (and very powerful). I remember reading absolutely stunning placebo-related science papers about it when I was student.
As for Shulgin's thoughts, I'm quite interested if you have a link or a reference !

I feel similarly in that I've gotten amazing effects, but I don't know how I'd rule put placebo completely.

And i do recognize that you said you cant prove it lol.

I find the "Psychedelics + mind-body relations / placebo effect" topic fascinating, as psychedelics play quite strongly in our mind with signifiance / correlation systems (hence sometimes some "psychiatric dangers" (delusions, false beliefs)). I feel that there is a strong relationship between the two (that's why I'm interested with a pointer to Shulgin's opinion)

I got amazing effects too from my microdosing experiments (on depression/anxiety and family life).
I really can't prove anything yes, It's only a personal opinion after a rather long, careful and (hopefully) rigorous self-experiment/analysis. A part of myself still don't rule out placebo-effect!
=> It's another "internet-random-dude opinion", not much worth

I'm all for placebo effects - they can be highly cost-effective.

Thanks to the power of the placebo effect, I can gain superpowers by blowing into this brown paper bag! <jumps out of window>

Wim-Hof - street version: the paperbag method !

 

[Voidmatrix]

@ermit Thank you for your response.

Wrt Shulgin, it was in the Nature of Drugs. Simply he considers placebo a drug and gives credit to rhe substance that precipitated the placebo effect because without that substance there would be no placebo effect.

One love

 

[The_Embalmer]

As someone who has been microdosing/macro dosing pretty frequently with both psilocybin and DMT for the past year and a half I have had no physical problems as a result and still carry out my running/daily physical tasks unaffected. Id say my heart is in better health from dmt and psilocybin because they help me quit and stay away from booze/cigarettes and bad eating habits. Even if it is a placebo it's a damn good one but I do agree that each case would be personalized to the individual and that should always be taken into consideration when adding any supplement to your diet.

 

[Varallo]

As someone who has been microdosing/macro dosing pretty frequently with both psilocybin and DMT for the past year and a half I have had no physical problems as a result and still carry out my running/daily physical tasks unaffected. Id say my heart is in better health from dmt and psilocybin because they help me quit and stay away from booze/cigarettes and bad eating habits. Even if it is a placebo it's a damn good one but I do agree that each case would be personalized to the individual and that should always be taken into consideration when adding any supplement to your diet.

The thing with heart decease is that it can go unnoticed, so not feeling unhealthy is not a good indicator for actual health, I do think your much better of not drinking and smoking , like said before all drugs have a positive and negative effects balance and as you say this is clearly impacted by the individuals lifestyle choices. If taking a psychedelic leads to not smoking and drinking the benefits will outweigh negative effects pretty quickly since there both so destructive.

Take care, and it’s really heart warming to hear it helped you quit smoking and drinking.

 

[The_Embalmer]

I mean that's just it though we're not promised tomorrow and I don't really know what Im preserving my body for anyway we don't win any trophy at the end of this life for being the most old without any ailments it's really completely up to you and what you see for yourself in your own skin. I suppose time will tell for sure but the quality of life has been a drastic improvement from the substances I was previously ingesting that were legit bad for my heart and were ruining my life/physical health.

But once again it is a case to case basis. If I was gonna develope cardiac problems later in my life It would be from the 7 years I spent putting street ready meth directly into my veins plus the half gallon of vodka id consume on the daily and not the microdoses of psilocybin or dmt i consume now. The human body is a lot more resilient than we give it credit for but yes once again I agree with you here in that there wouldn't really be any knowing as cardiac diseases can go pretty unnoticed for quite some time.

I just kind of think in contrast to dmt and psilocybin vs a lot of other drugs I have done that are legitimately bad for the heart and the direct symptoms experienced in the come downs of these drugs would be a lot less in contrast to whatever this study is trying to theorize. Like sure they might be bad for your heart but I'm curious on what scale now? Like compared to what ya know? I've never had a microdose of psilocybin make me short of breath or checking my pulse every 2 minutes but I'm sure someone out there has.


Anyway as someone who has been ironically a hypochondriac my entire life and specifically about cardiac problems I find it funny I have never been triggered by classic psychedelics in this way nor considered them to ever be bad for the heart, not psilocybin or DMT at least, things like LSD would make more sense due to its more vasoconstrictive stimulative properties and I've certainly had some physically perceived heart problems as the result of dirty acid on quite a few different occasions and certainly some RC compounds out there have left me with a heavy chest to a panic inducing degree like DOB or 25-i but psilocybin and DMT almost seem good for the body even though that wouldn't make any sense and I'm sure there are some undiscovered drawbacks we havent experienced yet but I personally have not had any physical ailments I can think of or anything disconcerting relating to physical health as the result of working with tryptamines daily over the course of this past year and a half.

I also understand it can be a bit more subtle and complicated than that with what this study is trying to suggest in repetitive overstimulation of the 5-ht2b receptor site over an extended period of time being the cause of the fibrosis and Once again not claiming I know anything about this just sharing experiences and obviously they are mostly only limited to physical perceptions as I haven't really been out to a doctor in some time but I can tell you from being in the hospital a year and half ago with liver failure back to running/stretching daily and eating healthy ill take whatever slight gimp the dmt or psilocybin may or may not be having on the heart.

Thank you for sharing this study though it was a good read and certainly something to always consider when incorporating a new supplement into your dietary regime or have already incorporated.


(I should have also said that the past year and a half is when I started working with psilocybin and DMT specifically for my problems with addiction and coming off alcohol and opiate dependency issues/chronic homelessness/ severe PTSD. This does not account for the plethora of psychedelics I abused through my adolescent years into early adulthood with no consideration or care for my body in mind at all during that time of my life.)

 

[Varallo]

Thanks for your very thoughtful response and sharing of your experience, it reminds me to not project my experience and thoughts onto others, my life is very different to yours and sometimes I forget that the alternatives are not always a question of just not doing something but that the alternative might be more complex.

I can’t imagine the struggle of being homeless and having to battle addiction and ptsd in those circumstances I applaud your efforts to help yourself and really hope for better times ahead. Luckily you seem well spoken and articulate about your situation and based on your intelligence think that you are able enough to work towards solving some of the struggles you face.

All the best and take care

 

[ermit]

Related links dump:

Directly related to our topic, a recent paper:
=> Serotonin 5-HT2B receptor agonism and valvular heart disease: implications for the development of psilocybin and related agent
https://doi.org/10.1080/14740338.2023.2248883

Furthermore, the duration of exposure to the 5-HT2B ligand is likely also contributory to the risk assessment of 5-HT2B-mediated VHD [Citation13]. The current paradigm with psychedelic implementation in psychiatry is intermittent exposure as opposed to daily and/or more frequent usage, suggesting an attenuated drug-induced VHD risk. Although not established as efficacious for any mental disorder, microdosing of psychedelics is generally recommended to be administered more frequently introducing legitimate questions about risk for drug-induced VHD, not only with intermittent macrodosing but also more frequent administration of microdosing.

Replicated results from phase 3 studies with psilocybin in TRD are expected in 2025. In addition, results from phase 2/3 studies conducted with lysergic acid diethylamide (LSD) and MDMA are also expected within this timeframe.

About the mechanisms linking 5HT-2B receptor and Valvular Heart Disease:
=> Serotonin Receptors and Heart Valve Disease – it was meant 2B
Serotonin Receptors and Heart Valve Disease – it was meant 2B

 

[The_Embalmer]

Alright well putting on my tinfoil hat here is there any corporations right now that wouldn't want microdosing to take off the same way that weed did? Could we now be running into seeing propagation that will come out from big pharma as a result to try and stop the upcoming microdose surge? Just throwing some thoughts out here because I mean reefer madness was a thing and I know big pharma for a long time really tried to push against weed with some of the most ridiculous theories and claims. We can't forget about the money behind a lot of this and the potential threat that another medicine you can grow in your home might have against a multi billion dollar a year revenue company.

 

[ermit]

Alright well putting on my tinfoil hat here is there any corporations right now that wouldn't want microdosing to take off the same way that weed did? Could we now be running into seeing propagation that will come out from big pharma as a result to try and stop the upcoming microdose surge?

IMHO, It's a perfectly legitimate concern.
However, I would not stress too much about it in the long-term, but yes, exercising caution and critical-thinking is always required when reading recent scientific papers. The scientific community "at large" is pretty wary of conflicting interests, but fact-checking and invalidation of rogue and dishonest studies takes time.

 

[Varallo]

Related links dump:

Directly related to our topic, a recent paper:
=> Serotonin 5-HT2B receptor agonism and valvular heart disease: implications for the development of psilocybin and related agent
https://doi.org/10.1080/14740338.2023.2248883



About the mechanisms linking 5HT-2B receptor and Valvular Heart Disease:
=> Serotonin Receptors and Heart Valve Disease – it was meant 2B
Serotonin Receptors and Heart Valve Disease – it was meant 2B

Thanks for your contribution on the subject, hopefully I have some time to read up during the weekend,

Alright well putting on my tinfoil hat here is there any corporations right now that wouldn't want microdosing to take off the same way that weed did? Could we now be running into seeing propagation that will come out from big pharma as a result to try and stop the upcoming microdose surge? Just throwing some thoughts out here because I mean reefer madness was a thing and I know big pharma for a long time really tried to push against weed with some of the most ridiculous theories and claims. We can't forget about the money behind a lot of this and the potential threat that another medicine you can grow in your home might have against a multi billion dollar a year revenue company.

Haha I’m not so sure about what incentive would drive the mechanics behind these claims, could be a factor but in my opinion it’s unlikely.

 

[610nanometres]

There are some things worth worrying about. This most definitely isn't one of them, in my mind.

 

[The_Embalmer]

https://www.npr.org/sections/shots-health-news/2024/06/27/nx-s1-5021788/magic-mushrooms-psilocybin-microdosing-psychedelics-trends

Seems pretty quickly dismissed for something that does happen and has happened before though. Obviously I'm not speaking in absolutes here but I certainly wouldn't put it past pharmaceutical companies to try to get into the heads of the individual during a time of surge and awareness around MD because it's becoming a pretty big thing with mushrooms and the awareness on that is spreading rapidly and if people can figure out they can grow their own for next to nothing and that it would most likely treat a lot of symptoms of anxiety and depression that would take a lot of money away from the pharmaceutical companies that are profiting off those prescriptions and that is where I could see incentive to release studies like this into the masses to make people suddenly think twice about microdosing so that big pharma would be able to get ahead of this in some way and have control of it. I mean has this not happened before? It's not much of a conspiracy as it is rich people seeing humans as numbers on a screen and doesn't care about what might be benefitting their mental health or releasing them from the constraints of an over-expedient consumptive populace that thrives on capitalism and needs its cattle farm to run with as little questions as possible.