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Mushrooms, Mycology and Psychedelics > Psychedelic Medicine, Research & Microdosing
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Psilocin and heart
    #28725734 -

Hello travelers,

Many of you might be aware of the literature surrounding classic psychedelics' 5HT2B agonism and its potential consequences on the heart valves. I don't know if psilocin would cause fibrosis of the heart valves in the same way that Fenfluramine does, for example.

There are a lot explorers that journey using these tools very seldom - say a few times a year, maybe even once a year. I am very curious as to how this level of usage affects the heart valves and if it is safe?

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Re: Psilocin and heart [Re: Shroomguy202]
    #28725803 -

Take a look at the video in this thread. I recommend the whole video very highly, however, she specifically addresses cardiotoxicity beginning at 11:30. The tldr is that controlled studies have not been done, but based on the information available and the way that medicines with similar properties behave, it is something to pay attention to and to take breaks if microdosing daily for long periods of time. Occasional use has not been shown to be a problem to date.


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Stoned Gummys | BRF Pucks | Primo Reusable Plates | Easy LI 4 Preserv & Propo
"Psychedelics are powerful substances. Nothing that powerful is completely safe... and nothing completely safe is that powerful!" - Abigail Calder at ALPS 2023
Don't Panic

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Re: Psilocin and heart [Re: ReverendMyc]
    #28725812 -

Thank you. I used to think that it was only an issue with microdosing because of the frequency of usage in microdosing regimens. However, I'm now constantly entertaining the thought that what if macro and heroic doses even taken very infrequently (like once or twice a year) can have a cumulative negative effect. And she said to take breaks while microdosing. Does that mean that any fibrosis that might have occurred will heal during abstinence? 

Edited by Shroomguy202 (04/04/24 02:28 PM)

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Re: Psilocin and heart [Re: Shroomguy202] * 1
    #28725857 -

Quote:
The distinctive valvular abnormality seen with fenfluramine is a thickening of the leaflet and chordae tendineae. One mechanism used to explain this phenomenon involves heart valve serotonin receptors, which are thought to help regulate growth. Since fenfluramine and its active metabolite norfenfluramine stimulate serotonin receptors, this may have led to the valvular abnormalities found in patients using fenfluramine. In particular norfenfluramine is a potent inhibitor of the re-uptake of 5-HT into nerve terminals


Does that help?  It's not really stress in the sense of a single event, but hormone dysregulation over many months that's causing damage.

So there's really nothing to heal from.  The damage is because the agonism is chronic.  Does that make sense?


--------------------
And if I only could
I'd make a deal with God
And I'd get him to swap our places
I'd be running up that road
Be running up that hill
With no problems

Edited by tree frog (04/04/24 03:15 PM)

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Re: Psilocin and heart [Re: tree frog]
    #28726702 -

I found the following from the research study entitled Microdosing psychedelics and the risk of cardiac fibrosis and valvulopathy: Comparison to known cardiotoxins published Jan 12 2024

"Previous research strongly suggests that agonists with a greater affinity for 5-HT2BR may pose the most risk of VHD. The affinity of a ligand for a receptor, expressed as the dissociation constant Ki, indicates the tightness of the binding interaction, though it is a limited indicator of functional efficacy. Though no single biomarker predicts VHD risk with complete accuracy, previous studies have established that 5-HT2BR agonists linked to fibrosis and VHD tend to have a Ki of below 15nM, including methylergonovine, ergotamine, pergolide, DHE, and several others discussed above (Table 1) (Papoian et al., 2017). Ropinirole and lorcaserin, which have not been associated with VHD, have Ki values of 4000 nM and 174 nM, respectively"


"In contrast, based on the 15 nM affinity threshold, the risk of VHD would be substantial for both LSD and psilocybin: LSD has a Ki value of 0.98 nM at 5-HT2BR, and psilocybin’s active metabolite psilocin has a Ki of 4.6 nM at 5-HT2BR (Figure 1) (Dinis-Oliveira, 2017; McKenna and Peroutka, 1989). Importantly, LSD and psilocin exert most of their psychoactive effects via 5-HT2AR (Vollenweider and Preller, 2020). The affinity of LSD at 5-HT2BR is similar to its affinity at 5-HT2AR, while psilocin shows even greater affinity for 5-HT2BR than 5-HT2AR,suggesting that both substances likely stimulate 5-HT2BR at any psychoactive dose (Tagen et al., 2023). Finally, MDMA’s relatively high affinity of 500 nM has not prevented it from causing cardiac abnormalities, although this exception might be explained by MDMA’s ability to potently release 5-HT (Mlinar and Corradetti, 2003); excessive amounts of 5-HT can also promote fibrotic signaling (Smith et al., 2009a, 2009b)."

It seems that psilocin exhibits characteristics that are suggestive of VHD risk. I think clinical trials are underway to answer more questions. Also, cannabis edibles are highly psychedelic. I think I've even read some reports of people experiencing visuals from higher doses. I think cannabis edibles are a better choice due to the fact it doesn't come with the same valvular heart risks like psilocybin mushrooms and LSD.

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Re: Psilocin and heart [Re: Shroomguy202] * 1
    #28726706 -

Right, but the disease is still caused by chronic dosing.  Hence, it's not an issue with macro doses, assuming you're not taking them several times a week.

The stimulation of that receptor essentially causes the cells to build extra tissue that causes obstruction.  That requires time and chronic receptor stimulation to occur.  A macro dose isn't causing damage the way you're asking, and there's nothing to heal.  It's like eating three double quarter pounders once in awhile vs. living off nothing but McDonald's for a year.  The former might give you a stomach ache, but the later might give you a heart attack.  Even if the 'dose' of the former was much larger.

Also, you may want to look at THCs affects on the heart before jumping to the conclusion that weed is safer.


--------------------
And if I only could
I'd make a deal with God
And I'd get him to swap our places
I'd be running up that road
Be running up that hill
With no problems

Edited by tree frog (04/05/24 08:54 AM)

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Re: Psilocin and heart [Re: tree frog]
    #28727010 -

Is that when macrodoses become problematic for the heart valves? When they are taken several times a week?

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Re: Psilocin and heart [Re: Shroomguy202]
    #28727240 -

Yeah I would think so. It's that receptor being stimulated chronically, which means very often or all of the time, which is causing the damage.

It's less about amount of dose, and more about frequency of dose. I don't think macadoses a couple of times of a year are going to hurt anybody, at least in regards to their heart.

Or even a couple of times a month.


--------------------
And if I only could
I'd make a deal with God
And I'd get him to swap our places
I'd be running up that road
Be running up that hill
With no problems

Edited by tree frog (04/05/24 04:38 PM)

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Re: Psilocin and heart [Re: tree frog]
    #28727824 -

Something that occurs to me is that if this was really an issue there would likely be case reports relating to it. Microdosing has been popular for a whole bunch of years and we've only heard this as a theory.

Microdosing enthusiasts generally follow regimes that include 2-4 day breaks between doses to increase efficacy and/or take tiny doses. Occasionally we see some people who are taking 300mg shrooms daily and sat on a tolerance so it is sub perceptual, but that's really rare as most stop because of anxiety and discomfort before long.

I'm not saying it's not a thing, just that it would be a uncomfortable thing to do to yourself and it's likely unsustainable for the vast majority of people. This could be why we haven't seen case reports of people having negative cardiac side effects from microdosing.

It'll be good to see some research completed so chronic users know the safety limits of these substances.

Shroomguy202 said:
I think I've even read some reports of people experiencing visuals from higher doses. I think cannabis edibles are a better choice due to the fact it doesn't come with the same valvular heart risks like psilocybin mushrooms and LSD.


Cannabis has poor psychological outcomes if used more than occasionally. The idea that it is harmless is a myth.



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The nearest we come to knowing truth is when we are witness to paradox.

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Re: Psilocin and heart [Re: Northerner]
    #28727833 -

I was referring to using edible cannabis sporadically, the same way one would traditionally trip on the classic psychedelics. Do you have experience or information of edible cannabis used in that way?

Edited by Shroomguy202 (04/06/24 04:00 AM)

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Re: Psilocin and heart [Re: Shroomguy202] * 1
    #28727840 -

THC is THC, the ROA does not matter.

Classic psychedelics used occasionally have not been indicated to cause physical harm. Research facilities around the world are feeding these things to people and asking them how they feel. The physical safety profile is well established.

There's significant studies showing healthy psychedelic users have improved mental well being. Though people with predisposition to psychosis are cautioned to avoid them.

If you don't want to eat the stuff definitely don't do it. It's not for everyone. But it's not a safety issue.


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The nearest we come to knowing truth is when we are witness to paradox.

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Re: Psilocin and heart [Re: Northerner]
    #28746551 -

This interesting. I hope they do more controlled studies about this subject in the future. For the meantime, I guess the positives outweight the negatives for me.

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Re: Psilocin and heart [Re: Shroomguy202] * 1
    #29005718 -

Please, everyone relax. Was taught in the 60s and 70s by Purdue and Indiana University to strongly question such studies, and to always look for the funding source. I was a data gatherer for suspect studies at many universities, questioning my own involvement later.

IN ANY CASE, it turns out that big Pharma's daily doses of SSRIs is as or more dangerous.


Anyway, averaging out the studies, it looks like a daily strong dose of SSRI can pose the same danger...without all the enjoyment and actual reversal of neg mood.

https://www.sciencedaily.com/releases/2023/01/230129193418.htm

https://www.research.chop.edu/cornerstone-blog/does-serotonin-contribute-to-heart-valve-disease-progression-in-patients-with-low-serotonin

https://columbiasurgery.org/news/columbia-surgery-researchers-find-link-between-serotonin-and-heart-valve-disease

Edited by ElectricEccentric (10/30/24 01:34 PM)

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Re: Psilocin and heart [Re: ElectricEccentric]
    #29005992 -

Thanks for the context, great post.


--------------------
The nearest we come to knowing truth is when we are witness to paradox.

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Re: Psilocin and heart [Re: Northerner]
    #29008236 -

Please, everyone relax. Was taught in the 60s and 70s by Purdue and Indiana University to strongly question such studies, and to always look for the funding source. I was a data gatherer for suspect studies at many universities, questioning my own involvement later.

IN ANY CASE, it turns out that big Pharma's daily doses of SSRIs is as or more dangerous. especially with VHD...valvular heart disease.


Anyway, averaging out the studies, it looks like a daily strong dose of SSRI can pose the same danger...without all the enjoyment and actual reversal of neg mood.

PLEASE SHARE THIS POST WITH ALL WHO YOU ARE CONCERNED ABOUT.

https://www.sciencedaily.com/releases/2023/01/230129193418.htm

https://www.research.chop.edu/cornerstone-blog/does-serotonin-contribute-to-heart-valve-disease-progression-in-patients-with-low-serotonin

https://columbiasurgery.org/news/columbia-surgery-researchers-find-link-between-serotonin-and-heart-valve-disease

Edited by ElectricEccentric (11/01/24 11:50 AM)


Edited by ElectricEccentric (11/01/24 02:05 PM)

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Re: Psilocin and heart [Re: ElectricEccentric] * 2
    #29011673 -

All of those articles are the same study.  The results were that SSRIs are damaging to people with a certain gene expression.

In the case of LSD and psilocybin, they both bind to a receptor that is known to cause vascular heart disease in medications that also bind to this receptor (5-HTB).

SSRI's most likely contribute to vascular heart disease because serotonin will also bind to this receptor.  Though at a much lower rate then more selective molecules, such as LSD and psilocybin.

In any event, LSD and psilocybin, have a much lower binding profile than medications that are currently on the market, in regards to the receptor of concern.  And psilocybin in particular has a higher binding efficiency than LSD, but a much shorter half-life.  However, one of these drugs of concern was pulled completely from the market due to its effect on this receptor.

So, I still would advise anybody wanting to micro-dose to take frequent breaks, and for anybody with vascular heart disease to stick with macro-dosing.

Because even if SSRIs are potentially dangerous, that doesn't mean psilocybin's receptor profile isn't also of concern.

Either way though, macrodosing should be relatively safe.  Assuming set and setting are accounted for.


--------------------
And if I only could
I'd make a deal with God
And I'd get him to swap our places
I'd be running up that road
Be running up that hill
With no problems

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Re: Psilocin and heart [Re: tree frog]
    #29040904 -

Despite the receptor binding indicating a potential risk of this with LSD, Albert Hoffman, it's inventor, who used it with some frequency at first and then occasionally later, died at 102 years of age.

He was also rather healthy and salient, indicating that psychedelics can be a part of a healthy and productive life.

Are there any animal studies being done on this subject?


--------------------
Mushroom Cultivation History

Blasphemy Tek

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Re: Psilocin and heart [Re: Nyxchaac] * 2
    #29041109 -

Nyxchaac said:
Are there any animal studies being done on this subject?


I want to be the guy who gets paid to dose bunnies with acid every day for years. Little guys will be my tripping buddies.


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The nearest we come to knowing truth is when we are witness to paradox.

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Re: Psilocin and heart [Re: Nyxchaac]
    #29041142 -

Oh too bad. He died at 102, poor boy. It's not
that I don't respect him. We all could use a little heart related death insţead of rotting to death. So yeah, relax.

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Re: Psilocin and heart [Re: Northerner]
    #29041230 -

Northerner said:
Nyxchaac said:
Are there any animal studies being done on this subject?


I want to be the guy who gets paid to dose bunnies with acid every day for years. Little guys will be my tripping buddies.


Right?!

I do recall heart defect issues being reported for substituted amphetamines RCs years ago, but those were different drugs. I think it involved products with a florine atom at the 4 position, but I forget.  Some vendors actually pulled the products because of it. I wonder if it was related to the same receptor activity?





--------------------
Mushroom Cultivation History

Blasphemy Tek

Edited by Nyxchaac (11/30/24 06:52 PM)

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