LSA pharmacology question

[Memantine]

Does LSA have high affinity for the 5-HT2B receptor similar to LSD and Psilocin?

Is the vasoconstriction experienced with LSA a result of α₁-adrenergic receptor agonism and is the sedation of LSA a result of α2A-adrenergic receptor agonism?

 

[serotonin2A]

LSA has probably not been tested a 5-HT2B but the expectation is that it is an agonist (affinity at 5-HT2A and 5-HT2B are correlated). Lysergamides usually bind to 5-HT2B.

Alpha1 probably partially contributes to vasoconstriction, which is the case with ergotamine. 5-HT2A activation can also cause vasoconstriction, so those receptors may also contribute, as well as other 5-HT receptors.

No one knows the extent to which LSA activates alpha2a, let alone how that impacts the subjective response. Sedation could also be caused by several other effects. For example, interactions with H1, which other lysergamides are known to bind to. Dopamine receptors could also potentially play a role.

 

[Cotcha Yankinov]

Sarpogrelate is a 5-HT2B antagonist meant specifically for vascular migraine, as I understand there are a fair bit of 5-HT2B receptors on the vascular smooth muscle walls of arteries, as well as 2A receptors.

Also, I think I heard that psilocybin is a 5HT2B partial agonist, so maybe it doesn't have quite the same effects as a full agonist in terms of vasoconstriction (and hopefully cardiac fibrosis).

 

[serotonin2A]

Best guess would be that almost any drug with LSD-like psychedelic effects is a 5-HT2B agonist. That shouldn't be terribly worrisome with these drugs because their use is almost always sporadic. Also, there is probably a genetic component to fibrosis -- not everyone who takes a 5-HT2B agonist chronically develops fibrosis.

 

[Cotcha Yankinov]

Do you think that psilocin as a partial agonist is of any concern? It also sounds like the functional differences/ biased ligands thing might come into play as well.

 

[serotonin2A]

Do you think that psilocin as a partial agonist is of any concern?

If someone were to ingest psilocybin or psilocin several times a day for a few months then they might develop problems.

It also sounds like the functional differences/ biased ligands thing might come into play as well.

A ligand is usually assumed to be unbiased unless there is evidence to the contrary.

 

[Memantine]

Psilocin is cardiotoxic



ABSTRACT
Introduction
: Natural hallucinogenic substances seem to be one of the addict agents most commonly used in
European countries. The important source of those psychodysleptics may be a spreading growth of Psilocybe genus mushrooms.

Material and Methods:

To verify a previously published hypothesis on cardiotoxicity of hallucinogens, the ex perimental study in the form of a three-month test on male Wistar rats was performed. The study groups received intraperitoneally psilocin (PSI) in a dose of 10 μg/kg body weight (b.w.) or beta-phenylethylamine (PEA) in a dose of 1 mg/kg b.w. dissolved in 5% ethanol every second day for 2 and 12 weeks. The control groups received 5% ethanol or 0.9% solution of NaCl for the same time periods. At the end of the experiment, biochemical blood parameters, ECG, and myocardial energetic status were examined, as well as histopathological and electron-microscopic examinations were performed. The decreased serum magnesium concentrations in the PSI-exposed animals were noted.

Results:

The obtained results showed that the repeated (12 weeks) administration of PSI produces in rats ECG
abnormalities in the form of tachycardia, myocardial ischaemia and aberrant intraventricular conduction. It was
also stated that long-term exposure to PSI and PEA exerts a crucial effect on the energy heart muscle metabolism, which has been reflected in the complex changes in the myocardial profile of purine concentrations. These
abnormalities corresponded with degenerative changes in cardiomyocyte mitochondria observed on histopathological and electron microscopy examinations.

Conclusions: The results of the study indicated a cardiotoxic effect of psilocin, manifested by functional and structural changes in cardiomyocytes and coronary arteries

http://old.imp.lodz.pl/nowy_pttox/abstracts/streszcz07/Borowiak ABSTRACT.pdf

 

[Weltmeister]

If you do psilocin every 2 days for 12 weeks cardiotoxic effects are probably the least of your worries. This study is not representative for the average psychedelic user.

 

[Memantine]

I hope so..

What do you mean with "least of your worries"? If you do shrooms every 2 days your 5-HT2A and 5-HT2C receptors will downregulate so you wont experience psychedelic effects anymore. But the 5-HT2B receptor in the heart valves wont downregulate.

 

[mb-909]

The psychological side effects may outweigh the physical side effects. Personally I have started taking psilocybin 1 year ago, with shorter and longer time intervals in between. I try to take it with at least 10 days between each trip. High dosed trips can be fun, but most of the time, especially with shorts breaks, it worsens my depression and psychotic symptoms. Low dosed trips helped me a lot in the long run.

Stress and therefor depression itself can lead to cardiotoxic effects. Honestly I wouldn't worry too much about it, as long as you eat healthy and exercise on a regular basis. It would be more concerning (in my opinon) if you take stim's or large junks of alcoholic beverages on a regular basis.

Pick your poison... There is no risk free medication/drug on the market (excluding the placebo effect).

Here is a dicussion on reddit about psilocybin and the possible side effects:

https://www.reddit.com/r/DrugNerds/...cin_and_5ht2b_agonism_induced_cardiotoxicity/