Pharmacology Novel peripherally-restricted super-selective 5ht2b antagonist

[psychetastic]

Hello everyone, I've noticed that very recently there has been discovered a very selective 5ht2b receptor antagonist that is VERY selective (578 times more selective for the 2B class than 2A or 2C) and also peripherally restricted, which means it doesn't cross that brain blood barrier (so doesn't act on the brain).

What does this mean? It means that the use of psychedelics or empathogens in people who are at risk of cardiovascular disease or have some heart condition now could use such substances safely. Many substances including LSD, mescaline, MDMA, (M)APB5/6, induce strain on the heart due to potent 5ht2b agonism, which on the long run if used too frequently can cause cardiovascular vulvopathy or hypertension.

A 5ht2b selective antagonism that doesn't enter the brain is ideal for this task, as prevents cardiovascular damage in the body while keeping the 5ht2b receptors on the brain intact so you can have the whole psychedelic experience.

I'll leave you the wikipedia link of the new substance here: VU0530244

 

[ShulginsReincarnation]

Hello everyone, I've noticed that very recently there has been discovered a very selective 5ht2b receptor antagonist that is VERY selective (578 times more selective for the 2B class than 2A or 2C) and also peripherally restricted, which means it doesn't cross that brain blood barrier (so doesn't act on the brain).

What does this mean? It means that the use of psychedelics or empathogens in people who are at risk of cardiovascular disease or have some heart condition now could use such substances safely. Many substances including LSD, mescaline, MDMA, (M)APB5/6, induce strain on the heart due to potent 5ht2b agonism, which on the long run if used too frequently can cause cardiovascular vulvopathy or hypertension.

A 5ht2b selective antagonism that doesn't enter the brain is ideal for this task, as prevents cardiovascular damage in the body while keeping the 5ht2b receptors on the brain intact so you can have the whole psychedelic experience.

I'll leave you the wikipedia link of the new substance here: VU0530244

Thanks for the thought, but if you look into the claims you are making regarding the effects of psychedelics on cardiovascular function you will find they are not common at all. Its based on exaggerated claims by people with very little medical knowledge. I have been paying close attention to what the leading doctors have had to say on the matter, and the general consensus is that its blown out of proportion by paranoid thinkers. No one in medicine is really concerned unless the person is using the compounds far FAR in excess of normal use. The reason these doctors say this is because (for one) no one is having such issues to date meaning that the risk is probably.... almost not there haha... Plus, as for mechanism of why it is not being seen in anyone, it is believed that a 4-6 hour psilocybin experience or an 8-12 hour LSD experience of a 12-14 hour mescaline experience once every few weeks at most (that is considered moderate use) will not cause issue due to limited agonism.

The rumor came from fenfluramine-phentermine combo in the 1990s which caused issues due to daily use. Nobody is consuming a half gram mescaline a day for months on end like people did with fen-phen because... well... why the fuck would they? lmao

So, yes, risk is possible... But probably not likely unless you are eating nothing but mushrooms and cactus all day every day for most of the days you are alive lol

Thank you though again as it may be helpful in very rare cases where the person wants to use the substances, but has a preexisting health issue.

 

[Hexagon Sun]

Thanks for the thought, but if you look into the claims you are making regarding the effects of psychedelics on cardiovascular function you will find they are not common at all. Its based on exaggerated claims by people with very little medical knowledge. I have been paying close attention to what the leading doctors have had to say on the matter, and the general consensus is that its blown out of proportion by paranoid thinkers. No one in medicine is really concerned unless the person is using the compounds far FAR in excess of normal use. The reason these doctors say this is because (for one) no one is having such issues to date meaning that the risk is probably.... almost not there haha... Plus, as for mechanism of why it is not being seen in anyone, it is believed that a 4-6 hour psilocybin experience or an 8-12 hour LSD experience of a 12-14 hour mescaline experience once every few weeks at most (that is considered moderate use) will not cause issue due to limited agonism.

The rumor came from fenfluramine-phentermine combo in the 1990s which caused issues due to daily use. Nobody is consuming a half gram mescaline a day for months on end like people did with fen-phen because... well... why the fuck would they? lmao

So, yes, risk is possible... But probably not likely unless you are eating nothing but mushrooms and cactus all day every day for most of the days you are alive lol

Thank you though again as it may be helpful in very rare cases where the person wants to use the substances, but has a preexisting health issue.

People taking dily microdoses for months or years are everytime more common. Talking from experience. I had heart issues/fuckanza after I dont know, maybe 2-3 years of this routine (and most probably due venlafaxine doctor´s advise, taken for 3 years approx, that one was probably the worst offender). So I dont have hard data to proof or disproof anything, but my experience says you better take it as a real possibility and also take measures (like supplementing hawthorn extracts as mentioned in another thread) if possible if you are into the 5htb persistent user/abuser profile

 

[ShulginsReincarnation]

People taking dily microdoses for months or years are everytime more common. Talking from experience. I had heart issues/fuckanza after I dont know, maybe 2-3 years of this routine (and most probably due venlafaxine doctor´s advise, taken for 3 years approx, that one was probably the worst offender). So I dont have hard data to proof or disproof anything, but my experience says you better take it as a real possibility and also take measures (like supplementing hawthorn extracts as mentioned in another thread) if possible if you are into the 5htb persistent user/abuser profile

I haven't even gotten around to it yet, but I am starting to see a lot of reports on how microdosing doesn't even work as proposed, and that it is just a trendy fad. But, yes, being cautious is good. Curious why one would take a 5ht2a agonist with venlafaxine though since venlafaxine should theoretically deminish the effects of such. Seems like a general bad idea to mix the two for the fact that it wouldn't really have effect, and also may havr cardiotoxic effects which you mentioned.

 

[Hexagon Sun]

I haven't even gotten around to it yet, but I am starting to see a lot of reports on how microdosing doesn't even work as proposed, and that it is just a trendy fad. But, yes, being cautious is good. Curious why one would take a 5ht2a agonist with venlafaxine though since venlafaxine should theoretically deminish the effects of such. Seems like a general bad idea to mix the two for the fact that it wouldn't really have effect, and also may havr cardiotoxic effects which you mentioned.

Two points. The microdosing deffo works and in my case it worked wonders for like 1or 2 years more or less non stop. Probably one of my happiest and more productive phases of my life. Sure it wont work for everybody and evertime but it have strong use cases to improve massively your quality of life.

Second point: I never mixed venlafaxine and psychs. First I spend the 3 years on venla, after quitting and passing some additional months sober I started the microdosing regime spontaneouly. I really didnt planned it, it just happened, and as I said, it worked like a charm. Of course YMMV, but I wouldnt ditch the idea cause someboda said is a trendy fact when you have solid evidence of people first hand saying the opposite

 

[ShulginsReincarnation]

Two points. The microdosing deffo works and in my case it worked wonders for like 1or 2 years more or less non stop. Probably one of my happiest and more productive phases of my life. Sure it wont work for everybody and evertime but it have strong use cases to improve massively your quality of life.

Second point: I never mixed venlafaxine and psychs. First I spend the 3 years on venla, after quitting and passing some additional months sober I started the microdosing regime spontaneouly. I really didnt planned it, it just happened, and as I said, it worked like a charm. Of course YMMV, but I wouldnt ditch the idea cause someboda said is a trendy fact when you have solid evidence of people first hand saying the opposite

Sure, anecdotal evidence is there for such and I don't argue that at all. I, myself, have noticed that microdosing with mushrooms is worthless in my case. However, LSD seems to do what SSRIs were supposed to do for me yet didn't. Oh, and did I mention there are zero side effects? But, there's no data to support the claim that this is common, or worthwhile for everyone to be doing. We need more scientific data is all.

But, with the microdosing we do have to be mindful of the 5ht2b receptor agonism then. This also needs more study either way.

I don't recall my original points in having said what I did exactly, but that is my response to yours based on what I could recollect of our previous conversation and that more recent reply you provided (for which I thank you as it allowed me to better elaborate.)