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5-HT2B heart valve toxicity. What substances are biggest offenders? MDMA LSD 4-FA?..

Beings

Beings

Bluelighter
Joined
Dec 13, 2005
Messages
245
We all know what fen-phen did to folks till 90s. A lot of other drugs activate 5-ht2b. Which ones would cause most damage if used excessively?

i.e. micro dosing on LSD daily? Rolling every weekend? Taking 4-fa?
 
Pretty much all psychedelics are strong 5-HT2B agonists. Yet we don't hear about heart valve toxicity in (ex)-hippies or heavy psych users in general.

Serotonin itself is obviously a full agonist of that receptors, yet we don't hear about heart valve toxicity in SSRI users for example either.

Not even in e-tards, although these obviously have a ton of other problems.

So..who knows? It seems to be a bit more complex than simple receptor agonism.
 
actually i did read report of "hippies" and heart problems a while ago but it didnt mean shit to me so i didnt save it and i cant reference one sadly :(


edit: i checked wiki and it just had one report of someone abusing shrooms and having heart problems at very young age of 20s so thats fucked up. anyway when i find the article of those hippies and heart problems ill post it, i read it like 5 years ago
 
Beings said:
We all know what fen-phen did to folks till 90s. A lot of other drugs activate 5-ht2b. Which ones would cause most damage if used excessively?

i.e. micro dosing on LSD daily? Rolling every weekend? Taking 4-fa?
Click to expand...


It was found that the people getting valve fibrosis from fenfluramine had a mutation in the HTRB2 gene -- I can't find the paper right now but you could search.
 
roi said:
Pretty much all psychedelics are strong 5-HT2B agonists. Yet we don't hear about heart valve toxicity in (ex)-hippies or heavy psych users in general.

Serotonin itself is obviously a full agonist of that receptors, yet we don't hear about heart valve toxicity in SSRI users for example either.

Not even in e-tards, although these obviously have a ton of other problems.

So..who knows? It seems to be a bit more complex than simple receptor agonism.
Click to expand...


There is a paper out there somewhere that I recently read that describes a HTR2B gene mutation that disposes to heart valve disease from fenfluramine. HTR2B encodes 5HT2B, it seems the mutation encodes the receptor in the heart in such a way that agonism causes the heart disease
 
roi said:
Pretty much all psychedelics are strong 5-HT2B agonists. Yet we don't hear about heart valve toxicity in (ex)-hippies or heavy psych users in general.

Serotonin itself is obviously a full agonist of that receptors, yet we don't hear about heart valve toxicity in SSRI users for example either.

Not even in e-tards, although these obviously have a ton of other problems.

So..who knows? It seems to be a bit more complex than simple receptor agonism.
Click to expand...


There is a paper out there somewhere that I recently read that describes a HTR2B gene mutation that disposes to heart valve disease from fenfluramine. HTR2B encodes 5HT2B, it seems the mutation encodes the receptor in the heart in such a way that agonism causes the heart disease
 
roi said:
http://cardiovascres.oxfordjournals.org/content/60/3/518.long

That mutation was only found in 1 of the 10 ex-fenfluramine users suffering from PPH, so their conclusion



is eh rather questionable.
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Different paper -- the one I read -- every singe person that presented with fenfluramine valve fibrosis had the mutation -- not the one you cited.

It was a specific polymorphism not identified with any poor function or other disease state.
 
roi said:
Pretty much all psychedelics are strong 5-HT2B agonists. Yet we don't hear about heart valve toxicity in (ex)-hippies or heavy psych users in general.

Serotonin itself is obviously a full agonist of that receptors, yet we don't hear about heart valve toxicity in SSRI users for example either.

Not even in e-tards, although these obviously have a ton of other problems.

So..who knows? It seems to be a bit more complex than simple receptor agonism.
Click to expand...


30-40% of people with Autism Spectrum Disorder have very high levels of serotonin in the blood -- it is diagnostic -- yet I have not heard about high levels of valve fibrosis or PAA in ASD
 
asecin said:
shugenja find the paper or stfu seriously
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This paper shows that the R393X mutation originally identified by Blanpain et al "presented 1) a strong gain of efficacy in cell proliferation as assessed by mitogen-activated protein kinase activity and thymidine incorporation, "

 http://molpharm.aspetjournals.org/content/67/4/983



There is a medscape reference "A R393X mutation in the 5-HT2B gene (HTR2B) was also found in patients with fenfluramine-induced PAH (in vitro experiments confirmed that the mutation turned Arg-393 into a stop codon, truncating the C-terminus of HTR2B)" -- the reference is to Blanpain (which is a single patient)

Still searching for the paper I originally brought up.
 
I've had weird fibrosis issues after MDMA so I would be very curious if you could find that study shugenja...
 
I used to take 5 meo dalt daily and plan to restart this, it fixes the 3d effect which is missing if you have shizo related issues, i never had it untill i got codeine working trough tramadol withdrawal and then 5 meo dalt induced a effect, which is amazing yet a normal aspect of life, this sounds like im a delusional idiot that thinks that normal life is being high on a trip as i cant explain it but then again i talked to someone else with severe anhedonia and he imediatly recognized the 3d effect i talked about, he had this during hes youth, lost it when he developped hes anhedonia and also noted psychedelics bring it back, i was taking it with seroquel as an aside the 5ht2a antagonism abolishes any excessive trippyness or whatever and a low dose ensures therapeutic 3d effects.

The man effect was the ability to fly, haha in all serieusness this sounds stupid or crazy to most ppl so i cant bother eplain to much, just randomly i come acress individuals with shizo related issues, such as anhedonia, avoidant personality disorder, eg social anxiety that stays with alcohol but goes with amphetamine, and a few other negative symptions ppl can only suffer from seperate from positive symptions.

Oh yes i recommened amphetamine with memantine to ppl with social anxiety in alot of cases after talking to them, with extreme long term succes, in before im a irresponsible idiot. I miss the old days when i helped ppl with my interventions, now when i look at social anxiety boards most ppl post about nardil which is a improvement over barely effective ssris but im doubtfull about its long term effectiveness.

This is all really offtopic but i will do everything i can again to spread info about the therapeutic use of drugs of abuse, low doses of psychedelics have been used in alot of cases for the long term treatment of depression, that said how exactly does 5ht2b agonism induce this damage? how many % of ppl suffer from this and are there any ways to prevent it? im a human guina pig with daily low doses of psychedelics, ibogaine, amp, memantine, nootropics and other random chemicals but then i accidently found synergetic combos and actually completely broke trough of shizo related anhedonia, going for complete remission of mental illness is the ultimate goal, making someones depression barable is crap, reducing someones anxiety to a manageable level is crap, everyone deserves to be as happy as most ppl.

Rant.... apologise for posting this here but i cant mention the 3d effect in a seperate thread, its impossible to describe so ppl wont take the thread serieusly, only related individuals understand this, and i want to rant about taking things that are impossible to take by abolishing the negatives, such as this heart issue.

Cardiac fibrosis takes years to develop, if one time mdma causes that i would try steroids excercise for one day and compete with jay cutler for mister olympia.

SSRIS arent psychedelic, so it seems so the way the receptor is activated causes the problem, or it may be related to the ammound of serotonine, ssris only cause a limited increase and receptors downregulate which is why they suck as antidepressants and releasers like mdai are alot more potent.

Again im curious for the mechanism, the mutation points to which receptor so if we know the mechanism we can intervene like how beta blockers block long qt syndrome, or block the receptor.

I used to take 2cd daily in the past but that purely was recreational, no therapeutic effects just euphoria, same thing with apvp, this post screams mania, yet still makes sense, not as bad as desoxy posts tough, oh well call it a early weekend then.
 
etards dont take e everyday which explains why they dont have any issues this is a chronic problem so that is absolutely no proof mdma wont cause this toxic issue.
 
MeDieViL said:
etards dont take e everyday which explains why they dont have any issues this is a chronic problem so that is absolutely no proof mdma wont cause this toxic issue.
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But remember, not everybody gets fibrosis from 5HT2B agonists, cabergoline -- has a risk of induced valvular fibrosis of 65 per 10,000 treatment person years -- pretty low actually.


And as for fenfluramine:

"Another recent investigation by Weissman et al. (14) evaluated the use of dexfenfluramine on valvular heart disease. Their study compared echocardiograms of 1,072 patients taking dexfenfluramine hydrochloride, sustained-release dexfenfluramine or placebo. Using the FDA case definition, significant aortic regurgitation was seen in only 5% of dexfenfluramine patients, 5.8% of patients on sustained-release dexfenfluramine, and 3.6% on placebo; significant mitral regurgitation occurred in 1.7%, 1.8%, and 1.2% of patients, respectively. Overall, no statistically significant increase occurred in the prevalence of clinically relevant heart valve regurgitation following dexfenfluramine use for up to three months compared with placebo. These findings are consistent with our own results, as well as those of the Framingham Heart Study, and they suggest that the short-term use of dexfenfluramine is not associated with a significant increased risk for valve disease."


http://content.onlinejacc.org/article.aspx?articleid=1126016

Basically same as general population

Here is some actual evidence regarding just how MDMA may cause valvulopathy and or fibrosis due to 5HT2B agonism

" Importantly, the EC50values for activating phosphoinositide hydrolysis at h5-HT2Breceptors for MDMA (2000 nM) and MDA (190 nM) are nearly identical to the plasma concentrations found in humans after a single recreational dose (150 mg) of MDMA in humans. For instance, after a single 150-mg dose of MDMA, de la Torre et al. (2000) reported a Cmax for MDMA of 2000 nM and a Cmax for MDA of 150 nM. "

http://molpharm.aspetjournals.org/content/63/6/1223.full

So you can reach (for a short while) just to the EC50 but peak plasma drops quickly due to excretion in normal users - due to the acid urine of most westerners, poor excreters due to alkaline urine (vegans) may be at risk.

Regardless, the half- life of MDMA is 1/10th that of cabergoline.


Now if you are actually taking MDA -- well that may be an issue, as recreational doses would result in plasma levels of 10 times the EC50. Again -- susceptibility is the issue as well as consistent activation of proliferation.
 
Yeah i tought it was low, never really researched it while i was taking 5 meo dalt daily, i never had the impression there was a big risk with all the ppl taking low daily treshold doses of psychedelics. Still figuring out how this occurs would be worthwhile tough as psychedelics would work for atypical depression, in contrast to sero antagonists working for melancholic. atleast the succes rate of mirtazepine is pretty much the sae as ssris, same as placebo, which doesnt mean they dont work as placebo peters out after 6 months and ppl often report poop out after 5 years, eg placebo is noise covering up the true therapeutic effect, which is still neglible.

Also with regards to therapeutic use of sero releasers we are talking like 30mg of mdai 3 times a day or so.
 
MeDieViL said:
Yeah i tought it was low, never really researched it while i was taking 5 meo dalt daily, i never had the impression there was a big risk with all the ppl taking low daily treshold doses of psychedelics. Still figuring out how this occurs would be worthwhile tough as psychedelics would work for atypical depression, in contrast to sero antagonists working for melancholic. atleast the succes rate of mirtazepine is pretty much the sae as ssris, same as placebo, which doesnt mean they dont work as placebo peters out after 6 months and ppl often report poop out after 5 years, eg placebo is noise covering up the true therapeutic effect, which is still neglible.

Also with regards to therapeutic use of sero releasers we are talking like 30mg of mdai 3 times a day or so.
Click to expand...


Many Psychedlics are 5HT2A/C agonists not 2B (at least not high preferential binding or activity)
 
From my limited knowledge and a bit of theory...

I mean it would follow that the worst would most likely be full agonists.

I don't know this, but I expect that structural phenomena guide a compound to fit more readily into 5-HT2b.

Less 5-HT2b activation would mean less damage, so maybe, broadly speaking, the more other serotonin sites that a 5-HT2b agonist hits, the more is displaced from 5-HT2b.

Also, overweight people put a lot of stress on their heart, which probably temporarily increases if they start exercising to lose weight.
 
Ho-Chi-Minh said:
Less 5-HT2b activation would mean less damage, so maybe, broadly speaking, the more other serotonin sites that a 5-HT2b agonist hits, the more is displaced from 5-HT2b.
Click to expand...

The phenomenon you are describing is called ligand depletion and it is negligable with monoamine receptors. The ligand concentration almost always vastly exceeds the concentration of serotonin receptors and even high levels of occupation do not appreciably reduce the free (unbound) ligand concentration.
 
Would this mean that theres no significant difference in 5HT2B activation between 100ug and 500ug of LSD ? Or am i just misinterpreting your post ?
 
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