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  • BDD Moderators: Keif’ Richards | negrogesic

4mmc safety

snmfmy said:
It's a very specific serotonin receptor affinity that you're talking about, not all serotonergic agents. And it also requires direct agonism of the cardiac 5HT2B receptors and or sustained large increases in circulating plasma serotonin levels.

It's the 5-HT2b receptor. The issue is either very high levels of circulating serotonin as opposed to increases in brain serotonin, or the actual compound agonizes the 5-HT2B receptor (as in MDA and MDMA).

Meow meow causes a very significant increase in BRAIN dopamine and serotonin. However, the levels drop very quickly (a Half-life less than a half an hour) as opposed to the 300 minutes Half-Life serotonin clearance for MDMA.

This is probably why it's more-ish, and also probably why you can redose all night long and still have euphoria.

The elimination half-life of 4-MMC is 2 hours.

While there have been reports of valvulopathy in heavy MDMA users, I've been unable to find actual corroborative data.

That being said, MDMA is unique because it actually agonizes the 5-HT2B receptor which is then induces serotonin release. In fact, this is required for many of the effects of MDMA. The 5-HT2B receptor in platelets is responsible for serotonin release into plasma and it is this action as well as direct agonism of cardiac 5-HT2b receptors that would likely be responsible for any valvulopathy.

Serotonin 5-HT2B Receptors Are Required for 3,4-Methylenedioxymethamphetamine-Induced Hyperlocomotion and 5-HT Release In Vivo and In Vitro - PMC

The “club drug” 3,4-methylenedioxymethamphetamine (MDMA; also known as ecstasy) binds preferentially to and reverses the activity of the serotonin transporter, causing release of serotonin [5-hydroxytryptamine (5-HT)] stores from nerve terminals. ...
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

I can't find any evidence that 4-MMC is an agonist at the 5-HT2B receptor.

All of that means It's really quite unlikely that meow meow is going to cause valvulopathy.
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So the fact most people binge on 4mmc doesnt mean that the serotonin button is constantly being pressed?


Also i put 4mmc into one of those receptor prediction software a while ago specifically looking for 5ht2b as i also couldnt find any studies/information about it online. It did pop up but seemed to predict a weaker binding affinity than the other serotonin + dopamine receptors which made me think its less of an issue than mdma. But then again most people who use mdma dont typically smash it often and if they do, then they typically burn out and eventually stop pretty quickly. Also 6apb has a stronger affinity and has been associated with heart valve thickening. But as you said theres nothing online about 4mmc, yet you'll find plenty of hidden communities of 4mmc enthusiasts who absolutely abuse the drug and have done for years on end some are still using since 08/09 and going strong. Which suggests it cant be that bad right?
 
ageingpartyfiend said:
Always feel shocked when I hear people say "no comedown from 4mmc"

If I took it (shudder) then it would probably be a 5/6 day almost-suicidal comedown, totally drained mentally and physically. Shocking nasty comedown form 1g. And yeah - was definitely 4mmc

Could just be too old for it now i guess and/or too many stims in the past. Will never touch it again that's for sure
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Never got a comedown from it either, just tired and dropped to sleep
 
mauve said:
Is valvulopahthy easily recognised? Or would it require a chest x-ray, scan or blood test for a diagnosis?
Click to expand...
I'm not a clinician so don't take my word for it, please reference medical texts for more information

I believe valvulopathy can be recognized by a change in heart sounds along with echocardiograms. If your physician is good at recognizing the changes in heart sounds you may get it noticed early. Some people may experience palpitations, shortness of breath, chest pain, etc
 
someguyontheinternet said:
Serotonin release agents also run the risk of valvulopathy when chronically administered, this is the reason that fenfluramine was pulled as an obesity medication

That being said, occasional use of both 4mmc and MDMA are unlikely to cause valvulopathy. Chronic, regular use is a different story entirely and I can definitely see 4mmc causing valvulopathies if used on a daily-weekly basis
Click to expand...
Incorrect.

The cause is agonism of 5- HT2b receptors.

The active metabolite of fenfluramine (norfenfluramine) is a potent agonist of 5-HT2B receptors in cardiac cells. That's why it can induce valvulopathy.

en.m.wikipedia.org

Norfenfluramine - Wikipedia

en.m.wikipedia.org en.m.wikipedia.org
 
Gregor_Stewart said:
So the fact most people binge on 4mmc doesnt mean that the serotonin button is constantly being pressed?


Also i put 4mmc into one of those receptor prediction software a while ago specifically looking for 5ht2b as i also couldnt find any studies/information about it online. It did pop up but seemed to predict a weaker binding affinity than the other serotonin + dopamine receptors which made me think its less of an issue than mdma. But then again most people who use mdma dont typically smash it often and if they do, then they typically burn out and eventually stop pretty quickly. Also 6apb has a stronger affinity and has been associated with heart valve thickening. But as you said theres nothing online about 4mmc, yet you'll find plenty of hidden communities of 4mmc enthusiasts who absolutely abuse the drug and have done for years on end some are still using since 08/09 and going strong. Which suggests it cant be that bad right?
Click to expand...
Well I binged on meow, at one point I did 12g over the course of three days. After about six months I just got bored of it
 
@snmfmy
Studies at the moment seem to suggest that it has a much stronger effect on the cardiac mitochondria. So i have hypothesised that coq10 supplementation could potentially be benefical.

www.talkingdrugs.org

Health Risks Associated with Mephedrone Use: What We Know So Far

Sam Iravani has combed through the data and spoken to the researchers, investigating the potential health harms of mephedrone - and how to reduce them.
www.talkingdrugs.org

"mephedrone was shown to cause a very high reduction in ATP levels in rat heart mitochondria, even at the lower concentrations tested. ATP provides energy to drive many processes in living cells, the lack of which can lead to a breakdown in the heart's continuous mechanical work (although to what extent this alone can actually drive heart failure is not clear)."
 
I mean meph was discovered way before it became popular in the scene in the 2010s I believe? So would it be far to early to say what the long term effects are, as akin to cocaine or mdma which has been studied and abused since the 70s i believe
 
Gregor_Stewart said:
So the fact most people binge on 4mmc doesnt mean that the serotonin button is constantly being pressed?


Also i put 4mmc into one of those receptor prediction software a while ago specifically looking for 5ht2b as i also couldnt find any studies/information about it online. It did pop up but seemed to predict a weaker binding affinity than the other serotonin + dopamine receptors which made me think its less of an issue than mdma. But then again most people who use mdma dont typically smash it often and if they do, then they typically burn out and eventually stop pretty quickly. Also 6apb has a stronger affinity and has been associated with heart valve thickening. But as you said theres nothing online about 4mmc, yet you'll find plenty of hidden communities of 4mmc enthusiasts who absolutely abuse the drug and have done for years on end some are still using since 08/09 and going strong. Which suggests it cant be that bad right?
Click to expand...
Not in the way you think.

Just because a substance causes serotonin release in the brain doesn't mean it causes massive serotonin release in the body.

Serotonin can't cross the blood brain barrier. What's in your brain stays in your brain. What's in your body stays in your body.

The issue with serotonergic drugs is not the release of serotonin or even the reuptake inhibition, it's actually agonism of the 5-HT2B receptor in cardiac cells.

Yes, very high levels of constantly circulating serotonin can also do the same thing but you really only have that from carcinoid tumors.

I can't find anything regarding 6-APB and valvulopathy. I'd be interested in whatever citation you could provide.

There are a lot of rumors that this drug or that drug is associated with fibrotic valvulopathy simply because they're a serotonin agonist, yet there's rarely evidence.

Let's actually look at the real data for fenfluramine and valvular disease:

"For dexfenfluramine or fenfluramine the 5-year cumulative incidence of valvular abnormality was 7.1 (95% CI 3.6-17.8) per 10,000 subjects for 1-3 months use and 35.0 (16.4-76.2) per 10,000 subjects for > 4 months use"

35 people out of 10,000 subjects (1/3 of 1%) that used fenfluramine daily for greater than 4 months.

Valvular Abnormalities with Dexfenfluramine and Fenfluramine

www.medsafe.govt.nz www.medsafe.govt.nz

That's the level of risk associated with fenfluramine. Kind of ridiculous isn't it?
 
snmfmy said:
Not in the way you think.

Just because a substance causes serotonin release in the brain doesn't mean it causes massive serotonin release in the body.

Serotonin can't cross the blood brain barrier. What's in your brain stays in your brain. What's in your body stays in your body.

The issue with serotonergic drugs is not the release of serotonin or even the reuptake inhibition, it's actually agonism of the 5-HT2B receptor in cardiac cells.

Yes, very high levels of constantly circulating serotonin can also do the same thing but you really only have that from carcinoid tumors.

I can't find anything regarding 6-APB and valvulopathy. I'd be interested in whatever citation you could provide.

There are a lot of rumors that this drug or that drug is associated with fibrotic valvulopathy simply because they're a serotonin agonist, yet there's rarely evidence.

Let's actually look at the real data for fenfluramine and valvular disease:

"For dexfenfluramine or fenfluramine the 5-year cumulative incidence of valvular abnormality was 7.1 (95% CI 3.6-17.8) per 10,000 subjects for 1-3 months use and 35.0 (16.4-76.2) per 10,000 subjects for > 4 months use"

35 people out of 10,000 subjects (1/3 of 1%) that used fenfluramine daily for greater than 4 months.

Valvular Abnormalities with Dexfenfluramine and Fenfluramine

www.medsafe.govt.nz www.medsafe.govt.nz

That's the level of risk associated with fenfluramine. Kind of ridiculous isn't it?
Click to expand...
Right when people take 5htp thinking it will raise their serotonin levels in the brain when all it does is circulates in the body?

Am I correct the data is showing quite a low risk?
 
Yea, my gut feeling was that there is nothing that would inevitably lead to cardiovascular issues, even if it was minor risk factor and I am glad I could have been confirmed to be correct.

But if you begin to decrease the intervals between the episodes of use, I would advice to recognize you might be running from some issues in your life and do something about it.
 
Gregor_Stewart said:
@snmfmy
Studies at the moment seem to suggest that it has a much stronger effect on the cardiac mitochondria. So i have hypothesised that coq10 supplementation could potentially be benefical.

www.talkingdrugs.org

Health Risks Associated with Mephedrone Use: What We Know So Far

Sam Iravani has combed through the data and spoken to the researchers, investigating the potential health harms of mephedrone - and how to reduce them.
www.talkingdrugs.org

"mephedrone was shown to cause a very high reduction in ATP levels in rat heart mitochondria, even at the lower concentrations tested. ATP provides energy to drive many processes in living cells, the lack of which can lead to a breakdown in the heart's continuous mechanical work (although to what extent this alone can actually drive heart failure is not clear)."
Click to expand...
"The isolated heart mitochondria were incubated with different concentrations of mephedrone (5, 10 and 20 µM)"

Isolated mitochondria. I didn't know that was such a thing in your body (because it's not).

I wouldn't be worried about mitochondrial damage based on that study.
 
mauve said:
Right when people take 5htp thinking it will raise their serotonin levels in the brain when all it does is circulates in the body?

Am I correct the data is showing quite a low risk?
Click to expand...
Actually one of the big issues with 5htp supplementation taken orally is the peripheral increase in serotonin

Iirc taking tryptophan results in better increases in brain 5ht
 
mauve said:
Right when people take 5htp thinking it will raise their serotonin levels in the brain when all it does is circulates in the body?

Am I correct the data is showing quite a low risk?
Click to expand...
Yes, it's a ridiculously low risk.

You're more likely to have congenital valvular dysfunction (heart murmur) (about 41 people out of 10,000).
 
snmfmy said:
"The isolated heart mitochondria were incubated with different concentrations of mephedrone (5, 10 and 20 µM)"

Isolated mitochondria. I didn't know that was such a thing in your body (because it's not).

I wouldn't be worried about mitochondrial damage based on that study.
Click to expand...
@snmfmy

The findings in isolated mitochondria open the door to understanding how mephedrone might interact with cellular components at a very detailed level. I understand it isnt a definite but its possible it could have this effect.
 
Gregor_Stewart said:
@snmfmy

Apologies i could only find data on 5apb


Suggestive that it can cause cardiotoxicity but i may just be reguritating what i have read about 6apb in the past. I think the fact the benzofurans are close to amiodarone aswell could be suggestive of potentially cardiotoxic effects.
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Like I said, look at the actual likelihood with a known 5-HT2B agonist. 35 out of 10,000 taking it daily.
 
Gregor_Stewart said:
@snmfmy

The findings in isolated mitochondria open the door to understanding how mephedrone might interact with cellular components at a very detailed level. I understand it isnt a definite but its possible it could have this effect.
Click to expand...
No, it just shows you that if you incubate isolated mitochondria in mephedrone long enough you get what they found.

It doesn't mean it would happen in the body.

In fact, it's kind of bad science for them to even propose that it necessarily would.

I think the reason they isolated the mitochondria is because they couldn't get enough 4-MMC through the cell membranes to actually affect the mitochondria. I mean they had all these rats that they've been giving massive doses of 4-MMC to, and they couldn't biopsy the heart after they sacrifice them to check the brain.

Come on. This is an example of getting grant money to do a study and say drugs are bad and they had to find something to show.
 
mauve said:
Right when people take 5htp thinking it will raise their serotonin levels in the brain when all it does is circulates in the body?

Am I correct the data is showing quite a low risk?
Click to expand...
5-HTP does cross the blood brain barrier. I don't know why you think it doesn't.

5-HT on the other hand, which is serotonin, does not cross the blood-brain barrier.
 
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