MDMA Pharmacology Notes

[Hilopsilo]

Idk if I posted this before but I often talk of how the 3month rule is completely arbitrary and there’s no harm in having 2night sessions so long as certain rules are followed (one being only having at most 6-7 sessions a year average). I’ve proven plenty how it’s safe from a neurotoxicity standpoint in another thread but many think the high will be dulled as well.

This study proves otherwise and goes along pretty much with what I’ve been saying. A second night roll can be better than the first.

https://www.researchgate.net/profile/Magi-Farre/publication/8629510_Repeated_doses_administration_of_MDMA_in_humans_Pharmacological_effects_and_pharmacokinetics/links/568304db08aebccc4e0e1ebd/Repeated-doses-administration-of-MDMA-in-humans-Pharmacological-effects-and-pharmacokinetics.pdf

-GC

wow this is very interesting, attempting to understand the abstract... sounds like the 2nd dose produced 29% higher peak blood levels, and a 77% increase in AUC (effectively, total blood-level-over-time?). Plus the clearly noted increased subjective effects.

IME, I really don't know how to describe it, the 2nd 100mg 24-48 hours later reaches this fever pitch where its like WOAH ITS ON NOW (that is very hard to imagine or compare to until you're there). My ego just got torn apart, we can deservedly cut to the good stuff. There's a lot of factors here, namely pushing it on the psych dose by this time too (needs an actual dose increase, but LSD seems to benefit from this "post roll/trip lobotomy window" as well). But three days in a row for anything, well, the idol gods of hedonism begin to metaphysically frown & jeer at me...

If anyone has any good resources on serotonin & the gut (& better yet, MDMA), post em up. I'm finding more & more stomach issues manifest themselves as anxiety, even when drugs aren't involved. You know when ya got the shits and it feels like pressure is being put on your anxiety-bone in your gut? I've been finding foods high in fiber & vitamin C to reduce my anxiety just by setting my digestive system straight. All my friends who can't enjoy MDMA their bad experience is accompanied by shitting all night, to be frank. But in any case, to me its undeniable that MDMA can totally get subdued by external & internal factors causing various types of discomfort.

 

[G_Chem]

Another cool article.. This one looks at the effects hormone release from MDMA has on various subjective effects. Notice they found increased DHEA correlated with euphoria.

This has got me looking to try something on my next roll. Take DHEA sometime in conjunction with MDMA to see if any poteniation occurs.

Subjective and hormonal effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans - PubMed

A typically used dose of MDMA produced effects commonly associated with stimulants and hallucinogens. Subjects liked MDMA. Correlations between cortisol and DHEA levels and some physiological and psychological effects are consistent with animal data suggesting that hormones modulate some...

pubmed.ncbi.nlm.nih.gov

-GC

 

[cosmosmariner]

Thanks for this article. I was only able to read the abstract. My favorite sentence was “Subjects like MDMA.” Love that.

I wonder what the mechanism would be for DHEA ?

 

[G_Chem]

Thanks for this article. I was only able to read the abstract. My favorite sentence was “Subjects like MDMA.” Love that.

I wonder what the mechanism would be for DHEA ?

Here’s a great article on it

https://d1wqtxts1xzle7.cloudfront.net/47656194/Modulation_of_neurotransmitter_systems_b20160730-17075-bxqqia-with-cover-page-v2.pdf?Expires=1654357541&Signature=dMLHtkIJzCYE3UfN4AYDkjVLyRUCmlBMupBz86amZV1DXLnqD9GSUe4TYMlNE8HwRu~b7Hb4d65ToNSES2sw2JlfJomulITb-P4ktHuO6ziCaswZ6kIf3W1r61AgG-eHX709N2yG3o0JAUQC5CfK2IFFjtYuzAS7VZgdYIV0ZyVkPINPtnZNIuEwx7Ah5Q79-lc0w7kjBgA4pDEETqjWzZZR6owlU8aiyHVg537EmZ3Xb-e1tbvAjRkEDdoWyT34TMIU66wo-QuZqmkvPhDaIO02jbTh0z3gwI6gvBJlPHfb8ormn~ME2fhlJMCYNPHD9BOPDvEZ8mKGSJ36EGPT8g__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA

-GC

 

[G_Chem]

Speaking of I’m thinking of trying DHEA and a micro/small dose of LSD today to see if there’s any interesting synergy, we’ll see if it ends up happening. Either way I’m beginning to take DHEA again so I can learn it’s effects a bit better before I go for the full on experiment of combining with MDMA in a month n a half or so.

-GC

 

[cosmosmariner]

Excellent. Please keep us posted. I’ll let you know about my DHEA / MDMA experiment. To wit: I will take 50 mg of DHEA for several weeks leading up to MDMA use. I will take the day before, but not the day of.

 

[cosmosmariner]

Here’s a great article on it

https://d1wqtxts1xzle7.cloudfront.net/47656194/Modulation_of_neurotransmitter_systems_b20160730-17075-bxqqia-with-cover-page-v2.pdf?Expires=1654357541&Signature=dMLHtkIJzCYE3UfN4AYDkjVLyRUCmlBMupBz86amZV1DXLnqD9GSUe4TYMlNE8HwRu~b7Hb4d65ToNSES2sw2JlfJomulITb-P4ktHuO6ziCaswZ6kIf3W1r61AgG-eHX709N2yG3o0JAUQC5CfK2IFFjtYuzAS7VZgdYIV0ZyVkPINPtnZNIuEwx7Ah5Q79-lc0w7kjBgA4pDEETqjWzZZR6owlU8aiyHVg537EmZ3Xb-e1tbvAjRkEDdoWyT34TMIU66wo-QuZqmkvPhDaIO02jbTh0z3gwI6gvBJlPHfb8ormn~ME2fhlJMCYNPHD9BOPDvEZ8mKGSJ36EGPT8g__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA

-GC

Thanks, GC. I couldn’t make this link work.

 

[G_Chem]

Thanks, GC. I couldn’t make this link work.

Here’s the ref info to look up..

“Modulation of neurotransmitter systems by dehydroepiandrosterone and dehydroepiandrosterone sulfate: Mechanism of action and relevance to psychiatric disorders

Iván Pérez-Neria, Sergio Montesa, Carmen Ojeda-Lópeza, Jesús Ramírez-Bermúdez , Camilo Ríos”

-GC

 

[cosmosmariner]

Here’s the ref info to look up..

“Modulation of neurotransmitter systems by dehydroepiandrosterone and dehydroepiandrosterone sulfate: Mechanism of action and relevance to psychiatric disorders

Iván Pérez-Neria, Sergio Montesa, Carmen Ojeda-Lópeza, Jesús Ramírez-Bermúdez , Camilo Ríos”

-GC

Thanks, GC. I was able to find it on pub med.

Thanks, GC. I couldn’t make this link work.

Wondering if DHEA, via dopamine increases, wouldn’t make MDMA more neurotoxic?

 

[G_Chem]

Thanks, GC. I was able to find it on pub med.

Wondering if DHEA, via dopamine increases, wouldn’t make MDMA more neurotoxic?

You know I was thinking that myself but then I also see mentions that DHEA is neuroprotective so idk..

On a side note been taking it about 4 days now at 6.25mg a day (heard only 2.5-5 is needed to restore to normal levels) and have had a ton more energy. I’ve also had cancer which is said to effect DHEA levels, I’m guessing I’m naturally deficient.

-GC

 

[cosmosmariner]

You know I was thinking that myself but then I also see mentions that DHEA is neuroprotective so idk..

On a side note been taking it about 4 days now at 6.25mg a day (heard only 2.5-5 is needed to restore to normal levels) and have had a ton more energy. I’ve also had cancer which is said to effect DHEA levels, I’m guessing I’m naturally deficient.

-GC

Thanks for sharing that. I’m glad you’re surviving. And interesting to hear about DHEA’s effect on you. I took it for a while but at 50 mg. Maybe I was taking way too much.

 

[cosmosmariner]

I’m taking 50 mg DHEA now for four weeks leading up, because I had that dose around. I know that’s probably too much, but might add data to the experiment.

 

[G_Chem]

I’m taking 50 mg DHEA now for four weeks leading up, because I had that dose around. I know that’s probably too much, but might add data to the experiment.

Perfect we are experimenting at the same time! I’ve been taking 6.25mg nightly and will be doing so for 4wks as well. This shall be interesting to compare notes

I might also have my brother try an acute dose the night before or so.

-GC

 

[cosmosmariner]

And different doses. Looking forward to sharing.

 

[Jabberwocky]

I’d like this thread to serve as a place to discuss the nuances of MDMA’s pharmacology.

First I was wondering why oral MDMA has more love to it then other ROA’s and found this article.

The effect of 3,4-methylenedioxymethamphetamine (MDMA, ?ecstasy?) and its metabolites on neurohypophysial hormone release from the isolated rat hypothalamus - PMC

Methylenedioxymethamphetamine (MDMA, “ecstasy”), widely used as a recreational drug, can produce hyponatraemia. The possibility that this could result from stimulation of vasopressin by MDMA or one of its metabolites has been investigated in vitro. ...

www.ncbi.nlm.nih.gov

This shows the metabolites HMMA and others have a significant hormone impact (including oxytocin the love hormone) compared to MDMA alone. These metabolites form more with oral administration.


Next, I’ve always wondered why product that smelled of safrole felt better than not. This may be why?..

Inhibition of human cytochrome P450 enzymes by the natural hepatotoxin safrole

The hepatotoxin, safrole is a methylenedioxy phenyl compound, found in sassafras oil and certain other essential oils. Recombinant cytochrome P450 (CY…

www.sciencedirect.com

It sounds like safrole may be a decent enzyme inhibitor.

Edit in more later.

-GC

The article doesn't address the route of administration with respect to why things happen. They gave the rats the drug orally, they haven't compared routes of administration.

There is absolutely no evidence that the route of administration causes some release of hormone differently than another route of administration.

In fact, they are very clear that hormone release is stimulated in a dose dependent manner.

They identify that prolactin is released but only at high doses of MDMA, that's why you get a limp dick when you take too much.

I booty bumped my E and felt the love a lot, in fact it is a more overwhelming Loved up roll by rectal administration, and it usually lasted longer.

Now I will say the subjective effects of an overwhelming serotonin surge caused by insufflation or IV administration may overwhelm the lovey feeling where oral and rectal administration don't. It does not mean that the hormones causing that feeling weren't released, the rush just overwhelmed it.

 

[G_Chem]

The article doesn't address the route of administration with respect to why things happen. They gave the rats the drug orally, they haven't compared routes of administration.

There is absolutely no evidence that the route of administration causes some release of hormone differently than another route of administration.

In fact, they are very clear that hormone release is stimulated in a dose dependent manner.

They identify that prolactin is released but only at high doses of MDMA, that's why you get a limp dick when you take too much.

I booty bumped my E and felt the love a lot, in fact it is a more overwhelming Loved up roll by rectal administration, and it usually lasted longer.

Now I will say the subjective effects of an overwhelming serotonin surge caused by insufflation or IV administration may overwhelm the lovey feeling where oral and rectal administration don't. It does not mean that the hormones causing that feeling weren't released, the rush just overwhelmed it.

Rectal is not a great comparison as a fair amount still goes through first pass metabolism. I’ve also heard many say it lasts shorter.

And I’m extrapolating from the fact that HMMA production occurs more through routes such as oral compared to intranasal or IV simply due to the fact more MDMA is reaching the brain as actual MDMA and not a metabolite. Hence why Cocaine and Ketamine suck orally compared to snorted/IV, same concept of increased metabolism before the parent drug can properly reach the brain. In this case though, MDMA seems to benefit from it not only due to increased HMMA, but also MDA particularly S-MDA.

Again rectal wouldn’t be a great comparison, not only for the reason above but depending how it’s done, if pushed too far in can increase first pass metabolism. If inserted too far you might as well be taking orally.

Btw good to have you back I missed debating you.

-GC

 

[Jabberwocky]

But the article still doesn't say that oral is better than rectal or whatever.

You could actually be correct that oral administration somehow causes some different release of hormones. But the article does not say that at all.

That's the only issue I have with your post, you are reading things into the data that don't exist, That's dangerous.

 

[Jabberwocky]

I have only scanned these articles, but to address the issue of safrole potentially inhibiting liver enzymes...super interesting...

If we are talking about P450, then adding grapefruit juice would theoretically mimic this effect, as grapefruit juice also inhibits P450. I have always heard how grapefruit juice potentiates a roll, but have been hesitant to try it due to an ER incident with a friend of mine involving CYP2D6.

Well that didn't have anything to do with grapefruit juice because grapefruit juice inhibits CYP3A4, not CYP2D6.

Obviously grapefruit juice can affect MDMA metabolism, just not CYP2D6.

CYP3A4 is one of the enzymes along with CYP1A2 and CYP2D6 commonly stated to metabolize MDMA.

What most people are unaware of is that CYP2C19 and CYP2B6 also contribute significantly to MDMA metabolism.

It is interesting that poor CYP2C19 metabolizers, end up with a higher percentage of MDA after MDMA metabolism. Then people who are normal or high metabolizers.

It is interesting to note that people that smoke at the same time as using MDMA depending on polymorphism also end up having more MDA post metabolism due to inhibition of CYP1A2.

 

[Jabberwocky]

Rectal is not a great comparison as a fair amount still goes through first pass metabolism. I’ve also heard many say it lasts shorter.

And I’m extrapolating from the fact that HMMA production occurs more through routes such as oral compared to intranasal or IV simply due to the fact more MDMA is reaching the brain as actual MDMA and not a metabolite. Hence why Cocaine and Ketamine suck orally compared to snorted/IV, same concept of increased metabolism before the parent drug can properly reach the brain. In this case though, MDMA seems to benefit from it not only due to increased HMMA, but also MDA particularly S-MDA.

Again rectal wouldn’t be a great comparison, not only for the reason above but depending how it’s done, if pushed too far in can increase first pass metabolism. If inserted too far you might as well be taking orally.

Btw good to have you back I missed debating you.

-GC

Not to belabor the point, but, just because an ROA bypasses first pass metabolism does not mean that there are different ratios of metabolites. It ends up in the liver regardless. And that person will metabolize things the same way as long as there aren't any confounding variables like taking other drugs or smoking cigarettes.

Initial bioavability which equals rush of course are going to be different. But the end result of metabolism will be the same.

From my own personal experience, rectal administration not only hits harder but also lasts longer and this is true for MDMA as well as MDA, and for almost every MDXX and benzofurans.

 

[G_Chem]

Not to belabor the point, but, just because an ROA bypasses first pass metabolism does not mean that there are different ratios of metabolites. It ends up in the liver regardless. And that person will metabolize things the same way as long as there aren't any confounding variables like taking other drugs or smoking cigarettes.

Initial bioavability which equals rush of course are going to be different. But the end result of metabolism will be the same.

From my own personal experience, rectal administration not only hits harder but also lasts longer and this is true for MDMA as well as MDA, and for almost every MDXX and benzofurans.

While this member is gone I feel the need to once again rebuttal. Yes ROA’s do effect metabolite production, if not we wouldn’t see a major increase of norketamine with oral that then decreases with each route that has increased BA.

I also never argued rectal wasn’t a good ROA, but depending on how far the drug is inserted will change the pharmacology, pushed too far it’s the same as taking it orally.


Now the reason I’m here.. @cosmosmariner im trying DHEA again. This time 12.5mg sometimes 25, and won’t stop until the day of… I’m not gonna take it on the actual days of rolling. Just wanted to let you know

It’ll be 4wks on like last time intended to do this..

-GC