The Fundamentals of MDMA, and an Approximation of its Effect by Assembling its Consti

[crispzips]

I recently came across this paperby a professor of biology at the University of Oklahoma, Thomas S. Ray. In ithe proposes the basis of the "entactogenic effect" of MDMA asImadazoline-1. And suggests that this can be demonstrated by combining aselective serotonin-2 agonist (MEM, DOET, DOB, 2-CB-Fly) and an Imadazolinedrug (the pharmaceuticals monoxodine or rilmenidine).

A new wayto have ecstasy? Very interesting, check it out.

Thepaper

Thepodcast version of the hypothesis

 

[Cotcha Yankinov]

Very interesting ideas he has, but I think it might be quite hard to replicate MDMA without reversal of the SERT because different agonists mediate downstream effects differently than endogenous serotonin, this is known as biased signaling and it is essentially why different drugs that work on serotonin (mostly 5-HT2A) can have such different effects.

So I think there is the possibility of biased signaling necessitating the need for endogenous serotonin rather than an agonist. The super majority of MDMA's effects (even dopamine release) have been isolated to depending on the SERT so I just don't think without interacting with the SERT you're going to capture the full magic of MDMA, you could do MDA's 5HT2A agonism and everythang tho.

 

[zikzak]

Here's from a Shulgin note:

8.0 mg 2C-B-fly and 2.0 mg of rilmenidine at 12:30 pm; cannabis vapor at 4:00:

The result was spectacular. I got a +4 experience from a pure imidazoline blood pressure
medication! It is probably the entactogenic core of MDMA. I tend to think of the effects
of MDMA as sweeter and gentler than this, but this was much stronger than any MDMA I have previously experienced.
It turns out that 2.0 mg of rilmenidine is a very high dose.
This is much more intense than the 0.2 mg of clonidine. Probably 1.0 mg would be
adequate, and more comparable to a typical dose of MDMA. It also lasted longer than
MDMA.... I took cannabis vapor. Within minutes my heart opened and the rilmenidine
fully blossomed. At this point I could not feel the cannabis at all, although I had taken it
only a few minutes before. I was astonished by the experience.
Not because it worked, I had already seen the clonidine work. I was astonished by the depth of the experience,
and I remained astonished for two weeks. I was ecstatic. Not ecstatic because it worked,
rather the mental state was ecstatic, somewhat unsober. I recalled Martin Ball calling 5-MeO-DMT
the “crown jewel of the entheogens”. I felt that rilmenidine must also be a
crown jewel. I described the state with superlatives.... Qualitatively, it is very hard to
characterize the rilmenidine state, apart from the depth of it. At 3:52 hours she asked me
how I feel, and I responded “It is like a peaceful lake, it feels eternal... in a peaceful
sense”. Perhaps most telling, just 25 minutes after taking the cannabis, 3:55 hours after 36
taking the rilmenidine, I spoke to my wife about what for me were the core issues in our
relationship. These are things that are very hard to discuss because they are painful, and
discussion tends to lead to anger. But we discussed it peacefully. I expressed my sadness
with tears. I believe this capacity for calm contemplation and discussion of painful
personal issues is a core feature of the entactogenic state of MDMA, and here I was
experiencing it with blood pressure medication.... For me it’s really, astonishingly
among the best psychedelic experiences I’ve ever had. Unbelievable.
(Shulgin 2016)
Pharm 2,p. 26-27