Kinda wild that MDMA is on the list with those other three (opioids, meth, and coke). Seems firmly in a less harmful tier to me.
What makes them equal pharmacologically?
Coke is not equal (I mean it is arguably zero harm if taken rarely, but pretty addictive and serious harm if taken regularly), MDMA and meth are extremely similar substances chemically (MA=meth) and have similar mechanisms of action. Same harm prevention techniques work great with both. The most important difference is MDMA being harder to abuse than meth is, because a number of reasons. Most of MDMA users take it occasionally for good, most of meth users take it regularly for harm. AFAIK. Obviously there are many exceptions.
Doses are incredibly portant when discussing the mechanisms of drugs and comparing them because a compound may interact with new and different proteins when the concentration gets high enough. Recreational doses for methamphetamine and cocaine are all over the place partially due to the fact that you can develop tolerance and increase your dose. This doesn't really happen with MDMA as much, and while you can take repeated doses they will rapidly stop working if taken within a small enough time frame. Methamphetamine and cocaine do not have the same tolerance build up
While cocaine is a triple reuptake inhibitor and does interact with serotonin, I don't think its comparable to MDMA
Causes dopamine efflux out of the uptake transporter*
The better criterion is the typical harm to the user. It's lower in MDMA because it's very difficult to use too much, seems to have a low potential for addiction, and is very rarely lethal. Generally usage patterns for MDMA users are much less harmful than illegal cocaine or meth users.
The studies I'm aware of were done on mice, which have a significantly different metabolism than humans. Not to mention there has been no mention of neurotoxicity from the current MAPS studies.
In any case, the idea that vyvanse shows that meth can easily be taken with small negative effects is wrong, because Vyvanse isn't meth, and meth is very rarely prescribed because it's worse for your health than other amphetamines, and even when it is prescribed it's typically far safer than steet meth.
> it's chemically different to meth you'd find on the street
Well yeah, but the MDMA on the street isn't really pure MDMA either.
https://astralcodexten.substack.com/p/know-your-amphetamines
> I doubt you can do MDMA even once weekly for a year without being much worse off in the end
I know some people who did this while in university (twice at a week at times). I would say it definitely did have some negative effect (mostly depressed mood - leading to actual depression in some cases but not others), but that this didn't persist long past the period of use (a few months), and none of these people still use MDMA with such regularity (a lot of them do still take it occasionally), all of them passed their degrees and have good jobs and normal lives now.