Microdosing psychedelics and the risk of cardiac fibrosis and valvulopathy: Comparison to known cardiotoxins
'Other ergolines have also been associated with the development of heart problems'. Cabergoline and pergolide are given as an examples... but they aren't ergolines, they are dihydroergolines with totally diferent minimum-energy conformations.
Concluding that a scaffold confirs activity rather than the relative spatial relationships of key moieties demonstrates a profound lack of understanding of how ligands WORK.
We know from aminorex/4MAR and (S) fenfluramine that chronic consumption of ligands with significant peripheral 5HT2b activity are indeed cardiotoxic but how much is a 'microdose' of MDMA? Because I've always doubted microdosing simply because while affinity data make look impressive, EC50 is actually the more useful metric. I can point to examples where the most POTENT member of a class wasn't the one with the lowest Ki, it was the one with the lowest ED50.
The conclusion appears to be 'we don't know' which does look an awful lot like 'if we had the funding...' because Silicon Valley investors and their money is soon parted.
I will make it simple - it's impossble to PROVE a negative but when someone has no positive data and makes invalid assumptions, the simple GIGO metric holds true. But it's a good way to get funding - to present risk.
I've always been very careful to state when something is outside my knowledge domain but the three authors are all psychologists/psychiatrists so I wouldn't expect it to be within their knowledge domain but for the first person credited, this is their first published work, and a lot of politics goes on so on the off-chance they are RIGHT, those other names want to be on there for the theorectical 'glory'.
