11βHSD1 inhibitor use in human disease- a systematic review and narrative synthesis, page-63

A behavioural test directly measures the desired outcome. Surely that's the ultimate test?

What if LTP (or any other hypothesised mechanism) isn't the mechanism via which elevated cortisol operates? AFAIK the mechanism is unknown, it's merely an association.

Also AFAIK LTP is most reliably measured by post mortem examination. Nobody would volunteer for clinical studies.

I agree that discovering the mechanism would be a huge scientific advance. But IMO it's not necessary to advance a potential drug.

Disclaimer. I have zero medical training.