https://astralcodexten.substack.com/p/highlights-from-the-comments-on-zulresso

Thanks to everyone who commented on Zounds! It's Zulresso and Zuranolone and on the followup Progesterone Megadoses Might Be A Cheap Zulresso Substitute. I'm constantly impressed by the expertise of commenters here and on how much better the biomedical comment threads are compared to some of the others. Among the things I learned:

— Metacelsus (who writes the blog De Novo) doubts the price estimates I posted:

There's no way it costs $10,000 to $20,000 a gram at scale. Those 3 chemical supply companies specialize in having a very large catalog of small quantities of chemicals for biologists to test in their experiments. (I have personally ordered from 2 out of those 3 for my research.) The price they charge per gram is not competitive at all.

He also wrote a longer blog post about the science of progesterone here.

— Douglas (who writes the blog A Mindful Monkey) clears up some mechanism details I missed:

From Stahl's: 'the precipitous decline in circulating and presumably brain levels of allopregnanolone hypothetically trigger the onset of a major depressive episode in vulnerable women. Rapidly restoring neurosteroid levels over a 60-hour period rapidly reverses the depression, and the 60 hour period seems to provide the time necessary for postpartum patients to accommodate their lower levels'. So the idea is the taper of the steroid is a helpful part.