A couple pages ago I talked about Neural Annealing, which is yet another concept that seems to be validated by scott's post.
The claim is that the brain can self-organize in different ways. Some organizations are stable, some are not, and overtime the brain will always take a stable one. Perhaps a decent analogy is to imagine the space of possible brain states as a landscape of peaks and valleys, and the brain like water, which with time will always assemble in the valleys, which are the stable states. Importantly, it's not all at once place; it would be distributed across several valleys, some deeper than others. The brain has several self-organizing principles, and some are more impactful and stable than others.
The self-organizing principles impact your life in several important ways. One is your mood, another is your aesthetic. Someone who's spent much of their life arguing for a cause will have that reflected in how their brain is organized, which will yield to an emotional reaction to arguments that support or attack the cause.
The states generally get more stable with age, which is why teenagers can totally flip their passions from one month to the next, while most 40+ year old people will have a lot of their structure finalized for the rest of their lives. That's why people so rarely change their wold view once they're old.
Getting from one valley to another requires raising the energy parameter of the brain. One way to do this is via extreme experiences, like falling in love or having a child born. Another is via meditation. The higher the energy level, the deeper the valleys you can get out of. This would be why cults like to use emotional rituals as a means of indoctrination. Yes, it's also for signaling purposes (that's the explanation your average competent rationalist would give you), but signaling could be achieved in less complicated ways. The emotional component is important. It makes the brain malleable and then imprints an aesthetic into it.
Under this theory, depression is primarily a particularly sticky and nasty self-organizing principle. It requires a high-energy state to get out of. It's the same mechanism that can improve my mood after meditating on the previous evening, only on a much larger scale. Unfortunately, most people can't raise their energy level of demand, and depression probably makes it harder to have peak experiences as well, thus solidifying itself.
That is, except for the fact that we have chemicals that reliably raise the energy level to something like... maybe the peak state that an expert meditator would achieve in a 1-month long retreat. Compared to that, what I can do is peanuts.
... under that model, "I had depression for years, nothing helped, then I took a psychedelic and it went away" is not a particularly implausible story.
A caveat is that it's probably not guaranteed to work. Raising the energy level, even by an extreme amount, just means the brain can self-organize differently. It doesn't mean it will self-organize well. That would be why the context matters. If you just take DMT out of nowhere, the expected effects may well be negative. I'd be especially concerned about epistemic effects. There's definitely evidence that people take them and then go on believing wacky things from there on. But still, even if they're not guaranteed to cure depression, at least they can plausibly do it.
I do think all of this is a rather bold model, but scott says more or less the same things in his post:
The point of psilocybin is to make your brain open to new thoughts, feelings, and ideas. If you take it without guidance from a professional, there is absolutely no reason to think that those new thoughts, feelings, and ideas will be healthy. That is to say, it seems just as plausible to me that an isolated psilocybin trip will make you worse as it is that it will make you better. Taking psilocybin without the accompanying therapy is like lifting weights without having been taught how to lift properly: it could conceivably just happen that you do it correctly, but there’s a good chance you won’t, and most likely you’ll just end up hurting yours
For a while I had this misconception that there would be therapy while you are on psilocybin, but that isn’t quite right. For the most part, the psilocybin experience is completely internal. You use the therapy leading up to it to understand what to do during the psilocybin session, and then use the therapy afterwards to take advantage of your increased neuroplasticity to mold your brain into what it needs to be.
My brain is now in a very impressionable state. The hard work is ahead of me.