“direct altruistic focus strategically so as to be of positive utility”

Vague and evasive. Say what you mean. If you want to keep poor people poor until some new technology comes out, you should say that. If you don’t think further development will ever be justified, you should say that (so that your contention can be discarded as absurd and impractical)

“From the sumatriptan RCT: 3% were pain-free at 10 minutes after placebo.”

This is an irrational comparison. You’re comparing your best case scenario anecdote to the results of an RCT.

It’s possible that one of those 3% of people would have an anecdote for sumatriptan as convincing as yours: causing rapid resolution of their headache. That anecdote would not be representative.

I’m not saying you’re wrong about psychedelics and cluster headache. I desperately hope you’re right and there is an easy fix. Anecdote leads people astray constantly and we have to have a high suspicion of it.

“The effect size is incredible and the percentage of people for whom it's effective for is very large” - What’s the source for this?

Impressive anectodes, but we see a lot of those in medicine. Trial or it didn’t happen.

Because development has been the human project for the last 10,000 years and if we accept that it has been and continues to be a mistake then the conclusion is... what? anarcho-primitivism/regressing to pre-industrial hunter-gather life/Return to Monke. That doesn't seem very practical.

Fair, I really mean pessimism rather than nihilism. On what basis can you reject philosophical pessimism - a self-consistent and valid belief that is seemingly impossible to prove/disprove - other than that it is just not pragmatic or constructive at all.

None of that suggested work seems very clarifying

The welfare ranges are extremely broad for the animals they do cover, and that's with questionable assumptions. I don't see how extending these to microbes would clarify anything.

Doing "more research" on the day-to-day experience of nematodes and how they respond to noxious stimuli or calculating their neural energy consumption as a proxy for their ability to suffer also doesn't seem clarifying. Imagine you knew all this information about nematodes. Still the fundamental question will remain how their "suffering" or "joy" compares to ours and how morally important it is. A lot of animal ethics is driven by our ability to relate to animals ("I can relate somewhat to a chicken and I wouldn't want to be a chicken in a cage") but this falls apart by the time we get to nematodes, so you have to rely solely on your numbers, which will be extremely uncertain.

I remain very puzzled how you ever see us getting low enough error bars on the joy/suffering of microscopic worms that we could make decision based on it.

How would you get the "Further human economic development" "necessary to build the knowledge and resources" to build a better world without supporting the development of developing countries?

Are you talking a top-heavy approach where we keep poor countries poor until fake/cultured meat is cheap enough to supplant farmed animals?

I guess. Can you formulate an argument against nihilism that's any more substantial than that?

The theory that human development has been evil is nihilistic and could well be true, much like the nihilistic theory that the existence of biological life itself could is net evil. On what basis do you reject this other than: "we can't do anything with that".

It will probably lead to increased suffering of animals (at least for a time) and this is necessary for the greater good of technological development. We're forced to consider the technological development a greater good because the alternative is to accept that the last 10,000 years of development was a mistake, which is not a viable belief.