This was the problem we saw in practice building an effects based system at work. It had a lot of nice properties, and type inference worked better than you might expect, but there was no way around the types with 100+ effects in the type signature, and people really disliked it.

There are some things you can do to make it more ergonomic. One mistake we made was not focusing on ergonomics early on, and that lead to people having some pretty sour experiences. It's something you really have to pay a lot of attention to.