Oscar winner Stone and "The Wolf on Wolf Street" star Hill play Annie and Owen, two strangers with personal problems who take part in a pharmaceutical drug trial.
A trailer shows the two characters in multiple, sometimes fantastical, settings during the experiment where they are told by the doctor leading the trial that "pain can be destroyed, the mind can be solved".
"It seemed like a great opportunity to dive into this world that was sort of different from ours but talking about a lot of the themes that we deal with today in modern society," Stone told Reuters at the show's red carpet premiere on Thursday.
"Disconnection from each other and trying to fix problems in a certain way and realizing that human connection really is a balm for all of us."
The show, which premieres on the streaming service on Sept. 21, is directed by Cary Fukunaga, known for "Beasts of No Nation" and his work on the series "True Detective".
"The biggest challenge of the show is that it reinvents itself each episode, that puts a lot of pressure on everybody," writer Patrick Somerville said. "We just had to make new worlds over and over again."
Stone and Hill, who worked together on 2007 comedy "Superbad", both starred in television shows earlier in their careers, but "Maniac" proved a different project for both actors, who are also executive producers on the series.
"I thought that it would be an exciting challenge to get to explore a character, in this case five characters, over five, six hours," Stone said.
"That's not something I've gotten to really do very much of. I did some TV at the beginning but never in this long form of 10 episodes...It was a really fun process."
The actors are the latest major stars picking leading roles on the small screen. Recent examples include Amy Adams in HBO's "Sharp Objects" and Julia Roberts in Amazon Studios' upcoming "Homecoming".
"Everybody is turning to TV and the stuff that they're producing it's...critically-acclaimed, winning Emmys so it's proving to be incredibly fruitful for them," Alex Ritman, UK correspondent for The Hollywood Reporter said.
"And off the back of that...being a big name on TV is beneficial to your film career. I don't think we live in a world where you're one or the other anymore."
(Reporting By Marie-Louise Gumuchian and Saskia O'Donoghue; Editing by Andrew Heavens)