The series was first premiered at Annecy International Animation Film Festival in June 2024, but was publicly announced at San Diego Comic-Con on July 26, 2024.

[5] Common Side Effects co-creators Joseph Bennett and Steve Hely were brought together and began development of the series in 2019 under production studio Bandera Entertainment founded by Mike Judge and Greg Daniels.

[10] Bennett and Hely sought to combine the crime thriller genre with comedy, inspired by the films of the Coen brothers, such as Burn After Reading.

[11] Inspiration for the story came from the co-creators' interest in medicine and the work of mycologist Paul Stamets and ethnobotanists Terence McKenna and Wade Davis.

[11] Animation for the series was produced by Green Street Pictures employing an international team of artists, including some working remotely from France, Portugal, Spain, and Mexico.