Common Side Effects

Premise

Two high school friends, Marshall and Frances, reconnect after Marshall discovers the Blue Angel Mushroom, a mushroom with healing effects that appears to cure all illnesses and injuries. In the process, they also uncover a conspiracy involving Reutical Pharmaceuticals, Inc., one of the largest pharmaceutical companies, and the government, to suppress all knowledge of said mushroom.

Characters

Main

Marshall Cuso (voiced by Dave King) is the knowledgeable, cautious protagonist of the series and was friends with Frances in high school. He is an accomplished expert in fungi who has done charity work in foreign countries and is sly in run-ins with the DEA.

Frances Applewhite (voiced by Emily Pendergast) is Rick's executive assistant and Marshall's high school lab mate and friend. Though initially hesitant about the effects of the Blue Angel, she eventually sees the monetary value in the mushrooms and is motivated to try and get them to Rick to take care of her mother, who was recently diagnosed with dementia.

Rick Kruger (voiced by Mike Judge) is the incompetent chief executive officer of Reutical, who constantly bothers Frances to do mundane tasks for him, such as booking reservations and changing the TV channel. He also enjoys farming simulator video games, often playing in improper settings such as work and formal events.

Agents Copano (voiced by Joseph Lee Anderson) and Harrington (voiced by Martha Kelly) are nonchalant best friends who work for the Drug Enforcement Administration.

Recurring

Nick (voiced by Ben Feldman) is Frances' lackadaisical, often oblivious boyfriend who loves VR gaming. Feldman also provides additional voices.

Jonas Backstein (voiced by Danny Huston) is a powerful Swiss financier and board member of Reutical with heavy insider ties to the federal government who is focused on destroying Marshall and the mushrooms.

Cecily (voiced by Sydney Poitier) is a Deputy National Security Director with influence over the DEA who secretly conspires with Jonas and Reutical.

Hildy (voiced by Sue Rose) is Marshall's idiosyncratic, mycologist mentor who seeks to possess the Blue Angel for her own ends.

Sonia Applewhite (voiced by Lin Shaye) is Frances' mother who has been diagnosed with dementia, and is Frances' main motivation for acquiring the Blue Angel mushroom.

Amelia (voiced by Shannon Woodward) is the laid-back mycologist hired by the DEA to gather information on the Blue Angel, also acting as a single mother and caretaker to her ill son, Wyatt. Woodward also provides additional voices.

Kiki (voiced by Christine Ko) is a researcher at Reutical. Young and knowledgeable on medicine and the pharmaceutical system, she acts as the devil's advocate for the company, disputing the arguments brought up by people such as Marshall.

Zane (voiced by Alan Resnick) is Marshall's self-trained herpetologist half-brother specializing in marine animals. He enjoys taking psychedelic drugs and illegally imports rare tropical animals.

Jimmer Jarvis (voiced by Mike Judge) is the Sheriff of Averesboro, North Carolina who becomes Marshall's next-door neighbor and ally.

Rusty (voiced by Steve Hely) is Jimmer’s redneck nephew who spends most of his time shooting guns or riding his BMX bike.

Additional & guest voices

Shalita Grant as Female DEA Agent / Susan / Kelly

Bob Stephenson as Connor / Samurai

Timothy Simons as DEA Dispatcher / Lawyer / Test Subject 3

Andy Daly as Mysterious Passenger / Christopher

Nicolas Cantu as Tommy

Development

Conception

Common Side Effects was created by Joe Bennett and Steve Hely, who were introduced through Bandera Entertainment, a production company founded by King of the Hill co-creators Mike Judge and Greg Daniels. Daniels had known Hely through their work together on The Office, while Judge knew Bennett as an animator. As Bandera was being established, Bennett and Hely were brought together through a "blind date", bonding over shared interests in mushrooms, the pharmaceutical and healthcare industries, and South America. The premise for Common Side Effects was developed in 2019 as a thought experiment about a hypothetical medicine which could cure "almost anything", and the consequences of its discovery.

From this premise, Bennett and Hely developed the show's main characters, Marshall Cuso, Frances Applewhite and Rick Kruger. Marshall was modeled after various mycologists and ethnobotanists, including Paul Stamets, Terence McKenna, Wade Davis and Richard Evans Schultes. He was further based on Chris Cooper's portrayal of John Laroche in Spike Jonze's Adaptation (2002). Frances was designed as an empathetic character, grounded in everyday struggles such as financial strain and caregiving for her mother, as well as a more practical counterpart to Marshall. Rick, a pharmaceutical CEO, was conceived as a character trapped in "the system" and caught up in its incentives, rather than being inherently evil.

Writing

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. The show was purchased by Amazon in 2019, who Hely stated "didn’t quite get it," and they eventually sold Common Side Effects to Warner Bros. Discovery.

Casting

Dave King was cast as Marshall Cuso after Bennett heard him on The Great Debates, a podcast co-hosted by Hely and King, who had known each other for decades and grew up in the same town. Although Bennett and Hely questioned casting King due to his limited professional experience, they embraced the casting after Adult Swim network executives called him "perfect" for the role. Emily Pendergast, who Hely had previously worked with on Veep, was cast for the versatility required of Frances' role, as well as her natural acting ability. Mike Judge, an executive producer for the show, was cast as Rick after Bennett and Hely sought out an actor whose presence would appeal when a character's would not, noting Rick's "charm[ing]" voice being similar to Hank Hill's.

Agents Copano and Harrington, two Drug Enforcement Administration (DEA) agents, were voiced by Joseph Lee Anderson and Martha Kelly, respectively. Anderson, who Hely thought had "a cool voice", worked with Hely's wife on the show Young Rock, and had more scenes written for him due to his intriguing portrayal of Copano. Kelly, who Bennett remarked had "always wanted to play a detective" and worked with on several of his short films, was highlighted for the comedic value in her uncharacteristic voice for the role of a DEA agent.

Many of the other characters' voice actors were chosen with little forethought, or were voiced by Bennett and Hely themselves. Bennett and Hely took a naturalist approach to voice acting, prioritizing natural speaking voices that fit a given character. They often instructed the voice actors to "do less acting", aiming to capture the authenticity in their performance and mannerisms.

Animation

Common Side Effects is animated by Green Street Pictures, a studio based in Pasadena, California founded by Joe Bennett, Sean Buckelew, James Merrill, and Benjy Brooke. The studio was founded in 2020 to create Scavengers Reign (2023), on which Bennett served as co-creator. Many of the artists who worked on Scavengers Reign went on to work on Common Side Effects. The studio worked with international artists from France, Portugal, Spain and Mexico, as well as Argentinian animation studio Le Cube. The show was animated using various products from the Adobe suite, as well as Adobe Animate, Toon Boom Harmony, and TVPaint Animation.

Release

The series was first announced by Adult Swim on June 16, 2023, during the Annecy International Animation Film Festival. On May 28, 2024, it was announced the pilot episode would be screened for its world premiere at the 2024 Annecy Festival on June 12. Adult Swim later screened the pilot during their "Night of New" event at San Diego Comic-Con 2024 on July 26; a "first look" trailer was additionally published to YouTube the same day. An additional "Night of New" screening took place at New York Comic Con on October 17.

A press release for the series was set for release on December 4, but held back due to the Killing of Brian Thompson, and was again held back on December 9 following the arrest of Luigi Mangione. On December 12, the official trailer was released, announcing the show's premiere on February 2, 2025 with two back-to-back episodes. The first season aired on Sundays between February 2 to March 30 at 11:30 pm ET/PT.

Two days before the first season's finale aired, on March 28, Adult Swim announced Common Side Effects had been renewed for a second season. Annecy unveiled the 2026 Annecy Festival's "Work in Progress" line-up on April 14, 2026, including the second season of Common Side Effects. The second season was previewed at the festival on June 25, and slated for release in early 2027. The season was further previewed at San Diego Comic-Con 2026 on July 24, and is scheduled to appear at New York Comic Con on October 9.

Common Side Effects is available to watch on HBO Max, where episodes stream the day after their airing. In the United Kingdom, the show is aired on Channel 4.

Reception

Common Side Effects has received widespread critical acclaim. On the review aggregator website Rotten Tomatoes, it holds a 100% approval rating from 28 critic reviews. It was additionally named one of the best TV shows of 2025 by media outlets including The New York Times, The Hollywood Reporter, the Los Angeles Times and The Guardian.