Ross (Jason Schwartzman) is a regular customer of Spider Mike (John Leguizamo), a methamphetamine dealer. Spider Mike and his girlfriend Cookie (Mena Suvari) are constantly arguing, and Ross strikes up a friendship with Nikki (Brittany Murphy), a fellow addict. Speed scab ridden Frisbee (Patrick Fugit), an avid gamer, is kicked out of the house by Spider Mike, who is furious over losing his stash. Nikki takes Ross to "The Cook" (Mickey Rourke), who supplies Spider Mike from a meth lab he has set up in a motel room.
The Cook gives a small amount of meth to Ross in exchange for bringing Nikki (his girlfriend) home, and says that he will get in touch with Ross if he needs a driver. Back at his apartment, Ross gets messages from his mother and his former girlfriend Amy, (Charlotte Ayanna) wishing him a happy birthday; Amy is also demanding that he pay back the money he owes her. Ross, assuming she still loves him, calls her and leaves a message. He then goes to the local strip club while high, leading to an intense pornographic hallucination. He takes one of the dancers, April (Chloe Hunter), home and has sex with her while they both use meth. As they finish, the Cook calls with an emergency regarding Nikki's dog. Ross, still high, leaves April handcuffed and tied to the bed, despite her protests, and duct-tapes her eyes and mouth shut to keep her quiet.
While Ross and Nikki take the dog to the veterinarian, policemen and a TV crew raid the trailer where Frisbee lives, falsely believing that a meth lab is located there. They take Frisbee and his overweight mother into custody, where they threaten him into cooperation in a drug bust. The same day, Ross and the Cook stop by a local gas station to pick up a case of ephedrine pills (one of the ingredients needed to make meth) and a soda. Next they go to a liquor store to purchase a six-pack of beer; here the Cook beats up another dealer after he slaps one of the cashiers for attempting to buy meth from Spider Mike. They then visit an adult film store, where the Cook memorably preaches about the values of pornography in America. Ross calls Amy's house again, but to no avail.
He drops the Cook off at his place and rushes home to April, who is still tied to the bed. She appears to forgive him, and they proceed to have more sex. In the Cook's motel room, he and Nikki have a fight after a prostitute arrives. Nikki ends their relationship, and calls Ross and asks him to take her to a bus station so she can go back to Las Vegas.
Ross leaves April again, who is still tied to the bed; she is subsequently rescued by Ross' lesbian neighbor (Debbie Harry). While Ross and Nikki are out, Frisbee is coerced by the cops to wear a wire and make a deal with Spider Mike so they can arrest him. When he enters, Cookie attempts to make love to him, her revenge on Spider Mike for his usage of a phone sex line. She finds the wire, and the cops rush in to make the drug bust. Spider Mike, furious at Frisbee's betrayal, shoots him in the testicles, and Spider Mike and Cookie are arrested. While this is happening, the Cook's meth lab catches fire and destroys his motel room. He takes off to the adult film store, where he is arrested after the owner (Rob Halford) calls the police. Once the Cook makes bail, he calls Ross asking for a ride to another dealer's house in the city after he drops Nikki off at the station.
Ross learns of everyone else's arrests, and agrees to drive him there, as well as visit Amy, who also lives in the city. The other dealer (Eric Roberts) provides the Cook with cash, some meth, and the equipment to start a new meth lab. Ross calls Amy again, and leaves a message asking to see her and that he has her money with him. The Cook promises six months' worth of meth to Ross in exchange for being his chauffeur; he agrees on the condition that he can see Amy first. Amy, who has gotten her life together and found steady work in the city, leaves him in the park after seeing that he is still an addict.
He gives her $100 of the money he owes her, and leaves with the Cook. Finally, after several days of nonstop frantic activity fueled by drug use, the main characters all go to sleep except for the Cook. As Ross naps in his car, the Cook walks into the trailer designated for his new meth lab. A few moments after being inside, the trailer, along with the Cook blow up...
a probable suicide..