Four lifelong stoners and friends (Kenny, Thurgood, Scarface, and Brian) live together in New York City. Thurgood, a janitor at a medical laboratory, brings home some unusually potent marijuana given to him by an unscrupulous scientist at the lab, and the four smoke it. When Kenny, a gentle kindergarten teacher, is out on a munchie run, he is arrested for accidentally killing a diabetic police horse by feeding it junk food.
His friends are forced to find $1,000,000 to bail him out before the other prisoners take advantage of his gentle nature.
Scarface gets the idea to have Thurgood steal medical marijuana from his work so that the three of them can sell it to raise money to free Kenny. While visiting Kenny in prison, Thurgood meets Mary Jane and pursues a romantic relationship, which is strained by his having to conceal his marijuana smoking and dealing from her, as she is adamantly anti drug.
When the success of the friends' marijuana business grows enough to raise the ire of local drug lord Samson Simpson, Samson extorts the friends for $20,000 a week. Mary Jane dumps Thurgood when she finds out Thurgood is dealing drugs. The friends plan a robbery of the medical laboratory to increase their earnings enough to both fend off Samson and free Kenny, but are arrested when they try to execute the plan.
Thurgood strikes a deal with the police to wear a listening device to a meeting with Samson in exchange for freeing Kenny and dropping the charges against him and his friends. The friends meet with Samson and the plan works. Kenny and his friends are freed and Thurgood meets with Mary Jane to say that he is giving up marijuana and wants to get back together. The film ends with the two reuniting.