Harry Goldfarb, played by Jared Leto, along with his close friend Tyrone Love (Marlon Wayans), navigate the gritty streets of Brooklyn, New York. Their lives revolve around drugs, which they fund through petty thefts such as Harry pawning his mother's television. On the other side of the City, Harry's mother, Sara Goldfarb, portrayed by Ellen Burstyn, is a widowed woman living alone in Brighton Beach. She constantly finds herself buying back her TV from the local pawn shop run by Abe Rabinowitz (Mark Margolis). Despite Abe urging her to turn Harry in for his misdeeds, Sara’s love for her son prevails—after losing her husband Seymour two decades ago, Harry represents her last connection to family.
As Harry and Tyrone devise a plan to make a fortune by selling heroin on the streets, they dream of escaping their mundane lives. Their scheme begins to yield profits, and they talk excitedly about acquiring a pound of high-quality heroin, believing this could be their ticket to a better life. Marion Silver (Jennifer Connelly), Harry's girlfriend, although distant from her own parents, indulges in their lifestyle. The trio spends their days engaging in drugs while fantasizing about a brighter future, with Harry envisioning a clothing store for Marion, where she can thrive as a designer.
Simultaneously, Sara becomes infatuated with television, particularly an infomercial hosted by the charismatic self-help guru Tappy Tibbons (Christopher McDonald), embodying the JUICE philosophy: Join Us In Creating Excitement. One day, she receives a call that she believes is an invitation to appear on the show, sparking her ambition to showcase Harry to the world. It’s a dream complicated by her inability to fit into the red dress she donned at Harry's graduation, a garment that carries memories of better times with her late husband. Encouraged by friends, she attempts a weight loss journey using a restrictive diet but soon turns to dangerous medications that only deepen her obsession and struggles.
As financially successful drug dealings unfold, Harry and Tyrone stow their cash in a shoe box hidden in the wall of Tyrone's apartment. This seemingly carefree summer turns ominous, as drug dependency begins to unravel their lives. Harry treats Sara to a new television set as Tyrone faces the consequences of his dealings, including jail time amidst escalating violence from rival drug gangs. In a poignant moment, Harry discovers that Sara's diet pills are actually methamphetamine, leading to a tense confrontation where Sara passionately asserts that her upcoming television debut rejuvenates her spirit.
Yet, as seasons shift from a hopeful summer to a desolate winter, the drugs that once provided an escape begin to suffocate them. Harry finds himself in dire circumstances, struggling with the rising void of addiction both in himself and Marion. Their relationship crumbles under the weight of desperation as Marion is compelled to turn to Arnold (Sean Gullette), her psychiatrist, for a loan that necessitates a painful compromise.
Meanwhile, Sara increasingly retreats into her hallucinatory world, eagerly anticipating her TV appearance while the reality of her situation deteriorates. Tensions rise as the trio's drug supplies dwindle, leading them into frenzied and risky situations. As Harry's arm festers from substance abuse and his mental health declines, he is forced to confront the harsh reality of his addiction during a harrowing hospital visit.
In a chilling crescendo, Sara's hallucinations intensify; she flees into the snowy streets, unable to discern reality from her fevered imagination. Subsequently, she is admitted to a mental hospital, where her condition continues to worsen. Simultaneously, Harry and Tyrone find themselves entangled in the criminal justice system, facing the brutal realities of addiction and despair.
In an unrelenting cycle of degradation, all four characters spiral into a hopeless state: Harry succumbing to the effects of his drug use, Marion trading her dignity for fleeting moments of high, Tyrone languishing in a prison cell, and Sara lingering in a mental institution, each left to grapple with their own demons. The film concludes with haunting imagery of their individual suffering, as Sara hallucinates her moment of glory on a television show while the true costs of addiction lay bare.
