Thrush starred in the Palme d'Or and Cesar award-nominated film Jimmy P: Psychotherapy of a Plains Indian.
Thrush, who is Cree, was born and raised in Calgary, Alberta, Canada, by parents who were chronic alcoholics. She recalls being called "Squaw" at Bowness High School and bullied because of her parents' illness. In grade nine she changed schools and attended Calgary's Plains Indian Cultural Survival School, where she felt accepted for the first time. Commenting on her experience at that school, she stated: "There were other Native students there, and I learned so many wonderful things about myself, about my culture, about my language, about drumming and singing. They filled in a lot of the voids that my soul was just begging for."
Her childhood hardships affected her profoundly. Though she acted in her first film at 17, it did not occur to her it could be a career. She planned to become a social worker and help children. She met Gordon Tootoosis, a First Nations actor, who told her: "If [acting] is what your heart wants, you need to follow it and be true." At this point her parents were sober. With no other ties to Calgary, at age 20 she moved to Vancouver and found an agent.

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