Background: Transgender and gender non-binary (TNB) youth living in the USA report elevated levels of substance use compared with their cisgender counterparts, with previous literature pointing to minority stressors as some of the factors that could facilitate such elevated levels. Yet, substance use and misuse prevalence and associated modifiable factors among TNB youth are not fully known. The current paper details the protocol for a systematic review aimed at (1) identifying substance use and misuse prevalence among TNB youth (ages <25) and related demographic disparities (based on racial, ethnic and gender identity, and sexual orientation), (2) examining factors associated with substance use and misuse among TNB youth and (3) examining protective factors against substance use and misuse among TNB youth.
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