Illicit drug use is a huge problem in the US prison system. The objectives of this study are (1) to systematically investigate the prevalence of bupropion abuse in American prisons along with associated problems, and (2) to synthesize available case reports on this topic in both prison and non-prison settings. Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses, we searched five databases (PubMed, Embase, Scopus, CINAHL, and PsycINFO) and used Covidence software for screening and reviewing identified articles. The final search date was February 21, 2023. Newcastle-Ottawa Scale and ROBINS-I tool were used for risk of bias assessment. We included original studies of populations aged 18 years and above in American prisons. We found 77 unique articles, none of which met our eligibility criteria. A synthesis of 22 case reports that we found showed bupropion abuse to be more common in young males, and intranasal administration was the most common method of abuse. More frequent desired and adverse effects were "cocaine-like highs" and seizures, respectively. Although several cases of bupropion abuse have been reported in US prisons, no study has been done to understand its prevalence and associated effects. The absence of original studies on bupropion abuse in US prisons and the observed patterns in this case report synthesis further highlight the need for a study to investigate the prevalence of bupropion abuse in US prisons. The limitations of this study include that it is an empty systematic review and the absence of all pertinent data in many of the included case reports. The authors did not receive any funding for this work. This systematic review was registered in PROSPERO with registration number CRD42021227561.

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