BACKGROUND: Bupropion is an antidepressant medication with expanding indications including smoking cessation, weight loss, attention-deficit/hyperactivity disorder, seasonal affective disorder, and amphetamine dependence. Despite its increasing popularity among providers, it has a well-known narrow therapeutic window that can lead to delayed onset of symptoms with extended-release formulations and devastating consequences in overdose. We have noticed some patients misusing bupropion via insufflation, which added a layer of complexity with regards to the therapeutic application of the drug. This route of use created difficult decisions regarding clinical monitoring in these patients. OBJECTIVES: To determine if prolonged observation is required after insufflation of bupropion and to further describe effects from this route of use. METHODS: This is a retrospective observational study reviewing all the cases of insufflated bupropion use reported to a single poison center without any other coingestants. RESULTS: The majority (85.7%) of patients had mild or moderate effects, and seizures occurred in 19.6% of cases; and the vast majority of patients were symptomatic by the time of the initial call to the poison center. We did not encounter any delayed effects after this route of use. CONCLUSIONS: This report describes the clinical effects reported, and the timing of these effects, after insufflation of bupropion.