Objective: In preclinical studies, lobeline inhibited hyperactivity induced by nicotine and amphetamine, and improved performance and learning in studies utilizing radial-arm maze and spatial-discrimination water maze. This laboratory proof-of-concept study investigated lobeline as a treatment for ADHD symptoms in adults (31.11 ± 7.08 years). Method: Using cognitive tasks and self-report measures, the effects of lobeline (0, 7.5, 15, or 30 mg, s.l.) and methylphenidate (0, 15, or 30 mg, p.o.) were assessed in nine volunteers with ADHD. Results: Evidence suggested that lobeline could modestly improve working memory in adults with ADHD, but no significant improvement in attention was observed. Lobeline administration was associated with mild adverse side effects (nausea). Conclusion: Further investigation of lobeline on working memory may be warranted.