Little ironweed (Vernonia cinerea) has been used in traditional medicine systems in parts of Asia and Africa for a variety of ailments, including as a folk remedy to support mental health and mood. Historical ethnobotanical records indicate that some traditional practitioners have recommended preparations of this plant as a tonic or to alleviate symptoms resembling depression, though these references are generally anecdotal and lack rigorous clinical substantiation.

There is a paucity of scientific research specifically examining the antidepressant effects of Little ironweed in humans. Some preliminary animal studies have investigated its central nervous system effects, showing potential sedative and anxiolytic activities, but these are limited in scope and not directly focused on depression. The mechanisms proposed in traditional use are mostly speculative, possibly related to the plant's antioxidant and anti-inflammatory properties, which have been documented in laboratory settings.

Overall, the use of Little ironweed for depression is justified primarily by traditional and anecdotal practices, not by robust scientific research. There are currently no well-designed clinical trials validating its efficacy or safety for depression in humans. As such, while it has a place in traditional medicine, the supporting evidence is weak, and its use for this indication should be approached with caution.