ABSTRACT: Background:To investigate the neurobiological evidence supporting the adaptogenic effects of Korean Red Ginseng in reducing the harmful consequences of stress using a double-blind, placebo-controlled trial. Method:Sixty-three subjects with high stress levels were randomized to receive an orally administered, double-blind, 6-week treatment with Korean Red Ginseng (n = 32) or placebo (n = 31). All participants underwent a comprehensive psychological evaluation using Beck Depression Inventory and Stress Response Inventory, cognitive evaluation using the continuous performance test, biological evaluation by measuring blood levels of lipids, catecholamines, inflammation markers, and heart rate variability at baseline and after 6 weeks. Results:At baseline, both groups showed no significant differences in age, sex, years of education, Beck Depression Inventory, and Stress Response Inventory. After 6 weeks, triglyceride levels were significantly increased within the normal limit in theKorean Red Ginseng group (F = 4.11, p = 0.048), and the epinephrine level was decreased in this group (F = 4,35, p = 0.043). The triglyceride increase was significantly associated with epinephrine decrease (B = -0.087, p = 0.041), suggesting that Korean Red Ginseng may stabilize the sympathetic nervous system. In addition, we detected a significant group by time effect in the visually controlled continuous performance test, suggesting positive effects of Korean Red Ginseng on cognition. Conclusion:Korean Red Ginseng might help to stabilize the sympathetic nervous system and improve cognition in individuals with high stress.