OBJECTIVE: Melissa officinalis (lemon balm) is contemporaneously used as a mild sedative and/or calming agent. Although recent research has demonstrated modulation of mood in keeping with these roles, no studies to date have directly investigated the effects of this herbal medication on laboratory-induced psychological stress. METHODS: In this double-blind, placebo-controlled, randomized, balanced crossover experiment, 18 healthy volunteers received two separate single doses of a standardized M. officinalis extract (300 mg, 600 mg) and a placebo, on separate days separated by a 7-day washout period. Modulation of mood was assessed during predose and 1-hour postdose completions of a 20-minute version of the Defined Intensity Stressor Simulation (DISS) battery. Cognitive performance on the four concurrent tasks of the battery was also assessed. RESULTS: The results showed that the 600-mg dose of Melissa ameliorated the negative mood effects of the DISS, with significantly increased self-ratings of calmness and reduced self-ratings of alertness. In addition, a significant increase in the speed of mathematical processing, with no reduction in accuracy, was observed after ingestion of the 300-mg dose.CONCLUSION: These results suggest that the potential for M. officinalis to mitigate the effects of stress deserves further investigation.