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Melissa officinalis has a long history of use in medicine, particularly in Europe where it has been used since the Middle Ages as a treatment for stress, anxiety, insomnia, indigestion, colic and depression. The Greek physician Theophrastus is thought to have been referring to this plant when he referred to the healing properties of a plant translated as "honey leaf." While rarely used or researched in isolation, the pleasant smelling herb is frequently combined with other sedative and anxiety-reducing herbs like valerian, hops or chamomile. Contemporary researchers have focused their attention on Melissa officinalis's nootropic — or cognitive enhancing — properties while investigating treatments for senility as well as on the plant's unusual antiviral activity against the herpes simplex virus. The plant is rich in a wide variety of phytochemicals, no single one of which can be considered responsible for all of its pharmacological effects.
Some research has focused exclusively on the essential oils of the plant. Rich in volatile oils that provide the plant with its pleasing aroma and the common name "lemon balm," much of its pain-relieving, muscle-relaxing, and antiseptic activity has been ascribed to the presence of the chemical eugenol. Its antiviral properties are believed to be the product of some of the plant's many terpene and terpenoid compounds, mostly produced within hair-like structures called glandular trichomes that are found on the leaves, flowers and stem.
Essential oil extractions of Melissa officinalis are distinct from whole ethanolic or aqueous extract, though they fail to capture many of its other active compounds. Much of the plant's cognitive performance enhancing properties are suspected to be produced by the phenol antioxidant rosmarinic acid, which is found in higher levels in the whole plant extract. This chemical may also be responsible for the purported anxiety and stress-relieving activity of the herb through its inhibition of an enzyme responsible for the degradation of gamma-amino butyric acid — the brain's natural inhibitory neurotransmitter.
Some research has also suggested that Melissa officinalis may have antithyrotropic activity. This may prove to be of some use in the treatment of hyperthyroidism or Grave's disease by interfering with the action of the overactive thyroid gland. Other research has indicated that the plant may increase serum levels of the potent antioxidants glutathione peroxidase and superoxide dismutase. More research is needed though as of 2011, to substantiate these findings.
Despite this wide range of medical applications, the action of this plant is believed to be quite mild. The United States Food and Drug Administration (FDA) classes Melissa officinalis as a generally safe food additive. The FDA does not, however, make any judgments about the safety or efficacy of the plant or its extracts in the treatment of any medical condition.
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