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Mastic has been harvested for at least 2,500 years since Greek Antiquity.[citation needed] The word mastic is derived from Greek: μαστιχειν, romanized: mastichein "to gnash the teeth",[citation needed] which is also the source of the English word masticate.[1][better source needed] The first mention of actual mastic 'tears' was by Hippocrates. Hippocrates used mastic for the prevention of digestive problems, colds and as a breath freshener. Roman emperors used mastic along with honey, pepper, and egg in the spiced wine conditum paradoxum. Under the Byzantine Empire, the trade of mastic was made the emperor's monopoly. In the Ottoman Empire, the sultan gathered the finest mastic crop to send it to his harem.

During the Ottoman rule of Chios, mastic was worth its weight in gold. The penalty for stealing mastic was execution by order of the sultan. In the Chios Massacre of 1822, the people of the Mastichochoria region were spared by the sultan to provide mastic to him and his harem. Sakız Adası, the Turkish name for the island of Chios, means "island of gum". The mastic villages are fortress-like, out of sight from the sea, surrounded by high walls and with no doors at street level (meaning that the villages were entered only by ladders), in order to protect the sap from invaders.

Although the liqueur is much younger, it is still tied up with Greek history. Digestive liqueurs, similar to Mastiha but made with grapes, were known as the Greek elixirs before the French Revolution.

The production of mastic was threatened by the Chios forest fire that destroyed some mastic groves in August 2012.

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