Ma fei san is the first anesthetic in the world and was invented by Hua Tuo, an outstanding doctor, in the 2nd century. Although Hua Tuo's ancient prescriptions are lost; the ingredients are thought to have included include cannabis and datura (a hallucinogenic plant), which later was recorded as an anesthetic during the Song Dynasty.

Specific cases of abdominal operations were relayed in Hua Tuo's official biography: A patient who suffered from abdominal pain for more than 10 days and had depilation (hair loss) of his beard and eyebrows asked Hua Tuo for treatment. The doctor diagnosed him as having deterioration in the abdomen, asked him to drink the ma fei san, and then cut open and explored his abdomen. The doctor removed the deteriorated part, sutured and plastered the abdomen, and administered some herbs. The patient recovered after 100 days.

This story is believed to be a treatment of acute appendicitis. According to a historical book, Hua Tuo "would cut them out, wash them, sew up the abdomen, and rub on an ointment; the illness would remit in four to five days."

There is also the story of general Guan Yu, whose arm was pierced by a poisoned arrow during a battle. Hua Tuo advised Guan to drink ma fei san and undergo surgery. However, General Guan refused. At last he calmly sat playing a board game as he allowed Hua Tuo to clean his flesh down to the bone to remove necrosis (dead tissue), with a little anesthetic. Finally Hua Tuo saved Guan's arm and life.

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