The history of medicinal cannabis extracts is vast and fascinating, dating back to ancient civilizations. The Ebers Papyrus of 1550 BC, recorded cannabis used for obstetrics and suggested anti-inflammatory properties. The Berlin Papyrus of 300 BC prescribed cannabis as an ointment to prepare for driving away fever and as a suppository. Cannabis was also used widely in Ancient Egypt, where Moses received the recipe for a holy anointing oil containing large amounts of cannabis. Jesus and his followers applied this oil topically to fight epilepsy, skin diseases, eye and menstrual problems. In Greece, historian Herodotus wrote about Scythian ‘vapor hotbox’ rituals around 450 BCE. The Taoist encyclopedia Wushang Biyao recorded the use of cannabis in ritual censers in China in 570 CE.

Physicians in China, who boast the earliest advancements in cannabis/hemp production (5000 BCE), began prescribing cannabis mixed with wine as an analgesic during surgical procedures. In the Arabic world, cannabis juice extract from the flowers and seeds was administered through the nostril to treat migraine, aching pains including uterine, and to prevent miscarriage. The earliest known compendium of pharmacology in Arabic (9th Century) also contained the first report of cannabis' muscle relaxant properties in relation to what was known as ‘the trembling’.

John Parkinson, one of the first of the great English botanists, wrote in 1640 that cannabis roots in a poultice were effective for treating tumors and other inflammation. Cannabis was also used successfully for treating cholera, tetanus, and bubonic plague.

Queen Victoria's personal physician, Sir Russell Reynolds, prescribed cannabis for her menstrual cramps. He claimed in the first issue of The Lancet that cannabis "when pure and administered carefully, is one of the most valuable medicines we possess."

In 1964, Israeli scientists Raphael Mechoulam, Yechiel Gaoni and colleagues at the Hebrew University of Jerusalem, synthesized THC in its pure form. A pharmaceutical formulation of (−)-trans-Δ9-tetrahydrocannabinol, known by its INN dronabinol, is available by prescription in the U.S. and Canada under the brand name Marinol.

The DEA’s own Judge Francis Young concluded at the end of a lengthy legal process in 1988 that "Marijuana has been accepted as capable of relieving the distress of great numbers of very ill people, and doing so with safety under medical supervision. It would be unreasonable, arbitrary, and capricious for DEA to continue to stand between those sufferers and the benefits of this substance in light of the evidence."