A patent for MDMA was originally filed on Christmas Eve 1912 by the German pharmaceutical company Merck, after being first synthesised for them by German chemist Anton Köllisch at Darmstadt earlier that year.^[1][2] The patent was granted in 1914; Köllisch died in 1916 unaware of the impact his synthesis would have. At the time, MDMA was not known to be a drug in its own right; rather, it was patented as an intermediate chemical used in the synthesis of a styptic (a drug intended to control bleeding from wounds.) Over half a century would pass before the first recorded ingestion of MDMA by humans.

The U.S. Army did, however, carry out lethal dose studies on animals of MDMA and several other compounds in the mid-1950s. It was given the name EA-1475, with the EA standing for either (accounts vary) "Experimental Agent" or "Edgewood Arsenal".^[3] The results of these studies were not declassified until 1969.

MDMA was legal in the United States until May 31, 1985 [7]. Before then, it was used both as an adjunct to psychotherapy and as a recreational drug. MDMA began to be used therapeutically in the mid-1970s after the chemist Alexander Shulgin introduced it to psychotherapist Leo Zeff. As Zeff and others spread word about MDMA, it developed a reputation for enhancing communication, reducing psychological defenses, and increasing capacity for introspection. However, no formal measures of these putative effects were made and blinded or placebo-controlled trials were not conducted. A small number of therapists–including George Greer, Joseph Downing, and Philip Wolfson–used it in their practices until it was made illegal.

MDMA appeared sporadically as a street drug in the late 1960s (when it was known as the "love drug"), but it came into prominence in the early 1980s in certain trendy yuppie bars in the Dallas area, then in gay dance clubs. From there use spread to rave clubs, and then to mainstream society. During the 1990s, along with the growing popularity of the rave subculture, MDMA use became increasingly widespread among young adults in universities and later in high schools. It rapidly became one of the four most widely used illegal drugs in the U.S., along with cocaine, heroin and cannabis.

In the late 1980s and early 1990s, ecstasy was widely used in the United Kingdom and other parts of Europe, becoming an integral element of rave culture and other psychedelic/dancefloor-influenced music scenes, such as Madchester and Acid House.