3,4-Methylenedioxymethamphetamine (MDMA) is a synthetic drug first made in 1912 by the German pharmaceutical company Merck. It was used as an intermediate chemical in making a drug intended to stop blood loss. At that time, MDMA itself was not tested pharmacologically.
In 1977, the chemist and psychedelics pioneer Alexander “Sasha” Shulgin introduced the drug to Leo Zeff, a psychotherapist and also an early proponent of psychedelics in therapy. Over the next twelve years, Zeff treated more than 4,000 patients with MDMA and trained 150 therapists to use it in their work.
During the 1980s, MDMA became a popular recreational drug at nightclubs and raves. In 1985, the Drug Enforcement Administration placed MDMA on the list of Schedule I controlled substances, effectively stalling research into its therapeutic potential.
Users typically consume MDMA orally in a pill or capsule and begin to feel its effects thirty to forty-five minutes later. MDMA is known as an empathogen because while it does alter mood and has some psychedelic qualities, its effect profile differs significantly from that of the classic psychedelics. Rather than mystical-type experiences, MDMA produces a mellower experience during which people feel more empathic, more open to bonding with others, and better able to process emotional or traumatic memories. The entire experience lasts about three to four hours.
MDMA interacts with neuronal connections (synapses) and causes the release of serotonin, norepinephrine, and dopamine neurotransmitters, with the largest effect being on serotonin. The transient increase in the actions of these neurotransmitters in the brain impacts arousal, attention, emotion, and memory. MDMA also activates the sympathetic branch of the autonomic nervous system, causing transient increases in heart rate and blood pressure.
In 2011, researchers published the results of the first clinical trial that showed MDMA could be used alongside therapy to treat post-traumatic stress disorder. Subsequent studies suggest it’s also effective at reducing social anxiety in autistic adults and in people with life-threatening illnesses, eating disorders, and substance-abuse disorders.
In 2021, researchers in the United States, Canada, and Israel published the results of a phase III clinical trial using MDMA-assisted therapy to treat post-traumatic stress disorder. The trial studied ninety participants and found that the treatment was safe and that for the majority of participants who received it, MDMA relieved many, or in some cases most, of their symptoms.
In the United States, MDMA is listed in Schedule I of the Controlled Substances Act. It’s illegal to use it recreationally or in therapy outside of specially approved research settings.
The early use of MDMA (‘Ecstasy’) in psychotherapy (1977–1985)
Drug Science, Policy, and Law, 2018
A Review of 3,4-methylenedioxymethamphetamine (MDMA)-Assisted Psychotherapy
Frontiers Psychiatry, 2019
Can MDMA Play a Role in the Treatment of Substance Abuse?
Current Drug Abuse Reviews, 2013
Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: a randomized, double-blind, placebo-controlled pilot study
Journal of Psychopharmacology, 2018
MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study
Nature Medicine, 2021
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