MDMA

DEFINITION: MDMA, or ecstasy, is a stimulant that is related to amphetamine and mescaline. It is considered a mind-altering drug that has properties similar to both amphetamines and hallucinogens.

• ALSO KNOWN AS: Adam; E; ecstasy; love drug; methylene dioxy methamphetamine; rave; X; XTC
• STATUS: Illegal in the United States and worldwide
• CLASSIFICATION: Schedule I controlled substance
• SOURCE: A synthetic material with no natural sources; smuggled and illegally produced in underground laboratories
• TRANSMISSION ROUTE: Ingested orally; snorted; smoked; injected intravenously or subcutaneously

History of Use

MDMA was first synthesized in Germany in 1912 for Merck Pharmaceuticals, which patented the substance in 1914. MDMA originally was intended to be an anticoagulant but was ineffective for that purpose. During World War I, however, the drug was taken as an appetite suppressant.

In the 1970s, attempts were made to use MDMA to facilitate psychotherapy. It was then that the drug was found to have hallucinogenic properties, which in 1985 led to its being declared an illegal substance. MDMA was classified as a schedule I controlled substance. Class I drugs are those that have a high potential for abuse and have no recognized medical value.

Because MDMA increases energy, endurance, and arousal, it became widely used in underground dance clubs in England in the 1980s because it allowed people to stay up and dance all night. These all-night events came to be called raves, and the drug itself became known as a club drug, party drug, or recreational drug. Its use in this manner spread to the United States around 1990. MDMA has remained popular in the club scene because it is both a hallucinogen and a psychoactive stimulant.

Effects and Potential Risks

MDMA is derived from methamphetamine and differs from it chemically in only one way that makes it resemble the hallucinogen mescaline. As such, it has the characteristics of both a stimulant and a hallucinogen. Its action is explained mainly by its effects on the serotonin pathways in the body, since it affects serotonin reuptake.

Most of the short-term effects of MDMA are attributable to the psychological changes from increased serotonin in the brain. These effects include feelings of pleasure, mood elevation, and heightened perception. Negative short-term effects include difficulty thinking clearly, agitation, and physical symptoms such as sweating, dry mouth, tachycardia (rapid heartbeat), fatigue, muscle spasms (especially jaw-clenching), and increased temperature.

Some ecstasy users engage in behavior known as “stacking,” or taking multiple doses of MDMA in one night. This may occur if the person wishes the positive effects of the drug to continue as they begin to wear off. Stacking can result in serious or even fatal physical problems. High blood pressure, extreme elevation of temperature, or cardiac arrhythmias may occur, sometimes resulting in death.

MDMA use often leads to aftereffects too, including depression, restlessness, and difficulty sleeping. Evidence shows that with long-term MDMA use, serotonin levels remain low in the brain, thus affecting brain function over time.

At the same time, scientists have worked with the pure form of MDMA in clinical trials approved by the Food and Drug Administration (FDA) in the hopes of finding a way to use the drug as part of a psychotherapy treatment for post-traumatic stress disorder (PTSD). The studies aimed to determine whether MDMA's potential medical benefits could outweigh negative health effects and often involved war veterans suffering from PTSD. The results of one clinical trial, which was published in the journal Nature Medicine in 2021, found that MDMA produces serotonin that may help promote fear-memory extinction. The study found patients showed marked improvement in PTSD symptoms after the treatment.

In August 2024, the FDA rejected Lykos Therapeutics' application to market an MDMA capsule as part of its MDMA-assisted therapy for PTSD, calling for further studies of the therapy's safety and efficacy. Researchers, surprised by the agency's rejection, wondered whether it would be likely to reject other hallucinogens as therapeutic drugs. Though Lykos stated that it would appeal the FDA's decision, the FDA investigated MDMA clinical trials the drugmaker had sponsored. By that time, the company had laid off about 75 percent of its staff, and the journal Psychopharmacology had retracted three articles Lykos researchers had published on their MDMA clinical trial data.

In 2025, the FDA released a public Complete Response Letter detailing their reasons for denying approval to Lykos Pharmaceuticals. They cited issues with the study's design and concerns about the accuracy of participants that utilized MDMA in the past. The Multidisciplinary Association for Psychedelic Studies (MAPS) argued against the FDA's letter, stating that what the FDA named as issues with the study's design were originally recommended by the organization. MAPS stated they would continue conducting research and would not stop trying to seek approval of MDMA's use for PTSD treatment.

Despite MDMA's initial rejection, studies continued into the drug's use as a PTSD treatment. Early in 2025, the US Department of Defense awarded Emory University and the University of Texas Health Science Center at San Antonio a grant of $4.9 million to conduct further research, including a clinical trial.

Bibliography

Baylen, Chelsea A., and Harold Rosenberg. “A Review of the Acute Subjective Effects of MDMA/Ecstasy.” Addiction, vol. 101, no. 7, 2006, pp. 933–47, doi:10.1111/j.1360-0443.2006.01423.x. Accessed 11 Sept. 2025.

Chason, Rachel. "Studies Ask Whether MDMA Can Cure PTSD." USA Today, 11 July 2014, www.usatoday.com/story/news/nation/2014/07/11/mdma-molly-therapy-ptsd-cure/10683963/. Accessed 11 Sept. 2025.

De la Torre, R., et al. “Non-Linear Pharmacokinetics of MDMA (‘Ecstasy’) in Humans.” British Journal of Clinical Pharmacology, vol. 49, no. 2, 2000, pp. 104–9.

Eisner, Bruce. Ecstasy: The MDMA Story. Ronin, 1993.

"Emory Expands PTSD Research with $4.9M DoD-Funded MDMA Study." Emory News Center, Emory University, 28 Feb. 2025, news.emory.edu/stories/2025/02/hs_bhc_ptsd_mdma_study/story.html. Accessed 11 Sept. 2025.

Keating, Fiona. "MDMA Used in World's First Trials to Treat Alcohol Addiction." Independent, 1 July 2017, www.independent.co.uk/news/uk/mdma-alcoholism-drugs-ecstasy-a7818086.html. Accessed 11 Sept. 2025.

Mills, Edward M., et al. “Uncoupling the Agony from the Ecstasy.” Nature, vol. 426, no. 6965, 2003, pp. 403–4, doi: 10.1038/426403a. Accessed 11 Sept. 2025.

Mitchell, Jennifer M., et al. "MDMA-Assisted Therapy for Severe PTSD: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study." Nature Medicine, vol. 27, 2021, pp. 1025–1033, doi.org/10.1038/s41591-021-01336-3. Accessed 11 Sept. 2025.

Walters, Jessica. "FDA Releases Complete Response Letter on Declining MDMA-Assisted Therapy for PTSD." Psychiatric Times, 5 Sept. 2025, www.psychiatrictimes.com/view/fda-releases-complete-response-letter-on-declining-mdma-assisted-therapy-for-ptsd. Accessed 11 Sept. 2025.

Whyte, Liz Essley. "FDA Widens Probe of Ecstasy-Based Drug Studies." The Wall Street Journal, 23 Aug. 2024, www.wsj.com/health/healthcare/fda-widens-probe-of-ecstasy-based-drug-studies-510307b0. Accessed 11 Sept. 2025.

Wing, Nick. "DEA Approves Study of Psychedelic Drug MDMA in Treatment of Seriously Ill Patients." Huffington Post, 18 Mar. 2015, www.huffingtonpost.com/2015/03/18/dea-mdma-study_n_6888972.html. Accessed 11 Sept. 2025.