What is 3,4-Methylenedioxymethamphetamine (MDMA)?

What is MDMA?

MDMA (3,4-methylenedioxymethamphetamine), commonly known as "ecstasy" or "molly," is a synthetic substituted amphetamine drug classified as a hallucinogen and drug of abuse that produces euphoria, increased empathy, and prosocial effects by causing massive release of serotonin, dopamine, and norepinephrine in the brain. 1, 2

Chemical Classification and Pharmacology

• MDMA is a ring-substituted phenethylamine derivative with structural similarities to both amphetamines and the hallucinogen mescaline 1, 3, 4
• It is categorized pharmacologically as a hallucinogen, specifically a phenylisopropylamine, alongside other substances with abuse potential 5
• MDMA acts as a releasing agent for monoamine neurotransmitters by interfering with vesicular storage and transporter function, dramatically increasing extracellular levels of serotonin (5-HT), dopamine (DA), and norepinephrine (NE) 2
• The drug produces its characteristic effects primarily through action at the serotonin transporter (SERT), stimulating massive serotonin release 6

Acute Effects and Clinical Presentation

• Recreational users experience euphoria, increased energy, enhanced empathy, and feelings of closeness with others 2, 3
• Acute adverse effects include hyperthermia, dehydration, bruxism (teeth grinding), and diaphoresis (excessive sweating) 2
• Post-intoxication phenomena can persist for days and include insomnia, anhedonia, anxiety, depression, and memory impairment 2
• MDMA produces subjective effects unlike classical psychostimulants or hallucinogens, being one of the few compounds capable of reliably producing prosocial behavioral states 3

Medical and Toxicological Concerns

• The U.S. Department of Veterans Affairs and Department of Defense explicitly recommends against using MDMA outside of approved clinical trial settings due to its classification as a drug of abuse and lack of regulatory approval 5
• MDMA increases risk of both ischemic and hemorrhagic stroke through multiple mechanisms including acute severe blood pressure elevations, cerebral vasospasm, vasculitis, endothelial dysfunction, and increased platelet aggregation 5
• The drug produces hemostatic and hematological abnormalities resulting in increased blood viscosity, which can precipitate acute coronary syndromes and cerebrovascular events 5
• Long-term use is associated with progressive myocyte damage and accelerated atherosclerosis 5
• There is evidence that repeated MDMA administration may lead to long-lasting neurotoxic effects on serotonin neurons in primates, with reductions in markers of central serotonin axons and terminals 6

Critical Clinical Pitfall

• Illicitly-acquired MDMA is frequently adulterated, contaminated, or completely replaced with other psychoactive drugs such as synthetic cathinones ("bath salts") or methamphetamine, often unknown to the user, which significantly complicates medical intervention for adverse events 2

Historical Context

• MDMA was first synthesized by Merck in 1912 as a precursor compound in a patent for synthesizing the styptic hydrastinine, not as an appetite suppressant as commonly misreported 7
• The substance was originally called "Methylsafrylamin" in laboratory journals and was never tested in humans by Merck 7

Regulatory Status

• The American College of Physicians recommends that MDMA should not be used therapeutically outside of approved clinical trials due to its cardiovascular risks, neurotoxic effects, abuse potential, and lack of regulatory approval 5