In short
Methylenedioxymethamphetamine (MDMA), also known as midomafetamine, is an investigational psychoactive substance. It is being studied in a Phase 2 clinical trial for young adults with chronic treatment-resistant major depressive disorder (MDD). The trial, authorised in the EU, plans to enrol 16 participants.
Methylenedioxymethamphetamine (MDMA), also called midomafetamine, is a psychoactive substance classified as an N-substituted amphetamine analog and a hallucinogen. It is widely known by the street name ecstasy or Molly. The World Health Organization has reviewed its health effects as part of a broader look at ring-substituted amphetamines.
Key points
- MDMA is being studied for chronic treatment-resistant major depressive disorder in young adults.
- The single registered trial is a Phase 2 pilot study with a planned enrolment of 16 participants.
- The trial uses a randomised, delayed-treatment controlled design to assess feasibility and safety.
- The primary focus is on recruitment, retention, and adverse events, not efficacy.
- MDMA is also known as ecstasy and is classified as a hallucinogen and entactogen.
What is methylenedioxymethamphetamine?
Methylenedioxymethamphetamine is an N-substituted amphetamine analog, which means it is a chemically synthesised substance structurally related to amphetamines. It is a small molecule with the chemical formula C11H15NO2. In the European Union, the active substance is registered as ±3,4-methylenedioxymethamphetamine hydrochloride (MDMA). It is not an authorised medicine; it is an investigational substance being studied in clinical trials.
How does methylenedioxymethamphetamine work?
MDMA enters neurons through monoamine transporters. Once inside the cell, it inhibits the vesicular monoamine transporter, which leads to increased concentrations of serotonin, norepinephrine, and dopamine in the cytoplasm. It then induces the release of these neurotransmitters by reversing their respective transporters. MDMA also acts as a weak agonist at 5-HT1 and 5-HT2 serotonin receptors. Its entactogenic effects — feelings of emotional openness and connection — are thought to be partly the result of indirect oxytocin secretion via activation of the serotonin system.
Which conditions is it used or studied for?
- Post-traumatic stress disorder (PTSD) — the European Medicines Agency has agreed a paediatric investigation plan for MDMA in the treatment of PTSD.
- Major depressive disorder (MDD) — a Phase 2 pilot study is evaluating MDMA-assisted therapy in young adults with chronic treatment-resistant MDD.
- Anxiety associated with terminal cancer — clinical trials are testing the therapeutic potential of MDMA for this condition.
How is methylenedioxymethamphetamine given?
MDMA is administered orally. The pharmaceutical form used in the registered paediatric investigation plan is a hard capsule. In the clinical trial for major depressive disorder, the intervention is described as midomafetamine 200 mg given orally.
What do the clinical trials show?
One clinical trial is registered in the EU Clinical Trials Information System for MDMA in major depressive disorder. The trial is a Phase 2 pilot study with a planned enrolment of 16 participants aged 18 to 25 years with chronic treatment-resistant MDD. It uses a randomised, delayed-treatment controlled design, meaning some participants receive MDMA-assisted therapy immediately while others start later. The primary outcomes are recruitment and retention, as well as the occurrence of moderate to severe adverse events, adverse events of special interest, and serious adverse events. The trial status is Authorised.