MDMA (midomafetamine)
Drugs of abuse
Drugs of abuse
A synthetic amphetamine («ecstasy») with stimulant and mild psychedelic effects; it floods the brain with serotonin and can cause dangerous hyperthermia.
Also called: 3,4-methylenedioxymethamphetamine, Ecstasy, Molly
Quick facts
- Group
- Drugs of abuse
- Target
- Monoamine transporters: serotonin transporter (SERT) first, plus VMAT2
- Used for
- No approved medical use · Clinical relevance
- Key effects
- Jaw clenching and teeth grinding · Nausea · Low mood
- Monitor
- Core temperature · Sodium · Neuromuscular signs
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows MDMA bound to the human vesicular monoamine transporter 2 (VMAT2); no structure of MDMA on SERT, its preferred target, is available.
Like other amphetamines, MDMA enters nerve terminals through the monoamine transporters and makes them run in reverse, so serotonin, dopamine and noradrenaline pour out into the synapse. It has a preference for the serotonin transporter, which explains the feelings of closeness and empathy and the large serotonin release, followed by intracellular depletion. The noradrenaline release drives tachycardia, hypertension and heat production.
- MDMA enters the neuron through SERT and other monoamine transporters
- The transporters run in reverse and release serotonin, dopamine, noradrenaline
- Euphoria and empathy; tachycardia, hypertension, heat
- Serotonin stores run low: low mood for days afterwards
Indications
- No approved medical use; studied only in research trials together with psychotherapy for post-traumatic stress disorder Post-traumatic stress disorder (PTSD) and acute stress disorder →
- Clinical relevance: stimulant intoxication and serotonin syndrome in emergency care Serotonin syndrome →
Adverse effects
Common
- Jaw clenching and teeth grinding
- Nausea, sweating and dry mouth
- Tachycardia and raised blood pressure
- Anxiety or panic
- Low mood, poor sleep and poor appetite in the days after use
Contraindications
- No medical use: there is no safe dose
- Especially dangerous with heart disease, hypertension, epilepsy or a psychiatric illness
- Especially dangerous with antidepressants (SSRIs, MAOIs) or other serotonergic drugs
Key interactions
- MAOIs, SSRIs, linezolid, tramadol and other serotonergic drugs
- Serotonin syndrome, which can be fatal with MAOIs
- CYP2D6 inhibitors (for example some antidepressants and antiretrovirals)
- Higher and longer MDMA exposure
- Other stimulants and alcohol
- More cardiovascular strain, dehydration and heat
What is monitored
- Core temperature, heart rate, blood pressure and ECG
- Sodium, glucose, creatine kinase, kidney function and liver tests
- Neuromuscular signs of serotonin syndrome (clonus, hyperreflexia)
- Mental state and suicide risk during the comedown
Pregnancy and breastfeeding
Amphetamine use in pregnancy is linked to miscarriage, preterm birth, low birth weight and withdrawal in the newborn; limited data also link prenatal MDMA to birth defects.
Nursing care
- Measure core temperature early and start cooling if it is high
- Keep a calm, low-stimulus environment and watch for seizures
- Check sodium in any confused patient, especially after heavy water intake
- Ask about all substances and medicines taken; screen for mixtures
- Offer referral for substance use support at discharge
Pharmacokinetics
- Absorption
- Taken by mouth as tablets, capsules or powder; street products vary widely in content
- Distribution
- Lipid-soluble: crosses the blood–brain barrier and the placenta
- Metabolism
- Liver, partly through CYP2D6
- Elimination
- Mostly in the urine, much of it unchanged
- Onset and duration
- Effects start within about an hour and last a few hours
Test yourself
Think of the answer, then tap the question to see it.
Which transporter does MDMA prefer, and what does that explain?
The serotonin transporter (SERT); the large serotonin release explains the empathy, the serotonin syndrome risk and the low mood afterwards.
How can MDMA use lead to severe hyponatraemia?
Users drink large volumes of water to offset the heat, which dilutes serum sodium and can cause seizures.
Which combination with MDMA carries the highest risk of fatal serotonin syndrome?
MDMA with a monoamine oxidase inhibitor (MAOI).
Connections
← Back to the class: Drugs of abuse
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: MDMA (Ecstasy/Molly) (National Institute on Drug Abuse (NIDA), 2024); Guía para el Manejo de Emergencias Toxicológicas (Ministerio de Salud y Protección Social; Organización Panamericana de la Salud, 2017).
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Representative model, for educational purposes only.