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Ecstasy/MDMA

Nicknames: molly, mandy, MD, xtc, E, dizz, pingers, eccies, ecstasy
Last reviewed: October 2026

Pharmacology

MDMA acts on a range of neurotransmitter systems in the brain; increasing serotonin, noradrenaline and dopamine levels to induce entactogenic and stimulant effects. It primarily acts as a monoamine releasing agent with a slight preference for serotonin over noradrenaline and dopamine. MDMA enters nerve cells through the monoamine transporters (SERT > NET, DAT) and reverses their direction. This causes serotonin, dopamine and noradrenaline to pour out of the neuron into the synapse, where they activate their respective receptors. To a lesser extent, a serotonin-noradrenaline-dopamine reuptake inhibitor (SNDRI). MDMA also acts on VMAT2 in a similar way to amphetamine, contributing to its ability to induce the release of monoaminergic neurotransmitters (for more information, see Amphetamines). Serotonin levels in the brain are thought to be depleted after MDMA use leading to the ‘comedown’, but typically return to normal within a couple of days.

It’s suggested that the oxytocin signalling system is involved in MDMA’s pro-social effects. In a Swiss study by Atila and colleagues, MDMA elevated oxytocin levels and produced its strong entactogenic effects in healthy patients, but failed to do the same in people with a genetic oxytocin deficiency.

MDMA’s weak psychedelic effects, though milder than the related drug MDA, are mediated by the serotonin 5-HT2A receptor. Meanwhile, MDMA’s activation of the 5-HT2B receptor, if repeated over the long term, is thought to be responsible for an increased risk of organ complications (e.g. valvular heart disease).

The duration of effects of MDMA is between 3–6 hours, with effects starting between 20 min and 1.5 hours after oral consumption. It’s thought that the short duration (compared to its elimination half life between 8–9 hours) is due to the brain rapidly developing a temporary tolerance to the drug’s effects. MDMA is broken down into several active metabolites including MDA primarily in the liver by a range of enzymes including COMT and CYP2D6.

MDMA interacts with a number of different drugs. There have been several deaths from people taking MDMA while on ritonavir, a CYP2D6 inhibitor. As a serotonergic drug, taking MDMA with MAOIs can lead to a life-threatening condition called serotonin syndrome. SSRIs and SNRIs have been known to block most of the subjective effects of MDMA.

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