MDMA acts primarily as a presynaptic releasing agent of serotonin, norepinephrine, and dopamine, which arises from its activity at trace amine-associated receptor 1 (TAAR1) and vesicular monoamine transporter 2 (VMAT2). MDMA is also a monoamine transporter substrate (i.e., a substrate for DAT, NET, and SERT), so it enters monoamine neurons via these neuronal membrane transport proteins; by acting as a monoamine transporter substrate, MDMA produces competitive reuptake inhibition at the neuronal membrane transporters (i.e., it competes with endogenous monoamines for reuptake). MDMA inhibits both vesicular monoamine transporters (VMATs), the second of which (VMAT2) is highly expressed within monoamine neurons at vesicular membranes. Once inside a monoamine neuron, MDMA acts as a VMAT2 inhibitor and a TAAR1 agonist. Inhibition of VMAT2 by MDMA results in increased concentrations of the associated neurotransmitter (serotonin, norepinephrine, or dopamine) in the cytosol of a monoamine neuron. Activation of TAAR1 by MDMA triggers protein kinase A and protein kinase C signaling events which then phosphorylates the associated monoamine transporters – DAT, NET, or SERT – of the neuron. In turn, these phosphorylated monoamine transporters either reverse transport direction – i.e., move neurotransmitters from the cytosol to the synaptic cleft – or withdraw into the neuron, respectively producing neurotransmitter efflux and noncompetitive reuptake inhibition at the neuronal membrane transporters. The actions increase the synaptic concentrations of monoamine neurotransmitters. MDMA has ten times more affinity for uptake at serotonin transporters compared to dopamine and norepinephrine transporters and consequently has mainly serotonergic effects. In summary, MDMA enters monoamine neurons by acting as a monoamine transporter substrate. MDMA activity at VMAT2 moves neurotransmitters out from synaptic vesicles and into the cytosol; MDMA activity at TAAR1 moves neurotransmitters out of the cytosol and into the synaptic cleft. MDMA also has weak agonist activity at postsynaptic serotonin receptors 5-HT1 and 5-HT2 receptors, and its more efficacious metabolite MDA likely augments this action. Cortisol, prolactin, and oxytocin quantities in serum are increased by MDMA.