Taking the antidepressant duloxetine before MDMA (ecstasy) blocks many of the drug's effects. In a controlled experiment with 16 healthy volunteers, duloxetine prevented MDMA from raising blood pressure, heart rate, and norepinephrine levels, and also reduced the subjective drug experience. This happened even though duloxetine increased MDMA concentrations in the blood. Laboratory tests on human cells confirmed that duloxetine stops MDMA from releasing the neurotransmitters serotonin and norepinephrine. These findings indicate that MDMA's psychological effects depend on its ability to release both serotonin and norepinephrine, and suggest duloxetine could help treat dependence on stimulant drugs.
Blocking the norepinephrine transporter with reboxetine reduces the cardiovascular and subjective stimulant effects of MDMA (ecstasy) in humans, even though MDMA and its active metabolite reach higher concentrations in the blood. In a double-blind, placebo-controlled crossover study with 16 healthy adults, reboxetine lowered MDMA-induced increases in plasma norepinephrine, blood pressure, heart rate, drug high, stimulation, and emotional excitement. The findings indicate that transporter-mediated norepinephrine release is essential for MDMA's cardiovascular and stimulant-like effects.