Acute effects of R-MDMA, S-MDMA, and racemic MDMA in a randomized double-blind cross-over trial in healthy participants

MDMA enantiomers S-MDMA and R-MDMA can produce different acute effects, so a randomized, double-blind, placebo-controlled cross-over trial tested how S- and R-MDMA compare in humans. In 24 healthy participants, 125 mg MDMA (racemic), 125 mg S-MDMA, 125 mg R-MDMA, 250 mg R-MDMA, and placebo were administered with at least 10-day washouts. The study measured subjective effects, autonomic and adverse effects, pharmacokinetics, and plasma oxytocin, prolactin, and cortisol. S-MDMA produced stronger stimulation and “drug high” ratings than R-MDMA (both doses) and racemic MDMA, along with higher blood pressure. Contrary to expectations, R-MDMA did not show more psychedelic-like effects than S-MDMA on altered states scales. S-MDMA also increased plasma prolactin, cortisol, and oxytocin more than MDMA and R-MDMA. Pharmacokinetics showed a much longer elimination half-life for R-MDMA than S-MDMA.