Psychological and Physiological Effects of MDMA (“Ecstasy”) after Pretreatment with the 5-HT2 Antagonist Ketanserin in Healthy Humans

MDMA (3,4-methylenedioxymethamphetamine, “Ecstasy”) mainly releases serotonin and dopamine. In animals, pretreatment with 5-HT2 antagonists has been shown to attenuate neurochemical and behavioral effects of MDMA. In humans, the role of 5-HT2 receptors in the action of MDMA has not been studied. We investigated the effect of pretreatment with the 5-HT2A/C antagonist ketanserin (50 mg p.o.) on subjective responses to MDMA (1.5 mg/kg p.o.) in 14 healthy volunteers using a double-blind placebo-controlled within-subject design. Subjective effects were rated by psychometric rating scales. Physiological effects measured were blood pressure, heart rate, and body temperature. Adverse effects were assessed during the sessions, and after one and three days. Ketanserin attenuated MDMA-induced perceptual changes, emotional excitation, and acute adverse responses but had little effect on MDMA-induced positive mood, well-being, extroversion, and short-term sequelae. Body temperature was lower under MDMA plus ketanserin compared to MDMA alone. The results suggest a contributing role for 5-HT2 receptors in the action of MDMA in humans.