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 seroton in and dopamine. In animals, pretreatment with 5-HT2 antagonists has been s hown 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 ketans erin (50 mg p.o.) on subjective responses to MDMA (1.5 mg/kg p.o.) in 14 he althy volunteers using a double-blind placebo-controlled within-subject des ign. Subjective effects were rated by psychometric rating scales. Physiolog ical effects measured were blood pressure, heart rate, and body temperature . Adverse effects were assessed during the sessions, and after one and thre e days. Ketanserin attenuated MDMA-induced perceptual changes, emotional ex citation, and acute adverse responses but had little effect on MDMA-induced positive mood, well-being, extroversion, and short-term sequence. Body tem perature was lower under MDMA plus ketanserin compared to MDMA alone. The r esults suggest a contributing role for 5-HT2 receptors in the action of MDM A in humans. (C) 2000 American College of Neuropsychopharmacology. Publishe d by Elsevier Science Inc.