Psychobiologic effects of 3,4-methylenedioxymethamphetamine in humans: methodological considerations and preliminary observations by Charles S. Grob et al in Behavioural Brain Research 73 (1996) 104-107

Abstract
3,4-Methylenedioxymethamphetamine (MDMA) is a phenethylamine with potent effects on serotonergic neurotransmission which has been the object of controversy over its potential as a therapeutic adjunct versus its possible risks for causing neurotoxic injury. This paper discusses ihe background, methodohgy and preliminary findings of the first FDA approved Phase I study prospectively evaluating the effects of MDMA administration in humans. Six subjects with prior experience with MDMA were adIninistered two different dosages of MDMA and an inactive placebo utilising a randomized, double-blind methodologic design. Dosages from 0.25 to l.0 mg/kg, p.o., were administercd. A11 subjects tolerated the procedures without any oven evidence of physical discomfort or psychological distrees. MDMA produced a modest increase in heart rate and blood pressure. The threshold dose for the stimulation of ACTH and prolactin appeared to be betwcen 0.5 and 0.75 mg/kg, with the two higher doses clearly stimulating both ACTH and prolactin. Methodology for assessing MDMA's effects on serotonergic neurotransmission is discussed.

Conclusions
Preliminary data have been presented on the first sanctioned prospective investigation of the psychobiologic effects of MDMA in humans. Although our findings of the first 6 subjects studied are intriguing, definitive conclusions must await further controlled inquiry of the effects of higher dose administration. The study design calls for additional subjects to receive MDMA in the 1.0-1.75 mg/kg range, which then will be followed by the study of 1.75-2.5 mg/kg dosages. Past studies have suffered from lack of prospective design thus impeding adequate elucidation of not only MDMA's inherent risk for causing harm but also its potentia1 for therapeutic application. An emotional and acrimonious political atmosphere has clouded careful and imppartial examination of MDMA's full range of effects. Precedent now has been established to conducting sanctioned investigation in human subjects under safe and controlled condition. Technical advances will allow for more careful monitorlng and assessment of the psychobiologic effects of MDMA in humans. Cntical questions concerning MDMA's putative risks to public health versus potential benefits of new treatment modalities await to be answered. Prospective research designs utilising the controlled administration of MDMA to humans offer the best hoppe of revealing its true, inherent, risk/benefit ratio.