Drs. Lewis Seiden and George Ricaurte expressed a deep reluctance to support the human use of MDMA in any patient population due to the uncertain and very narrow range of doses that would be both low enough to produce no neurotoxicity and high enough to produce a therapeutically desired outcome. The threshold level of MDMA in primates needed to cause some neurotoxicity was in the range of a single oral dose of2.5 – 5.00 mg/kg. Due to the wide range of variability of response in humans, it is therefore possible that doses of 1.5 mg/kg (around the therapeutic dose) will cause some neurotoxicity in humans, however slight.
Dr. Ricaurte was also concerned by new evidence demonstrating that the previously observed recovery of damaged serotonin nerve terminals was only a temporary phenomenon, with gains in serotonin levels plateauing after four months and dissipating over the next year or so. Even though evidence demonstrates administration of fluoxetine (Prozac) completely blocks MDMA’s neurotoxic effect, Dr. Ricaurte was generally uncomfortable with polypharmacy, especially in research contexts.
Drs. Lewis Seiden and George Ricaurte expressed a deepened understanding of the range and number of the anecdotal reports of MDMA’s therapeutic potential and suggested a vigorous research effort to find compounds that lacked MDMA’s neurotoxic potential yet retained its therapeutic qualities. Balancing the risks and benefits, Drs. Seiden and Ricaurte expressed fewer reservations about well designed human studies with patients with terminal illness. They recognized that there are still no cases in the literature of any individuals suffering from significant observable adverse neurological consequences from possible MDMA neurotoxicity. Non-subtle consequences of neurotoxicity, if there actually are going to be any, might take at least fifteen or twenty years of use to develop. They indicated a strong possibility they would support a well designed study in terminal patients that limited MDMA to oral doses around 1.5 mg/kg and limited number and frequency to four or five exposures with two weeks or more between sessions.