Winter 1995 Vol. 05, No. 3 Clinical Trials and Tribulations
As of February 1995, our FDA approved, Phase I research protocol of MDMA completed full study of six subjects. Following further FDA approval, we have initiated studies with our second group of six subjects. Several additional subjects with long personal histories of MDMA use have received evaluations of various aspects of brain function, but have not been enrolled in the MDMA administration arm of the study.
Our basic protocol includes psychiatric interviews and neuropsychological testing prior to the first experimental MDMA session. Each subject participates in three experimental sessions, during two of which he/she will receive one of two different dosages of MDMA, and during the third, an inactive placebo. Both the subject as well as the medical research team will be blind as to what substance will be administered during each particular session. During each of the three experimental sessions, which last a full six hours, subjects will have an indwelling intravenous catheter from which blood samples will be drawn every twenty minutes, for pharmacokinetics and neuroendocrine parameters. Frequent blood pressure, heart rate, respiratory rate and temperature recordings will also be obtained. At set intervals, psychological rating scales will be filled out by the subjects. Two weeks after the final MDMA administration session, repeat neuropsychological testing will again be performed.
Additional neuropsychiatric research procedures conducted on several subjects enrolled in the MDMA administration study, as well as others who have not received MDMA in the experimental setting but have had a history of extensive past use of MDMA, include sleep electroencephalography, fenfluramine challenge testing, brain SPECT (single photon emission computed tomography) scans and brain spectroscopy.
We have completed studies with our first group of six subjects. Doses administered (orally) ranged from 0.25 mg/kg to 1.0 mg/kg. Vital signs were not significantly affected by MDMA administration although heart rate and blood rate were increased modestly by the drug. All six subjects who completed the protocol tolerated the MDMA administration well without evident difficulty. One additional subject who had been recruited in the study dropped out after one experimental drug session, complaining of anxiety during the session. After the subject had withdrawn from the protocol, the blind was broken, revealing that he had been administered an inactive placebo during his only session.
Additional data on measures of brain function are beginning to show evidence of very interesting trends which should greatly improve our understanding of MDMA’s effects on the central nervous system, particularly serotonergic neurotransmission. Our SPECT scans, thus far consisting of six subjects with histories of MDMA use and several normal controls, are particularly intriguing. We are currently preparing to submit our findings for publication in the neuropsychiatric and pharmacologic literatures, following which we will provide an extensive review for the MAPS Bulletin.
We are currently planning to conduct extensive evaluations of twelve additional subjects, according to the protocol described. Following completion of the Phase I study of all eighteen normal volunteer subjects, we will submit our data to the FDA for review. At that time, we will also apply for permission to conduct Phase II studies of MDMA’s potential efficacy in the treatment of specific clinical disorders, including refractory depression and pain in individuals suffering from end-stage cancer.
We are currently still in the process of recruiting subjects who have a history of prior use of MDMA. Because of the sensitivity to travel and time zone changes of the neuroendocrine parameters we are measuring, we are restricting our subjects for the MDMA administration arm of the study to those who live in the Southern California area. We are also interested in interviewing adolescents who have had past experiences with MDMA, although minors cannot be included in the MDMA administration phase of the study. Anyone interested in volunteering should call Gayle Nakasaki at (310) 222-4266. Potential subjects should keep in mind that an extensive time com-mittment is required from participants in the study. Of final note is that we are particularly interested in evaluating individuals with an extensive history of past MDMA use (at least 100 times) for our SPECT scan protocol. These subjects will not necessarily be enrolled in the MDMA administration arm of the study, and need not live in Southern California.
Donations in support of our continued research are necessary and would be greatly appreciated.