Spring 1994 Vol. 04, No. 4 Laying the Groundwork
Efforts are underway to initiate human research with 3,4-methylenedioxymethamphetamine (MDMA) at Harbor-ULCA Medical Center. Comprehensive work-ups of several individuals with extensive histories of past use of MDMA have been performed. These evaluations have focused on the effects of MDMA use on sertonergic neurotransmitter function, and have examined such parameters as sleep electroencephalograms (EEG), fenfluramine challenge tests, SPECT brain scans and neuropsychological testing. Our preliminary data (which we hope to report on in a subsequent MAPS newsletter) has turned out to be quite fascinating. We believe this study will shed considerable light on the psychophysiological mechanisms by which MDMA exerts its unique effects.
We currently have FDA approval to conduct two studies of MDMA administration in humans. The first sudy will be an examination of MDMA’s general safety parameters. It will involve a gradual ascending dose model to determine the threshold for subjective psychological effects as well as analgesia. This study is a prelude to other potential studies involving MDMA and patients who have terminal illness.
Safety and dose-finding study
The safety and dose-finding study in healthy volunteers will involve three separate experimental sessions in the Clinical Studies Center at the Harbor-UCLA Medical Center. The sessions will utilize each of two different dosages of MDMA as well as an inactive placebo. Both subjects and research personnel will be blind as to what is administered at each session. We will start with what we consider to be a sub-threshold dose (0.25 mg/kg) and gradually increase the dosages with successive subjects into the range we anticipate will induce the unique MDMA effect. Parameters to be examined in this study include blood pressure, temperature, electrocardiograms, hepatic function, renal function and thyroid function. A variety of measures will be utilized to quantify both acute psychological effect as well as neurophychological function. Non-invasive assessment of pain perception and analgesia will also be pursued. Given that this study is anticipated to be preparatory to an extensive investigation of the use of MDMA as a putative therapeutic modality in individuals with end-stage medical illness associated with refractory pain and psychological distress, we will also work with the guided imagery models we hope to eventually employ in these future studies.
Serotonin system study
Our second study of MDA administration in humans will involve a careful and extensive evaluation of effects on parameters of brain function. Given that concerns of the past decade with the phenomena described as "serotonergic neurotoxicity", it is imperative that we conduct objective and fair-minded studies into the effects of MDMA on parameters influenced by serotonergic neurotransmitter function. Although there is laboratory evidence that low dose MDMA causes no discernible lasting effect to brain structures, there is no doubt on the basis of animal histopathologic investigations that repeated parenteral administration of high dosages of MDMA will exert profound changes to serotonergic neuronal distribution.
What the implications of this animal data are to the functional status of individual human beings who take MDMA, however, is not at all clear. Are we looking at a "neurotoxic" phenomena which will inevitably lead to deterioration of neuropsychiatric function over time, or are we in fact observing the histopathological substrate for what may eventually be recognized as therapeutic "neuroplasticity"? Without access to data from research studies of human use of MDMA, we can only conjecture as to what the implications may be. Fortunately, we have reached the point where it is now possible to conduct the level of comprehensive, well-controlled methodological studies into the effects of MDMA in human subjects which will be essential to answer these critical questions.
The extensive investigation of MDMA effects on parameters of serotonergic neurotransmitter function is under way at the Harbor-UCLA Medical Center. My primary collaborator on this project is Dr. Russell Poland, a senior researcher in the Department of Psychiatry. Subjects enrolled in this particual study will be required to come into the Clincal Studies Center at Harbor-UCLA on six separate occasions. They will receive comprehensive neuropsychiatric assessments to include neuroendocrine challenge tests, sleep electroencephalograms, brain SPECT scand and neuropsychological testing. Extensive investigation of these parameters we anticipate will provide for us an enhanced understanding of the effects of MDMA use on serotonergic neurotransmitter status and its functional consequences.
We are currently recruiting subjects to take part in both of the studies described above. We are looking for both male and female volunteers who would be willing to invest the necessary time, energy and inconvenience that participation would require. We are particularly interested in identifying prospective subjects who have used significant amounts of MDMA but have relatively little experience with other drugs. Our subjects will need to be between the ages of 21 and 65, be in good medical and psychiatric health and have had prior first hand experience with the self administration of MDMA. The criteria that subjects must be health professions was recently waived by the FDA with the stipulation that participants be sufficiently knowledgeable of the controversy over MDMA’s effects that true informed consent be possible. Anyone interested in participating in these studies can call our research coordinator, Carla Edwards, at (310) 222-1663.
Although Dr. Poland and I recently received a small "in-house" grant from the Harbor-UCLA Research and Education Institute, we must acquire significant additional funding to carry out our investigational plans. This funding we have obtained is actually specified for the study extensively evaluating serotonergic parameters of brain function, and will enable us to collect pilot data which we will use in a submission to a large government granting agency. We are at this point without designated funding for the smaller scale, dose-finding and safety study, which is a necessary first step for the work we hope to do with individuals with end-stage medical illness. It is our strong hope, however, that together with the generous support of MPAS, we will be able to identify sufficient funding sources which will allow this work to begin. There is much at stake here. There are many questions to be asked and answered. There are myths to be dispelled. There is new knowledge to acquire and paths to explore. This is an exciting time. With the necessary funding support, we are ready to commence a series of research investigations which we anticipate will begin to address these very important issues.