Ecstasy : the clinical, pharmacological, and neurotoxicological effects of the drug MDMA

This volume represents the proceedings of the third in a series of annual inter­ national symposia. The first, The Neuroregulation of Autonomic, Endocrine, and Immune Systems, was held in Indianapolis in the fall of 1985. The second, Psychological and Biological Approaches to the Understanding of Human Disease, was held in Bielefeld, Germany in the fall of 1986. The theme of this series concerns the communication between the central nervous system and the other major systems of the body, and the purpose is to monitor the frontiers of research into these neuronal/hormonal regulatory interactions and their application to medicine. The present volume deals with the role of peptides and amino acids in these information transfer processes. Great strides have been made in exploring the important role of amino acids and pep tides in neuroregulation, and the ongoing biotechnology revolution promises signi­ ficant scientific and medical advances throughout the next decade and beyond. The work described in this volume captures the great excitement and pro­ mise of this biomedical renaissance. This meeting was cosponsored by Searle/ Monsanto and Washington University and held in St. Louis in the early fall of 1986. A major contributor to these proceedings was Dr. Thomas O'Donohue whose chapter deals with his work in characterizing the endogenous ligands for the PCP and sigma opioid receptors. Tom's personality and career personi­ fied the dedication of this series to the principle of a broad multidisciplinary approach to scientific problems. This symposium entitled Calcium, Neuronal Function and Transmitter Re­ lease, was in the framework of the regional meeting of the International Union of Physiological Sciences, that took place in Jerusalem between August 26-31, 1984. The symposium dealt with the role of calcium ions in regulation of a large number of important processes in modern neurobiology, from molecular and cellular points of view. In this context, we consider heart and most cells as'honorary neurons'. The meeting was comprised of lectures and quite intense discussions. We hope that the transcription of the discussions which follow the articles will give the reader a feeling of the intense, but pleasant atmosphere that per­ vaded during this symposium. It is our pleasure to thank Mrs. Miriam Silber, the assistant editor of this book, for her hard work in transcribing the discussions, retyping large portions of the book, and getting the approval of the authors. We express our thanks to Dr. Halina Meiri and Dr. Simona Ginsburg for their editorial assis­ tance. The unfailing help of Ms. Rachel Klein and Ms. Shoshana Wineberg is greatly appreciated. xxvii SECTION 1 CALCIUM CHANNELS, TRANSPORTERS & CALCIUM REGULATED CHANNELS EFFECTS OF TEMPERATURE ON SINGLE CHANNEL AND WHOLE CELL Ca CURRENTS A. M. BROWN, D. L. KUNZE, H.D. LUX AND D. L. WILSON INTRODUCTION Calcium tall currents have a large,fast component which Is not detectable when the currents are turned on or acti­ vated from the completely rested state (Brown et aI, 1983). The first two'Brain Heart Conferences'in Jerusalem in 1978 and 1983 were based upon the common interests of clinically orientated neurologists and cardiologists in the problems of centr'al autonomic control and autonomic disturbances of the cardiovascular system. The relatively slow scientific progress, at least clinically, in this area may be due to the fact that neither cardiologists nor neurologists felt competent in both topics. Furthermore, it has become increasingly difficult to have an overall view of the basic research and its clinical applications in this field. New research methods, based on a comtination of morphological, biochemical, and physiological techniques, have enabled the functional differentiation of various areas of the brain and subsequently also of the autonomic nervous system. The simple dualistic concept of an antagonistic sympathetic-parasympathetic regulation of the circulatory system is no longer valid. It is clear that numerous neurotransmitters, in particular the neuropeptides, are involved in a highly differentiated subdivision of the autonomic system. One of the aims of the IIIrd International Brain Heart Conference was therefore to supply a synopsis of the latest developments in basic research undertaken in this field by exceptionally competent scientists, to clinically orientated neurologists and cardiologists, and thus to provide new impulses for clinical research. Our understanding of the functioning of the brain has grown rapidly over the last decade or two. So has our recognition of the possible role of brain dysfunction in diseases considered earlier to be of peripheral or somatic origin. This culminates naturally in a focus on the nature of the influence of the brain on other systems such as the autonomic, neuroendocrine and immune systems. And we must come full circle and question the nature of the influence of these systems on the function of the brain. Thus, we gain a picture of a complex regulatory interaction, fine tuned in normal circumstances to provide each system with necessary information about the status of the other systems and the basis to respond appropriately to changes in each other. This volume provides the proceedings of the first of a series of international symposia intended to review the state-of-the-art understanding and frontier exploration of the above described interregulatory phenomena, with some emphasis on the relevance of this information to the etiology and treatment of disease. The purpose of this first symposium was to lay the groundwork for this continuing endeavor. To accomplish such a goal required bringing together diverse multidisciplinary professionals - eg neurobiologists, immunol­ ogists, psychiatrists, cardiologists and students amongst others. There was once an old Chinese man working on a hill with a boy. On the plain, near the sea, rested the village, the inhabitants eagerly engaged in their daily activities. Suddenly, the old man noticed that a huge wave, far distant in the sea, was approaching the shore endangering all. The only safe place was the hill. So, he began waving his hands and screaming aloud, to no avail. The villagers were too busy with their own work and paid little heed to the old man, who was considered a bit eccentric. But soon flames were on the hill, the wheat fields ablaze. The old man had resorted to this ultimate step to alert his fellow citizens. Now, they all went running towards him, angry about their burning crop, and in the process, avoided the imminent danger. For some mysterious reason, my mind focused on this story prior to the Symposium on the Role of DNA, which took place in Ravello, Italy at the end of May 1985. Having made a call for people to meet and reflect for a few days, the analogy began to take shape. Ravello was indeed a hill, magically overlooking the sea from medieval quarters. True, its countryside is filled with vineyards, not wheat fields, but that is an improvement on the story. However, what was the wave? Perhaps, the growing amount of data on cloned brain genes that threatens to engulf neurobiologists. The variety of viewpoints expressed in this book illustrate the many contro­ versies surrounding MDMA [1]. On the one hand, the proponents ofMDMA use believe this agent offers a unique psychoactive effect that may have important clinical applications, especially in the field of psychotherapy. On the other hand, the scientific data concerning the neurotoxic effects of the drug are unequivocal. The most striking feature of the human information of MDMA is the paucity of data that has been generated on the drug since it was patented in 1914. As pointed out by Beck (Chapter 6) and others, a clear need exists for better epidemiological and clinical data on MDMA. In the absence of such data, arguments both for and against the cotinued use ofMDMA with humans will be difficult to support. Unfortunately, the currently available data must be used to develop rational policies for potential human users of MDMA. At the present time, there are no data indicating that recreational doses of MDMA permanently damage the human brain. Nonetheless, based on a review of the contents of this book as well as on informal discussions with approximately 200 recreational users of MDMA, the following personal observations suggest that MDMA is radically different from other recreational drugs. At the end of September 1984 Dr. M. Velickovi~ and Prof. H. Prechtl with the help of the International Cerebral Palsy Society organized an international conference on'New develop­ ments in the assessment of early brain damage'in Bled, Yugo­ slavia. I was invited as a speaker at this conference and I went there, curious, but without too much knowledge about the central theme: cerebral palsy. During the conference and a satellite meeting I became impressed by the quality of various contributions and also by the great variety of problems related to the etiology, early diagnosis, management and psychosocial aspects of cerebral palsy. Today, in many areas of biology and medicine, progress seems to require concentration on a very narrow field. As a consequence many conferences are highly specialized and most (young) scientists rightly consider this as most useful for their own work. On the other hand the care of patients and counselling of parents and other close relatives require a multidisciplinary approach. Also, advances in the study of complicated un­ resolved medical biological pr'oblems are often made unex­ pectedly by using ideas, theories, approaches or methods from other disciplines. Front Matter....Pages i-xv History of MDMA....Pages 1-20 The Therapeutic Use of MDMA....Pages 21-35 Testing Psychotherapies and Drug Therapies: The Case of Psychedelic Drugs....Pages 37-52 Recreational Use of MDMA....Pages 53-62 Human Deaths and Toxic Reactions Attributed to MDMA and MDEA....Pages 63-75 The Public Health Implications of MDMA Use....Pages 77-103 Structure-Activity Relationships of MDMA and Related Compounds: A New Class of Psychoactive Agents?....Pages 105-131 Neurochemical Effects of MDMA....Pages 133-150 Neurochemical Effects of Methylenedioxymethamphetamine in the Rat: Acute Versus Long-Term Changes....Pages 151-169 MDMA Effects in Brain: Pharmacologic Profile and Evidence of Neurotoxicity from Neurochemical and Autoradiographic Studies....Pages 171-199 A Tissue Culture Model of MDMA Toxicity....Pages 201-211 Effect of MDMA-Like Drugs on CNS Neuropeptide Systems....Pages 213-224 Neuroendocrinological Effects of MDMA in the Rat....Pages 225-239 Back Matter....Pages 241-244 Edited By Antonio Giuditta, Barry B. Kaplan, Claire Zomzely-neurath. Based On The Symposium Role Of Dna In Brain Activity Held In Ravello, Italy On May 27-29, 1985, As A Satellite Meeting Of The 10th Meeting Of The International Society For Neurochemistry, Held In Riva Del Garda, Italy On 19-24 May 1985. Includes Bibliographies And Indexes. Prechtl with the help of the International Cerebral Palsy Society organized an international conference on "New develop ments in the assessment of early brain damage" in Bled, Yugo slavia. Edited By Rami Rahamimoff, Sir Bernard Katz. The Symposium Was Held In Jerusalem During The Regional Meeting Of The International Union Of Physiological Sciences. Includes Bibliographies. Proceedings of Symposium on Calcium, Neuronal Function and Transmitter Release, held at International Union of Physiological Sciences, August 28-31, 1984 Proceedings of the Third Annual International Symposium on Neuronal Control of Bodily Function: Basic and Clinical Aspects - November 4-7, 1986 Edited By H. Galjaard, H.f.r. Prechtl, M. Veličkovič. Includes Bibliographies.