Ibogaine: Proceedings from the First International Conference

by Kenneth R. Alper, Geoffrey A. Cordell, Stanley Glick

Overview

This book presents the Proceedings from the First International Conference on Ibogaines, held in November of 1999 at New York University's School of Medicine. In essence, it presents significant new data on neurobiological, clinical, sociocultural, and policy aspects of ibogaine.

Ibogaine is a natural product derived from the bark of the root of the African shrub Tabernathe iboga. It has a history of use as a medicinal and ceremonial agent in West Central Africa, and has been alleged to be effective as a treatment for substance dependence. The study of Ibogaine may shed light on the neurobiology of addiction and lead to the development of new medication for the treatment of addiction.

Currently, there is lack of formal approval for the use of ibogaine, and the demand of the addicts themselves has led to a distinctive unofficial network which has provided ibogaine treatment in non-medical settings. If critical safety concerns can be adequately addressed, ibogaine may provide an inexpensive and practical treatment approach, well adapted to environments where resources are severely limited and there is pressing need for clinical services for heroin addicts, such as Eastern Europe.

This is a paperback edition of Volume 56 of The Alkaloids (ISBN: 0-12-469556-6) edited by Geoffrey A. Cordell, University of Illinois at Chicago, U.S.A.

Product Details

ISBN-13:	9780120532063
Publisher:	Elsevier Science
Publication date:	09/01/2001
Series:	Alkaloids Series
Pages:	360
Product dimensions:	0.80(w) x 6.00(h) x 9.00(d)

About the Author

Professor Emeritus Geoffrey A. Cordell obtained his Ph.D. in synthetic natural product chemistry at the University of Manchester in 1970. After two years as a NATO postdoctoral fellow at the Department of Chemistry, M.I.T., he joined the College of Pharmacy, University of Illinois at Chicago (UIC). A Professor since 1980, he served as a Department Head for 12 years and as Interim Dean of the College of Pharmacy for almost three years, as well as holding several other senior academic and research administrative positions at the Department, College, and Campus levels. He was the Co-founder of the US - Thai Consortium for Pharmacy Education, which developed and trained faculty for six new schools of pharmacy in Thailand. He retired from the University of Illinois in 2007. Since 1983, he has served as President of Natural Products Inc., a consulting company.

He is the author of about 600 research publications, book chapters, comprehensive reviews and professional publications; is the author of two books, with three more in progress; the editor of 37 books, including 29 volumes in the series “The Alkaloids: Chemistry and Biology”; is Associate Editor-in-Chief of the Chinese Journal of Natural Medicines; and a member of the Editorial Advisory Board of 26 international scientific journals. He is a former President of the American Society of Pharmacognosy, and is also an Honorary Member.

In 1981, he was an Alexander von Humboldt Fellow at the University of Munich with Professor Hildebert Wagner. He is an elected Fellow of the Royal Chemical Society, the Linnean Society of London, the American Society of Pharmacognosy, and the American Association of Pharmaceutical Scientists. In addition to assisting international organizations and corporations in several countries around the world to develop their research and academic programs, he is an Honorary Professor at Sichuan University, Chengdu, China; and at Amity University, Noida, India. He is also a Visiting Professor at universities in Peru, Malaysia, and Brasil, and an International Collaborative Partner of the UTAR Global Research Network in Malaysia in the areas of biodiversity and cancer. In addition, he is a member of the International Advisory Board of several natural product research institutes. His interests include the chemistry and biosynthesis of alkaloids, the sustainability and quality control of medicinal agents, the remote detection of biologically active natural products, and the use of vegetables as chemical reagents.

Read an Excerpt

The use of, abuse of, and dependence on a variety of licit and illicit substances constitute the major public health problem facing the United States and many other countries. Drug abuse is the leading cause of new HIV infections, a major cause of cancer deaths as well as automobile and boat accidents, the largest contributor to our burgeoning prison population, and the largest cause of crime, violence, domestic and child abuse, and community destruction. In the United States there are more than 50 million nicotine addicts, at least 15 million alcoholics and problem drinkers, more than 3 million marijuana addicts, 2 to 3 million cocaine addicts, and more than a million heroin addicts. The number of "hardcore" addicts to illicit drugs is well over 6 million. It is not surprising, given these numbers and social costs, that theories abound as to ways to improve the situation. From total prohibition to total legalization and numerous steps in between, arguments rage as to the best approach. For experienced observers of the situation, not blinded by partisan beliefs and rhetoric, it appears clear that there is no one answer.

Mencken's observation about simple solutions, "there is always a well-known solution to every human problem-neat, plausible, and wrong," is as true now as in 1920 when he made it. Pure "supply reduction" models founder on the rocks of "need" and "greed"-the desire for the euphoric effects of these agents, and the willingness of individuals to take risks to provide them because of the large profits. Likewise, the pure "demand reduction" model shows its inadequacy by the lack of interest of many addicts in stopping and the failures of our current prevention and treatment programs to either prevent or treat sufficiently. We need both a balanced model and better prevention and treatment methods.

The current view of addiction is a marriage of brain and behavior. Sophisticated imaging procedures and basic science research into the neurobiology of reward have identified key elements in the reinforcing effects of various psychoactive substances. Motivational circuits underlie the desirability of abused drugs. Brain changes after prolonged use help keep the habit going, as well as increase the likelihood of relapse after hard-won abstinence. In one sense, the reward circuitry has been "hijacked" by the rapid intense effects of chemicals at the expense of the more usual rewarding behaviors. Successful treatment thus often requires both medications-to help addicts cope with the brain changes and urges-and relapse prevention techniques and learning-to help addicts regain the ability to get rewards from nonchemical means. The failure of many treatment attempts is a testimony to the difficulty of the task.

Because of this difficulty, there is a constant search for new methods-better, faster, easier. The search for a "quick fix" is not limited to addicts-researchers, treatment providers, family members, friends and policy makers share it at times as well. The fact that it hasn't yet been found doesn't mean it can't be found, so efforts continue. The story of ibogaine for addiction is part of that search. One hundred years ago, as well as recently, treatment of withdrawal was often seen as synonymous with treatment of addiction. Numerous drugs and techniques-some innocuous, some lethal, most in between-were tried to improve withdrawal. None were successful for the larger task of healing addiction, although some have worked reasonably well in treating withdrawal. We still cannot successfully treat a substantial number of addicted individuals. The difficulty may lie both in the persistence of brain changes and the difficulty of making lifestyle changes. The search has been hampered by the intensive warfare between those who believe any medication is a "crutch", and those who view addiction as a medical disorder that may ultimately yield to a combination of medications and behavioral techniques, as employed in other chronic medical conditions. It has also been hampered by the lack of interest of major pharmaceutical firms in devoting resources to the search. Stigma connected to addiction and a perceived lack of possible profitability in a medication have contributed to this unwillingness. Medications could have a variety of roles some, more likely to be found than others: providing a rapid, safe effective withdrawal; decreasing craving; providing a "window of opportunity" for the individual to develop relapse prevention skills and alternative reinforcers; reversing brain changes; blocking or ameliorating the effects of the abused substances; and providing a cost-effective way of reaching larger numbers of individuals.

The diffusion of psychedelic drugs into the larger culture in the 1960s led to a variety of different uses. While some used them for "recreational" purposes, escapism, and altered sensory experiences, others used them in religious activities, serious exploration of altered states, and, at times, formal therapy. LSD, for example, was used in the treatment of alcoholism. Although initially it appeared to yield promising results, manifested by a high percentage of abstinence, follow-up studies demonstrated no sustained efficacy, and efforts were mainly dropped. The rise in the street use of the drug among the young may have contributed in part to the loss of interest among researchers, but lack of efficacy appears to have been a major factor. In contrast, the use of peyote to treat alcoholism in some Native American groups has persisted for decades, perhaps because of its restriction to clear religious ceremonial occasions.

Ibogaine appears to have followed in a similar path therapeutically as LSD, but it did not become a street drug, probably because of some unpleasant side effects and possibly weak reinforcing effects. Initially it was touted as both a rapid effective withdrawal method and a cure for heroin and cocaine addiction. Later, as relapses became apparent, it was labeled as an "addiction interrupter," and still later as useful mainly for a small group of "motivated" individuals. Unlike LSD, a variety of groups with very different agendas pushed its use for therapy-as described succinctly in the chapter by Alper et al. in this volume. Because, as noted earlier, commercial interest in addiction treatment medications was minimal, pressure by these disparate groups was aimed at government agencies-especially the National Institute on Drug Abuse (NIDA) and the Food and Drug Administration (FDA)-and individuals, including this author, who were mistakenly, or more likely deliberately for reasons such as their position on other issues of interest to certain groups, targeted for coercive actions. Whether the actions against NIDA were ultimately helpful, harmful, or insignificant in getting the desired results is not totally clear. My own view is there may have been a short-term gain, but a long-term loss, because of the perceived marginalization of the drug.

More important for the long-term goal of developing new medications for addiction was the persistence of scholarly research on ibogaine in both animals and humans. Such research laid out possible mechanisms of action and found metabolites or congeners that may be of more interest than the parent compound. Ultimately the usefulness, or lack thereof, of ibogaine and related compounds in the treatment of addiction will rise or fall on such research. If the drug does have useful effects, it may be possible to develop synthetic agents that produce desired actions on addiction without undesirable effects. In any event, Alper is to be congratulated for both the enormous effort to put together the scientific conference on which this book is based and the book itself, which can bring the findings to a larger audience than was present at the meeting. The need for new medications to treat addiction is as great as ever. Whether or not ibogaine is useful is a scientific question that can be answered neither by street demonstrations nor by avoiding careful, controlled research. As scientists, our obligation is to keep looking for safe effective methods to prevent and treat this great international scourge.

Herbert Kleber
Columbia University College of Physicians and Surgeons

Table of Contents

Mechanisms of Action of Ibogaine: Relevance to Putative Therapeutic Effects and Development of a Safer Iboga Alkaloid Congener (Stanley Glick, Isabelle Maisonneuve, Karen Szumlinski)

Ibogaine as a Glutamate Antagonist: Relevance to its Putative Antiaddictive Properties (Phil Skolnick)

Drug Discrimination Studies with Ibogaine (Scott Helsley, Richard Rabin, J.C. Winter)

Changes in Gene Expression and Signal Transduction Following Ibogaine Treatment (Emmanuel Onaivi, B. Emmanuel Akinshola, Syed Ali)

Characterization of Multiple Sites of Action of Ibogaine (Henry Sershen, Audrey Hashim, Abel Lajtha)

Comparative Neuropharmacology of Ibogaine and Its O-Des Methyl Metabolite, Noribogaine (Michael Baumann, John Pablo, Syed Ali, Richard Rothman, Deborah Mash)

Ibogaine in the Treatment of Heroin Withdrawal (Deborah Mash, Craig Kovera, John Pablo, Rachel Tyndale, Frank Ervin, Jeffrey Kamlet, W. Lee Hearn)

Sigma Receptors and Iboga Alkaloids (Wayne Bowen)

Ibogaine Neurotoxicity Assessment: Electrophysiological, Neurochemical, and Neurohistological Methods (Zbigniew Binienda, Andrew Scallet, Larry Schmued, Syed Ali)

Modulation of the Effects of Rewarding Drugs by Ibogaine (Linda Parker, Shepard Siegel)

Anxiogenic Action of Ibogaine (Piotr Popik, Magorzata Wrobel)

"Returning to the Path": The Use of Ibogaine in Equatorial African Ritual Context and the Binding of Time, Space, and Social Relationships (James W. Fernandez, Renate Fernandez)

Contemporary History (Kenneth Alper, Dana Beal, Charles Kaplan)

From the Roots Up: Ibogaine and Addict Self-Help (Geerte Frenken)

Case Studies of Ibogaine Treatment: Implications for Patient Management Strategies (Howard Lotsof, Norma Alexander)