The Alkaloids

TABLE of CONTENTS

CONTRIBUTORS FOREWORD BY HERB KLEBER PREFACE BY GEOFFREY A. CORDELL PREFACE BY KENNETH R. ALPER AND STANLEY D. GLICK NUMBERING OF IBOGA ALKALOIDS

ix   xv  xix  xxi xxiii

Ibogaine: A Review KENNETH R. ALPER I. II. III. IV. V. VI. VII. VIII. IX. X.   Introduction, Chemical Properties and Historical Time Line. Mechanisms of Action Evidence of Efficacy in Animal Model Evidence of Efficacy and Subjective Effects in Humans Pharmacokinetics Safety Learning, Memory and Neurophysiology Anthropological and Sociological Perspectives Economic and Political Perspectives Conclusions References  2  6  12  16  19  22  27  30  31  32  33   Mechanisms of Action of Ibogaine: Relevance to Putative Therapeutic Effects and Development of a Safer Iboga Alkaloid Congener STANLEY D. GLICK, ISABELLE M. MAISONNEUVE AND KAREN K. SZUMLINSKI

I. II. III. IV. V. VI. VII. VIII.

Introduction Behavioral and Neurochemical Methods Opioid Interactions Stimulant Interactions Metabolism and Distribution of Ibogaine and 18-MC Toxicity Mechanisms Discussion References

39  41  42  45  48  48  49  50  52

Ibogaine as a Glutamate Antagonist: Relevance to Putative Antiaddictive Properties PHIL SKOLNICK

I. II. III.

Overview NMDA Antagonist Properties of Ibogaine Are the NMDA Antagonist Properties of Ibogaine Relevant to its Putative Antiaddictive Properties? References

55  56  58  61

Drug Discrimination Studies with Ibogaine SCOTT HELSLEY, RICHARD A. RABIN AND J.C. WINTER

I. II. III.

Introduction Ibogaine in Drug Discrimination Studies Summary References

63  65  75  76

Comparative Neuropharmacology of Ibogaine and Its O-Desmethyl Metabolite, Noribogaine MICHAEL H. BAUMANN, JOHN PABLO, SYED F. ALI, RICHARD B. ROTHMAN AND DEBORAH C. MASH

I. II. III. IV. V. VI.

Introduction Pharmacokinetics Neurochemical Mechanisms Neuroendocrine Effects Adverse Consequences Conclusions References

80  82  85 100 103 107 109

Characterization of Multiple Sites of Action of Ibogaine HENRY SERSHEN, AUDREY HASHIM AND ABEL LAJTHA

I. II. III. IV. V. VI. VII. VIII.

Introduction Issues Related to Ibogaine in the Treatment of Drug Dependence Effects of Ibogaine on Drug-Induced Behavior Binding Site Activity Functional Activity Stimulant Drug Actions/Behaviors Current Non-Ibogaine Drug Treatment Protocols Conclusions References

115 117 119 119 122 124 127 129 130

Changes in Gene Expression and Signal Transduction Following Ibogaine Treatment SAMUEL S. ONAIVI, B. EMMANUEL AKINSHOLA, SYED F. ALI

I. II. III. IV. V.

Introduction In Vitro Action of Cocaine on Ca2+ and Protein Kinase C Signaling Effects of Ibogaine on the Action of Cocaine in Vivo Expression of Genes Regulated by Ibogaine Using cDNA Micro Analysis Conclusions References

136 142 146 149 151 152

Ibogaine in the Treatment of Heroin Withdrawal DEBORAH C. MASH, CRAIG A. KOVERA, JOHN PABLO, RACHEL TYNDALE, FRANK R. ERVIN, JEFFREY D. KAMLET AND W. LEE HEARN

I. II. III. IV. V. VI. VII. VIII. IX. X. XI.

Introduction Identification of a Primary Metabolite of Ibogaine Cytochrome P450 Metabolism and Genetic Polymorphisms Ibogaine Pharmacokinetics Setting and Study Design Physician Ratings of Withdrawal Subject's Self-Report of Withdrawal Symptoms Acute Detoxification and Behavioral Outcomes Cardiovascular Changes and Side Effects of Ibogaine Mechanism of Action Conclusion and Future Directions References

156 157 158 160 161 162 163 163 165 167 169 170

Sigma Receptors and Iboga Alkaloids WAYNE D. BOWEN

I. II. III. IV. V. VI.

Introduction Sigma Receptors Binding of Iboga Alkaloids to Sigma Receptors Effect of Iboga Alkaloids on Intracellular Cystolic Calcium Effect of Iboga Alkaloids on Cellular Morphology and Induction of Apoptosis Summary and Discussion References

173 174 178 180 181 184 188

Ibogaine Neurotoxicity Assessment: Electrophysiological, Neurochemical, and Neurohistological Methods ZBIGINEW K. BINIENDA, ANDREW C. SCALLET, LARRY C. SCHMUED, AND SYED F. ALI

I. II. III. IV.

Introduction Electroencephalography and Ibogaine Other Studies of Ibogaine Neurotoxicity at FDA/NCTR Conclusions References

193 194 200 209 209

Modulation of the Effects of Rewarding Drugs by Ibogaine LINDA A. PARKER AND SHEPARD SIEGEL

I. II. III. IV. V. VI.

Introduction Ibogaine-Morphine Interactions Ibogaine and Morphine Reward Ibogaine and Other Drugs of Abuse Ibogaine and Cravin: Future Directions Conclusions References

212 212 213 219 220 222 223

Anxiogenic Action of Ibogaine PIOTR POPIK AND MALGORZATA WROBEL

I. II. III.

Introduction Ibogaine and Anxiety Discussion References

227 229 231 232

"Returning to the Path": The use of Iboga[ine] in Equatorial African Ritual Context and the Binding of Time, Space, and Social Relationships JAMES W. FERNANDEZ AND RENATE L. FERNANDEZ

I. II. III. IV. V. VI.

Introduction Time Binding in Professional and Religious Worlds Pathologies of the Colonial World and the Role of Iboga in Religious Movements A Comparison of the Introduction and Maintenance of Iboga Use in Bwiti and in Therapeutic Settings (INTASH) The Contemporary of Ethnography of Iboga Use Conclusions References

235 236 237 239 243 247 247

A Contemporary History of Ibogaine in the United States and Europe KENNETH R. ALPER, DANA BEAL AND CHARLES D. KAPLAN

I. II. III. IV.

Introduction Ibogaine Treatment Scenes: History and Description The Political Subculture of Advocacy Conclusions References

250 250 267 277 279

From the Roots Up: Ibogaine and Addict Self-Help GEERTE FRENKEN

I. II. III. IV. V.

Introduction of Ibogaine and Addict Self-Help in the Netherlands Intake and Treatment Psychological Aspects of the Ibogaine Treatment Experience Aftercare Conclusions References

283 285 287 289 290 292

Case Studies of Ibogaine Treatment: Implications for Patient Management Strategies HOWARD S. LOTSOF AND NORMA E. ALEXANDER

I. II. III. IV. V. VI.

Introduction Drug-User Group Self-Help Organizations Regulatory Development and Clinical Research Settings Psychological Aftereffects Discussion References

293 294 298 302 306 309 312

CUMULATIVE INDEX OF TITLES INDEX

315 325

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