Iboga / Ibogaine An Overview with a Semi-Academic Approach 1 2. November 2008 Table of contents INTRODUCTION 6 IBOGA: GEOGRAPHY, HISTORY, CHEMISTRY & BIOLOGY 8 SHORT OVERVIEW 8 TRADITIONAL USE / HISTORY 9 BWITI CULTURE 10 CONTEMPORARY USE – BY SASHA SHULGIN FROM THIKAL 21 TABERNANTHE IBOGA USED BY ANIMALS 22 CHEMICAL PROPERTIES AND STRUCTURE 23 IBOGAINE HCL 23 SYNTHESIS 25 BIOLOGY: OTERH FORMS OF IBOGAINE AVAILABLE 26 TABERNANTHE IBOGA 26 VOACANGA AFRICANA 28 TABERNAEMONTANA 31 PLANTS CONTAINING IBOGAINE ACCORDING TO THIKAL 31 METHODS OF EXTRACTION 32 MAKING A TABERNANTHE IBOGA EXTRACT 32 ISOLATION OF IBOGAINE FROM TABERNANTHE IBOGA 33 EXTRACTION STUDIES OF TABERNANTHE IBOGA AND VOACANGA AFRICANA 34 PREPARATION OF V.AFRICANA EXTRACT 35 IBOGAINE FROM TRACHELOSPERMUM JASMINOIDES 35 18-METHOXYCORONARIDINE 26 PHARMACOLOGY 36 PHARMACOKINETICS AND METABOLISM 41 IBOGAINE ACTS AT THE NICOTINIC ACETYLCHOLINE RECEPTOR TO INHIBIT CATECHOLAMINE RELEASE 42 EFFECTS ON SPECIFIC NEUROTRANSMITTER SYSTEMS 42 EFFECTS 50 DURATION AND TYPICAL STAGES OF THE IBOGA EXPERIENCE 50 MECHANISMS OF ACTION 52 IBOGAINE FOR SELF-DEVELOPMENT 53 IBOGA VISIONS 54 THE CLINICAL SIGNIFICANCE OF IBOGAINE VISIONS 56 STIMULATING EFFECTS 57 VOMITTING 57 NEAR DEATH EXPERIENCES 59 SIDE-EFFECTS 60 IBOGAINE RELATED FATALITIES 60 2 U.S. MAN DIES AT ALTERNATIVE DETOX CLINIC IN TIJUANA 66 LETHALITY AND NEUROTOXIC EFFECTS 68 IBOGAINE NEUROTOXICITY 69 TOXICOLOGY 70 IBOGAINE NEUROTOXICITY: A RE-EVALUATION. 71 USAGE 72 SAFETY-RELATED INFORMATION 72 WOMEN 73 THOUGHTS ON SAFETY - EXCLUSION/INCLUSION REQUIREMENTS 74 BAD TRIPS 76 ADMINISTRATION 77 MINI-SESSIONS 79 INGESTING IBOGA/IBOGAINE 79 DOSAGE 80 IMPORTANT INFORMATION FOR THOSE THINKING OF TAKING IBOGAINE 80 TREATMENT REGIMEN AND DOSE 83 PRODUCT IDENTITY 85 INTAKE AND SAFETY ISSUES 88 INCLUSION CRITERIA 93 OTHER INCLUSION CRITERIA 94 EXCLUSION CRITERIA 95 OTHER EXCLUSION CRITERIA 96 TREATMENT LOCATION 98 SET AND SETTING 98 ADDICTION TREATMENT 99 FEAR OF DETOXIFICATION 99 OBSTACLES WITHIN TRADITIONAL TREATMENT 99 USE AGAINST ADDICTION 100 USE AS AN ANTI-ADDICTIVE 101 HISTORY OF ANTI-ADDICTIVE USE 102 IBOGAINE IN THE TREATMENT OF HEROIN WITHDRAWAL 104 IBOGAINE FOR COMBATTING DRUG DEPENDENCIES ACCORDING TO HOWARD LOTSOF 104 INTERESTING STUDIES CONCERNING IBOGAINE AND ADDICTION 109 DECREASED DRUG CRAVING DURING INPATIENT DETOXIFICATION WITH IBOGAINE 109 FACILITATION OF MEMORY RETRIEVAL BY THE “ANTI-ADDICTIVE” ALKALOID IBOGAINE 110 DEVELOPMENT OF IBOGAINE AS A PHARMACOTHERAPY FOR DRUG DEPENDENCE 111 TREATMENT OF ACUTE OPIOID WITHDRAWAL WITH IBOGAINE. 112 MECHANISMS OF ANTIADDICTIVE ACTIONS OF IBOGAINE. 112 FIGHTING THE URGE TO DRINK: MOLECULE MODERATES HEAVY-DRINKING RATS 113 OBSERVATIONS ON TREATMENT WITH IBOGAINE 115 PREPARATION OF A TREATMENT 116 THE PATIENT 116 3 TREATMENT PREPATATION 117 THE EXPERIENCE 118 OPTIMIZING THE IBOGAINE TREATMENT SETTING 121 AN IBOGAINE TREATMENT PROTOCOL 121 IMPORTANT RECOVERY TIPS THAT CAN HELP YOU STAY CLEAN 130 OTHER TIPS THAT ARE VERY HELPFUL 131 IBOGAINE VERSUS OTHER TREATMENT MODALITIES 131 IBOGAINE AND METHADONE 133 IBOGAINE IN PSYCHOTHERAPY: PSYCHOANALYSIS ACCORDING TO NARANJO 134 AFTER EFFECTS 139 POST IBOGAINE 139 POST IBOGAINE REHAB AND THERAPY 139 SEVEN MONTH POST-IBOGAINE-SESSION TIMELINE. 140 POST IBOGAINE PROBLEMS 143 PSYCHOLOGICAL AFTEREFFECTS 144 POST IBOGAINE TREATMENT THERAPY 144 IMMEDIATE PSYCHOLOGICAL EFFECTS FOLLOWING IBOGAINE TREATMENT 147 FURTHER STUDIES: ADDICTION TREATMENT, EFFECTS & SAFETY 149 ANIMAL STUDIES 149 1. LOCOMOTOR ACTIVITY. 149 2. TREMOR. 150 3. ANXIETY AND FEAR. 151 4. EFFECTS ON SELF-ADMINISTRATION OF OTHER DRUGS. 151 5. EFFECTS ON DRUG DEPENDENCE. 152 6. PAIN AND ANALGESIA. 153 7. AGGRESSION. 153 8. INTEROCEPTIVE PROPERTIES. 154 9. REINFORCING EFFECTS. 154 10. EFFECTS ON LEARNING AND MEMORY. 155 11. CARDIOVASCULAR ACTIONS. 155 EFFECTS OF IBOGA ALKALOIDS ON MORPHINE AND COCAINE SELF-ADMINISTRATION IN RATS: RELATIONSHIP TO TREMORIGENIC EFFECTS AND TO EFFECTS ON DOPAMINE RELEASE IN NUCLEUS ACCUMBENS AND STRIATUM. 155 IBOGAINE EFFECTS ON SWEET PREFERENCE AND AMPHETAMINE INDUCED LOCOMOTION: IMPLICATIONS FOR DRUG ADDICTION. 156 ACUTE AND PROLONGED EFFECTS OF IBOGAINE ON BRAIN DOPAMINE METABOLISM AND MORPHINE-INDUCED LOCOMOTOR ACTIVITY IN RATS. 157 EFFECTS AND AFTEREFFECTS OF IBOGAINE ON MORPHINE SELF-ADMINISTRATION IN RATS. 157 EFFECTS OF IBOGAINE ON ACUTE SIGNS OF MORPHINE WITHDRAWAL IN RATS: INDEPENDENCE FROM TREMOR. 158 LONG-LASTING IBOGAINE PROTECTION AGAINST NMDA-INDUCED CONVULSIONS IN MICE. 158 ENHANCEMENT OF MORPHINE ANTINOCICEPTION BY IBOGAINE AND NORIBOGAINE IN MORPHINE- TOLERANT MICE. 159 THE EFFECTS OF SIGMA, PCP, AND OPIATE RECEPTOR LIGANDS IN RATS TRAINED WITH IBOGAINE AS A DISCRIMINATIVE STIMULUS. 159 4 HUMAN STUDIES. 160 PHARMACOKINETICS, SAFETY, AND PRELIMINARY EFFICACY MEASURES 161 MODULATION OF MORPHINE-INDUCED ANTINOCICEPTION BY IBOGAINE AND NORIBOGAINE. 166 REPORTS & REVIEWS OF USERS 166 LINKS ON REPORTS / EXPERIENCES OF T.IBOGA USE 166 USE OF IBOGAINE HCL: REPORTS/EXPERIENCES 167 VOCANGA AFRICANA EXPERIENCES / REPORTS 168 EXPERIENCES / REPORTS OF TABERNAEMONTANA USE 168 ART INSPIRED BY IBOGA 180 "THE RISE AND FALL OF ADDICTION" - IN MEMORY OF THE LATE PAUL KATAN 180 LEGAL STATUS 182 INSURANCE 182 LEGALITY 182 DRUG TESTING 183 PATENTS ON IBOGA 184 OPTIONS FOR TREATMENT 184 FURTHER LITERATURE 189 WEBSITES ABOUT IBOGA 189 BOOKS 189 ARTICLES 190 ARTICLES ON 18-METHOXYCORONARIDINE 219 5 Introduction "The Catholic church is a beautiful theory for Sunday, the iboga on the contrary is the practice of everyday living. In church, they speak of God, with iboga, you live God" (Nengue Me Ndjoung Isidore, ecumenical Bwitist religious leader)1 Ibogaine's development as a putative treatment of substance-use disorders may certainly be described as unusual. In Western Europe and the United States, the use of ibogaine originated among individuals using drugs for the purpose of altering consciousness in the early 1960s, a period identified historically with the widespread introduction, and ethnographic and ethnobotanical studies of hallucinogens. The work of Timothy Leary and R. Gordon Wasson , as well as the media attention focused on psychedelics, led to the establishment of the group, in which ibogaine's apparent utility to treat opiate, cocaine, and amphetamine dependence was first described. Historically, the lines of this research can be traced to Aldous Huxley and Lewis Lewin and, with some liberty, into prehistory. This chapter reviews the use of ibogaine in three different contexts; a drug user group, a self-help organization, and a clinical research setting. Each section is followed by the self-report of a subject who has taken ibogaine within the setting being reviewed. These settings contrast with the use of iboga in Gabon, Africa as a practice of the Bwiti, an African religion sometimes referred to as an initiation society, as documented by Fernandez and Gollnhofer, during which ibogaine-containing plants are provided in rites to assist in the transition from adolescence into adulthood, for psychiatric healing, or for other purposes.2 Ibogaine therapy has emerged in the last twenty years as a viable option for motivated chemically dependent individuals who wish to cease their dependence. The extremely costly regulatory approval process and the reluctance by major pharmaceutical firms to pursue regulatory approval in the West has led to the formation of non-medical ibogaine treatment movements in many countries. This document is intended for medical doctors as well as, for lay-healers who have little or no medical experience, but who are nevertheless concerned with patient safety and the outcome of Ibogaine treatments. The NIDA draft clinical protocol, however, may be useful to researchers in formal drug development. It is the responsibility of those treatment providers to safely conduct the procedure despite possible limitations of clinical knowledge, patient compliance, money, time etc. The safety of Ibogaine treated patients is the primary objective of this document. Reported Ibogaine-related problems or fatalities might very likely be avoided if simple screening, dosing and monitoring guidelines are adhered to. However, this must be taken 1 http://www.ebando.org/en/EN.iboga.htm 2 http://www.doraweiner.org/alexanderlotsof.html 6 in some context as, in 1999 there were 116,000 drug related fatalities in United States hospitals associated with FDA approved medications. This manual includes selected portions of the National Institute on Drug Abuse (NIDA) Draft Ibogaine Clinical Protocol obtained under a Freedom of Information Act (FOIA) request. Selections are principally directed towards safety issues. Aspects of the therapeutic sessions from the NIDA protocol are included as well as, bibliographical citations relevant to the sections from the protocol. More recent reports providing updated information are included in the Additional Documents section. Any comments of the author(s) within the selected protocol text are indicated by "[ ]" brackets. The "*" asterisk is used to indicate tests procedures or surveys not included in NIDA's 1993, draft protocol but, suggested either in discussion with the FDA or by later publication. In a memorandum dated March 10, 1995, Dr. Curtis Wright, Medical Review Officer, Pilot Drug Evaluation Unit, FDA wrote, "I think that ibogaine research will be propelled forward by its advocates, as it will be very hard to make a case that it is unsafe to take a drug into man when there is such substantial documented human