The ibogaine medical subculture

The Ibogaine Dossier

NYU Conference on Ibogaine Nov 5-6, 1999

variety iboga fruit

T. iboga roots

Spiritual Entity
Mitsogo Bwiti
Photo by Gollnhofer

Graphic
Art Buro, Amsterdam
Squatter Movement

Prepared for ICASH
International Coalition
for Addict Self-Help

The ibogaine medical subculture

Journal of Ethnopharmacology 115 (2008) 9-24

Kenneth R. Alper ^a,b, Howard S. Lotsof ^c, Charles D. Kaplan ^d
^a Department of Psychiatry, New York University School of Medicine, New York, NY 10016, USA
^b Department of Neurology, New York University School of Medicine, New York, NY 10016, USA
^c Dora Weiner Foundation, 46 Oxford Place, Staten Island, NY 10301, USA
^d Department of Psychiatry and Neuropsychology, Maastricht University, 6200 MD Maastricht, The Netherlands

Elsevier © 2008 doi:10.1016/j.jep.2007.08.034

Abstract

Aim of the study: Ibogaine is a naturally occurring psychoactive indole alkaloid that is used to treat substance-related disorders in a global medical subculture, and is of interest as an ethnopharmacological prototype for experimental investigation and possible rational pharmaceutical development. The subculture is also significant for risks due to the lack of clinical and pharmaceutical standards. This study describes the ibogaine medical subculture and presents quantitative data regarding treatment and the purpose for which individuals have taken ibogaine.

Materials and methods: All identified ibogaine "scenes" (defined as a provider in an associated setting) apart from the Bwiti religion in Africa were studied with intensive interviewing, review of the grey literature including the Internet, and the systematic collection of quantitative data. Results: Analysis of ethnographic data yielded a typology of ibogaine scenes, "medical model", "lay provider/treatment guide", "activist/selfhelp", and "religious/spiritual". An estimated 3414 individuals had taken ibogaine as of February 2006, a fourfold increase relative to 5 years earlier, with 68% of the total having taken it for the treatment of a substance-related disorder, and 53% specifically for opioid withdrawal.

Conclusions: Opioid withdrawal is the most common reason for which individuals took ibogaine. The focus on opioid withdrawal in the ibogaine subculture distinguishes ibogaine from other agents commonly termed "psychedelics", and is consistent with experimental research and case series evidence indicating a significant pharmacologically mediated effect of ibogaine in opioid withdrawal. © 2007 Elsevier Ireland Ltd. All rights reserved.

Keywords: Ibogaine; Iboga alkaloid; Substance-related

1. Introduction

Ibogaine is the most studied of the iboga alkaloids (Bartlett et al., 1958), a group of naturally occurring and synthetic indole alkaloids, some of which reportedly reduce opioid withdrawal symptoms and drug self-administration in humans (Luciano, 1998; Alper et al., 1999; Mash et al., 2001) or preclinical models (Glick et al., 2001). Presently in the setting of homes, hotel rooms and private clinics in North America and Europe, individuals in increasing numbers are taking ibogaine in what has been termed, "a vast uncontrolled experiment" (Vastag, 2005).

1.1. History

The ritual eating of iboga has been a psychopharmacological sacrament in the Bwiti religion for several centuries, and was likely practiced among Pygmies in much earlier times (Fernandez, 1982). In Gabon and elsewhere in West Central Africa, ibogaine is ingested in the form of scrapings of Tabernanthe iboga root bark. The ritual aim of eating iboga has been conceptualized as "binding"; the binding across time through ancestral contact, or binding participants socially on the basis of a common shared experience of a distinctive consciousness and system of belief (Fernandez, 1982; Fernandez and Fernandez, 2001). In the colonial era Bwiti became a context of collective psychological resistance to the anomie and demoralization related to the strain on indigenous community and family institutions. Bwiti offered a dignified realm of spiritual endeavor, "the work of the ancestors" and social cohesion. Following Gabonese independence in 1960, Bwiti has remained constellated with national identity and contemporarily retains significant social and political importance (Swiderski, 1988; Samorini, 1995).

Iboga has not commonly been used to treat addiction in the traditional African Bwiti context. Iboga has been sought as a treatment for some somatic conditions, in particular for infertility (Fernandez, 1982). In the colonial era the indigenous community experienced a crisis due to a sharp decline in fertility caused by venereal disease stemming from prostitution and the separation of men from their families by the large-scale physical relocation of indigenous workers. The possibility of an objective basis for the use of iboga in this setting is suggested by evidence associating iboga alkaloids with antimicrobial activity or effects on cell-mediated immunity. Iboga alkaloids are reportedly active against Candida albicans in the intact animal (Yordanov et al., 2005). In vitro studies indicate reversal of multidrug resistance in human cancer cells (Kam et al., 2004) and activity against Mycobacterium tuberculosis (Rastogi et al., 1998), human immunodeficiency type 1 virus (Silva et al., 2004), and the tropical parasite Leishmania amazonensis (Delorenzi et al., 2002).

The first observation of ibogaine as treatment for substance related disorders in 1962 involved a network of lay drug experimenters who ingested a variety of hallucinogens and systematically recorded their experiences (Lotsof and Alexander, 2001). Withdrawal symptoms were unexpectedly absent in heroin-dependent individuals who had taken ibogaine. Common to various sociological definitions of the term "subculture" is a system of beliefs, norms and values apart from a superordinate culture (Clarke, 1974; Dowd and Dowd, 2003). The ibogaine subculture has elicited wariness from the "superordinate culture" of conventional clinical medicine (Kleber, 2001), and has been invoked regarding the null hypothesis that ibogaine's reported effect in opioid withdrawal is not pharmacologically mediated, but is instead accounted for by suggestion and ritual (Sharpe and Jaffe, 1990). The ibogaine subculture is also significant as the setting of case report evidence that influenced the decision of the National Institute on Drug Abuse (NIDA) to pursue its ibogaine project (Alper, 2001), and the Food and Drug Administration (FDA) to approve a clinical trial (Mash et al., 1998).

Ibogaine is unscheduled in most of the world, with the exception of the US, Belgium, Denmark, France, Sweden, Switzerland, and Australia where it is illegal. Ibogaine has not been popular as a recreational drug regardless of its legal status (Kleber, 2001), and apparently only two arrests involving ibogaine are known to have occurred in the US (Ranzal, 1967; Lane, 2005). Iboga alkaloids reportedly are not self-administered, and do not produce withdrawal signs following chronic administration in animals (Aceto et al., 1992). As of late 2006, ibogaine hydrochloride (HCl)was available for $400-$500 USD per gram (ethnogarden.com, 2006), and the dosage typically used for opioid withdrawal is in the range of 1-2 g. Purity on the order of 97-98% has been reported on certificates of analysis for supplies of ibogaine HCl used in the subculture. Ibogaine is also available as Tabernanthe iboga extract or dried root bark.

1.2. Clinical use

Ibogaine, either as Tabernanthe iboga root bark or ibogaine HCl is the only iboga alkaloid that has reportedly been administered to humans, with apparently only one exception, a study in which 12 normal volunteers were evaluated with some brief neuropsychological tests after receiving the naturally occurring iboga alkaloid ibogaline (Schmid, 1967). Ibogaine HCl has been typically administered as a single oral dose in the range of 10-25 mg/kg of body weight. Patients physically dependent on opioids have described significant attenuation of withdrawal symptoms within several hours of ingesting ibogaine, with subsequently sustained resolution of the opioid withdrawal syndrome (Alper et al., 1999; Mash et al., 2001). The advantages attributed to ibogaine are higher tolerability relative to other standard treatments for acute opioid withdrawal, and an interval of diminished drug craving that may last days to months following a treatment. Individuals also take ibogaine in search of psychological or religious insight, typically at dosages lower than those used in the treatment of opioid withdrawal.

There are no randomized controlled clinical trials of ibogaine, and the available clinical data is limited mainly to two open label case series. One series from the US and the Netherlands included self-reported outcomes of a consecutive series of 52 treatments involving 41 different individuals, some of who were treated on multiple occasions mainly for the indication of dependence on opioids or stimulants (Alper, 2001). Thirty-six percent of the treatments were associated with self-reported intervals of 6 months or longer of abstinence from the primary drugs of dependence for which treatment had been sought.Asubset of 33 individuals were treated for the indication of opioid withdrawal with a single dose of ibogaine averaging 19.3 mg/kg (Alper et al., 1999). Twenty-five of these patients had full resolution of opioid withdrawal without drug seeking behavior that was sustained throughout a 72-h period of post-treatment observation, and another four individuals denied withdrawal symptoms but expressed their preference to continue to use heroin. The other series, from a clinic in St. Kitts consists of 32 patients treated with a fixed dose of 800 mg of ibogaine HCl for the indication of withdrawal from heroin (Mash et al., 2001). Physician-rated structured instruments indicated resolution of withdrawal signs and symptoms at 24 h after the last use of opioids (an interval of abstinence commonly associated with significant withdrawal symptoms) thatwas sustained during subsequent observation for 1 week following ibogaine administration.

An unpublished Dutch doctorandus thesis (Bastiaans, 2004) presents data obtained from 21 subjects who responded to a Web-based questionnaire adapted from the European Addiction Severity Index a mean of 21.8 months after they had taken ibogaine for treatment of a substance-related disorder. Seventeen of the 21 patients (81%) identified opioids as the primary drug of dependence for which they had sought treatment. Five individuals reported stopping the use of all substances following treatment with ibogaine, and another nine reported stopping the use of their primary drug while continuing to use alcohol or cannabis. Nineteen patients reported stopping their use of their primary drug for at least a week following treatment, suggesting frequent resolution of acute opioid withdrawal.

1.3. Preclinical research

Research utilizing animal models has involved the iboga alkaloids ibogaine (Alper, 2001) and its desmethylated metabolite noribogaine (Baumann et al., 2001), and a synthetic congener, 18-methoxycoronaridine (18-MC) (Maisonneuve and Glick, 2003). Eleven of the 13 published preclinical studies of iboga alkaloids in opioid withdrawal indicate a significant attenuation of opioid withdrawal signs in the rat (Dzoljic et al., 1988; Sharpe and Jaffe, 1990; Maisonneuve et al., 1991; Glick et al., 1992; Cappendijk et al., 1994; Rho and Glick, 1998; Parker et al., 2002; Panchal et al., 2005), mouse (Frances et al., 1992; Popik et al., 1995; Layer et al., 1996; Leal et al., 2003), and primate (Aceto et al., 1992). Iboga alkaloids are also reported to reduce the self-administration of morphine (Glick et al., 1991; Glick et al., 1994; Glick et al., 1996; Maisonneuve and Glick, 1999; Pace et al., 2004), cocaine (Cappendijk and Dzoljic, 1993; Glick et al., 1994), amphetamine (Maisonneuve et al., 1992), methamphetamine (Glick et al., 2000; Pace et al., 2004), alcohol (Rezvani et al., 1995; Rezvani et al., 1997; He et al., 2005) and nicotine (Glick et al., 1998; Glick et al., 2000), and to diminish dopamine efflux in the nucleus accumbens (NAc), which is regarded as a correlate of drug salience (Berridge, 2007), in response to opioids (Maisonneuve et al., 1991; Glick et al., 1994; Glick et al., 2000; Taraschenko et al., 2007b) or nicotine (Benwell et al., 1996; Maisonneuve et al., 1997; Glick et al., 1998).

1.4. Mechanisms of action

Initially, ibogaine's mechanism of action was hypothesized to involve antagonism at the N-methyl-d-aspartate-type glutamate (NMDA) receptor (Skolnick, 2001). However, 18-MC, which has negligible NMDA receptor affinity, also reduces opiate withdrawal and drug self-administration in the animal model (Glick et al., 2001). Antagonism of the α3β4 nicotinic acetylcholine receptor (nAChR) is a possible mechanism of action, as indicated by a series of studies of iboga alkaloids and nicotinic agents (Fryer and Lukas, 1999; Glick et al., 2002a,b; Pace et al., 2004; Taraschenko et al., 2005). The α3β4 nAChR is relatively concentrated in the medial habenula and interpeduncular nucleus, where 18-MC's antagonism of α3β4 nAChRs diminishes sensitized dopamine efflux in the NAc (Taraschenko et al., 2007a,b).

Ibogaine's mechanism of action has frequently been suggested to involve the modification of neuroadaptations related to prior drug exposure (Rabin and Winter, 1996b; Popik and Skolnick, 1998; Alper, 2001; Glick et al., 2001; Sershen et al., 2001; Levant and Pazdernik, 2004). Ibogaine may modulate intracellular signaling linked to opioid receptors, and potentiates the morphine-induced inhibition of adenylyl cyclase (AC) (Rabin and Winter, 1996b), an effect that is opposite to the activation of AC that is classically associated with opioid withdrawal (Sharma et al., 1975). In animals, ibogaine enhances the antinociceptive effect of morphine or other opioids without by itself having an effect on nociception (Schneider and McArthur, 1956; Schneider, 1957; Frances et al., 1992; Bagal et al., 1996), and inhibits the development of tolerance to morphine antinociception (Cao and Bhargava, 1997). Prior exposure to morphine potentiates ibogaine’s diminution of sensitized dopamine efflux in the NAc in response to morphine (Pearl et al., 1996) or ibogaine's enhancement of morphine antinociception (Sunder Sharma and Bhargava, 1998), suggesting an effect on neuroadaptations related to opioid tolerance or dependence.

Increased glial cell line-derived neurotrophic factor (GDNF) in the ventral tegmental area has been suggested to mediate decreased ethanol consumption following the administration of ibogaine to rats (He et al., 2005; He and Ron, 2006). GDNF enhances the regeneration of dopaminergic function (Ron and Janak, 2005) and is increased by antidepressant treatment (Hisaoka et al., 2007). The hypothesis that GDNF may mediate improvement in hedonic functioning and mood in chronic withdrawal from addictive substances is appealing, but does not appear likely to explain efficacy in acute opioid withdrawal.

Although designated as a hallucinogen, ibogaine's use in opioid withdrawal distinguishes it from other compounds that are commonly termed "psychedelics", namely the serotonin type 2A receptor agonist classical hallucinogens such as lysergic acid diethylamide (LSD), psilocybin and mescaline, or the serotonin releasing substituted amphetamine 3,4-methylenedioxymethamphetamine (MDMA). In contrast with ibogaine, there is no preclinical or case report evidence that suggests a significant therapeutic effect of classical hallucinogens or MDMA in acute opioid withdrawal. Ibogaine's effects in opioid withdrawal do not appear to involve serotonin agonist or releasing activity (Wei et al., 1998; Glick et al., 2001). Serotonergic neurotransmission does not appear to play a significant role in mediating the expression of the opioid withdrawal syndrome, which remains unchanged even after extensive lesioning of the raphe (Caille et al., 2002).

The phenomenology of the subjective state produced by ibogaine has been attributed with the quality of a "waking dream" and distinguished from the state associated with classical hallucinogens (Goutarel et al., 1993; Lotsof and Alexander, 2001). The visual phenomena associated with ibogaine tend to occur with greatest intensity with the eyes closed, and to be suppressed with the eyes open, and often involve a sense of location within an internally represented visual or dream landscape, in contrast to an alteration of the visual environment experienced with the eyes open while awake which is often reported with classical hallucinogens. The occurrence of an atropine-sensitive electroencephalogram (EEG) rhythm in animals treated with ibogaine (Schneider and Sigg, 1957; Depoortere, 1987) suggests a waking neurophysiological state with an analogy to rapid eye movement sleep (Goutarel et al., 1993; Alper, 2001).

1.5. Research objectives of this study

A previous publication provides a history and description of the ibogaine subculture in the U.S. and Europe from its origin in 1962 until early 2001 (Alper et al., 2001). The major objectives of this study are the qualitative analysis of observational and textual data (Bailey, 1994; Malterud, 2001) to provide an updated description as well as a typology of the ibogaine medical subculture, and the systematic collection of quantitative data regarding treatment and the purpose for which individuals took ibogaine.

2. Methods

The Institutional Review Board of the New York University School of Medicine approved this research.

2.1. Observational methods

The providers of ibogaine treatment were conceptualized as participants in a global medical subculture and studied from an "observing participant" research perspective (Gold, 1958). The qualitative and quantitative information was obtained from face to face discussions, phone conversations and e-mail correspondence with treatment providers and other participants.

2.2. Study sample

The study included only treatment providers who had already publicly identified their activities by maintaining Web sites, publishing in the lay or scientific press, presenting at public meetings, or posting to ibogaine list servers. Because ibogaine is not regulated in most of the world, providers are very often open about their activity.

A "scene" is defined in this study as a provider of ibogaine in an associated setting. The term "ibogaine subculture" refers to all ibogaine scenes collectively outside of Africa. The sample in this study that represented the ibogaine subculture consisted of all known presently or previously existing ibogaine scenes outside of Africa involving publicly identified providers, with the exception of a scene in Gabon which was included that involved European and US participants and African Bwiti adept providers. Otherwise no systematic attempt was made to study the Bwiti religious context in Africa. No data was encountered regarding the use of Lambarene, a tablet that was marketed in France between 1939 and 1970 that contained an estimated 8mg of ibogaine (Goutarel et al., 1993).

2.3. Excluded scenes

A large ibogaine scene was alleged to have existed in the Christiana squatter community in Copenhagen but was concluded to lack corroborative evidence on the basis of communication with the Danish Drug Users Union and former Christiana residents (Alper et al., 2001). Reported ibogaine scenes in Pakistan and Thailand were not included due to lack of independent verification. Due to the inability to obtain quantitative data, the study did not include a sample of probably about 20 individuals who were provided ibogaine by Dan Lieberman, a South African ethnobotanist who died in a motor vehicle accident in August 2000. Psychologist Leo Zeff and others administered ibogaine (typically as a single doses in the range of 150-300 mg) and other hallucinogens as an adjunct to psychotherapy beginning in the 1950s in a scene that existed on the West Coast of the US (Stolaroff, 2004) that was excluded due to a lack of quantitative data.

2.4. Data collection

The data collection for this study began with a previously published description and history of the ibogaine subculture as of early 2001 (Alper et al., 2001). The authors subsequently continued their contact with the ibogaine subculture by email, phone, and in person. Quantitative information thatwas assessed systematically from the providers included cumulative numbers of people treated, percentage seeking treatment for addiction and specifically acute opioid withdrawal, as well as ibogaine form and dosage and the cost of treatment. The approach to pretreatment medical screening and laboratory evaluation, and monitoring during the treatment was also discussed. The estimates of cumulative numbers of subjects treated obtained from providers are current as of February 2006 except for the figure for the St. Kitts Clinic, which is taken from an abstract published in June 2005 (Mash et al., 2005).

To determine if any further scenes existed in addition to those of which the authors were aware, in May of 2005 a series of messages was posted to Mindvox (Kroupa, 2006), the most frequently used ibogaine list server. The Internet, which is an important aspect of the ibogaine subculture and comprises an extensive unpublished "grey literature" (Boukacem-Zeghmouri and Schöpfel, 2006) was searched monthly from May 2005 to February 2006 using the terms "ibogaine" or "iboga" alone, and combined with the term "treatment". The list server postings and Internet searches yielded no usable information regarding new scenes that had not already been previously obtained by longstanding, ongoing contact with subculture participants. In May of 2005, and again near the conclusion of data gathering in February 2006, all known treatment providers were systematically contacted to update the quantitative information. The typology of scenes was created between the first and second data collections.

The study also reviewed the academic literature, and the "white literature" (Boukacem-Zeghmouri and Schöpfel, 2006) including public media and officially published government or industrial documents. Databases with white literature content including ProQuest, LexisNexis, and the New York Times, and academic literature databases including PubMed, PsycInfo, JSTOR, UMI Dissertation Abstracts, WorldCat, and the SAGE Sociology Full-Text Collection were searched utilizing the terms "ibogaine" and "iboga". The references cited by the articles retrieved utilizing the above searches were reviewed until they no longer yielded new references containing the search terms. The above searches yielded relatively little material that was new to the authors because of their extensive prior use of the iboga alkaloid conventional and nonconventional literature, as well as substantial access to ibogaine-related material that is not indexed in any searchable database (Lotsof, 1985; Alper, 2001; Alper et al., 2001; Lotsof and Wachtel, 2003; Lotsof, 2007).

2.5. Data validation

Triangulation of the data, i.e., viewing the data from multiple observational perspectives (Malterud, 2001; Denzin and Lincoln, 2005), was possible for all of the currently operating scenes listed in Table 1 on the basis of independent corroboration from provider and patient participants in the same scenes, providers regarding other providers, and other informants. Most treatment providers interviewed in the present study had previously supplied data that was published 5 years earlier (Alper et al., 2001) and were known to at least two of the authors. For three medical model scenes that no longer exist (Lexington 1955-1956, Santiago 1966-1967, and Zürich 1980-1989) textual evidence was used for validation. This study omitted providers who had not publicly disclosed their activity, which would tend to lead toward underestimation of the total numbers of individuals who have taken ibogaine. This is particularly likely for scenes involving small numbers of patient participants, such as individuals obtaining ibogaine from the Internet. In order to account for this effect, estimates of hidden populations were obtained from individuals with extensive contact with the subculture as described below in Section 3.2.

2.6. Data analysis

A typology of scenes was constructed (Bailey, 1994), based on the classificatory dimensions of setting and the provider's set and credentials. The setting is the physical and ecological location in which the treatment takes place: a clinic or hospital, a private residence or hotel, or a religious shrine. A provider is an individual or group that administers ibogaine to the patient participant, and specifies the form and dose to be given. The provider determines the parameters of the treatment such as setting, inclusion and exclusion criteria, and medical monitoring. Providers may or may not have a credential as a licensed physician. The provider's set consists of the beliefs, expectations, attitudes and motivation that determine the intention to provide ibogaine. Provider set subsumes beliefs and expectations regarding ibogaine as a treatment for substance-related disorders, a psychotherapeutic adjunct, or religious sacrament. Motivational aspects of set may include the giving of care, activism, or ritual.

Quantitative data included the number of individuals who took ibogaine, and the number who took it for the treatment of a substance-related disorder, and specifically for acute opioid withdrawal. This data for each scene was included in Table 1, and the totals for each of the four types of scenes are indicated in Table 2.

3. Results

3.1. Typology

As indicated in Table 1, four types of scenes were identified and classified on the basis of the features of treatment setting, provider credentials and provider set; "medical model", "lay provider/guide", "activist/self-help" and "religious/ceremonial".

3.1.1. Medical model

In this type of scene the provider is a licensed physician. In the variation of the medical model type involving clinical research, some roles of the provider are distributed among authors of the study protocol and the physician investigator who prescribes ibogaine. Settings of the medical model are medical hospitals or clinics, or clinical research facilities, which are officially credentialed according to national and local requirements in a given country, as well as offices or residential settings in the case of treatment intended as psychotherapy. The set of the treatment provider includes the aim of emulating existing conventional medical standards in the treatment of addiction, clinical research, and/or psychotherapy.

Historically, the use of ibogaine in the medical model began in the 1950s, when clinicians and researchers viewed ibogaine much as they did other compounds classified as hallucinogens. Some, such as Jan Bastiaans, M.D. (Snelders and Kaplan, 2002), Leo Zeff, Ph.D. (Stolaroff, 2004), and Claudio Naranjo, M.D. (Naranjo, 1973), were interested in ibogaine as an adjunct to psychotherapy. Ibogaine, like other hallucinogens,was of interest as an experimental model of psychosis (Turner et al., 1955; Fabing, 1956; Salmoiraghi and Page, 1957; Schneider and Sigg, 1957). As with other hallucinogens, ibogaine may have also been investigated for military or intelligence purposes as a "truth serum", or a means of "brainwashing" or incapacitating an adversary which was the focus of MKULTRA (1977), a US Central Intelligence Agency project acknowledged to have existed from 1953 until 1964. Harris Isbell, M.D., an apparent participant in the MKULTRA project, directed the Addiction Research Center in Lexington, Kentucky where he reported administering ibogaine to human subjects in a letter to the Ciba Pharmaceutical, the manufacturer at that time (Isbell, 1955).

The medical treatment model presently exists mainly in countries adjacent to the US, such as Mexico, where ibogaine is subsumed within a physician's legal prerogative to prescribe experimental treatment, or Saint Kitts, where the government includes ibogaine in its national formulary and provides specific approval to the clinic there to administer it. The most common setting is a private clinic with less frequent use of hospitals. The clinics' Web sites tend to emphasize images that suggest comfort, safety, and the experience and expertise of the clinical team.

The standard of care varies among scenes in the medical model, but typically at a minimum involves pretreatment laboratory and electrocardiogram (EKG), vital signs and evaluation of the medical and psychiatric history, and some participation of nurses and physicians. The most intensive approach appears to have been that developed at the St. Kitts clinic (see Table 1). A recently started clinic in Mexico reported a similar clinical standard (villaserena.org, 2006). Prior to treatment with ibogaine, opioid dependent patients are converted to equivalent doses of orally administered short acting opioids. All centrally acting medications are tapered and discontinued for at least three serum half lives, although no specific drug interactions with ibogaine have yet been identified. Evaluation includes pretreatment Holter monitor and 12 lead EKG, and the following continuously during the treatment: EKG, vital sign and pulse oximetry monitoring, intravenous access, and the presence on site of an emergency physician with advanced cardiac life support certification and a registered nurse in the room with the patient continuously throughout the treatment (Mash et al., 2000, 2001).

Table 1
Ibogaine scenes: quantitative and descriptive features, grouped by scene type

Scene, year began- (year ended, if applicable) Reason for taking ibogaine: n^a, n(%)^b [n (%)]^c Other non-substance-related reason for taking ibogaine Dose/form Setting/provider, medical evaluation and monitoring Cost

Medical model type

US, 1955 Lexington, KY (Isbell, 1955) 8 (research, subjects not seeking treatment) Research, determination of psychoactive threshold 50-300 mg ibogaine HCl Clinical research, US Public Health Service Hospital, Lexington, KY; Harris Isbell, M.D. Subjects were prisoners with prior histories of opioid dependence who had been abstinent for periods of months Volunteers / prisoners

Chile, 1966-1967 Santiago (Naranjo, 1973) 30 None Adjunct to psychotherapy 3-5 mg/kg ibogaine HCl Claudio Naranjo, M.D., psychiatrist. Ibogaine administered in office setting in context of ongoing psychotherapy N/A

Switzerland, 1980-1989 Zurich (Prins, 1988) 34 None Adjunct to psychotherapy 4-10 mg/kg ibogaine HCl Peter Baumann M.D., psychiatrist. Ibogaine administered in office or residential setting, given in context of ongoing psychotherapy N/A

US, 1994-1995 Miami FL (Mash et al., 1998) 15 (Phase I clinical trial subjects not seeking treatment) FDA approved clinical research 1-4 mg/kg ibogaine HCl Phase I/II dose-ranging study. Juan Sanchez-Ramos, Ph.D., M.D., Principal Investigator, Deborah Mash, Ph.D., Co-Investigator. Jackson Memorial Hospital in Miami Volunteers

Panama, 1994-1995 Panama City (Luciano, 1998) 11, 11 (100%)
[9 (82%)] Substance dependence only 10-25 mg/kg ibogaine HCl Hospital Centro Medico Paitilla, full medical staff. Pretreatment evaluation included EKG, blood chemistry, medical and psychiatric history No cost to $35,000 USD

Brazil, 1994-Sao Paulo (Sandberg,2006) 9, 9 (100%)
[1 (11%)] Substance dependence only 10-20 mg/kg ibogaine HCl Hospital Maternidade Maria Perpetua Piedade Goncalves, full medical staff. Pretreatment evaluation includes EKG, blood chemistry, medical and psychiatric history $3000 USD

St. Kitts, 1996- (Mash et al., 2001) 400, 400 (100%)
[316 (79%)]^d Substance dependence only 600-1200 mg ibogaine HCl See text for description of the approach to medical evaluation and< monitoring developed by Jeffrey Kamlet, M.D $10,000 - $12,500 USD

Mexico, 2001- Playas de Tijuana, Baja California (Ibogaine Association, 2006) 283, 252 (89%)
[186 (74%)] psychotherapeutic, spiritual 12-18 mg/kg ibogaine HCl Clinic or hospital. Pretreatment evaluation includes EKG, blood chemistry, medical and psychiatric history. Continuous EKG monitoring and presence of a nurse in the room with the patient during the treatment $4000 USD

Mexico, 2005- Cancun (villaserena.org, 2006) 34, 34 (100%)
[6 (18%)] Substance dependence only 8-18 mg/kg ibogaine HCl Clinic, private rooms. See text regarding medical evaluation and monitoring $6000 USD

Lay provider/guide type

US, 1962-1963 New York City (Lotsof and Alexander, 2001) 20; none sought treatment, 7 were opioid dependent Lay experimentation and research, Psychotherapeutic 0.14-19.0 mg/kg ibogaine HCl Apartments, private homes. No medical support. Self-administration and systematic self-observation $15 USD for 500 mg

Central America, Caribbean, 1993- (Taub, 2006) 607, 455 (75%)
[309 (68%)] Psychotherapeutic, spiritual 9-36 mg/kg ibogaine HCl Rented cottages in resort settings, private residences. Pretreatment medical and psychiatric history, EKG and blood chemistry No cost to $4000 USD

Italy/France, 1994- (Naeher, 2006) 101, 44 (44%)
[34 (77%)] Psychotherapeutic, spiritual 10-23 mg/kg ibogaine HCl Apartment. Physician available. Pretreatment medical and psychiatric history, EKG and blood chemistry $1500 USD

Netherlands, 1999- Breukelen (Glatt, 2006) 200, 160 (80%)
[144 (90%)] Psychotherapeutic, spiritual 2-6 g Tabernanthe iboga extract (estimated 15% ibogaine) Private home. Use of other "plant medicine or fungi" in combination with ibogaine. Pretreatment medical and psychiatric history, no medical testing No cost to $2000 USD

Czech Republic, 2000- (Mariano, 2006) 102, 94 (92%)
[73 (71%)] Psychotherapeutic, spiritual 900-1600 mg ibogaine HCl Apartments and private homes. Medical assessment by local consulting clinic, including medical and psychiatric history, EKG and blood chemistry £600 GBP

UK, 2000- London, West Sussex (Conn, 2006; Wells, 2006) 83, 54 (65%)
[46 (85%)] Psychotherapeutic, spiritual 14-20 mg/kg, or 250-2000 mg ibogaine HCl Multiple Providers; apartment or private home. Pretreatment medical and psychiatric history, EKG and blood chemistry £400 - £850 GBP

Canada, 2002-Vancouver, Toronto (ibogatherapyhouse.net, 2007) 64, 52 (81%)
[36 (69%)] Psychotherapeutic, spiritual 16-23 mg/kg ibogaine HCl Multiple Providers; dedicated clinic, private residences. Pretreatment medical and psychiatric history, EKG and blood chemistry. Emergency medical technician on premises during treatment at clinic $1000 - $3500 CAD

South Africa, 2004- Eldoraigne (Rossouw, 2006) 36, 36 (100%)
[23 (64%)] Substance dependence only 15-19 mg/kg ibogaine HCl Treatments conducted in private residences. Pretreatment medical and psychiatric history, EKG and blood chemistry. Arrangement for very rapid response emergency medical support $3000 USD

Activist/Self-Help type

Netherlands, 1989-1993 Rotterdam, other Dutch cities (Alper et al., 2001) 40, 40 (100%)
[37 (93%)] Substance dependence only 10-29 mg/kg ibogaine HCl Multiple treatment providers; private residences and hotels. Pre and post-treatment medical evaluation. Strong involvement of activist drug user network No cost to $18,000 USD

US, 2003- New York, San Francisco, other U.S. cities (Freedomroot.com, 2007) 160, 160 (100%)
[152 (95%)] Substance dependence only 21-24 mg/kg ibogaine HCl The "ibogaine underground"; multiple treatment providers. Private residences and hotels. Pretreatment medical and psychiatric history, EKG and blood chemistry No cost to $1500 USD

Religious/Ceremonial type

Slovenia/Croatia, 1995- Ljubljana (Sacrament of Transition, 2006) 433, 424 98%
[403 (95%)] Psychotherapeutic, spiritual 20 mg/kg ibogaine HCl Religious Ritual, treatment guide/priest. The Republic of Slovenia officially recognizes the Church of the Sacrament of Transition as a religion. Private homes. Initiates are interviewed and sign a statement attesting to their good health without clinical evaluation D 750 EUR

France, 2000- (Meyaya, 2006) 378 45 (12%)
[36 (80%)]^d Bwiti initiation, psychotherapeutic, spiritual, general health issues Dried root bark, 6-10 teaspoons^e Bwiti Religious ritual. Chateau, private residences. Nganga (ritual leader or priest) with African and European assistants. Requires only a doctor's or the prospective patient's statement assuring good health without clinical evaluation. D 650 EUR

France/UK, 2003- (myeboga.com, 2006) 316, 32 (10%)
[6 (19%)] Bwiti initiation, psychotherapeutic, spiritual, general health issues Dried root bark 3-4 teaspoons^e Bwiti religious ritual, retreat. Resort settings, private residences. European initiates of the African Bwiti tradition with African and European assistants. Pretreatment medical and psychiatric history, blood chemistry and EKG. Medical doctor in attendance throughout the treatment D 500 EUR

Gabon, 1999- (Ebando, 2006) 50, 8 (16%)
[5 (63%)] Bwiti initiation, psychotherapeutic, spiritual, general health issues, fertility Infusion, 20-25 teaspoons of fresh root bark scrapings Bwiti religious ritual. Bwiti chapels in which Europeans and non-Africans are accepted. Prospective interview by a Nganga, without clinical evaluation $4000 USD (for 1 month stay)

^a n = number of individuals within each scene who took ibogaine.
^b n (%) = subset of n who took ibogaine for the treatment of any substance-related disorder, expressed as absolute number, and as (%) of n.
^c [n (%)] = subset of n who took ibogaine for the treatment of opioid withdrawal expressed as absolute number, and as (%) of the number of individuals who took ibogaine for the treatment of any substance-related disorder.
^d Data regarding the number of individuals taking ibogaine for opioid withdrawal among all those who took ibogaine for the treatment of any substance-related disorder were missing for the St. Kitts and France 2000 scenes. For these scenes, the proportion seeking treatment specifically for opioid withdrawal relative to all those seeking treatment for any substance-related disorder was assumed to be the same as the rest of the sample. This yielded estimates of (0.79 × 400 = 316) for St. Kitts, and (0.79 × 45 = 36) for France 2000.
^e One teaspoon of dried Tabernanthe iboga root rugs,talk.politics.drugs Date: 2 Apr 1995 13:57:51 GMT Organization: None Lines: 1957 Approved: news-answers-request@gza.com Expires: 7 May 1995 13:57:43 GMT Message-ID: NNTP-Posting-Host: bloom-picayune.mit.edu Summary: This is a list of organisations active in drug law reform, with information on how to contact them. X-Last-Updated: 1995/03/26 Originator: faqserv@bloom-picayune.MIT.EDU Xref: nic.umass.edu alt.activism:75701 alt.drugs:111715 talk.politics.drugs:33924 alt.answers:7985 talk.answers:638 news.answers:40937 Archive-name: drugs/law-reformers Last-modified: 1995/03/26 Version: 1.34 LIBERTY ACTIVISTS' LIST v 1.34 03/1995 So you're sick of the "War on Drugs"? Here's an international list of over 200 organisations which support drug law reform, although most of them are in the US. Look for one in your area. Please distribute this list widely, and send in any groups which are not listed already. There's an active group here for almost any taste. Joining your favourite organisation is best, though if you're worried about persecution, just send anonymous money or a letter of appreciation. Take advantage of your democratic rights while you still have some! If you're already in a law reform organisation, you can use this list to contact others with similar interests, and share information or facilities. Just knowing that there are others working on these issues can be a big morale booster. The power of pro-liberty organisations can be multiplied many times by fast and efficient communication, which spreads news and promotes co-ordinated action. Electronic mail and conferencing is the most efficient way to achieve these necessary abilities. For example, this list doubled its size in eight months of circulation over the Internet. I strongly encourage active groups and individuals to use this powerful technology. This listing was originally kicked off with a list of groups reproduced with permission from the February, 1992 issue of _High Times_ magazine (contact details at the end of the list). Since then, it has grown considerably through the kindness of those who have contributed additional entries, including Chris Klausmeier, Macca Macpherson, Dave Thomson and Keith Lim. Please reproduce and distribute widely with this acknowledgment. Post it on bulletin boards if you can. PLEASE SEND NEW LISTINGS I don't know any more about most of these groups, than what appears here. If you know about other active groups not listed here, or if any entries need correction, please e-mail me at "aldis@zeta.org.au", or mail to the address below, for incorporation in future editions of this list. Aldis Ozols GPO Box 127 SYDNEY 2001 AUSTRALIA * * * * * *AUSTRALIA* Adelaide University NORML c/- Clubs Association University of Adelaide Adelaide 5000 Internet: daroussy@teaching.cs.adelaide.edu.au groo@smug.student.adelaide.edu.au Australian Hemp Products 227 Grinsell Street Kotara, Newcastle, NSW 2289 Phone: +61 49 52 7802 Fax: +61 49 52 5211 (Grant Steggles) Australian Parliamentary Group for Drug Law Reform c/- Michael Moore, MP GPO Box 1020 Canberra ACT 2601 Phone: +61 6 205 0166 Fax: +61 6 205 0431 Notes: A group of Members of Parliament supporting the reform of drug laws. BIO-Logical PRODUCTS PO Box 768 Potts Point NSW 2011 Phone: +61 2 983 9857 Fax: +61 2 440 0140 Notes: Sells clothing made of hemp, and distributes information about the uses of hemp for paper, fuel, etc. Brisbane HEMP PO Box 332 Albert St 4002 Phone: +61 7 844 7499 Notes: Meetings at 50 Baynes St, West End on Monday nights at 7.30pm. Flinders NORML c/- Clubs and Societies Association, Inc. Flinders University Bedford Park, SA 5042 Hemp For Paper Consortium c/- Harmsens 430 Tinderbox Road TINDERBOX TAS 7054 Phone: +61 02 29 2063 IDUN Communication Centre, NUAA PO Box 822 Bondi Junction 2022 New South Wales Phone: +61 2 369 3455 Fax: +61 2 369 3282 (Dave Burrows) Note: Injecting Drug User Group Network, promoting drug law reform, harm reduction, education, outreach, and research. Mullers and Packers Union, C/o Clubs and Societies, Monash University, Clayton, Victoria 3168 Internet: c/- smalshy@yoyo.cc.monash.edu.au (a 'donated' account - messages will be passed on to the Secretary of the club) Notes: President is Tony Carden. Last Contacted: 2/93 New South Wales NORML GPO Box 91 Sydney, NSW 2001 Notes: This group is no longer very active, though some members can be contacted at the above address. Nimbin HEMP PO Box 177 Nimbin, NSW 2480 Phone: +61 66 89 1602 South Australia HEMP PO Box 7013 Hutt Strett Adelalaide 5000 Phone: +61 8 293 2838 West Australia HEMP PO Box 115 Mirrabrooke 6061 Phone: +61 9 344 1445 West Australia NORML PO Box 907 Morley, WA 6062 (Carl Turney) *BELGIUM* International Anti-Prohibitionist League (Europe) 97 Rue Belliard, Rem.512 1040 Brussels Phone: (32 2) 230 4121 Fax: (32 2) 230 3670 *CANADA* Assembly of the Church of the Universe 329 Wentworth St. North Hamilton, Ontario L8L 5W1 CANADA (416) 521-1804 (Rev. Bros. Walter A. Tucker & Michael A. Baldasaro) Notes: officially registered religious organisation Last Contacted: Dec 93 B.C. Anti-Prohibitionist League P.O. Box 8179 Victoria, B.C. V8W 3R8 CANADA (604) 382-7758 Last Contacted: Apr 94 Canadian Association for the Legalisation of Marijuana (C.A.L.M.) (B.C.) R.R. 1, Site 850D, Comp 2 Grand Forks, B.C. V0H 1H0 CANADA Last Contacted: Sep 93 Canadian Foundation for Drug Policy 70 MacDonald Street Ottawa, Ontario K2P 1H6 CANADA (613) 238-5909 (temporary number until a separate one is acquired) Fax: (613) 238-2891 (also temporary) Last Contacted: Dec 94 Canadian Hemp Association 312 Adelaide St. W. Suite 608 Toronto, Ontario M5V 1R2 CANADA cha@io.org (416) 977-4159 (Robin Ellins) Notes: A national organization to facilitate and promote the growth of a hemp industry in Canada. Last Contacted: Jun 94 (C.H.A. post to alt.hemp) Fane of the Psilocybe Mushroom Association P.O. Box 8179 Victoria, B.C. V8W 3R8 CANADA Notes: officially-registered religious organization; publishes Sporeprint newsletter Last Contacted: Apr 94 Freedom Party of Ontario P.O. Box 2214, Station A London, Ontario N6A 4E3 CANADA (519) 433-8612 Notes: officially-registered Ontario political party; supports individual choice without either condoning or condemning cannabis use. Friends International 370-1027 Davie St. Vancouver, B.C. V6E 4L2 CANADA (604) 681-3704 (Leeroy Campbell, Jan Campbell) Notes: publishes Hempfest Times newsletter Last Contacted: Jun 94 HEMP BC 1281 West Georgia 9th floor Vancouver B.C. V6E 3J7 CANADA marc_emery@mindlink.bc.ca (604) 681-4620 (Marc Emery) (604) 681-4604 (fax line) Last Contacted: Jun 94 HEMP Canada PO Box 37154 769 Southdale Road East London, Ontario N6E 1B0 CANADA (519) 686-1415 (Mike Bourque - Director) Last Contacted: Apr 94 Hemp Lobby Hornby Island (604) 335-1276 (John West) Last Contacted: May 93 Hemp to Save the Rainforest 830 Gulfview Place Victoria, B.C. V8Y 2R6 CANADA (Thurles Loughran) Last Contacted: Mar 94 Hempsters #114-1472 Commercial Drive Vancouver B.C. V5L 3X9 Last Contacted: May 94 International Anti-Prohibitionist League (Canada) c/o Marie-Andree Bertrand PO Box 6128 University of Montreal Criminology Dept. Montreal, Quebec H3C 3S7 CANADA Last Contacted: Sep 93 League for Ethical Action on Drugs (LEAD) 1047 Yarmouth Street Port Coquitlam, B.C. V3C 5H4 CANADA (604) 942-1910 (Dana Larsen) Notes: uses a harm-reduction philosophy in lobbying for drug policy reform Last Contacted: Jun 94 Libertarian Party of Canada 922 Cloverley St. North Vancouver, B.C. V7L 1N3 CANADA (604) 980-7370 Last Contacted: Sep 93 Ligue antiprohibitioniste du Quebec 4566 rue de la Roche Montreal, Quebec H2J 3J6 CANADA (514) 454-7744 NAUN 155 Sherbourne Street #310 Toronto M5A 3W2 CANADA (Stean Collins) Note: Injecting Drug User Group Network, promoting drug law reform, harm reduction, education, outreach, and research. NORML B.C. Depot 4, P.O. Box 7193 Victoria, B.C. V9B 4Z3 CANADA (604) 474-4771 (Norm Cholette) Last Contacted: Sep 93 NORML Canada R.R. #1 King City, Ontario L0G 1K0 CANADA (416) 833-3167 (Umberto Iorfida) (416) 833-3577 (Computer line) Last Contacted: Sep 93 Patriotic Canadians for Hemp Box 293 Ucluelet B.C. V0R 3A0 CANADA (604) 726-7239 (Chris Bennett, Tracy Chester) Notes: a.k.a. Sister Sativa's Genuine Hemp, Mama Indica's Hempseed Treats Last Contacted: Jun 94 Society of Free Thinkers (SOFT) P.O. Box 327 Paradise Newfoundland and Labrador (NfLb) A1L 1C7 CANADA Notes: Not solely dedicated to drug law reform. Methods include posters, letters and leaflets. Anonymity is granted to members, upon request. Last Contacted: Jan 93 Simon Fraser University League for Ethical Action on Drugs (SFU LEAD) c/o SFSS Clubs Administration Simon Fraser University Burnaby, B.C. V5A 1S6 CANADA (604) 291-3181 (SFSS General Office: messages) Notes: area of interest is in finding policy alternatives to the WoD that do not infringe on civil liberties. Last Contacted: Jun 94 Total Hemp Corporation (THC) 328 West Hastings St. Vancouver, B.C. V6B 1K6 CANADA (604) 682-4149 (Ian Hunter) (604) 942-1910 (Dana Larsen) Last Contacted: Jun 94 *CANADA - INDIVIDUALS* Kris Laing (604) 285-2856 Last Contacted: May 94 J. Wayne Marsden (604) 668-6886 Notes: Libertarian Party candidate Last Contacted: Sep 93 *DENMARK* Fri Hash Bevaegelsen (Movement for legalization of marijuana) Hampens plads 1, Christiania Baadsmandsstraedet 43, 1407 KBH K Phone: +45 32966614 Internet: Nicolaj Tscherning Moller *FINLAND* Suomen kannabisyhdistys PL 20 SF-00770 Helsinki Internet: sky@katto.kaapeli.fi WWW: http://katto.kaapeli.fi/~sky/ *FRANCE* Collectif d'Information et de Recherche Cannabique (CIRC) (Association for Marijuana Research and Information) 118-130 av. Jean Jaures 75019 PARIS CEDEX 19 Phone: +33 1 42 38 04 83 Fax: +33 1 42 38 02 99 Minitel: 3615 CIRC MLC: Mouvement for a Controlled Legalization President: Francis Caballero. Attorney. 59, av. Victor-Hugo 750016 Paris FRANCE Phone: +33 1 42 22 48 23 *GERMANY* AKZEPT (Bundesverband fu"r akzeptierende Drogenarbeit und humane Drogenpolitik e.V.) Friedrichstrasse 165 10117 Berlin Phone: +49 30 229 9043 ARCHIDO (Archiv und Dokumentationszentrum fu"r Drogenliteratur e.V.) Universita"t Bremen Fachbereich 8 Postfach 33 04 40 28334 BREMEN Phone: +49 421 218 3173 Fax: +49 421 218 4265 Notes: Working on a federal level for drug legalisation in Germany. Bundesarbeitsgemeinschaft Kritischer Polizistinnen und Polizsten (Hamburger Signal) e.V. c/o Reinhard Borchers Gaertnerstrasse 21 D-20253 Hamburg Phone: +49 40 422 5843 Fax: +49 40 422 9322 Internet: R.Borchers@cl-hh.comlink.de Notes: An organisation of German Policemen and Policewomen. Last contact: Feb 95 EIGDU C/- DAH Secretariate Berlin Dieffenbachstrasse 33 10967 Berlin Phone: +49 30 690087 56 Fax: +49 30 690087 42 (Werner Hermann) Note: Injecting Drug User Group Network, promoting drug law reform, harm reduction, education, outreach, and research. H.A.N.F. e.V. Hanf als Nutzpflanze foerdern c/o Gecko Headshop Osterfelder Str. 2 42103 Wuppertal Phone: +49 202 304295 Fax: +49 202 316795 Kommunale Drogenpolitik (Verein fu"r akzeptierende Drogenarbeit e.V.) Kreuzstra(ss)e 29 28203 Bremen Phone: +49 421 76045 Fax: +49 421 75727 *HOLLAND* See *NETHERLANDS, THE* *ISRAEL* Israel Organization For the Reformation of Pot Laws, The PO Box 11438 Ariel 44839 Phone: +972 3 936 5407 Last contact: Jan 95 *ITALY* CORA - Coordinamento Radicale Antiproibizionista c/o Partito Radicale Transnazionale (Transnational Radical Party) Via di Torre Argentina 76 00186 ROMA (ITALY) Phone: +39 6 689791 Fax: +39 6 68805396 Telex: +39 6 610495 PRLIFEI Note: CORA also has a BBS. Its phone number is +39 6 69920412, or on the Internet, "telnet agora.stm.it". In particular, look at 'Conference Drugs' and 'News Cora' for info on Cora activities. *NETHERLANDS, THE* IRDRHR (International Institute for Resource-sharing on Drugs and Human Rights) Drugs Peace Institute PO Box 15563 1001 NB Amsterdam giro 6663463 *NETHERLANDS, THE - INDIVIDUALS* Guido H. Koppes Tuinstraat 47-07 5038 DA Tilburg Phone: +31 13 356331 Internet: Guido Koppes *NEW ZEALAND* ADUN C/- Mainline communications 33 Hill Cresent, New Lynn Auckland 1007 Phone: +64 9 826 0977 Fax: +64 9 826 0977 Internet: Barry F Ryker Note: Injecting Drug User Group Network, promoting drug law reform, harm reduction, education, outreach, and research. Auckland University NORML C/- AUSA Private Bag 92019 Auckland University Auckland Christchurch NORML c/- PO Box 22301 Christchurch Internet: C/- Greg Kerdemelidis Dunedin University NORML c/- OUSA PO Box 1436 Dunedin Hamilton NORML PO Box 19088 Hamilton Notes: Branch contact is Kath (phone 855 0762). Nelson Polytech NORML Contact: c/- Nelson Polytech Students' Association Last Contacted: September 1993 NZ NORML PO Box 19467 Avondale Auckland 7 Phone: (09) 828 4707 (Mike Finlayson) Notes: Palmerston North contact is: Linda Davis c/- Student Mail, City Court Hostel, B2-4, Massey University. Hawkes Bay contact is: Johnny Ropitini c/- Ropitini, Kakirawa Flats, Miriama Rd, RD 11, Paki Paki, Hastings. Wellington NORML C/- P.O.Box 11639 Wellington Notes: Located at Shop 272, Cuba St, Welington. Open every Friday night 5.30 pm to 8.00 pm, and Saturday morning from 10.00 am to 1.00 pm. *NORWAY* Fremskrittspartiets Ungdom Box 8867 Youngstorget N-0028 Oslo Phone: (+47) 22 41 07 69 Fax (+47) 22 42 32 55 Notes: This is the youth organisation of the Progress Party. A recent committee meeting voted in favour of cannabis legalisation, and it is likely that the national assembly of the youth organisation will accept this as policy in early 1994. The mani body of the party does not as yet support this. *SLOVENIA* STIGMA Saranoviceva 5 61000 Ljubljana Slovenia Phone: +386 61 133 7011 Fax: as for voice phone (Dare Kocmur) Note: Injecting Drug User Group Network, promoting drug law reform, harm reduction, education, outreach, and research. *SWITZERLAND* Verein Schweizer Hanf Freunde (Swiss Association of Hemp Friends) Postfach 323 9004 St. Gallen Last Contacted: Jan 93 *UNITED KINGDOM* Alchemy 261 Portobello Road London W11 Bridge (Drug Advice) Equity Chambers Piccadilly Bradford Phone: +44 274 72 3863 Campaign to Legalise Cannabis International 54c Peacock Street Norwich NR3 1TB CODD (Committee for an Open Debate on Drugs) BCM Entwine, London WC1N 3XX European Movement for Normalisation of Drug Policy (British Section) c/- Dr Russell Newcombe c/- 10 Maryland Street LIVERPOOL L1 9BX Phone: +44 51 709 3511 Fax: +44 51 709 4916 Legalise Cannabis Campaign BM Box 2455 London WC1N 3XX Phone: +44 71 585 1031 Libertarian Alliance 25 Chapter Chambers Esterbrooke Street London SW1P 4NN Phone: +44 71 821-5502 Fax: +44 71 834-2031 Internet: liberty@capital.demon.co.uk National Council for Civil Liberties 21 Tabard Street London SE1 4LA Phone: +44 71 403 3888 Peoples Right To Smoke Marijuana PO Box 23 Chigwell, Essex IG7 5EH Release (Drugs Legal & Emergency service) 169 Commercial Road London E1 6BW Phone: +44 71 377 5905 (daytime), +44 71 603 8654 (24-hour helpline) *UNITED STATES OF AMERICA* Note: This portion of the list has been extensively revised by Chris Klausmeier, with extensive help and prodding from Brian at University of Massachusetts at Amherst Cannabis Reform Coalition. Advocates for Self-Government 3955 Pleasantdale Road, #106-A Atlanta, GA 30340 Phone: (404)417-1304, (800)932-1776 Fax: (404)417-1305 Notes: The Advocates for Self-Government is a non-profit educational organization. Our purpose is to present the freedom philosophy honestly and persuasively to opinion-makers so that they can encounter, evaluate, and when ready embrace the ideals of self-government. Contributions are tax deductible under section 501(c)(3). Last Contacted: July 1993 Alabama TEACH Rt 3 Box 620 Blountsville, AL 35031 (Johnny Bynum) Alaskans for Hemp Awareness 1013 E. Dimond Blvd. #227 Anchorage, AK 99515 Phone/Fax: (907) 248 HEMP Internet:opioids with or without the additional ingestion of cocaine (Alper et al., 1999; Marker and Stajic, 2002). Deaths not involving the above factors have been associated with the use of Tabernanthe iboga alkaloid extract (Alper, 2001) or dried root bark (Kontrimaviciute et al., 2006b). This subset of fatalities may reflect a general hazard associated with the use of indigenous ethnopharmaceutical forms outside of their traditional context by the uninformed or inexperienced (Callaway and Grob, 1998; Maas and Strubelt, 2006). For example, one death (Kontrimaviciute et al., 2006b) involved ingestion of an amount of powdered dried root bark that is at least twice the maximum upper limit used by the providers in this study who are traditional African Bwiti adepts. Other potential hazards may be associated with the lack of pharmaceutical standards for ibogaine, including unregulated procedures for manufacturing and storage or the possibility of naturally co-occurring toxic alkaloids (Singbartl et al., 1973; Jenks, 2002; Kontrimaviciute et al., 2006a).

Cerebellar Purkinje cell degeneration reported in rats administered ibogaine at high dosages of 100 mg/kg (O'Hearn and Molliver, 1993, 1997) prompted concern regarding potential neurotoxicity. The FDA was aware of this research at the time it approved the Phase I study; other work indicated no evidence of neurotoxicity rats at the dosage of 40 mg/kg typically used to study drug self-administration and withdrawal (Molinari et al., 1996). Evidence of neurotoxicity due to ibogaine is reportedly absent in mice (Scallet et al., 1996), primates (Mash et al., 1998) and a postmortem neuropathological examination of a woman who had taken ibogaine four times in the prior 15 months at doses up to 30 mg/kg. In the Phase I study, quantitative dynamic measures of cerebellar motor function were unremarkable in human subjects that received low doses of ibogaine of 1 and 2 mg/kg (Mash et al., 1998). The study was never finished due to contractual disputes with eventual litigation among the study sponsors, unrelated to clinical issues. The σ2 receptor mediates neurotoxic injury (O'Hearn and Molliver, 1997; Bowen, 2001), and is apparently not involved in effects of ibogaine on drug self-administration and withdrawal (Glick et al., 2001). This suggests that the therapeutic and neurotoxic effects of iboga alkaloids can be resolved from one another by rational drug design, as indicated by the example of 18-MC, which has lower affinity for the σ2 receptor and is not associated with evidence of neurotoxicity even at very high dosages (Maisonneuve and Glick, 2003).

4.4. Suggestions for future research

Experimental pharmacologists are increasingly interested in the development of approaches to addiction that extend beyond the present repertoire of agonist or antagonist actions, and instead are targeted at effects on intracellular signaling downstream from the receptor (Bonci and Carlezon, 2005). Ibogaine may provide a prototypic example of an agent with such novel mechanisms of action. Future work should replicate and extend on prior research indicating that iboga alkaloids modulate signal transduction in second messenger pathways linked to G proteincoupled receptors (GPCRs) (Rabin and Winter, 1996a,b).

Constitutive spontaneous activity without the binding of an agonist (Costa and Cotecchia, 2005) occurs in GPCRs such as opioid receptors (Shoblock and Maidment, 2006). Constitutive signaling mediated by conformational states of receptorassociated proteinsmaybe modulated relatively rapidly and span a wide signal range, consistent with a possible role in the highly dynamic neuroadaptations associated with opioid tolerance and withdrawal. It may be worthwhile to investigate the possibility that iboga alkaloids interact allosterically or orthosterically with GPCRs to affect constitutive signaling.Apossible role of orphan receptors should be also considered (Civelli et al., 2006).

Functional and clinical evidence of muscarinic cholinergic actions of iboga alkaloids includes the occurrence of a state with some neurophysiological and behavioral features common to REM sleep (Schneider and Sigg, 1957; Depoortere, 1987; Goutarel et al., 1993; Alper, 2001), and recent work suggesting that muscarinic acetylcholine receptors (mAChRs) as well as nAChRs in the habenulopeduncular pathway mediate the effects of 18-MC on dopamine efflux in the NAc (Taraschenko et al., 2007a,b). Ibogaine interacts with cholinergic neurotransmission in multipleways; as a strong antagonist at nAChRs (Daly, 2005), binding to mAChRs with affinities on the order of approximately 10 M with actions that are not well characterized with regard to antagonist versus agonist effects, and according to an older literature, inhibition of acetylcholinesterase (Vincent and Sero, 1942). The knockout mouse, which exists for each of the five basic subtypes of mAChRs (Wess et al., 2003), provides an in vivo approach that makes it possible to study functional correlates of activity at mAChRs such as the EEG or cardiac electrophysiology, as well as the role of mAChRs in ibogaine’s effects on models of substance-related disorders.

Structure-function relationships mediating toxic and therapeutic effects of iboga alkaloids have been identified and utilized to guide rational synthesis (Glick et al., 1994; Kuehne et al., 2003; Maisonneuve and Glick, 2003). Preclinical toxicological testing, and if appropriate, clinical research on iboga alkaloids will require the development of pharmaceutical synthetic and chemical manufacturing technology in order to produce adequate quantities of investigational drug in conformance with international Good Manufacturing Practice standards. The chemical, manufacturing and control stage of pharmaceutical development generally is accomplished in the private sector, but the pharmaceutical industry historically has shown less interest in developing drugs for substance-related disorders relative to other indications (Gorodetzky and Grudzinskas, 2005), indicating an important need for involvement of the public sector.

5. Conclusions

The estimated number of participants in the ibogaine subculture increased fourfold relative to the prior estimate of 5 years earlier, an average yearly rate of growth of approximately 30%. The existence and expansion of the subculture indicates a demand for newtreatment, which is sought regardless of medical risk, inconvenience, expense, and in some cases legal prohibition. Across a diversity of settings, most individuals who took ibogaine did so for the treatment of a substance-related disorder, specifically for opioid withdrawal. Ibogaine's effect in opioid withdrawal is consistent with case series and preclinical evidence, and is unlikely to be mediated by placebo. The mechanism of ibogaine's action in opioid withdrawal merits further investigation as a paradigm for neurobiological research and rational pharmaceutical development.

Conflict of interest statement

We declare that we have no conflict of interest. Howard Lotsof was awarded multiple patents on the use of ibogaine in substance-related disorders, which he divested in 1998.

Acknowledgements

The authors gratefully acknowledge Geoffrey Cordell, Ph.D., James W. Fernandez, Ph.D., Renate L. Fernandez, Ph.D., Marc Galanter, M.D., and Stephen Sifaneck, Ph.D. for their review and helpful comments regarding this paper.

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The ibogaine medical subculture

Journal of Ethnopharmacology 115 (2008) 9-24

Kenneth R. Alper a,b, Howard S. Lotsof c, Charles D. Kaplan d

Abstract

1. Introduction

1.1. History

1.2. Clinical use

1.3. Preclinical research

1.4. Mechanisms of action

1.5. Research objectives of this study

2. Methods

2.1. Observational methods

2.2. Study sample

2.3. Excluded scenes

2.4. Data collection

2.5. Data validation

2.6. Data analysis

3. Results

3.1. Typology

3.1.1. Medical model

Table 1

4.4. Suggestions for future research

5. Conclusions

Conflict of interest statement

Acknowledgements

References

Kenneth R. Alper ^a,b, Howard S. Lotsof ^c, Charles D. Kaplan ^d