Scientific Research on Ibogaine

Alper, KRa,b, Lotsof, HSc, Kaplan, CDd.

Department of Psychiatry, New York University School of Medicine, New York, NY 10016, USA Department of Neurology, New York University School of Medicine, New York, NY 10016, USA kra1@nyu.edu

Dora Weiner Foundation, 46 Oxford Place, Staten Island, NY 10301, USA
Department of Psychiatry and Neuropsychology, Maastricht University, 6200 MD Maastricht, The Netherlands

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/self-help”, 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.

DC, Duque, L, Kamlet, JD, Ervin, FD and Allen-Ferdinand, K.

University of Miami School of Medicine, Miami, FL. McGill University, Montreal, Canada and Healing Visions, St. Kitts, WI

The apparent ability of ibogaine to interrupt dependence on heroin and cocaine was first described in the early 1960s. Anecdotal accounts of the acute and long-term effects of ibogaine have included only a small series of case reports of opiate and cocaine addicts(Sheppard, 1994; Sisko, 1993; Alper et al., 1999) with observations provided for only 7, 4 and 14 subjects, respectively.

Thus, objective investigations of ibogaine’s effects on craving for drugs and alcohol and on the signs and symptoms of opiate withdrawal are not available.

We have evaluated the safety and pharmacokinetics of ibogaine in the setting of an inpatient detoxification in over 400 patient volunteers assessed from 1996 to the present.

We have attempted to collect data from this study using Food and Drug Administration guidelines for good clinical practices. Our clinical experience to date indicates that ibogaine has little toxicity in doses ranging from 1 to 14 mg/kg. Oral administration of ibogaine to opiate-dependent individuals was associated with significant blockade of the characteristic opiate-withdrawal signs and symptoms. 

We have also examined whether ibogaine affects drug craving using multidimensional craving questionnaires for heroin and cocaine. To the extent that physical, psychological, and emotional well-being might impact their self-reports of craving during their course of stay, participants also completed standardized questionnaires about their health both before and after ibogaine treatment and at program discharge. 

To assess whether the benefits of ibogaine on drug craving would persist outside of a controlled environment, one month follow-up data were also collected. The results of ibogaine research conducted offshore indicates that ibogaine diminishes drug cravings and improves mood. Ibogaine may be an adjunct to brief intervention to help patients to reduce risky or hazardous drug and alcohol use. Ibogaine also motivates some drug-dependent patients to enter treatment with the goal of long-term abstinence. (Supported in part by the Addiction Research Fund).

Prog Neuropsychopharmacol Biol Psychiatry. 2003 Aug;27(5):781-5.

Leal MB, Michelin K, Souza DO, Elisabetsky E.

Faculdade de Farmacia, Pontifi;cia Universidade Catolica do Rio Grande do Sul, Rua da Republica 580/306, Cep: 90050-320, RS, Porto Alegre, Brazil

Ibogaine (IBO) is an alkaloid with putative antiaddictive properties, alleviating opiates dependence and withdrawal. The glutamate N-methyl-D-aspartate (NMDA) receptors have been implicated in the physiological basis of drug addiction; accordingly, IBO acts as a non-competitive NMDA antagonist. 

The purpose of this study was to evaluate the effects of IBO on naloxone-induced withdrawal syndrome in morphine-dependent mice, focusing on the role of NMDA receptors. 

Jumping, a major behavioural expression of such withdrawal, was significantly (P<.01) inhibited by IBO (40 and 80 mg/kg, 64.2% and 96.9% inhibition, respectively) and MK-801 (0.15 and 0.30 mg/kg, 67.3% and 97.7%, respectively) given prior to naloxone. 

Coadministration of the lower doses of IBO (40 mg/kg) and MK-801 (0.15 mg/kg) results in 94.7% inhibition of jumping, comparable to the effects of higher doses of either IBO or MK-801. IBO and MK- 801 also significantly inhibited NMDA-induced (99.0% and 71.0%, respectively) jumping when given 30 min (but not 24 h) prior to NMDA in nonaddictive mice. 

There were no significant differences in [3H]MK-801 binding to cortical membranes from naive animals, morphine-dependent animals, or morphine- dependent animals treated with IBO or MK-801. 

This study provides further evidence that IBO does have an inhibitory effect on opiate withdrawal symptoms and suggests that the complex process resulting in morphine withdrawal includes an IBO-sensitive functional and transitory alteration of NMDA receptor.

Prog Neuropsychopharmacol Biol Psychiatry. 2002 Feb;26(2):293-7.

Parker LA, Burton P, McDonald RV, Kim JA, Siegel S.Department of Psychology, Wilfrid Laurier University, Waterloo, Ontario, Canada. lparker@wlu.ca

It has been reported that ibogaine interferes with somatic withdrawal reactions in rats chronically treated with morphine. The present experiments demonstrated that ibogaine also interferes with motivational withdrawal reactions and somatic withdrawal reactions in rats treated with morphine on only two occasions. 

On each of two conditioning trials, naloxone was administered 24 h following an injection of morphine. Four hours prior to each naloxone administration, rats were injected with either ibogaine or saline. In two experiments, ibogaine interfered with naloxone-precipitated withdrawal. 

In Experiment 1, ibogaine-treated rats displayed a weaker aversion to the withdrawal-paired chamber, and in Experiment 2, ibogaine-treated rats displayed fewer somatic withdrawal reactions than did saline treated rats.

Alkaloids Chem Biol. 2001;56:155-71.

Mash DC, Kovera CA, Pablo J, Tyndale R, Ervin FR, Kamlet JD, Hearn WL.Departments of Neurology and Pharmacology, University of Miami School of Medicine, Miami, FL 33124, USA.

Ibogaine is a naturally occurring psychoactive indole alkaloid derived from the roots of the rain forest shrub Tabernanthe iboga. It has been suggested that the alkaloid reduces craving for opiates and other illicit drugs and has ameliorative effects in acute opioid withdrawal.

However, objective investigations of ibogaine’s effects on drug craving, and the signs and symptoms of opiate withdrawal, have not been done in either research or conventional treatment settings. We have had the opportunity to describe the clinical experience of a series of patients undergoing opiate detoxification with ibogaine. The study was conducted in a 12-bed freestanding facility in St. Kitts, West Indies. 

The treatment program had a planned duration of 12 to 14 days and stated goals of: 

(1) safe physical detoxification from opiates, 

(2) motivational counselling, and 

(3) referral to aftercare programs and community support groups (12 step programs). 

Physical dependence on opiates is characterized by a distinctive pattern of signs and symptoms that make up the naturalistic withdrawal syndrome. Objective signs of opiate withdrawal were rarely seen and none were exacerbated at later time points. 

The results suggest that ibogaine provided a safe and effective treatment for withdrawal from heroin and methadone. These preliminary results demonstrate that single doses of ibogaine were well tolerated in drug-dependent subjects. 

Our observations of the safety of ibogaine have not been limited to opiate-dependent subjects. To date, we have evaluated ibogaine’s safety in more than 150 drug- dependent subjects that were assigned to one of three fixed-dose treatments under open label conditions; 8, 10, 12, mg/kg ibogaine. To date, no significant adverse events were seen under these study conditions. 

J Pharmacol Exp Ther. 2001 May;297(2):531-9.

Baumann MH, Rothman RB, Pablo JP, Mash DC.Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA. mbaumann@intra.nida.nih.gov

Ibogaine is a naturally occurring compound with antiaddictive properties. When administered to primates, ibogaine is rapidly o-demethylated to form the metabolite 12-hydroxyibogamine (noribogaine). Peak blood levels of noribogaine exceed those of ibogaine, and noribogaine persists in the bloodstream for at least 1 day. 

Very few studies have systematically evaluated the neurobiological effects of noribogaine in vivo. In the present series of experiments, we compared the effects of IV administration of ibogaine and noribogaine (1 and 10 mg/kg) on motor behaviours, stress hormones, and extracellular levels of dopamine (DA) and serotonin (5-HT) in the nucleus accumbens of male rats. Ibogaine caused dose-related increases in tremors, whereas noribogaine did not. 

Both ibogaine and noribogaine produced significant elevations in plasma corticosterone and prolactin, but ibogaine was a more potent stimulator of corticosterone secretion. Neither drug altered extracellular DA levels in the nucleus accumbens. 

However, both drugs increased extracellular 5-HT levels, and noribogaine was more potent in this respect. Results from in vitro experiments indicated that ibogaine and noribogaine interact with 5-HT transporters to inhibit 5-HT uptake. The present findings demonstrate that noribogaine is biologically active and undoubtedly contributes to the in vivo pharmacological profile of ibogaine in rats. 

Noribogaine is approximately 10 times more potent than ibogaine as an indirect 5-HT agonist. More importantly, noribogaine appears less apt to produce the adverse effects associated with ibogaine, indicating the metabolite may be a safer alternative for medication development.

Ann N Y Acad Sci. 2000;914:394-401.

Mash DC, Kovera CA, Pablo J, Tyndale RF, Ervin FD, Williams IC, Singleton EG, Mayor M.Department of Neurology, University of Miami School of Medicine, Florida 33136, USA. dmash@med.miami.edu

Ibogaine is an indole alkaloid found in the roots of Tabernanthe Iboga (Apocynaceae family), a rain forest shrub that is native to western Africa. Ibogaine is used by indigenous peoples in low doses to combat fatigue, hunger, and thirst, and in higher doses as a sacrament in religious rituals. 

Members of American and European addict self-help groups have claimed that ibogaine promotes long-term drug abstinence from addictive substances, including psychostimulants and opiates. Anecdotal reports attest that a single dose of ibogaine eliminates opiate withdrawal symptoms and reduces drug craving for extended periods of time. 

The purported efficacy of ibogaine for the treatment of drug dependence may be due in part to an active metabolite. The majority of ibogaine biotransformation proceeds via CYP2D6, including the O-demethylation of ibogaine to 12-hydroxyibogamine (noribogaine). Blood concentration-time effect profiles of ibogaine and noribogaine obtained for individual subjects after single oral dose administrations demonstrate complex pharmacokinetic profiles. Ibogaine has shown preliminary efficacy for opiate detoxification and for short-term stabilization of drug-dependent persons as they prepare to enter substance abuse treatment. 

We report here that ibogaine significantly decreased craving for cocaine and heroin during inpatient detoxification. Self-reports of depressive symptoms were also significantly lower after ibogaine treatment and at 30 days after program discharge. Because ibogaine is cleared rapidly from the blood, the beneficial aftereffects of the drug on craving and depressed mood may be related to the effects of noribogaine on the central nervous system.

Neurochem Res. 2000 Aug;25(8):1083-7.