NYU Conference on Ibogaine Nov 5-6, 1999
Ibogaine in the Treatment of Narcotic Withdrawal
The 37th International Congress on Alcohol and Drug Dependence
University of California, San Diego
La Jolla, California, USA
August 20th - 25th, 1995
H. S. Lotsof*, E. Della Sera1,, C.D. Kaplan2
1Clinica del Nino, David, Chiriqui, Rep. of Panama, 2 IPSER, Univ. of Limburg, Maastricht, The Netherlands *corresponding author, NDA International, Inc., PO Box 100506, Staten Island, NY 10310-0506
IBOGAINE: A BRIEF HISTORY
Ibogaine, a naturally occurring alkaloid found in Tabernanthe iboga and other plant species of Central West Africa, was first reported to be effective in interrupting opiate narcotic dependence disorders in U.S. patent 4,499,096 (Lotsof, 1985); cocaine dependence disorders in U.S. patent 4.587,243 (Lotsof, 1986) and poly-drug dependence disorders in U.S. patent 5,152,994 (Lotsof, 1992). The initial studies demonstrating Ibogaine's effects on cocaine and heroin dependence were accomplished in a series of focus group experiments by H. S. Lotsof in 1962 and 1963. Additional data on the clinical aspects of Ibogaine in the treatment of chemical dependence were reported by Kaplan (1993), Sisko (1993), Sanchez-Ramos & Mash (1994), Sheppard (1994), Judd (1994) and Mash et al. (1995).
Prior to Ibogaine's evaluation for the interruption of various chemical dependencies, the use of Ibogaine was reported in psychotherapy by Naranjo (1969, 1973) and at the First International Ibogaine Conference held in Paris (Zeff, 1987). The use of Ibogaine-containing plants has been reported for centuries in West Africa in both religious practice and in traditional medicine (Fernandez, 1982; Gollnhofer & Sillans 1983, 1985) Overviews of the history of Ibogaine research and use were published by Goutarel et al. (1993) and Popik et al. (1995)
Claims of efficacy in treating dependencies to opiates, cocaine, and alcohol in human subjects were supported in preclinical studies by researchers in the United States, the Netherlands and Canada. Dzoljic et al. (1988) were the first researchers to publish Ibogaine's ability to attenuate narcotic withdrawal. Stanley D. Glick et al. (1992) at Albany Medical College published original research and a review of the field concerning the attenuation of narcotic withdrawal. Maisonneuve et al. (1991) determined the pharmacological interactions between Ibogaine and morphine, and Glick et al. (1992) reported Ibogaine's ability to reduce or interrupt morphine self-administration in the rat. Woods et al. (1990) found that Ibogaine did not act as an opiate, and Aceto et al. (1991) established that Ibogaine did not precipitate withdrawal signs or cause dependence.
Cappendijk and Dzoljic (1993) published Ibogaine's effect in reducing cocaine self-administration in the rat. Broderick et al. (1992) first published Ibogaine's ability to reverse cocaine-induced dopamine increases and later, on Ibogaine's reduction of cocaine-induced motor activity and other effects (1994). Broderick et al.'s research supported the findings of Sershen et al. (1992), that Ibogaine reduced cocaine-induced motor stimulation in the mouse. Sershen (1993) also demonstrated that Ibogaine reduced the consumption of cocaine in mice. Glick (1992) and Cappendijk (1993) discovered in the animal model that multiple administrations of Ibogaine over time were more effective than a single dose in interrupting or attenuating the self-administration of morphine and cocaine, supporting Lotsof and his findings in human subjects (1985).
Popik et al. (1994) determined Ibogaine to be a competitive inhibitor of MK-801 binding to the NMDA receptor complex. Popik's findings were supported by Mash et al. (1995). MK-801 has been shown to attenuate tolerance to opiates (Trujillo & Akil 1991) and alcohol (Khanna et al. 1993). MK-801 has also shown a blockade of "reverse tolerance" of stimulants (Karler et al. 1989). Ibogaine's effects on dopamine, a substance hypothesized to be responsible for reinforcing pleasurable effects of drugs of abuse, and the dopamine system were found by Maisonneuve et al. (1991), Broderick et al. (1992) and Sershen et al. (1992). Ibogaine binding to the kappa opiate receptor was reported by Deecher et al. (1992). Both Ibogaine and its principal metabolite, desmethyl ibogaine were shown to target serotonin transporters and to elevate serotonin levels by Mash et al. (1995). The possibility of an endogenous substance that may mimic Ibogaine was suggested to be norharman by Cappendijk et al. (1994). Thus we begin to see a broad spectrum of mechanisms by which Ibogaine may moderate use of substances so diverse as opiate narcotics, stimulants and alcohol.
ATTENUATION OF OBJECTIVE SIGNS OF NARCOTIC WITHDRAWAL
The purpose of this paper is to specifically address Ibogaine's effects on narcotic withdrawal signs. Previous anecdotal reports have been provided by Lotsof (1985), Kaplan (1993), Sisko (1993) and Sheppard (1994). The data provided in this paper draws on the work of Lotsof in 1962 and 1963; Sisko, Adriaans and Frenken whose studies were conducted between 1989 and 1991 in The Netherlands, the experimental therapies of Bastiaans and Lotsof also conducted in The Netherlands from 1991 through 1993 and research conducted by Della Sera, Alvarado and Smith in the Republic of Panama in 1994 and 1995 with the approval of the Panamanian Ministry of Health.
This paper deals exclusively with objective withdrawal signs consisting of diarrhea, yawning, rhinorrhea, piloerection, lacrimation, mydriasis, shivering, restlessness, vomiting, muscle twitches, abdominal cramps, sweating, anxiety and the inability to sleep. In order to determine the effects of Ibogaine on narcotic withdrawal signs a separate evaluation of the effects of Ibogaine were determined in non-narcotic dependent patients. Ibogaine was shown to produce two signs in non-narcotic dependent patients in a significant manner: The inability to sleep and vomiting.
IBOGAINE'S STIMULANT EFFECT
Ibogaine, among its many distinct actions, exerts a stimulant effect that may last 48 hours or longer. There are a minority of patients who may sleep within 24 hours and one instance of a psychotic patient in Europe administered Ibogaine who did not sleep for 7 days. All patients are informed about Ibogaine's stimulant action, but most dismiss it during discussions prior to treatment stating that they have stayed awake for days. It is provided to these patients that such actions on their part were usually due to the use of narcotics and/or stimulants, however, it is not until the patients are actually treated with Ibogaine that it becomes clear that Ibogaine's stimulant action is distinct from those experienced with heroin and/or cocaine.
Approximately 20 hours post Ibogaine administration all patients exhibit exhaustion concurrent with restlessness and the inability to sleep. This is seen in Ibogaine only patients, narcotic dependent patients, cocaine dependent patients and poly-drug dependent patients.
IBOGAINE'S EFFECT ON VOMITING
Vomiting is experienced by approximately 30% of patients to whom Ibogaine is administered whether they are narcotic dependent or not (Naranjo, 1969, 1973 & Lotsof, 1995). Vomiting under the effects of Ibogaine are specifically potentiated by movement and patients should be allowed to remain as still as possible. This is of course problematic under clinical research conditions where neurological testing requiring movement occurs and must be taken into account. Under the conditions of Ibogaine therapy, patients should remain still and in bed.
It should also be noted that there is a distinction between the subjective effects of vomiting induced by Ibogaine and vomiting induced by narcotic withdrawal. This distinction has been provided in interviews by the majority of patients who have exhibited vomiting. Vomiting due to Ibogaine is acute. The incident occurs, is generally brief and the event is over. If vomiting occurs on Ibogaine on a number of occasions, the incidents generally follow similar experiences of brevity.
Vomiting produced by narcotic withdrawal has been subjectively described by patients as chronic, prolonged and more extensive then that produced by Ibogaine.
Yawning is a sign rarely seen in Ibogaine only or Ibogaine treated narcotic dependent patients and is associated with the protracted stimulant effect believed caused by Ibogaine's principal metabolite, desmethyl ibogaine. Diarrhea occurred in a few patients approximately six days after treatment with Ibogaine and was controlled with a single dose of anti-diarrhea medication.
While preclinical research (Dzoljic 1989 and Glick 1992) demonstrate only partial elimination of narcotic withdrawal signs, the human experience provides for virtual elimination of withdrawal signs including diarrhea, rhinorrhea, piloerection lacrimation, mydriasis, shivering, muscle twitches, abdominal cramps and anxiety. Sweating is exhibited in 16% to 25% of the narcotic dependent patients treated with Ibogaine. It was seen in 16% of the non Dutch patients and in 25% of the total patient group with the inclusion of the Dutch patients. It may be hypothesized that the distinctions among the Dutch and other patients may be due to the method of administration that for the Dutch was smoking or possibly to distinctions in the type of heroin that in The Netherlands was a brown variety or to the potency of the heroin.
It should be noted that all patients treated with Ibogaine had undergone some other form(s) of treatment for narcotic withdrawal and that the patients almost universally considered Ibogaine to be more effective, more humane and to provide greater dignity in the withdrawal process.
The most unique effect in the treatment of narcotic withdrawal for the researchers was the finding that Ibogaine had the ability to attenuate narcotic withdrawal signs during the 2 to 4 day treatment period not only for heroin, but for Methadone as well. Patients using up to 180mg/day of Methadone were treated with Ibogaine. Patients using up to 120mg/day of Methadone were detoxified to abstinence. In one case where Dutch addict self-help groups treated a couple, each using 180mg/day of methadone, the patients reduced their Methadone use to 30mg/day. In discussion with the late Nico Adriaans, one author suggested that under these circumstances the treatments might be considered to be unsuccessful. Mr. Adriaans replied, that they "Were a considerable success as no one in the Dutch Methadone establishment had ever seen a reduction of 180mg/day of Methadone to 30mg/day of Methadone in a 1 week period without extreme discomfort." Mr. Adriaans was a field worker for the European Addiction Research Institute at Erasmus University Rotterdam, as well as one of the motivating forces in the Dutch addict self-help movement.
While this paper briefly treats Ibogaine's effects on objective signs of narcotic withdrawal, one of the aspects of Ibogaine that makes it particularly interesting in the treatment of substance-related disorders is Ibogaine's ability to interrupt the craving to seek and use opiates, stimulants, alcohol, nicotine or combinations of those drugs seen in poly-drug dependent patients (Kaplan, 1993; Lotsof, 1985, 1986, 1989, 1991, 1995; Sheppard 1994 and Sisko 1993).
The effects of Ibogaine on opiate withdrawal are clearly defined in the chart: Objective Opiate Withdrawal and Ibogaine Signs: Human Observations, that follows.
The issue of objective signs of anxiety experienced by 3% of Ibogaine treated narcotic dependent patients are believed to be expressions of trauma (Bastiaans, 1991) and will be discussed in future publications.
|
Signs |
Opiate Withdrawal |
Ibogaine |
Ibogaine + Opiates |
|---|---|---|---|
|
Diarrhea Yawning Rinorrhea Piloerection Lacrimation Mydriasis Shivering Restlessness Vomiting Muscle Twitches Abdominal Cramps Sweating Anxiety Sleeplessness |
Yes
Yes Yes Yes Yes Yes Yes Yes Chronic Yes Yes Yes Yes Yes |
No
Rare No No No No No Post 20 Hrs ibogaine Acutre/motion related No No No No Yes |
*3% - 12%, 6 days post
Rare No No No 5% (moderate) No Post 20 Hrs ibogaine Acutre/motion related No No *16% - 25% **3% Yes |
* Principally seen in Dutch patients and may be due to route of administration (smoking) and strength or type of heroin (brown).
** This effect is hypothesized to be due to psychological trauma experienced by the patients previous to treatment with Ibogaine.
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*Correspondence: H.S. Lotsof, NDA International, Inc., PO Box 100506, Staten Island, NY 10310-0506, USA., tel: 1 718 442-2754, email: ibogaine@desk.nl
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