IBOGAINE: A BRIEF HISTORY
INCLUDING RESEARCH CONDUCTED IN 1995 & 1996
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.
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
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's findings in human subjects
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.
Studies not previously discussed have been accomplished concerning both
Ibogaine and its principal metabolite desmethyl ibogaine
(12-hydroxyibogamine or noribogaine) as well as, studies that have
demonstrated the complexity of addiction via the interaction of various
neurohormonal systems that are effected by Ibogaine or desmethyl ibogaine.
Schechter and Gordon (1993) determined that Ibogaine from the three
principal sources of the drug; Sigma Chemical, The National Institute on
Drug Abuse and NDA International, Inc. (ENDABUSE, NIH 10567) would allow
pre-clinical work using any research samples from the above suppliers to
be comparable. Sershen et al (1994) reviewed the effects of Ibogaine on
serotonergic and dopaminergic interactions in the striatum of mice and
rats and then (1995) published on Ibogaine actions on kappa opioid and
5-HT induced changes on dopamine release. Pearl et al. (1995), continuing
research of the Albany Medical College Ibogaine working group published on
the effects of prior morphine exposure to enhance Ibogaine's effects in
reducing morphine-induced locomotor stimulation. Rezvani et al.
demonstrated that Ibogaine would reduce alcohol intake in
alcohol-preferring rats (1995) adding to previous pre-clinical
demonstrations that Ibogaine would reduce the self-administration of
opiates and cocaine thus supporting Lotsof's clinical findings that
Ibogaine was effective for attenuating opiate, stimulant and alcohol
self-administration. Hough et al. added significant understanding to the
actions of Ibogaine in the publication of data on tissue distribution of
Ibogaine from intraperitoneal and subcutaneous injections. The paper
concluded that the persistence of the Ibogaine in fat may contribute to
Ibogaine's long duration of action and that Ibogaine is subject to
substantial "first pass" effect after IP dosing, but not after SC dosing.
Responding to the concern of neurotoxicity in rats found by O'Hearn et
al. (1993), Molinan et al. (1994) published that Ibogaine at therapeutic
doses in the rat did not produce neurtoxicity, supporting Mash's (1995)
data that Ibogaine did not demonstrate neurotoxicity from multiple
administrations at therapeutic doses in monkeys or humans.
Concerning desmethyl ibogaine (noribogaine), Pearl et al. (1995) provided
an important insight into the mechanisms of actions of that drug in a
radioligand-binding study that showed desmethyl ibogaine to bind to all
opiate receptors. Rezvani et al. (1995) published data showing
noribogaine, like Ibogaine, to also reduce alcohol intake in rats.
Inherent in a review of the papers herein discussed and in discussions
with the researchers, a significant understanding of the actions and
interrelated actions of ibogaine and noribogaine are provided.
Ibogaine information source: http://www.desk.nl/~ibogaine/
BIBLIOGRAPHY: IBOGAINE & NORIBOGAINE
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