Neurologic, Electroencephalographic and General Medical Observations in
Subjects Administered Ibogaine
Daniel J. Luciano, M.D., Department of Neurology, NYU School of Medicine, New
Edgardo A. Della Sera, M.D., Centro Medico Paitilla, Panama City, Panama.
Ezequiel G. Jethmal, M.D., Centro Medico Paitilla, Panama City, Panama.
IBOGAINE is a potentially hallucinogenic indole alkaloid with anecdotal
antiaddictive properties against multiple drugs of abuse. Medical literature
concerning the administration of this substance to humans is sparce. Ibogaine
HCL (20-25 mg/kg) was administered orally to five subjects addicted to cocaine
and/or opiates. Subjects underwent continuous intensive medical, neurologic and
electroencephalographic observation. Movement-induced nausea and vomiting
was seen in several subjects, all developed transient ataxia, and several
experienced visual hallucinosis. No general medical, EKG or EEG abnormalities
were seen. No subjects experienced withdrawal symptoms 24 hours after
treatment, and two subjects were free of withdrawal or craving one week after
Ibogaine (NIH 10567, Endabuse[TM]) is an indole alkaloid derived from the
West African bush, Tabernanthe iboga. Historically, the crude extract has been
used by native tribes in Gabon; in low doses as a stimulant, and in high doses as
an hallucinogenic agent utilized in folk rituals (1). Ibogaine has also been
utilized in the psychotherapeutic milieu, largely for its abreactive properties
(2,3). More recently, anecdotal reports have indicated that ibogaine has potential
antiaddictive properties against multiple drugs of abuse, including opiates,
stimulants and alcohol (4-9). Drug use is reportedly abruptly terminated without
the development of withdrawal symptoms or drug-craving. There is also a body of
recent animal research to support such claims (10-16). Pharmacologic studies
suggest that ibogaine may act via interactions with the opioid, dopaminergic,
serotonergic and/or glutamatergic neurotransmitter systems (13,17-21).
Reports of ibogaine administration to humans have been largely anecdotal
and medically unsupervised. The few reports by physicians have utilized lower
dosages of ibogaine (300-400 mg) than those reported effective in the
interruption of polysubstance abuse (20-25 mg/kg), and descriptions of its effects
have concentrated more on the visual imagery induced and the psychodynamic
effects of treatment (2,3). The present report is intended to enlarge the small
medically supervised literature concerning the acute effects of human treatment
with ibogaine, particularly in the setting of chemical dependence. Specific
attention was paid to general medical, neurologic and electroencephalographic
The present study represented a collaborative effort between the University of
Miami, CITA (Centro Internacional para el Tratamiento de Addiciones) and NDA
International. Subjects were obtained by private application to NDA International
for the Endabuse procedure. A total of five subjects were studied. Initial
screening evaluations were performed at the University of Miami (subjects 1-3),
or the Hospital for Joint Diseases (subjects 4,5). Evaluations consisted of general
medical, neurologic and psychiatric examinations. In Panama (Centro Medico
Paitilla), further screening was performed, which included EKG, EEG, cranial
MRI scan, CBC, SMA-20, urinalysis, HIV and hepatitis serology, alcohol and drug
screens. Study exclusions included: seizure disorder, hypertension,
cardiac/hepatic/renal disease, or DSM-4 Axis 1 diagnoses. Treatment was
conducted by the Panamanian authors at the Centro Medico Paitilla (Panama
City) and was approved by the IRB of that institution. Informed consent was
obtained from all subjects prior to treatment.
Three subjects (1,2,3) were evaluated neurologically by the primary author in
Panama City before, during and immediately after treatment in Panama City. The
other two subjects had neurologic and EEG evaluations performed in New York
approximately one week before and after treatment, and also had EEGs
performed during treatment. Neurologic observations for these subjects were
provided by the secondary authors, who were in attendance during treatment in
The subjects were first administered a 1 mg/kg test dose of ibogaine
hydrochloride (OMNICHEM SA, Belgium) orally in capsule form. Patients were
attended continuously by nursing and physician staff, and vital signs were
performed every 30 minutes. The next day 0.5 mg/kg was administered to rule-
out the possibility of a hypersensitivity reaction. On the morning after the second
test dose administration, subjects were pretreated with two tablets of
domperidone 10 mg, given one hour apart, in hopes of preventing the
development of nausea and vomiting. They then received approximately 25
mg/kg of ibogaine hydrochloride orally, with 75% of the dosage given initially,
and the remaining 25% one hour later. The subjects then rested in bed in a
relatively darkened hospital room with continuous medical monitoring.
Vital signs and EKG were recorded every 30 minutes for four hours, and then
hourly for eight hours. Acute symptomatic treatment was provided when
necessary, such as the administration of metoclopramide for nausea and
vomiting. Neurologic examinations were performed on the first three subjects by
the primary author immediately prior to treatment, and 1, 2, 4, 8 and 24 hours
after the ingestion of ibogaine. Gross neurologic examinations were performed by
the secondary authors for subjects 4 and 5 during treatment, and a
comprehensive exam was performed by the primary author one week later in
New York. EEG studies were performed immediately pretreatment, as well as
four and 24 hours after the ingestion of ibogaine. These were 30 minute EEG
studies utilizing a Stellate system with electrodes placed according to the 10-20
system of electrode placement. A certified psychotherapist was in attendance at
all times to provide acute counselling as necessary.
Vomiting may occur in up to 30% of those given ibogaine, with or without
narcotic dependency, and is movement sensitive (2,3,6). Domperidone was
administered in our subjects prophylactically, but three experienced movement-
induced vomiting early in the course of treatment and were treated with
metoclopramide 10 mg IV. In two of these subjects, since vomiting occurred early,
an additional 5 mg/kg of ibogaine was administered orally to assure absorption
of the appropriate dose. In the third subject, the dose was readministered as a
rectal infusion due to persistent vomiting . As a result of such vomiting, some
patients were at points reluctant to rise from bed for a full neurologic evaluation.
In all subjects, baseline neurologic examinations were normal. Signs of
transient cerebellar dysfunction developed in all subjects, generally by two hours
after ingestion. All neurologic examinations were normal 24 hours after
treatment. In all cases, EEGs were normal in the awake or awake and drowsy
states, before, during and after treatment.
Visual hallucinosis occurred in two subjects, initially noted within the
first two hours after ingestion. The hallucinations were noted only with eyes
closed. Notably, subjects remained oriented and fully responsive, and
demonstrated no evidence of psychological or physiologic anxiety, whether or not
During the study there were no significant general medical or
electrocardiographic abnormalities noted.
On the morning after treatment, subjects demonstrated no psychological or
physiologic evidence of drug withdrawal, nor was there evidence of craving or
drug-seeking behavior. In the case of subjects 4 and 5, there was no evidence of
drug withdrawal or craving when seen one week later in New York. Subjects 1
through 3 returned home following treatment and were thus not seen by the
authors in follow-up.
Overall, ibogaine was well-tolerated, aside from the occurrence of early
motion-induced nausea and vomiting in several subjects, which likely reflects
acute vestibulocerebellar dysfunction. Thus, subjects treated with ibogaine should
remain relatively immobile, and prophylactic treatment with antiemetics seems
warranted to ensure effective treatment. There was otherwise no evidence of
general systemic side-effects due to ibogaine.
In animal studies of ibogaine, tremor and ataxia are frequent acute effects
of treatment (13,22,23), and suggest the presence of transient cerebellar
dysfunction. Some concern has been raised by O'Hearn et al., who reported
indirect evidence of possible cerebellar Purkinje cell damage in rats given 100
mg/kg of ibogaine (23). However, the ibogaine dosage used in this study was
much higher than that used in the Endabuse procedure (20-25 mg/kg). Molinari
et al. have replicated these findings at a dose of 100 mg/kg, but have found no
evidence of neuropathologic changes at a dose of 40 mg/kg (24). Similarly,
Sanchez-Ramos and Mash found no neuropathologic changes in green monkeys
given ibogaine 5-25 mg/kg daily for four days (25). In our subjects, ataxia and
rare tremor were seen transiently, but there was no clinical evidence of
persistent cerebellar dysfunction following treatment.
Past animal research has suggested that high doses of ibogaine may result
in seizures (22,26) However, there is also animal data suggesting that ibogaine
may have an anticonvulsant effect (27). In rats, ibogaine (10-30 mg/kg
intraperitoneal) caused only an increase in EEG rhythmic theta range activity,
but there was no report of epileptiform activity being seen (28). In cats, EEG
arousal patterns have been described (29). In our subjects, the first humans
studied electroencepha-lographically during ibogaine intoxication, EEGs were
normal and there was no clinical or electroencephalographic evidence of seizure
Despite the powerful hallucinogenic properties of ibogaine, all subjects
maintained intact reality testing and responsivity during treatment and
demonstrated no signs or symptoms of anxiety or thought disorders. In three
subjects visual hallucinosis occurred during treatment. Hallucinosis was present
only with the subjects eyes closed, as described by Sigg (29,30), and patients
were typically reluctant to discuss these at any length. One patient described
simple moving geometric spheres, like "asteroids in space," akin to the decription
by Sigg of "disks dancing up and down the walls." (30). Another described vivid
memories of early childhood, similar to the reactions decribed by Naranjo (2,3). It
is notable that at least short-term interruption of drug use was achieved whether
or not patients experienced visual hallucinosis. In some subjects who did not
experience hallucinosis the heightened awareness of the psychodynamic factors
behind their addictions may still have contributed to successful treatment.
However, this does not preclude the possibility that the antiaddictive effects of
ibogaine may be more closely related to potential neurotransmitter effects rather
than psychological abreation. These matters will require further research in
order to determine ibogaine's mechanism of action.
In our subjects there were no signs or symptoms of drug withdrawal or
craving immediately after treatment. In addition, when examined one week after
treatment the two subjects examined at that time remained free of symptoms
Though drug testing was not performed at that time, there were no observable
signs of recurrent drug use. There was also no reason for these subjects to conceal
recurrent drug use, as they had sought treatment on their own, at their own
expense. The post-treatment period of observation in this study was limited and
long-term follow-up will be helpful in assessing the long-term benefits of
ibogaine treatment. The authors recognize the methodological weakness of not
obtaining post-treatment drug screens and suggest that this be overcome in future
research with appropriate evaluations.
The present report represents one of the few medically supervised trials
of ibogaine for the interruption of human addiction syndromes, and describes the
effects of the highest dosages of ibogaine yet reported in a scientific human study.
The results indicate that ibogaine is generally well-tolerated and produces
transient cerebellar dysfunction, not unlike that produced by other intoxicants,
with no signs of persistent neurologic effects. The absence of withdrawal
symptoms or drug craving following treatment supports the anecdotal human
reports of ibogaine's efficacy in the treatment of multiple addiction syndromes.
Though the number of subjects in this study is small, and the period of follow-up
limited, the results suggest that ibogaine does acutely interrupt addictive
behavior without untoward consequences, providing a symptom-free window of
opportunity that may permit major changes in patients lives, particularly in the
presence of an appropriate psychosocial support structure. Such treatment may
offer a viable alternative to less effective, more prolonged and costly methods of
1) Fernandez JW. Bwiti: an Ethnography of Religious Imagination in Africa. Princeton
Press: Princeton; 1982.
2) Naranjo C. Psychotherapeutic possibilities of new fantasy-enhancing drugs.
Clin Toxicol 1969;2(2):209-224.
3) Naranjo C. The Healing Journey: New Approaches to Conciousness. Pantheon: New
4) Sisko B. Interrupting drug dependency with ibogaine; a summary of four case
histories. MAPS Bulletin 1993;IV:15-24
5) Sheppard SG. A preliminary investigation of ibogaine: case reports and
recommendations for further study. J Substance Abuse Treat 1994;11(4):379-385.
6) Lotsof HS. Ibogaine in the treatment of chemical dependence disorders:
clinical perspectives. MAPS Bulletin 1995;5(3):16-27.
7) Lotsof HS. Rapid method for interrupting the narcotic addiction syndrome.
U.S. Patent no. 4,499,096 (1985).
8) Lotsof HS. Rapid method for interrupting the cocaine and amphetamine abuse
syndrome. U.S. Patent no. 4,587,243 (1986).
9) Lotsof HS. Rapid method for attenuating the alcohol dependency syndrome.
U.S. Patent no. 4,857,523 (1989).
10) Dzoljic ED, Kaplan CD, Dzoljic MR. Effects of ibogaine on naloxone
precipitated withdrawal syndrome in chronic morphine dependent rats. Arch Intl
11) Glick SD, Rossman K, Steindrof S, Maisonneuve IM, Carlson JN. Effects and
aftereffects of ibogaine on morphine self-administration in rats. Eur J Pharmacol
12) Glick SD, Rossman K, Rao NC, Maisonneuve IM, Carlson JN. Effects of
ibogaine on acute signs of morphine withdrawal in rats: independence from
tremor. Neuropharm 1992;31(5):497-500.
13) Glick SD, Kuehne ME, Raucci J, Wilton TE, Larson D, Keller RW, Carlson NJ.
Effects of iboga alkaloids on morphine and cocaine self-administration in rats:
relationship to tremorigenic effects and to effects on dopamine release in nucleus
accumbens and striatum. Brain Res 1994;657:14-22.
14) Cappendijk SLT, Dzoljic MR. Inhibitory effects of ibogaine
on cocaine self-administration in rats. Eur J Pharmacol 1993;241:261-265.
15) Sershen H, Hasim A, Lajtha A. Ibogaine reduces preferences for cocaine
consumption in C57BL/6By mice. Pharmacol Biochem Behav 1994;47(1):13-19.
16) Rezvani AH, Overstreet DH, Lee YW. Attenuation of alcohol intake by
ibogaine in three strains of alcohol-preferring rats. Pharmacol Biochem Behav 1995;
17) Glick SD, Rossman K, Wang S, Dong N, Keller RW. Local effects of ibogaine
on extracellular levels of dopamine and its metabolites in nucleus accumbens and
striatum: interactions with d-amphetamine. Brain Res 1993;628:201-208.
18) Popik P, Layer RT, Skolnick P. The putative anti-addictive drug ibogaine is a
competitive inhibitor of [3H]MK-801 binding to the NMDA receptor complex.
19) Popik P, Layer RT, Skolnick P. 100 years of ibogaine: neurochemical amd
pharmacological actions of a putative anti-addictive drug. Pharmacol Rev
20) Mash DC, Staley JK, Pablo JP, Holohean AM, Hackman JC, Davidoff RA.
Properties of ibogaine and its principal metabolite (12-hydroxyibogamine) at the
MK-801 binding site of the NMDA receptor complex. Neurosci Let 1995;192:53-
21) Mash DC, Staley JK, Baumann MH, Rothman RB, Hearn WL. Identification of
a primary metabolite of ibogaine that targets serotonin transporters and elevates
serotonin. Life Sci 1995; 57(3):45-50.
22) Ibogaine toxicity studies. CIBA-Geigy Pharmaceuticals, ca 1956.
23) O'Hearn E, Long DB, Molliver ME. Ibogaine induces glial activation in
parasagittal zones of the cerebellum. NeuroReport 1993;4:299-302.
24) Molinari HH, Maisonneuve IM, Glick SD. Ibogaine neurotoxicity: a re-
evaluation. Brain Res (in press).
25) Sanchez-Ramos J, Mash D. Ibogaine research update: phase I human study.
MAPS Bulletin 1994:4;11.
26) Sero I. Une apocynacee d'Afrique Equatoriale: Tabernanthe Iboga. These Doci Univ
(Pharm). Doulandoure: Toulousse, 1944.
27) Chen G, Bohner B. A study of central nervous system stmulants. J Pharmacol
Exp Ther 1958;123(3):212-215.
28) Depoortere H. Neocortical rhythmic slow activity during wakefulness and
paradoxical sleep in rats. Neuropsychobiol 1987;18:160-168.
29) Schneider JA, Sigg EB. Neuropharmacological studies on ibogaine, an indole
alkaloid with central stmulant properties. Ann NY Acad Sci 1957;66:765-766.
30) Schneider JA, Sigg EB. Pharmacologic analysis of tranquilizing and
central stimulating effects. In: HH Pennes (ed); Psychopharmacology;
Pharmacologic Effects on Behavior. 1958, Hoeber: New York:75-98.