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PAPER
TOXICOLOGY
Kenneth R. Alper,
1
M.D.; Marina Stajic
´,
2
Ph.D.; and James R. Gill,
3
M.D.
Fatalities Temporally Associated with the
Ingestion of Ibogaine
ABSTRACT: Ibogaine is a naturally occurring psychoactive plant alkaloid that is used globally in medical and nonmedical settings for opioid
detoxification and other substance use indications. All available autopsy, toxicological, and investigative reports were systematically reviewed for the
consecutive series of all known fatalities outside of West Central Africa temporally related to the use of ibogaine from 1990 through 2008. Nineteen
individuals (15 men, four women between 24 and 54 years old) are known to have died within 1.5–76 h of taking ibogaine. The clinical and post-
mortem evidence did not suggest a characteristic syndrome of neurotoxicity. Advanced preexisting medical comorbidities, which were mainly cardio-
vascular, and ⁄or one or more commonly abused substances explained or contributed to the death in 12 of the 14 cases for which adequate
postmortem data were available. Other apparent risk factors include seizures associated with withdrawal from alcohol and benzodiazepines and the
uninformed use of ethnopharmacological forms of ibogaine.
KEYWORDS: forensic science, toxicology, ibogaine, iboga alkaloid, substance abuse, human, fatality, opioid, opioid detoxification,
ethnopharmacology
The iboga alkaloids are a group of monoterpene indole alkaloids,
some of which reportedly reduce the self-administration of drugs of
abuse and opiate withdrawal symptoms in animal models and
humans (1,2). Ibogaine (Fig. 1), the most extensively studied iboga
alkaloid, occurs in the root bark of the West African Apocynaceous
shrub Tabernanthe iboga Baill. In Gabon, eboga, the scrapings of
the root bark, has been used as a psychopharmacological sacrament
in the Bwiti religion for several centuries (3,4). Elsewhere, includ-
ing North America, Europe, and South Africa, ibogaine is used for
the purpose of acute opioid detoxification, and to reduce craving
and maintain abstinence from opioids and other abused substances
including stimulants and alcohol, as well as for psychological or
spiritual purposes (5).
Ibogaine is used most frequently as a single oral dose in the
range of 10–25 mg ⁄kg of body weight for the specific indication
of detoxification from opioids (5,6). It is most commonly used in
the form of the hydrochloride (HCl), which certificates of analysis
typically indicate is 95–98% pure, with present retail prices in the
range of c. $125–$250 USD per gram. Ibogaine is also used in the
form of alkaloid extracts or dried root bark (Fig. 2).
Ibogaine is a schedule I substance in the United States, and simi-
larly is illegal in France, Denmark, Sweden, Belgium, Switzerland,
and Australia. However, it is unregulated in most countries, where
it is neither illegal nor officially approved. Lay providers administer
ibogaine in nonmedical settings and have accounted for the
majority of treatments (5). Ibogaine is administered in medical set-
tings in countries such as Mexico and South Africa, where physi-
cians have the legal prerogative to prescribe unapproved
medications.
Published case series and individual accounts regarding ibogaine
foropioiddetoxificationtendtobeconsistentwithregardtorapid
remission of acute withdrawal symptoms following a single admin-
istration that is subsequently sustained without further ibogaine
treatment or the use of opioids (1,6,7). This effect of ibogaine
appears to be pharmacologically mediated and not accounted for
by placebo, which has clinically negligible effects in opioid detoxi-
fication (8–10). In the naloxone-precipitated withdrawal model of
opioid detoxification, iboga alkaloids have attenuated opioid with-
drawal signs in 13 of 14 independent replications in two rodent
and two primate species (11–24). Ibogaine administered to rats or
mice as a single dose reduces the self-administration of morphine
(25–28), cocaine (26,29,30), and alcohol (31,32), with sustained
treatment effects for 48–72 h averaged for an entire sample, and an
even longer duration in individual animals (25,26,28,30). The
serum half-life of ibogaine in the rat is c. 1–2 h (33,34), indicating
that the prolonged effect on self-administration outlasts the presence
of ibogaine itself, without compelling evidence that it is mediated
by a long-lived metabolite (35).
Ibogaine does not appear to be an abused substance. The
National Institute on Drug Abuse (NIDA) did not identify potential
abuse as an issue in the context of its research program on iboga-
ine, which included preclinical testing and the development of a
clinical trial protocol (1). Animals do not self-administer 18-meth-
oxycoronaridine (18-MC), a closely structurally related ibogaine
congener with the same effects as ibogaine on self-administration
and withdrawal in preclinical models (36). Aversive side effects
such as nausea and ataxia limit ibogaine’s potential for abuse.
Ibogaine potentiates the lethality of opioids (33,37–39). This is
apparently because of an enhancement of opioid signaling (1,40),
and not because of binding at opioid receptors as an agonist (such
1
Departments of Psychiatry and Neurology, New York University School
of Medicine, 550 First Avenue, New York, NY 10016.
2
Department of Forensic Toxicology, New York City Office of Chief
Medical Examiner and Department of Forensic Medicine, New York Uni-
versity School of Medicine, 520 First Avenue, New York, NY 10016.
3
New York City Office of Chief Medical Examiner and Department of
Forensic Medicine, New York University School of Medicine, 520 First
Avenue, New York, NY 10016.
Received 28 July 2010; and in revised form 17 Nov. 2010; accepted 20
Nov. 2010.
J Forensic Sci, March 2012, Vol. 57, No. 2
doi: 10.1111/j.1556-4029.2011.02008.x
Available online at: onlinelibrary.wiley.com
398 2012 American Academy of Forensic Sciences
as methadone) or antagonist. Doses of ibogaine used in opioid
detoxification do not produce signs of overdose in individuals who
lack tolerance to opioids, such as African Bwiti adepts, or individu-
als in non-African contexts who take ibogaine for psychological or
spiritual purposes or the treatment of addiction to substances other
than opioids. If ibogaine was acting as an opioid agonist, it would
not be tolerated by opioid-nave individuals because the methadone
dosage of 60–100 m g ⁄day that is used to stabilize withdrawal
symptoms in the maintenance treatment of opioid-dependent
patients (41) substantially exceeds the estimated LD
50
of 40–50 mg
in humans who are not pharmacologically tolerant to opioids (42).
Other evidence that ibogaine alters signaling through opioid recep-
tors but is not itself an orthosteric agonist includes its potentiation
of morphine analgesia in the absence of a direct analgesic effect
(22,38,39,43–47). Ciba Pharmaceutical patented the use of ibogaine
to reduce tolerance to opioid analgesics in 1957 (47).
Although ibogaine contains an indole ring and is designated as a
‘‘hallucinogen,’’ it is pharmacologically distinct from the ‘‘classi-
cal’’ hallucinogens such as LSD, mescaline, or psilocybin, which
are thought to act by binding as agonists to the serotonin type 2A
(5-HT
2A
) receptor (48). Serotonin agonist or releasing activity does
not appear to explain ibogaine’s effects in opioid withdrawal
(2,49). There is no anecdotal or preclinical evidence for a signifi-
cant effect of classical hallucinogens in acute opioid withdrawal,
and in the animal model ablation of 90% of the raphe, the major
serotonergic nucleus of the brain does not significantly affect the
expression of opioid withdrawal (50). Descriptions of subjective
experiences associated with ibogaine differ from those associated
with the classical hallucinogens (5,48,51). The visual effects of
classical hallucinogens are typically most strongly experienced with
the eyes open and limited to alterations of colors, textures, and pat-
terns. In contrast, the psychoactive state associated with ibogaine is
experienced most intensely with the eyes closed and has been
described as ‘‘oneiric’’ and likened to a ‘‘waking dream,’’ with
Iboga alkaloid R1R2R3
Ibogaine OCH3HH
Noribogaine OH H H
Ibogamine H H H
Ibogaline OCH3OCH3H
Tabernanthine H OCH3H
Voacangine OCH3HCO
2CH3
FIG. 1—Chemical structures of ibogaine and its major metabolite norib-
ogaine, and the alkaloids ibogamine, ibogaline, tabernanthine, and voacan-
gine that co-occur with ibogaine in T. iboga. In the Chemical Abstracts
system the positions of R
1
,R
2
, and R
3
on the ibogamine parent structural
skeleton are respectively numbered 12, 13 and 18, whereas in the Le Men
and Taylor system these same positions are numbered 10, 11 and 16.
FIG. 2—Forms of availability of ibogaine: Ibogaine is available in form of the hydrochloride (HCl) dried root bark, or alkaloid extract. The upper left
photo shows 96% pure ibogaine HCl in the form of powder in the upper left quadrant of the photo. In the lower left quadrant of the photo are five capsules.
The four lighter colored capsules contain 96% pure ibogaine HCl; the smaller two contain 120 mg and the larger two contain 250 mg respectively. The larg-
est capsule is darker and contains 330 mg of 85% ibogaine HCl. In the lower right quadrant of the photo is ground dried root bark. The upper right photo
shows alkaloid extract with an estimated total iboga alkaloid content of about 40–50%. The lower photo shows a partially scraped dried Tabernanthe iboga
root, with external bark layer, an inner bark layer, and wood. The alkaloid content is mainly concentrated in the inner root bark layer, which is exposed
along the lower border of the bare wood in left middle portion of the photo (photos courtesy of Robert Bovenga Payne and Rocky Caravelli).
ALPER ET AL. •FATALITIES TEMPORALLY ASSOCIATED WITH THE INGESTION OF IBOGAINE 399
interrogatory verbal exchanges involving ancestral and archetypal
beings, and movement and navigation within visual landscapes.
Another frequently described experience is panoramic memory, the
recall of a rapid, dense succession of vivid autobiographical visual
memories. Mechanistically, these subjective experiences associated
with ibogaine might possibly suggest functional muscarinic cholin-
ergic effects, which are prominent in the mechanisms of dreaming
and memory (52). In animals, ibogaine is reported to enhance spa-
tial memory retrieval (53,54), and to produce an atropine-sensitive
EEG rhythm (55,56), commonly regarded as a model of REM
sleep (57).
Ibogaine’s highest affinity receptor interactions are as an agonist
at the r
2
receptor, and an antagonist at the N-methyl-d-aspartate-
type (NMDA) glutamate and a3b4 nicotinic acetylcholine recep-
tors (1,2,58). Initially, ibogaine’s mechanism of action in drug
self-administration and withdrawal was hypothesized to involve
NMDA receptor antagonism (59); however, this hypothesis is now
viewed as unlikely because the synthetic ibogaine congener 18-
MC has negligible NMDA receptor affinity but is equally effec-
tive as ibogaine in reducing withdrawal and self-administration in
the animal model (2). Studies of iboga alkaloids and nicotinic
agents (60–64) provide some support for antagonism of the a3b4
nicotinic receptor as a possible mechanism of action with regard
to drug craving and self-administration but do not appear to
explain detoxification in the setting of extensive physical depen-
dence on opioids. Likewise, the increased expression of glial cell-
derived neurotrophic factor may mediate reduction in drug craving
and self-administration (32) but does not explain ibogaine’seffect
in opioid detoxification.
Ibogaine was administered to human subjects in a clinical Phase
I dose escalation study under a physician-initiated Investigational
New Drug Application approved by the FDA in 1993 (65). The
study was eventually discontinued because of disputes related to
contractual and intellectual property issues (66); however, the avail-
able safety data indicated no adverse events (65). Most of the
available preclinical pharmacological, toxicological, and pharmaco-
kinetic data on ibogaine are derived from research supported by
NIDA between 1991 and 1995. NIDA eventually ended its iboga-
ine project without having initiated a clinical trial apparently
because of its high cost and complexity relative to NIDA’sexisting
resources (1). Ibogaine’s underlying structure cannot be patented
because it is naturally occurring, which limits the financial incen-
tive for its development. Ibogaine continues to be used in unregu-
lated contexts with associated risks because of a lack of clinical
and pharmaceutical standards (5).
Deaths have occurred temporally related to the use of ibogaine.
This article presents a systematic review of all available autopsy,
toxicological, and investigative reports on the consecutive series
consisting of all known fatalities temporally related to the use of ib-
ogaine that have occurred outside of West Central Africa from
1990 through 2008.
Materials and Methods
The Institutional Review Board of the New York University
School of Medicine and the General Counsel of the New York City
Office of Chief Medical Examiner (OCME) approved this research.
Identification of Cases
This series spans the time interval beginning with the first
reported fatality in 1990 (1) until December 2008. Eighteen of the
19 fatalities in this series were found through contact with ibogaine
treatment providers since the mid-1990s (5,6,67,68). One of these
fatalities was also investigated by the OCME (69) as are all unex-
pected, violent, and suspicious deaths in New York City. One fatal-
ity was found by literature search (70). The ethnographic
methodology and access to the network of the providers of iboga-
ine treatment and other participants in the ibogaine subculture are
described in detail elsewhere (5,67).
All fatalities were followed up by contact with appropriate
medico-legal death investigation agencies to obtain all available
autopsy and toxicology reports, inquest testimony, and other inves-
tigative reports. In addition to documentary evidence, in most
instances, treatment providers and other first-hand observers of the
death scene were interviewed. Systematic evaluation of the litera-
ture included Medline searches from 1966 to June 2010 utilizing
PubMed and ISI Web of Knowledge with the search terms ‘‘iboga-
ine’’ combined with ‘‘death’’ or ‘‘fatality’’ in addition to searches of
periodical and nonindexed ‘‘grey’’ literature as described elsewhere
(5,67).
Analytical Toxicology
Various methodologies for toxicological analysis of ibogaine
(molecular weight 310.44) have been previously described, includ-
ing liquid chromatography with flourimetric detection (71), gas
chromatography ⁄mass spectrometry (GC ⁄MS) (72–76) liquid chro-
matography ⁄mass spectrometry (LC-MS) (70,75,77–80), and liquid
chromatography-tandem mass spect rometry (LC-MS ⁄MS) (81–83).
There is a potential for confusion because of the use of two differ-
ent schemes for numbering the iboga alkaloid parent ibogamine
skeleton (84), the Chemical Abstracts system, which is common in
the biological and medical literature, and the Le Men and Taylor
system, which tends to be favored by natural products and synthetic
chemists and is also frequently encountered in the biological
literature (see Fig. 1).
Ibogaine screening usually is not included in most routine foren-
sic toxicological laboratories and a suspicion of use is required for
analysis, which is typically performed by a referral laboratory. For
two fatalities in this series (cases #3 and #10 in Table 1), the
Forensic Toxicology Laboratory at the OCME performed the analy-
sis. The presence of ibogaine was confirmed by GC ⁄MS and the
concentration determined using GC with a nitrogen phosphorus
detector (69).
Cause of Death
The certified cause of death is included in Table 1, entitled
‘‘Official cause of death.’’ The certified cause of death is that which
is indicated by the official documentation, that is, autopsy report or
death certificate, by the local authority that investigated and
recorded the death. The available documentation varied greatly with
regard to investigative rigor, level of detail, and geographic location
of the official entity that issued the report. As an approach to con-
trolling for this variance, a coauthor (JRG, a board-certified foren-
sic pathologist) made a determination regarding the cause of each
deathonthebasisofallavailabledata,whichinadditiontothe
official documentation, included any information that was provided
by treatment providers and other first-hand observers of the death
scene, or friends and acquaintances of the decedent. Table 1 pro-
vides the conclusions of this systematic, critical evaluation of all
available evidence in the far right-hand column entitled ‘‘Proximate
cause of death.’’
The cause of death is defined as the original, etiologically spe-
cific, underlying medical condition that initiates the lethal sequence
400 JOURNAL OF FORENSIC SCIENCES
TABLE 1—Worldwide known fatalities outside of West Central Africa temporally associated with the ingestion of ibogaine, 1990–2008.
Age ⁄Gender,
Reason for
Ibogaine Use Country Year Circumstance
Time Interval
from Most
Recent
Ingestion of
Ibogaine
Until Death
Ibogaine Form,
Dose
Ibogaine
(Blood, mg ⁄L
or mg ⁄kg)
Other
Toxicology
(mg ⁄L)
Other Autopsy
or Historical
Findings
Official Cause
of Death
Proximate Cause
of Death
144F
Psychological ⁄
spiritual (1)
France 1990 Witnessed
to become
unre-
sponsive
during
treatment
4 h Ibogaine
HCl
300 mg (c.
4.5 mg ⁄kg)
0.24
Liver: 0.17
Kidney: 0.3
Negative Hypertension;
prior left
ventricular
myocardial infarct,
marked
3-vessel coronary
artery
atherosclerosis,
inverted T waves
noted on EKG
3 months prior to
death
Acute heart
failure
(autopsy)
Acute ibogaine
intoxication.
Contributing
conditions:
atherosclerotic
and hypertensive
cardiovascular
disease
224F
Opioid
detoxification (6)
Netherlands 1993 Died during
ibogaine
treatment;
gurgling
sounds
19 h Ibogaine HCl
29 mg ⁄kg
Cardiac: 0.74
Femoral vein:
0.75
Morphine:
‘‘trace’’ <0.01
Noribogaine:
Cardiac: 11.28
Femoral
vein: 3.96
Charred tin foil
found in room
Undetermined;
role of ibogaine
unknown due to
lack of information
relating levels to
toxic effects
(autopsy)
Acute intoxication
due to the
combined
effects of
ibogaine and
morphine
336M
Opioid
detoxification,
cocaine
dependence (69)
USA 1999 Found dead
at home.
A syringe
found near
body
8–9 h Ibogaine HCl;
believed to be
16–20 mg ⁄kg
Subclavian
vein: 9.3
Brain: 18.6
Liver: 18.1
Benzoyl-
ecgonine: 0.6
Opiates: 0.1
(Morphine:
<0.1)
Depression,
adverse life
events prior to
treatment;
decedent was
aware of dangers
of use of cocaine
or heroin
concurrently
with ibogaine
Acute intoxication
due to the
combined effects
of opiates, cocaine,
and ibogaine
(autopsy)
Acute intoxication
due to the
combined effects
of opiates,
cocaine, and
ibogaine
440M
Opioid
detoxification
United
Kingdom
2000 Died in
bathroom;
vomited
immediately
prior to death
40 h Tabernanthe
iboga alkaloid
extract 6 g
administered
over c.6h
0.36 Other toxicology:
negative
Noribogaine:
detected
Ibogamine:
detected
Hepatitis C with
liver fibrosis,
pulmonary and
cerebral edema
Fatal reaction to
Tabernanthe iboga
preparation.
Contributing
condition:
Hepatitis C
(autopsy)
Acute ibogaine
intoxication
5. 35 F
Psychological ⁄
spiritual
Germany 2002 Found dead
in bed
(complained
of not feeling
well the
day before)
1.5 h Ibogaine HCl
500 mg
(c.8mg⁄kg)
Unknown Unknown Childhood
heart surgery
congenital,
moderate
coronary artery
atherosclerosis
Heart
failure ⁄
intoxication
(autopsy)
Acute ibogaine
intoxication
(unknown if
other drugs
involved).
Contributing
conditions:
atherosclerotic
cardiovascular
disease
Continued.
ALPER ET AL. •FATALITIES TEMPORALLY ASSOCIATED WITH THE INGESTION OF IBOGAINE 401
TABLE 1—Continued.
Age ⁄Gender,
Reason for
Ibogaine Use Country Year Circumstance
Time Interval
from Most
Recent
Ingestion of
Ibogaine
Until Death
Ibogaine Form,
Dose
Ibogaine
(Blood, mg ⁄L
or mg ⁄kg)
Other
Toxicology
(mg ⁄L)
Other Autopsy
or Historical
Findings
Official Cause
of Death
Proximate Cause
of Death
6. 32 M
Opioid
detoxification
(self-administered
by opiate abuser)
USA 2003 Found dead
in bed at his
residence
Unknown Bag of brown
powder at scene
that tested
positive for
ibogaine
(alkaloid
extract
vs
powdered
dried root
bark)
Cardiac: 0.95
Femoral
vein: 1.5
Liver: 8.0
Urine: 26
Vitreous: 0.54
Gastric: 2.9
Bile: 0.54
Benzoylecgonine
0.1
Methadone:
<0.1
Nordiazepam:
<0.1
Moderate
coronary
artery
atherosclerotic
stenosis.
History of opiate
abuse, and had
been in
methadone
maintenance
treatment
at time
of death
Ibogaine
intoxication.
Contributing
conditions:
atherosclerotic
cardiovascular
disease,
cocaine use
(autopsy)
Acute ibogaine
intoxication.
Contributing
conditions:
atherosclerotic
cardiovascular
disease,
chronic
cocaine abuse
754M
Opioid
detoxification,
alcohol
dependence
Mexico 2003 Died at
ibogaine
treatment
facility
60 h Ibogaine HCl
13 mg ⁄kg
Unknown Unknown Obesity, chronic
alcoholism,
smoker
(unclear if
autopsy was
performed;
report
unavailable)
Pulmonary
thromboembolism
(death
certificate)
Insufficient
information
845M
Opioid
detoxification,
alcohol
dependence
Mexico 2004 Died at
ibogaine
treatment
facility
20 h Ibogaine HCl
15 mg ⁄kg
Unknown Unknown Chronic
alcoholism,
obesity, cardiac
pacemaker
Acute hemorrhagic
pancreatitis.
Contributing
conditions:
Chronic
alcoholism,
obesity, opiate
pain medication
dependency
(autopsy)
Acute
hemorrhagic
pancreatitis
(during
ibogaine
treatment)
complicating
chronic
alcoholism
948F
Opioid
detoxification
Mexico
(autopsied
in the US)
2005 Died at
ibogaine
treatment
facility
2 days Ibogaine HCl
14 mg ⁄kg
0.82
Liver: 0.72
Diazepam: 0.06
Oxazepam:
0.39
Temazepam (trace)
Prior gastric
bypass surgery
with 135 lb
weight loss in
8 months
preceding death.
Fibromyalgia,
benzodiazepine
dependence that
was not
disclosed
to treatment
providers
Sudden cardiac
death due to
acute myocardial
infarct due to
acute coronary
syndrome.
Contributing
conditions:
Fibromyalgia,
chronic pain
medication
dependency
(autopsy)
Acute myocardial
infarct due to
coronary artery
atherosclerosis
during ibogaine
therapy for
opiate
dependence
complicating
chronic
fibromyalgia
Continued.
402 JOURNAL OF FORENSIC SCIENCES
TABLE 1—Continued.
Age ⁄Gender,
Reason for
Ibogaine Use Country Year Circumstance
Time Interval
from Most
Recent
Ingestion of
Ibogaine
Until Death
Ibogaine Form,
Dose
Ibogaine
(Blood, mg ⁄L
or mg ⁄kg)
Other
Toxicology
(mg ⁄L)
Other Autopsy
or Historical
Findings
Official Cause
of Death
Proximate Cause
of Death
10 43 M
Opioid
detoxification,
alcohol
dependence
USA 2005 Witnessed
cardiac arrest
during self-
administered
ibogaine treatment.
Witnessed apparent
generalized
tonic-clonic
seizure 17 h after
ibogaine ingestion
27 h Ibogaine HCl,
dose unknown
2.8 Diazepam: 0.03
Trimetho-
benzamide: 0.85
Benzoylecgonine:
detected
Ibogamine,
ibogaline:
detected
Dilated
cardiomyopathy,
coronary
artery
atherosclerosis,
pulmonary
edema
Hepatitis B
Valvular
heart disease.
Contributing
conditions:
Dilated
cardiomyopathy
(autopsy)
Acute ibogaine
intoxication.
Contributing
conditions:
Mitral
insufficiency
with dilated
cardiomyopathy
11 51 M
Opioid
detoxification,
methamphetamine
and alcohol
dependence
Mexico 2005 Died at ibogaine
treatment facility
24 h Ibogaine HCl
12 mg ⁄kg
Unknown Unknown Autopsy not
performed
Cardiorespiratory
arrest due to
acute myocardial
infarction (death
certificate,
clinical diagnosis
of attending
physician)
Insufficient
information
12 38 M
Opioid
detoxification
Mexico 2006 Died at ibogaine
treatment facility.
Found dead within
1 h of having last
been seen alive
12 h Ibogaine HCl
13 mg ⁄kg
Unknown Cocaine and
morphine
metabolites
Cutaneous
abscesses,
hepatitis.
Autopsy was
done, but
inadequate for
determination of
a proximate
cause of death
Pulmonary
thromboembolism
(death certificate)
Insufficient
information
13 48 M
Unknown (70)
France 2006 Ingested root bark
of Tabernanthe
iboga followed by
vomiting and
dyspnea
53 h 18 ‘‘soup-spoons’’ of
a mixture of
powdered
Tabernanthe iboga
root bark and
sweetened condensed
milk over 10 h
Vena cava: 6.6
Femoral vein: 5.4
Brain: 12.5
Liver: 40.5
Other
toxicology:
negative
Noribogaine:
Vena cava: 15.5
Femoral vein: 5.6
Brain: 18.7
Liver: 50.5
Ibogamine:
detected
Pulmonary
edema.
Buprenorphine
tablets and
‘‘different objects
and burned-out
parts of plants
found at the
death
scene suggested
that some sort of
esoteric ritual
may have taken
place.’’ History
of substance
abuse
Acute ibogaine
intoxication
(autopsy)
Acute ibogaine
intoxication
(unknown if
other drugs
involved)
Continued.
ALPER ET AL. •FATALITIES TEMPORALLY ASSOCIATED WITH THE INGESTION OF IBOGAINE 403
TABLE 1—Continued.
Age ⁄Gender,
Reason for
Ibogaine Use Country Year Circumstance
Time Interval
from Most
Recent
Ingestion of
Ibogaine
Until Death
Ibogaine Form,
Dose
Ibogaine
(Blood, mg ⁄L
or mg ⁄kg)
Other
Toxicology
(mg ⁄L)
Other Autopsy
or Historical
Findings
Official Cause
of Death
Proximate Cause
of Death
14 28 M
Opioid
detoxification
The Netherlands 2006 Fluctuating
level of
consciousness
following
immersion in a
warm bath
for a 4-h period
prior to death.
Subject was
observed and at no
time was his head
underwater, ruling
out drowning
76 h Tabernanthe
iboga alkaloid
extract, 7.5
grams over
c.18h
Unknown Quantitative
toxicology results
not available
but ibogaine
and cannabinoid
concentrations
reportedly ‘‘low.’’
Negative for
other drugs
of abuse
and ethanol
Choroid plexus
papilloma
involving
hippocampus
with hypoxic
damage to
hippocampus.
Large duodenal
ulcer with
accumulation of
blood in
duodenum
Not conclusive
regarding
proximal
cause of death.
Possible causal
and ⁄or
contributing
factors were
hemorrhagic
complications
of duodenal
ulcer, increased
intracranial
pressure resulting
from obstruction
of third ventricle,
and ⁄or partial
seizures originating
from the temporal
lobe
‘‘Toxicological
cause not likely’’
(autopsy)
Hemorrhagic
complications
of duodenal
ulcer
15 30 M
Opioid
detoxification
South Africa 2006 ‘‘Gurgling sounds’’
on expiration.
Died en route to
hospital after
appearing to
respond to
resuscitative
efforts
8 h Ibogaine HCl
17 mg ⁄kg
(1.75 g)
Single dose
Not tested Not tested Autopsy not
performed
‘‘Cardio-respiratory
collapse
secondary to drug
related illness’’
(death certificate)
Insufficient
information
16 27 M
Unknown
France 2006 Discovered dead
in meditation
room at a center
oriented
toward
psychological ⁄
spiritual use
£20 h Powdered root
bark (7.2% ibogaine,
0.6% ibogamine).
The actual
amount ingested
was not provided
in the report.
The medical
examiner estimated
13 teaspoons at
1.5-g dried
bark ⁄teaspoon
would have
been required to
achieve the
measured
ibogaine blood
concentration
Peripheral
blood
immediately
following
death: 0.65
Peripheral
blood at
autopsy
8 days
following
death: 1.27
Peripheral blood
immediately
following death:
Methadone: 0.077
Diazepam: 0.413
Oxazepam: 0.09
Temazepam: 0.04
Ibogamine: 0.05
Peripheral blood at
autopsy 8 days
following death:
Ibogamine: 0.10
History of
dependence
on multiple
substances
including crack
cocaine,
benzodiazepines,
and alcohol
Drug overdose
due to ibogaine,
methadone,
diazepam, and
temazepam
(autopsy)
Acute
intoxication
due to the
combined
effects of
ibogaine,
methadone, and
diazepam
Continued.
404 JOURNAL OF FORENSIC SCIENCES
TABLE 1—Continued.
Age ⁄Gender,
Reason for
Ibogaine Use Country Year Circumstance
Time Interval
from Most
Recent
Ingestion of
Ibogaine
Until Death
Ibogaine Form,
Dose
Ibogaine
(Blood, mg ⁄L
or mg ⁄kg)
Other
Toxicology
(mg ⁄L)
Other Autopsy
or Historical
Findings
Official Cause
of Death
Proximate Cause
of Death
17 45 M
Opioid
detoxification
USA 2006 Found dead in
bed following
ibogaine treatment
at a private
residence
8–12 h Ibogaine HCl
22 mg ⁄kg
1.4 Diazepam:
77 ng ⁄ml
Fentanyl:
1.2 ng ⁄ml
Norfentanyl:
1.5 ng ⁄ml
Qualitative
urine screen
detected
Oxycodone,
Alpha-
hydroxyalprazolam,
Oxazepam,
Temazepam,
Ephedrine ⁄
pseudo-ephedrine
Hepatic steatosis Mixed drug
intoxication
(autopsy)
Acute
intoxication
due to the
combined effects
of ibogaine,
fentanyl, and
diazepam
18 33 M
Opioid
detoxification,
crack cocaine
dependence
Mexico 2007 Died at ibogaine
treatment facility
6.5 h Ibogaine HCl
11 mg ⁄kg
Not tested Not tested.
History of
having been
caught using
crack cocaine in
the bathroom
during a prior
admission to the
clinic
Family history
of pulmonary
thromboembolism
in patient’s father.
Autopsy was
done, but
inadequate for
determination of
a proximate
cause of death
Pulmonary
thromboembolism
(death
certificate,
clinical diagnosis
of attending
physician present
at time of death)
Insufficient
information
19 41 M
Opioid
detoxification,
cocaine
dependence
Mexico
(autopsied
in the US)
2007 Died at
ibogaine
treatment
facility.
Developed
shortness of
breath
and became
unresponsive
during
ibogaine
treatment
6 h Ibogaine HCl
13 mg ⁄kg
(1080 mg)
Not tested Not tested Cardiac
hypertrophy
Triglycerides:
397 mg ⁄dL
Fatal arrhythmia
during drug
addiction
treatment with
cardiac
hypertrophy
(autopsy)
Acute ibogaine
intoxication
(unknown if
other drugs
involved).
Contributing
conditions:
Cardiac
hypertrophy
ALPER ET AL. •FATALITIES TEMPORALLY ASSOCIATED WITH THE INGESTION OF IBOGAINE 405
of events (85). A competent cause of death includes the proximate
(underlying) cause, defined as that which in a natural and continu-
ous sequence, unbroken by any efficient intervening cause,
produces the fatality and without which the end result would not
have occurred. Contributing conditions were additional disorders
contributory to death but unrelated to the underlying cause of
death.
The conclusion that death was caused by an acute intoxication
requires that three conditions be met: the toxicological results are
within the range typically encountered in such fatalities, the history
and circumstances are consistent with a fatal intoxication, and the
autopsy fails to disclose a disease or physical injury that has an
extent or severity inconsistent with continued life (86). In deaths
caused by drug intoxication with more than one drug in concentra-
tions greater than trace amounts, it is customary to include all of
the identified drugs in the cause of death.
Results
We report a summary of 19 ibogaine-associated deaths that have
occurred worldwide between 1990 and 2008 including the probable
causes of death based on the available clinical and pathologic infor-
mation (see Table 1). There were 15 men and four women with a
mean age of 39.1 € 8.6 years ranging from 24 to 54 years. In 18
decedents, the estimated time intervals were available from the
most recent ingestion of ibogaine in any form until death, and the
mean interval was 24.6 € 21.8 h and ranged from 1.5 to 76 h. In
one other fatality (case #6) the time interval between death and the
time when the decedent was last noted to be alive was 20 h, the
decedent had been dead for at least several hours at the time the
body was found. The time interval from the most recent ingestion
of ibogaine until death in this instance was likely less than 76 h,
but it was not included in the calculation of the mean interval.
Fifteen individuals took ibogaine for the indication of opioid
detoxification, four of who were also dependent on alcohol, three
on cocaine, and one on methamphetamine. Two individuals used it
for a spiritual ⁄psychological purpose and had no known substance
abuse history, and two took it for unknown reasons but had a his-
tory of substance abuse. Ibogaine was given as the HCl form in 14
instances, as an alkaloid extract in two (cases #4 and #14), dried
root bark in two (cases #13 and #16), and a brown powder that
was probably either root bark or alkaloid extract in another (case
#6). In the 12 fatalities where ibogaine was given as the HCl and a
dose was reported, the mean dose was 14.3 € 6.1 mg ⁄kg (range
4.5–29 mg ⁄kg). In the 10 fatalities in which ibogaine blood con-
centrations were determined, the mean was 2.38 € 3.08 mg ⁄L
(range 0.24–9.3 mg ⁄L), obtained at a mean of 25.5 € 17.8 h fol-
lowing the ingestion of ibogaine (range 4–53 h). In addition, com-
monly abused drugs (including benzodiazepines, cocaine, opiates,
and methadone) were detected in eight of 11 decedents on whom
toxicological analysis for abused substances was performed.
Twelve of the decedents had medical comorbidities including
liver disease, peptic ulcer disease, brain neoplasm, hypertensive and
atherosclerotic cardiovascular disease, and obesity. Among the three
decedents in which no other drugs of abuse were detected in post-
mortem toxicology analysis, one had advanced heart disease and
another had liver fibrosis. Full toxicology and autopsy results were
not available in eight and five decedents, respectively.
Discussion
In this series, 19 deaths occurred between 1990 and 2008, with
an interval of 76 h or fewer between the most recent ingestion of
ibogaine and death. In 14 instances, an autopsy was performed that
allowed the determination of the proximate cause of death. The
lack of clinical and pharmaceutical controls in settings in which ib-
ogaine has been given, and the limited data regarding toxic concen-
trations of ibogaine in humans make the determination of the
causes of these deaths difficult. Nonetheless, advanced comorbidi-
ties and contributing conditions appear to include preexisting medi-
cal, particularly cardiovascular disease, and drug use around the
time of treatment.
This series of fatalities is consecutive in the sense that it repre-
sents a systematic application of an intensive methodology for iden-
tifying cases over the time interval spanned by this study. It is
possible that additional fatalities may have occurred which were
missed by death investigation agencies and this study. In the United
States, this could relate to the surreptitiousness regarding the use of
ibogaine because of its status as a schedule I substance, and indi-
viduals aware that ibogaine was used in temporal association with
a fatal outcome might be reluctant to disclose that history. Without
investigative information about the recent use of ibogaine, special-
ized analysis for ibogaine may not be performed. Under these cir-
cumstances, the cause of death of an individual treated with
ibogaine for a substance use indication could be certified as a typi-
cal multidrug intoxication, particularly in view of the likelihood of
detecting other drugs of abuse in these deaths. In most of the
world, however, ibogaine is not illegal. In this series, outside of the
United States, ibogaine was not illegal at the time of occurrence of
the fatality in any country in which the fatality occurred.
In at least five instances, providers contacted the first author
immediately regarding the death, and in a number of others,
another individual close to the provider relayed the information,
usually with the provider’s consent. Their motivation to disclose
this information included the wish to understand the causality of
the death and prevent a future occurrence, abreaction regarding a
traumatic event, and anxiety regarding legal liability. In a country
in which ibogaine is not illegal, however, concealing its use is not
necessarily perceived to be, or actually safer than disclosing it.
Regardless of their distress regarding a death, experienced treatment
providers such as those in Mexico or the Netherlands were aware
that they did not face significant legal consequences. In a prior
study by the first author of this article that surveyed the settings
and extent of ibogaine use (5), it was estimated that 20–30% of the
actual total number of ibogaine treatments had been missed by that
study. Six of the series of 19 fatalities in this article occurred in
settings and circumstances that are likely to have otherwise been
hidden from the medical ethnographic study mentioned previously
(5). While it is likely that some deaths temporally related to the
use of ibogaine escaped inclusion in this series, it is also possible
that treatments that are associated with a fatal outcome may come
to attention relatively more frequently than those that are not.
For the purpose of this discussion, the terms ‘‘proximate cause’’
and ‘‘contributing condition’’ are used as they are defined previ-
ously in the methods section and appear in the extreme right-hand
column of Table 1. A striking factor in this series of deaths is the
identification of a comorbidity or intoxication (in addition to iboga-
ine) that could adequately explain or contribute to the death in 12
of 14 decedents that have adequate postmortem data. There are
multiple possible pathways by which ibogaine may cause or con-
tribute to death in these instances and include toxicological interac-
tions with substances of abuse and direct cardiac effects.
Cardiac disease was a contributing condition or proximate cause
in six deaths, suggesting cardiac mechanisms are an important
mediator of fatal outcomes. Although preclinical toxicological test-
ing by NIDA did not indicate prolongation of the QT interval (87),
406 JOURNAL OF FORENSIC SCIENCES
it has been observed during ibogaine treatments with continuous
EKG monitoring (88). Blockade of the potassium voltage-gated ion
channel encoded by the human ether-a-go-go-related gene (hERG)
is regarded as the most common cause of drug-related QT prolon-
gation (89,90), which is associated with torsades de pointes (TdP),
a morphologically distinctive polymorphic ventricular tachycardia.
The effect of ibogaine differs from that of the hERG channel
antagonist WAY-123.398 in studies of chromaffin cells (91–93);
however, ibogaine is an hERG channel antagonist in the low
micromolar range in human embryonic kidney tsA-201 cells (94).
Ibogaine has low micromolar affinity for sodium channels
(2,95,96), which might also possibly relate to cardiac risk in view
of the possible association of sodium channel blockade with slow-
ing of intraventricular conduction and the subsequent development
of a re-entrant circuit resulting in ventricular tachyarrhythmia
(89,97), and there is evidence for altered sodium channel function-
ing in some drug-induced forms of long QT syndrome (98–101).
QT prolongation is also regarded as a general correlate of car-
diac instability that is associated with arrhythmias other than TdP
(89,102,103), and with multiple risk factors relevant to the present
study including bradycardia, coronary artery disease, dilated cardio-
myopathy, recent myocardial infarction, ventricular hypertrophy,
and liver disease (89,104). Bradycardia has been reported in
humans in association with the ingestion of ibogaine in medical
(88,105) and nonmedical (106) settings, and in some preclinical
studies (33,36,107,108). The frequently altered nutritional status of
substance abusers puts them at risk of hypomagnesemia and hypo-
kalemia (90), which are associated with QT prolongation, as are
bulimia and anorexia (109). Methadone is associated with QT pro-
longation, particularly in the presence of other drugs (110). Alcohol
or cocaine use is associated with prolongation of the QT interval
both acutely (111,112) and during withdrawal (113–115). In
patients with alcohol dependence, QT prolongation has been
observed to persist for 7 days after the last intake of alcohol (116),
and withdrawal seizures contribute further independent and additive
risk (114). Epileptic seizures, even in the absence of substance use
or withdrawal, are an independent risk factor for QT prolongation
(117).
A case report of QT prolongation and ventricular arrhythmia in
association with the ingestion of T. iboga alkaloid extract (118)
illustrates the variety of potential arrhythmogenic factors in the
clinically uncontrolled settings in which ibogaine has been used.
The patient survived in that case, which is not included in this pres-
ent series. The patient had taken ‘‘Indra,’’ an apocryphal brand of
alkaloid extract that subsumes multiple sources of diverse origin,
composition, and conditions of storage (67). Multiple confounding
risk factors for QT prolongation and ventricular arrhythmia were
present. The patient had presented with a witnessed generalized
tonic-clonic seizure (GTCS) in the setting of acute alcohol with-
drawal with hypomagnesemia and hypokalemia. Although the
report made no mention of toxicological testing for illicit drugs, the
patient had a prior history of cocaine abuse and a history of buli-
mia and had been purging prior to admission.
Bradycardia is a functional effect of potential medical signifi-
cance that could possibly involve muscarinic cholinergic transmis-
sion. Ibogaine binds with reported affinities in the 10–30 lM range
to M1 and M2 muscarinic cholinergic receptors and is generally
assumed to act as an agonist (1,2); however, functional studies have
not been performed. Although ibogaine is concentrated in brain tis-
sue relative to serum in the animal model (119) and in the two
cases reported here that reported on brain levels (cases #3 and
#13), an older literature (120,121), as well as more recent data
(122), indicates that the inhibition of acetylcholinesterase by
ibogaine in vitro is negligible over the range of ibogaine concentra-
tionsobservedinbothbloodandbrain in this series. It is unclear
whether the apparent association of ibogaine with bradycardia could
possibly be related to orthosteric agonist actions at muscarinic cho-
linergic receptors, or to effects involving sodium channels (123) or
other signal transduction pathways.
Pulmonary thromboembolism (PE) was the reported cause of
death in three deaths (cases #7, #12, and #18) all of which
occurred in Mexico. Two were not under direct observation at the
time of the death. In all three of these cases, autopsy reports were
inadequate as a basis for the determination of a proximate cause of
death due the lack of evidence of systematic examination of the
lungs and pulmonary vasculature. In Mexico, the death certificate
provides the clinical conclusion reached by the physician who pro-
nounced the death. In case #18, the attending physician patient
observed the patient directly and based the clinical diagnostic
impression of PE on acute dyspnea, tachypnea, and desaturation
indicated by pulse oximetry. Although an adequate autopsy is lack-
ing, the clinical picture mentioned previously is frequently seen
with PE (124), and in instances where there is verification by a
subsequent autopsy, the prospective clinical diagnosis of PE is less
commonly falsely positive than falsely negative (125). The dece-
dent had a family history of PE, and if he did indeed die from
venous thrombotic disease, the family history suggests a possible
etiological contribution because of genetic risk (126). Other possi-
ble risk factors for PE include travel to the treatment location (127)
and ⁄or inactivity and immobility during the treatment (128). Intra-
venous drug use is a risk factor for deep venous thrombosis
(129–131), and hence for PE, and appears to be associated with
injection per se, independent of the use of opioids versus other
substances (132).
In this series, there appeared to be no clinical or postmortem evi-
dence suggestive of a characteristic syndrome of neurotoxicity. Ib-
ogaine’sr
2
agonist activity potentiates excitatory transmission in
the olivocerebellar projection, where the redundancy of inputs to
cerebellar Purkinje cells renders them vulnerable to excitotoxic
injury (133,134). This is believed to be the mechanism of degener-
ation of cerebellar Purkinje cells observed in rats given substan-
tially larger dosages of ibogaine than those used to study drug self-
administration and withdrawal (135). Subsequent research found no
evidence of neurotoxicity in the primate (65) or mouse (136) at
dosages that produced cerebellar degeneration in the rat, or in the
rat at dosages used in studies of drug self-administration and with-
drawal (137). Neuropathological examination revealed no evidence
of degenerative changes in a woman who had received four sepa-
rate doses of ibogaine ranging between 10 and 30 mg ⁄kg over a
15-month interval prior to her death due to a mesenteric artery
thrombosis with small bowel infarction 25 days after her last inges-
tion of ibogaine (65).
In one fatality in this series, a GTCS occurred (case #10), which
might have been due to alcohol or benzodiazepine withdrawal. In
another death (case #14), a brain neoplasm might have explained
the possibility of complex partial seizures mentioned in the autopsy
report. The neurodegeneration observed in the rat following high
dosages of ibogaine has mainly involved the cerebellum (134,135),
which is an unlikely location for a seizure focus in humans. Sei-
zures originating from the cerebellum in humans appear to be lim-
ited to rare instances in which a focus is located in a tumor mass
distinct from normal cerebellar tissue, most commonly a gangliogli-
oma (138). Furthermore, cerebellar stimulation is viewed as a pos-
sible antiepileptic treatment (139), and ibogaine has been observed
to protect against convulsions in animal models (140–142), which
has been attributed to NMDA antagonist activity. Ibogaine causes
ALPER ET AL. •FATALITIES TEMPORALLY ASSOCIATED WITH THE INGESTION OF IBOGAINE 407
serotonin release in selected brain regions in the animal model
(49), and seizures are sometimes seen in serotonin syndrome (143),
but characteristic features of serotonin syndrome such as hyperther-
mia or rigidity were not present and a clinical picture suggestive of
serotonin syndrome does not appear to have been evident in this
series.
The apparent potentiation of both the analgesic (22,38,39,43–47)
and toxic (33,37–39) effects of opioids by ibogaine may be medi-
ated by enhanced transduction of signaling via opioid receptors
(40), which might have been a factor in deaths involving the use
of opioids in temporal proximity to the ingestion of ibogaine. In
one fatality (case #2), it appeared that the decedent smoked heroin
following ibogaine treatment and shortly before death (6). Toxico-
logical analysis detected a low morphine concentration that none-
theless was in the range measured in human subjects within
30 min after inhalation of volatilized heroin (144), similar to the
methodofsmokingheroinbyheatingtinfoilknownas‘‘chasing
the dragon’’ (145), and suggests possible potentiation of opioid tox-
icity by ibogaine in this death. Ibogaine increases cocaine-induced
stereotypic motor behavior in the animal model (146), suggesting
that ibogaine might also potentiate the toxicity of stimulants as
well as opioids.
Postmortem toxicological analysis detected commonly abused
drugs in eight of the 11 cases in which toxicological analysis was
performed in this series. When considering a drug intoxication
death because of multiple substances, it usually is not possible to
differentiate the individual roles and complex interactions of these
substances in causing the death. These deaths typically are certified
as intoxications because of the combined effects of all substances
detected. Therefore, it is not possible to determine whether the
deaths in which drugs of abuse were detected were because of ib-
ogaine alone, to one or more of the drugs of abuse, or a combina-
tion. There is also a general effect of the number of abused
substances, with a larger number associated with a greater risk of
death independent of the identity of specific substances involved
(147). The unexplained variance of lethal outcome as a function of
dose further adds to the difficulty of the determination of causality
for ibogaine and drugs of abuse. For example, morphine concentra-
tions associated with heroin overdose overlap substantially with
concentrations obtained from living current heroin users (148),
which may relate to the wide ranges of tolerance among opioid-
dependent individuals, and within the same individual at different
time points.
Systemic disease is a confounding factor that contributes to the
mortality associated with substance use and further complicates the
identification of the cause of death.Theriskofdeathmayrepresent
a complex interaction involving a substance of abuse against a
backdrop of systemic medical illness related to addiction. For
example, the risk of death from opioid overdose is associated with
cardiac hypertrophy and atherosclerotic disease (149), which were
contributing conditions in this case series and which in turn are
associated with a history of methamphetamine and cocaine use
(150,151). The role of advanced preexisting medical comorbidities
in this series of fatalities appears to be an instance of a more gen-
eral association between systemic disease and risk of fatal overdose
(149).
The reported elimination half-life of ibogaine in humans is on
the order of 4–7 h (7,70), and that of noribogaine is apparently
longer (7,35). Ibogaine is relatively lipophilic and accumulates pref-
erentially in tissues containing a high density of lipids, such as
brain or fat (119). Ibogaine undergoes demethylation to noribogaine
via cytochrome P450 2D6 (CYP2D6) (152), which is expressed in
the brain (153), where noribogaine may be ‘‘trapped’’ because it is
more polar than ibogaine and may cross the blood–brain barrier
more slowly. Postmortem redistributionofdrugsanddrugmetabo-
lites may occur due to passive drug release from drug reservoirs,
cell autolysis, and putrefaction (154,155). In the three instances in
which peripheral and cardiac concentrations of ibogaine were
reported (cases #2, #6, and #13), the concentrations from the femo-
ral and cardiac or vena cava sites were similar. However, the two
that reported noribogaine concentrations (cases #2 and #13) demon-
strated evidence for postmortem redistribution of noribogaine with
ratios of c. 3:1 between cardiac and peripheral blood. The one
instance that reported ibogaine concentrations at two time points
(case #16) indicated 0.65 mg ⁄L in blood at autopsy and 1.27 mg ⁄L
days following death.
The available data do not provide a basis for a reliable estimate
of toxic concentrations of ibogaine. In humans administered fixed
oral doses of ibogaine of 10 mg⁄kg, mean peak blood levels were
0.74 € 0.08 and 0.90 € 0.17 mg ⁄L in extensive and poor CYP2D6
metabolizers, respectively (7). In series of cases reported here, the
mean dosage was 14.3 € 6.1 mg ⁄kg (range 4.5–29 mg ⁄kg), and
the mean blood level was 2.38 € 3.08 mg⁄L. The presence of coin-
toxicants and comorbidities, difference in dosages used, and the
higher variance in dosages and blood levels in the present series
does not provide for a meaningful comparison regarding a lethal
dosage or level in humans.
In the rat, the animal model that is predominantly used in
research on ibogaine, the dose that is usually used in models of
drug self-administration and opioid withdrawal is 40 mg⁄kg admin-
istered intraperitoneally (i.p.) (1,2). This dose is approximately one-
third of the LD
50
of ibogaine administered i.p. (33), which in turn
is approximately one-half to one-third of the LD
50
by the intraga-
stric route of administration (33,156). The animal data indicate a
significant effect of abused substances on toxicity associated with
ibogaine (33,37–39), and taken together with the clinical evidence
for the effect systemic disease on fatal overdose (149) suggests that
interactions involving cointoxicants and medical comorbidities pre-
clude a reasonable estimate regarding a lethal dosage or level of ib-
ogaine in humans.
Cointoxicants or contributing medical comorbidities were not
reported in only two fatalities for which there were an adequate
postmortem examination and toxicological analysis (cases #4 and
#13). These two deaths involved the ingestion of crude alkaloid
extract in one case, and root bark in the other. The overall compo-
sition, age, and origin of these sources of ibogaine are unknown.
The iboga alkaloid content of T. iboga root bark extracts depends,
among other factors, on the extraction method. The total alkaloid
content of the root bark is c. 2–8% of the dry weight of the root
bark, about half of which is iboga alkaloids, 80% of which is ib-
ogaine (157,158). Utilization of water-soluble extractants yields an
extract with an alkaloid fraction composed of c. 40% ibogaine,
10% related iboga alkaloids, and 50% other alkaloids, whereas uti-
lization of an organic solvent such as acetone or methanol yields
a total alkaloid fraction with relatively less non-iboga alkaloid con-
tent (157). Other iboga alkaloids that co-occur with ibogaine in
T. iboga root bark include ibogamine, ibogaine, tabernanthine, and
voacangine (157–159) (see Fig. 1). The overall iboga alkaloid
composition of T. iboga alkaloid extracts may range from c. 15%
to 50% (157) (C. Jenks, personal communication). Sources of ib-
ogaine HCl are restricted and tend to be known to providers,
and certificates of analysis have generally been available and
corroborated when verified by independent laboratories, which up
to the present time has distinguished ibogaine from the counterfeit-
ing and adulteration seen with commonly abused ‘‘street’’ drugs
(160).
408 JOURNAL OF FORENSIC SCIENCES
Inexperience and lack of information regarding the use of ethno-
pharmacological forms of ibogaine may itself constitute a salient
domain of risk, independent of the uncertain composition of alka-
loid extracts and the undefined potential toxicity of the alkaloids
that co-occur with ibogaine in T. iboga root bark. For example,
one decedent (case #13) (70) may have ingested an amount of
dried T. iboga root bark in excess of that which would typically be
given in a full Bwiti initiation ceremony (5). The blood ibogaine
concentration in this case was the second highest in the series, even
though it was measured an estimated 53 h after ingestion, and does
not take into account the likely presence of other alkaloids. This
case additionally suggests that the bioavailability of the alkaloid
content of dried root bark may be high.
The incidence of fatalities may have decreased in the recent past.
As indicated in Table 1, in 2008, there were no known fatalities,
and in 2007, there were 2. In contrast, there were a total of nine
fatalities that occurred in 2005 and 2006. It is unlikely that this
reflects a decline in the number of individuals treated, which
appears to be continuing the trend of growth evident over the last
decade (5). Greater recognition of medical risk on the part of treat-
ment providers may have been a factor in the apparent reduction in
the incidence of fatalities. Pretreatment screening including basic
blood chemistries and EKG, the exclusion of patients with signifi-
cant medical, particularly cardiac illness, and the recognition of the
need to stabilize physical dependence on alcohol and benzodiaze-
pines prior to ibogaine treatment has gradually become more
widely accepted norms in the settings of ibogaine use (161). This
might to a significant extent reflect the collective, cumulative expe-
rience of the fatal outcomes presented here.
In conclusion, in this series of 19 cases, advanced preexisting
medical comorbidities, which were mainly cardiovascular, and ⁄or
one or more commonly abused substances explained or contributed
to the death in 12 of the 14 cases for which adequate postmortem
data were available. Significant factors in this series appear to
include preexisting medical, particularly cardiovascular disease,
possible PE, drug use during treatment, seizures associated with
withdrawal from alcohol and benzodiazepines, and the uninformed
use of ethnopharmacological forms of ibogaine.
Acknowledgment
We gratefully acknowledge the valuable assistance of How-
ard Lotsof in identifying cases and providing documents.
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Additional information and reprint requests:
Kenneth R. Alper, M.D.
Associate Professor of Psychiatry and Neurology
New York University School of Medicine
Brain Research Laboratories
8th Floor Old Bellevue Administration Building
462 First Avenue
New York, NY 10016
E-mail: kra1@nyu.edu
412 JOURNAL OF FORENSIC SCIENCES
