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Ibogaine is an alkaloid purported to be an effective drug dependence treatment. However, its efficacy has been hard to evaluate, partly because it is illegal in some countries. In such places, treatments are conducted in underground settings where fatalities have occurred. In Brazil ibogaine is unregulated and a combined approach of psychotherapy and ibogaine is being practiced to treat addiction. To evaluate the safety and efficacy of ibogaine, we conducted a retrospective analysis of data from 75 previous alcohol, cannabis, cocaine and crack users (72% poly-drug users). We observed no serious adverse reactions or fatalities, and found 61% of participants abstinent. Participants treated with ibogaine only once reported abstinence for a median of 5.5 months and those treated multiple times for a median of 8.4 months. This increase was statistically significant (p < 0.001), and both single or multiple treatments led to longer abstinence periods than before the first ibogaine session (p < 0.001). These results suggest that the use of ibogaine supervised by a physician and accompanied by psychotherapy can facilitate prolonged periods of abstinence, without the occurrence of fatalities or complications. These results suggest that ibogaine can be a safe and effective treatment for dependence on stimulant and other non-opiate drugs.
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Journal of Psychopharmacology
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DOI: 10.1177/0269881114552713
published online 29 September 2014J Psychopharmacol
Eduardo Ekman Schenberg, Maria Angélica de Castro Comis, Bruno Rasmussen Chaves and Dartiu Xavier da Silveira
Treating drug dependence with the aid of ibogaine: A retrospective study
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DOI: 10.1177/0269881114552713
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Introduction
Problems related to drug use, abuse and dependence have been
receiving increasing attention worldwide. The number of users of
illicit drugs, such as cannabis, opioids, cocaine, and crack is esti-
mated to be around 149–271 million (Degenhardt and Hall,
2012). On the other hand, lifetime use of licit drugs such as alco-
hol and tobacco is estimated at 55% and 30% of the world popu-
lation, respectively (Storr et al., 2010). The consumption of such
drugs has been associated with considerable morbidity and mor-
tality (Degenhardt and Hall, 2012) as well as social problems
(Nutt et al., 2007; 2010), making drug use, abuse and dependence
one of the most important public health concerns in psychiatry.
Despite high rates of dependence, safe and effective pharma-
cological addiction treatments are still lacking. While pharmaco-
logical interventions do exist for opioid dependence treatment,
they are targeted towards craving reduction (Nutt and Lingford-
Hughes, 2008). One alternative approach for the treatment of opi-
oid dependence is the use of ibogaine, a monoterpene alkaloid
with strong psychoactive properties (Alper, 2001; Brown, 2013).
Given its long-lasting and varied effects, a classification of ibo-
gaine has proved challenging. Nevertheless, some have proposed
classifying the compound as a hallucinogen, psychedelic or onei-
rogen (Alper and Lotsof, 2007).
Ibogaine is only one of a dozen alkaloids present in the root bark
of the Ta be r na n th e i bo g a plant, traditionally used in Gabon,
Cameroon and other parts of West central Africa in Shamanic
rituals of the Bwiti religion (Alper, 2001). Around 1960, ibogaine
gained more attention in the West when Howard Lotsof, an opioid-
dependent patient, discovered that ibogaine might be a useful
therapeutic tool in the treatment of drug addiction, particularly in the
alleviation of opioid craving (Alper, 2001; Brown, 2013).
After these initial uncontrolled case reports, non-clinical,
clinical and laboratory-based research has sought to assess ibo-
gaine’s efficacy in the treatment of opioid addiction. At least two
case studies have demonstrated the drug’s effectiveness at reduc-
ing cravings during opioid withdrawal: one from 32 patients
treated at a clinic (Mash et al., 2001), and another from 33
patients treated in non-medical settings (Alper et al., 1999).
Corroborating ibogaine’s therapeutic effects in the treatment of
opioid dependence are results from animal research, which have
shown reductions in withdrawal signs in morphine-dependent ani-
mals (Dzoljic et al., 1988; Glick et al., 1992; Leal et al., 2003;
Treating drug dependence with the aid of
ibogaine: A retrospective study
Eduardo Ekman Schenberg1, Maria Angélica de Castro Comis2, Bruno
Rasmussen Chaves3 and Dartiu Xavier da Silveira4
Abstract
Ibogaine is an alkaloid purported to be an effective drug dependence treatment. However, its efficacy has been hard to evaluate, partly because
it is illegal in some countries. In such places, treatments are conducted in underground settings where fatalities have occurred. In Brazil ibogaine
is unregulated and a combined approach of psychotherapy and ibogaine is being practiced to treat addiction. To evaluate the safety and efficacy
of ibogaine, we conducted a retrospective analysis of data from 75 previous alcohol, cannabis, cocaine and crack users (72% poly-drug users).
We observed no serious adverse reactions or fatalities, and found 61% of participants abstinent. Participants treated with ibogaine only once
reported abstinence for a median of 5.5 months and those treated multiple times for a median of 8.4 months. This increase was statistically
significant (p < 0.001), and both single or multiple treatments led to longer abstinence periods than before the first ibogaine session
(p < 0.001). These results suggest that the use of ibogaine supervised by a physician and accompanied by psychotherapy can facilitate prolonged
periods of abstinence, without the occurrence of fatalities or complications. These results suggest that ibogaine can be a safe and effective treatment
for dependence on stimulant and other non-opiate drugs.
Keywords
Ibogaine, dependence, addiction, cocaine, crack
1 Universidade Federal de São Paulo, Departamento de Psiquiatria,
Instituto Plantando Consciência, São Paulo, Brazil
2Instituto Plantando Consciência, São Paulo, Brazil
3M.P.P.G Hospital, Santa Cruz do Rio Pardo, Brazil
4 Universidade Federal de São Paulo, Programa de Orientação e
Atendimento a Dependentes (PROAD), Departamento de Psiquiatria,
Instituto Plantando Consciência, São Paulo, Brazil
Corresponding author:
Eduardo Ekman Schenberg, Universidade Federal de São Paulo,
Departamento de Psiquiatria; Instituto Plantando Consciência. Rua
Teixeira da Silva 251 apt 41, Jardim Paulistano, São Paulo, SP 04002-
030, Brazil.
Email: eduardoschenberg@gmail.com
552713JOP0010.1177/0269881114552713Journal of PsychopharmacologySchenberg et al.
research-article2014
Original Paper
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2 Journal of Psychopharmacology
Parke et al., 2002; Sharpe and Jaffe, 1990), attenuation of mor-
phine-induced place preference (Parker and Siegel, 2001), reduc-
tion in self-administration to morphine (Glick et al., 1991, 1994)
and decreases in dopamine efflux in the nucleus accumbens or
striatum after cocaine or morphine administration (Glick et al.,
1994; Maisonneuve et al., 1991). Furthermore, animal research has
also indicated a potential efficacy of ibogaine in reducing self-
administration of alcohol (Rezvani et al., 1995), amphetamine
(Maisonneuve et al., 1992) and cocaine (Cappendijk and Dzoljic,
1993; Glick et al., 1994).
In recent decades, ibogaine’s therapeutic potential coalesced
in what was termed “a medical subculture” (Alper et al., 2008) or
a “vast, uncontrolled experiment” (Vastag, 2005) with more than
3000 documented cases reported until 2006 (Alper et al., 2008).
This is attributed, at least in part, to ibogaine’s hallucinogenic
action, which can induce very potent and prolonged psychologi-
cal and emotional effects.
However, in some places where the substance is illegal, ibo-
gaine or iboga extracts are used without quality control and with-
out the supervision of trained and qualified medical staff. Such
conditions may be responsible for some of the fatalities that have
been reported after ibogaine ingestion (Alper et al., 2012).
Although it is not possible to determine a single factor to explain
these adverse reactions (Alper et al., 2012), the presence of a
Long-QT Syndrome is the most accepted explanation (Hoelen
et al., 2009; Koenig et al., 2013, 2014; Maas and Strubelt, 2006;
Paling et al., 2012; Pleskovic et al., 2012).
Prolongation of the electrocardiogram QT interval, the tradi-
tional measure of ventricular de- and repolarization, is associated
with ventricular arrhythmia that can be caused by prolongation of
ventricular repolarization or repolarization with disturbances
(Van Noord et al., 2010). One of the most common causes of QT
prolongation is the use of drugs, including anti-psychotic, anti-
histaminic and gastrointestinal compounds. Importantly, QT pro-
longation has been reported in alcohol use (Aasebø et al., 2007)
and withdrawal (Cuculi et al., 2006; Kino et al., 1981; Otero-
Antón et al., 1997) as well as cocaine use (Hoffman, 2010). QT
prolongation during alcohol withdrawal may persist for 7 days
after alcohol consumption has ceased (Kino et al., 1981), while
for cocaine it significantly diminishes after a week of cocaine
abstinence (Levin et al., 2008).
These effects generally result from pharmacological inhibitory
actions at delayed rectifier potassium channels encoded by the
human ether a go-go related gene (hERG) (Van Noord et al., 2010).
Once ibogaine induces this pharmacological action (Koenig et al.,
2013, 2014), it may potentiate QT prolongation from acute drug
use or even from withdrawal, possibly causing a potentially fatal
ventricular arrhythmia (Van Noord et al., 2010). Therefore, care-
fully monitoring QT prolongation has been proposed as an impor-
tant safety measure (Roden, 2008). Yet this remains controversial,
mainly due to the fact that not all QT prolongations are actually
proarrhythmic, and that some proarrhythmias are found in the
absence of QT prolongation (Hondeghem, 2008).
However, given that most of the fatalities associated with ibo-
gaine occurred many hours or even days after ibogaine ingestion,
acute toxic effects possibly related to QT prolongation may not
explain some of these cases (Alper et al., 2012). As such, the
occurrence of comorbidities, detected in 12 of the 14 reported
cases, may have contributed to some of these deaths. Such
comorbidities included liver disease, peptic ulcer disease, brain
neoplasm, hypertensive and atherosclerotic cardiovascular dis-
ease and obesity (Alper et al., 2012). Taken together, the com-
plexity of these fatalities suggests that new studies about
ibogaine’s effect on the ECG are needed.
Despite the reported adverse reactions, the therapeutic use of
ibogaine seems to be growing more prevalent, particularly among
opioid-dependent individuals (Brown, 2013). Yet, evidence for
the use of ibogaine in the treatment of other addictions, such as
psychostimulant dependence, is still scarce, despite considerable
research from animal models that suggests ibogaine has thera-
peutic potential for treating non-opioid drug dependence
(Cappendijk and Dzoljic, 1993; Glick et al., 1994; Maisonneuve
et al., 1992; Rezvani et al., 1995).
Given the current lack of pharmacological interventions for
treating psychostimulant dependence, such as cocaine and
crack-cocaine, the assessment of ibogaine’s therapeutic poten-
tial in treating stimulant dependence is of particular importance,
especially because most pharmacological treatments for stimu-
lant dependence revolve around the use of benzodiazepines to
alleviate symptoms of withdrawal (Nutt and Lingford-Hughes,
2008). In Brazil, although opioid consumption is extremely low
(Eckschmidt et al., 2013; Fonseca et al., 2010), ibogaine has
been used in the treatment of addiction to other classes of drugs
since 2001. Given that there are important behavioral and neu-
robiological differences between addiction to opioids and to
psychostimulants (Badiani et al., 2011), it is imperative to
assess both the efficacy and safety of using ibogaine in the
treatment of psychostimulant dependence. Here we provide a
report based on retrospective results from an ibogaine treatment
currently being practiced in Brazil, in order to assess the safety
and efficacy of ibogaine in the treatment of addiction to non-
opioid substances.
Methods
We retrospectively evaluated data from a residential, private
clinic in Curitiba, Paraná, Brazil, which treats patients with sub-
stance use disorders using cognitive behavioral therapy (CBT).
The clinic owner, a psychologist, works in association with a
physician who administers ibogaine hydrochloride (ibogaine
HCl) in a private hospital in Santa Cruz do Rio Pardo, São Paulo,
Brazil. Patients paid for the treatment, since both the clinic and
the hospital are private institutions.
Patients were psychologically and physically evaluated at the
clinic by a multi-professional team, including psychiatrists, psy-
chologists, nurses, physiotherapists and music therapists. Drug
dependence was reportedly established using the diagnostic criteria
from the Diagnostic and Statistical Manual for Mental Disorders
(DSM-IV).
When the clinic first opened, patients were required to stay
abstinent for at least 30 days prior to ibogaine administration, but
this was later extended to 60 days after a new protocol was estab-
lished. This change was reported as necessary to prevent any
pharmacological interactions with ibogaine. This period was also
considered important to ensure that patients were motivated to
follow treatment procedures and to stop using drugs. The absti-
nence period could be achieved either at home or at the center as
a 24-hour residential patient at the clinic.
Upon arrival at the clinic, if patients exhibited any violent
behavior, they were confined to a special isolated room for a few
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Schenberg et al. 3
days. All patients were advised to stay at the clinic or at home
after the ibogaine session, away from other people, duties or any
kind of social activity for at least 7 days. Participants were only
accepted into the ibogaine treatment if they agreed to comply
with the psychological follow-up.
According to the general protocol provided, the inclusion cri-
teria for the ibogaine treatment were general conditions of good
health, as measured by routine clinical exams (electrolyte levels,
aspartate aminotransferase, alanine aminotransferase, bilirubins,
gamma glutamyl transferase, creatinine, blood sugar and hemo-
gram), an absence of psychiatric comorbidities, strong psycho-
logical motivation to remain abstinent and willingness to
participate in the psychotherapy before and after ibogaine admin-
istration, with familial support. Exclusion criteria were preg-
nancy, surgery in the last 6 months, uncontrolled high blood
pressure, uncontrolled diabetes, cardiac arrhythmias, renal insuf-
ficiency, hepatic insufficiency, Alzheimer’s disease and
Parkinson’s disease.
Ibogaine HCl was imported from a Canadian provider
(Phytostan Enterprises, Inc.), individually for each patient, in
powder form (5 g). Upon arrival, ibogaine was weighed and
placed in capsules by a local pharmacy at the request of the phy-
sician responsible for importing ibogaine.
Patients were typically given a dose of 17 mg/kg, but this was
subject to change depending upon the patients’ weight at the time
of treatment. Ibogaine administration was preceded by a 20 mg
dose of domperidone, a dopamine D2/D3 receptor antagonist
prescribed to reduce potential nausea from the ibogaine (Lotsof
and Watchel, 2003) between 30 to 45 minutes prior to ibogaine
administration. Doses were divided and administered in multiple
capsules and if a patient exhibited a weak response to the initial
dose, an additional 100 to 200 mg was administered to the patient.
A total dose of 20 mg/kg was never exceeded.
Ibogaine was administered in the morning, around 9 a.m., with
patients having been previously advised to eat just only a light
breakfast that morning in order to prevent nausea. The acute effects
lasted approximately 10 hours. Patients stayed in bed in a private
hospital room, in silence. The physician responsible for the proce-
dure remained in the hospital throughout the entire treatment and
visited the patient’s private room every 25 or 30 minutes.
During the effects of ibogaine, the doctor avoided influencing
the patients’ experiences, but provided any psychological or
emotional support if needed. This typically involved reassuring
clients that all effects and reactions were part of the experience.
Patients were encouraged to be quiet, calm and confident. Blood
pressure, cardiac frequency and oxygen saturation were meas-
ured at each of the visits to the patient room. Patients stayed in
the hospital overnight, and were dismissed only after 24 to 48
hours. After leaving the hospital, they returned to the clinic for
further psychological therapy.
Based on psychological evaluation of the patient in the
months following ibogaine administration, it was sometimes
decided by the psychologist and the physician that another ibo-
gaine session might be beneficial to the therapeutic outcome.
This was typically decided if patients experienced intense crav-
ings, lapses (here defined as a brief return to drug use, with the
patient rapidly asking again for help) relapses (here defined as a
complete return to drug use), difficulty in changing old-habit pat-
terns related to drug use, continued involvement with previous
friends who were also drug users, or difficulty in reintegrating
with the family. The decision to take another dose or not was
always decided upon through close consultation between the
patient, family and therapeutic team.
Patient data were provided to the researchers separately by
the clinic staff and by the physician responsible for both the
ibogaine administration and patients’ assistance during ibo-
gaine sessions. In addition, lapse, relapse and abstinence data
were obtained directly from the patients or their close relatives
through telephone conversations. These data were obtained
from 5–20 minute interview, without using specific question-
naires or rating scales. Abstinence was defined as not using any
drugs, with the exception of the occurrence of brief lapses.
Data were then entered in a Microsoft Excel database,
which was subsequently analyzed using SPSS 17.0 statistical
software. Parametric data were analyzed by a Student’s t-test
and non-parametric data were analyzed using a Mann–Whitney
U test or a Friedman’s test followed by a Wilcoxon signed-rank
test with Bonferroni correction. Associations between categor-
ical variables were evaluated by Pearson Chi-square tests.
Level of significance was set at p < 0.05, after Bonferoni cor-
rection when appropriate. Data are expressed in mean ± stand-
ard deviation. Median and range are also reported for the
examined variables.
All procedures for the study were approved by the Research
Ethical Committee from Universidade Federal de São Paulo prior
to the start of the research. However, all the treatment procedures
had been previously conducted independently of the participation
of the University and of the authors of the present investigation
(except BRC who is responsible for the ibogaine administration).
Patients consented to participating in the study at the start of each
telephone conversation, where they would be asked about lapses,
relapses, drug use and abuse history and their current pattern of
use or abstinence.
Results
Patient information
Data were gathered from 75 drug-dependent patients (67 male, 8
female) who underwent a total of 134 ibogaine HCl sessions.
Fifty-five patients (73%) were contacted by telephone, six (8%)
were contacted and met in-person, and 14 (19%) were not avail-
able at the time of contact, but their data were provided by the
patients’ parents (11 cases), wives (2 cases), or ex-wife (1 case).
Among those 14 individuals that could not be reached, 10 were
residential patients at other clinics for drug dependence treat-
ment at the time of contact, one was working abroad, two were
in jail, and one was hospitalized due to an accident unrelated to
ibogaine use.
There were no statistically significant differences (U = 186.5;
p = 0.16) between the ages of male (34.16 ± 8.33 years old) and
female (29.50 ± 5.31 years old) participants. Men were signifi-
cantly heavier (79.32 ± 12.25 kg) than women (67.74 ± 4.02 kg)
(U = 94.0; p < 0.01). There were no significant differences
(U = 174.0; p = 0.89) in the number of previous treatments com-
pleted by male (5.40 ± 0.91) and female (3.83 ± 3.31) partici-
pants prior to joining the ibogaine program. Only six patients
(8%) reported no drug treatments previous to joining the ibo-
gaine program. One man had been in jail previous to joining the
ibogaine treatment.
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4 Journal of Psychopharmacology
Patient drug use history
Of the patients, 48 (64%) reported lifetime use of alcohol, 61
(81%) of cannabis, 62 (83%) of snorted cocaine, six (8%)
reported previous use of injected cocaine and 51 (68%) reported
having had previously used crack-cocaine. Some 54 patients
(72%) were users of multiple substances: alcohol, cannabis,
cocaine, and crack. Tobacco use was reported by 11 patients
(15%). Opioid use was reported by only one female patient, who
came from Italy with the specific purpose of undergoing ibogaine
treatment. Other drugs mentioned included methamphetamine
(one patient), “acid”, “ecstasy”, and prescription substances such
as benzydamine (Benflogin) and metylphenidate (Ritalin).
There were no statistically significant associations between
gender and use of alcohol (Chi2 = 0.284, p = 0.594, n = 50), can-
nabis (Chi2 = 0.129, p = 0.719, n = 62), cocaine (Chi2 = 0.127,
p = 0.722, n = 63) or crack (Chi2 = 0.053, p = 0.818, n = 68).
Participants reported initiation of alcohol use at a younger age
than other drugs (13.79 ± 2.97, range 7–21), followed by canna-
bis (15.25 ± 3.09, range 11–30), cocaine (19.21 ± 4.57, range
12–32) and then crack (25.20 ± 7.25, range 14–50). There were
no significant differences between men and women regarding the
age of onset of use for alcohol (t = 0.106, p = 0.916, n = 47), can-
nabis (t = -1.891, p = 0.064, n = 59) or cocaine (t = 0.303,
p = 0.763, n = 58). However, men started using crack (25.88 ± 7.31,
range 15–50, n = 41) significantly later then women (19.60 ± 3.51,
range 14–23, n = 5) (U = 41.0, p = 0.030, n = 46).
Ibogaine sessions
Although the physician has been working with ibogaine since
2001, the first treatment session with ibogaine in this sample took
place on 9 January 2005 and the last on 22 March 2013. Twenty
ibogaine HCl sessions (20%) occurred between 2008 and 2009,
53 (40%) between 2010 and 2011 and 52 (40%) between 2012
and March 2013.
All 75 patients underwent at least one ibogaine session.
Among those, 33 (44%) took it twice, 14 (19%) took it three
times, five patients (7%) participated in four sessions, two (3%)
were administered ibogaine five times, and one patient (1%) took
it nine times. Five women (63%) participated in only one ibo-
gaine session, and three (38%) were administered ibogaine twice.
There was no significant association between gender and the
number of ibogaine sessions (Chi2 = 2.166, p = 0.826).
The mean time interval between the first and second ibogaine
sessions among all participants was 245.34 ± 226.297 days
(range 31–979), 303.14 ± 277.93 days (range 48–1012) between
the second and third, 111.60 ± 100.30 days (range 24–267)
between the third and fourth, 95.50 ± 72.83 days (range 44–147)
between the fourth and fifth. Only one patient continued taking
ibogaine after the fifth session (he took a total of nine treatments).
Between the fifth and sixth session there was an interval of 87
days, followed by an interval of 93 days before the seventh ses-
sion, of 88 days before the eighth session and more 96 days
before the ninth session.
Ibogaine dosage
The dose in the first ibogaine session was significantly higher
among men (14.81 mg/kg ± 1.61, n = 67) than among women
(12.03 mg/kg ± 0.85, n = 8) (U = 19.0, p < 0.001). Only three
women participated in a second ibogaine session, rendering data
unsuitable to statistical comparison with the second dose of men.
The second dose of the male patients was 13.75 mg/kg ± 2.10
(n = 31), whereas for women it was 11.85 mg/kg ± 0.21. In the
third session, the dose for men was 13.34 mg/kg ± 2.28 (n = 14),
and in the fourth it was 12.22 mg/kg ± 3.04 (n = 5). Only two
male patients participated in a fifth ibogaine session; the doses
were 7.5 mg/kg and 14.89 mg/kg. The one patient who took ibo-
gaine over five times took a fixed dosage of 7.5 mg/kg in the
sixth through ninth administrations.
Relapses and abstinence status
All women reported that they were abstinent at the time of con-
tact, and only two reported having had a relapse after the initial
ibogaine session. Both of these women then took ibogaine a sec-
ond time and have reportedly not relapsed since. Forty-eight
men (72%) stated that they were abstinent, but 10 of those were
currently undergoing other treatment interventions. Except for
those 10, 38 (57%) men achieved abstinence with no other
treatments.
After the first ibogaine session, 22 of the male patients (29%)
recovered without relapses, whereas 53 (71%) relapsed. After the
second session, 15 patients (45%) maintained sobriety, and 18
reported relapse (55%). After the third session, eight (57%)
remained abstinent, and six (43%) relapsed. After the fourth ses-
sion, one patient did not relapse (20%), and four relapsed (80%).
After the fifth session, one patient maintained abstinence (50%),
and one patient relapsed, and continued to take ibogaine four
more times. These data are visually depicted in Figure 1. There
was a significant association between gender and relapse after the
first ibogaine session, with men relapsing more frequently than
women (Chi2 = 9.009; p = 0.007).
Duration of abstinence
With the data obtained, it was possible to calculate the period of
abstinence after the first ibogaine session and after all ibogaine
sessions for 66 patients. Data regarding days of abstinence just
before the first ibogaine session were also provided by 41
patients. There were no significant differences in the number
of days of abstinence before taking ibogaine between men
(190 ± 265.82) and women (75.26 ± 60.36) (U = 53.50; p = 0.11).
There was a significant increase in the period of abstinence
achieved when comparing the days before the first ibogaine ses-
sion (88.30 ± 15.92, median = 60.00), after the first ibogaine
session (298.76 ± 42.26, median = 165.00), and after all sessions
combined (419.15 ± 52.86, median = 252.00) (Friedman
Chi2 = 23.471; p < 0.001), as shown in Figure 2.
Seventeen men reported abstinence since their ibogaine
session, but with the occurrence of one and only relapse during
this abstinence period. Thirteen of them were administered
ibogaine only once. For this subsample, the number of days of
abstinence between the most recent ibogaine session and the
relapse (138.06 ± 105.07, range 16–365 median = 120.00) was
significantly shorter than the time of abstinence achieved after
this relapse until contact with researchers (547.41 ± 369.21,
range 48–1292 median = 520.00) (Z = -3.385; p < 0.001).
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Schenberg et al. 5
Figure 1. Summary of relapse occurrence in the 75 contacted patients after each ibogaine session. The numbers inside the larger blue circles
represent the number of patients who participated in each treatment stage. Each step in the tree corresponds to one ibogaine administration.
Numbers in the smaller light blue filled circles indicate the number of patients who had stopped at that point of treatment, and therefore were
not administered ibogaine again. All upward blue arrows indicate patients who did not relapse after a given ibogaine administration. Downward
red arrows point to the number of patients who did relapse after a given session. Each column represents the outcome of a given ibogaine
administration (first, second, third and so on).
Figure 2. Abstinence duration data. Top = Days of abstinence spent at an inpatient clinic immediately previous to ibogaine administration. Middle
= Days of abstinence after first ibogaine session. Bottom = Days of abstinence after all ibogaine sessions. Vertical lines in the histograms depict the
corresponding median.
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6 Journal of Psychopharmacology
Adverse reactions
No serious adverse effects, such as cardiac arrhythmias or fatali-
ties, occurred in any patient. However, some mild adverse effects
that have previously been reported in the ibogaine literature did
occur frequently, but only during the acute effects of ibogaine.
These include nausea, ataxia, vomiting, tremors, headaches and
mental confusion. Importantly, not a single patient complained
about ibogaine’s physical or psychological effects, even in cases
in which the experienced effects were considered very strong or
unpleasant, or in cases where relapses occurred within a short
period of time after treatment.
On the other hand, four patients (5%) complained about the
psychotherapeutic process or other activities during the intern-
ment period at the clinic, or during the post-ibogaine psychother-
apeutic sessions.
Discussion
The most important result from the present data is that no fatali-
ties occurred as a result of ibogaine administration in the con-
trolled dosing (between 7.5 and 20 mg/kg) and medical setting
described here. Furthermore, not a single case of serious negative
reactions, such as cardiac arrhythmias or persistent ataxia, was
reported. These data are relevant in a scenario where at least 19
deaths have been associated with iboga or ibogaine consumption
until 2008 (Alper et al., 2012), two fatalities reported in 2013
(Jalal et al., 2013; Mazoyer et al., 2013) and at least three more
cases of complications (Paling et al., 2012) reported to date. It is
important to note that the dose used in the current work is far
from the LD50 observed in studies with mice (263 mg/kg)
(Kubiliene et al., 2008). This important safety precaution could
be achieved in the current protocol only because ibogaine was
not obtained from underground providers, since ibogaine is not
controlled or prohibited in Brazil (Anvisa, 2014). The lack of
persistent ataxia in the present study is a particularly important
indicator of the absence of cerebellar toxicity, an effect observed
after high doses (100 mg/kg) were administered to rats (Molinari
et al., 1996; O’Hearn and Molliver, 1997; Xu et al., 2000).
The absence of fatalities in the present results suggests a rela-
tive safety of the use of ibogaine hydrochloride in a controlled
hospital setting. It is also important to note that in at least five of
the 21 (24%) previously documented fatalities, the substance
ingested was not ibogaine HCl (Alper et al., 2012). Moreover,
many of the documented fatalities occurred in underground treat-
ments, where a physician was often not present (Alper et al.,
2012; Jalal et al., 2013; Mazoyer et al., 2013; Paling et al., 2012).
Another factor that may have contributed to the absence of medi-
cal complications in the present account might be the almost
complete lack of opioid use history among the patients involved
in the study. Indeed, pharmacological interactions between opi-
oids and ibogaine have been implicated in some of the previous
reported cases of fatalities (Alper et al., 2012; Brown, 2013).
Finally, the treatment protocol includes a long mandatory absti-
nence period prior to the administration of ibogaine. This likely
contributed significantly to the safety of the therapeutic approach
by preventing any potential pharmacological interactions
between the treatment and other drugs of abuse.
Given that Long-QT Syndrome, potentially induced by ibo-
gaine, may be responsible for some fatalities, electrocardiograms
before and during ibogaine administration may be a reliable prac-
tice to reduce this kind of adverse effect. In the present work,
however, results of electrocardiograms previous to ibogaine
administration were provided to the researchers for only 36 patients
(48%), because some of these treatments occurred many years ago.
To our knowledge, this is the first report to assess the outcome
of the use of ibogaine for the treatment of patients who abused
alcohol, cannabis, cocaine, and crack but not opioids (with only
one European patient having a previous history of opioid use). This
is likely the result of the generally low incidence of opioid abuse in
Brazil (Baltieri et al., 2004; Fonseca et al., 2010). It is important to
emphasize, however, that in this sample, alcohol and cigarette use
may have been under reported by the patients, since these data
were not obtained using a structured questionnaire. Thus, when
asked about previous drug use, they may not have reported alcohol
and cigarettes because these substances often do not fit into the
cultural conception of a “drug.” It should also be noted that it was
not possible to specifically confirm the adopted criteria of depend-
ence or distinguish between different types of drug dependence.
Considering the occurrence of relapses after ibogaine adminis-
trations, the present results are very encouraging. Although there
were only eight women in the sample, all were found abstinent at
the time of contact. Among men, 51% were also abstinent at the
time of contact, and an additional 10 participants were also absti-
nent, but were participating in other drug dependence treatment
interventions.
Since we were not able to analyze abstinence periods as a func-
tion of number of ibogaine treatments completed given the decreas-
ing number of patients participating in subsequent ibogaine
sessions, we analyzed only the length of abstinence achieved after
the first session as compared with the average abstinence period
achieved after all subsequent sessions combined. Despite this
caveat, participants reported surprisingly long periods of absti-
nence, reaching a median of 5.5 months after the first ibogaine
session and 8.4 months after all subsequent ibogaine sessions. This
increase was statistically significant, corroborating previous
reports that participating in more than one ibogaine session may be
beneficial in achieving long-term abstinence (Brown, 2013). The
abstinence periods reported after completing both a single and
multiple ibogaine sessions was also significantly longer than the
required period of abstinence achieved before ibogaine administra-
tion (median = 60). However, one might argue that this presents a
potential confound in evaluating the treatment outcome of ibo-
gaine, because the present sample only included individuals capa-
ble maintaining the one or two-month abstinence period required
before the first ibogaine session. Yet contrary to this reasoning,
most clients were only able to achieve and maintain sobriety as
full-time residents in the clinic, where some were provided benzo-
diazepines to assist in the treatment process. Moreover, 69 patients
(92%) had already tried other treatments for their drug-related
problems without success. In patients’ oral reports, most of those
who recovered reported that the ibogaine session(s) were indeed
essential to their recovery, although they acknowledged they may
not have succeeded without the accompanying psychological treat-
ment. The fact that 44% decided to participate in more than one
ibogaine session further attests to the fact that they saw benefits in
using ibogaine as part of their treatment. Furthermore, the propor-
tion of patients reporting full abstinence (100% for women, 51%
for men) was considerably greater than the less than 26% reported
from psychotherapy alone (Ouimette et al., 1997). Even when
at UNIV FEDERAL DE SAO PAULO on September 30, 2014jop.sagepub.comDownloaded from
Schenberg et al. 7
compared with other pharmacological interventions, the therapeu-
tic outcome of ibogaine is robust: the abstinence period achieved
after ibogaine treatment tended to be much longer than that
observed in recent clinical trials for the treatment of psychostimu-
lant dependence with the drug topiramate (Johnson et al., 2013;
Mariani et al., 2012). However, we must be cautious when compar-
ing data from this retrospective study with clinical trials due to
methodological differences and biases.
Given that the present study employed retrospective method-
ology based on answers from unstructured interviews and data
collected over a long period of time, it is not possible to infer a
causal relationship between ibogaine and the observed outcomes.
Indeed, only a randomized double-blind clinical trial could accu-
rately assess this. Another important limitation to the present
results is that data on both relapse occurrence and abstinence
periods achieved were obtained directly from the patients’ (or
close relatives’) reports.
Considering the limitations of self-reported data, it was recently
suggested that, besides abstinence and relapse, it is also very
important to take into account secondary measures to better evalu-
ate drug dependence treatment outcomes (Tiffany et al., 2011).
According to these authors, the most important variables to evalu-
ate, in addition to reductions in drug use, are change in self-effi-
cacy, psychosocial functioning, network support/social support,
craving, and quality of life. Thus, it will be important to also con-
sider these additional variables in future studies of ibogaine in the
treatment of drug dependence.
Future studies should also seek to establish the advantages
and disadvantages of using ibogaine instead of other related psy-
chedelic compounds, such as LSD, which has therapeutic poten-
tial in the treatment of alcoholism (Krebs and Johansen, 2012).
While ibogaine may be more effective at treating a wider range of
chemical dependencies (e.g. opioids, alcohol, cocaine, crack)
than other psychedelic substances, it may present higher risks for
medical complications. For example, LSD has very low toxicity
and none of the effects on heart rhythm (Hintzen and Passie,
2010) that ibogaine does.
Despite the limitations of the present report, outlined above,
the present data are the first formal clinical report to our knowl-
edge that suggests that ibogaine has a strong therapeutic potential
in the treatment of dependence to stimulants and other non-opiate
drugs and that the medical complications previously reported can
be avoided by administering the compound in the presence of a
physician in a safe and legal medical setting.
Acknowledgements
We would like to thank the clinical staff responsible for this intervention
for providing their data and their patients’ contacts, and all the patients
and/or families who cooperated with the research. We would also like to
thank G. Loewinger for his help with English correction of the whole
manuscript.
Conflict of interest
BRC has a financial interest in this work given that the ibogaine treatment
is part of his private practice.
Funding
This research was partially financed by Instituto Plantando Consciência,
a Brazilian non-profit organization.
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Background: Psychedelic substance use in ritualistic and ceremonial settings dates back as early as 8,500 BCE. Only in recent years, from the mid-20th century, we have seen the re-emergence of psychedelics in a therapeutic setting and more specifically for the treatment of addiction. This article aims to review research over the past 40 years using classic (psilocybin, lysergic acid diethylamide [LSD], dimethyltryptamine [DMT], mescaline) and atypical (ketamine, ibogaine, 5-MeO-DMT, 3,4-methylenedioxymethamphetamine) psychedelics for the treatment of addiction. Summary: We will start with an overview of the pharmacology and physiological and psychological properties of psychedelic substances from pre-clinical and clinical research. We will then provide an overview of evidence gathered by studies conducted in controlled research environments and naturalistic and ceremonial settings, while we identify the proposed therapeutic mechanisms of each psychedelic substance. Key messages: Classic and atypical psychedelics show promise as therapeutic alternatives for the treatment of addiction, through the improvement of psychological and physiological symptoms of dependence. A more comprehensive understanding of the ancient and present-day knowledge of the therapeutic potential of psychedelics can facilitate hope for psychedelic therapeutics in the treatment of addiction, especially for individuals who have failed other conventional treatment methods.
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Integrative Addiction and Recovery is a book discussing the epidemic of addiction that is consuming our friends, family, and community nationwide. In 2016, there were 64,000 drug overdoses, and addiction became the top cause of accidental death in America in 2015. We are in a crisis and in need of a robust and integrated solution. We begin with the definition of addiction, neurobiology of addiction, and the epidemiology of varying substances of abuse and treatment guidelines. Section II reviews different types of addiction such as food, alcohol, sedative-hypnotics, cannabis, stimulants (such as cocaine and methamphetamine), opiates (including prescription and illicit opiates), and tobacco, and evidence-based approaches for their treatment using psychotherapy, pharmacotherapy, as well as holistic treatments including acupuncture, nutraceuticals, exercise, yoga, and meditation. We also have chapters on behavioral addictions and hallucinogens. Section III reviews co-occurring disorders and their evidence-based integrative treatment and also overviews the holistic therapeutic techniques such as acupuncture and TCM, Ayurveda, homeopathy, nutrition, nutraceuticals, art and aroma therapy, and equine therapy as tools for recovery. We have unique chapters on shamanism and ibogaine, as well as spirituality and group support (12 steps included). The final section deals with challenges facing recovery such as trauma, acute/chronic pain, and post acute withdrawal. Integrative Addiction and Recovery is an innovative and progressive textbook, navigating this complex disease with the most comprehensive approach.
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Ibogaine is a potent atypical psychedelic that has gained considerable attention due to its antiaddictive and antidepressant properties in preclinical and clinical studies. Previous research from our group showed that ibogaine suppresses sleep and produces an altered wakefulness state, which resembles natural REM sleep. However, after systemic administration, ibogaine is rapidly metabolized to noribogaine, which also shows antiaddictive effects but with a distinct pharmacological profile, making this drug a promising therapeutic candidate. Therefore, we still ignore whether the sleep/wake alterations depend on ibogaine or its principal metabolite noribogaine. To answer this question, we conducted polysomnographic recordings in rats following the administration of pure noribogaine. Our results show that noribogaine promotes wakefulness while reducing slow-wave sleep and blocking REM sleep, similar to our previous results reported for ibogaine administration. Thus, we shed new evidence on the mechanisms by which iboga alkaloids work in the brain.
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The comparative effectiveness of 12-step and cognitive–behavioral (C-B) models of substance abuse treatment was examined among 3, 018 patients from 15 programs at U.S. Department of Veterans Affairs Medical Centers. Across program types, participants showed significant improvements in functioning from treatment admission to a 1-year follow-up. Although 12-step patients were somewhat more likely to be abstinent at the 1-year follow-up, 12-step, C-B, and combined 12-Step–C-B treatment programs were equally effective in reducing substance use and improving most other areas of functioning. The finding of equal effectiveness was consistent over several treatment subgroups: Patients attending the “purest” 12-step and C-B treatment programs, and patients who had received the “full dose” of treatment. Also, patients with only substance abuse diagnoses, those with concomitant psychiatric diagnoses, and patients who were mandated to treatment showed similar improvement at the 1-year follow-up, regardless of type of treatment received. These data provide important new evidence supporting the effectiveness of 12-step treatment.
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The chapter discusses some of the evidences that ibogaine modulates drug effects in animals. Results of research with ibogaine indicate that the alkaloid may modulate the rewarding properties of drugs and interfere with withdrawal reactions in animals. Ibogaine has been reported to modulate the development of morphine tolerance in rats. There are two commonly used methods for evaluating drug reward in animals” drug self-administration and place preference conditioning. In drug self-administration, an animal must make some response, such as a lever press, which is followed by a presentation of the drug reward. The place-conditioning paradigm is an alternative measure of drug reward. With this procedure, during a training period, rats are confined to one distinctive compartment following injection of a drug and an alternative compartment following injection of an inert substance. Advocates for ibogaine—as an antiaddictive medication—argue that ibogaine modulates a variety of addictive disorders, not only opiate addiction. Animal evidence reported above also indicates that ibogaine modulates the rewarding properties of stimulants when evaluated in the self-administration paradigm or in the place preference paradigm.