The Efficacy of Ibogaine in the Treatment of Addiction; an open label, single fixed dose pilot-study of the efficacy of ibogaine in opiod-dependent subjects

Addiction is one of the most challenging consequences of chronic substance use.
Considered together, tobacco, alcohol and illicit drug use are implicated in
over 12% of mortality worldwide. Addiction treatment methods remain limited in
number and long-term success rates are poor. This applies in particular to
addiction to opioids. There is a great need for more effective treatment
modalities.

In animal studies and case reports, ibogaine appears to attenuate the
physiological symptoms associated with opiate withdrawal and prevents relapse
that most often occurs following acute detoxification by reducing craving and
thus enhancing the possible effectiveness of post-detoxification-treatment .

The main hypotheses of this investigation are:
• A single administration of ibogaine is effective in interrupting the opioid
dependence syndrome, as measured by craving and drug use.
• Detoxification by means of Ibogaine reduces craving during several months
which gives a window of opportunity in which treatment as usual can take place
with less dropout and better results.
• The adverse short and long term somatic and psychological effects of Ibogaine
are relatively mild and transient in nature.

1. To investigate, in patients with opioid dependence, the short and long term
effects of a single administration of ibogaine on craving and substance use
during a six month follow up period.
2. To investigate what effect ibogaine causes on Event Related Potentials
(ERP), and functional MRI neuroimaging, as a measure of cognitive processes
linked to craving.
3. To investigate the decrease in numbers of drop-out during treatment after
detoxification.
4. To investigate the safety of ibogaine during acute in-hospital opioid
withdrawal and during a 6 month post treatment evaluation.
5. Secondary objectives concern the exploration of possible predictive factors
for response on ibogaine (demographics, pretreatment ERP*s).

This is an exploratory, open label study without control condition.

The pilot is divided into an in-patient and an out-patient phase:

1. The first phase, the in-patient phase, consists of (minimal) 10 days of
hospitalization. During a short in-patient stabilization period including
comprehensive medical and psychiatric assessment, patients will receive short
acting oral morphine sulphate as opioid substitution therapy instead of
methadone. This is to prevent the presence of opioids in the body after
treatment with ibogaine. In this pre-treament phase patiente are in the clinic
of Iriszorg.
Thereafter a single dose of ibogaine will be administered orally (10 mg/kg
body weight). During and directly after the administration of the ibogaine
patients will be monitored intensively, with respect to somatic and mental
signs, including cardiovascular monitoring. During an directly after ibogaine
administration patients will stay at the department of psychiatry of the
Radboud UMC.

2. Next patients will return to the clinic of Iriszorg for minimally one week
and will be prepared for the out-patient follow-up trajectory. During this week
patient and therapist will be develop an individual treatment plan consisting
in a proposal how to handle changes in life after stopping methadone and how to
anticipate periods with recurring craving. Upon hospital discharge at at least
at 2, 4, 8,12 and 24 weeks follow-up visits will be scheduled in order to
provide the therapy and to evaluate the long term effects of the intervention.
During this phase, conventional *treatment as usual* will be provided based on
Community Reinforcement Approach (CRA), including Cognitive Behavioral Therapy.

Burden associated with participation:
During the screening a physical exam will be performed as well as an ECG and
blood sampling for a routine blood testing. There will be a psychiatric exam
including Mini International Neuropsychiatric Interview (MINI), and Addiction
Severity Index (ASI). Patients will be hospitalized for at least 10 days. This
burden is comparable to the burden of a standard opioid detox. On top of this
an EEG (1 hour) and a fMRI investigation will performed during the first days
of hospitalization.
During the detox phase patients may suffer from nausea. This will be addressed
with the anti-emetic medication metoclopramide prior to the ingestion of
ibogaine. Although patients who undergo a opioid detox often experience nausea
(which is also addressed with a standard prescription of anti-emetics),
ibogaine may have an extra nauseating effect.
During the detox phase patients may experience ataxia during several hours.
They might experience intense dreamlike images which might get emotional value
and meaning during and after the detox. This will be addressed by letting
people lie on a bed in a darkened room with medical, psychiatric and nursing
care at site.
During the detox people are ECG monitored every 30.

Risks:
The dominant risk during the detox phase with ibogaine is the possibility of
heart rhythm disturbances (bradycardia and/or QT-prolongation). Extreme
bradycardia or QT-prolongation (which may lead to Torsade des Pointes) may
involve the risk of a cardiac arrest.
This risk has never been assessed in a study. During detoxification of 400
patients in hospital conditions severe side effects were not observed (Mash
2005). The suspicion of these risks is based on case-histories in which cardiac
fatalities occurred in a period after the ibogaine ingestion.
These risks are addressed by a thorough medical screening so all patients with
(possible) factors that might enhance the effect of ibogaine on the heart
rhythm are excluded from treatment. Hospitalization during 10 days, change of
long acting to short acting substitution opioids and urine-monitoring of
illegal drug-use. This will guarantee a maximum stability.
During treatment participants will be monitored on cardiac activity by use of
ECG. This will be supervised by an internist/cardiologist who also will perform
medical treatment in case of a cardiac emergency.