Departments of Pharmacy and Psychological Medicine, University of Otago
THE ROLE OF CYP2D6 IN THE PHARMACOKINETICS OF
IBOGAINE AND NORIBOGAINE INFORMATION SHEET FOR INTERESTED INDIVIDUALS
Thank you for showing an interest in this project. Please read this information sheet carefully
before deciding whether or not it is appropriate for you to take part. Your participation is
entirely voluntary. If you decide not to take part, it will not affect any future care or treatment.
If you do agree to take part in the study, you are free to withdraw at any time without having
to give a reason and this will in no way affect any future health care. The following sheet
explains what the study will involve.
Please read the information in the rest of this information sheet carefully.
What is the Aim of the Project?
Ibogaine is a naturally occurring psychoactive chemical produced by plants. At low doses, it
has been used for centuries by indigenous people in West Africa as an aid against hunger,
thirst and fatigue. At very high doses it is used in religious rituals to produce dream-like
hallucinations. In 1939 – 1970 it was sold under the brand name Lambarène in France as a
“neuromuscular stimulant”. Since 1962 a network of lay experimental drug users have
reported that ibogaine at high doses decreases opioid withdrawal symptoms in opioid
dependent subjects. It is likely that the majority of the effects of ibogaine in humans are
produced by the metabolite noribogaine rather than ibogaine itself. The conversion of
ibogaine into noribogaine is mainly via an enzyme called CYP2D6. This enzyme belongs to
the cytochrome P450 family and is involved in the metabolism of many drugs in the body.
The study aims to characterize conversion of ibogaine to noribogaine based on measures of
CYP2D6 activity.
CYP2D6 activity can be estimated with the help of dextromethorphan (a cough medicine)
that is also converted into its metabolite by CYP2D6.
Half of the participants in this study will also be given the antidepressant paroxetine for the
duration of the study, and the other half of the participants will receive placebo (a sugar pill).
Paroxetine can temporarily reduce activity of CYP2D6. Paroxetine is a medication used to
treat depression, and the doses used in this study, are about ½ of those used to treat severe
depression. Paroxetine and placebo capsules will be given double–blind (neither you nor the
study technician will know which capsule you are taking.
The schedule of medications in this study is shown in the table. This will be discussed further
in the section below.
Medications/
Days
Dextromethorphan 30mg
Paroxetine OR placebo. 1
cap days 1-3, 2 caps after
Ibogaine 20mg
1
2-3
4-6
x
7
8
9-15
x
x
x
x
x
x
x
Ibogaine Pharmacokinetics PIS and Consent/ Ver 22/11/12. Northern Y Regional Ethics Committee 12/04/031
Departments of Pharmacy and Psychological Medicine, University of Otago
What will Participants be Asked to Do?
Day 1: At the first visit, we will collect details about you and your health. We will collect blood
and urine samples to check that these are normal. You will be asked to take a single dose of
dextromethorphan (a cough medicine) and not to eat or drink for one hour before this, or for
two hours afterwards. We will collect your urine for the next 5 hours. During this time a
number of tests (see below) will be made. The overall time participants will have to stay on
this day will be approximately 6.5 hours.
Day 2-3: You will be asked to take a capsule in the morning. This might contain the
antidepressant paroxetine, or placebo (neither you nor the study technician will know what is
in the capsule). The overall time participants will have to stay on these days will be
approximately 15 minutes.
Day 4-6: You will be asked to take two capsules in the morning (paroxetine or placebo). The
overall time participants will have to stay on these days will be approximately 15 minutes.
Day 7: Along with your two capsules, you will be asked to take a single dose of
dextromethorphan and not to eat or drink for one hour before or two hours after dosing. We
will collect your urine for the next 5 hours. During this time a number of Day-1 tests (see
below) will be made. The overall time participants will have to stay on this day will be
approximately 6 hours.
Day 8: This is a busy day. You will be asked to take single dose of ibogaine in the morning,
along with your two capsules. After the administration a small blood sample will be taken
every 30 minutes for 2 hours and approximately hourly for the next 12 hours. We will repeat
the Day-1 tests (see below). The overall time participants will have to stay on this day will be
approximately 13 hours.
Day 9: You will take your two capsules, and a single blood sample will be taken. We will
repeat a number of the Day-1 tests. The overall time participants will have to stay on this day
will be approximately 1 hour.
Day 10-14: You will take your two capsules, and a single blood sample will be taken. The
overall time participants will have to stay will be approximately 15 minutes.
Day 15: You will take your two capsules, and a single blood sample will be taken. We will
repeat a number of the Day-1 tests. We will check your blood and urine again to ensure
these are normal. The overall time participants will have to stay on this day will be
approximately 1 hour.
All medications will be given orally.
The blood samples will be drawn on day 8 via an indwelling butterfly cannula that stays
attached to your arm during this day. On days 9-14, blood samples will be drawn with a
needle. Urine samples on Days 1 and 7 will be collected in plastic containers.
Testing (Days 1, 7, 8, 9 and 15): These include
 Computerised tests of memory and attention. These tests assess a range of functions,
including memory, reaction time, and measures of attention
 Temperature and vital signs
 Pupillometry (a measure of how your eye reacts to light)
 Cold Pressor testing (a measure of how sensitive you are to cold temperatures, based
on your reaction to having your hand in cold water)
 Tolerability: we want to know any side-effects you notice, plus self-ratings of “sleepy”,
“energetic”, “nausea”, “anxious”, “calm” at same time as vital signs.
What Type of Participants are we looking for?
 Men and women, aged between 20-40 years.
 Women must be sterilized. (We do not have any information on the possible effects of
ibogaine on embryos, and must ensure the risk of pregnancy for female participants is
minimized). Males must be using effective barrier contraception methods (condom).
Ibogaine Pharmacokinetics PIS and Consent/ Ver 22/11/12. Northern Y Regional Ethics Committee 12/04/031
Departments of Pharmacy and Psychological Medicine, University of Otago
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You must be in good general health.
Your blood and urine tests must be within normal ranges.
You cannot be taking any medication (as these could interact with the medications in
this study).
What Are The Side-Effects And Risks?
Every subject will receive a dose of ibogaine 20 mg. This is about 1/30th of the dose used for
treatment of opioid withdrawal symptoms. Side effects are unlikely at this dose, but might
include increased restlessness and energy, or nausea.
For the 50% of participants who will receive paroxetine: Paroxetine is an antidepressant.
You will receive 10 mg/day on days 2-3 and 20 mg/day on day 4-15. This is about ½ of the
daily dose for treating severe depression. Most people do not report any side effects at
these doses. The most common side effects include nausea, insomnia and sleepiness.
Dextromethorphan is a medicine for coughs and colds. You will receive single 30 mg doses
which are similar to the doses used for treating coughs and colds. Side effects are
uncommon at this dose but might include feeling sleepy or itchy.
Risks include: the side effects from the study medications (as described above), and
discomfort from the blood sampling.
Will I be paid for my participation on this project?
Yes. We estimate that there are 30 hours of participation over the entire study. For
completing the study you will receive $412.50.
Will it be any costs for my participation on this project?
No. There will be no costs for you regarding this project.
Can Participants Change their Mind and Withdraw from the Project?
You may withdraw from this project at any time and without any disadvantage of any kind.
What Data or Information will be Collected and What Use will be Made of it?
We are collecting urine and blood samples from you at different times. Furthermore
information about your performance in several tests will be collected. (e.g. sensitivity to cold,
memory and attention testing) We will record any side effects you report, and other safety
measures (blood pressure, heart rate, temperature etc.).
We will measure the following concentrations:
 dextromethorphan and its metabolite in urine.
 ibogaine and noribogaine in blood.
The tests for memory, attention and sensitivity to cold will identify if ibogaine influences
certain types of brain activity.
The results will be published in an international scientific journal. The data included in this
publication will in no way be linked to any specific participant and your identity will not be
recorded with the data. If you want access to your personal data later you will need to record
the identification number used for your particular tests. You are most welcome to request a
copy of the results of the project should you wish.
The data collected will be securely stored in such a way that only those involved in the
research program will be able to gain access to it. At the end of the project any personal
information will be destroyed immediately except that, as required by the University's
Ibogaine Pharmacokinetics PIS and Consent/ Ver 22/11/12. Northern Y Regional Ethics Committee 12/04/031
Departments of Pharmacy and Psychological Medicine, University of Otago
research policy, any raw data on which the results of the project depend will be retained in
secure storage for ten years, after which it will be destroyed.
What if you have any Questions?
If you have any questions about our project, either now or in the future, please feel free to
contact us via the details given below.
Contact Details:
Professor Paul Glue, Dept. of Psychological Medicine; tel 021 243 3372; email:
paul.glue@otago.ac.nz
Dr Helen Winter, Dept. of Pharmacy; tel 03 479 7272; email: helen.winter@otago.ac.nz
Kira Garbe, Masters Student, Dept. of Psychological Medicine; tel 022 188 3949; email:
garki748@student.otago.ac.nz
ACC statement:
In the unlikely event of a physical injury as a result of your participation in this study, you will
be covered by the accident compensation legislation with its limitations. If you have any
questions about ACC please feel free to ask the researcher for more information before you
agree to take part in this trial.
Health and disability statement:
If you have any queries or concerns about your rights as a participant in this study you may
wish to contact a Health and Disability Services Consumer Advocate, telephone: (03) 479
0265 or freephone 0800 37 77 66 or freefax 0800 2787 7678 (0800 2 SUPPORT) or email
advocacy@hdc.org.nz. If there is a specific Maori issue/concern please contact Linda
Grennell at 0800 377 766.
This project has been reviewed and approved by the Northern Y Regional Ethics Committee
(NTY/12/04/031)
Ibogaine Pharmacokinetics PIS and Consent/ Ver 22/11/12. Northern Y Regional Ethics Committee 12/04/031
Departments of Pharmacy and Psychological Medicine, University of Otago
Ibogaine Pharmacokinetics PIS and Consent/ Ver 22/11/12. Northern Y Regional Ethics Committee 12/04/031