Clinical use of ibogaine

1
Clinical use of ibogaine

• Given most often for opiate detoxification, and
  also for dependence on other drugs such as
  methamphetamine and cocaine.
• Typically administered as a single oral dose in
  the range of 10 to 25 mg/kg of body weight.
• Advantages attributed by those who have been
  treated with ibogaine are higher tolerability
  relative to other standard treatments for acute
  opioid withdrawal, and post-treatment interval of
  diminished drug craving that may last days to
  month.
• Low dose protocols involving repeated
  administration of 10 to 50 mg/day are becoming
  increasingly common particularly for the
  treatment of stimulant dependence.

2
Evidence for effectiveness
3
Reports from people who have taken ibogaine
medical ethnography

• Consistency among reports of treatment
  experiences and outcomes
• The strongest attribution of efficacy is for the
  indication of acute opioid detoxification.
• Variable interval of reduced drug craving
  following treatment, often on the order of weeks
  to months
• The reports of individuals who have taken
  ibogaine may have mechanistic significance e.g.
  descriptions of panoramic memory and oneiric
  state.

4
Published Ibogaine Case Studies

• One paper describing 33 treatments for opioid
  dependence complete resolution of withdrawal
  signs in 29 (88)1.
• Open label prospective study in St. Kitts N32.
  Rating scales indicating resolution of withdrawal
  signs and symptoms at 24 hours, sustained
  improvement in depression scale scores at 1
  month2.
• 3 treatments, one for opioid dependence (Luciano
  et al. 1998)

1. Alper, KR, Lotsof, HS, Frenken, GMN, Luciano,
DJ, and Bastiaans, J (1999). Treatment of Acute
Opioid Withdrawal with Ibogaine. American Journal
on Addictions 8 234-242.2. Mash DC, Kovera CA,
Pablo J, Tyndale R, Ervin FR, Kamlet JD, et al.
Ibogaine in the treatment of heroin withdrawal.
Alkaloids Chem Biol. 200156155-71. 3. Luciano,
DJ. (1998). Observations on treatment with
Ibogaine. American Journal on Addictions 7,
89-90.
5
Post-treatment outcomes
Table Self-reported abstinence from the drug for
which treatment had been sought following a total
of 52 ibogaine treatments. This data influenced
NIDAs decision to begin its ibogaine project.
Table from Alper, K.R., Lotsof, H.S., 2007. The
use of ibogaine in the treatment of addictions.
In Winkelman, M., Roberts, T. (Eds.),
Psychedelic Medicine. Praeger/Greenwood
Publishing Group, Westport, CT, pp. 43-66.
6
June 1962. A heroin dependent lay drug
experimenter serendipitously experiences the
resolution of withdrawal following the use of
ibogaine.
7
The nexus of harm reduction and ibogaine Nico
Adriaans (1958-1995)

• Nico Adriaans was active in a network of Dutch
  heroin users involved in ibogaine treatment.
• Adriaans founded and led the "Rotterdamse
  Junkiebond, the first drug users union.
• The Junkiebond greatly influenced Dutch drug
  policy towards adopting the harm reduction
  model.It initiated the first needle exchange in
  Rotterdam in 1981, as well as other harm
  reduction interventions.

• Not a hippie, a term which denotes
  irresponsibility and hedonism

8

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Major statistical findings regarding the ibogaine
subculture

• The number of people who took ibogaine increased
  four-fold between 2001 and 2006 to an estimated
  total of 4,300- 4,900.
• 68 took ibogaine for substance-related
  disorders.
• 53 took ibogaine specifically for the treatment
  of opioid withdrawal i.e., detoxification from
  typically high levels of physical dependence on
  opioids such as heroin and oxycontin

10
Graphic by an Amsterdam squatter for the
International Coalition for Addict Self-Help, a
group of Dutch Heroin users involved in ibogaine
treatments.
Opioid dependence is the central clinical focus
of the ibogaine subculture
11
Left panel from triptych Rise and Fall of
Addiction by Geerte Frenken
12
Ibogaine in the animal model
13
All models are wrong, some models are useful-
George E. P. Box
14
Ibogaine in the animal modelMorphine
withdrawal, an animal model of detoxification

• A model of opioid detoxification based on the
  reduction of naloxone-precipitated withdrawal
  signs in a morphine-dependent rat.
• Ibogaine reduced naloxone-precipitated opiate
  withdrawal in 11 independent replications in 3
  different animal species the rat, mouse and
  primate.

15
US patent for use of ibogaine to reduce opioid
analgesic tolerance, Ciba Pharmaceutical
Corp.,1957
16
In animals, reduced drug self-administration in
following ibogaine treatment has been reported
for

• Morphine
• Cocaine
• Amphetamine
• Nicotine
• Alcohol

17
How does it work?
18
Placebo?
19
Placebo responder ?
20
The published literature indicates no clinically
significant placebo effect in opioid
detoxification.

• Very few published clinical studies of opioid
  detoxification involving the three major
  treatments (methadone, buprenorphine, clonidine)
  even have a placebo condition.
• In these few studies that did include placebo,
  the placebo group had significantly greater signs
  of withdrawal and dropped out of the study more
  often versus any active treatment.

21
There is no clinically significant placebo effect
in opioid detoxification.

• Clinical example
• Go to Newark, West Baltimore, or the Bronx.
• Sell a dummy bag of baking soda and maltose.
• Return to the same location the following day.
• See how long you live.

22
Is ibogaine working as an opioid agonist?
23
Evidence against ibogaine as an opioid agonist
substitute

• Individuals who are successfully detoxified with
  a single dose of ibogaine do not go back into
  withdrawal.
• Doses of ibogaine, given to non-dependent
  individuals, which may be higher than those used
  to treat opioid withdrawal, do not produce opioid
  overdose. (In this regard, consider that LD50 of
  methadone is 40 mg, whereas dosages of 80 mg/day
  are often used in opioid substitution
  maintenance.)
• Ibogaine and noribogaine lack some properties
  expected of a ? agonist, such as analgesia, but
  do potentiate opioid analgesics.

24
Opiate receptor
Cell surface

• Cell interior

25
Signal transmission through the opiate receptor
causes opiate effects such as euphoria or the
high or reduction of pain
26
Opiates, or opiate receptor agonists bind to the
opiate receptor and increase signal transmission
through the receptor
µ
Opiate agonist
?
?

• Examples of opiate agonists include
• From the opium poppy heroin, morphine
• Synthetic methadone, oxycontin, fentanyl
• Naturally occurring in the body endorphins

27
Opiate receptor antagonists bind to the opiate
receptor and block signal transmission through
the receptor
Opiate antagonist
X
?

• Examples of opiate antagonists include
• Naloxone (short acting)
• Naltrexone (long acting)

28
Transmission through opiate receptors is reduced
in the dependent state due to the development of
tolerance
Normal
Dependent / tolerant
?
?
29
Ibogaine reverses opiate tolerance/ dependence,
possibly by changing the signaling through the
receptor
Pretreatment Dependent / tolerant
Post-treatment
?
?
30
Ibogaine might increase signal transmission
through opiate receptors by an effect that is
independent of substitute/agonist binding to the
receptor.
Pretreatment Dependent / tolerant
Post-treatment
CHANGE
?
?
This is a very important scientific possibility
that could lead to fundamentally new treatment,
and to a better understanding of the biological
basis of addiction.
31
WE DONT KNOW
32
Risks
33
Clinical features of fatalities that have
occurred within 72 hours of the ingestion of
ibogaine

• Significant preexisting medical, particularly
  cardiac disease (e.g recent MI, cardiomyopathy),
  with bradyarrhythmia and/or possible QTc
  prolongation as possible mechanisms
• At least one death has involved alcohol
  withdrawal seizures, which are dangerous on their
  own, and also contribute to cardiac risk due QT
  prolongation. Ibogaine will not prevent seizures
  due to withdrawal from benzodiazepines or
  alcohol.
• Pulmonary embolism (PE), related to risk factors
  such as travel, immobility within a treatment, or
  generally increased liability towards
  thromboembolic events in IVDUs
• Use of opiates or stimulants during a treatment
  due to potentiation of toxicity
• Use of indigenous forms of uncertain origin and
  composition such as root bark or various extracts
  by the inexperienced and uninformed

34

The prevailing of true intention over obsession
is both a cardinal spiritual goal and a
desired outcome of pharmacological treatment
of addiction.