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Transcript
Ibogaine in opioid
detoxification
Kenneth Alper, M.D. Associate professor of
Psychiatry and Neurology, New York University
Presentation on ibogaine at Drug Policy Alliance
Conference in Albuquerque, New Mexico, November
14, 2009 .
Dr. Alper's presentation was one of a panel of six
presentations organized and moderated by Howard
Lotsof entitled "Ibogaine in Opiate Detoxification:
How do we know it works? How does it work?"
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.
Evidence for effectiveness
Reporting 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.
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 N=32. 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. 2001;56:155-71.
3. Luciano, DJ. (1998). Observations on treatment with Ibogaine. American Journal on Addictions 7, 89-90.
Post-treatment outcomes
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.
June 1962, a heroin dependent lay drug experimenter
serendipitously experiences the resolution of
withdrawal following the use of ibogaine.
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
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
Opioid dependence is the central clinical
focus of the ibogaine subculture
Graphic by an Amsterdam squatter for the International Coalition for Addict
Self-Help, a group of Dutch Heroin users involved in ibogaine treatments.
Triptych “Rise and Fall of Addiction” by Geerte Frenken
Left panel from triptych “Rise and Fall of Addiction” by Geerte Frenken
Ibogaine in the animal
model
“All models are wrong, some models are
useful”- George E. P. Box
Iboga Alkaloid efficacy in the animal
model: morphine withdrawal
• 11published independent replications in the rat, mouse
and primate
US patent for use
of ibogaine to reduce
opioid analgesic
tolerance, Ciba
Pharmaceutical Corp.,
1957
In animals, reduced drug self-administration in
following ibogaine treatment has been reported for
• Morphine
• Cocaine
• Amphetamine
• Nicotine
• Alcohol
How does it work?
Placebo?
Placebo responder ?
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.
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.
Is ibogaine working as an
opioid agonist?
Opiate receptor
Cell surface
Cell interior
Signal transmission through the opiate
receptor causes opiate effects such as
euphoria or the “high” or reduction of pain
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
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)
Transmission through opiate receptors is reduced in the
dependent state due to the development of tolerance
Normal
↓
Dependent / tolerant
↓
Ibogaine appears to reverse opiate tolerance/ dependence
by normalizing transmission through opiate receptors
Pretreatment
Dependent / tolerant
↓
Post-treatment
↓
Evidence against ibogaine or
noribogaine as an opioid 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 μ
agonist, such as analgesia (but do potentiate opioid
analgesics)
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
↓
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.
WE DON’T KNOW
Risks
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
Ibogaine and methadone in drug-related
fatalities per treatment episode (TE)
•Ibogaine (all known treatment episodes [TEs] 1989-2006): 11 fatalities
(at least 3 in which anatomically verified, preexisting medical conditions were
Identified as the cause of death by the medical examiner with no mention of
ibogaine, total 8 ibogaine-related); 3,414 TEs (1 ibogaine-related death/427 TEs)1
•Methadone (Australia 2000-2003; national registration data): 282 fatalities
that met author’s criteria for methadone-related death (medical examiner
mentioned methadone as a cause of death or overdose during methadone
treatment); 102,615 TEs (1 methadone-related death /364 TEs)2,3
•Methadone (Utah 2004; Controlled substance and medical examiner
databases): 110 fatalities in which medical examiner mentioned methadone
as a cause of death; 52,350 methadone prescriptions
(1 methadone-related death /476 methadone prescriptions)4
1. Alper, K.R., Lotsof, H.S. and Kaplan, C.D., (2008). The ibogaine medical subculture. Journal of Ethnopharmacology 115, 9-24.
2. Gibson, A.E. and Degenhardt, L.J., (2007). Mortality related to pharmacotherapies for opioid dependence: a comparative analysis of coronial
records. Drug and Alcohol Review 26, 405-410.
3. Gibson, A. and Degenhardt, L.,(2005). Mortality related to naltrexone in the treatment of opioid dependence: A comparative analysis. NDARC
Technical Report No. 229. National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia 92 pp.
4. Sims SA, Snow LA, Porucznik CA (2007): Surveillance of methadone-related adverse drug events using multiple public health data sources.
Journal of Biomedical Informatics 40:382-389.
The prevailing of
true intention
over obsession…
…is both a
Cardinal spiritual
goal and a
desired outcome
of pharmacological
treatment of
addiction…
…