What if I told you that there was a natural compound, present in the bark and roots of a tree, that reduces or eliminates the addiction, craving, and withdrawal of drugs like heroin?  What if I then told you that you couldn’t have it?  That’s the story of ibogaine, an alkaloid found in the small tree Tabernanthe iboga, native to west central Africa.  But like most things in life, there’s more to the story.

Tabernanthe iboga by Giorgio Samorini (CC)

Tabernanthe iboga, or simply iboga, is a rainforest shrub indigenous and common to west central Africa.  It has small green leaves and orange, oval shaped fruit.  It is a small, pretty tree that may grow well in the southeastern parts of the US.  I may have to try growing it.  But it is not the ornamental properties that make iboga so special.  Iboga has been used for hundreds of years by native Africans, and most recently by the Bwiti practitioners of Gabon.

Bwiti is a fast growing spiritual discipline (it is often referred to as a cult or secret society) practiced by the Mitsogo and Fang peoples of Gabon.  Practitioners and initiates are asked to consume a large basket of iboga roots throughout the day, during which they experience dissociative (out-of-body) hallucinations.  When they have reached this point, they are said to have “met Bwiti.”  Hours of dancing, and invoking the spirits of their ancestors, later, they sleep for five to seven days (1).  Sign me up.

The substance responsible for these out-of-body, dissociative, experiences? Ibogaine, a bitter tasting indole alkaloid.  Ibogaine is strange to me.  It recieves so much attention as a dissociative psychedelic and cure-all for addiction, yet at the receptor level in the body it does nothing extraordinary.  It weakly binds many different receptors throughout several systems, yet excels at none.  It is truly a “Jack of all trades, master of none.”

If we compare serotonin receptor 5HT2A binding of LSD (2.9 nM) against ibogaine (16 uM), we see that ibogaine is 5000 times less potent than LSD.  Given that a high dose of LSD is 0.5 mg, and a dose of 2500 mg of pure ibogaine likely lethal,  it is unlikely that serotonin agonism at 5HT2A is the root of its psychedelic properties.  More reasonable is N-methyl-D-aspartate (NMDA) receptor antagonism by ibogaine.  Notable NMDA antagonists are PCP and ketamine, two well known dissociatives.  PCP and ketamine bind NMDA with an affinity of 0.5 uM, while that of ibogaine is 3.1 uM, a six-fold difference (2).  So given that iboga root bark contains ~5% ibogaine, a 1000 mg dose of root powder may contain 50 mg of ibogaine.  That compares quite well with typical PCP doses that range from 0.5-10 mg.  A 1000 mg dose of ibogaine root powder was chronicled on Erowid (11):

“I became aware of something hovering over me. It began rifling through all the images, experiences, and scenes stored in my memory. You could tell that it had access to every file and nothing was left hidden. Every secret, every dream, every disappointment, they were all laid bare before it.”

Iboga powder by Kgjerstad (CC 3.0)

This seemingly powerful, introspective summary of their lives: the good, the bad, the highs, and the lows, is one of the explanations as to why ibogaine appears to be successful in treating addiction.  In the U.S. opiate addiction, such as heroin, is treated by replacing heroin with another opioid, methadone, to which they also become addicted.  Often times the “cure” is worse than the disease, as depicted in the excellent documentary “Methadonia.”  Ibogaine is not likely to work as a replacement therapy because its binding and activity on the opiate receptors is very low, on the order of 1000 times less than typical opiates and opioids.  As an example, and bending the rules of pharmacology a bit, a dose of ibogaine root powder equal to 20 mg of oxycodone would be around 400 grams – nearly one pound!

But it does seem to work.  In animal models, pretreatment with ibogaine reduces the self administration of many drugs, from opiates, to cocaine, and even alcohol (3).  The exact nature and mechanism of action is unclear, as ibogaine has what is gently described as a “complex pharmacology.”  Some suggest that it is due to its actions on the kappa-opioid receptor, but from my previous works in pharma, I know that those actions are dysphoric – the opposite of euphoric – and not good.  Regardless, both the National Institute on Drug Abuse (4) and the FDA saw fit to allow human clinical trials (5). A brief summary of the clinical trial conducted by Dr. Mash:

“After treatment with ibogaine, opiate-dependent subjects were less likely to anticipate positive outcomes from heroin (or other opiate) use . . . (and) also decreased participants’ desire and intention to use heroin.” (5)

Clinical trials have halted, presumeably for safety issues, but I have heard that it could also have been due to some disagreements over the property rights of ibogaine treatment.  Despite this, there is a large underground movement for ibogaine therapy (6).  There are clinics outside of the U.S., particularly in Mexico and Central America, that offer addiction treatment.  And due to its wide spread availability online, ibogaine therapy is being conducted in hotels and homes throughout the U.S. and Europe.

A successful ibogaine therapy story from Erowid (12):
“I am not addicted to methadone. I had NO severe drug withdrawal….after a 10 year methadone habit and a 25 year drug dependency, this is no less than a miracle.”

The exact success rate of this therapy is unknown, but from many of the accounts I have read , it appears to work, with addicts reporting no craving or withdrawal for months later.  However, it is suggested to repeat  ibogaine therapy every six-months or so.

How does it work?  I don’t know.  Does it work?  I don’t know.  The fact that a large number of people, several thousand per year, report that it works is good enough for me.  But therein lies the problem for those in the U.S.  Ibogaine is a schedule I drug, the same classification as heroin, LSD, and marijuana.  No doubt due to its hallucinatory effects.  Schedule I drugs are those that are deemed to have a high potential for abuse with no accepted medical value.  This makes ibogaine possession and use illegal in the U.S.  It also makes it exceedingly difficult for legitimate researchers to study.

Is everything around ibogaine rainbows and butterflys?  No.  There are numerous deaths associated with ibogaine.  A 52 year old male was being treated in a hotel room by a “therapist” for his alcoholism.  He died 12-24 hours after treatment due to cardiac issues brought upon by ibogaine (7).  In another, a 25 year old underwent ibogaine therapy to cure him of his heroin addiction.  He died after two days due to multi-organ failure (8).  And also, a 48 year old male with a long history of substance abuse underwent ibogaine treatment by a man from Gabon.  The individual died 53 hours later (9).

Ibogaine is certainly a complex drug.  It has a rich history, a complex pharmacological profile, and a potential seen by many to be a wonder drug.  Is it safe?  That depends on the dose of course.  There are no 100% safe drugs on the market, or anywhere.  Everything has a risk, and it is on the user to be aware, and made aware, of those risks, lest you wind up like the suspended doctor for prescribing ibogaine for internet porn addiction (10).  Gotta end with a smile.

References:

1. Pope, Harrison G. “Tabernanthe Iboga: An African Narcotic Plant of Social Importance.” Economic Botany 23.2 (1969): 174-84.
2. Glick,S.D., Maisonneuve, I.M., Szumlinski, K.K. “Mechanisms of action of ibogaine: relevance to putative therapeutic effects and development of a safer iboga alkaloid congener.” Alkaloids Chem Biol. 56 (2001): 39-53.
3. Glick,S.D., Maisonneuve, I.M. “Mechanisms of antiaddictive actions of ibogaine.” Annals of the New York Acad. of Science. 844 (1998): 214-226.
4. Kenneth R. Alper, Howard S. Lotsof, Geerte. “Treatment of Acute Opioid Withdrawal with Ibogaine.” American Journal on Addictions 8.3 (1999): 234-42.
5. Mash, Deborah C., Craig A. Kovera, John Pablo, Rachel F. Tyndale, Frank D. Ervin, Izben C. Williams, Edward G. Singleton, and Manny Mayor. “Ibogaine: Complex Pharmacokinetics, Concerns for Safety, and Preliminary Efficacy Measures.” Annals of the New York Academy of Sciences 914.1 (2000): 394-401.
6. Halper, Kenneth R., Howard S. Lotsof, and Charles D. Kaplan. “The Ibogaine Medical Subculture.” Journal of Ethnopharmacology 115.1 (2008): 9-24.
7. Papadodima, Stavroula A., Artemis Dona, Christos I. Evaggelakos, Nikolaos Goutas, and Sotirios A. Athanaselis. “Ibogaine Related Sudden Death: A Case Report.” Journal of Forensic and Legal Medicine 20.7 (2013): 809-11.
8. Jalal, Shwan, Edouard Daher, and Raymond Hilu. “A Case of Death Due to Ibogaine Use for Heroin Addiction.” The American Journal on Addictions 22.3 (2013): 302.
9. Kontrimaviciute, V., O. Mathieu, J.-C. Mathieu-Daude, P. Vainauskas, T. Casper, E. Baccino, and F. M. M. Bressolle. “Distribution of Ibogaine and Noribogaine in a Man Following a Poisoning Involving Root Bark of the Tabernanthe Iboga Shrub.” Journal of Analytical Toxicology 30.7 (2006): 434-40.
10. Dyer, C. “Doctor Is Suspended for Prescribing a Drug for Pornography “addiction” without Giving the Risks.” British Medical Journal 343.Oct17 1 (2011): D6699.
11. “Erowid Experience Vaults: Ibogaine – A Psycho-Spiritual Experience.” https://www.erowid.org/experiences/exp.php?ID=76892.
12. “Erowid Experience Vaults: Ibogaine – A Gift of Freedom.” https://www.erowid.org/experiences/exp.php?ID=1948.