What is Ibogaine?

Ibogaine is a compound found in the leaves of an African shrub called Iboga, and studies indicate it may have anti-addictive properties.

-

Ibogaine is one of several chemical compounds found in the plant (shrub) Tabernanthe iboga.1 The plant is also known by just its species name, iboga. Traditionally, iboga is used in cultural and religious rituals by the indigenous peoples of Central Africa. They also use it in various dilutions for alleviating hunger, fatigue, and thirst. Some of the other compounds found in iboga are noribogaine, tabernanthine, ibogamine, ibogaline, and catharanthine.

The Chemistry of Ibogaine

Ibogaine was first isolated by Dybowski and Landrin in 1901.2 The crystalline structure of ibogaine was determined in 1960.3 It was first synthesized in the lab by Bûchi,4 and a simplified total synthesis was published in 2012.5 A detailed summary of ibogaine synthesis is found in Wasko et al., 2018.6

Ibogaine crystallizes into prismatic needles from ethanol.7 In addition to ethanol, it is soluble in ether, chloroform, acetone, and benzene. It is practically insoluble in water. The hydrochloride salt of ibogaine is soluble in water, as well as methanol and ethanol. It is slightly soluble in acetone and chloroform, but practically insoluble in ether.

What Are the Some of the Effects of Ibogaine?

Ibogaine is cardiotoxic at micromolar levels.8–11 Specifically, studies have noted a prolongation of the heart’s QTc interval. Ibogaine has also been shown to be neurotoxic in rodents.12 At higher doses, the effects include tremors, convulsions, nervous behavior, and paralysis of the limbs.13 However, the doses used in these studies are below what would be used in a clinical setting.8

The shrub Tabernanthe iboga. Image from Wikimedia Commons.

In the early 1960s, subjective reports of the anti-addictive properties of ibogaine began surfacing, most notably from a young heroin addict named Howard Lotsof.14 Lotsof was born in the Bronx, New York in 1943 and was severely addicted to heroin by the time he was 19 years old. By his own account, the desire of he and six of his friends to take heroin disappeared almost immediately after self-administration of an extract of the T. iboga root. Lotsof became one of the most vocal advocates of ibogaine use for the treatment of addiction. In 1985, he was granted a patent for the treatment of cocaine and heroin addiction using ibogaine.15

Research indicates that ibogaine may be effective in treating opiate addiction.16–19 The data show that it doesn’t just reduce opioid use, but can result in complete abstinence, along with having “long-term positive psychological outcomes.” 19

A 2018 study found that the positive effects of ibogaine for treating opioid dependence lasted twelve months.16 In a 2018 review paper, Mash et al. recommended using a single oral dose of ibogaine during detoxification “to transition drug dependent individuals to abstinence.” 17

What Receptors Does Ibogaine Use?

In terms of pharmacodynamics, ibogaine shows no clear preferences, having a moderate to a weak affinity for a variety of receptors and transport proteins (see summary in Wasko et al. 2018). As a result, the hallucinogenic effects of ibogaine cannot be attributed to the activation of the serotonin 5-HT2A receptor (Ki = 16 µM).12

However, ibogaine’s principal metabolite noribogaine has a sub-micromolar affinity (0.61 µM) as a partial agonist of the kappa opioid receptor.20 The mechanism of the dissociative effects caused by ibogaine may be similar to that of ketamine and other NMDA (N-methyl-D-aspartate) channel blockers.21,22

Ibogaine also binds in the low micromolar range to the mu opioid receptor, as does noribogaine in the sub-micromolar range.23,24 This may explain the ability of ibogaine to decrease self-administration of morphine in rats.25,26

Studies indicate that ibogaine’s anti-opiate effects may be due to its non-competitive antagonist action at nicotinic acetylcholine receptor subtypes including α1ß1 and α3ß4.27,28

More Research is Needed on the Constituents of the Iboga Plant

Scientists have only begun to scratch the surface to reveal the chemistry, pharmacology, and therapeutic applications of ibogaine and other compounds from Tabernanthe iboga. The early indications for use in treating opioid addiction and alcoholism are encouraging.

Despite what has been learned from studies, much ibogaine’s pharmacodynamics remains a mystery, as research appears to be focusing on its main metabolite noribogaine. Still, there is much to be learned about all the compounds from this naturally occurring source.

Among the many questions that need answering is whether there is an entourage effect with iboga compounds like what is seen with cannabis and the compounds in psilocybin mushrooms (aka magic mushrooms). Clearly, the research and development of iboga compounds is a wide-open area for study.

0 Comments
Inline Feedbacks
View all comments
    References
  1. Popik P, Layer RT, Skolnick P. 100 Years of Ibogaine: Neurochemical and Pharmacological Actions of a Putative Anti-Addictive Drug. Pharmacological Reviews. 1996;47(2):235-253.
  2. Dybowski J, Landrin E. Plant Chemistry. Concerning Iboga, its excitement-producing properties, its composition, and the new alkaloid it contains, ibogaine. CR Acad Sci. 1901;133:748.
  3. Arai G, Coppola J, Jeffrey GA. The structure of ibogaine. Acta Crystallographica. 1960;13(7):553-564. doi:10.1107/S0365110X60001369
  4. Bûchi G, Coffen DL, Kocsis K, Sonnet PE, Ziegler FE. The Total Synthesis of Iboga Alkaloids. Journal of the American Chemical Society. 1966;88(13):3099-3019. doi:10.1021/ja00965a039
  5. Jana GK, Sinha S. Total synthesis of ibogaine, epiibogaine and their analogues. Tetrahedron. 2012;68(35):7155-7165. doi:10.1016/j.tet.2012.06.027
  6. Wasko MJ, Witt-Enderby PA, Surratt CK. DARK Classics in Chemical Neuroscience: Ibogaine. ACS Chem Neurosci. 2018;9(10):2475-2483. doi:10.1021/acschemneuro.8b00294
  7. Alper KR. Chapter 1 Ibogaine: A review. In: The Alkaloids: Chemistry and Biology. Vol 56. Academic Press; 2001:1-38. doi:10.1016/S0099-9598(01)56005-8
  8. Alper KR, Stajić M, Gill JR. Fatalities Temporally Associated with the Ingestion of Ibogaine. Journal of Forensic Sciences. 2012;57(2):398-412. doi:10.1111/j.1556-4029.2011.02008.x
  9. Koenig X, Hilber K. The Anti-Addiction Drug Ibogaine and the Heart: A Delicate Relation. Molecules. 2015;20(2):2208-2228. doi:10.3390/molecules20022208
  10. Henstra M, Wong L, Chahbouni A, Swart N, Allaart C, Sombogaard F. Toxicokinetics of ibogaine and noribogaine in a patient with prolonged multiple cardiac arrhythmias after ingestion of internet purchased ibogaine. Clinical Toxicology. 2017;55(6):600-602. doi:10.1080/15563650.2017.1287372
  11. Vlaanderen L, Martial LC, Franssen EJF, Voort PHJ van der, Oosterwerff E, Somsen GA. Cardiac arrest after ibogaine ingestion. Clinical Toxicology. 2014;52(6):642-643. doi:10.3109/15563650.2014.927477
  12. Glick SD, Kuehne ME, Maisonneuve IM, Bandarage UK, Molinari HH. 18-Methoxycoronaridine, a non-toxic iboga alkaloid congener: effects on morphine and cocaine self-administration and on mesolimbic dopamine release in rats. Brain Research. 1996;719(1):29-35. doi:10.1016/0006-8993(96)00056-X
  13. Kubilienė A, Marksienė R, Kazlauskas S, Sadauskienė I, Ražukas A, Ivanov L. Acute toxicity of ibogaine and noribogaine. Medicina. 2008;44(12):984. doi:10.3390/medicina44120123
  14. Hevesi D. Howard Lotsof Dies at 66; Saw Drug Cure in a Plant. The New York Times. https://www.nytimes.com/2010/02/17/us/17lotsof.html. Published February 17, 2010.
  15. Lotsof HS. Rapid method for interrupting the narcotic addiction syndrome. February 1985. https://patents.google.com/patent/US4499096A/en?oq=US4499096A.
  16. Noller GE, Frampton CM, Yazar-Klosinski B. Ibogaine treatment outcomes for opioid dependence from a twelve-month follow-up observational study. The American Journal of Drug and Alcohol Abuse. 2018;44(1):37-46. doi:10.1080/00952990.2017.1310218
  17. Mash DC, Duque L, Page B, Allen-Ferdinand K. Ibogaine Detoxification Transitions Opioid and Cocaine Abusers Between Dependence and Abstinence: Clinical Observations and Treatment Outcomes. Front Pharmacol. 2018;9. doi:10.3389/fphar.2018.00529
  18. Brown TK, Alper K. Treatment of opioid use disorder with ibogaine: detoxification and drug use outcomes. The American Journal of Drug and Alcohol Abuse. 2018;44(1):24-36. doi:10.1080/00952990.2017.1320802
  19. Davis AK, Barsuglia JP, Windham-Herman A-M, Lynch M, Polanco M. Subjective effectiveness of ibogaine treatment for problematic opioid consumption: Short- and long-term outcomes and current psychological functioning. Journal of Psychedelic Studies. 2017;1(2):65-73. doi:10.1556/2054.01.2017.009
  20. Maillet EL, Milon N, Heghinian MD, et al. Noribogaine is a G-protein biased κ-opioid receptor agonist. Neuropharmacology. 2015;99:675-688. doi:10.1016/j.neuropharm.2015.08.032
  21. Anis NA, Berry SC, Burton NR, Lodge D. The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate. British Journal of Pharmacology. 1983;79(2):565-575. doi:10.1111/j.1476-5381.1983.tb11031.x
  22. Mash DC, Staley JK, Pablo JP, Holohean AM, Hackman JC, Davidoff RA. Properties of ibogaine and its principal metabolite (12-hydroxyibogamine) at the MK-801 binding site of the NMDA receptor complex. Neuroscience Letters. 1995;192(1):53-56. doi:10.1016/0304-3940(95)11608-Y
  23. Glick SD, Maisonneuve IM. Development of Novel Medications for Drug Addiction: The Legacy of an African Shrub. Annals of the New York Academy of Sciences. 2000;909(1):88-103. doi:10.1111/j.1749-6632.2000.tb06677.x
  24. Glick SD, Maisonneuve IM, Szumlinski KK. 18-Methoxycoronaridine (18-MC) and Ibogaine: Comparison of Antiaddictive Efficacy, Toxicity, and Mechanisms of Action. Annals of the New York Academy of Sciences. 2000;914(1):369-386. doi:10.1111/j.1749-6632.2000.tb05211.x
  25. Glick SD, Rossman K, Steindorf S, Maisonneuve IM, Carlson JN. Effects and after effects of ibogaine on morphine self-administration in rats. European Journal of Pharmacology. 1991;195(3):341-345. doi:10.1016/0014-2999(91)90474-5
  26. Maisonneuve IM, Keller RW, Glick SD. Interactions between ibogaine, a potential anti-addictive agent, and morphine: an in vivo microdialysis study. European Journal of Pharmacology. 1991;199(1):35-42. doi:10.1016/0014-2999(91)90634-3
  27. Arias HR, Rosenberg A, Targowska-Duda KM, et al. Interaction of ibogaine with human α3β4-nicotinic acetylcholine receptors in different conformational states. The International Journal of Biochemistry & Cell Biology. 2010;42(9):1525-1535. doi:10.1016/j.biocel.2010.05.011
  28. Fryer JD, Lukas RJ. Noncompetitive Functional Inhibition at Diverse, Human Nicotinic Acetylcholine Receptor Subtypes by Bupropion, Phencyclidine, and Ibogaine. J Pharmacol Exp Ther. 1999;288(1):88-92. http://jpet.aspetjournals.org/content/288/1/88.