Ibogaine

12-methoxyibogamine

Overview

Ibogaine belongs to Psychedelics.

Key safety note: Ibogaine's defining hazard is cardiotoxicity: by blocking the hERG (Kᵥ11.1) potassium channel it prolongs the QT interval and can trigger torsades de pointes and fatal cardiac arrest: sometimes hours after dosing and during the long noribogaine tail.[13][14][16][18][19]
Effects
Subjective effects vary. What a substance feels like depends on dose, individual physiology, mindset, and setting. The points below describe commonly reported effects, not guaranteed, uniform, or desirable outcomes.
  • A biphasic experience: an acute 'visionary' or oneirophrenic phase (dream-like, panoramic and often autobiographical visual imagery), followed by a long introspective/evaluative phase.
  • Prominent physical effects: severe nausea and vomiting, marked ataxia and impaired coordination, tremor, and a slowed heart rate.
  • A prolonged residual-stimulation phase (24–72 hours or more) with insomnia. A subsequent low-mood 'grey day' is well recognised and can, in some people, progress to a lasting depressive episode or mania.
  • Qualitatively distinct from serotonergic psychedelics and closer to the harmala alkaloids. It does not dilate the pupils or raise blood pressure the way LSD does.
Dosing & duration
Harm-reduction note: These are commonly cited reference ranges, not a recommendation or a “safe” dose. Potency, purity, body chemistry, tolerance, and drug combinations vary widely. Start low, go slow, wait for full effects before redosing, and never assume an unknown product matches these figures. Missing data is not evidence of safety.

Oral. Ibogaine must never be taken without prior cardiac screening (ECG/QTc) and continuous cardiac monitoring: the doses used are large, the drug and its long-lived metabolite block hERG channels, and unsupervised use has caused fatal arrhythmias. Effects and blood levels also depend strongly on CYP2D6 metabolizer status, so a given dose is far less predictable between individuals than the numbers below suggest.

Dose ranges

Low / stimulant (historical Lambarène)

8–50 mg

Lower psychoactive

200–400 mg

Full visionary / single 'flood' dose

≈1,000–1,500 mg (roughly 10–20 mg/kg)

Duration

onset

1–3 h

peak

≈2 h

total

Acute effects 18–36 h, residual stimulation and insomnia 24–72 h or longer

Chemical & Physical Properties
FormulaC20H26N2O
Molar mass310.43 g/mol
StateNot reported
Melting point148–153 °C (free base, reported values vary)
Boiling pointNot reported
DensityNot reported
Vapor pressureNot reported
pKaNot reported
LogP3.9 (predicted, XLogP3)
SolubilitySoluble in chloroform
Refractive indexNot reported
Identifiers & Synonyms
CAS83-74-9
CAS (enantiomer)
PubChem CID197060
InChIKeyHSIBGVUMFOSJPD-CFDPKNGZSA-N
InChIInChI=1S/C20H26N2O/c1-3-13-8-12-9-17-19-15(6-7-22(11-12)20(13)17)16-10-14(23-2)4-5-18(16)21-19/h4-5,10,12-13,17,20-21H,3,6-9,11H2,1-2H3/t12-,13+,17+,20+/m1/s1
SMILESCC[C@H]1C[C@@H]2C[C@@H]3[C@H]1N(C2)CCC4=C3NC5=C4C=C(C=C5)OC

Synonyms

  • Ibogaine
  • Tabernanthe iboga alkaloid
  • Iboga
Pharmacodynamics & Biochemistry

Ibogaine has an unusually promiscuous, low-affinity pharmacology: rather than acting potently at a single receptor it binds many targets in the high-nanomolar to micromolar range. Its highest affinity is at the sigma-2 (σ2) receptor (Kᵢ ≈ 90–400 nM). It also interacts with the NMDA-receptor PCP/MK-801 site, κ- and μ-opioid, α3β4 nicotinic acetylcholine and sigma-1 receptors, and inhibits the serotonin and dopamine transporters and VMAT2. Unlike classic serotonergic psychedelics, ibogaine is only a weak ligand of 5-HT2A and does not act as a direct 5-HT2A agonist (it fails to produce the rodent head-twitch response). Its distinctive dream-like, oneirogenic effects are qualitatively closer to the harmala alkaloids than to LSD or psilocybin. Animal drug-discrimination work implicates 5-HT2A/2C, σ2 and opioid signalling, but not the NMDA, 5-HT1A or 5-HT3 receptors, in its subjective effects. Antagonism of α3β4 nicotinic acetylcholine receptors is a leading candidate mechanism for its reported anti-addictive effects, and is the property carried forward into synthetic analogues such as 18-MC. Much of ibogaine's activity is mediated by its major active metabolite noribogaine (12-hydroxyibogamine), formed by CYP2D6 O-demethylation. Noribogaine is a more potent serotonin-reuptake inhibitor (Kᵢ ≈ 41 nM) and a G-protein-biased κ-opioid receptor agonist (Kᵢ ≈ 0.7 µM). Unlike ibogaine it does not bind σ2, and it has a much longer half-life and reaches higher plasma levels than the parent drug. Block of the hERG (Kᵥ11.1) cardiac potassium channel (Kᵢ ≈ 710 nM) underlies ibogaine's most dangerous effect: prolongation of the QT interval with a risk of torsades de pointes and fatal arrhythmia.

Biological targets

  • Sigma-2
  • SERT
  • hERG
  • NMDA
  • nAChR
  • DAT
  • KOR
  • MOR
  • Sigma-1
  • 5-HT2A

Binding & functional measurements

TargetMeasurementSpecies
σ2 receptorKi 200 nMRat/guinea pig/calf
SERTKi 549 nMHuman
hERGKi 710 nMHuman
NMDAKi 1,010 nMRat/bovine/human
nAChRKi 1,050 nMHuman
DATKi 1,980 nMHuman
σ1 receptorKi 2,500 nMGuinea pig/calf
KORKi 3,700 nMHuman
MORKi 6,920 nMHuman
Pharmacokinetics
BioavailabilityOral, variable and influenced by CYP2D6 metabolizer status
Tmax≈2 h
Half-lifeIbogaine ≈ 7 h, active metabolite noribogaine ≈ 24–50 h
VdNot reported
Protein bindingNot reported
MetabolismHepatic CYP2D6 O-demethylation to the active metabolite noribogaine (12-hydroxyibogamine). Ibogaine is also deposited in fat and released slowly
ExcretionRenal and biliary
Toxicology & Safety
Harm-reduction note: Toxicity and risk depend on dose, route, purity, combinations, setting, and individual health factors. Missing harms should never be interpreted as evidence of safety.

Not reported

Ibogaine's defining hazard is cardiotoxicity: by blocking the hERG (Kᵥ11.1) potassium channel it prolongs the QT interval and can trigger torsades de pointes and fatal cardiac arrest: sometimes hours after dosing and during the long noribogaine tail. Multiple deaths have been documented in case series and reviews, typically in unsupervised or medically unscreened settings and frequently involving pre-existing heart disease or co-used opioids or other QT-prolonging drugs. It should only ever be considered with prior cardiac screening, continuous ECG monitoring and emergency care available. Acute effects also include severe ataxia, tremor and protracted nausea/vomiting, and afterwards a low-mood 'grey day' that can develop into a lasting depression or, less often, mania. High doses cause Purkinje-cell degeneration in the rat cerebellum. This has not been confirmed in primates or humans, but human safety is not established. Limited or absent controlled-trial data must never be read as evidence of safety.[13][14][16][18][19]

Legal Status
Legal note: Legal status can change over time and may vary by country, region, formulation, analogue status, prescription context, and enforcement practice. Always confirm with current official sources before relying on this section.
Interactions & Contraindications

Drug interactions

QT-prolonging drugs (some antipsychotics, antibiotics, antiarrhythmics) Additive QTc prolongation with many antipsychotics, methadone and certain antibiotics or antiarrhythmics greatly increases the risk of torsades de pointes.[13][18]
Opioids Often taken to interrupt opioid dependence, but combining it with opioids, or dosing before withdrawal is established, adds cardiac and respiratory risk and has featured in fatalities.[16][18]
SSRIs, SNRIs, Tramadol, MAOIs Ibogaine and noribogaine inhibit serotonin reuptake, so combinations raise the risk of serotonin toxicity.[3]
Strong CYP2D6 inhibitors (e.g. paroxetine, fluoxetine) Paroxetine, fluoxetine, bupropion or quinidine reduce conversion to noribogaine and raise parent-drug exposure. Poor CYP2D6 metabolisers are similarly affected, making the response less predictable.[20]

Contraindications

Cardiovascular disease, hypertension or arrhythmia any personal or family history of cardiac conduction disease, long-QT syndrome or significant cardiovascular disease, baseline QTc prolongation, or low potassium or magnesium.[13][18]
Concurrent MAOI, SSRI/SNRI or other serotonergic medication concurrent QT-prolonging, opioid or serotonergic medication.[18]
Kidney or liver impairment hepatic or renal impairment.
Pregnancy or breastfeeding[18]
Personal or family history of psychosis, schizophrenia or bipolar disorder history of psychosis or bipolar disorder.
Usage & Context
  • Investigational treatment for opioid and other substance-use disorders (interruption of withdrawal and craving). Only two randomized controlled trials exist and efficacy and safety remain unconfirmed.
  • Traditional sacramental and initiatory use of Tabernanthe iboga root bark by the Bwiti of Gabon and neighbouring Central African peoples.
  • Used at 'legal gray area' clinics abroad (e.g. Mexico, Costa Rica, the Netherlands, New Zealand, South Africa), while remaining federally illegal in the United States.
Sources & Evidence
  1. PubChem: Ibogaine (CID 197060) — identifiers & properties
  2. Wikipedia: Ibogaine (pharmacology table, dosing, phases & legal status) CC BY-SA 4.0
  3. Wasko MJ, Witt-Enderby PA, Surratt CK (2018). DARK Classics in Chemical Neuroscience: Ibogaine. ACS Chem Neurosci 9:2475-2483.

    PMID 30216039 · doi:10.1021/acschemneuro.8b00294

  4. Glick SD, Maisonneuve IM, Szumlinski KK (2001). Mechanisms of action of ibogaine: relevance to putative therapeutic effects and development of a safer iboga alkaloid congener. Alkaloids Chem Biol 56:39-53.

    PMID 11705115 · doi:10.1016/s0099-9598(01)56006-x

  5. Popik P, Layer RT, Skolnick P (1995). 100 years of ibogaine: neurochemical and pharmacological actions of a putative anti-addictive drug. Pharmacol Rev 47:235-53.

    PMID 7568327

  6. Sweetnam PM, Lancaster J, Snowman A, et al. (1995). Receptor binding profile suggests multiple mechanisms of action are responsible for ibogaine's putative anti-addictive activity. Psychopharmacology (Berl) 118:369-76.

    PMID 7568622 · doi:10.1007/BF02245936

  7. Helsley S, Fiorella D, Rabin RA, et al. (1998). Behavioral and biochemical evidence for a nonessential 5-HT2A component of the ibogaine-induced discriminative stimulus. Pharmacol Biochem Behav 59:419-25.

    PMID 9476990 · doi:10.1016/s0091-3057(97)00451-6

  8. Mash DC, Staley JK, Pablo JP, et al. (1995). Properties of ibogaine and its principal metabolite (12-hydroxyibogamine) at the MK-801 binding site of the NMDA receptor complex. Neurosci Lett 192:53-6.

    PMID 7675310 · doi:10.1016/0304-3940(95)11608-y

  9. Antonio T, Childers SR, Rothman RB, et al. (2013). Effect of Iboga alkaloids on µ-opioid receptor-coupled G protein activation. PLoS One 8:e77262.

    PMID 24204784 · doi:10.1371/journal.pone.0077262

  10. Maillet EL, Milon N, Heghinian MD, et al. (2015). Noribogaine is a G-protein biased κ-opioid receptor agonist. Neuropharmacology 99:675-88.

    PMID 26302653 · doi:10.1016/j.neuropharm.2015.08.032

  11. Arias HR, Rosenberg A, Targowska-Duda KM, et al. (2010). Interaction of ibogaine with human alpha3beta4-nicotinic acetylcholine receptors in different conformational states. Int J Biochem Cell Biol 42:1525-35.

    PMID 20684041 · doi:10.1016/j.biocel.2010.05.011

  12. Straub CJ, Rusali LE, Kremiller KM, et al. (2023). What We Have Gained from Ibogaine: α3β4 Nicotinic Acetylcholine Receptor Inhibitors as Treatments for Substance Use Disorders. J Med Chem 66:107-121.

    PMID 36440853 · doi:10.1021/acs.jmedchem.2c01562

  13. Koenig X, Kovar M, Boehm S, et al. (2014). Anti-addiction drug ibogaine inhibits hERG channels: a cardiac arrhythmia risk. Addict Biol 19:237-239.

    PMID 22458604 · doi:10.1111/j.1369-1600.2012.00447.x

  14. Alper K, Bai R, Liu N, et al. (2016). hERG Blockade by Iboga Alkaloids. Cardiovasc Toxicol 16:14-22.

    PMID 25636206 · doi:10.1007/s12012-015-9311-5

  15. Thurner P, Stary-Weinzinger A, Gafar H, et al. (2014). Mechanism of hERG channel block by the psychoactive indole alkaloid ibogaine. J Pharmacol Exp Ther 348:346-58.

    PMID 24307198 · doi:10.1124/jpet.113.209643

  16. Alper KR, Stajić M, Gill JR (2012). Fatalities temporally associated with the ingestion of ibogaine. J Forensic Sci 57:398-412.

    PMID 22268458 · doi:10.1111/j.1556-4029.2011.02008.x

  17. Maas U, Strubelt S (2006). Fatalities after taking ibogaine in addiction treatment could be related to sudden cardiac death caused by autonomic dysfunction. Med Hypotheses 67:960-4.

    PMID 16698188 · doi:10.1016/j.mehy.2006.02.050

  18. Litjens RP, Brunt TM (2016). How toxic is ibogaine?. Clin Toxicol (Phila) 54:297-302.

    PMID 26807959 · doi:10.3109/15563650.2016.1138226

  19. Ona G, Rocha JM, Bouso JC, et al. (2022). The adverse events of ibogaine in humans: an updated systematic review of the literature (2015-2020). Psychopharmacology (Berl) 239:1977-1987.

    PMID 34406452 · doi:10.1007/s00213-021-05964-y

  20. Schep LJ, Slaughter RJ, Galea S, et al. (2016). Ibogaine for treating drug dependence. What is a safe dose?. Drug Alcohol Depend 166:1-5.

    PMID 27426011 · doi:10.1016/j.drugalcdep.2016.07.005

  21. Alper KR, Lotsof HS, Frenken GM, et al. (1999). Treatment of acute opioid withdrawal with ibogaine. Am J Addict 8:234-42.

    PMID 10506904 · doi:10.1080/105504999305848

  22. Glue P, Lockhart M, Lam F, et al. (2015). Ascending-dose study of noribogaine in healthy volunteers: pharmacokinetics, pharmacodynamics, safety, and tolerability. J Clin Pharmacol 55:189-94.

    PMID 25279818 · doi:10.1002/jcph.404

  23. DEA Diversion Control Division: Controlled Substance Schedules (ibogaine — Schedule I, US)
  24. GOV.UK: Psychoactive Substances Act 2016 (UK) OGL v3.0

Further Information