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Iboga

Scientific Name(s): Tabernanthe iboga Baill.
Common Name(s): Bitter grass, Iboga, Ibogaine, Leaf of God, Thie-pelakano

Medically reviewed by Drugs.com. Last updated on Jan 23, 2019.

Clinical Overview

Use

Iboga has been used ritually as a hallucinogen. Studies suggest that ibogaine, one of the iboga alkaloids, has potential in the treatment of addiction to several substances. The US Drug Enforcement Agency (DEA) has placed ibogaine into Schedule I of the Controlled Substances Act (CSA).

Dosing

Strict medical supervision is necessary. Ibogaine has been used in single doses of 500 to 800 mg in a clinical study, and 17 mg/kg in a drug dependency treatment center.

Contraindications

Fatalities have been associated with the use of ibogaine; concomitant opioid use and comorbidities (eg, cardiovascular disease, depression, posttraumatic stress disorder, anxiety, stress, schizophrenia, epilepsy, or other imbalances in the autonomic nervous system) increase the risk of life-threatening complications including sudden cardiac death. Ibogaine should only be used under the supervision of an experienced health care provider.

Pregnancy/Lactation

Avoid use. Information regarding the safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Mild acute effects occur frequently and include nausea, vomiting, ataxia, tremors, headaches, and mental confusion. Manic episodes lasting 1 to 2 weeks have also been reported and manifested as sleeplessness, irritability, impulsivity, emotional lability, grandiose delusions, rapid tangential speech, aggressive behavior, and suicidal ideation.

Toxicology

Large doses of iboga can induce agitation, hallucinations, vomiting, ataxia, muscle spasms, weakness, seizures, paralysis, arrhythmias, urinary retention, respiratory insufficiency, and cardiac arrest.

Scientific Family

  • Apocyanaceae (dogbane)

Botany

T. iboga is a small, evergreen, bushy shrub that is indigenous to Gabon, the Democratic Republic of Congo (Zaire), and the Republic of Congo, and is cultivated throughout west Africa.Duke 1985 A native of the undergrowth of tropical forests, the plant grows ideally in composted, well-drained soil in a protected, partly shady position.Duke 1985 It bears dark green, narrow leaves and clusters of white tubular flowers on an erect and branching stem; the yellowish-orange fruit is about the size of an olive. Traditionally, the yellow-colored root has been used as a medicine and is the source of the hallucinogenic principle; iboga is the only member of the dogbane family known to be used as a hallucinogen.Schultes 1976

History

West African cultures use the root of iboga in initiation rites to cause a near-death experience as a catalyst for spiritual discovery and as an aphrodisiac and stimulant; the growing use of iboga has been said to be an important force against the spread of Christianity and Islam in its native growing regions.Maas 2006, Schultes 1976 Use of iboga has been legally prohibited in the United States since 1970 following several fatalities; a known risk of the Gabon initiation rituals.Maas 2006, Vastag 2002 A chance discovery of the antiaddictive properties of iboga led to the issue of a patent for the use of ibogaine in the treatment of opioid dependence.Vastag 2002 A growing number of clinics using ibogaine in Western countries have been established, including those in Panama and the Caribbean island of St. Kitts.Maas 2006

Chemistry

Indole alkaloids comprise approximately 6% of the root.Lewis 1977 The 3 principal alkaloids found in the rootbark are ibogaine, ibogamine, and tabernanthine.6 Research has focused largely on the pharmacology of ibogaine. It is distinguished from the other alkaloids in its class by the presence of a methoxy group on the ibogamine molecule.Iboga 2004 Other compounds found in iboga include coronaridine, ibogaline, voacangine, isovoacangine, and conophararyngine. The 18-methoxylated analog of coronaridine has been investigated as a safer and possibly more effective alternative to ibogaine and coronaridine.Iboga 2004

Uses and Pharmacology

The effects of iboga may be dose dependent. Low doses appear to act on the cerebella to stimulate the sympathetic nervous system, as well as increasing muscle strength and endurance, and are used among indigenous African populations as an aphrodisiac and to increase mental alertness and endurance when hunting. Higher doses lead to vagal dominance and induce psychedelic effects and a "feigned death;" users report a state of dreaming without loss of consciousness. Large doses induce hallucinations; however, this dose is close to the level of toxicity and is avoided by traditional users. Hallucinations are typically accompanied by anxiety and apprehension. The autonomic nervous system is affected by ibogaine by means of various neurotransmitter systems and the fastigial nucleus.Maas 2006

The US Drug Enforcement Agency (DEA) has placed ibogaine into Schedule I of the Controlled Substances Act (CSA)is a Schedule 1 hallucinogenic substance in the United States.FDA 2015

Drug addiction

Initial investigation resulted from anecdotal reports of self-treated addicts who experienced a marked lack of desire to continue with opiate abuse following iboga ingestion. Subsequently, ibogaine and 18-methoxycoronaridine have been studied for the treatment of drug addiction.

The highly lipophilic ibogaine is subject to extensive biotransformation, primarily by the cytochrome P450 (CYP450) 2D6 enzyme, and disappears fairly rapidly from the bloodstream (half-life = 7.5 hours).Mash 2001 Significant interindividual differences are evident in the metabolism of ibogaine; clinical studies have classified individuals as extensive or poor metabolizers. Blood levels of noribogaine, an active metabolite, remain elevated 24 hours after a single dose, partially explaining the long duration of action. In addition, ibogaine is stored in fat and a slow release from fat stores has been hypothesized to further contribute to the protracted effects of the drug.Glick 2001

The pharmacology of ibogaine is complex and is thought to have multiple actions that are reflected in the ability of the drug to treat diverse addictions.Glick 2001 Ibogaine and noribogaine act on several neurotransmitter systems in the brain that may contribute to the ability to suppress autonomic changes, objective signs, and subjective distress associated with opiate withdrawal. Noribogaine binds to numerous sites in the CNS including serotonin, dopamine, and sigma receptors, kappa- and mu-opioid receptors, and the n-methyl-d-aspartate ion channel. Noribogaine elevates serotonin concentrations in the brain, a possible explanation for its antidepressive effects. The sustained presence of noribogaine in the CNS coupled with its agonist activity at opioid receptors may produce the self-tapering effect in opiate-dependent patients following abrupt discontinuation of opiates.

Animal data

Numerous studies have been published demonstrating the antiaddictive effects of ibogaine in animals.Vastag 2002, Glick 2001 Studies have reported reductions in self-administration of morphine, heroin, cocaine, alcohol, and nicotine in rodents receiving ibogaine,Vastag 2002 as well as attenuated signs of morphine withdrawal. An increase in antiaddictive effects by repeated daily or weekly treatments also has been documented.Glick 2001

Clinical data

Research into the effects of ibogaine resulted from anecdotal evidence noting a positive effect on opioid withdrawal in heroin-dependent subjects. Subsequently, several case series have described the use of a single dose of ibogaine 500 to 800 mg in patients undergoing opiate detoxification under medical supervision.Mash 2000, Lotsof 2001 Objective signs of withdrawal were rarely seen, and none were exacerbated at later time points. Adverse effects were minor.Lotsof 2001 All participants were successful in the detoxification process, and many were able to maintain abstinence after discharge. Another case series of 52 patients undergoing treatment with ibogaine reported that 19% of patients remained sober for 1 year or longer, and 52% did not use heroin or cocaine for a period of 2 months to 1 year after treatment.Vastag 2002

A retrospective study was conducted among 75 drug-dependent patients being treated for substance dependence at a Brazilian clinic that used ibogaine in combination with psychotherapy. The physician- and psychologist-run program used strict patient acceptance criteria including a 60-day abstinence period prior to check-in, good general health, familial support, and strong motivation to participate in psychotherapy before and after ibogaine treatment. Additionally, patients remained in the clinic in a private bed, in silence, for approximately 10 hours after the ibogaine dose, with psychological or emotional support as needed to keep them quiet, calm, and confident. Social interactions and activities were highly discouraged for at least 1 week after ibogaine treatment – an approach mimicking that employed by traditional Gabon healers when using ibogaine during initiation rituals.Maas 2006, Schenberg 2014 Typical ibogaine doses administered in the Brazilian clinic were 17 mg/kg. Overall, self-reported abstinence rates were 57% in men and 100% in women; 71% of men relapsed after the first dose. Average duration of abstinence prior to ibogaine therapy was 88 days (±16 days), 299 days (±42 days) after a single ibogaine dose, and 419 days (±53 days) after all doses combined (P < 0.001). No serious adverse effects were reported; mild short-term effects (ie, nausea, vomiting, ataxia, tremors, headaches, mental confusion) occurred frequently.Schenberg 2014

However, life-threatening adverse events have been reported within days of the first dose of ibogaine administered for treatment of substance addiction (ie, heroin, benzodiazepines, alcohol). Urine tests confirmed the presence of opioids in 2 of these 3 cases. Signs and symptoms included nausea, vomiting, urinary retention, unresponsiveness, QT prolongation, torsades de pointes, and respiratory insufficiency.Paling 2012

Other uses

The leishmanicidal activities of coronaridine and its synthetic analog 18-methoxycoronaridine have been studied in vitro.Delorenzi 2002 Both alkaloids demonstrated dose-dependent effects against the parasite but were nontoxic toward murine macrophages. Calculated 90% inhibitory concentrations were 22 and 16 mcg/mL for coronaridine and 18-methoxycoronaridine, respectively. Tabernanthine has cardiac conduction effects characteristic of a calcium channel antagonist; it also has other pharmacologic actions caused by the inhibition of cellular calcium metabolism and related to the turnover of intracellular calcium released by noradrenaline.Hajo-Tello 2985, Miller 1983

Dosing

Strict medical supervision is necessary. Maximum blood levels and elimination half-life of ibogaine vary among individuals.Mash 2001 Due to documented toxicity, ibogaine should be used only under supervision of a health care provider experienced in its use.Vastag 2002

The authors of a review of clinical trial and toxicology data recommend a maximum oral dosage limit of less than 1 mg/kg as an initial dose in the treatment of drug dependence, which can then be increased incrementally, to avoid potentially life-threatening adverse effects.Vastag 2002

A single dose of ibogaine 500 to 800 mg has been used in clinical trials for the treatment of opioid addictionMash 2001; dividing the dose and administering smaller doses over several days or weeks has been suggested as a safer alternative.Glick 2001 An average single dose of 17 mg/kg has been used in a Brazilian clinic in combination with psychotherapy under close medical supervision with second, third, and fourth single-dose sessions provided at mean-time intervals of 245 days (±226 days), 303 days (±278 days), and 112 days (±100 days), respectively.Schenberg 2014

Pregnancy / Lactation

Avoid use. Information regarding the safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented. Ibogaine is metabolized by CYP450 enzymes, particularly CYP2D6.Mash 2001 Use with agents that affect these enzymes may alter the pharmacokinetics of ibogaine.

Adverse Reactions

Anecdotal reports indicate that ibogaine slows heart rate. This effect has been observed in awake and free-moving rats in which high intraperitoneal doses (100 and 200 mg/kg) decreased heart rate without altering blood pressure.Glick 2001 Single doses of ibogaine have been well tolerated in clinical studies with no clinically important adverse effects reported.Mash 2001 The most frequently observed effects included ataxia, mild tremor, and nausea soon after drug administration. Hypotension occurred in some cocaine-dependent patients, but responded to volume repletion. Manic episodes lasting 1 to 2 weeks have also been reported in a few cases, manifested as sleeplessness, irritability, impulsivity, emotional lability, grandiose delusions, rapid tangential speech and aggressive behavior, and suicidal ideation.Marta 2015

Fatalities have been associated with the use of ibogaine; concomitant opioid use and comorbidities (eg, cardiovascular disease, depression, posttraumatic stress disorder, anxiety, stress, schizophrenia, epilepsy, or other imbalances in the autonomic nervous system) increase the risk of life-threatening complications including sudden cardiac death.Jalal 2013, Litjens 2016, Maas 2006, Mazoyer 2013, Papadodima 2013, Vlaanderen 2014

Toxicology

Neurodegeneration of Purkinje cells and gliosis of Bergmann astrocytes in the cerebella of rats have been observed. Damage appeared to be dose dependent; all rats receiving doses of ibogaine 100 mg/kg showed damage while no damage was detected in rats receiving doses of 25 mg/kg.Xu 2000

Symptoms of overdose include agitation, hallucinations, vomiting, ataxia, muscle spasms, weakness, seizures, paralysis, arrhythmias, urinary retention, respiratory problems, and cardiac arrest.Asua 2013, Jalal 2013, Mazoyer 2013, Paling 2012, Papadodima 2013 Serum concentrations subsequent to ibogaine intoxication have ranged from 360 to 10,800 mcg/L. Approximately 5 hours after ingesting ibogaine 2,400 mg for a spiritual experience, ibogaine serum levels were 948 mcg/L in a young healthy male who survived subsequent ventricular fibrillation, cardiac arrest, coma, and seizures; he suffered permanent cognitive and neurologic deficits.Vlaanderen 2014 Fatalities have been reported following ibogaine ingestion; cases have included the use of ibogaine in individuals with a history of and/or current illicit substance use, coronary disease, and liver disease, as well as in healthy individuals.Asua 2013, Jalal 2013, Mazoyer 2013, Papadodima 2013, Xu 2000 Individuals with cardiovascular disease, depression, posttraumatic stress disorder, anxiety, stress, schizophrenia, epilepsy, or other imbalances in the autonomic nervous system are likely to be at increased risk of sudden unexplained cardiac death with ibogaine ingestion.Maas 2006

References

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Delorenzi JC, Freire-de-Lima L, Gattass CR. In vitro activities of Iboga alkaloid congeners coronaridine and 18-methoxycoronaridine against Leishmania amazonensis. Antimicrob Agents Chemother. 2002; 46:2111-2115.12069962
Duke JA. CRC Handbook of Medicinal Herbs. Boca Raton, FL: CRC Press; 1985.
Glick S, Maisonneuve IM, Szumlinski KK. Mechanisms of action of ibogaine: relevance to putative therapeutic effects and development of a safer iboga alkaloid congener. Alkaloids Chem Biol. 2001;56:39-53.
Hajo-Tello N, Dupont C, Wepierre J, Cohen Y, Miller R, Godfraind T. Effects of tabernanthine on calcium and catecholamine stimulated contractions of isolated vascular and cardiac muscles. Arch Int Pharmacodyn Ther. 1985;276(1):35-43.4051637
Jalal S, Daher E, Hilu R. A case of death due to ibogaine use for heroin addiction case report. Am J Addict. 2013;22(3):302.23617876
Lewis WH, Elvin-Lewis MPF. Medical Botany: Plants Affecting Man's Health. New York: Wiley; 1977.
Litjens RP, Brunt TM. How toxic is ibogaine? Clin Toxicol (Phila). 2016;54(4):297-302.26807959
Lotsof HS, Alexander NE. Case studies of ibogaine teatment: implications for patient management strategies. Alkaloids Chem Biol. 2001;56:293-313.11705114
Maas U, Strubelt S. Fatalities after taking ibogaine in addiction treatment could be related to sudden cardiac death caused by autonomic dysfunction. Med Hypotheses. 2006;67(4):960-964.16698188
Marta CJ, Ryan WC, Kopelowicz A, Koek RJ. Mania following use of ibogaine: a case series. Am J Addict. 2015;24(3):203-205.25877487
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Mazoyer C, Carlier J, Boucher A, Peoc’h M, Lemeur C, Gaillard Y. Fatal case of a 27-year-old male after taking iboga in withdrawal treatment: GC-MS/MS determination of ibogaine and ibogamine in iboga roots and postmortem biological material. J Forensic Sci. 2013;58(6):1666-1672.23919354
Miller RC, Godfraind T. The action of tabernanthine on noradrenaline-stimulated contractions of 45Ca movements in rat isolated vascular smooth muscle. Eur J Pharmacol. 1983;96(3-4):251-259.6676107
Paling FP, Andrews LM, Valk GD, Blom HJ. Life-threatening complications of ibogaine: three case reports. Neth J Med. 2012;70(9):422-424.23123541
Papadodima SA, Dona A, Evaggelakos CI, Goutas N, Athanaselis SA. Ibogaine related sudden death: a case report. J Forensic Leg Med. 2013;20(7):809-811.24112325
Schenberg EE, de Castro Comis MA, Chaves BR, Da Silveira DX. Treating drug dependence with the aid of ibogaine: a retrospective study. J Psychopharmacol. 2014;28(11):993-1000.25271214
Schep LJ, Slaughter RJ, Galea S, Newcombe D. Ibogaine for treating drug dependence. What is a safe dose? Drug Alcohol Depend. 2016;166:1-5.27426011
Schultes RE. Hallucinogenic Plants. New York: Golden Press; 1976.
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US Food and Drug Administration. CFR – Code of Federal Regulations. Title 21: Food and Drugs. Part B – Authority to control; standards and schedules. http://www.fda.gov/regulatoryinformation/legislation/ucm148726.htm. Accessed August 13, 2015.
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Vlaanderen L, Martial LC, Franssen EJ, van der Voort PH, Oosterwerff E, Somsen GA. Cardiac arrest after ibogaine ingestion. Clin Toxicol (Phila). 2014;52(6):642-643.24940646
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