Iboga
Tabernanthe iboga Baill. Family: Apocyanaceae (dogbane)
Iboga , leaf of God , thie-pelakano , bitter grass
 
Clinical Overview
Uses
Iboga is used ritually as an hallucinogen. Studies suggest that ibogaine, one of the iboga alkaloids, has potential in the treatment of addiction to several substances. Use of iboga is illegal in the United States.

Dosing
Ibogaine has been used in single doses of 500 to 800 mg in the treatment of drug addiction; strict medical supervision is essential.

Contraindications
Several deaths have been associated with the use of ibogaine; use of the agent without the supervision of an experienced physician is contraindicated.

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

Interactions
None well documented.

Adverse Reactions
Ataxia, bradycardia, hypotension, mild tremor, and nausea have been reported.

Toxicology
Large doses of iboga can induce convulsions, paralysis, and death from respiratory failure. Dose-dependent brain damage has been observed in rodents.

 
Botany
Tabernanthe 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. 1 A native of the undergrowth of tropical forests, the plant grows ideally in composted, well-drained soil in a protected, partly shady position. 2 It bears dark green, narrow leaves and clusters of white tubular flowers on an erect and branching stem; the fruit is about the size of an olive and is yellowish-orange in color. Traditionally, the yellow-colored root is 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. 3
 
History
West African cultures use the root of iboga in initiation rites 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. 3 Use of iboga has been legally prohibited in the United States since 1970. 4 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. 4 A growing number of clinics using ibogaine have been established, including those in Panama and the Caribbean island of St. Kitts.
 
Chemistry
Indole alkaloids comprise approximately 6% of the root. 5 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. 6 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. 6
 
Uses and Pharmacology
The effects of iboga appear to be dose dependent. Low doses increase 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 induce psychedelic effects, and 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.
Drug addiction   Initial investigation was sparked by 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 2D6 enzyme, and disappears fairly rapidly from the bloodstream (t½ = 7.5 hours). 7 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. 8
The pharmacology of ibogaine is complex, and it is thought to have multiple actions; this is reflected in the ability of the drug to treat diverse addictions. 8 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 NMDA (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. 4 , 8 Studies have reported reductions in self-administration of morphine, heroin, cocaine, alcohol, and nicotine in rodents receiving ibogaine 4 and attenuate signs of morphine withdrawal. An increase in antiaddictive effects by repeated daily or weekly treatments also has been documented. 8
Clinical data   Research into the effects of ibogaine resulted from anecdotal evidence of a group of lay people who noted 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. 9 , 10 Objective signs of withdrawal were rarely seen, and none were exacerbated at later time points. Adverse effects were minor. 10 All subjects 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 a year or longer, and 52% did not use heroin or cocaine for a period of 2 months to 1 year after treatment. 4
Other uses   The leishmanicidal activities of coronaridine and its synthetic analog 18-methoxycoronaridine have been studied in vitro. 11 Both alkaloids demonstrated dose-dependent effects against the parasite but were nontoxic toward murine macrophages. Calculated 90% inhibitory concentrations were 22 and 16 μg/mL for coronaridine and 18-methoxycoronaridine, respectively. Tabernanthine has cardiac conduction effects characteristic of a calcium channel antagonist; it also has other pharmacologic actions that are caused by the inhibition of cellular calcium metabolism and are related to the turnover of intracellular calcium released by noradrenaline. 12 , 13
 
Administration & Dosage
Maximum blood levels and elimination t½ of ibogaine vary between individuals. 7 Because of the documented toxicity of ibogaine, use in any circumstances other than under supervision of a physician experienced in the use of the drug is strictly contraindicated. 4 A single dose of ibogaine 500 to 800 mg has been used in clinical trials for the treatment of opioid addiction 7 ; dividing the dose and administering smaller doses over several days or weeks has been suggested as a safer alternative. 8
 
Pregnancy/Lactation
Information regarding the safety and efficacy in pregnancy and lactation is lacking. Avoid use.
 
Interactions
None well documented. Ibogaine is metabolized by cytochrome P450 enzymes, particularly CYP2D6. 7 Use in conjunction 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. 8 Single doses of ibogaine have been well tolerated in clinical studies with no clinically important adverse effects reported. 7 The most frequently observed effects included ataxia, mild tremor, and nausea soon after drug administration. Hypotension occurred in some cocaine-dependent patients; this responded to volume repletion. No electrocardiac abnormalities were produced or exaggerated in subjects free of a history of cardiovascular risk factors.
 
Toxicology
Large doses of iboga can induce convulsions, paralysis, and death from respiratory failure. Several deaths have been associated with use of ibogaine. 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. 14
 
References
 

1. Duke JA. CRC Handbook of Medicinal Herbs . Boca Raton, FL: CRC Press; 1985.

 

2. Tabernanthe iboga. Available at: http://www.shaman-australis.com/Website/subcat 124.htm . Accessed October 25, 2004.

 

3. Schultes RE. Hallucinogenic Plants . New York: Golden Press; 1976.

 

4. Vastag B. Addiction treatment strives for legitimacy. JAMA . 2002;288:3096, 3099.  PubMed

 

5. Lewis WH, Elvin-Lewis MPF. Medical Botany: Plants Affecting Man's Health . New York: John Wiley & Sons; 1977.

 

6. Tabernanthe iboga. Available online at: http://www.iboga.org/us/eplant01.htm . Accessed October 25, 2004.

 

7. Mash DC, Kovera CA, Pablo J, et al. Ibogaine in the treatment of heroin withdrawal. Alkaloids Chem Biol . 2001;56:155-171.  PubMed

 

8. 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.

 

9. Mash DC, Kovera CA, Pablo J, et al. Ibogaine: complex pharmacokinetics, concerns for safety, and preliminary efficacy measures. Ann N Y Acad Sci . 2000;914:394-401.  PubMed

 

10. Lotsof HS, Alexander NE. Case studies of ibogaine teatment: implications for patient management strategies. Alkaloids Chem Biol . 2001;56:293-313.  PubMed

 

11. 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.  PubMed

 

12. 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;276:35-43.  PubMed

 

13. 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;96:251-259.  PubMed

 

14. Xu Z, Chang LW, Slikker W Jr, Ali SF, Rountree RL, Scallet AC. A dose-response study of ibogaine-induced neuropathology in the rat cerebellum. Toxicol Sci . 2000;57:95-101.