Iboga (ibogaine)
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 Apr 21, 2023.
Clinical Overview
Use
Studies suggest that ibogaine, one of the iboga alkaloids, has potential application in the treatment of addiction to several substances. The US Drug Enforcement Agency (DEA) has designated ibogaine a Schedule I substance under the Controlled Substances Act (CSA).
Dosing
Strict medical supervision is necessary with use. Single oral doses of ibogaine ranging from 500 to 1,000 mg have been used in clinical trials for the treatment of opioid addiction. In patients with drug dependence in a Brazilian drug dependency clinic, an average single dose of 17 mg/kg in combination with psychotherapy was used under close medical supervision. Some literature suggests that based on limited animal data, and applying appropriate safety factors, a maximum initial oral dosage limit of less than 1 mg/kg for the treatment of drug dependence should be adhered to.
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 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. It grows well in the undergrowth of tropical forests, ideally in composted, well-drained soil in a protected, partly shady position.Duke 1985 The plant 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 medicinally 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
Iboga has been used ritually as a hallucinogen. West African cultures use the root of iboga in initiation rites (ie, 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 use of ibogaine in the treatment of opioid dependence.Vastag 2002 Clinics using ibogaine have been established in Western countries, including in Panama and the Caribbean island of St. Kitts.Alper 2007
Chemistry
Indole alkaloids comprise approximately 6% of the root.Lewis 1977 Besides ibogaine (80%), other major components of T. iboga root bark extracts include ibogaline (15%), ibogamine (up to 5%), and, to a lesser extent, tabernanthine and voacangine.Corkery 2018, Koenig 2015, Lavaud 2017 Research has focused largely on the pharmacology of ibogaine. Numerous other compounds are found in iboga (eg, coronaridine, isovoacangine, conophararyngine). The 18-methoxylated analogue of coronaridine (18-methoxycoronaridine [18-MC]) has been investigated as a safer and possibly more effective alternative to ibogaine and coronaridine. 18-MC also exhibits antiaddictive effects and is less toxic in animals than ibogaine.Koenig 2015
Uses and Pharmacology
The DEA has designated ibogaine a Schedule I substance under the CSA. It is a Schedule I hallucinogenic substance in the United States.FDA 2019
The pharmacology of ibogaine is complex, with multiple possible actions reflected by its ability to treat diverse addictions.Glick 2001 The effects of ibogaine may be dose dependent. Low ibogaine doses appear to act on the cerebella to stimulate the sympathetic nervous system, as well as increase muscle strength and endurance. Higher doses lead to vagal dominance (ie, a "feigned death") and induce psychedelic effects; users report a state of dreaming without loss of consciousness.Davis 2017, Maas 2006, Shep 2016 Large doses also induce hallucinations, and iboga has been used ritually as a hallucinogen; it has been suggested that ibogaine's hallucinogenic properties allegedly contribute to its efficacy in treating dependence disorders.Shep 2016
The autonomic nervous system is affected by ibogaine by means of various neurotransmitter systems and the fastigial nucleus.Maas 2006 Ibogaine and noribogaine act on several neurotransmitter systems in the brain, potentially contributing to an ability to suppress autonomic changes, objective signs, and subjective distress associated with opiate withdrawal. They interact with acetylcholine, serotonin, and dopamine systems, as well as show a micromolar affinity to numerous receptor sites such sigma receptors, kappa- and mu-opioid receptors, and the N-methyl-D-aspartate ion channel. Noribogaine also 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. In addition, ibogaine is able to alter the expression of several proteins, substance P, and brain-derived neurotrophic factor. Noribogaine might be less neurotoxic than ibogaine.Litjens 2016
The highly lipophilic ibogaine is subject to extensive biotransformation, primarily by the CYP2D6 enzyme, and disappears fairly rapidly from the bloodstream (half-life of 7.5 hours).Mash 2001 Interindividual differences are evident regarding 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 its protracted effects.Glick 2001
Cardiac conduction effects
In vitro data
The iboga alkaloid 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.Hajo-Tello 1985, Miller 1983
Drug dependence
Animal data
Numerous animal studies have been published demonstrating the antiaddictive effects of ibogaine.Glick 2001, Vastag 2002 Studies have reported reductions in self-administration of morphine, heroin, cocaine, alcohol, and nicotine in rodents receiving ibogaine, as well as attenuated signs of morphine withdrawal.Vastag 2002 The antiaddictive effects seem to increase with repeated daily or weekly treatments.Glick 2001
Clinical data
Clinical research into the effects of ibogaine in substance use disorders (eg, opioid dependence, cocaine dependence) stemmed from anecdotal evidence noting a positive effect on opioid withdrawal in heroin-dependent subjects. Subsequently, several case series have described the use of single doses of ibogaine ranging from 500 to 1,000 mg in patients undergoing opiate detoxification under medical supervision. Objective signs of withdrawal were rarely seen, and none were exacerbated at later time points. Adverse effects were minor. Participants were successful in the detoxification process, and many were able to maintain abstinence after discharge.Corkery 2018, Lotsof 2001, Mash 2000, Mash 2018 One 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 evaluated use of ibogaine in combination with psychotherapy among 75 drug-dependent patients being treated at a Brazilian drug dependency clinic. 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 The typical ibogaine dose administered was 17 mg/kg. All women in the study (n=8) reported that they were abstinent at the time of contact, and only 2 reported having had a relapse after the initial ibogaine session; both women then took ibogaine a second time and have reportedly not relapsed since. Of the male subjects (n=67), 48 (72%) stated that they were abstinent, but 10 of those were also undergoing other treatment interventions; the other 38 (57%) men achieved abstinence with no other treatment.Schenberg 2014 The average duration of abstinence prior to ibogaine therapy was 88 days (±16 days). After a single ibogaine dose, the average duration of abstinence was 299 days (±42 days). After all doses of ibogaine combined, the average duration of abstinence increased to 419 days (±53 days) (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
In an observational study, 30 subjects (25 males, 5 females) meeting Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) criteria for opioid dependence received a mean total dose of ibogaine hydrochloride 1,540±920 mg. Subjects averaged 3.1±2.6 previous treatment episodes for opioid dependence. Using Subjective Opioid Withdrawal Scale (SOWS) and Addiction Severity Index Composite scores, the study showed that ibogaine appeared to have a substantive treatment effect in opioid detoxification. Group statistics and individual trajectories appear to indicate reduced drug use at 1 month, which was sustained up to 12 months in a subgroup of subjects. Results also suggest ibogaine has a clinical effect in some subjects in whom other previous treatments for opioid use disorder (OUD) have failed.Brown 2018
In one study, opioid withdrawal and drug craving scores were evaluated in participants with OUD (N=50) who underwent a week-long detoxification treatment protocol with ibogaine. The Addiction Severity Index was used for baseline characterization of OUD. Clinical Opioid Withdrawal Scale, SOWS, and Brief Substance Craving Scale scores were collected at 48 and 24 hours prior to ibogaine administration, as well as 24 and 48 hours after ibogaine administration. At 48 hours following ibogaine administration, withdrawal and craving scores were lowered compared to baseline. A total of 78% of patients did not exhibit objective clinical signs of opioid withdrawal, 79% reported minimal cravings for opioids, and 68% reported subjective withdrawal symptoms in the mild range. Results suggest that ibogaine facilitates reduced opioid withdrawal and craving in participants with OUD.Malcolm 2018
Parasiticidal activity
In vitro data
The leishmanicidal activities of coronaridine and its synthetic analogue 18-MC have been studied in vitro. Both alkaloids demonstrated dose-dependent effects against the parasite but were nontoxic toward murine macrophages. Calculated 90% inhibitory concentrations were 22 mcg/mL and 16 mcg/mL for coronaridine and 18-MC, respectively.Delorenzi 2002
Psychological effects
Clinical data
A small study in healthy male volunteers (N=21) evaluated effects of a single low dose of ibogaine on mood state and cognitive function. Results did not identify stimulant effects after a single dose of ibogaine 20 mg; cognitive function and mood state were unaffected. However, there was a correlation between ibogaine concentration and performance in a measure of selective attention.Forsyth 2016
Dosing
Strict medical supervision is necessary with use. 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
A no observed adverse effect level has not been established for oral ibogaine. Some literature suggests that based on animal data, a theoretical initial ibogaine dose could be approximated at 0.87 mg/kg body weight, a substantially lower dose than has typically been administered in the treatment of drug dependence. When basing dosing on such data, many factors need to be considered (eg, intra- and interspecies variability, susceptible populations) to avoid morbidities and mortalities.Schep 2016 Another older source suggests that based on limited animal data, and applying appropriate safety factors, a maximum initial oral dosage limit of less than 1 mg/kg for the treatment of drug dependence should be adhered to; this dose may be increased incrementally using appropriate clinical trials that closely monitor indices of human toxicity, to establish a safe and effective dosage.Vastag 2002
Single oral doses of ibogaine ranging from 500 to 1,000 mg have been used in clinical trials for the treatment of opioid addiction.Corkery 2018, Mash 2000, Mash 2001, Mash 2018 This yields peak plasma levels of around 11 mcg/mL about 2 hours after ingestion. More than 90% is eliminated after 24 hours.Corkery 2018 Dividing the dose and administering smaller doses over several days or weeks has been suggested as a safer alternative.Glick 2001
In patients with drug dependence in a Brazilian drug dependency clinic, an average single dose of 17 mg/kg in combination with psychotherapy was used under close medical supervision, with single-dose sessions provided at mean-time intervals of 245 days (±226 days) between the first and second dose, 303 days (±278 days) between the second and third dose, 112 days (±100 days) between the third and fourth dose, and 96 days (±73 days) between the fourth and fifth dose.Schenberg 2014
Pregnancy / Lactation
Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.
Interactions
None well documented. Ibogaine is metabolized by CYP 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 and, at high doses, can damage the nervous system.Willyard 2015 In several patients in clinical studies, a rise in blood pressure and a decline in pulse rate have been recorded 1 to 5 hours after ibogaine doses of 10 to 25 mg/kg.Litjens 2016
In clinical studies, single doses of ibogaine for detoxification have generally been well tolerated, with no clinically important adverse effects reported. The most frequently observed adverse effects included ataxia, mild tremor, and nausea soon after drug administration. Hypotension occurred in some cocaine-dependent patients but was likely due to volume depletion, a likely consequence of cocaine abuse; volume repletion rapidly normalized hypotension in these cases.Mash 2001, Mash 2018 Manic episodes lasting 1 to 2 weeks have also been reported in a few cases, manifesting as sleeplessness, irritability, impulsivity, emotional lability, grandiose delusions, rapid tangential speech and aggressive behavior, and suicidal ideation.Marta 2015
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
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, 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
An autopsy was performed on a woman who received 4 doses of ibogaine (10 to 30 mg/kg) over a period of 15 months, the last administration being approximately 25 days prior to her death of natural causes. There were no signs of damage to the cerebellum, and Purkinje cells were normal.Litjens 2016 However, 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
A review identified 19 cases worldwide of death temporally associated with ingestion of ibogaine from 1990 to 2008, 15 of which were associated with use in detoxification; it should be noted that in 6 cases, cardiac complications were listed as a contributing factor.Alper 2012 With no formal controlled clinical studies on the effects of ibogaine, knowledge regarding risks of use are based on an increasing number of case reports showing increased risk of sudden death, arrhythmias, and seizures. In the absence of specific treatment for ibogaine toxicity, heightened clinical suspicion and thorough supportive care is key to diagnosis and treatment.Meisner 2016
Symptoms of overdose include agitation, hallucinations, vomiting, ataxia, muscle spasms, weakness, seizures, paralysis, arrhythmias and QT prolongation, urinary retention, respiratory problems, and cardiac arrest.Asua 2013, Grogan 2019, Jalal 2013, Mazoyer 2013, Paling 2012, Papadodima 2013, Steinberg 2018 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, a young healthy man experienced ventricular fibrillation followed by cardiac arrest, coma, and seizures; ibogaine serum levels were 948 mcg/L. While the patient survived, he suffered permanent cognitive and neurologic deficits.Vlaanderen 2014
Fatalities have been reported following ibogaine ingestion, including in individuals with a history of and/or current illicit substance use, coronary disease, or 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 The ibogaine congener 18-MC is likely associated with a reduced risk of torsades de pointes arrhythmia induction because it has lower affinity for HERG channels than ibogaine.Koenig 2015
References
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