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Ibogaine is a psychoactive indole alkaloid derived from plants such as Tabernanthe iboga, characterized by Hallucinogen and Oneirogen effects. Traditionally used by African Pygmies, it has undergone controversial research for the treatment of substance use disorders. Ibogaine exhibits complex pharmacology by interacting with multiple neurotransmitter systems, notably affecting Opioid receptor, serotonin, Sigma receptor, and NMDA receptor receptors, while its metabolite noribogaine primarily acts as a serotonin reuptake inhibitor and κ-opioid receptor receptor agonist.
The psychoactivity of the root bark of the iboga tree, T. iboga, one of the plants from which ibogaine is , was first discovered by forager tribes in Central Africa, who passed the knowledge to the Bwiti tribe of Gabon. It was first documented in the 19th century for its spiritual use, later isolated and synthesized for its psychoactive properties, briefly marketed in Europe as a stimulant, and ultimately researched—and often controversial—for its potential in treating addiction despite being classified as a controlled substance. Ibogaine can be Semisynthesis produced from voacangine, with its total synthesis achieved in 1956 and its structure confirmed by X-ray crystallography in 1960. Ibogaine has been studied for treating substance use disorders, especially opioid addiction, by alleviating withdrawal symptoms and cravings, but its clinical use and development has been limited due to regulatory barriers and serious safety risks like cardiotoxicity. A 2022 systematic review suggested that ibogaine and noribogaine show promise in treating substance use disorders and Comorbidity depressive symptoms and psychological trauma but carry serious safety risks, necessitating rigorous clinical oversight.
Ibogaine produces a two-phase experience—initially visionary and Oneirogen with vivid imagery and altered perception, followed by an introspective period marked by lingering side effects like nausea and mood disturbances, which may persist for days. Long-term risks include mania and heart issues such as long QT syndrome, and potential fatal Drug interaction with other drugs.
Ibogaine is federally illegal in the United States, but is used in treatment clinics abroad under legal gray areas, with growing media attention highlighting both its potential and risks in addiction therapy. It has inspired the development of non-hallucinogenic, non-cardiotoxic analogues like 18-MC and tabernanthalog for therapeutic use. In 2025, Texas allocated $50 million for clinical research on ibogaine to develop FDA-approved treatments for opioid use disorder, co-occurring substance use disorders, and other ibogaine-responsive conditions.
The visionary phase is a dreamlike, conscious state called oneirophrenia. Visual effects are almost always present and are often described as films or slideshows. These may be accompanied by increases in long-term recall of visual memory, resulting in autobiographical content. Other changes to sensation and perception may occur, including auditory hallucinations or distortions. Nausea and vomiting can be severe. Subjects may experience extreme confusion and/or a depressed mood. The visionary stage typically lasts 4–8 hours, but may last longer with especially high doses.
The introspective is poorly defined, often simply as 24 or 36 hours post-treatment. Sensation and perception return to normal, but nausea, headaches, and other side effects linger. Insomnia, irritability, and mood changes are often seen, including depression and sometimes mania. Depression can persist well after 36 hours, known as a "grey day"; the effect is well-recognized. A persistently low mood can progress into major depressive disorder, a chronic condition. For the treatment of opioid or alcohol addiction, the subjective experiences do not appear to be important, although they are correlated to some secondary measures (e.g. satisfaction in self-assessments).
Ibogaine has potential for adverse drug interaction with other psychedelic agents and prescription drugs. Death can occur, especially if consumed with opioids or in people with Comorbidity such as cardiovascular disease or neurological disorders.
In limited human research, neuropathology revealed no evidence of neuronal degenerative changes in an adult female patient who had received four separate doses of ibogaine ranging between 10 and 30 mg/kg over a 15-month interval. A published series of fatalities associated with ibogaine ingestion found no evidence for consistent neurotoxicity.
Ibogaine affects many different neurotransmitter systems simultaneously and hence has complex pharmacology. The specific targets mediating the effects of ibogaine are not fully clear. The drug is a cyclic compound derivative of serotonin, and hence may be expected to have serotonin actions, but shows relatively low affinity for serotonin receptors. In any case, it appears that the serotonin 5-HT2A, 5-HT2C, sigma receptor σ2, and μ- and/or κ-opioid receptors are involved in the subjective effects of ibogaine based on animal study. Conversely, the NMDA receptor, serotonin 5-HT1A and 5-HT3, and sigma σ1 receptors do not appear to be involved.
Noribogaine is most potent as a serotonin reuptake inhibitor. It acts as a moderate κ-opioid receptor agonist and weak μ-opioid receptor agonist or weak partial agonist. It is possible that the action of ibogaine at the kappa opioid receptor may indeed contribute significantly to the psychoactive effects attributed to ibogaine ingestion; Salvia divinorum, another plant recognized for its strong hallucinogenic properties, contains the chemical salvinorin A, which is a highly selective kappa opioid agonist. Noribogaine is more potent than ibogaine in rat drug discrimination assays when tested for the subjective effects of ibogaine.
There has been uncertainty about which biological target interactions mediate the psychoactive and other effects of ibogaine. Rodent drug discrimination studies with ibogaine have been employed to help elucidate these interactions. Ibogaine partially substitutes for the serotonergic psychedelics LSD and DOM and this can be blocked by the serotonin 5-HT2 receptor antagonist pizotifen. Similarly, LSD and DOM partially substitute for ibogaine and this can be blocked by the serotonin 5-HT2A receptor antagonist pirenperone. The serotonin releasing agent and potent serotonin 5-HT2 receptor agonist fenfluramine also partially substitutes for ibogaine. The preferential serotonin 5-HT2C receptor agonists MK-212 and mCPP partially substitute for ibogaine as well and this can be blocked by the serotonin 5-HT2 receptor antagonist metergoline. The preceding findings suggest that serotonin 5-HT2A and 5-HT2C receptor activation are involved in the subjective effects of ibogaine. Conversely, the serotonin 5-HT1A and 5-HT3 receptors do not appear to be involved.
Although serotonin 5-HT2A receptor signaling appears to be involved in the effects of ibogaine, neither ibogaine nor its major active metabolite noribogaine appear to act as direct serotonin 5-HT2A receptor agonists. Relatedly, it has been said that the hallucinogenic effects of ibogaine cannot be ascribed to serotonin 5-HT2A receptor activation. However, ibogaine has been found to have significant in vivo occupancy of the serotonin 5-HT2A receptor, suggesting that it is still a ligand of the receptor.
The β-carbolines or bear a resemblance to ibogaine both in terms of chemical structure and subjective effects. Relatedly, harmaline and 6-methoxyharmalan fully substitute for ibogaine, whereas harmine, harmane, harmalol, and tryptoline partially substitute for ibogaine. As with the case of ibogaine, the psychedelic DOM partially substitutes for harmaline and this further supports a role of serotonin 5-HT2A receptor activation in the effects of ibogaine as well as of harmala alkaloids like harmaline. However, like ibogaine, harmala alkaloids like harmaline failed to act as direct agonists of the serotonin 5-HT2A receptor even at very high concentrations in vitro.
Ibogaine shows appreciable affinity for the NMDA receptor. However, the NMDA receptor antagonists phencyclidine (PCP) and dizocilpine (MK-801) fail to substitute for ibogaine and ibogaine fails to substitute for these NMDA receptor antagonists in rodents and/or monkeys. Hence, NMDA receptor antagonism does not appear to be involved in the subjective effects of ibogaine. Neither μ-opioid receptor agonists nor κ-opioid receptor agonists like U-50,488 substitute for ibogaine. In addition, the opioid antagonist naloxone did not substitute for ibogaine. However, naltrexone partially substitutes for ibogaine. In addition, the mixed opioid agonists and antagonists pentazocine, diprenorphine, and nalorphine partially substituted for ibogaine and this could be antagonized by naloxone. The preceding findings suggest a role of but not the NMDA receptor in the effects of ibogaine.
The non-selective sigma receptor agonists ditolylguanidine and (+)-3-PPP partially substitute for ibogaine, whereas the σ1 receptor-selective agonists (+)-SKF-10,047 and pentazocine failed to substitute for ibogaine. These findings suggest a role of σ2 receptor signaling in the effects of ibogaine.
In contrast to the findings in drug discrimination studies, ibogaine fails to produce the head-twitch response, a behavioral proxy of psychedelic drug effects, in rodents. As such, it has been said that ibogaine does not appear to be acting primarily or exclusively as a serotonergic psychedelic. This is said to be in accordance with its hallucinogenic effects being distinct from those of serotonergic psychedelics.
Induction of gamma oscillations with a profile that resembles that of REM sleep may be involved in the hallucinogenic and oneirogenic effects of ibogaine.
Ibogaine's major active metabolite noribogaine has similar discriminative stimulus properties as ibogaine, but only partially substitutes for ibogaine. It appears that the stimulus properties of ibogaine may be primarily mediated by noribogaine.
Crystalline ibogaine hydrochloride is typically produced by semisynthesis from voacangine in commercial laboratories. It can be prepared from voacangine through one-step demethoxycarbonylation process too.
In 2025, researchers at the University of California, Davis Institute for Psychedelics and Neurotherapeutics reported the total synthesis of ibogaine, ibogaine analogues, and related compounds from pyridine.
There are two pathways (-)-coronaridine can take to become (-)-ibogaine. The first pathway begins with a P450 enzyme, ibogamine-10-hydroxylase (I10H), and methylation of noribogaine-10-Ο-methyltransferase (N10OMT) to produce (-)-voacangine. Polyneudridine aldehyde esterase-like 1 (PNAE1) and a spontaneous decarboxylation can convert (-)-voacangine to (-)-ibogaine. The second pathway consists of PNAE1 and the spontaneous decarboxylation occurring first to yield (-)-ibogamine, then the reaction of I10H-mediated hydroxylation and N10OMT-catalyzed O-methylation to produce (-)-ibogaine.
Due to environmental concerns and low levels in Tabernanthe iboga, ibogaine is often produced via semi-synthesis starting with voacangine, a naturally-occurring alkaloid in Voacanga africana.
From the 1930s to 1960s, ibogaine was sold in France in the form of Lambarène, an extract of the Tabernanthe manii plant, and promoted as a mental and physical stimulant. It was formulated at doses of 200mg extract containing low doses of 4 to 8mg ibogaine per tablet. The drug enjoyed some popularity among post-World War II athletes. Lambarène was withdrawn from the market in 1966 when the sale of ibogaine-containing products became illegal in France. Another formulation was Iperton, which contained Tabernanthe iboga extract 40mg per dose unit.
In 2008, Mačiulaitis and colleagues stated that in the late 1960s, the World Health Assembly classified ibogaine as a "substance likely to cause dependency or endanger human health". The U.S. Food and Drug Administration (FDA) also assigned it to a Schedule I classification, and the International Olympic Committee banned it as a potential doping agent.
Anecdotal reports concerning ibogaine's effects appeared in the early 1960s. Its anti-addictive properties were discovered accidentally by Howard Lotsof in 1962, at the age of 19, when he and five friends—all heroin addicts—noted subjective reduction of their craving and Drug withdrawal symptoms while taking it. Further anecdotal observation convinced Lotsof of its potential usefulness in treating substance addictions. He contracted with a Belgian company to produce ibogaine in tablet form for clinical trials in the Netherlands, and was awarded a United States patent for the product in 1985. The first objective, placebo-controlled evidence of ibogaine's ability to attenuate opioid withdrawal in rats was published by Dzoljic et al. in 1988. Diminution of morphine self-administration was reported in preclinical studies by Glick et al. in 1991. Cappendijk et al. demonstrated reduction in cocaine self-administration in rats in 1993, and Rezvani reported reduced alcohol dependence in three strains of "alcohol-preferring" rats in 1995.
As the use of ibogaine spread, its administration varied widely; some groups administered it systematically using well-developed methods and medical personnel, while others employed haphazard and possibly dangerous methodology. Lotsof and his colleagues, committed to the traditional administration of ibogaine, developed treatment regimens themselves. In 1992, Eric Taub brought ibogaine to an offshore location close to the United States, where he began providing treatments and popularizing its use. In Costa Rica, Lex Kogan, another leading proponent, joined Taub in systematizing its administration. The two men established medically monitored treatment clinics in several countries.
In 1981, an unnamed European manufacturer produced 44 kg of iboga extract. The entire stock was purchased by Carl Waltenburg, who distributed it under the name "Indra extract" and used it in 1982 to treat heroin addicts in the community of Christiania. Indra extract was available for sale over the Internet until 2006, when the Indra web presence disappeared. Various products are currently sold in a number of countries as "Indra extract", but it is unclear if any of them are derived from Waltenburg's original stock. Ibogaine and related indole compounds are susceptible to oxidation over time.
The National Institute on Drug Abuse (NIDA) began funding clinical studies of ibogaine in the United States in the early 1990s, but terminated the project in 1995. Data demonstrating ibogaine's efficacy in attenuating opioid withdrawal in drug-dependent human subjects was published by Alper et al. in 1999. A cohort of 33 patients were treated with 6 to 29 mg/kg of ibogaine; 25 displayed resolution of the signs of opioid withdrawal from 24 hours to 72 hours post-treatment, but one 24-year-old female, who received the highest dosage, died. Mash et al. (2000), using lower oral doses (10–12 mg/kg) in 27 patients, demonstrated significantly lower objective opiate withdrawal scores in heroin addicts 36 hours after treatment, with self-reports of decreased cocaine and opiate craving and alleviated depression symptoms. Many of these effects appeared sustainable over a one-month post-discharge follow-up.
In the United States, although some cities and states have decriminalized psychedelic chemicals, plants and , ibogaine has had minimal legislation, and remains illegal under federal law, as of 2023. The US Drug Enforcement Administration enforces ibogaine as a Schedule I substance under the Controlled Substances Act.
Neurotoxicity
Laboratory studies in rats indicate that high-dose ibogaine may cause degeneration of cerebellum Purkinje cells. However, subsequent research found no evidence of neurotoxicity in a primate.
Pharmacology
Pharmacodynamics
Pharmacokinetics
Ibogaine is metabolized in the human body by cytochrome P450 2D6 (CYP2D6) into noribogaine (more correctly, O-desmethylibogaine or 12-hydroxyibogamine). Both ibogaine and noribogaine have a plasma half-life around 2hours in rats, although the half-life of noribogaine is slightly longer than that of the parent compound. In humans, the elimination half-life of ibogaine is about 7hours whereas the half-life of noribogaine is 24 to 50hours. Ibogaine may be deposited in fat and metabolized into noribogaine as it is released. After ibogaine ingestion in humans, noribogaine shows higher plasma levels than ibogaine and is detected for a longer period of time than ibogaine.
Chemistry
Ibogaine is a substituted tryptamine. It has two separate chiral centers, meaning that four different stereoisomers of ibogaine exist, which are difficult to resolve. (1997). 9780963009692, Transform Press. ISBN 9780963009692
Synthesis
One recent total synthesis of ibogaine and related drugs starts with 2-iodo-4-methoxyaniline which is reacted with triethyl((4-(triethylsilyl)but-3-yn-1-yl)oxy)silane using palladium acetate in DMF to form 2-(triethylsilyl)-3-(2-((triethylsilyl)oxy)ethyl)-1H-indole. This is converted using N-iodosuccinamide and then fluoride to form 2-(2-iodo-1H-indol-3-yl)ethanol. This is treated with iodine, triphenyl phosphine, and imidazole to form 2-iodo-3-(2-iodoethyl)-1H-indole. Then, using 7-ethyl-2-azabicyclo2.2.2oct-5-ene and cesium carbonate in acetonitrile, the ibogaine precursor 7-ethyl-2-(2-(2-iodo-1H-indol-3-yl)ethyl)-2-azabicyclo2.2.2oct-5-ene is obtained. Using palladium acetate in DMF, the ibogaine is obtained. If the exo ethyl group on the 2-azabicyclo2.2.2octane system in ibogaine is replaced with an endo ethyl, then epiibogaine is formed.
Derivatives
A synthetic derivative of ibogaine, 18-methoxycoronaridine (18-MC), is a selective α3β4 antagonist that was developed collaboratively by neurologist Stanley D. Glick (Albany) and chemist Martin E. Kuehne (Vermont). This discovery was stimulated by earlier studies on other naturally occurring analogues of ibogaine, such as coronaridine and voacangine, that showed these compounds to have anti-addictive properties. More recently, non- and less-hallucinogenic analogs, tabernanthalog and ibogainalog, were engineered by scientists attempting to produce non-cardiotoxic ibogaine derivatives by removing the lipophilic isoquinuclidine ring. In animal models, both molecules failed to produce cardiac arrhythmias, and tabernanthalog failed to produce any head twitch response, suggesting psychedelic effects were absent.
Biosynthesis
Ibogaine biosynthesis begins with tryptophan undergoing enzymatic decarboxylation by tryptophan decarboxylase (TDC) to form a tryptamine. Secologanin, an iridoid synthesized from isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), is reacted with tryptamine to make strictosidine. A glycosidic bond cleavage of strictosidine by strictosidine β-deglucosidase (SGD) produces a lactol. The lactol opens and produces an aldehyde, then condenses to form an iminium. Through isomerization and reduction by geissoschizine synthase 1 (GS1), 19E-geissoschizine is yielded. The indole is oxidized and the molecule undergoes intramolecular Mannich reaction and Grob fragmentation to form preakuammicine. Preakuammicine is highly unstable and therefore reduced to stemmadenine by oxidation-reduction reactions (REDOX 1 and REDOX 2). Stemmadine is acylated by stemmadine Ο-acetyltransferase (SAT) to yield stemmadine acetate. Through oxidation by precondylocarpine acetate synthase (PAS) and reduction by dihydroprecondylocarpine acetate synthase (DPAS), an enamine intermediate is formed. The intermediate undergoes fragmentation to produce an iminium that tautomerizes to yield dehydrosecodine. Coronaridine synthase (CorS) catalyzes the isomerization of dehydrosecodine and an unusual cycloaddition is completed. The iminium is reduced by DPAS and NADPH to form (-)-coronaridine.
Natural occurrence
Ibogaine occurs naturally in iboga root bark. Ibogaine is also available in a total alkaloid extract of the Tabernanthe iboga plant, which also contains all the other iboga alkaloids and thus has only about half the potency by weight of standardized ibogaine hydrochloride.
History
The use of iboga in African spiritual ceremonies was first reported by French and Belgian explorers in the 19th century, beginning with the work of French naval physician and explorer of Gabon Marie-Théophile Griffon du Bellay. The first botanical description of the Tabernanthe iboga plant was made in 1889. Ibogaine was first isolated from T. iboga in 1901 by Dybowski and Landrin and independently by Haller and Heckel in the same year using T. iboga samples from Gabon. Complete synthesis of ibogaine was accomplished by G. Büchi in 1966. Since then, several other synthesis methods have been developed.
(1965). 9780124695085, Elsevier. ISBN 9780124695085
Society and culture
Legal status
, the legal status of ibogaine varies widely among countries, as it may be illegal to possess or use, may be legalized, may be decriminalized, or is under consideration for future legislation.
Treatment clinics
Ibogaine treatment clinics have emerged in Mexico, Bahamas, Canada, the Netherlands, South Africa, and New Zealand, all operating in what has been described as a "legal gray area". Costa Rica also has treatment centers. Covert, illegal neighborhood clinics are known to exist in the United States, despite active DEA surveillance. While clinical guidelines for ibogaine-assisted detoxification were released by the Global Ibogaine Therapy Alliance in 2015,> addiction specialists warn that the treatment of drug dependence with ibogaine in non-medical settings, without expert supervision and unaccompanied by appropriate psychosocial care, can be dangerous — and, in approximately one case in 300, potentially fatal.
Media
Documentary films
Print media
(1997). 9781570270291, Autonomedia. ISBN 9781570270291
(2025). 9780767907422, Broadway Books. ISBN 9780767907422 and in a 2003 article for The Guardian titled "Ten years of therapy in one night".
Television drama
Ibogaine factors into the stories of these episodes from television drama series:
Radio and podcasts
Research
Addiction treatment
A 2022 systematic review of 24 studies involving 705 participants suggests that ibogaine and noribogaine show promise in treating substance use disorders and Comorbidity depressive symptoms and psychological trauma, but carry serious safety risks, necessitating rigorous clinical oversight.
Texas research initiative
In 2025, the state of Texas allocated $50 million to fund clinical research on ibogaine, aiming to develop a U.S. Food and Drug Administration-approved treatment for opioid use disorder, co-occurring substance use disorders, and other ibogaine-responsive conditions. The initiative, supported by former Governor Rick Perry, established a consortium of universities, hospitals, and drug developers, with the goal of positioning Texas as a leading center for psychedelic medicine research.
Psychotherapy
Ibogaine was used as an adjunct to psychotherapy by Claudio Naranjo, documented in his book The Healing Journey. He was awarded patent in 1974.
See also
External links
Categories: Alkaloids Found In Apocynaceae, Alkaloids Found In Iboga, Azepinoindoles, Dream, Drug Rehabilitation, Entheogens, Experimental Hallucinogens, Herg Blocker, Indole Alkaloids, 5-methoxytryptamines, Nicotinic Antagonists, Nmda Receptor Antagonists, Oneirogens, Phenol Ethers, Plant Toxins, Prodrugs, Psychedelic Drugs, Psychoplastogens, Hallucinogens, Serotonin Receptor Agonists, Sigma Agonists, Vmat Inhibitors
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