# Ibogaine

Ibogaine is a psychoactive indole alkaloid obtained either by extraction from plants in the family Apocynaceae such as Tabernanthe iboga, Voacanga africana, and Tabernaemontana undulata or by semisynthesis from the precursor compound voacangine, another plant alkaloid. The total synthesis of ibogaine was described in 1956. Structural elucidation by X-ray crystallography was completed in 1960.
The psychoactivity of the root bark of the iboga tree, Tabernanthe iboga, one of the plants from which ibogaine is extracted, was first discovered by the Pygmy tribes of Central Africa, who passed the knowledge to the Bwiti tribe of Gabon. French explorers, in turn, learned of it from the Bwiti tribe and brought ibogaine back to Europe in 1899–1900, where it was subsequently marketed in France as a stimulant under the trade name Lambarène until the 1960s. It was also marketed as Iperton. Although ibogaine's anti-addictive properties were first widely promoted in 1962 by Howard Lotsof, its Western medical use antedates that by at least a century.
During an 18-year timeline, 19 fatalities temporally associated with the ingestion of ibogaine were reported, from which six subjects died of acute heart failure or cardiopulmonary arrest. Its prohibition in many countries has slowed scientific research. Various derivatives of ibogaine designed to lack psychedelic properties, such as 18-MC, are under preliminary research.

## Psychoactive effects

Ibogaine is derived from the root of Tabernanthe iboga, a plant known to exhibit psychedelic effects in its users. The experience of ibogaine occurs in a visionary phase and an introspection phase. The visionary phase has been described as oneirogenic, referring to the dreamlike nature of its psychedelic effects, and lasts for 4 to 6 hours. The second phase, the introspection phase, is responsible for the psychotherapeutic effects. It can allow people to conquer their fears and negative emotions. Ibogaine catalyzes an altered state of consciousness reminiscent of dreaming while fully conscious and aware, so that memories, life experiences, and issues of trauma can be processed.

## Uses
### Medical

Clinical studies of ibogaine to treat drug addiction began in the early 1990s, but concerns about cardiotoxicity terminated those studies. A 2022 review indicated that severe adverse effects, including deaths, have impeded progress toward clinical adoption of ibogaine for use in opioid abstinence. Evidence to determine whether ibogaine is useful for treating addiction is insufficient.

## Adverse effects

Immediate adverse effects of ibogaine ingestion may include nausea, tremors leading to ataxia, headaches, and mental confusion. In long-term use, manic episodes may last for several days, possibly including insomnia, irritability, emotional instability, delusions, aggressive behavior, and thoughts of suicide. In the heart, ibogaine causes long QT syndrome at higher doses, apparently by blocking hERG potassium channels and slowing the heart rate. Ibogaine should not be used during pregnancy or breastfeeding.
Ibogaine has potential for adverse interactions with other psychedelic agents and prescription drugs.
Death may occur with the use of ibogaine, especially if consumed with opioids or in people with existing morbidities, such as cardiovascular disease or neurological disorders.

### Neurotoxicity

Laboratory studies in rats indicate that high-dose ibogaine may cause degeneration of cerebellar Purkinje cells. However, subsequent research found no evidence of neurotoxicity in a primate.
In limited human research, neuropathological examination revealed no evidence of neuronal degenerative changes in a woman 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.

## Pharmacology
### Pharmacodynamics

Ibogaine (and metabolite) :
| Site | Ibogaine | Noribogaine |
| MORTooltip μ-Opioid receptor | 2,000–100,000 | 700–3,000 |
| DORTooltip δ-Opioid receptor | >100,000 | 5,000–25,000 |
| KORTooltip κ-Opioid receptor | 2,000–4,000 | 600–1,000 |
| 5-HT$_{2A}$ | 16,000 | >100,000 |
| 5-HT$_{2C}$ | >10,000 | >10,000 |
| 5-HT$_3$ | 2,600 | >100,000 |
| σ$_1$ | 2,500–9,000 | 11,000–15,000 |
| σ$_2$ | 90–400 | 5,000–19,000 |
| NMDATooltip N-Methyl-D-aspartate receptor | 1,000–3,000 | 6,000–15,000 |
| nAChTooltip Nicotinic acetylcholine receptor | 20 | 1,500 |
| SERTTooltip Serotonin transporter | 500 | 40 |
| DATTooltip Dopamine transporter | 2,000 | 2,000 |
| Values are K$_i$ (nM). The smaller the value, the more strongly the drug binds to the site. |||
Ibogaine affects many different neurotransmitter systems simultaneously.
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.

### 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 two hours in rats, although the half-life of noribogaine is slightly longer than that of the parent compound. 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.

### 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-azabicyclo[2.2.2]oct-5-ene and cesium carbonate in acetonitrile, the ibogaine precursor 7-ethyl-2-(2-(2-iodo-1H-indol-3-yl)ethyl)-2-azabicyclo[2.2.2]oct-5-ene is obtained. Using palladium acetate in DMF, the ibogaine is obtained. If the exo ethyl group on the 2-azabicyclo[2.2.2]octane system in ibogaine is replaced with an endo ethyl, then epiibogaine is formed.
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.

### 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.
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.

## 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.
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 200 mg extract containing low doses of 4 to 8 mg 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 40 mg 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 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.

## Society and culture
### Legal status

As of 2024, 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.
In the United States, although some cities and states have decriminalized psychedelic chemicals, plants and mushrooms, 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.

### 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

* Detox or Die  [d] (2004). Directed by David Graham Scott. Scott begins videotaping his heroin-addicted friends. Before long, he himself is addicted to the drug. He eventually turns the camera on himself and his family. After 12 years of debilitating, painful dependence on methadone, Scott turns to ibogaine. Filmed in Scotland and England, and broadcast on BBC One as the third installment in the documentary series One Life.
* Ibogaine: Rite of Passage  [d] (2004). Directed by Ben Deloenen. Cy, a 34-year-old heroin addict, undergoes ibogaine treatment with Dr. Martin Polanco at the Ibogaine Association, a clinic in Rosarito, Mexico. Deloenen interviews people formerly addicted to heroin, cocaine, and methamphetamine, who share their perspectives about ibogaine treatment. In Gabon, a Babongo woman receives iboga root for her depressive malaise. Deloenen visually contrasts this Western, clinical use of ibogaine with the Bwiti use of iboga root, but emphasizes the Western context.
* Facing the Habit  [d] (2007). Directed by Magnolia Martin. Martin's subject is a former millionaire and stockbroker who travels to Mexico for ibogaine treatment for heroin addiction.
* Tripping in Amsterdam (2008). In this short film directed by Jan Bednarz, Simon "Swany" Wan visits Sara Glatt's iboga treatment center in Amsterdam. Current TV broadcast the documentary in 2008 as part of their "Quarter-life Crisis" programming roster.
* I'm Dangerous with Love  [d] (2009). Directed by Michel Negroponte. Negroponte examines Dimitri Mobengo Mugianis's long, clandestine career of treating heroin addicts with ibogaine.
* One of the five segments of "Hallucinogens DMT" (2012), Season 2, Episode 4 of Drugs, Inc. on National Geographic Channel, a former heroin user treats addicts with ibogaine in Canada. He himself used ibogaine to stop his abuse of narcotics.
* The "Underground Heroin Clinic" segment of "Addiction" (2013). Season 1, episode 7 of the HBO documentary series Vice examines the use of ibogaine to interrupt heroin addiction.
* The Ibogaine Safari (2014). A documentary by filmmaker Pierre le Roux which investigates the claims of painless withdrawal from opiates such as nyaope/heroin in South Africa by taking several addicts on an adventure "safari" while taking ibogaine. The documentary won the award for 'Best Documentary Short' at the 2014 Canada International Film Festival.
* Iboga Nights  [d] (2014). Directed by David Graham Scott.
* Dosed  [d] (2019). A documentary by Tyler Chandler and Nicholas Meyers. Synopsis- After years of no success with prescription drugs, a suicidal Adrianne seeks help from underground healers with her depression, anxiety, and opioid addiction by utilizing illegal psychedelics like magic mushrooms and iboga.
* "Synthetic Ibogaine - Natural Tramadol" (2021). This episode of the documentary series Hamilton's Pharmacopeia on Vice on TV, follows a struggling local addict to an ibogaine ritual.
* Lamar Odom Reborn  [d] (2022). A documentary by Mike "Zappy" Zapolin, in which famous NBA athlete (and former Keeping Up With the Kardashians star) Lamar Odom seeks out ibogaine and other therapies to heal PTSD, anxiety, and addiction.

#### Print media

* While in Wisconsin covering the primary campaign for the United States presidential election of 1972, gonzo journalist Hunter S. Thompson submitted a satirical article to Rolling Stone accusing Democratic Party candidate Edmund Muskie of being addicted to ibogaine. Many readers, and even other journalists, did not realize that the Rolling Stone piece was facetious. The ibogaine assertion, which was completely unfounded, did significant damage to Muskie's reputation, and was cited as a factor in his loss of the nomination to George McGovern. Thompson later said he was surprised that anyone believed it. The article is included in Thompson's post-election anthology, Fear and Loathing on the Campaign Trail '72 (1973).
* Author and Yippie Dana Beal co-wrote the 1997 book The Ibogaine Story.
* American author Daniel Pinchbeck wrote about his own experience of ibogaine in his book Breaking Open the Head (2002), and in a 2003 article for The Guardian titled "Ten years of therapy in one night".
* Author and musician Geoff Rickly based his debut novel Someone Who Isn't Me on his real-life experiences with heroin addiction and an ibogaine clinic in Mexico.
* American investigative journalist, Rachel Nuwer, published a comprehensive feature for Reason magazine titled Can This Psychedelic Help Cure Opioid Addiction? In the article, Rachel speaks with experts in the field of opioid use disorder (OUD) and how ibogaine shows promising results for effective treatment and recovery. This is particularly true for those patients that also suffer from traumatic brain injuries (TBI).

#### Television drama

Ibogaine factors into the stories of these episodes from television drama series:
* "Patent Pending". FBI: Most Wanted. Season 4. Episode 6. 15 November 2022. CBS.
* "Via Negativa". The X-Files. Season 8. Episode 7. 17 December 2000. Fox Broadcasting Company.
* "Getting Off". CSI: Crime Scene Investigation. Season 4. Episode 16. 26 February 2004. CBS.
* "Users". Law & Order: Special Victims Unit. Season 11. Episode 7. 4 November 2009. NBC.
* "Echoes". Nikita. Season 1. Episode 16. 24 February 2011. The CW Television Network.
* "One Last Time". Homeland (TV series). Season 3. Episode 9. 24 November 2013. Showtime.
* "Bon Voyage". Graceland (TV series). Season 3. Episode 7. 6 August 2015. USA Network.

#### Radio and podcasts

* "Sink or Swim. Act Two. I'm Not a Doctor But I Play One at the Holiday Inn.". This American Life. Episode 321. 1 December 2006. — A former heroin addict realizes that he wants to help other addicts kick their habits. The problem is, he wants to do this using a hallucinogenic drug - ibogaine - that is completely illegal, and which requires medical expertise he doesn't have.
* In January 2025, former Texas Governor Rick Perry and W. Bryan Hubbard, appeared on The Joe Rogan Experience. The trio discussed advances in public policy towards ibogaine and eventual FDA clinical trials. Hubbard was the former Chairman and Executive Director of the Kentucky Opioid Abatement Advisory Commission until he was asked to resign in December 2023. Since 2024, Hubbard has continued his campaign outside Kentucky and now works with the REID Foundation as the Executive Director of the American Ibogaine Initiative.

## Research
### Addiction treatment

The most-studied therapeutic effect of ibogaine is the possible reduction or elimination of addiction to opioids. Research suggests that ibogaine may be useful in treating dependence on other substances such as alcohol, methamphetamine, and nicotine, and may affect compulsive behavioral patterns not involving substance abuse or chemical dependence. Researchers note that there remains a "need for systematic investigation in a conventional clinical research setting."
Many users of ibogaine report experiencing visual phenomena during a waking dream state, such as instructive replays of life events that led to their addiction, while others report therapeutic shamanic visions that help them conquer the fears and negative emotions that might drive their addiction. It is proposed that intensive counseling, therapy, and aftercare during the interruption period following treatment is of significant value. Some individuals require a second or third treatment session with ibogaine over the course of 12 to 18 months. A minority of individuals relapse completely into opiate addiction within days or weeks.

### Psychotherapy

Ibogaine was used as an adjunct to psychotherapy by Claudio Naranjo, documented in his book The Healing Journey. He was awarded patent CA 939266 in 1974.