The psychoactivity of the root bark of the iboga tree,T. iboga, one of the plants from which ibogaine isextracted, was first discovered byforager tribes in Central Africa, who passed the knowledge to theBwiti tribe ofGabon. It was first documented in the 19th century for its spiritual use, later isolated and synthesized for its psychoactive properties, briefly marketed inEurope as astimulant, and ultimately researched—and often controversial—for its potential in treating addiction despite being classified as a controlled substance.
Ibogaine can besemisynthetically produced fromvoacangine, with itstotal synthesis achieved in 1956 and its structure confirmed byX-ray crystallography in 1960. Ibogaine has been studied for treating substance use disorders, especiallyopioid addiction, by alleviating withdrawal symptoms and cravings, but its clinical use and development has been limited due to regulatory barriers and serious safety risks likecardiotoxicity.
Ibogaine produces a two-phase experience—initially visionary anddream-like with vivid imagery andaltered perception, followed by an introspective period marked by lingering side effects likenausea and mood disturbances, which may persist for days. Long-term risks includemania and heart issues such aslong QT syndrome, and potential fatalinteractions 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 like18-MC andtabernanthalog for therapeutic use. In 2025, Texas allocated $50 million forclinical research on ibogaine to developFDA-approved treatments foropioid use disorder, co-occurringsubstance use disorders, and other ibogaine-responsive conditions.
Ibogaine-containing shredded bark ofT. iboga for consumption.
Ibogaine is derived from the root ofTabernanthe iboga, a plant known to exhibit hallucinogenic effects in people who consume it.[11] It is described as having a typical dose range of 1,000 to 1,500mgorally, with these doses producinghallucinogenic effects, and aduration of 18 to 36hours.[1][3] However, lower doses like 200 to 400mg orally are also active.[1][2] In addition, very low doses of ibogaine like 8 to 30mg orally have been used and reported to producestimulant effects.[12][2] Theonset of the drug is 1 to 3hours[2][13][14] and peak effects have been described as being reached after 2hours.[1] With full hallucinogenic doses, ibogaine is described as having three different phases of effects.[2] The first phase is theacute orvisionary phase, which onsets after 1 to 3hours and has a duration of 4 to 8hours; the second phase is theevaluative orintrospective phase, which starts after 4 to 8hours and has a duration of 8 to 20hours; and the third phase isresidual stimulation, which onsets after 12 to 24hours and has a duration of 24 to 72hours or longer.[2] Each of these phases is described as having distinct qualitative effects.[2]
Thevisionary phase is a dream-like, conscious state calledoneirophrenia. 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 adepressed mood. Thevisionary stage typically lasts 4–8 hours, but may last longer with especially high doses.[15][16]
Theintrospective 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 sometimesmania. Depression can persist well after 36 hours, known as a "grey day"; the effect is well-recognized. A persistently low mood can progress intomajor 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).[17]
Immediate adverse effects of ibogaine ingestion may include nausea, vomiting, tremors leading toataxia, headaches, and mental confusion.[18] In long-term use,manic episodes may last for several days, possibly includinginsomnia, irritability, emotional instability,delusions, aggressive behavior, and thoughts ofsuicide.[18] In the heart, ibogaine causeslong QT syndrome at higher doses, apparently by blockinghERGpotassium channels and slowing theheart rate.[19][20] Ibogaine should not be used during pregnancy or breastfeeding.[18]
Laboratory studies in rats indicate that ibogaine at high doses may cause degeneration ofPurkinje cells in thecerebellum.[21][22][23][24] This also occurred with the related drugharmaline.[23][24] However, subsequent research found no evidence of thisneurotoxicity with ibogaine in a primate.[25] In limited human research,neuropathological examination 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.[25] A published series of fatalities associated with ibogaine ingestion also found no evidence for consistent neurotoxicity.[21][26]
Ibogaine's majoractive metabolitenoribogaine has similardiscriminative stimulus properties as ibogaine in rodentdrug discrimination tests, but only partially substitutes for ibogaine.[47][2] It appears that the stimulus properties of ibogaine may be primarily mediated by noribogaine.[47][2] Noribogaine is most potent as aserotonin reuptake inhibitor. It acts as a moderateκ-opioid receptor agonist[37] and weakμ-opioid receptor agonist[37] or weak partial agonist.[36] It is possible that the action of ibogaine at the κ-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 chemicalsalvinorin A, which is a highly selective κ-opioid agonist. Noribogaine is more potent than ibogaine in rat drug discrimination assays when tested for the subjective effects of ibogaine.[48]
There has been uncertainty about whichbiological target interactions mediate thepsychoactive and other effects of ibogaine.[46][47][2] Rodent drug discrimination studies with ibogaine have been employed to help elucidate these interactions.[47][2] Ibogaine partially substitutes for theserotonergic psychedelicsLSD andDOM and this can be blocked by the serotonin5-HT2 receptorantagonistpizotifen.[47] Similarly, LSD and DOM partially substitute for ibogaine and this can be blocked by the serotonin5-HT2A receptor antagonistpirenperone.[47][2][49] Theserotonin releasing agent andpotent serotonin 5-HT2 receptor agonistfenfluramine also partially substitutes for ibogaine.[47] The preferential serotonin5-HT2C receptor agonistsMK-212 andmCPP partially substitute for ibogaine as well and this can be blocked by the serotonin 5-HT2 receptor antagonistmetergoline.[47] The preceding findings suggest that serotonin 5-HT2A and 5-HT2C receptor activation are involved in the subjective effects of ibogaine.[47][2] Conversely, the serotonin5-HT1A and5-HT3 receptors do not appear to be involved.[47][2]
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.[34] In addition, in contrast to the findings in drug discrimination studies, ibogaine fails to produce thehead-twitch response, a behavioral proxy ofpsychedelic effects, in rodents.[46][50] As such, it has been said that ibogaine does not appear to be acting primarily or exclusively as a serotonergic psychedelic[46][50] and that its hallucinogenic effects cannot be ascribed to serotonin 5-HT2A receptor activation.[6] In any case, ibogaine has still been found to have significantin-vivooccupancy of the serotonin 5-HT2A receptor, suggesting that it is still aligand of the receptor.[47]
Theβ-carbolines orharmala alkaloids bear a close resemblance to ibogaine both in terms ofchemical structure and subjective effects.[47] Relatedly,harmaline and6-methoxyharmalan fully substitute for ibogaine in drug discrimination tests, whereasharmine,harmane,harmalol, andtryptoline partially substitute for ibogaine.[47][2][51] 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.[47] However, like ibogaine, harmala alkaloids like harmaline bound to the serotonin 5-HT2A receptor but failed to act as direct agonists of the receptor even at very high concentrationsin vitro.[51] In addition, whereas ibogaine and noribogaine bind to κ-opioid receptors, harmala alkaloids like harmine and harmaline show no affinity for these receptors.[52]
Ibogaine's hallucinogenic effects not being mediated by serotonin 5-HT2A receptor activation has been said to be in accordance with its hallucinogenic effects in humans being qualitatively distinct from and unlike those of serotonergic psychedelics but instead similar to those of harmala alkaloids.[50][53][54] It is also in accordance with the fact that unlike serotonergic psychedelics likeLSD, neither ibogaine nor harmala alkaloids causepupil dilation orincrease blood pressure in humans.[53] Conversely, unlike serotonergic psychedelics, ibogaine and harmaline are said to causebalance disturbances andvomiting to a greater extent than any otherpsychoactive drug besidesalcohol.[53]
Ibogaine shows appreciable affinity for theNMDA receptor.[47] However, the NMDA receptor antagonistsphencyclidine (PCP) anddizocilpine (MK-801) fail to substitute for ibogaine and ibogaine fails to substitute for these NMDA receptor antagonists in rodents and/or monkeys.[47][2] Hence, NMDA receptor antagonism does not appear to be involved in the subjective effects of ibogaine.[47][2] Neitherμ-opioid receptor agonists norκ-opioid receptor agonists likeU-50,488 substitute for ibogaine.[47] In addition, theopioid antagonist naloxone did not substitute for ibogaine.[47] However,naltrexone partially substitutes for ibogaine.[47] In addition, the mixed opioid agonists and antagonistspentazocine,diprenorphine, andnalorphine partially substituted for ibogaine and this could be antagonized by naloxone.[47] The preceding findings suggest a role ofopioid receptors but not the NMDA receptor in the effects of ibogaine.[47][2]
Induction ofgamma oscillations with a profile that resembles that ofREM sleep may be involved in the hallucinogenic and oneirogenic effects of ibogaine.[46][55]
Ibogaine is metabolized in the human body by cytochrome P450 2D6 (CYP2D6) intonoribogaine (more correctly, O-desmethylibogaine or 12-hydroxyibogamine). Both ibogaine and noribogaine have aplasma half-life around 2hours in rats,[58] although the half-life of noribogaine is slightly longer than that of the parent compound.[6] In humans, theelimination half-life of ibogaine is about 7hours whereas the half-life of noribogaine is 24 to 50hours.[6][7][8] Ibogaine may be deposited in fat and metabolized into noribogaine as it is released.[59] After ibogaine ingestion in humans, noribogaine shows higher plasma levels than ibogaine and is detected for a longer period of time than ibogaine.[60]
Ibogaine is asubstituted tryptamine. It has two separatechiral centers, meaning that four different stereoisomers of ibogaine exist, which are difficult toresolve.[1]
One recenttotal synthesis[61] 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 usingpalladium acetate inDMF to form 2-(triethylsilyl)-3-(2-((triethylsilyl)oxy)ethyl)-1H-indole. This is converted using N-iodosuccinamide and thenfluoride to form 2-(2-iodo-1H-indol-3-yl)ethanol. This is treated withiodine,triphenyl phosphine, andimidazole to form 2-iodo-3-(2-iodoethyl)-1H-indole. Then, using 7-ethyl-2-azabicyclo[2.2.2]oct-5-ene andcesiumcarbonate inacetonitrile, 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 bysemisynthesis fromvoacangine in commercial laboratories.[62][63] It can be prepared from voacangine through one-step demethoxycarbonylation process too.[64]
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 frompyridine.[65][66]
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).[67] This discovery was stimulated by earlier studies on other naturally occurring analogues of ibogaine, such ascoronaridine andvoacangine, that showed these compounds to have anti-addictive properties.[68][69]
More recently, non- and less-hallucinogenic analogues,tabernanthalog andibogainalog, were engineered by scientists attempting to produce non-cardiotoxic ibogaine derivatives by removing thelipophilic isoquinuclidine ring. In animal models, both molecules failed to producecardiac arrhythmias, and tabernanthalog failed to produce any head twitch response, suggesting psychedelic effects were absent.[34][70] Other deconstructed analogues of ibogaine, such as5-MeO-IsoqT, have also been developed and studied.[71][34]
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.[72]
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.[72]
Ibogaine occurs naturally in iboga root bark. Ibogaine is also available in a total alkaloid extract of theTabernanthe iboga plant, which also contains all the other iboga alkaloids and thus has only about half the potency by weight of standardized ibogaine hydrochloride.[62]
Due to environmental concerns and low levels inTabernanthe iboga, ibogaine is often produced via semi-synthesis starting with voacangine, a naturally-occurring alkaloid inVoacanga africana.[72]
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 andexplorer ofGabonMarie-Théophile Griffon du Bellay.[73] The first botanical description of theTabernanthe iboga plant was made in 1889. Ibogaine was first isolated fromT.iboga in 1901 by Dybowski and Landrin[74] and independently by Haller and Heckel in the same year usingT. iboga samples fromGabon. Complete synthesis of ibogaine was accomplished by G. Büchi in 1966.[75] Since then, several other synthesis methods have been developed.[76]
From the 1930s to 1960s, ibogaine was sold in France in the form of Lambarène, an extract of theTabernanthe manii plant, and promoted as a mental and physical stimulant.[77] It was formulated at doses of 200mg extract containing low doses of 4 to 8mg ibogaine per tablet.[78][77] 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.[79][77] Another formulation was Iperton, which containedTabernanthe iboga extract 40mg per dose unit.[78]
Anecdotal reports concerning ibogaine's effects appeared in the early 1960s.[80] Its anti-addictive properties were discovered accidentally byHoward Lotsof in 1962, at the age of 19, when he and five friends—all heroin addicts—noted subjective reduction of their craving andwithdrawal symptoms while taking it.[81] 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 Dzoljicet al. in 1988.[82] Diminution ofmorphine self-administration was reported in preclinical studies by Glicket al. in 1991.[83] Cappendijket al. demonstrated reduction incocaine self-administration in rats in 1993,[84] and Rezvani reported reducedalcohol dependence in three strains of "alcohol-preferring" rats in 1995.[85]
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.[86] InCosta Rica, Lex Kogan, another leading proponent, joined Taub in systematizing its administration. The two men established medically monitored treatment clinics in several countries.[87]
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 ofChristiania.[11] 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 relatedindole compounds are susceptible tooxidation over time.[88][89]
TheNational 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.[90] Data demonstrating ibogaine's efficacy in attenuating opioid withdrawal in drug-dependent human subjects was published by Alperet al. in 1999.[91] 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. Mashet 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.[92]
As of 2024[update], the legal status of ibogaine varies widely among countries, as it may be illegal to possess or use, may be legalized, may bedecriminalized, or is under consideration for future legislation.[93]
Ibogaine treatment clinics have emerged inMexico,Bahamas,Canada, theNetherlands,South Africa, andNew Zealand, all operating in what has been described as a "legal gray area".[95][96]Costa Rica also has treatment centers.[87] Covert, illegal neighborhood clinics are known to exist in the United States, despite activeDEA surveillance.[97] While clinical guidelines for ibogaine-assisted detoxification were released by the Global Ibogaine Therapy Alliance in 2015,[98][99] 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.[96]
Detox or Die (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 onBBC One as the third installment in the documentary seriesOne Life.[100]
Ibogaine: Rite of Passage (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, aBabongo 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.[101]
Facing the Habit (2007). Directed by Magnolia Martin. Martin's subject is a former millionaire and stockbroker who travels to Mexico for ibogaine treatment for heroin addiction.[102]
Tripping in Amsterdam (2008). In this short film directed by Jan Bednarz, Simon "Swany" Wan visits Sara Glatt's iboga treatment center in Amsterdam.[103]Current TV broadcast the documentary in 2008 as part of their "Quarter-life Crisis" programming roster.
I'm Dangerous with Love (2009). Directed by Michel Negroponte. Negroponte examinesDimitri Mobengo Mugianis's long, clandestine career of treating heroin addicts with ibogaine.[104]
One of the five segments of "Hallucinogens DMT" (2012),Season 2, Episode 4 ofDrugs, Inc. onNational Geographic Channel, a former heroin user treats addicts with ibogaine in Canada. He himself used ibogaine to stop his abuse of narcotics.[citation needed]
The "Underground Heroin Clinic" segment of "Addiction" (2013).Season 1, episode 7 of theHBO documentary seriesVice examines the use of ibogaine to interrupt heroin addiction.[105][106]
The Ibogaine Safari (2014). A documentary by filmmaker Pierre le Roux which investigates the claims of painless withdrawal from opiates such asnyaope/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 2014Canada International Film Festival.[107][108]
Iboga Nights (2014). Directed by David Graham Scott.[109]
Dosed. 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.[110]
"Synthetic Ibogaine - Natural Tramadol" (2021). This episode of the documentary seriesHamilton's Pharmacopeia onVice on TV, follows a struggling local addict to an ibogaine ritual.[111]
Author and musicianGeoff Rickly based his debut novelSomeone Who Isn't Me on his real-life experiences with heroin addiction and an ibogaine clinic in Mexico.[119]
American investigative journalist,Rachel Nuwer, published a comprehensive feature forReason magazine titledCan This Psychedelic Help Cure Opioid Addiction?[120] In the article, Rachel speaks with experts in the field ofopioid use disorder (OUD) and how ibogaine shows promising results for effective treatment and recovery. This is particularly true for those patients that also suffer fromtraumatic brain injuries (TBI).[121]
"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.[122]
In January 2025, formerTexas GovernorRick Perry and W. Bryan Hubbard, appeared onThe Joe Rogan Experience. The trio discussed advances in public policy towards ibogaine and eventual FDA clinical trials.[123][124] Hubbard was the former Chairman and Executive Director of the Kentucky Opioid Abatement Advisory Commission until he was asked to resign in December 2023.[125] 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.[126]
Ibogaine has been studied for its potential medical use in treating substance use disorders, particularly opioid addiction, by reducing withdrawal symptoms and cravings, though its use and clinical development have been limited by regulatory restrictions and serious safety concerns including cardiac risks.[10][127]
A 2022systematic review of 24 studies involving 705 participants suggests that ibogaine and noribogaine show promise in treating substance use disorders andcomorbiddepressive symptoms andpsychological trauma, but carry serious safety risks, necessitating rigorous clinical oversight.[128]
In 2025, the state of Texas allocated $50 million to fund clinical research on ibogaine, aiming to develop aU.S. Food and Drug Administration-approved treatment for opioid use disorder, co-occurring substance use disorders, and other ibogaine-responsive conditions.[129][130] The initiative, supported by former GovernorRick Perry, established a consortium of universities, hospitals, and drug developers, with the goal of positioning Texas as a leading center forpsychedelic medicine research.[129]
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^Hwu C, Havel V, Westergaard X, Mendieta AM, Serrano IC, Hwu J, et al. (10 March 2025). "Deciphering Ibogaine's Matrix Pharmacology: Multiple Transporter Modulation at Serotonin Synapses".bioRxiv10.1101/2025.03.04.641351.
^Alper K, Bai R, Liu N, Fowler SJ, Huang XP, Priori SG, et al. (January 2016). "hERG Blockade by Iboga Alkaloids".Cardiovasc Toxicol.16 (1):14–22.doi:10.1007/s12012-015-9311-5.PMID25636206.
^abcdefgOna G, Reverte I, Rossi GN, Dos Santos RG, Hallak JE, Colomina MT, et al. (December 2023). "Main targets of ibogaine and noribogaine associated with its putative anti-addictive effects: A mechanistic overview".J Psychopharmacol.37 (12):1190–1200.doi:10.1177/02698811231200882.PMID37937505.Significantly, when assessing the structural and functional plasticity of both IBO and NOR, it was found that NOR, rather than IBO, induces neural plasticity. NOR specifically increases dendritic arbor complexity with an EC50 value comparable to ketamine (Ly et al., 2018). Despite a weak binding affinity, this effect seems to be at least partially mediated by the 5-HT2A receptor, since ketanserin, a selective 5-HT2 serotonin receptor antagonist, blocked this effect (Ly et al., 2018).
^abGrella B, Teitler M, Smith C, Herrick-Davis K, Glennon RA (December 2003). "Binding of beta-carbolines at 5-HT(2) serotonin receptors".Bioorganic & Medicinal Chemistry Letters.13 (24):4421–4425.doi:10.1016/j.bmcl.2003.09.027.PMID14643338.[...] several β-carbolines, including harmaline (1) and its positional isomer 6-methoxyharmalan (4) substituted for the hallucinogenic (5-HT2A agonist) phenylalkylamine [DOM] in a drug discrimination task with rats trained to discriminate DOM from saline vehicle.10 However, neither harmaline (1; Ki=7790 nM) nor 6-methoxyharmalan (4; Ki=5600 nM) binds with high affinity at 5-HT2A receptors, and both were found to lack action as 5-HT2A agonists in a phosphoinositol (PI) hydrolysis assay.5,9 [...] At this time, it is not known if the actions of 1 and 4 in the PI hydrolysis assay reflect their low affinity, low efficacy, or whether the actions of the β-carbolines (in drug discrimination and/or other assays) is attributable to, or compromised by, their actions at other populations of receptors—particularly 5-HT receptors—or by possible interactions with the serotonin transporter.
^Deecher DC, Teitler M, Soderlund DM, Bornmann WG, Kuehne ME, Glick SD (February 1992). "Mechanisms of action of ibogaine and harmaline congeners based on radioligand binding studies".Brain Res.571 (2):242–247.doi:10.1016/0006-8993(92)90661-r.PMID1377086.
^abPalhas M, Corne R, Mongeau R (October 2025)."Changing your mind: neuroplastic mechanisms underlying the therapeutic effect of psychedelics in depression, PTSD, and addiction".Prog Neuropsychopharmacol Biol Psychiatry.142 111533.doi:10.1016/j.pnpbp.2025.111533.PMID41130352.In what may be the most detailed mechanistic study to this day, Ly et al. (2018) have shown LSD, DMT, noribogaine, psilocybin, DOI, and, to a lesser extent, MDMA, to increase neuritogenesis and dendritic spine density in rat cortical cell cultures, through a 5-HT2A-dependent mechanism. Although BDNF levels were not significantly altered, these effects could be abolished by co-administration of a TrKB antagonist or rapamycin, suggesting a causal involvement of the mTOR pathway via BDNF-TrKB signaling (Ly et al., 2018). [...] Ly et al. (2018) confirmed the absence of ibogaine effect on BDNF levels but nonetheless showed increased synaptogenesis. It is likely that this molecule's complex pharmacology (low-affinity 5-HT2A interaction, weak SERT inhibition, NMDA antagonism, and kappa-opioid agonism) obscures our exploration of these mechanisms. Indeed, the 5-HT2A receptors seem involved as the intra-VTA infusion of DMT induces comparable anti-addictive effects to that of ibogaine (Vargas-Perez et al., 2017), and the synaptogenesis induced by ibogaine is blocked by ketanserin, a 5-HT2A/2C antagonist (Ly et al., 2018).
^abLy C, Greb AC, Cameron LP, Wong JM, Barragan EV, Wilson PC, et al. (June 2018)."Psychedelics Promote Structural and Functional Neural Plasticity".Cell Rep.23 (11):3170–3182.doi:10.1016/j.celrep.2018.05.022.PMC6082376.PMID29898390.Notably, the anti-addictive alkaloid ibogaine (Alper, 2001; Belgers et al., 2016) was the only psychedelic tested that had absolutely no effect (Figure S4). This was a surprising result because we hypothesized that ibogaine's long-lasting anti-addictive properties might result from its psychoplastogenic properties. Previous work by He et al. (2005) clearly demonstrated that ibogaine increases the expression of glial cell line-derived neurotrophic factor (GDNF) and that this plasticity-promoting protein is critical to ibogaine's anti-addictive mechanism of action. Because several reports have suggested that noribogaine, a metabolite of ibogaine, might actually be the active compound in vivo (Zubaran et al., 1999; Baumann et al., 2000, 2001), we decided to test its ability to promote neuritogenesis in cultured cortical neurons. Gratifyingly, noribogaine robustly increased dendritic arbor complexity with an EC50 value comparable to ketamine (Figure S3), providing additional evidence suggesting that it may be the active compound in vivo.
^Krengel F, Mijangos MV, Reyes-Lezama M, Reyes-Chilpa R (July 2019). "Extraction and Conversion Studies of the Antiaddictive Alkaloids Coronaridine, Ibogamine, Voacangine, and Ibogaine from Two Mexican Tabernaemontana Species (Apocynaceae)".Chemistry & Biodiversity.16 (7) e1900175.doi:10.1002/cbdv.201900175.ISSN1612-1872.OCLC8185274820.PMID31095891.S2CID157058497.
^Pace CJ, Glick SD, Maisonneuve IM, He LW, Jokiel PA, Kuehne ME, et al. (May 2004). "Novel iboga alkaloid congeners block nicotinic receptors and reduce drug self-administration".European Journal of Pharmacology.492 (2–3):159–67.doi:10.1016/j.ejphar.2004.03.062.ISSN0014-2999.OCLC110898054.PMID15178360.
^Glick SD, Kuehne ME, Raucci J, Wilson TE, Larson D, Keller RW, et al. (September 1994). "Effects of iboga alkaloids on morphine and cocaine self-administration in rats: relationship to tremorigenic effects and to effects on dopamine release in nucleus accumbens and striatum".Brain Research.657 (1–2):14–22.doi:10.1016/0006-8993(94)90948-2.ISSN0006-8993.OCLC4923262393.PMID7820611.S2CID1940631.
^Warren AL, Lankri D, Cunningham MJ, Serrano IC, Parise LF, Kruegel AC, et al. (June 2024)."Structural pharmacology and therapeutic potential of 5-methoxytryptamines".Nature.630 (8015):237–246.Bibcode:2024Natur.630..237W.doi:10.1038/s41586-024-07403-2.PMC11152992.PMID38720072.Further elaboration to isoquinuclidine-containing tryptamines related to ibogaine led to a complete loss of 5-HT1A activity (Supplementary Table 1 and Extended Data Fig. 3). [...] Extended Data Fig. 3 | Global structure-activity landscape of tryptamine psychedelics at 5-HT1A and 5-HT2A receptors and their synthesis. [...] 5-MeO-DMT can be viewed as a deconstruction of ibogaine, a oneirogen with a complex polycyclic tryptamine structure (bottom of the circle). Iboga compounds show no activity at 5-HT1A and 5-HT2A receptors, but this activity re-emerges by deconstruction of the isoquinuclidine core to simple mono-cyclic tryptamines such as 5-MeOPipT (5-methoxypiperidinyl-tryptamine) and 4-F,5-MeO-PyrT (4-fluoro, 5-methoxypyrrolidinyl-tryptamine, right hemi-circle). [...] Supplementary Table 1: EC50 and Efficacy Summary of Tryptamine Analogs and Commercial Ligands [...]
^abcMaciulaitis R, Kontrimaviciute V, Bressolle FM, Briedis V (March 2008). "Ibogaine, an anti-addictive drug: pharmacology and time to go further in development. A narrative review".Hum Exp Toxicol.27 (3):181–194.Bibcode:2008HETox..27..181M.doi:10.1177/0960327107087802.PMID18650249.
^Dzoljic ED, Kaplan CD, Dzoljic MR (1988). "Effect of ibogaine on naloxone-precipitated withdrawal syndrome in chronic morphine-dependent rats".Archives Internationales de Pharmacodynamie et de Therapie.294:64–70.ISSN0003-9780.OCLC115924585.PMID3233054.
^Köck P, Froelich K, Walter M, Lang U, Dürsteler KM (July 2022). "A systematic literature review of clinical trials and therapeutic applications of ibogaine".Journal of Substance Abuse Treatment.138 108717.doi:10.1016/j.jsat.2021.108717.PMID35012793.
