- Ibogaine is not listed as a scheduled substance by the United Nations but is a controlled or illegal compound in many Western countries, with the notable exception of New Zealand.
- Ibogaine has the potential to decrease a patient’s misuse of opioids, cocaine and alcohol. It reduces symptoms of withdrawal after the administration of a single dose.
- Ibogaine treatment is being offered in several countries around the world, with (average) costs ranging from $2,500 to $10,000 per treatment.
Author: Floris Wolswijk is the founder of Blossom. He started Blossom in 2019 to help translate psychedelic research to a broader audience. Since then, he has grown the database to encompass 2000 papers and hundreds of other valuable resources. Floris has an MSc in Psychology and offers psychedelic-assisted coaching at FLO.
Ibogaine is a naturally occurring psychoactive compound derived from plants such as the roots of the iboga tree (Tabernanthe iboga), though it can also be chemically synthesised. It has been used for over 100 years by the Bwiti tribe of Gabon and holds particular spiritual significance for practitioners of the Bwiti religion in West Africa. Ibogaine also has an established history as a treatment for substance use disorders, particularly in South American countries such as Mexico and Guatemala, where it operates in a legal grey area, being unregulated but not illegal.
Case reports and open-label studies around the world where its use is permissible have found that ibogaine appears to have the potential for rapidly relieving individuals from the grips of addiction and withdrawal. It is currently being researched for the treatment of methadone withdrawal in Spain, alcoholism in Brazil, and opioid withdrawal in the UK and the Netherlands. However, ibogaine’s relatively unsafe profile, leading to at least 20 deaths in the past 30 years, has prompted researchers to research alternatives that offer the benefits without the cardiac risks.
Index of the Ibogaine Compound Page
Clinical Trials and Research into Ibogaine | In Collaboration with BrainFutures
This research section is excerpted from the esteemed non-profit BrainFutures’ 2024 ‘Psychedelic Medicine‘ report. Our joint exploration delves into the latest advancements and insights in the field, reflecting BrainFutures’ commitment to pioneering research and development. To gain a comprehensive understanding of the full psychedelic landscape, we encourage readers to download the complete report (for free). Any updates to the research section after the report’s release are indicated in bold.
IN THIS REVIEW
BrainFutures’ research reviews 23 peer-reviewed studies with ibogaine, including three RCTs and six open-label studies totaling 387 participants, along with one meta-analysis (of animal studies) and 12 reviews. Overall, the investigators found ibogaine to be effective at ameliorating opioid addiction rapidly and for extended periods of time, and eliminating or attenuating withdrawal symptoms. Ongoing research includes three active or recruiting studies on ibogaine for substance use disorders, and one active trial on ibogaine for traumatic brain injury.
VOLUME AND TYPE OF RESEARCH
Since 1950, just over 500 studies have been conducted on ibogaine in total, many evaluating the pharmacological effects and mechanisms of action. About 70 studies are related to ibogaine’s capacity to treat opioid addiction in animals and humans. Of those, one RCT and seven reviews have been published.
AREAS OF RESEARCH SHOWING EFFICACY
- Substance Use Disorder, including opioid addiction
SAMPLE OF RESEARCH FINDINGS
- A single ibogaine treatment reduced opioid withdrawal symptoms and achieved opioid cessation or sustained reduced use in dependent individuals.
- Ibogaine treatment resulted in substantial reduction in use and withdrawal symptoms from oxycodone, heroin, or both at one, three, and 12 months post-treatment.
- The iboga congener 18-MC (18-methoxycoronaridine) appears from animal and preliminary human studies to be non-psychedelic, with a stronger safety profile than ibogaine while maintaining similar anti-addictive properties.
In the available research and anecdotal reports, ibogaine has been found to be effective at rapidly interrupting or reducing future opioid use in those with addiction, and in alleviating or eliminating withdrawal symptoms, including cravings. For the majority of participants, these results show long-term durability, often reported to last several months, and, in some cases, even years. Ibogaine does have a concerning side effect of lowering blood pressure in most individuals and/or extending the time it takes for the heart’s ventricle to contract and relax, which can be a co-factor in mortality as a rare event— and almost exclusively in cardiac-compromised individuals and/or in those who concealed other drug use. Thus, while the anti-addiction properties of ibogaine should not be understated, adequate patient screening is necessary before administering the compound. Additionally, strict monitoring during the dosing experience (and until subjective effects subside) is recommended. When weighing the risks of this intervention, consideration should be given to the high risks of rampant opioid addiction going unaddressed and the risks that some TAUs used to address opioid addiction carry.
Ibogaine is an alkaloid commonly extracted from the root bark of the Tabernanthe iboga, a West Central African shrub. For centuries, it has been used ritualistically and medicinally, mostly by people of the Bwiti religion from the Gabon and Cameroon regions (Richer, 2009).
In the 1800s, French and Belgian explorers first reported on the shrub’s powerful effects as a stimulant, aphrodisiac, and performance enhancer, as well as an alleged vision-inducing agent when taken in higher doses, and in 1864, French physician and ethnobotanist Marie- Théophile Griffon du Bellay brought some of the initial specimens to Europe (Pope, 1969).
By 1901, researchers Jan Dybowsky and Edouard Landrin were the first to make an extract of the iboga root, and called the alkaloid ibogaine (International Center for Ethnobotanical Education, Research and Service [ICEERS], 2019). For about a decade after ibogaine came on the scene, it was “recommended as a treatment for ‘asthenia’ at a dosage of 10 to 30 mg per day” (Brown, 2013). Initial interest in ibogaine’s applications for mental health conditions, however, was modest. As one publication reports:
“The alkaloid was subsequently tested in Western clinical settings and was recommended as a stimulant for the treatment of convalescence and neurasthenia [physical and mental challenges and fatigue thought to be due to emotional causes]. Despite such recommendations, ibogaine never enjoyed wide clinical use and was neglected by researchers for almost 30 years” (Popik & Skolnick, 1999). In the late 1930s, the compound started to be marketed in France as Lambarene, an 8-mg stimulant to help with depression and lack of physical strength and energy, among other conditions. It later went on to be sold as Iperton, a 40-mg tonic and stimulant, and used by athletes as a performance enhancer (Popik & Skolnick, 1999).
By the later part of the 1950s, ibogaine was being explored as a catalyst for psychotherapeutic engagement. Chilean psychiatrist Dr. Claudio Naranjo, MD became among the most well-known clinicians using the compound as an adjunct to psychotherapy, and obtained a French patent for that purpose in 1969 (Myeboga, n.d.; Brown, 2013).
Ibogaine’s potential for its most promising application as an addiction treatment was discovered quite unexpectedly in 1962. A 19-year-old New Yorker, Howard Lotsof, who had a heroin addiction, took ibogaine recreationally. When its effects dissipated some 30 hours later, so too did his craving for heroin (Pinchbeck, 2003). Lotsof also noticed that he did not experience any withdrawal symptoms, and soon shared the drug with a group of 20 psychedelic enthusiasts. Most were around the same age as Lotsof. Of the seven men from the group who had also been addicted to heroin, five immediately stopped using the drug following the session, and abstained for at least another six months (Brown, 2013; Alper et al., 2001).
Inspired by the potential of the compound, Lotsof became one of ibogaine’s most ardent champions, a role that would prove pivotal toward advancing the drug’s anti-addiction research. A major roadblock to that aim came shortly after Swiss chemist George Büchi, D.Sc. first synthesized ibogaine in 1966 (Corkery, 2018). The following year, the compound became illegal in the U.S. and in other countries, and it eventually joined other psychedelics as a Schedule I drug in 1970. Like with other psychedelics, this meant that research dollars and federal approval were to be limited.
Lotsof continued to advocate for the U.S. Congress, federal agencies, and pharmaceutical companies to invest research dollars in studying ibogaine’s potential. He obtained several patents for the drugs as a fast-acting treatment for narcotic, alcohol, and nicotine addictions (Brown, 2013). Lotsof also founded NDA International, Inc.—a drug research, development, and testing company (Brown, 2013). In the early 1990s, NDA International co-sponsored non-medicalized human studies in the Netherlands and in Panama in partnership with two organizations focused on addiction treatment—Dutch Addict Self-Help (DASH) and the International Coalition of Addict Self-Help (ICASH) (Hevesi, 2010; Brown, 2013). One of the goals was to gather effectiveness data from these informal studies. This research, combined with available preclinical data, encouraged the National Institute on Drug Abuse (NIDA) to eventually support more preclinical animal research on ibogaine for treating opioid addiction. This started in the early 1990s, but NIDA abandoned the effort within five years.
Prior to this decision, in 1993, the FDA had granted University of Miami researcher Deborah Mash, PhD and her team a Phase I pharmacokinetics and safety trial of ibogaine, which was later revised and reapproved in 1995 to include cocaine-dependent subjects (Brown, 2013). After NIDA’s 1995 decision to step away from human ibogaine research, the FDA wrote NIDA’s director of Medications Development Division urging the agency to reconsider—the FDA recommended that NIDA fund at least a small Phase 1 safety study in humans, but to no avail (Doblin, n.d.). NIDA cited safety reasons as one of its concerns for pulling out (Oaklander, 2021). Mash and her team tried applying for a NIDA grant based on some preliminary research, but funding was denied, and the dose escalation trials at the University of Miami could not be completed (Doblin, n.d.; Brown, 2013).
Despite concerns from federal officials about ibogaine’s risk potential as well as limited research from controlled studies, ibogaine’s use as a treatment for SUDs grew by a reported 400 percent between 2001 and 2006, further bolstering an “ibogaine medical subculture” of clinical and lay practitioners across different parts of the world (Alper et al., 2008). An ethnographic study reported four distinct “scenes” of these providers types: medical model, made up of licensed physicians with treatment done in medical or clinical research facilities; lay provider/treatment guide, consisting of providers that lack medical credentials and in settings that are nonclinical; activist/self-help, with providers who are ibogaine activists (eager to widen its use and acceptance), and also in nonclinical settings; and religious/spiritual, lay providers or traditional healers in a ceremonial or spiritual setting (Alper et al., 2008).
Preclinical studies in animals, case reports, and open-label studies in humans support anecdotal evidence of ibogaine’s effectiveness in addressing opioid and other substance use addictions. Completed controlled trials would allow for further exploration of this compound’s potential as an anti-addiction treatment. Some persistent safety concerns seem to impede this level of research from advancing more quickly (Brown, 2013) and are addressed in the “Tolerability of Ibogaine” section below.
Today, ibogaine is classified as a pharmaceutical in New Zealand, Brazil, and South Africa, with administration privileges restricted to licensed medical practitioners (MAPS, 2017). The use of ibogaine as a treatment for addictions is also available in medical facilities in other countries, including in Mexico, Canada, and the U.K., and Denmark.
Tolerability of Ibogaine
The clinical dosage of ibogaine for anti-addiction treatment is generally at 15 to 20 mg/kg, given in only a single administration (Brown, 2013). The onset, duration, and quality of experiences is summarized in a 2013 review:
“The onset of the “acute” phase occurs within 1-2 hours of ingestion and lasts for 4-8 hours and is often marked by emotional intensity and the experience of location and interaction within a “waking dream.”… With ibogaine, commonly reported themes during the acute stage include visions of, and interrogatory exchanges with, ancestral or archetypal persons or beings; placement in and movement within a dream-like visual landscape; and panoramic recall of personal experiences or past events. Some reports indicate that these visions appear only when the viewer’s eyes are closed, and that when the eyes are open, people and things in the surrounding environment appear normal… The “evaluative” stage begins [four to eight] hours after ingestion and lasts for [eight to] 20 hours. During this phase the subject’s attention continues to be inwardly directed rather than towards external stimuli, and the emotional tone tends to diminish in intensity… The panoramic recall slows considerably or entirely as the patient reflects upon and evaluates the experiences of the acute phase. The material contemplated during this stage may consist of experiences from the dreamlike period as well as recollections of other memories and often concerns traumatic or highly emotional experiences, important personal relationships, or impactful decisions the patient has made. The onset of the final stage, called the “residual stimulation” phase is roughly 12 to 24 hours after ingestion; this period generally lasts for 24-72 hours or even longer. Reports of this phase suggest that the patient returns to a normal state of attention to the external environment during this time. [D]rug dependent patients… reveal that the most common themes emerging from the interpretation of the experience included a sense of insight into destructive behaviors (86.7 [percent] of respondents), a felt need to become abstinent (68.3 [percent]), the experience of having been cleansed, healed, and reborn (50.0 [percent]), and the sense of having a second chance at life (40.0 [percent])” (Brown, 2013).
The review goes on to report that subjects “[experience] a sharp reduction in drug cravings and signs of withdrawal within one to two hours” lasting up to 18 hours, with an absence of cravings lasting for several days to a couple of months—though some case reports have these outcomes lasting years in some cases.
Mild side effects of ibogaine can begin immediately after administration of the compound. They may include dry mouth, ataxia (a lack of muscle control), nausea, and vomiting, which can last from 12 to 24 hours (Obembe, 2012).
A review of existing animal and human studies in 2008 also noted potentially neurotoxic and cardiotoxic side effects of ibogaine (Mačiulaitis et al., 2008). Tremors and postural instability have been observed in human subjects, and in one study, six out of 39 participants experienced significantly lowered resting pulse rate. Hypotension (low blood pressure) has also occurred in some cocaine-dependent subjects, requiring close monitoring (Mačiulaitis et al., 2008).
Although rare, serious adverse events related to ibogaine treatment have resulted in death. A 2015 review (Koenig & Hillber, 2015) indicated that between 1990 and 2008, 19 people died within 1.5–76 hours after ingesting large doses of ibogaine. Most died from cardiac arrest, and the majority also had some history of cardiovascular disease or some other significant health condition, often related to long-term substance abuse. Ibogaine’s toxicity was not found to be a cause of any of these fatalities. The authors reported, “These adverse reactions were hypothesized to be associated with ibogaine’s propensity to induce cardiac arrhythmias.” They also stated that because most treatments are done underground or outside of documented settings, the number of people who have experienced adverse effects (and the total number who have engaged in the treatment) is unknown.
Building on the work of Koenig and Hillber (2015) and Alper (2012), Genis Ona, PhD and colleagues (2021) conducted a systematic review of reports of adverse effects in studies of ibogaine and noribogaine (psychoactive metabolite of ibogaine) from 2015–2020. The authors note that there has been little consistency in terms of dosage and study design, so it is difficult to draw broad conclusions. However, this review largely confirms earlier work that highlights potential cardiac side effects. The most common problem was QTc prolongation (when the heart takes longer than usual to contract and relax), as well as tachycardia (accelerated heart rate of 100+ beats per minute), and low blood pressure. Physical symptoms such as tremors and weakness were also found, as well as multiple reports of seizures. It is important to note that no prolonged adverse reactions to ibogaine were reported in controlled settings. The authors conclude by recognizing that the available safety data are insufficient: “Considering that a growing number of people worldwide are using these drugs in search for a treatment for substance use disorders, Phase [1 and 2] trials are urgent[ly] needed to assess their tolerance and safety, dose–effect relationships, and possible drug-drug interactions.”
In short, ibogaine treatment health risks are greater when a participant has pre-existing medical cardiac condition(s), when dosages are higher than normally indicated for SUD treatment, and/or when other drugs (e.g. opioids or other narcotics) are taken soon before or after ingesting ibogaine (Brown, 2013). It is also important to consider that currently there is limited long-term safety data available on the intervention. In light of all of these considerations, treatment for patients with cardiovascular concerns (especially prolonged QTc Interval or hypertrophic cardiomyopathy) is contraindicated, and it is recommended that any session is conducted with proper medical supervision.
The ibogaine dose associated with better addiction treatment effectiveness is also associated with the above risks. Research has found that a lower dose does not present the same side effects and risk profile. In 2016, an RCT was completed on 21 healthy male volunteers with a low dose (20 mg total in a single administration) of ibogaine to analyze its effect on mood states and cognitive function, comparing psychometric test and mood rating results pre-intervention and two hours after administration (Forsyth et al., 2016). The low dose was reported to have “minimal influence” on either metric reading type. This may lead to further research to evaluate dosage risk versus efficacy.
Undoubtedly, serious side effects, including fatalities, from potential new treatment interventions must be given serious consideration. However, this assessment must also weigh the risks of a condition going untreated and the risks of treatments as usual. In the case of drug addictions, more than 840,000 Americans have died since 1999 from a drug overdose (CDC, 2021a)— meaning the risks of leaving this condition untreated are astronomically high. What is more, prescription medication given by doctors, including those meant to curb the addiction crisis, can add to this epidemic (CDC, 2021d). For instance, over the past 20 years, approximately 250,000 of the 840,000 overdose deaths in the U.S. involved prescription opioids. First-line FDA-approved TAUs for opioid addiction fall into this category of prescription opioid drugs—methadone (opioid full agonist) and buprenorphine (a partial opioid agonist). These treatments have FDA black box warnings and carry their own overdose risk, including the risk of death.
Although studies show that retention in these treatments is associated with lower mortality rates for people dependent on opioids (Sordo et al., 2017), maintaining treatment retention can often be problematic. With methadone, for example, both the required multiple trips per week to a clinician’s office for drug administration (prior to being approved for self-administration) and the long-term need for treatment get in the way of treatment retention. Ultimately, methadone is responsible for 5,000 deaths per year, a sixfold increase over the past decade, and it is involved in 30 percent of accidental overdose deaths (CDC, 2012; Vestal, 2015). This is not to say that methadone should not be administered for opioid addiction treatment, rather that it too, like ibogaine, comes with risks.
Beyond the risk of death, methadone and buprenorphine carry other serious risks, such as addiction to the treatment drug and long-term health effects of the treatment drug. For all of these reasons, providers and patients are left looking for other effective anti-addiction treatment options. By comparison, ibogaine’s risk profile—especially when given in a medical setting—is likely no greater than TAU, it is non-addictive as evidenced across studies, and it has potentially better outcomes than TAU. All of this means ibogaine should be a research priority in light of our current national addiction crisis, which causes 50,000 people to die every year (National Center for Drug Abuse Statistics, 2019).
“More Americans died from drug overdoses last year than ever before.”
A 2021 article in Time magazine summarizes these competing considerations. It states:
“More Americans died from drug overdoses last year than ever before, aggravated by the COVID-19 pandemic. Weekly counts of drug overdoses were up to 45 percent higher in 2020 than in the same periods in 2019, according to research from the U.S. Centers for Disease Control and Prevention published in February. Available treatments can’t meet the need. They aren’t effective for everyone, may require long-term adherence and are sometimes addictive themselves… Ibogaine is one of the most promising psychedelics for addiction. Few people have heard of it, it’s illicit in the U.S., and nobody does it for fun. It’s not pleasant. It could kill you. But for extinguishing addiction—and a range of other issues—many people swear there’s nothing like it” (Oaklander, 2021).
Ibogaine as a Potential Treatment for Substance Use Disorders
In the 1980s, preclinical trials in animals began in an attempt to further validate or discount the anecdotal reports of ibogaine’s outcomes in humans. The results from this substantialbody of preclinical evidence are broadly consistent across studies and suggest: a) ibogaine chemically interrupts addiction to opioids, amphetamine, methamphetamine, cocaine, alcohol, and nicotine as evidenced by reductions in self-administration of the drugs; b) signs of attenuation of opioid withdrawal have also been observed; and c) safe levels of ibogaine are well-tolerated but monitoring of human patients is warranted to manage for any possible toxic effects (Glick & Maisonneuve, 2000; Alper et al., 2008; Belgers et al., 2016).
After Lotsof first observed ibogaine’s potential as an anti-addiction treatment in the early 1960s, most research on its effect with humans has come from case reports from informal treatment networks across the world. The reports tend to provide consistent results—participants attest that the compound alleviated craving and withdrawal symptoms of their substance use disorders.
In 1999, Kenneth Alper, MD and colleagues completed a retrospective study that included many of these earlier reports. The study included 33 patients—26 who had sought treatment in the Netherlands for opioid addiction from 1989–1993, as well as the seven heroin addicts from Lostof’s group session in the 1960s. In this early nonmedical open-label study, patient IV heroin use was treated with ibogaine at an average dose of 19 mg/kg. Outcomes resulted in successful withdrawal with no further drug-seeking behavior in 25 of the 33 participants “sustained throughout the 72-hour period of posttreatment observation” (Alper et al., 1999). One participant died during treatment, with researchers suspecting “surreptitious heroin use.” Of the remaining seven participants, the study stated that two patients experienced drug abstinence with attenuated withdrawal signs, four patients continued drug-seeking behavior without withdrawal signs, and one patient showed drug-seeking behavior with continued withdrawal signs.
These quasi-clinical treatments were taking place beyond just the U.S. and the Netherlands. Reports of providers in Panama, Britain, Slovenia, the Czech Republic, Canada, Mexico, and Italy were also known (Brown, 2013; MAPS, 2003).
Alper and colleagues completed a 2007 ethnographic analysis of clients from this international network of informal treatment providers. More than 3,400 people had taken ibogaine as of 2006—68 percent of participants had done so to treat a substance abuse disorder, and 53 percent were specifically wrestling with opioid dependence (Alper et al., 2008). After reviewing and analyzing the data, the study concluded that, “Ibogaine’s effect in opioid withdrawal is consistent with case series and preclinical evidence, and is unlikely to be mediated by placebo.”
A review in 2013 conducted by Thomas Brown, PhD offered an outcome study focused on ibogaine treatment for opioid addiction. It provided a literature review covering preclinical studies, safety concerns, and findings thus far related to the compound’s treatment success with opioid-dependent patients. The review concluded by stating:
“In sum, the human studies of ibogaine treatment provide some preliminary support for the efficacy of ibogaine in alleviating the considerable discomforts of withdrawal from opiates and other addictive drugs, and thereby in facilitating detoxification from these substances in a comparatively painless manner… The limited research results achieved so far suggest that opiate and cocaine cravings are significantly reduced for up to [one] month following treatment and that a substantial minority of patients remain abstinent for several months.”
Brown’s review recommended future long-term outcome studies to better understand the durability of the effect of ibogaine as an addiction treatment intervention. Two observation studies published in 2017 and 2018, including one led by Brown, helped answer that call.
In New Zealand, where ibogaine treatment is legally available, an open-label study on 14 participants (50 percent female) between ages 18 and 47 with opioid addiction was conducted (Noller et al., 2018). The study was designed to offer long-term follow-up data. Dependencies of the enrollees included methadone (10), codeine (three), and poppy seeds (one). Participants received staggered oral doses of 200 mg capsules over 24–96 hours for a total of 55 mg/kg of ibogaine with benzodiazepine and sleep aids. One death did occur during treatment while a participant was under medical supervision (and for which the provider was later found to have failed in their duty of care). With regard to the remaining participants, the study found at the 12-month follow-up that “a single ibogaine treatment reduced opioid withdrawal symptoms and achieved opioid cessation or sustained reduced use in dependent individuals.” The unfortunate fatality did raise safety issues relative to the importance of better standardized prescreening, dosing, and medical supervision protocols.
Another open-label observation study was conducted in Mexico, enlisting 30 individuals (five female) diagnosed with opioid dependence on oxycodone, heroin, or both (Brown & Alper, 2018). A mean total dose of 1,540 ± 920 mg ibogaine was given. Outcomes were taken at one, three, six, nine, and 12 months post-treatment. The study found that treatment with ibogaine led to substantial reduction in use and withdrawal symptoms at one, three and 12 months. At the one-month mark, 50 percent of the participants had been opioid-free since treatment, and 40 percent reported a 75 percent reduction in their drug use; at the three-month follow-up, 33 percent reported being opioid-free for the past month. The study reports, “improvement in Drug Use scores was maximal at [one] month, and subsequently sustained from [three] to 12 months.” The researchers concluded that:
“Ibogaine was associated with substantive effects on opioid withdrawal symptoms and drug use in subjects for whom other treatments had been unsuccessful… ibogaine appeared to have a substantive treatment effect in opioid detoxification, and group statistics and individual trajectories appear to indicate an effect of reducing drug use at [one] month, which was sustained up to 12 months in a subgroup of subjects… No adverse medical events occurred in this study.”
Another review in 2018 was authored by Deborah Mash, PhD and colleagues. After NIDA funding dried up in the mid-1990s, Mash moved her studies off-shore to Saint Kitts, West Indies. This 2018 review looked at the methods and outcomes of ibogaine treatment for opioid use disorder at a 12-bed treatment facility on the island. Participants took part in a 12-day inpatient protocol designed to assess the safety and open-label efficacy of ibogaine-assisted therapy for treating opioid or cocaine dependency. The review included 191 individuals (47 female) from a series of treatment cohorts, who were given oral doses of ibogaine (8–12 mg/kg). The research concluded that ibogaine, “unlike a methadone or buprenorphine taper, is a rapid detoxification method, shortening the time needed for withdrawal to [two to three] days.” In addition, the study reported no significant adverse events “following administration of ibogaine in a dose range that was shown to be effective for blocking opioid withdrawal symptoms in this study.”
This 2018 review found that ibogaine treatment for opioid dependence in patients without preexisting conditions did not lead to cardiac side effects. Cardiac side effects were exclusively observed in some patients without preexisting conditions who were treated for cocaine dependence. Therefore, all participants were carefully screened prior to admission, and potential or occurring low blood pressure and low resting heart rate in the cocaine group was effectively mediated by IV fluids. The authors reinforce earlier review findings on ibogaine risks:
“Unfortunately, deaths related to ibogaine have been described for persons seeking detoxification from drugs and alcohol involving variable product purities of ibogaine (HCl or extract) (Alper et al., 2012; Noller et al., 2018). Many of the forensic investigations of ibogaine deaths lacked postmortem toxicologic measures of ibogaine or its metabolite noribogaine in blood (Alper et al., 2012). Ibogaine fatalities are frequently associated with higher doses of ibogaine (>20 mg/kg), which are well above those used in our study, suggesting that there is an increased risk for toxicity at higher doses depending on CYP2D6 genotype [a rating of person’s ability to metabolize drugs]. Also, multiple doses of ibogaine ‘stacked’ over time following the initial ‘flood’ dose were reported for many of these cases…
A review of the available information suggests advanced drug-related comorbidities and contributing conditions, including cardiovascular disease and polydrug abuse in the days or hours prior to ibogaine treatment, may have contributed to the AEs and possible drug-related fatalities (Kontrimavici et al., 2006; Kubiliene et al., 2008; Alper et al., 2012). Because ibogaine is a medicinal investigational product, these observations underscore the importance of strict inclusion/exclusion criteria to ensure patient safety” (Mash et al., 2018).
“Ibogaine significantly decreased craving for cocaine and heroin during inpatient detoxification.”
Mash and colleagues’ previous research leading up to this review involved systematic investigations of ibogaine as a treatment for opioid withdrawal dating back to 2000. This early comparative study concluded that ibogaine showed efficacy as an inpatient detoxification treatment for cocaine and heroin users, with opiate cravings significantly reduced at 36 hours and one month, and further, depressive symptoms remained significantly alleviated at 30-day follow-up (Mash et al., 2000). The authors stated:
“Ibogaine significantly decreased craving for cocaine and heroin during inpatient detoxification. Self-reports of depressive symptoms were also significantly lower after ibogaine treatment and at 30 days after program discharge. Because ibogaine is cleared rapidly from the blood, the beneficial aftereffects of the drug on craving and depressed mood may be related to the effects of noribogaine [a metabolite of ibogaine that is produced in the body] on the central nervous system.”
Deepening this 2000 research, Mash and colleagues published a 2001 review hypothesizing that the mechanism of action leading to successful withdrawal from opiates could be related to noribogaine, the psychoactive metabolite metabolized in the body from ibogaine following ingestion (Mash et al., 2001). In this study, the researchers used a single 800-mg dose of ibogaine, and withdrawal symptoms were rated at one hour before ibogaine dosing, and again at several intervals post-treatment. Withdrawal symptoms were significantly lower at 12 and 24 hours after dosing, at discharge approximately one week later, and at one-month follow-up.
When reflecting on the work she led in Saint Kitts over the past two decades, Mash noted:
“Not only were patients able to safely and successfully transition into sobriety, we found no evidence of additional abuse potential. Given the limitation in currently available treatments, ibogaine represents an enormous leap forward for [opioid use disorder] sufferers” (DemeRx, 2020).
Adding to the long-term outcomes for ibogaine treatment, an unpublished Dutch doctorandus thesis by Ehud Bastiaans collected survey data, based on the European Addiction Severity Index, to evaluate the post-treatment outcomes of 21 people who had undergone ibogaine treatment for opioid dependence (Bastiaans, 2004). The research found that 90 percent remained abstinent from all drugs for at least one week. The average length of abstinence for all participants was 3.5 years: 24 percent were entirely abstinent; 43 percent were free from opioids for an average of 1.5 years but may have used cannabis or alcohol; 33 percent returned to substance use, although the majority were using smaller quantities of opioids. Relating to quality of life, 58 percent reported improvements in medical health, and 96 percent reported improvement in psychological well-being.
Research on Compounds Related to Ibogaine
As the opioid crisis accelerates and current therapies fall short, the need for effective treatment options persists. Scientists and chemical engineers are looking for ways to modify ibogaine to preserve its powerful anti-addiction properties while reducing or eliminating serious adverse effects, in particular, the risk of cardiovascular failure (Brown, 2013). The research behind three potentially promising compounds related to ibogaine—noribogaine, 18-methoxycoronaridine, and tabernanthalog—are outlined below.
Noribogaine is a metabolite of ibogaine. Researchers have speculated that this compound may be responsible for some of ibogaine’s anti-withdrawal and anti-craving effects because it persists in the body much longer than ibogaine (Glue et al., 2015). Two clinical trials have explored the safety and tolerability of noribogaine: one Phase 1 RCT study published in 2015 with healthy subjects, and another RCT published in 2016 with opioid withdrawal syndrome patients (Glue et al., 2015; Glue et al., 2016). While the 2015 study found no adverse effects, some participants in the 2016 study experienced adverse side effects, including QTc prolongation, which is associated with bradycardia (heart rate < 60 beats per minute) and arrhythmia (Ona, 2021, Köck et al., 2021). The 2016 study also did not find any statistically significant decrease in withdrawal symptoms. This study and later reviews have noted that the noribogaine dosage level used in this study (between 60 and 180 mg) may not have been large enough to elicit an anti-withdrawal effect (Ona, 2021; dos Santos, Bouso, & Hallak, 2016).
A synthetic derivative of ibogaine,18-methoxycoronaridine is another promising compound. Animal studies have shown that 18-MC has similar outcomes in terms of reduction of substance use, but without affecting heart rate.
In an early study of 18-MC on rats, Dr. Stanley Glick, MD, PhD and Dr. Isabelle Maisonneuve, PhD found that while the compound’s effects on drug self-administration were equivalent to ibogaine, 18-MC appeared “much safer.” The researchers concluded:
“Even at high doses, 18-MC does not mimic ibogaine in producing neurotoxic (Purkinje cells in cerebellum) or cardiovascular (bradycardia) effects… Considered together, all of the data indicate that 18-MC should be safer than ibogaine and at least as efficacious as an anti-addictive medication” (Glick & Maisonneuve, 2000).
Further studies have continued to bear out these initial findings. Koenig and Hilber’s research (2015) stated: “[T]he ibogaine congener 18-MC is likely associated with a reduced risk of TdP arrhythmia induction, because it shows considerably lower affinity for hERG channels [essentially the potassium channel that, in-part, controls electrical activity to the heart] than ibogaine. We encourage researchers to develop ibogaine-like drugs with preserved anti-addictive properties.”
In 2021, a Phase 1 trial sponsored by a U.S. company of 18-MC in Australia, targeting opioid disorder treatment, was completed (MindMed, 2022b). The trial examined the safety and effects of varied doses of 18-MC on healthy volunteers. A planned Phase 2a trial in 2022 for opioid withdrawal was delayed due to FDA’s request for more preclinical research, prompting MindMed to reallocate resources (MindMed, 2022c). While initial studies hinted at 18-MC’s potential as an anti-obesity treatment, recent updates do not expand on this possibility (Lavaud & Massiot, 2017).
The ibogaine analog tabernanthalog has recently been synthesized and tested in rodents with promising results (Cameron et al., 2021). The study authors stated: “[S]everal safety concerns have hindered the clinical development of ibogaine, including its toxicity, hallucinogenic potential and tendency to induce cardiac arrhythmias… [T]hrough careful chemical design, it is possible to modify a psychedelic compound to produce a safer, non-hallucinogenic variant that has therapeutic potential” (Cameron et al., 2021).
The research team is optimistic about the potential uses of TBG, including not only addiction treatment but also potentially comorbid conditions such as depression and PTSD (Peters & Olson, 2021). More studies are needed before TBG could be used to treat patient populations.
FUTURE IBOGAINE STUDIES
As of January 2024, more rigorous ibogaine trials have been initiated and are ongoing, including a Phase 2 RCT on ibogaine for alcoholism in Brazil (dos Santos, 2021), a Phase 1/Phase 2a double-blind RCT on single-dose ibogaine for opioid withdrawal (DemeRX IB, Inc., 2021), an open-label, single-dose trial on opioid dependence in the Netherlands (Radboud UMC, 2021), and a trial on ibogaine for methadone withdrawal in Spain (ICEERS, 2020). These new studies indicate that the international research community is taking the promise of ibogaine for addiction treatment seriously.
While ibogaine comes with documented health risks including death, it also demonstrates repeated success in treating addiction and in eliminating or attenuating withdrawal symptoms. Given the serious nature of our current opioid addiction and related death epidemic, BrainFutures sees value in ibogaine’s potential addictiontreatment capabilities. Considering that other treatments for opioid dependency also carry health risks—including addiction and long-term-use side effects not associated with ibogaine treatment—it is BrainFutures’ hope that ibogaine will garner more attention as a potential ally in the fight to curb addictions and reduce related deaths.
To date, there are no completed Phase 1, 2, or 3 clinical trials on high-dose ibogaine (proper). Currently, the compound is only being researched in a limited capacity around the world, with no U.S. studies. In the years ahead, further controlled studies (including pharmacological engineering) of this powerful substance should be supported—enabling more rigorous research on ibogaine’s safety, efficacy, and effectiveness for addiction treatment.
Commercial Development and Availability of Ibogaine
This landscape gives an overview of the availability of ibogaine as a treatment, focussing on the medical aspect (versus recreational/growth). It covers the latest in commercial developments, legal perspectives, and patents. We end the section with a reflection on the opportunities and challenges facing ibogaine as a therapeutic.
As research continues to demonstrate ibogaine’s potential as an anti-addictive compound, several companies and organisations have begun ramping up efforts to further develop ibogaine or related substances into approved medications. However, ibogaine remains unavailable in most countries outside of underground settings due to its designation as an illegal Schedule I substance. This section explores current commercial development initiatives, legal status, and treatment availability involving ibogaine.
In recent years, a fledgling pharmaceutical industry has emerged seeking to unlock the therapeutic potential of psychedelic compounds like ibogaine. Companies are pursing both above-board clinical trials and drug development pathways as well as underground treatment models.
Pharmaceutical Companies Developing Ibogaine
DemeRx IB, an atai Life Sciences platform company, is actively working on developing ibogaine for treating opioid use disorder (OUD). The company’s commitment to medical-model drug development pathways sets it apart in the field of psychedelic therapeutics. In 2021, DemeRx initiated a Phase 1/2a clinical trial of ibogaine hydrochloride (DMX-1002) for OUD. This trial commenced enrollment and dosing of recreational drug users and healthy volunteers at the Manchester clinical unit of MAC Clinical Research in the UK, with a focus on assessing safety, tolerability, pharmacokinetics, and efficacy. The Phase 1/2a trial is crucial for providing safety data and informing future studies in patients with OUD
In August 2023, DemeRx reported data from the Phase 1 study of DMX-1002. The study achieved plasma concentrations and psychedelic experiences consistent with previous ibogaine studies. The treatment-related adverse events and side effects were generally mild to moderate in severity, with no serious adverse events reported. These results enable discussions with regulatory authorities regarding the progression of DMX-1002 into a proof-of-concept study in OUD. Notably, in November 2023, atai Life Sciences acquired all remaining shares of DemeRx IB, integrating DMX-1002 as a wholly-owned asset and streamlining the company’s clinical and administrative operations
The approval for the Phase I/IIa clinical trial allows DemeRx to study ibogaine in ‘healthy normal’ participants before moving to a second trial stage with opioid-dependent patients. The trial will pause to allow the MHRA to evaluate human safety data and nonclinical study results. Approximately 110 patients will be recruited for the trial, including 30 recreational drug users in Stage 1 and 80 opioid-dependent patients in Stage 2.
MindMed is a publicly-traded biotech company developing 18-methoxycoronaridine (18-MC), an ibogaine analogue, into an FDA-approved drug for opioid withdrawal and other addictions. The company believes that 18-MC could preserve ibogaine’s anti-addictive properties while eliminating cardiotoxic side effects. In 2021, MindMed completed the first Phase 1 clinical trial of 18-MC in Australia, which demonstrated its safety and tolerability in healthy volunteers across various doses.
The company initially planned to launch a Phase 2 trial for opioid withdrawal in 2022 but (indefinitely) delayed further trials because of additional preclinical studies that were requested by the FDA before they could proceed. This further request, coupled with tightening finances has resulted in a current stall of developments by the company into 18-MC.
Delix Therapeutics, a company specializing in neuroplasticity-promoting therapeutics, has made progress in its clinical research in 2023. They initiated a Phase I trial for DLX-001, a non-hallucinogenic psychoplastogen, and completed dosing for the first cohort. The trial did not report any significant adverse events or psychotomimetic effects, allowing for a dosage increase in the next cohort. The trial also confirmed the oral administration’s viability and pharmacokinetic properties of DLX-001. Additionally, Delix Therapeutics has expanded its research team and formed partnerships to support drug discovery efforts.
The trial’s findings also indicated a close alignment between predicted and observed pharmacokinetic parameters in human subjects, suggesting the potential for preclinical findings to be replicated in clinical settings. Additionally, the trial established the viability of oral administration of DLX-001, determining its bioavailability and oral pharmacokinetic characteristics. The novelty of DLX-001’s mechanism of action has been a point of interest (and much discussion), especially as it initiates a new paradigm in the treatment of depression without causing hallucinatory responses.
The Multidisciplinary Association for Psychedelic Studies (MAPS), a non-profit, has contributed to the early research on ibogaine, particularly in the context of treating opioid addiction. MAPS completed two observational studies on the long-term effects of ibogaine treatment at independent ibogaine treatment centers in Mexico and New Zealand. These studies were published in the American Journal of Drug and Alcohol Abuse, emphasizing ibogaine’s potential as a treatment for opioid dependence and advocating for further investigation through rigorously controlled studies.
In the Mexico study, 30 participants who had not found success with other treatments received ibogaine treatment. This study reported significant reductions in opioid withdrawal symptoms and drug use. Specifically, 12 out of 30 participants experienced a 75% reduction in drug use 30 days following treatment, and 33% reported no opioid use three months later. However, it’s important to note that this study had limitations, such as a small number of participants, no control group, and reliance on self-reporting.
The New Zealand study also demonstrated the efficacy of ibogaine in reducing opioid withdrawal symptoms and aiding in either complete cessation or sustained reduction of opioid use for up to 12 months following a single treatment. This study included 14 participants, with one participant disqualified and another who died during treatment, highlighting the need for careful monitoring and consideration of potential risks.
Psychedelic Clinics/Retreat Centres Offering Ibogaine Treatment
While pharmaceutical companies pursue formal drug development pathways, dozens of psychedelic clinics and retreat centers have already begun offering ibogaine treatments for addiction across the globe. These (underground) providers operate in countries where ibogaine is (sometimes) illegal but not criminalized for personal use.
Popular ibogaine retreat locations include Mexico, Canada, Costa Rica, and the Caribbean Islands. Many advertise themselves as medically supervised wellness centers focused on holistic healing. However, regulation and medical standards vary greatly between different providers. Some employ physicians, nurses, and credentialed therapists to monitor treatments, while others rely on coaches with no formal clinical training.
At licensed clinics, patients typically receive a comprehensive medical screening to check for ibogaine contraindications before undergoing an ibogaine “flood” dose session. This is followed by integrative aftercare services like psychotherapy and mindfulness training to complement ibogaine’s biological anti-addictive effects with emotional healing. The cost per treatment ranges from $2,500 to over $10,000 depending on the program’s length and luxury.
While retreat-style ibogaine treatments remain unregulated, they demonstrate continued interest in ibogaine’s therapeutic potential despite its illegal status. Some view such clinics as pioneering an underground model that could inform future legal medically-supervised protocols. However, others argue that lax medical oversight at some facilities poses unacceptable safety risks to vulnerable patients.
Beond, as one of the psychedelic clinics offering ibogaine treatment, stands out in the current landscape of providers. Nestled in a serene environment, Beond caters to individuals seeking relief from various addictions through the therapeutic use of ibogaine. Unlike some retreat centers, Beond places a strong emphasis on the safety and efficacy of its treatments. This commitment is reflected in their rigorous medical screening process, which is designed to identify any contraindications to ibogaine use, ensuring that the treatment is as safe as possible for each patient.
At Beond, the ibogaine experience is not just about the administration of the substance; it’s about a holistic healing journey. The clinic offers a comprehensive program that includes a high-dose ibogaine session, often referred to as a “flood” dose, which is believed to reset addiction patterns and alleviate withdrawal symptoms. Following the initial treatment, Beond provides an integrative aftercare program. This program typically includes psychotherapy, mindfulness training, and other wellness practices aimed at reinforcing ibogaine’s biological effects with emotional and mental healing. The goal is not just to treat addiction but to foster a transformative experience that can lead to long-term recovery and personal growth. While the cost of treatment at Beond can vary, it reflects the clinic’s commitment to providing a high-quality, comprehensive service that covers all aspects of the healing process.
Root Healing in Sintra, Portugal, offers a distinctive approach to psychedelic therapy, emphasizing the Bwiti tradition in treating conditions like substance use disorder, depression, anxiety, PTSD, and Parkinson’s disease. Their method contrasts with the more common Western medical model, integrating spiritual and cultural elements into treatment. The clinic ensures patient safety through medical screenings and provides ethically-sourced iboga. Root Healing’s holistic care extends beyond the retreat, including counseling and post-treatment integration calls, aiming for comprehensive healing and support.
Legal Status and Availability of Ibogaine
Despite promising evidence and surging commercial interest, ibogaine remains illegal worldwide, including the US and most of Europe where it is classified as a Schedule I controlled substance with high abuse potential and no medical utility. This designation creates barriers for research and pharmaceutical development.
Some drug policy experts argue that ibogaine’s scheduling is outdated given recent data showing its anti-addictive effects. Advocacy groups like the Multidisciplinary Association for Psychedelic Studies (MAPS) are lobbying regulators to ease restrictions on psychedelics like ibogaine for medical use. However, any changes allowing ibogaine treatments would likely depend on completed Phase 3 trials confirming safety and efficacy.
A few countries have adopted more permissive policies on ibogaine. Mexico, Canada, Brazil, and South Africa allow the medical use of ibogaine in research or medically-supervised treatment programs (for substance use disorders). This has enabled both pharmaceutical trials and underground addiction treatment clinics to operate legally in these regions, although enforcement approaches still vary.
The legal status of ibogaine in these countries aims to balance expanding access for therapeutic use with the need for oversight around safety. However, regulators still view non-medical and recreational use of ibogaine as illegal and dangerous without proper medical screening and supervision. Recent licensing frameworks for psychedelics in Canada and psilocybin reform in the US could prompt other jurisdictions to reconsider restrictions on ibogaine.
In a significant move, the Kentucky Opioid Abatement Advisory Commission has proposed using a portion of opioid settlement funds for medical research to further evaluate the effectiveness of ibogaine in treating opioid addiction. This initiative, backed by a legal settlement with pharmaceutical companies and potentially matched by private investors, represents a new approach to exploring ibogaine’s potential in addiction treatment. This development could position Kentucky as a leader in the United States for ibogaine research and its application in addressing the opioid crisis.
Patents Related to Ibogaine
This quick overview of patents related to ibogaine is just a preview of the wealth of information available from our friends at Psychedelic Alpha. Please also see their ibogaine patent tracker which list all known patents.
Despite ibogaine’s illegal Schedule I status in the US and most countries, interest persists in developing this compound into an approved medication for substance use disorders. As such, numerous groups have filed for or obtained patents related to ibogaine over the past few decades.
Ibogaine’s complex patent landscape dates back to the 1980s when Howard Lotsof, who originally discovered ibogaine’s anti-addictive properties, filed for multiple patents via his company NDA International. Lotsof patented ibogaine to treat heroin, cocaine, alcohol, nicotine, and other substance addictions.
Since then, Dr. Deborah Mash has become a leader in ibogaine research, first studying the compound in FDA-approved trials in 1993 before setting up offshore clinical programs. Mash holds dozens of patent applications related to ibogaine’s metabolite noribogaine for treating substance abuse and other indications. Her company DemeRx is actively pursuing noribogaine’s development.
Overall, ibogaine patents cover composition of matter, methods of extraction, production routes, formulations, analogs/derivatives, and therapeutic uses. For example, tabernanthalog is a recently developed non-hallucinogenic ibogaine analog with promising medical potential. Navigating existing ibogaine patents has proven challenging for some companies.
While safety concerns have slowed mainstream acceptance, patent activity reflects ongoing commercial interest in unlocking ibogaine’s clinical utility. Recent US state funding for ibogaine PTSD and addiction research could spur more patent filings if initial trials deliver positive results. As larger trials ensue, intellectual property protection will play a key role in justifying investments for developing this controversial compound.
What if You’re Seeking Ibogaine Treatment?
Disclaimer: The goal of Blossom is to provide objective information to inform readers, not to directly recommend or endorse any specific treatment options. This section on pursuing ibogaine treatment does not constitute medical or clinical advice. Blossom has not vetted any of the ibogaine providers mentioned in this report or evaluated their safety, credentials, or outcomes. Those considering ibogaine are strongly advised to conduct thorough independent research and consult a licensed healthcare professional before undergoing any medical intervention.
TRAVEL TO LEGAL CLINICS ABROAD
If you’re seeking ibogaine treatment, several avenues are available, each with its own set of considerations. Traveling to legal clinics abroad, like those in Mexico, Canada, Costa Rica, or South Africa, is often seen as the most reputable option. These clinics offer medically-supervised treatments, including necessary health screenings and physician monitoring, with aftercare typically involving psychotherapy integration. However, the cost can range from $3,000 to over $10,000, depending on the clinic’s amenities.
PARTICIPATE IN UNDERGROUND CEREMONIES
Alternatively, some individuals in the US opt for underground ceremonies, which operate in legal gray areas. These ceremonies, often framed within a religious context, may lack medical oversight, and safety varies greatly depending on the practitioner’s expertise. While more affordable, they involve risks due to minimal medical supervision and the integrative spiritual elements they incorporate.
OBTAIN IBOGAINE ILLEGALLY
Another risky option is obtaining ibogaine illegally, such as ordering online from unverified sources. This approach carries significant risks, including uncertain product purity and potency, and lacks medical support for potential complications. Furthermore, possession of ibogaine can lead to legal penalties in countries where it is prohibited. This method is not recommended unless one is extremely knowledgeable about quality sourcing, testing, and self-administration.
In any of these contexts, careful consideration around screening, dosing, monitoring for adverse effects, and integration support is crucial. The potential benefits of ibogaine as an addiction treatment must be weighed against the safety concerns. Seeking thorough professional medical advice is strongly recommended when considering ibogaine treatment options.
These are the institutes, from companies to universities, who are working on Ibogaine research.
Hive is building out a network of psychedelic clinics with a focus on Europe (Malta, Portugal, London) and on anti-addiction with the use of ketamine- and ibogaine-assisted therapy.
PsyRx is a drug development company developing GMP-standard naturally sourced psychedelics including psilocybin and ibogaine.
MindMed is one of the largest companies in the psychedelics space and is developing various psychedelics for mental health disorders.
atai Life Sciences is one of the biggest companies in the psychedelics field. The company aims to be a platform and has nine subsidiary companies working on everything from psilocybin for depression to DMT administration.
Root Healing retreats are led by highly trained and empowered Iboga Providers. Each retreat is steeped in the Missoko Bwiti tradition, ensuring a holistic and potent experience for their guests.
Ceiba is a federally registered not-for-profit corporation in Canada that provides education and regranting around ibogaine treatments.
These are some of the best-known people, from researchers to entrepreneurs, working with Ibogaine.
José Carlos Bouso is a Clinical Psychologist with a PhD in Pharmacology and is the current Scientific Director at ICEERS.
Rafael dos Santos is a postdoctoral fellow at the Graduate Program in Mental Health at the Faculty of Medicine of Ribeirão Preto (FMRP-USP), where he also works as an accredited advisor.
Linked Research Papers & Trials
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