IBOGAINE | +40 articles

[mr peabody]

Thillen Naidoo and his wife were desperate and
willing to try anything to ease his addiction

Can a psychedelic from Africa cure cocaine addiction?*

by Stephanie Hegarty | BBC World Service

Since the 1960s a disparate group of scientists and former drug addicts have been advocating a radical treatment for addiction - a psychedelic called ibogaine, derived from an African shrub, that seems to obliterate withdrawal symptoms from heroin, cocaine and alcohol. So why isn't it widely used?

For nearly 15 years, Thillen Naidoo's life was ruled by crack cocaine. Growing up in Chatsworth, a township on the outskirts of Durban in South Africa, he was surrounded by drugs.

After a troubled childhood and the death of his father, he turned to cocaine.

Though he held down a job as a carpenter and could go for days or even weeks without a hit, his wild drug binges often ended in arguments with his wife Saloshna and sometimes even physical abuse.

By the time he met Dr Anwar Jeewa at the Minds Alive Rehab Centre in Chatsworth, Naidoo had tried to quit several times and failed. "Those were dark, dark days," he says.

Jeewa offered a radical solution, a psychedelic drug used in tribal ceremonies in central Africa that would obliterate his cravings.

But Naidoo was anxious. "I didn't know what this ibogaine thing was," he says. "I never expected it to work."

After several medical tests he was given the pill.

A few hours later he lay in bed, watching flying fish swarm above his head. He felt the room move around him and a constant buzz rang in his ears. Scenes from his childhood flashed up briefly before his eyes and each time someone approached to check he was OK he felt a rush of fear.

The psychedelic effect wore off overnight but for the next few days Thillen was in a haze. When he returned home a week later, he realised he no longer craved cocaine. Six months later, he is still clean.

He attends a therapy group two days a week, where he learns the skills necessary to maintain a lifestyle without drugs.

"My mind has shifted now from what I used to be," he says. "I can look back at my childhood and deal with those issues without sobbing and feeling sorry for myself."

Dr Anwar Jeewa

Jeewa estimates he has treated around 1,000 people with ibogaine but it remains largely unacknowledged by the medical mainstream.

The drug, derived from the root of a central African plant called iboga, had been used for centuries by the Bwiti people of Gabon and Cameroon, as part of a tribal initiation ceremony.

But it wasn't until 1962, when a young heroin addict called Howard Lotsof stumbled upon ibogaine, that its value as an addiction treatment was uncovered.

Lotsof took it to get high but when the psychedelic effects wore off, he realised he no longer had the compulsion to take heroin. He became convinced that he had found the solution to addiction and dedicated much of his life to promoting ibogaine as a treatment.

As far as scientists understand, ibogaine affects the brain in two distinct ways. The first is metabolic. It creates a protein that blocks receptors in the brain that trigger cravings, stopping the symptoms of withdrawal.

"Ibogaine tends to remove the withdrawals immediately and brings people back to their pre-addiction stage," says Jeewa. With normal detox this process can take months.

Its second effect is much less understood. It seems to inspire a dream-like state that is intensely introspective, allowing addicts to address issues in their life that they use alcohol or drugs to suppress.

Howard Lotsof's early campaign had little success and ibogaine was banned in the US, along with LSD and psilocybin mushrooms, in 1967.

In most other countries it remains unregulated and unlicensed. Lotsof set up a private clinic in the Netherlands in the 1980s and since then similar clinics have emerged in Canada, Mexico and South Africa.

These clinics operate in a legal grey area. But a small group of scientists is still working to bring ibogaine into the mainstream.

In the early 1990s, Deborah Mash, a neuroscientist and addiction specialist at the University of Miami, came upon the work of Dr Stanley Glick, a scientist who had researched the effect of ibogaine on rats.

Glick hooked rats on morphine, an opiate painkiller, by allowing them to self-administer it through a tube. He then gave them ibogaine and found they voluntarily stopped taking morphine.

Howard Lotsof

Around the same time, Mash was contacted by Howard Lotsof. They began working together and in 1995 secured full approval from the US Food and Drug Administration (FDA) to investigate its potential in humans.

But these tests cost millions of dollars, and Mash applied for five separate public grants but each one was declined.

Usually, this money would come from big pharmaceutical companies but drugs like ibogaine offer little potential for profit.

It only has to be taken once, unlike conventional treatments for heroin addiction such as methadone which is a substitute and addictive itself.

"One very cynical reason they are not being developed is that there is no patent on these drugs anymore so there is no pharmaceutical company involvement," says Ben Sessa.

Pharmaceutical companies make money by patenting new chemicals but ibogaine is a naturally occurring substance and is difficult to secure a patent on.

It also comes with some risks. Ibogaine slows the heart rate and when administered to rats in very high doses, it has been proved to damage the cerebellum, a part of the brain associated with motor function.

There are 10 deaths known to be associated with the drug and its unregulated use has prompted some horror stories. Online forums are littered with stories of unscrupulous practitioners administering ibogaine in hotel rooms or in the patient's home with no medical support.

One alcoholic says he paid $10,000 and it didn't work at all. His respiration was not monitored and he didn't have any physical or psychological check-ups beforehand.

"The 'visions/trip' were so excruciating I never wanted to be altered again. I felt I was near death during the trip because I was having trouble breathing."

Stanley Glick

Ibogaine also has something of an image problem, says Glick.

"It has too much political baggage associated with it. By the time everybody became aware of it there was already scepticism because this was not something that came from a drug development programme."

After failing to get funding, Mash opened a private clinical research centre on the island of St Kitts in the Caribbean in 1996. There she collected data on 300 addicts detoxed through ibogaine.

She says all patients showed an effect on their addiction, 70% went into remission for several months and many for years. The clinic's first two patients are still drug-free 16 years later.

"Cocaine addiction is a terrible addiction," she says. "Getting people off crack? Good luck. We did it, we were able to break out intractable addicts."

Determined to bring the treatment to more people, Mash is now working with the private sector to create a version of the drug that will be more attractive to pharmaceutical companies.

She is working to isolate noribogaine, a substance created by ibogaine in the liver, which she believes is responsible for inhibiting cravings, taking away the psychedelic effect. But she continues to push for research into the whole drug.

Glick doesn't believe noribogaine will ever be approved in the US. "If for no other reason than that it is too closely related to ibogaine," he says.

He is developing an alternative but he regrets that significant testing into ibogaine has never been done.

According to a psychiatrist and addiction specialist, Dr Ben Sessa, the timing for this research could finally be right.

The past two years have seen the first scientific study published into the use of MDMA on trauma victims and psilocybin for psychotherapy, and a similar study into LSD is expected this year.

David Nutt

"Radical options are needed," says David Nutt, head of the UK's Independent Scientific Committee on Drugs, but he maintains some scepticism about so-called wonder cures.

"The history of medicine is littered with people doing interesting, challenging things, but when you do proper control tests they reveal a massive placebo effect," he says.

What is needed, he says, is a single blind study in which one group of addicts takes a standardised dose of the drug and another group takes a placebo, both followed by a full 12-step detox treatment plan. He estimates that would cost about $2.37 million (£1.5 million).

Clinicians like Jeewa would like to see the drug licensed but says people need to understand its limits.

"Once you have a patient that is drug free and whose brain is back to its full potential then you can help them change their lifestyle," says Jeewa.

"Ibogaine helps to interrupt addiction but it's not a cure or a magic bullet," he says. "It has to be taken in the right setting and treatment has to be followed up with psychosocial care."

Ibogaine: The risks

- Ibogaine has been associated with 19 deaths and given it is largely unregulated, the actual toll could be much higher

- According to a report published in the Journal of Forensic Science, 14 of these deaths were due to pre-existing health problems

- In New Zealand, the only country to have regulated the drug, the medical advisory board Medsafe reported that "the number of deaths due to methadone, the most controlled substance, were a little higher that those associated with ibogaine"

- Ibogaine is illegal in the US, France, Sweden, Denmark, Belgium, Poland, Croatia and Switzerland

The problem with addiction research

- Measuring success scientifically with addiction is problematic - addicts can be clean for months or even years before relapsing

- Most existing addiction treatments were created as a by-product of other research. Methadone was initially developed as a pain killer for German soldiers during WWII

- In the last 20 years, only one new drug has been developed for opiate addiction

- Buprenorphine, sold as Suboxone, is a substitute drug much like methadone but it can be subscribed by a doctor and taken at home rather than in a clinic

- "The treatment of addiction is woefully poor in the western world," says Ben Sessa. "After about 150 years of study into alcohol addiction, abstinence rates after a year are no better than about 25%."

- For opiates, abstinence rates after a year are about 10%

*From the article here :

Can a hallucinogen from Africa cure addiction?

A hallucinogen called ibogaine seems to obliterate withdrawal symptoms from heroin, cocaine and alcohol. So why isn't it widely used?

www.bbc.com

 

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The Psychedelic Shrub that Cures Addiction in One Dose

by Kastalia Medrano | INVERSE

In West Africa, the roots of a native shrub contain a psychoactive substance called ibogaine. In small doses, ibogaine produces a mild euphoric effect somewhat comparable to other stimulant plants, like khat in the Horn of Africa or piri piri in the Amazon. But in large doses, its psychedelic effects are extraordinary.

Ibogaine's closest analog is ayahuasca, a drug used for shamanic purposes in South America and increasingly appropriated by foreigners chasing its promise of fantastical hallucinations and inner clarity. Ibogaine takes all that and doubles down. With the exception of the colorful visual patterns associated with ayahuasca, pretty much everything about ibogaine is more extreme, more profound. An ayahuasca trip lasts around four hours; a trip on ibogaine can last more than a day. Ayahuasca facilitates lucid dreaming; ibogaine facilitates way more intense lucid dreaming. The effects are so literally flooring that people typically remain horizontal for the duration, trying not to move, lest they vomit. They see God. They talk to the dead. Paralyzing forks in the road of their personal lives melt smoothly into a single path forward.

"With ibogaine, it's much more intense," Bruno Gomes, a Brazil-based psychologist who's been working with ibogaine for drug dependency since 2010, tells Inverse by phone. "People have a lot of memories about deceased parents, about moments in their lives, meaningful moments or sometimes not meaningful."

With ayahuasca, it's common to feel calmer, less depressed, and more present and engaged with life for a week or so after the initial trip. The afterglow from ibogaine, however, can last for months. Substance addiction simply vanishes, according to some, with no symptoms of withdrawal.

Why, in an age when nearly every party drug is being pushed into federal trials for addiction and mental illness, when drug tourists who fetishize the mysticism associated with indigenous psychedelics are in the market for ever-bigger thrills, and when the opioid epidemic is killing tens of thousands each year, have so few Americans heard of ibogaine?

Ibogaine is an active substance derived from the bark of the iboga tree. It's commonly used for religious purposes by people indigenous to Cameroon and Gabon, who ingest it by stripping the root bark and eating it. Unlike the traditionally ritualistic use of ayahuasca, it's traditional for a person to take a high dose of ibogaine just once in their life.

In 1962, a teenage heroin addict from The Bronx named Howard Lotsof happened upon an extract of the substance in powder form. He took it searching for a high, found one, and also found that when it wore off, it took his desire for heroin with it. Six friends who were also junkies tried it; five went clean immediately, with none of the painful withdrawal for which heroin is notorious.

Lotsof became a lifelong activist for the research of ibogaine for drug dependency.

Ibogaine had been studied at low doses for its stimulant effect in western cultures before, including by the CIA in the 1950s. But Lotsoff was the first to realize its high-dose potential for addiction recovery, and in the wake of his discovery a subculture of heroin and cocaine users seeking it to help with cravings and withdrawal spread across the United States, as well as other countries like the Netherlands.

It's most common for Americans seeking ibogaine these days to try Mexico or the Bahamas. A few will make the trip to Gabon, but it's not exactly the most time- or cost-effective way to indulge a curiosity, even a potentially life-saving one. (Gomes also says that, from what he's heard, people in Gabon don't tend to be thrilled with the arrival of strangers at their door, bringing some combination of heroin addiction and/or misguided expectation of mysticism.) The most important thing is to just make sure the practitioner overseeing its administration is a legit one. Taken properly, ibogaine is generally very safe. Taken improperly, without clearing any number of pre-existing medical issues, you can die.

Other countries like New Zealand and Canada have recently begun to legislate therapeutic uses, and it's a de facto national treasure in Gabon, where members of the Bwiti religion use it in coming-of-age ceremonies. But the sparse body of controlled research, coupled with the very real risk of death, has kept it from making any real headway in the States. The Multidisciplinary Associate for Psychedelic Studies (MAPS) has had some success introducing clinical trials in other countries, but FDA regulation still seems a ways off for any U.S.-based research. It remains a Schedule I drug, even as the opioid crisis continues to grow.

In Brazil, which has no such crisis, Gomes and his colleagues work with patients addicted to (predominately) crack cocaine. Though they'll meet with their patients a number of times, they'll administer ibogaine to each person only once. Speaking at the MAPS Psychedelic Science Conference in California late last month, Gomes said most people he sees are addicts for whom traditional therapy and the various Anonymous programs have failed. They tend to be impatient with the precursor meetings and adherence to controlled settings, wanting mostly to get the drug, take it, and leave cured.

Ibogaine's place in the global consciousness is such that most people in most cultures still haven't heard of it, but that the ones who have tend to view it as sort of no-strings-attached miracle drug. Part of Gomes' work is to install a more comprehensive and less reductive understanding of ibogaine's usage; it's a tool, possibly a singular one, but it's not magic. The effects might not wear off for months, but they do wear off, and so addicts seeking treatment will still need to implement some lifestyle changes going forward.

The reason ibogaine remains comparatively anonymous in the West despite its potential as a psychedelic powerhouse probably have something to do with the geographical distance to its traditional usage compared to, for instance, peyote in the Southwest, and the fact that it's also just a hard substance to physically procure. Ibogaine may be lesser-known outside Gabon than its peers, but that doesn't mean that increased demand hasn't hiked the prices dramatically over the last decade or so. Iboga trees also need eight years to mature before the bark is ripe, so to speak, for harvesting, and in order to harvest the plants you do need to kill them. Labs have begun to produce a sort of synthetic ibogaine from the plant Voacanga africana in an effort to make the drug more environmentally and economically sustainable, but it's still very much a nascent field.

Gomes took ibogaine four years ago. He'd already been treating patients with it for another four years before that and admitted that seeing them before and after, coupled with their descriptions of extraordinary experiences, led him to some preconceived expectations that didn't end up bearing out. But what he did experience changed him profoundly; his description of it is also pretty close to what hordes of drug tourists and New Agers will be chasing when they decide they want, the next time, something beyond peyote or ayahuasca.

"It didn't even seem to be my thinking, you know?" Gomes recalls. "It was like a very intense flood of thoughts, a river of thoughts from my head, and with this river, I got three very important things that I needed to deal with, in three situations in my life, concerning my job, concerning my studies, and concerning my personal life with my girlfriend - I got a way to go forward. In the last four years I've taken this trail, and it has helped all of those things make sense."

https://www.inverse.com/article/31461-ibogaine-cure-addiction​

 

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​

Ibogaine and Cardiac Arrhythmia: The Heart of the Matter*

Even at therapeutic doses, ibogaine may cause potentially life-threatening cardiac arrhythmia. Science is beginning to unravel the pharmacological factors that may underlie ibogaine-induced cardiotoxicity.​

by Christopher M. Teske, BS | Psychedelic science Review | 1 Dec 2021

Ibogaine has shown promising anti-addictive effects in both animal models and human trials, aiding those in search of a novel treatment for addiction and the compulsive behaviors that accompany it. One study found that 91.7% of opioid or cocaine-dependent participants felt ibogaine was useful in addressing substance abuse issues.1 Despite ibogaine’s demonstrated efficaciousness and mainstream acclaim, literature regarding its potential to induce potentially fatal heart arrhythmias and case reports on ibogaine-associated fatalities are accumulating as its pharmacology is further studied.​

The Popularization of Ibogaine Treatment​

The use of ibogaine in the West, and particularly as a remedy for substance addiction, was spearheaded by Howard Lotsof in the early 1960s. Lotsof was then a teenager struggling with a heroin addiction, discovering serendipitously after his self-experimentation with ibogaine that he had no desire to use heroin. In addition, he experienced no physical withdrawal symptoms upon cessation. Lotsof would go on to publish many research papers regarding ibogaine’s utility as a remedy for addiction and was awarded many patents over the years for the treatment of numerous specific substance dependencies using ibogaine. He remained an active voice on the issue for decades, serving as a patient advocate for those suffering from addiction and penning the Ibogaine Patients’ Bill of Rights, defining the rights given to ibogaine patients and their own responsibilities upon admission and intake into an ibogaine therapy program. The Bill of Rights has aided in keeping patients safe and ensuring their satisfaction during treatment.

While ibogaine has been studied with relative fervor for several decades, the opioid crisis and its implications have brought it to center stage. As addiction and its consequences continue to greatly impact peoples’ lives, ibogaine has been viewed by many as a lost hope and a reputable antidote. According to data obtained by the Center for Disease Control (CDC), a record high of 93,331 overdose deaths occurred in 2020 amid the COVID-19 surge, 20,000 deaths greater than in the previous year. The CDC noted that this was the largest single-year increase recorded since 1993. A great deal of literature has noted ibogaine’s growing visibility within the media and its popularity as a sought-after remedy for addiction, particularly in the context of opioids and opiates. While a general interest arose concurrently with an increase in opioid consumption in the 1990s, public interest in ibogaine has reached its zenith alongside other, more traditional psychedelics.​

Ibogaine’s Cardiotoxic Effects​

As ibogaine’s pharmacology has been further studied, research has accumulated that it has the propensity to cause cardiac arrhythmia by blocking hERG potassium channels in the heart. These channels are essential for normal electrical activity within the heart and for proper coordination of the heartbeat. Ibogaine has been shown to reduce outward potassium flow through the hERG channels, which is important as myocardial cells in the heart reach a phase in the cardiac cycle called repolarization. As in neurons, depolarization involves a steep increase in membrane potential, sending an electrical potential throughout the heart that facilitates its contraction. Afterward, a repolarization phase occurs, returning the membrane to its negative resting potential. The outward flow of positively charged potassium ions through hERG channels aids in the repolarization process.

Ibogaine’s potential to inhibit the potassium current through the channel is concentration-dependent and may result in abnormal electrical activity, causing cardiac arrhythmia and/or sudden cardiac death. Researchers note that blood plasma levels occur in low micromolar ranges after treatment with 500-1,000 milligrams of ibogaine, doses typically used in treating addiction. This finding was associated with another case report of abnormal electrical activity in the heart upon ibogaine intake, evidenced by electrocardiogram (ECG), called long QT. Long QT syndrome, in which the repolarization of the heart following a full heartbeat is prolonged, can result in a rapid, irregular heartbeat, cardiac arrest, and sudden death. An example of long QT on an ECG is shown below (Figure 1, c).

Recent research has illustrated that the long-lived, active metabolite of ibogaine, noribogaine, also inhibits hERG channels. This research implies that noribogaine may be the major proarrhythmic compound, and not ibogaine itself. Indeed a number of cardiac-related fatalities in vulnerable individuals have occurred following the ingestion of ibogaine. A considerable portion of these deaths most commonly took place several days post-ingestion, or upon the use of very small doses. The literature notes that this warrants the development of ibogaine derivatives less liable to block hERG channels while retaining ibogaine’s anti-addictive properties.

Figure 1: Both ibogaine and noribogaine impair the heart’s electrical activity. a) Action potential (AP) recordings from human cardiomyocytes under control conditions and upon exposure to a 3 µM solution of ibogaine (ibo, top) or noribogaine (noribo, bottom). b. Analysis of the dampening of AP repolarization by ibogaine and noribogaine. APD, or AP duration, in milliseconds, was greater in cardiomyocytes exposed to a 3 µM ibogaine or noribogaine solution as compared to a control. This further demonstrates the prolonged AP caused by ibogaine or noribogaine exposure. c. The proposed mechanism for cardiac arrhythmia following ibogaine intake. The figure depicts the sequence of events at the level of the ion channel, cell, and organ. Both ibogaine and its metabolite noribogaine (yielded by CYP2D6 enzymes in the liver) block hERG potassium channels. This slows the repolarization phase of the ventricular AP, prolonging the QT interval and causing cardiac arrhythmias to precipitate. From Rubi, et al., 2017.​

Derivatives of Derivatives​

Numerous ibogaine derivatives have been synthesized, with 18-methoxycoronaridine (18-MC) demonstrating a promising efficacy in treating a wide range of compulsive behaviors. In rodent models, treatment with 18-MC reduced self-administration of morphine, cocaine, methamphetamine, nicotine, and even sucrose.18-MC has also been shown to reduce food intake in obese rats, likely due to its effects on dopamine release in the brain’s nucleus accumbens, the reward center thought to be mutually involved in addiction and compulsive eating. 18-MC also inhibits hERG channels, but to a lesser extent than ibogaine or noribogaine. This likely makes it a safer lead compound to develop ibogaine derivatives from, with less concern of cardiotoxicity.

Many commercially successful pharmaceuticals have been discontinued due to their propensity for disrupting hERG channels and causing arrhythmia or sudden death, lending these findings particular significance. The hERG channel is an “anti-target”, a site where off-target binding of drugs or their metabolites may have serious consequences. A pharmacophore of 18-MC derivatives have also been synthesized, many exhibiting greater efficacy than 18-MC itself, namely the methoxyethyl congener ME-18-MC. ME-18-MC has demonstrated anti-addictive properties, but with greater potencies by weight and at a quantity half of 18-MC’s minimum effective dose.​

Conclusion​

Long since Howard Lotsof’s pioneering self-experimentation, we’ve learned a great deal about ibogaine and its anti-addictive properties. With this knowledge has come the understanding that ibogaine has pharmacological problems of its own, namely its propensity to induce cardiac arrhythmia and potentially cause sudden death by blocking hERG potassium channels, important in regulating the heart’s electrical activity and rhythm. The development of ibogaine derivatives, including 18-MC and its own derivatives such as ME-18-MC, may provide an answer to the possible safety issues ibogaine may present. These derivatives allow for the anti-addictive properties of ibogaine to be maintained, while the affinity for hERG channels and the potential for complications related to cardiotoxicity are reduced. This serves to ensure safer access to what many consider an important compound for the treatment of addiction and compulsive behaviors.

*From the article including footnotes here :

Ibogaine and Cardiac Arrhythmia: The Heart of the Matter

Even at therapeutic doses, ibogaine may cause potentially life-threatening cardiac arrhythmia. Science is beginning to unravel the pharmacological factors that may underlie ibogaine-induced…

psychedelicreview.com

 

[mr peabody]

Ibogaine's effect on cocaine craving - A double-blind, placebo-controlled pilot study

Pedro Luis Prior, Sergio Luiz Prior

Cocaine dependence is a prevalent mental disorder, with no specific treatment at the moment. Ibogaine is an extract from an African root, with evidence pointing to its success in treating several addictive disorders. There are very few human studies evaluating ibogaine's efficacy in cocaine dependence.

A double blind, placebo controlled study was conducted with 20 patients, split in 2 groups: the ibogaine group received a single dose of 1800 mg of encapsulate ibogaine extract, and the placebo group received a single capsule of sugar powder. All patients were followed for a 24 week period, with biweekly visits to a psychiatric professional, in which a urine sample was collected in order to detect cocaine use.

Data analyzes was performed using ANOVA for repeated measures for comparison of data between groups and between members of the same group. Urine samples were compared (positive results) using measure ANOVA statistical tests with the Least Squares Difference for post hoc two group comparisons. Statistical significance was 5% for all the referred tests.

Statistical significance was observed in the ibogaine group after treatment, in comparison with baseline (time zero) and with the placebo group at any time of analysis. No such improvement was observed in the placebo group.

The current study found that Ibogaine is an effective treatment for cocaine dependence, and more studies with larger samples are necessary in order to establish its efficacy and validity.

Background

Cocaine dependence is one of the most prevalent of all addictive disorders, and is at rise in numbers in most populations around the globe. There are currently no consensus on which treatment approach is more indicated for such patients, whether it be counseling, behavioral interventions or pharmacotherapy.

Cocaine chronic use is directly related to airway lesion formation, pulmonary emphysema and precancerous and cancerous lesions of respiratory tract. It may also have immediate response in the cardiovascular system, with greater chance of myocardial infarction, electrophysiological abnormalities and cardiac arrest.

Several substances have been postulated as possible treatment options for cocaine dependence, by controlling craving and abstinence symptoms in the acute stage of drug withdrawal, or by preventing drug relapse in the chronic stage of drug dependence. Although some of the studied medications have shown positive effect in one or both stages of cocaine addiction, they are still considered only moderately successful in treating the condition.

An effective pharmacological agent, preferably accessible and inexpensive, able to reduce symptoms in the acute stage of cocaine withdrawal and prevent drug relapse in the chronic stage of dependence, would help in rehabilitating patients to a normal life.

Ibogaine is a natural alkaloid, extracted from Tabernanthe iboga, a plant used in several initiatory rituals in West Central Africa. Evidence of its efficacy in drug dependence was, unfortunately, based almost entirely on anecdotal and personal experiences of physicians in less than ideal clinical environments. More evidence has amassed in open label trials and case reports in the last 20 years, however there have been very few double blind, placebo controlled trials conducted with scientific protocol in drug dependent patients, and most of these studies concentrated on heroin and opioid dependence. Our goal was to conduct such a study, focused on cocaine dependence in a population in Santos, Sao Paulo, Brazil.

According to our preliminary results, ibogaine is able to reduce symptoms in an acute stage of cocaine dependence, and reduced drug relapse in the chronic stage of the condition. There are bases for conducting studies with larger samples and for longer periods of time.

https://www.academia.edu/37956100/I...ot_Study?auto=download&campaign=weekly_digest​

 

[mr peabody]

Thillen Naidoo and his wife were desperate and
willing to try anything to ease his addiction

Can a psychedelic from Africa cure cocaine addiction?*

by Stephanie Hegarty | BBC World Service

Since the 1960s a disparate group of scientists and former drug addicts have been advocating a radical treatment for addiction - a psychedelic called ibogaine, derived from an African shrub, that seems to obliterate withdrawal symptoms from heroin, cocaine and alcohol. So why isn't it widely used?

For nearly 15 years, Thillen Naidoo's life was ruled by crack cocaine. Growing up in Chatsworth, a township on the outskirts of Durban in South Africa, he was surrounded by drugs.

After a troubled childhood and the death of his father, he turned to cocaine.

Though he held down a job as a carpenter and could go for days or even weeks without a hit, his wild drug binges often ended in arguments with his wife Saloshna and sometimes even physical abuse.

By the time he met Dr Anwar Jeewa at the Minds Alive Rehab Centre in Chatsworth, Naidoo had tried to quit several times and failed. "Those were dark, dark days," he says.

Jeewa offered a radical solution, a psychedelic drug used in tribal ceremonies in central Africa that would obliterate his cravings.

But Naidoo was anxious. "I didn't know what this ibogaine thing was," he says. "I never expected it to work."

After several medical tests he was given the pill.

A few hours later he lay in bed, watching flying fish swarm above his head. He felt the room move around him and a constant buzz rang in his ears. Scenes from his childhood flashed up briefly before his eyes and each time someone approached to check he was OK he felt a rush of fear.

The psychedelic effect wore off overnight but for the next few days Thillen was in a haze. When he returned home a week later, he realised he no longer craved cocaine. Six months later, he is still clean.

He attends a therapy group two days a week, where he learns the skills necessary to maintain a lifestyle without drugs.

"My mind has shifted now from what I used to be," he says. "I can look back at my childhood and deal with those issues without sobbing and feeling sorry for myself."

Dr Anwar Jeewa

Jeewa estimates he has treated around 1,000 people with ibogaine but it remains largely unacknowledged by the medical mainstream.

The drug, derived from the root of a central African plant called iboga, had been used for centuries by the Bwiti people of Gabon and Cameroon, as part of a tribal initiation ceremony.

But it wasn't until 1962, when a young heroin addict called Howard Lotsof stumbled upon ibogaine, that its value as an addiction treatment was uncovered.

Lotsof took it to get high but when the psychedelic effects wore off, he realised he no longer had the compulsion to take heroin. He became convinced that he had found the solution to addiction and dedicated much of his life to promoting ibogaine as a treatment.

As far as scientists understand, ibogaine affects the brain in two distinct ways. The first is metabolic. It creates a protein that blocks receptors in the brain that trigger cravings, stopping the symptoms of withdrawal.

"Ibogaine tends to remove the withdrawals immediately and brings people back to their pre-addiction stage," says Jeewa. With normal detox this process can take months.

Its second effect is much less understood. It seems to inspire a dream-like state that is intensely introspective, allowing addicts to address issues in their life that they use alcohol or drugs to suppress.

Howard Lotsof's early campaign had little success and ibogaine was banned in the US, along with LSD and psilocybin mushrooms, in 1967.

In most other countries it remains unregulated and unlicensed. Lotsof set up a private clinic in the Netherlands in the 1980s and since then similar clinics have emerged in Canada, Mexico and South Africa.

These clinics operate in a legal grey area. But a small group of scientists is still working to bring ibogaine into the mainstream.

In the early 1990s, Deborah Mash, a neuroscientist and addiction specialist at the University of Miami, came upon the work of Dr Stanley Glick, a scientist who had researched the effect of ibogaine on rats.

Glick hooked rats on morphine, an opiate painkiller, by allowing them to self-administer it through a tube. He then gave them ibogaine and found they voluntarily stopped taking morphine.

Howard Lotsof

Around the same time, Mash was contacted by Howard Lotsof. They began working together and in 1995 secured full approval from the US Food and Drug Administration (FDA) to investigate its potential in humans.

But these tests cost millions of dollars, and Mash applied for five separate public grants but each one was declined.

Usually, this money would come from big pharmaceutical companies but drugs like ibogaine offer little potential for profit.

It only has to be taken once, unlike conventional treatments for heroin addiction such as methadone which is a substitute and addictive itself.

"One very cynical reason they are not being developed is that there is no patent on these drugs anymore so there is no pharmaceutical company involvement," says Ben Sessa.

Pharmaceutical companies make money by patenting new chemicals but ibogaine is a naturally occurring substance and is difficult to secure a patent on.

It also comes with some risks. Ibogaine slows the heart rate and when administered to rats in very high doses, it has been proved to damage the cerebellum, a part of the brain associated with motor function.

There are 10 deaths known to be associated with the drug and its unregulated use has prompted some horror stories. Online forums are littered with stories of unscrupulous practitioners administering ibogaine in hotel rooms or in the patient's home with no medical support.

One alcoholic says he paid $10,000 and it didn't work at all. His respiration was not monitored and he didn't have any physical or psychological check-ups beforehand.

"The 'visions/trip' were so excruciating I never wanted to be altered again. I felt I was near death during the trip because I was having trouble breathing."

Stanley Glick

Ibogaine also has something of an image problem, says Glick.

"It has too much political baggage associated with it. By the time everybody became aware of it there was already scepticism because this was not something that came from a drug development programme."

After failing to get funding, Mash opened a private clinical research centre on the island of St Kitts in the Caribbean in 1996. There she collected data on 300 addicts detoxed through ibogaine.

She says all patients showed an effect on their addiction, 70% went into remission for several months and many for years. The clinic's first two patients are still drug-free 16 years later.

"Cocaine addiction is a terrible addiction," she says. "Getting people off crack? Good luck. We did it, we were able to break out intractable addicts."

Determined to bring the treatment to more people, Mash is now working with the private sector to create a version of the drug that will be more attractive to pharmaceutical companies.

She is working to isolate noribogaine, a substance created by ibogaine in the liver, which she believes is responsible for inhibiting cravings, taking away the psychedelic effect. But she continues to push for research into the whole drug.

Glick doesn't believe noribogaine will ever be approved in the US. "If for no other reason than that it is too closely related to ibogaine," he says.

He is developing an alternative but he regrets that significant testing into ibogaine has never been done.

According to a psychiatrist and addiction specialist, Dr Ben Sessa, the timing for this research could finally be right.

The past two years have seen the first scientific study published into the use of MDMA on trauma victims and psilocybin for psychotherapy, and a similar study into LSD is expected this year.

David Nutt

"Radical options are needed," says David Nutt, head of the UK's Independent Scientific Committee on Drugs, but he maintains some scepticism about so-called wonder cures.

"The history of medicine is littered with people doing interesting, challenging things, but when you do proper control tests they reveal a massive placebo effect," he says.

What is needed, he says, is a single blind study in which one group of addicts takes a standardised dose of the drug and another group takes a placebo, both followed by a full 12-step detox treatment plan. He estimates that would cost about $2.37 million (£1.5 million).

Clinicians like Jeewa would like to see the drug licensed but says people need to understand its limits.

"Once you have a patient that is drug free and whose brain is back to its full potential then you can help them change their lifestyle," says Jeewa.

"Ibogaine helps to interrupt addiction but it's not a cure or a magic bullet," he says. "It has to be taken in the right setting and treatment has to be followed up with psychosocial care."

Ibogaine: The risks

- Ibogaine has been associated with 19 deaths and given it is largely unregulated, the actual toll could be much higher

- According to a report published in the Journal of Forensic Science, 14 of these deaths were due to pre-existing health problems

- In New Zealand, the only country to have regulated the drug, the medical advisory board Medsafe reported that "the number of deaths due to methadone, the most controlled substance, were a little higher that those associated with ibogaine"

- Ibogaine is illegal in the US, France, Sweden, Denmark, Belgium, Poland, Croatia and Switzerland

The problem with addiction research

- Measuring success scientifically with addiction is problematic - addicts can be clean for months or even years before relapsing

- Most existing addiction treatments were created as a by-product of other research. Methadone was initially developed as a pain killer for German soldiers during WWII

- In the last 20 years, only one new drug has been developed for opiate addiction

- Buprenorphine, sold as Suboxone, is a substitute drug much like methadone but it can be subscribed by a doctor and taken at home rather than in a clinic

- "The treatment of addiction is woefully poor in the western world," says Ben Sessa. "After about 150 years of study into alcohol addiction, abstinence rates after a year are no better than about 25%."

- For opiates, abstinence rates after a year are about 10%

*From the article here :

Can a hallucinogen from Africa cure addiction?

A hallucinogen called ibogaine seems to obliterate withdrawal symptoms from heroin, cocaine and alcohol. So why isn't it widely used?

www.bbc.com

 

[mr peabody]

The future of medical ibogaine*

Psychedelics Today | Apr 22 2019

Ibogaine is a psychedelic chemical found in the West African shrub Iboga. Bizarre in chemical structure and psychoactive properties, the drug remains mysterious to scientists and psychonauts alike. At high doses, ibogaine causes intense, unforgivingly introspective and dream-like hallucinatory experiences that can last upwards of 24 hours. The African psychedelic might have remained nothing more than a curiosity in the West if not for the discovery of its ability to disrupt physical and psychological drug addiction. Thousands of anecdotal reports and preliminary scientific research provide evidence that a single dose of ibogaine can eliminate both withdrawal symptoms and craving in drug addicts. In the United States, ibogaine remains a schedule 1 drug, and those seeking treatment must pilgrimage to countries that do not regulate it or take a chance with illegal underground treatment centers. What will it take for ibogaine to become medically available in the United States?

New drugs must undergo a rigorous vetting process to move from discovery to the legal market. To become a prescriptible medication, drugs must pass through clinical trials regulated by the Food and Drug Administration (FDA). These trials consist of a pre-testing phase, four clinical phases, and regulatory checkpoints throughout. Advancing to the next phase is predicated on successful completion of the prior phase.

Before moving to clinical trials, researchers must collect extensive pre-clinical data and submit an Investigational New Drug (IND) application to the FDA. Pre-clinical studies use rodent models to determine how effective the drug is for its intended purpose and its safety.

Phase 1 is the first set of studies to determine the safety and efficacy of the drug in humans. If these studies are successful, researchers can proceed to Phase 2, which are well-controlled studies with larger populations. Phase 3 studies test safety and efficacy with different dosages of the drug in even larger populations comprised of various demographics. While the time it takes to move through all phases varies, this process can take many years. After successful Phase 3 trials, the FDA reviews the data and the researchers submit a New Drug Application (NDA). The FDA reviews the NDA and the drug’s labeling to ensure accurate and sufficient information is provided to the consumer and drug-provider. The drug production facility is also inspected by the FDA for health and quality assurance. If the drug is approved, it will be released on the market and available for prescription. Phase 4 trials occur only after the drug has been approved and is publicly available. In Phase 4, the drug manufacturer must continuously monitor the effects of the drug in patients and submit safety reports to the FDA.

For ibogaine to come to market, it must pass through each of these clinical phases of study. Remarkably, ibogaine began the process of becoming an FDA approved therapeutic medication in the early 1990’s. Pre-clinical and Phase 1 trials conducted by Dr. Deborah Mash at the University of Miami supported the anecdotal evidence that patients had significantly reduced drug withdrawal and craving following ibogaine administration. These trials ended prematurely as a result of several factors, including criticism from the pharmaceutical industry, the apparent costliness to continue, and an intellectual property lawsuit between Mash and Howard Lotsof. No clinical trials have been conducted with ibogaine since this preliminary work over 20 years ago.

Another issue facing the medical legalization of ibogaine is that it cannot simply be prescribed in pill form by a doctor. The drug must be administered in a therapeutic setting, potentially as an aid to psychotherapy, as is the case with MDMA. Pre- and post-counseling are vital to ensure proper translation and integration of the psychedelic experience, as well as addressing the underlying problems that contribute to drug abuse. Furthermore, patients must implement changes outside of the clinic to ensure successful treatment outcomes. This means getting away from the external factors that contribute to drug abuse, which can include leaving relationships with friends, family or partners, and/or moving to a new area. While legalization for medical application is important, there must also be infrastructure developed to support proper administration of the drug.

There have been cases of death associated with taking ibogaine. However, none of these cases have been a result of overdose or toxicity. Individuals with certain heart conditions are at a higher risk of cardiovascular-related death after consuming ibogaine, and taking drugs of abuse with ibogaine may cause adverse reactions that can result in death. Rather than supporting the case against legalization, the risk of death for certain patients further evidences the necessity of legalization: unlike some clandestine ibogaine sources, regulated treatment centers would have the resources to screen patients for comorbidities (reasons not to ingest the drug) prior to ibogaine administration.

While the legal status of ibogaine in the US makes research a significant challenge, countries in which ibogaine is unregulated provide the opportunity to study its use in legal clinics. In 2017, the Multi-Disciplinary Association for Psychedelic Studies (MAPS) sponsored two studies investigating the efficacy of ibogaine in Mexico and New Zealand. With abundant data available for legal collection across multiple fields of study, scientists are just beginning to scratch the surface of ibogaine research. Those interested in studying ibogaine should not be discouraged by the barriers in the United States and should look abroad for more opportunities.

*From the article here :

The Future of Medical Ibogaine

Ibogaine is a psychedelic chemical found in the West African shrub Iboga. Bizarre in chemical structure and psychoactive properties, the drug remains mysterious to scientists and psychonauts alike. At high doses, ibogaine causes intense, unforgivingly introspective and dream-like hallucinatory...

psychedelicstoday.com

 

[mr peabody]

Ibogaine treatment for problematic opioid consumption: Short- and long-term outcomes

A. Davis, A. Windham-Herman, J. Barsuglia, M. Lynch, M. Polanco

Very few studies have reported the effectiveness of ibogaine as a treatment for chronic opioid use. This study evaluated the acute subjective effects of ibogaine, outcomes on problematic opioid consumption, and the long-term associations with psychological functioning. Using online data collection, 88 patients who received ibogaine treatment in Mexico between 2012 and 2015 completed our survey.

Most participants (72 percent) had used opioids for at least 4 years and 69 percent reported daily use. Most (80 percent) indicated that ibogaine eliminated or drastically reduced withdrawal symptoms. Fifty percent reported that ibogaine reduced opioid craving, some (25 percent) reporting a reduction in craving lasting at least 3 months. Thirty percent of participants reported never using opioids again following ibogaine treatment. And over one half (54 percent) of these abstainers had been abstinent for at least 1 year, with 31% abstinent for at least 2 years. At the time of survey, 41 percent of all participants reported sustained abstinence (>6 months). Although 70% of the total sample reported a relapse following treatment, 48 percent reported decreased use from pretreatment levels and an additional 11% eventually achieved abstinence. Treatment responders had the lowest rates of depressive and anxious symptoms, the highest levels of subjective well-being and rated their ibogaine treatment as more spiritually meaningful compared with treatment non-responders.

The results suggest that ibogaine is associated with reductions in opioid use, including complete abstinence, and has long-term positive psychological outcomes. Future research should investigate the efficacy of ibogaine treatment using rigorous longitudinal and controlled designs.

https://www.stichtingopen.nl/subjec...m-outcomes-current-psychological-functioning/​

 

[mr peabody]

Brazilian doctor, Bruno Rasmussen, on treating cocaine addiction with ibogaine*

Interesting interview segment with a Brazilian Iboga researcher Bruno Rasmussen. The article is translated into English.

The R7 interviewed physician and researcher Dr. Bruno Rasmussen on the advances in research and details of stimulent addiction treatment with ibogaine. Ramussen also gives an overview of psychedelic medicine.

How long have you been researching and participating in research groups for a chemical dependency treatment?

For 23 years, but independently. Together with other researchers, since 2012.

When did you start your studies with psychedelic medicine?

The most important academic studies, related to ibogaine, began in 2012, through a team composed by psychiatrist Dartiu Xavier, from PROAD of UNIFESP; Eduardo Schenberg, neuroscientist; Maria Angelica Comis, psychologist; And I, a clinical doctor. This study was published in 2014 in the Journal of Psychopharmacology.

What are the results?

At that time patients who had taken ibogaine for chemical dependence from 2005 to 2013 were interviewed and followed up, and a result of 62% of abstinent patients after treatment was reached. In addition, we observed that ibogaine, applied within the appropriate clinical safety standards, in a hospital environment, is effective and safe, with no significant adverse events.

These results also led to the publication of statements from the Coned-SP (State Council on Drug Policies of the State of Sao Paulo text below) that stipulated that treatment with ibogaine must necessarily be performed in a hospital environment, with medical, psychiatric and psychological follow-up.

Have there been other advances?

After that, we did another research, a qualitative study, with the participation of the psychiatrist Luis Fernando Tofoli, from Unicamp, and Joao Felipe Alexandre, from UFABC, who showed a great improvement in the quality of life After treatment with ibogaine, even in patients who came to relapse, with shorter and less profound episodes of relapse. This second study was published now in April 2017 in the Journal of Psychedelic Studies. We also have a third study, from the same team, on the same subject, which is in the process of being published, which shows similar results.

Regarding MDMA, I participate in another group that is undergoing training to conduct research on substance use in people with PTSD. This research is occurring in a coordinated way in other parts of the world, especially in the United States, and should begin here in Brazil in the coming months.

Other studies, with Ayahuasca, have been conducted at USP in Ribeirao Preto and UFRN, for depression, and have occurred in recent years as well. But I have no connection with the latter.

Which substances are already under study in Brazil?

In terms of psychedelic medicine, Ayahuasca, for depression; Ibogaine, for chemical dependence; And MDMA, for posttraumatic stress disorder. Brazil has been strong in this type of research, as was clear at the MAPS conference held last April in Oakland, attended by more than 3,000 people, where several lectures were from Brazilians, including me.

How do you evaluate the outcome in the volunteer group?

Regarding ibogaine, I evaluate the results as excellent. No current approach offers comparable results and, interestingly, in such a short time, since most patients taking ibogaine require only one dose, which is applied during a 24-hour hospital stay.

As for Ayahuasca and depression, great results too, and with the same characteristic, very fast results. Regarding MDMA, in Brazil the research is still in the initial phase, but I was able to follow some patients who did this treatment in the USA, for post-traumatic stress (in this case, veterans), and the results were also very good. In 82% of cases, after 3 sessions the patients no longer met the criteria for the disorder.

How long does conventional chemotherapy treatment take without ibogaine?

A few months, most often about 9 months, with a relapse rate greater than 70%.

In the case of Ibogaine, specifically, how is the procedure in Anvisa to allow the medicinal use of the plant?

Well, in the case of ibogaine, the use of the plant in nature, although it is the traditional way of using it, is not so interesting, since innumerable variables (plant type, soil, climate, mode and time of Influence purity and result.

Therefore, it is safer and with more predictable results if the extracted and purified substance, which is called ibogaine HCL, is used. This substance, although not yet registered with Anvisa, may be imported for personal, non-commercial use, by the patient's own initiative, according to Decree 8.077 of August 2013 and Anvisa Resolution 28/2011.

In order to avoid the bureaucracy of this importation process, it would be important for the medication to be registered in Brazil, which is a long and bureaucratic process, but I am confident that this will happen in the medium term, since this process is already under way.

How does Ibogaine work in the treatment of chemical dependence?

Ibogaine increases the manufacture, by brain cells called glial cells, of a factor called GDNF (Glial Cell-Derived Neurotrophic Factor). It is considered a neuronal growth factor, which causes the neurons to proliferate and connect or reconnect with each other. This effect apparently rebalances the neurotransmitters (dopamine, serotonin) and brings a sense of sustained well-being, which decreases the patient's need for drug use.

In addition, during the effect of ibogaine, the patient enters a state called onirophrenia, which is the daydream, a moment of expansion of consciousness in which the person can re-evaluate attitudes, feelings, where he has insights related to his problems.

This ends up functioning as an intensive, concentrated, drug-induced "psychotherapy" and is very effective in increasing the patient's understanding of the problem he is facing.

Is the patient at risk of becoming a chemical dependent of ibogaine?

No, the experience with ibogaine is not pleasant, it does not give pleasure, there is no reported case of use of ibogaine for recreation purposes.

Are there different levels of crack dependents? In your research have you already detected any profile of controlled use of crack or in all cases the user ends up falling into a severe dependency after a period of crack use?

In relation to any drug, including alcohol, there are always patients who abuse more than others, and also always have people who can make a use less harmful or more controlled. This also happens in relation to crack. But it is less common than with regard to cocaine or alcohol for example. But it's not all crack users who have seen zombies as is believed.

There are many cases of relapse and multiple hospitalizations of dependents. With psychedelic medicine, is the risk of relapse lower? Is a long period of hospitalization necessary for treatment with psychedelic medicine having the necessary effect?

That's the great advantage of psychedelic medicine, it's the response time. Always very fast, in one or at most a few sessions, you can already see the result. In the case of ibogaine, as I have said, most of the time, it is a single dose. And the hospitalization is necessary for a very short period, only during the application of the medicine.

Some patients may require a 30-day hospitalization period prior to application to better prepare for withdrawal of certain medications that should be discontinued prior to taking ibogaine and other Undesirable drug interactions. But this hospitalization period will always be much shorter than in traditional treatments. And that is what makes the industry of clinical dependence not like ibogaine, and spreads misrepresented information, because commercially it does not interest a drug that decreases the length of stay.

In addition, as the second study shows, relapses after ibogaine are shorter, deeper and with a faster recovery from normal life.

The Spanish psychologist Genis On, who also studies psychedelic medicine, talks about the importance of a psychotherapeutic process to accompany the treatment and that the use of psychedelic substances act as a coadjuvant and not as a main treatment. What do you think this is and what should be the preparation and evaluation of the patient before starting treatment.

I agree with him 100%. Ibogaine and other substances can be considered as facilitators of psychotherapy and, without it, there is nothing to be facilitated, so efficacy drops a lot. Ibogaine is not a miracle, it is a tool that along with other procedures, increases the chance of the patient returning to a normal life. But there is no point in reaching and taking ibogaine without proper monitoring, the result will be frustrating.

How would this adequate monitoring be?

The preparation should consist of some consultations with a psychotherapist, to explain to the patient what will happen during the experience, to adjust the person's expectations to reality, and to diagnose any comorbidities (diseases that the person may present, of dependence), which may be contraindications to treatment (e.g. schizophrenia). And after the shot, a follow-up is also important, to help one digest the experience and prepare to resume normal life.

In addition, a medical evaluation is also important to make sure that the patient has no heart, kidney, liver disease, which could compromise the safety or efficacy of the medication.

*From the article here :
http://iboga.io/brasileiros-estudam-...ontra-o-crack/​

 

[mr peabody]

The drug ibogaine is derived from the shrub Tabernanthe iboga.
​

Ibogaine re-engineered for potential use in the clinic*

by Gabriela Manzano-Nieves & Conor Liston | NATURE | 9 Dec 2020

An analogue of the psychedelic drug ibogaine has been developed. The analogue mirrors ibogaine’s ability to treat addiction and depression in animal models, has fewer side effects and is much simpler to synthesize.

The discovery in the 1940s and 1950s that the drugs lysergic acid diethylamide (LSD) and psilocybin had psychoactive properties ignited intense interest in whether psychedelic compounds could be useful in the clinic1. But in the 1970s, increasing concerns about safety and the drugs’ potential for abuse led to research becoming increasingly restricted. In the past decade, there has been a renewed interest in the therapeutic potential of psychedelic compounds, with preliminary findings indicating promise for drugs including LSD, psilocybin and ibogaine in combating treatment-resistant depression, post-traumatic stress disorder and anxiety in people who have terminal cancer. Writing in Nature, Cameron et al. report the synthesis of a non-psychedelic analogue of ibogaine that could have the potential to treat addiction and depression.

Ibogaine is a naturally occurring alkaloid found in the West African rainforest shrub Tabernanthe iboga. Preclinical data and small-scale studies indicate that ibogaine might be useful for reducing drug cravings, withdrawal symptoms and the risk of relapse in opioid and alcohol addictions. This might be because of ibogaine’s ability to modulate neuronal growth and maintenance and to alter the strength of the connections between neurons (synaptic plasticity). However, ibogaine has several undesirable properties. First, it can cause dangerous irregularities in heartbeat and neurotoxicity. Second, the drug produces long-lasting hallucinations at therapeutic doses. Third, ibogaine is technically complicated to synthesize, limiting its production.

Cameron et al. set out to engineer an ibogaine analogue that retained its therapeutic potential but had less-severe side effects. The authors first systematically deleted key structural elements of the molecule, and found that ibogaine’s tetrahydroazepine ring is crucial for promoting growth and branching of neurons in culture, as well as in the brains of mice. The group subsequently synthesized ibogaine analogues that retained their tetrahydroazepine ring and growth-promoting effects, but had more favourable toxicity profiles.

These efforts produced one particularly promising candidate for further study — a new compound called tabernanthalog (TBG), which can be easily synthesized in a single step from readily available starting materials. Cameron and colleagues used established assays in rodents and zebrafish to compare TBG and ibogaine. They showed that TBG had lower psychedelic potential than ibogaine, as measured by its propensity to elicit head-twitching behaviour in mice. It also showed less cardiac and developmental toxicity in zebrafish, especially at low doses. Together, these data indicate that TBG is probably a much safer alternative to ibogaine, although more studies will be needed to fully understand TBG’s toxicity across a range of doses and in acute or chronic dosing regimens.

Next, the group evaluated TBG’s potential therapeutic properties. First, they assessed its antidepressant potential. They exposed mice to seven days of unpredictable, mild stressors, and then tested the animals on the forced-swim test — a commonly used assay for antidepressant compounds, in which mice alternate between periods of swimming and immobility. Compounds that reduce immobility in this test tend to have antidepressant properties in humans. TBG had rapid antidepressant-like effects on immobility behaviour just one day after treatment, to a degree comparable to ketamine, a rapidly acting antidepressant. However, TBG’s effects were not as durable as those of ketamine one week later. Future studies should assess whether TBG’s antidepressant-like effects could be extended by modifying the dosing regimen or combining it with other interventions.

Second, Cameron et al. tested whether TBG could modify opioid and alcohol use in two rodent models of addiction. In a binge-drinking model, mice were offered the choice between drinking water and 20% ethanol, then subjected to withdrawal of the ethanol, in cycles over seven weeks, to produce binge-drinking behaviour. TBG treatment reduced alcohol consumption rapidly, with sustained effects lasting at least two days, comparable to effects often observed with other anti-addiction drugs.

In an opioid-seeking model, rats learnt to press a lever to receive an intravenous infusion of heroin. In this setting, TBG caused a rapid reduction in heroin consumption. Perhaps most compellingly, Cameron and colleagues found that TBG effectively eliminated relapse in rats that had been subjected to heroin withdrawal for 12–14 days after TBG treatment. This remarkably durable protection from relapse is rarely observed after a single treatment with other drugs, and suggests that TBG might be especially useful for reducing relapse behaviour in people recovering from drug addiction.

Of note, TBG treatment also rapidly reduced sucrose-seeking behaviour in rats. This finding suggests that TBG could be acting acutely, not to diminish the rewarding properties of drug abuse, but instead to modulate learnt behaviours more generally. This is an equally interesting alternative explanation that suggests TBG could be useful for modifying a variety of habitual behaviours, and remains to be explored.

How does TBG work? The authors showed that it potently activates the serotonin 2A receptor (5-HT2AR) protein. Co-treatment with ketanserin, a 5-HT2AR inhibitor, blocked TBG’s effects on immobility in the forced-swim test, implicating this signalling pathway in the drug’s antidepressant-like properties. The growth-promoting effects of TBG on neurons were likewise blocked by ketanserin. These findings raise the intriguing possibility that TBG acts rapidly through a 5-HT2AR signalling pathway to produce therapeutic behavioural effects, which might then be sustained through effects on neuron growth and plasticity, as has been observed in studies of ketamine. Studies will be needed to evaluate whether and how synaptic plasticity is required, and how synaptic plasticity and 5-HT2AR signalling together influence behaviour and neuronal function through effects on specific cell types and circuits.

Cameron and colleagues’ work builds a foundation for future investigations into whether TBG and other ibogaine analogues can be used to treat addictions and depression. Animal models of psychiatrically relevant behaviours are notoriously complex, and no single model faithfully recapitulates all aspects of a psychiatric disorder11. Not all compounds that have promising behavioural effects in rodents turn out to be therapeutically useful. Extensive studies in other animal models, and later in clinical trials, will be needed to elucidate how TBG works; to understand the relationship between drug dosing, therapeutic effects and adverse side effects; to establish safe and effective dosing regimens in humans; and, ultimately, to confirm its clinical efficacy.

Indeed, Cameron et al. are careful to emphasize that this report is just a first step in that direction, not an invitation to immediately begin using TBG, ibogaine or related compounds in the clinic or in unsupervised settings. Instead, their work presents a highly compelling case for pursuing this fundamentally new class of therapeutic compound. It also provides a road map for future efforts to engineer new analogues of psychedelic compounds that retain their potential therapeutic benefits while minimizing adverse side effects and other unwanted properties.
​

Nature 589, 358-359 (2021)

doi: https://doi.org/10.1038/d41586-020-03404-z

*From the article here :

Psychedelics re-engineered for potential use in the clinic

A safer analogue of the psychedelic compound ibogaine.

www.nature.com

 

[mr peabody]

What are the risks of ibogaine treatment?

by Amelia Walsh & Dr. Lynn Marie Morski, MD, Esq| PSYCHABLE

Ibogaine is an alkaloid found in the root bark of the west equatorial Africa perennial shrub, Tabernanthe iboga. The root bark of Tabernanthe iboga has been used for millennia in west Africa, where its use is a sacred sacrament and for reasons of celebration, as well as a rite of passage and initiation into the Bwiti tribe for younger people.

In 1962, Howard Lotsof, who was dependent on heroin and interested in psychoactive substances, ingested ibogaine and came out of the experience with no dependency to heroin. He went on to give several friends ibogaine who had similar results. In the 1980s, Lotsof patented ibogaine for several substance abuse treatments and began administering ibogaine at a clinic in the Netherlands.

In the early 1990s, other ibogaine providers, such as Eric Taub, begin performing ibogaine sessions in other parts of the world and quietly in America. This eventually would lead to medically monitored, holistic, and therapeutic treatment centers launched in Mexico and Central America. This was the beginning of the ibogaine clinic movement that still exists today.

What is ibogaine?

Ibogaine has a diverse and complicated pharmacological profile. Ibogaine inhibits serotonin and dopamine transporters, NMDA and nicotinic acetylcholine receptors, and binds to mu and kappa opioid receptors. There is also some evidence that ibogaine has antimicrobial properties, as well as neuroprotective properties. Ibogaine also produces neuroplasticity and may have neuroadaptive properties. This may be in relation to its ability to modulate neurotrophic factors GDNF and BDNF.

While scientists don’t fully understand the entirety of ibogaine’s mechanism of action, there are decades of anecdotal ibogaine “trip reports” hailing ibogaine as a “wonder drug”; a psychedelic that can tackle almost any mental health or substance use disorder. It’s important to remember ibogaine is not a cure or a magic bullet, although it may be a powerful catalyst for change in some individuals. Studies on many ibogaine enthusiast claims are lacking, but one anecdotal report that seems consistent is that ibogaine is incredibly individualized, meaning that the experience varies widely from person to person.

Though there is a lot of promise with the benefits of ibogaine, and studies on its utility for treating substance use are promising, the dangers are sobering. Ibogaine has a significant effect on the cardiac system, and fatalities and hospitalizations do occur, even in medically monitored clinics. Ibogaine-related complications are often due to previous medical conditions, substance intake, compromised physiology, and cardiac history. While complications can largely be avoided with proper screening, monitoring, and careful dosing, one should always weigh the risks of treatment and explore all options other than ibogaine before making a decision, and thoroughly vet the ibogaine center they choose to attend if ibogaine is the best solution for them.

What makes ibogaine dangerous?

Ibogaine has a significant effect on the cardiac system. It is a potassium hERG channel blocker. Blocking these potassium channels can cause arrhythmias and QT prolongation. QT prolongation related to ibogaine can last several days.

The QT interval is the time it takes the heart to recharge between beats. This means that ibogaine makes the heart take longer to recharge between beats. QT interval prolongation increases the risk of a ventricular arrhythmia called torsades de pointes that often results in cardiac arrest. QT prolongation can also cause palpitations, lightheadedness, syncope, and arrhythmias. Ibogaine may cause bradycardia and hypotension, and in higher doses, may cause seizures. Vomiting, which may disturb electrolyte levels and lead to dehydration, can be common. Ibogaine is broken down in the liver and metabolized into its longer-acting metabolite noribogaine by the liver pathway CYP2D6. Those with impaired liver function may therefore have a higher risk of adverse effects from Ibogaine.

The population of people seeking out ibogaine tends to be a population of people who may have compromised physiology and are seeking out ibogaine to restore their health. However, if an ibogaine patient is young, isn’t taking any QT-prolonging substances, has a healthy liver and heart, and is monitored by a reputable clinic, the risk is lower. Regardless, anyone seeking out ibogaine treatment should be screened and prepped by a reputable ibogaine provider.

The exact number of ibogaine deaths is unknown. Due to the unregulated nature of the industry, many deaths go unreported. A study that reviewed 19 deaths from 1990 to 2008 found that people died anywhere from about one hour to three days after ingesting ibogaine. However, these deaths were attributed to prior medical conditions and other substances in relation to ibogaine and not ibogaine toxicity alone.

However, there are also reports of people suffering fatal and near-fatal events at ibogaine treatment centers and under the care of ibogaine providers. In New Zealand, during a study on ibogaine, one participant died during treatment. Additionally, the lack of regulation in the ibogaine industry allows anyone to call themselves a professional, and there can be dangerous consequences to the lack of oversight. Juliana Mulligan, an ibogaine integration specialist, suffered six cardiac arrests during her ibogaine treatment at an ibogaine center that didn’t follow safety protocols in Guatemala. Some estimate that up to 1 in 300 people who take ibogaine will suffer a fatal reaction. This emphasizes the importance of pre-screening and only taking ibogaine at a reputable and safe center.

Mental health risks

There are also psychological risks to consider, especially because the experience can last for longer than a day. Mental health conditions like schizophrenia and a history of mania may increase the risk of prolonged mania or psychosis following the ibogaine experience. Acute confusional states, also sometimes called fugue states, have also been reported in clients with a history of substance use.

Ibogaine may reveal underlying mental health conditions. Mental health diagnoses can often help providers make decisions for safe ibogaine therapy candidates, but specific behavioral patterns may help providers determine inclusion and exclusion criteria. People who have been hospitalized for bipolar disorder, borderline personality disorder, depersonalization, psychosis, or mania should share these experiences with their providers to determine if ibogaine is the best course of action. Before ingesting any ibogaine, it is recommended to undergo a full psychiatric evaluation with the ibogaine center one chooses.

Because of the risks of complications, the simplest thing one can do to reduce risk is to only use ibogaine with a skilled provider’s supervision.

What are the side-effects?

Ibogaine is known for its intense rapid-eye-movement dream-like visionary state that some say reveals life-changing epiphanies. However, the experience has also been described as unpleasant. Side-effects of ibogaine include ataxia, sweating, irregular heart rhythm, temperature changes, insomnia, nausea, chest pain, dry mouth, and tremors. Ibogaine can cause tachycardia and bradycardia, raise or lower blood pressure, and cause seizures. Anecdotal reports from clients suggest movement triggers vomiting and dizziness. Closed and open-eyed visuals have been reported as well as auditory hallucinations.

Ibogaine not only lowers tolerance to opiates but will potentiate opiates if introduced or still in the system. Ibogaine also lowers tolerance to alcohol and stimulants. Those who choose to use substances after ibogaine should assume they have returned to a pre-substance dependent state and be very careful.

Ibogaine can last a long time. Most people are under the effects for around 12-24 hours, but it is not uncommon to be in bed for over a day or to be experiencing side effects of ibogaine for 48 hours, and insomnia may persist for up to a week. Some people may have a challenging time holding down fluids for over a day. Choosing a center that can administer anti-nausea therapies in the case of prolonged nausea or vomiting will help eliminate the risk of depleted electrolytes during ibogaine treatment.

How to stay safe?

There is no shortage of risks when it comes to ibogaine treatment. And yet, people describe it as life-changing, and people around the world seek it out. The important question is whether it can be experienced safely and how?

Due to the QT-prolonging effects of ibogaine, medications that can affect regular heartbeat and/or prolong the QT need to be avoided for a period of time before ibogaine ingestion. Similarly, medications that inhibit the CYP2D6 liver pathway slow down the metabolism of ibogaine and may increase dangerous side effects. Other medications may also pose a treatment risk. Ideally, an ibogaine provider will be familiar with a client’s medication regimen and can give a thorough plan for tapering and cessation of medications if necessary.

Ibogaine is also contraindicated with cardiac medications (specifically beta-blockers and antiarrhythmic medications), SSRIs, antipsychotics, and other mood stabilizers. OTC meds such as omeprazole and Benadryl can prolong the QT interval, as well as quinine-based substances such as tonic water, grapefruit, bitter lime and lemon, and cranberry.

Some supplements and herbs should also be stopped before ibogaine treatment. As a general rule, the risk of cardiac, liver, or other dangerous side effects increases when ibogaine is taken with many different types of medications – prescribed or OTC, supplements, narcotics, and herbs. This is not a complete list of substances to avoid, and ibogaine should only be considered after being carefully screened by a reputable ibogaine provider or clinic.

Ibogaine and substance withdrawal

Ibogaine appears helpful in managing cravings associated with several addictive drugs, however is only helpful in the management of withdrawal symptoms in the case of opioids. Due to risks associated with withdrawal from some substances, persons wishing to use ibogaine for management of other drug addictions may be asked to detoxify prior to ibogaine use. Stimulants are an example due to their effect on the cardiac system and alcohol is an example due to its risk of seizure during withdrawal.

Persons using benzodiazepines might want to taper off this medication before their ibogaine therapy sessions due to the claim that benzodiazepines may dampen the visual experience. However, benzodiazepine cessation and ibogaine both carry a risk of seizures. To avoid this risk with ibogaine, one needs to be away from benzodiazepines for an extended period of time. Benzodiazepine withdrawal can be dangerous and should be done under medical guidance. As a result, it may be recommended that benzodiazepine-dependent individuals stay on benzodiazepines for their ibogaine experience and taper off afterward. While benzodiazepines aren’t specifically contraindicated with ibogaine, side-effects of benzodiazepines can pose some risk to ibogaine treatment if not administered safely and monitored consistently throughout treatment. Individuals who are using benzodiazepines are safest with experienced ibogaine providers who have a medical set-up, medical staff, and are experienced with benzodiazepines.

Ibogaine treatment center safety

When in-depth pre-screening, preparation, protocols, medical monitoring, an emergency plan, and follow-up are put into place, ibogaine can be experienced in a much safer way. However, even with precautions, ibogaine treatment carries some level of risk to it in all doses. Ibogaine is not a DIY substance. It should never be taken at home alone due to the risk of fatality, even in small doses. Fatalities have occurred in doses as low as 3mg/kg, and adverse events have been reported in doses as low as 3mg and 10mg.

The best way to experience ibogaine safely is to book a stay at a reputable ibogaine treatment center. However, finding a reputable center can be overwhelming.

The internet is full of Google ads, forums, testimonials, recommendations from anonymous people, and websites for ibogaine centers. Ibogaine is a Schedule I substance in America and illegal in a handful of other western countries. As a result, internet searches often lead to centers around the world where ibogaine therapy is an unregulated industry. There is no across-the-board training program, certification, or medical oversight that anyone working with ibogaine is required to abide by. This allows for many different types of centers and methods of providing the medicine. It also provides access to something many have reported being life-saving that is illegal in America and other places. However, the lack of regulation also means that centers do not have to follow any sort of medical, ethical, or professional standard for their clients. This is why finding a safe, ethical, and reputable center is imperative and is vital for one’s healing process and safety.

Ibogaine: What are the Risks, & How do I Stay Safe?

Medical Editor: Dr. Lynn Marie Morski, MD, Esq What are the risks of ibogaine treatment? History of Ibogaine Treatment Ibogaine is an alkaloid found in

psychable.com

 

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IBOGAINE: A Case Report

by T. Engelhardt | SEMANTIC SCHOLAR

Ibogaine is a psychedelic alkaloid derived from a western African shrub. Although in recent years some degree of experimental evidence has emerged favouring the use of ibogaine in the management of substance abuse disorders, these developments have been overshadowed by concerns about its safety and several cases of unexplained sudden cardiac death have been associated with its use. Among its pleiotropic receptor effects, ibogaine has central 5HT-2A agonist activity, and through this mechanism it prolongs the QT interval. Although ibogaine is not approved by any drug administration agency in the world, its unauthorized use in clandestine detoxification clinics is steadily growing worldwide. We describe the first case of severe ibogaine toxicity in the UK and highlight the complexities posed by its management.

A young Afro-Caribbean man was admitted to hospital with vomiting and agitation, after being found by his relatives in a state of confusion. He had ingested a total of 7 g of ibogaine to soothe the symptoms of heroin withdrawal. He denied ingestion of alcohol or any other drugs and he had not used heroin or methadone for 72 h. There was no family history of heart disease. Initial laboratory blood tests, arterial blood gas analysis, cardiac enzymes, and urine toxicology were unremarkable The patient was in sinus bradycardia,with marked prolongation of the QTc interval (600 ms). Several brief, self-terminating bursts of polymorphic tachycardia (VT) occurred. The VT was initially associated with tonic-clonic seizures and the patient rapidly deteriorated, losing cardiac output, and developing torsades de pointes cardiac arrest. Spontaneous cardiac output was initially restored by defibrillation (200 J), but pulseless torsades depointes recurred despite treatment with i.v. magnesium (8 mmol), atropine (2 mg), epinephrine (4 mg), and isoprenaline (5 mg min).

The patient was defibrillated several more times and required tracheal intubation to secure his airway. Transcutaneous overdrive pacing immediately shortened the QT interval and controlled the ectopic ventricular activity. The transcutaneous pacemaker was promptly replaced with a temporary transvenous pacing wire. The patient was paced at a rate of 80 beats min for48h, without furtherepisodesof VT. The patient’s bradycardia resolved and the QT interval spontaneously returned to 420 ms. The pacing wire was removed and the patient was weaned from mechanical ventilation. No further abnormalities were detected on subsequent ECGs and a transthoracic echocardiogram was normal. A review by a consultant cardiologist determined that no further electrophysiological testing was required. The patient had an uneventful recovery and was rapidly discharged.

https://www.semanticscholar.org/pap...ardt/0ad195780b70bef84afbb8907704bac75519031b​

 

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Ibogaine and Neurodegenerative Diseases

This is a summary on existing research into the influence of Ibogaine on glial cell line-derived neurotrophic factor (GDNF) levels in the brain, and the beneficial impact that an increase in this protein can have. While existing studies have examined these areas, few have identified a possible link between Ibogaine, GDNF expression and neurodegenerative diseases.

Both Parkinson's Disease and ALS are chronic disorders with no known cure, and require management with drugs that can have considerable side effects, causing a very poor quality of life for terminal stage sufferers of these diseases. By contrast, a low dose regime of Ibogaine or Iboga alkaloid extract would be of low toxicity and free of serious side effects.

GDNF has been shown to have potent neurotrophic factor in both rodent and primate models of Parkinson's Disease. Direct brain infusion of GDNF into the brains of five Parkinson sufferers resulted in a 39% improvement in the off-medication motor sub-score of the Unite Parkinsons Disease Rating Scale and a 61% improvement in the activities of daily living sub score. Positron emission tomography (PET) scans of dopamine uptake showed a significant 28% increase in putamen dopamine storage after 18 months, indicating a direct effect of GDNF on dopamine function. Furthermore, after one year, no serious clinical side effects were observed. The use of Iboga alkaloid extract or Ibogaine would provide a longer term and much less invasive method of GDNF administration than direct brain infusion. Thus, further research on Ibogaine and GDNF is certainly warranted.

Regarding motor neuron disease (ALS), the little research that has occurred in this area, such as gene transfer of neurotrophic factors, suggests potential in the treatment of motor neuron disease. Again, Ibogaine therapy may offer a straightforward, non-invasive, cheap, low-toxicity method of treatment for sufferers of this disease.

CKBR-12 for Parkinson’s - Genesis Ibogaine Center

CKBR-12, an Ibogaine derivative medicine developed by Phytostan Pharmaceuticals is currently being investigated and used exclusively by Genesis as a medication to treat Parkinson’s disease (PD). It has been found to upregulate glial cell line-derived neurotrophic factor (GDNF) expression in the...

genesisibogainecenter.com

 

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A non-hallucinogenic version of the psychedelic drug ibogaine has been developed by David Olson at UC Davis Department of Chemistry. The new compound
shows potential for treating psychiatric disorders including addiction in animal models and may work by increasing connectivity between nerve cells.

Non-psychedelic ibogaine compound could treat addiction, depression*

by Andy Fell | UC Davis | 9 Dec 2020

A non-hallucinogenic version of the psychedelic drug ibogaine has been developed by David Olson and colleagues at the UC Davis Department of Chemistry. The new compound shows potential for treating psychiatric disorders including addiction in animal models and may work by increasing connectivity between nerve cells.

“Psychedelics are some of the most powerful drugs we know of that affect the brain,” said David Olson, assistant professor of chemistry at UC Davis and senior author on the paper. “It’s unbelievable how little we know about them.”

Ibogaine is extracted from the plant Tabernanthe iboga. There are anecdotal reports that it can have powerful anti-addiction effects such as reducing drug cravings and preventing relapse. But there are also serious side-effects, including hallucinations and cardiac toxicity, and the drug is a Schedule 1 controlled substance under U.S. law.

Olson’s laboratory at UC Davis is one of a few in the U.S. licensed to work with Schedule 1 substances. They set out to create a synthetic analog of ibogaine which retained therapeutic properties without the undesired effects of the psychedelic compound. Olson’s team worked through a series of similar compounds by swapping out parts of the ibogaine molecule. They engineered a new, synthetic molecule which they named tabernanthalog or TBG.

Models of anxiety, depression and addiction

Unlike ibogaine, the new molecule is water-soluble and can be synthesized in a single step. Experiments with cell cultures and zebrafish show that it is less toxic than ibogaine, which can cause heart attacks and has been responsible for several deaths.

TBG increased formation of new dendrites (branches) in rat nerve cells, and of new spines on those dendrites. That’s similar to the effect of drugs like ketamine, LSD, MDMA and DMT (the active component in the plant extract ayahuasca) on connections between nerve cells.

TBG did not, however, cause a head twitch response in mice, which is known to correlate with hallucinations in humans.

A series of experiments in rodent models of depression and addiction show that the new drug has promising positive effects. These animal models – conducted in accordance with NIH regulations and reviewed and approved by Institutional Animal Care and Use Committees – remain vital to investigating complex psychiatric disorders.

Mice trained to drink alcohol cut back their consumption after a single dose of TBG. Rats were trained to associate a light and tone with pressing a lever to get a dose of heroin. When the opiate is taken away, the rats develop signs of withdrawal and press the lever again when given the light and sound cues. Treating the rats with TBG had a long-lasting effect on opiate relapse.

Olson thinks that TBG works by changing the structure of neurons in key brain circuits involved in depression, anxiety, post-traumatic stress disorder and addiction.

“We’ve been focused on treating one psychiatric disease at a time, but we know that these illnesses overlap,” Olson said. “It might be possible to treat multiple diseases with the same drug.”

Indeed, psychedelic therapies have been attracting new interest in recent years. But taking patients on individual ‘trips’ is time consuming and costly, requiring hours of close medical supervision apart from the possible negative effects.

“We need a drug that people can keep in their medicine cabinet, and this is a significant step in that direction,” Olson said.



David Olson, an assistant professor in the UC Davis departments of Chemistry and Biochemistry and Molecular Medicine, is investigating whether sub-hallucinogenic doses of psychedelic compounds like LSD and dimethyltryptamine could lead to new treatments for depression, anxiety and related disorders without the unwanted psychedelic effects. Olson has started a company, Delix Therapeutics Inc., which has licensed TBG-related technology from UC Davis for further development.​

*From the article here:

New Compound Related to Psychedelic Ibogaine Could Treat Addiction, Depression

A non-hallucinogenic version of the psychedelic drug ibogaine, with potential for treating addiction, depression and other psychiatric disorders, has been developed by researchers at the University of California, Davis. A paper describing the work is published Dec. 9 in Nature. “Psychedelics are...

www.ucdavis.edu

 

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Ibogaine

Psychedelic Science Review

Ibogaine is an alkaloid compound that was first isolated from the plant Tabernanthe iboga that grows in Central Africa. Specifically, the plant is a shrub also known as iboga.

Traditionally, iboga plants are used in cultural and religious rituals by the indigenous peoples of Central Africa. They also use it in various dilutions for alleviating hunger, fatigue, and thirst.​

The Chemistry of Ibogaine​

Ibogaine was first isolated by Dybowski and Landrin in 1901. Its crystal structure was solved in 1960. The first synthesis by done in 19664 and a simplified total synthesis was published in 2012. A detailed summary of ibogaine synthesis is found in Wasko et al., 2018.

Ibogaine crystallizes into prismatic needles from ethanol. In addition to ethanol, it is soluble in ether, chloroform, acetone, and benzene. It is practically insoluble in water. The hydrochloride salt of ibogaine is soluble in water, as well as methanol and ethanol. It is slightly soluble in acetone and chloroform, but practically insoluble in ether.​

The Pharmacology of Ibogaine​

Ibogaine is cardiotoxic at micromolar levels. Specifically, studies have noted a prolongation of the heart’s QTc interval. Ibogaine has also been shown to be neurotoxic in rodents. At higher doses, the effects include tremors, convulsions, nervous behavior, and paralysis of the limbs. However, the doses used in these studies are below what would be used in a clinical setting.

In terms of pharmacodynamics, ibogaine shows no clear preferences, having a moderate to weak affinity for a variety of receptors and transport proteins. As a result, the psychedelic effects of ibogaine cannot be attributed to the activation of the serotonin 5-HT2A receptor (Ki = 16 µM). However, ibogaine’s principal metabolite noribogaine has sub-micromolar affinity (0.61 µM) as a partial agonist of the kappa opioid receptor. The mechanism of the dissociative effects caused by ibogaine may be similar to that of ketamine and other NMDA (N-methyl-D-aspartate) channel blockers.

Ibogaine also binds in the low micromolar range to the mu opioid receptor, as does noribogaine in sub-micromolar range. This may explain the ability of ibogaine to decrease self-administration of morphine in rats.

Studies indicate that ibogaine’s anti-opiate effects may be due to its noncompetitive antagonist action at nicotinic acetylcholine receptor subtypes including α1ß1 and α3ß4.​

The applications and potential of ibogaine​

In the early 1960’s, subjective reports of the anti- addictive properties of ibogaine began surfacing, most notably from a young heroin addict named Howard Lotsof. Lotsof was born in the Bronx, New York in 1943 and was severely addicted to heroin by the time he was 19 years old. By his own account, the desire of he and six of his friends to take heroin disappeared almost immediately after self-administration of an extract of the T. iboga root. Lotsof became one of the most vocal advocates of ibogaine use for the treatment of addiction. In 1985, he was granted a patent for the treatment of cocaine and heroin addiction using ibogaine.

Research indicates that ibogaine may be effective in treating opiate addiction. The data show that it doesn’t just reduce opioid use, but can result in complete abstinence, along with having “long-term positive psychological outcomes.” A 2018 study found that the positive effects of ibogaine for treating opioid dependence lasted twelve months. In a 2018 review paper, Deborah Mash et al. recommended using a single oral dose of ibogaine during detoxification “to transition drug dependent individuals to abstinence.”

*From the article (including references) here :

Ibogaine

Ibogaine is an psychedelic compound first isolated from the plant Tabernanthe iboga that grows in Central Africa. Ibogaine has dissociative effects and anti-addictive properties.

psychedelicreview.com

 

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​

How Ibogaine emerged as an addiction treatment in the west

by Faye Sakellaridis | LUCID | 26 May 2022

In 1962, Howard Lotsof, a 19 year-old New Yorker with a daily heroin dependency, tried a mysterious substance extracted from a West African shrub given to him by a chemist friend. Within 30 hours, after a long and intense trip, his desire for heroin was gone.

Lotsof was astounded. A day and a half went by without using, yet he had zero withdrawal symptoms. The experience itself was illuminating too. “Ibogaine showed him that heroin was something that emulated death,” says anthropologist and ibogaine researcher Thomas Kingsley Brown, PhD. “Before taking ibogaine, he regarded heroin as something that gave him comfort.”

Curious to see if the effects could be duplicated, Lotsof gave it to seven friends who were also addicted to heroin. After the experience, five immediately quit. “The other two said they could have stopped but they just didn’t want to. They liked using,” says Brown.

Ibogaine is the potent psychedelic compound with anti-addictive properties found in the shrub Tabernanthe iboga. It was first isolated in 1901 by J. Dybowski and Ed. Landrin, and introduced to the Western public in France in the 1930s, where a diluted preparation of it was marketed as a mental and physical stimulant. Lotsof sparked its association with treating opioid-dependency, going on to advocate for further research into it, and inspiring many medical practitioners to administer this treatment.

But the history of its usage goes far beyond the west, to the jungles of West and Central Africa, where its steward communities use it as a ceremonial sacrament to this day.

Ibogaine’s ritual history in West Africa

Tabernanthe iboga grows primarily in Gabon, along with surrounding areas like the Congo and Cameroon, where the Pygmy people originally resided. The ritual use of iboga can be traced back to the Pygmies, who introduced it to the Bantu people in the late 1800s, when French colonizers pushed the Bantus out of their coastal villages towards Gabon. The Pygmies initial use of iboga is unknown, likely dating back hundreds, possibly thousands, of years, says Brown.

From this cultural mixing emerged Bwiti, a spiritual tradition which incorporates animism and ancestor worship. Iboga plays a central role in Bwiti as a sacrament for spiritual growth and community bonding, used in healing rituals and initiation rites.

Gabon has at least forty different ethnic groups, resulting in a myriad of Bwiti branches. Most ceremonies involve music (participants play a number of traditional instruments, including percussion, harp and mouth bow) and dance to induce a prolonged trance state, lasting up to five days.

Although the majority of the Gabon population is Christian, most Bwiti practitioners have not adopted Christianity into their practice, with the exception of the Fang people, whose syncretic practice incorporates Christian elements. Bwiti has been persecuted by Christians since its inception, and faces condemnation by missionaries to this day. Aside from the church, Bwiti is well-accepted in Gabon, and a number of government officials and members of the police and army can be found among its initiates.

Ibogaine’s emergence as a treatment for opioid addiction

After his experience, Lotsof was single-mindedly dedicated to lobbying for ibogaine to be taken seriously as a treatment for addiction. His widow, Nora Lotsof, remembers him as “a real gentleman who believed whole-heartedly that anyone with a substance abuse problem should have the right to choose when, and by what means, to stop self-medicating.”

In the 1980s, by which point ibogaine had already been added to the list of forbidden Schedule 1 substances during the War on Drugs, Lotsof founded the NDA International, an organization that promoted research into ibogaine.

In 1986, Lotsof developed a patent for ibogaine as an addiction treatment, and through NDA, co-sponsored human studies on ibogaine in the Netherlands and Panama with other addiction treatment groups in the early 90s.

With the results of these studies, Lotsof was able to persuade the National Institute on Drug Abuse to conduct further research into ibogaine, eventually leading to F.D.A. approval of a Phase 1 clinical trial. Unfortunately, the trial was never completed, in part due to lack of funding and criticism from pharmaceutical companies.

Despite this setback, Lotsof continued to advocate for ibogaine with other researchers and doctors, and work with independent ibogaine clinics in Mexico, Europe, and the Caribbean.

Ibogaine in the modern day

The psychedelic renaissance, which is ushering in a new wave of acceptance for these substances, has raised awareness about ibogaine in psychedelic communities, among newcomers and veterans alike. However, ibogaine remains a Schedule 1 drug which, unlike other psychedelic substances, like psilocybin, has no significant research that could bring it towards FDA approval on the horizon.

Still, ibogaine clinics have been administering this treatment in places where it’s legal or unregulated since the 1990s by physicians and advocates who, like Lotsof, fervently stand by ibogaine’s potential. The Mexico-based ibogaine clinic Beond is staffed with physicians like Dr. Jeffrey Kamlet and Dr. Felipe Malacara, who’ve been successfully using ibogaine to treat addiction for decades in various clinics outside the U.S.

Recent developments have been made around the cultivation and exportation of ibogaine, which has been illegally harvested in Gabon for use in the West. Since the Nagoya Protocol, an international treaty established in 2014 that calls for the fair and equitable sharing of genetic resources, a number of ibogaine organizations are teaming up with Gabonese officials to develop a legal distribution channel for ibogaine that will allow Gabonese communities to benefit.

Among the groups participating is Beond, who will buy Nagoya-compliant iboga when it becomes available, and contribute a portion of their clinic’s proceeds towards projects that support Gabonese communities and indigenous leaders.

How Ibogaine Emerged as an Addiction Treatment in the West - Lucid News

Ibogaine began to be used for treating addiction in the 60s, but its origins stretch back to West African indigenous communities, where it is a ritual sacrament.

www.lucid.news

 

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What I learned from treating 400+ patients with ibogaine

by Bruno Gomes, M.A. | March 13, 2017

Since the middle of the 90s, there has been a renewed interest in the possible positive effects of many different plants and substances such as LSD, “magic” mushrooms and psilocybin, ayahuasca or iboga. Many new and rigorous scientific studies have been showing promising evidence that those substances are suitable for the treatment of many diseases and disorders such as obsessive-compulsive disorder, post-traumatic stress disorder, substance abuse or even depression. With so many possibilities, we could easily assume that psychedelics are the new panacea capable of curing any ailment. But, what is this cure? How does it happen? How similar are those curing processes to those of conventional medicine?

I’m a psychologist in Brazil and, after more than ten years working with homeless crack-cocaine users, I got involved with ayahuasca and ibogaine treatments, curious about what they could offer. Could these substances help my patients, who I have been struggling so hard to take care of? Since then, I have studied and assisted a group of recovering homeless individuals using ayahuasca, a brew made with Amazonian plants, most commonly Psychotria viridis and Banisteriopsis caapi. I’ve also treated around 400 patients with problematic drug use by using ibogaine. Ibogaine is a substance derived from the root bark of the African plant iboga (Tabernanthe iboga). Both ayahuasca and ibogaine have intense effects on the user’s perception of the world and oneself.

These substances are classified as entheogens, hallucinogens and plant teachers, depending on how they are used. The ayahuasca treatment I studied integrated the rituals of 2 traditional ayahuasca cultures - vegetalismo, with its purges and diets, and the musical healing rituals of Santo Daime. In this context, the brew is considered a plant teacher: a substance with a spirit that communicates with humanity through its effects. The ibogaine treatment, on the other hand, is much more similar to regular medicine. Ibogaine is extracted from the plant, processed by a pharmaceutical laboratory, and then prescribed by a medical doctor in a hospital.

These contexts affect the use and understanding of the substances, therefore changing what is experienced by the patient. This is even more evident when comparing different ayahuasca rituals. The same ayahuasca decoction in the context of a Santo Daime ritual, with bright light and everyone singing together—and then in a Shipibo indigenous ritual, in complete darkness, guided only by the curandero’s voice—will elicit a very different experience.

Especially interesting in this complex relationship between setting and experience is the element of mystery. Within a medical context, and never having heard about the African traditional cults with iboga, many patients that I’ve given ibogaine to still reported seeing or being visited by the “iboga spirit”; usually an old African woman or ancestral healer.

The reports and testimonials about these 2 substances are very impressive: the intensity of the experiences, as well as the sudden and deep transformations gained through them, attract more users every day; either looking for something new or different, or a spiritual or healing experience. Together with these reports, new scientific research on ayahuasca and iboga shows promising new and effective treatments for problematic drug use and alcoholism. There’s also constantly new data to show psychedelic substances use in treatment of obsessive-compulsive disorder, tobacco dependence and PTSD.

In the context of these reports, patients interested in ibogaine treatment often expect a new and powerful medicine. As aspirin reduces fever, they expect ibogaine to take their drug dependency away; something fast and effective that solves the problem for good. It would be perfect if ibogaine or ayahuasca could cure with the speed of aspirin, no matter the setting. With aspirin, it doesn’t matter where one takes it or if one believes in it, it will still reduce fever. With psychedelics, it’s not like that: the patient’s expectancy, his trust in those responsible for the experience, as well as what happens in the surrounding environment, will exert an intense influence on the experience.

These factors not only affect the experience, but also the outcome. The experience with the substance needs to be part of a process in which certain things happen before and after the experience itself. A recent study at Johns Hopkins' showed the impressive effects of psilocybin sessions in stopping cigarette smoking in patients for more than 6 months. But, psilocybin has this effect when inserted in a process like the one on the study, with sessions of cognitive-behavioral therapy. It’s not as simple as eating psilocybin “magic” mushrooms and then losing the craving to smoke, although it would be wonderful if it were that easy!

How can an intense psychedelic experience lead to important changes in daily life? We need to desire them, and make a determined effort to change. Usually, those kinds of changes are supported in a relationship, be it with a therapist, a doctor, a healer, a shaman, a religious leader, or a group. Each one of the psychedelic substances tested exist within a context: specific ways of understanding the substance use and different ways of dealing with them; sometimes, in a religious, modern or traditional ritual. Those relationships are important for the patient when going through the process, and also to give meaning to the experience.

Many patients arrive expecting a “magic pill,” a new medicine that would solve everything for them, and that has a negative effect on their process. I receive patients in my office before, and after they take ibogaine. Most of the time I can clearly see a difference: they are calmer, it’s easier to face daily challenges and focus on what is important in their lives, and there’s a lack of craving. But it doesn’t mean that the addiction is cured, and not all of them can take advantage of these effects to really overcome their problem.

After ibogaine, many patients are aware of all they need to change in their lives; but really changing their habits is usually harder, as it depends on the patients. If the substance had solved everything for them, why change anything else in their routine? Many of them can’t get out of their established routines, and after, they just go on living in the same way: going to the same bars, meeting the same friends, looking for the same types of pleasures, and one day or another they’ll return to problematic drug use. When we need to change, it will always require effort from ourselves, but if we expect for someone or something to solve our problems for us, it may not be possible.

So, despite the increasing interest in ayahuasca, iboga, ibogaine, psilocybin, and other psychedelics in general, those substances, and the experiences they trigger, are still a new and vast continent to be explored. We are only now beginning to understand the complex interactions between psychedelic substances, psychology, and the setting in which people consume the psychedelic substances. It seems that psychedelics function differently from the traditional Western medicine remedies, and may be better understood as a therapeutic tool.

https://chacruna.net/treating-patients-with-ibogaine-ayahuasca/​

 

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Can Ibogaine Treat Depression?

by Sophie Saint Thomas & Dr. Benjamin Malcolm, PharmD, MPH, BCPP

From tribal ceremonies in Africa to the treatment of opioid use disorder in the West, people are using ibogaine, but can it treat depression?

Ibogaine is notorious for potent anti-addictive effects and works differently from other psychedelics, although has higher medical risks and is not well studied in depression.. Despite ibogaine’s risks, in select persons, it could be worth considering, particularly if depression occurs alongside or is associated with an opioid use disorder or other addiction.

What is ibogaine?

Ibogaine is an alkaloid derived most commonly from the root bark of the Tabernanthe iboga shrub, although also found in other plant species (e.g. voacanga). Ibogaine is classified as a psychedelic and hallucinogen, although is perhaps most accurately described as an oneiric (producing a lucid dream-like state) substance. It targets different receptors and neurotransmitters than psychedelics like psilocybin or MDMA. For example, ibogaine seems to primarily work on opioid, glutamate, and dopamine neurotransmitter systems, while psilocybin and MDMA work primarily on serotonin. Ibogaine is long-acting and is metabolized to another compound, noribogaine, that has an even longer duration of action.

Due to the endangered status of the iboga shrub, most ibogaine providers are currently working with voacanga derived ibogaine hydrochloride, a sustainable alternative to iboga-derived ibogaine. However, when we talk about ibogaine, we are usually talking about what we know from experience with iboga extracts. The Pygmy tribes of equatorial west Africa have been using iboga for millennia as a rite of passage, a tool to connect to ancestral roots, and as a method for medicinal healing.

French explorers noticed and set their eye on the practice of using iboga root bark in tribal ceremonies in the 19th century, in particular, the naval physician Gabon Marie-Théophile Griffon du Bellay. The psychedelic made it’s way back to France, where it was first isolated from T. iboga in 1901 using T. iboga samples from Gabon. It was sold in France as Lambarène, as a stimulant and a mental and physical performance enhancement drug, during the 1930s to 1960s, and even taken by World War II athletes before it became illegal in 1966.

In the United States, ibogaine was first lauded for its anti-addictive properties in 1962 by Howard Lotsof, when he broke his heroin addiction with a single dose. He went on to found the Global Ibogaine Therapy Alliance (GITA) and patented ibogaine as an ‘interrupter of narcotic addiction’. Most published ibogaine research focuses on addiction. Research, studies, and even anecdotal reports indicate that ibogaine is anti-addictive for many substances, such as opioids, alcohol, nicotine, and cocaine. In addition, ibogaine is unique in that it appears to almost completely eliminate the withdrawal effects of opioids.

It is still used around the world today, both therapeutically and ceremonially. Due to barriers to access, the potential for adverse effects, long duration of action, and reputation for not being the most pleasant experience, there is little to no recreational value in ibogaine. Many people travel to countries with legal grey areas where the substance is ‘unregulated or ‘unscheduled’, such as Mexico, South Africa, and Canada. There are also treatment centers in Costa Rica, the Bahamas, and other clandestine locations.

Ibogaine can cause fatality from arrhythmias or cardiopulmonary arrest. While many more persons die on a daily basis of opioid overdoses in the US than have ever been reported to die from use of ibogaine, these risks argue the case that ibogaine should only be taken under medical supervision with monitoring and emergency medical support available.

Can ibogaine treat depression?

There is little evidence from studies that ibogaine is able to treat depression. his is perhaps because the limited research has focused on the potent anti-addictive effects. It stands to reason that if ibogaine can effectively help a person recover from heavy addictions to substances like heroin and cocaine, that person’s mood could significantly improve as a result. Similarly, if ibogaine can eliminate withdrawal symptoms, it may plausibly help post-acute withdrawal symptoms such as depression. Many psychedelic-assisted therapies appear to have ‘transdiagnostic’ potential, meaning they can treat a number of mental illnesses. This flexibility is perhaps due to the rewiring of core traumas that underlie negative emotional states and substance use disorders. Specifically, ibogaine promotes neurogenesis and neuroplasticity due to its mechanism of action with neurotrophic factors GDNF and BDNF that may explain how it resets addiction neurocircuitry or targets the lack of motivation or interest in pleasurable activities that accompanies depression (e.g. anhedonia). Given other psychedelics such as ketamine and psilocybin have much more data supporting their benefits in depression and much lower medical risks than ibogaine, it may be more reasonable to try other psychedelic therapies before considering ibogaine unless opioid use disorder or another serious addiction is present for depression.

What can I expect from an ibogaine experience?

As with all psychedelics, dose, set, and setting factor into the quality of experience. Persons should undergo medical screening that measures electrolytes, liver function, and their heart (EKG) as well as avoid any contraindicated medications (including antidepressants, many psychiatric medications, and even some OTC medications).

The experience lasts intensely for 12-18 hours and could last 24 hours or more total. Nausea and vomiting can occur and participants may feel off-balance or dizzy if they try standing up. Expect to be in bed or lying down for at least the first 12-18 hours of your trip.

In general, ibogaine trips can be summarized into three parts:​

1. Visionary phase: The visionary (or acute) phase starts one to three hours after consumption and usually lasts for four to eight hours, some individuals report longer. People describe it as an awake but dreamlike state (oneiric). There are intense hallucinations, such as visits from otherworldly beings, ancestors, and past life or repressed memories. Unlike visuals on LSD, whereas the person experiences hallucinations immediately around them, an ibogaine trip is more an introspective review, akin to a lucid dream, of one’s self as the ego takes a backseat.​
2. Introspection phase: The introspection (or evaluative) stage is where the healing takes place. It begins about four to eight hours after taking ibogaine and can last eight to 20 hours. While still psychoactive, this phase usually has fewer visions or memories and more thoughts and inner dialogues often related to processing trauma and the intentions or reasons for seeking out ibogaine. Some people report they are able to process the revelations they experienced in the visionary stage and others describe life-changing epiphanies.​
3. Residual stimulation phase: The residual stimulation phase begins 12 to 24 hours after taking ibogaine and can last 24 to 72 hours or more. This is the phase where the person begins to integrate their ibogaine experience into everyday life. There is usually a day after ibogaine that is emotionally challenging that is sometimes referred to as a “grey day”. The“ibogaine glow” many speak of usually begins once someone sleeps after their grey day.​

While this acts as a loose guide to the ibogaine experience, it varies from individual to individual.

Though ibogaine shows tremendous potential in addiction medicine, due to the intensity and duration of the experience, potential adverse effects, and access limitations, it’s worth looking into other psychedelics such as ketamine- or psilocybin-assisted therapies for depression first.

Can Ibogaine Treat Depression?

Medical Editor: Dr. Benjamin Malcolm, PharmD, MPH, BCPP From tribal ceremonies in Africa to the treatment of opioid use disorder in the West, people are

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Resets & relapses: Ibogaine's role in combating opioid addiction

by Benjamin Taub | Talking Drugs | 9 Dec 2015

In a recent TED Talk, journalist Johann Hari suggested that "The opposite of addiction is not sobriety. The opposite of addiction is connection." In other words, drug misuse often occurs as an attempt to fill the void when the social bonds that give meaning to our lives are missing or broken.

To highlight his point, Hari cites Bruce Alexander's Rat Park experiment, in which rodents kept in solitary confinement displayed a high propensity for drug misuse, while those with social stimulation did not. Naturally, this experiment is unlikely to ever be repeated using human subjects, although having spent the past year working at an ibogaine treatment centre, my experiences all point towards a very similar conclusion.

By way of introduction, ibogaine is a highly psychoactive alkaloid found in the root bark of a West African shrub called iboga. Because of its potent hallucinogenic effects, the plant has been used in spiritual healing and initiation rituals by indigenous communities for centuries, and in 1962 somehow found its way into the hands of a heroin-dependent New Yorker named Howard Lotsof.

After ingesting the substance and undergoing an intense psychedelic trip, Lotsof was astounded to discover that his opiate withdrawals and cravings had completely vanished -- an effect which has since been confirmed by a number of small-scale clinical studies.

As a consequence, an underground network of global ibogaine providers has sprung up over recent decades in places like Mexico, Costa Rica and New Zealand. However, with the substance being outlawed in several countries (including the US) and totally unregulated by the mainstream pharmaceutical industry, it remains off the table as an official treatment option.

Therefore, while some have labeled ibogaine a magic bullet for addiction -- citing the many anecdotal reports of people who have managed to end years of drug misuse with just a single dose of ibogaine -- the reality is that research into its long-term effects has been stunted, making it hard to separate the facts from the hype.

Yet if there's one thing I've learned from working with ibogaine, it's that it doesnt cure addiction all by itself. Rather, as the following case studies highlight, when combined with the healthy restructuring of someones social environment, it can provide a unique and powerful tool in the quest of those seeking to tackle their addiction.

Erika's story

"I saw myself shrink into oblivion and just disappear off the face of the Earth, before re-emerging as a new-born baby. It's like I've been given the chance to start again as a completely new person -- like a second opportunity."

This was how Erika described her ibogaine experience immediately after her treatment. Like almost all patients, she felt her withdrawals completely disappear soon after ingesting the substance, while at the same time undergoing an intense physical and psychological detox, which manifested itself as a vision of her own death. She described the sensation as 'a kind of bodily and mental reset.'

However, within two months of her treatment, Erika relapsed. Trying to come to terms with how this happened, she explained that although she didn't feel any physical cravings, she simply did not know how to live without drugs, and was unable to occupy the social world of people not suffering from addiction.

"I tried to make new friends so that I could leave all my old contacts behind and start again, but none of them really understood me," she said. "So in the end I had nowhere to go with this second opportunity that ibogaine had given me."

As a result, she soon found herself back at the house of her ex-boyfriend, who had always been her main supplier of heroin, and it wasn't long before she began using again.

Summing up, Erika stated that "ibogaine can give you the chance to start over, but if you go back to all your old places and your old people, it won't work. You'll just become your old self again."

Erika's story exemplifies Hari's point, that tackling addiction requires more than just physical sobriety; it involves the construction of a new lifestyle, supported by new social relations.

By allowing users to temporarily shed parts of their ego, along with their withdrawals, the ibogaine-reset effect represents just the first step of this process: it offers a doorway out of the world of addiction, but doesn't necessarily provide anywhere else to go; it breaks a persons bond with a drug, but doesnt replace that bond with a new and healthier one.

Therefore, as the following case demonstrates, successfully leaving addiction behind can more often than not only be achieved by connecting to others.

David's story

"I visualised all the bad relationships in my life, and realised I had to end them. Then I saw myself covered in black horns, which began falling off one by one. It was like the old me was dying and I was becoming a new person, like a total reset."

David's description of his ibogaine experience bears many similarities to that of Erikas, with the main difference being that one year later, he hasn't relapsed. This he attributes to his ability to develop his identity as a new person, not only in his own eyes but those of others as well.

"Since my treatment, everyone says I'm a different person" he explains. This has enabled him to repair many of his broken relationships and transform his social environment. For instance, he claims that "even my mother, who previously wanted nothing to do with me, says I'm completely different now, so shes accepted me back into the house. We've even gone into business together."

Thus, while ibogaine provided David with the tools to overcome his cravings and face his demons, it was the support of those around him that ultimately helped. Unlike Erika he had somewhere else to go. His final assessment of ibogaine subsequently mirrors Hari's opening sentiments: "Ibogaine gives you that reset that everyone talks about, but it only works if you have a support network which you can integrate into the process. As long as you can do that, you'll be OK afterwards."

Resets & Relapses: Ibogaine's Role in Combating Opiate Addiction

In a recent TED Talk, journalist Johann Hari suggested that “the opposite of addiction is not sobriety. The opposite of addiction is connection”.

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​

Ibogaine Treatment and Opiates*

by Shea Prueger and Katie Stone

Ibogaine is well known for its role in opiate addiction treatment. Ibogaine has been shown to eliminate acute opiate withdrawal symptoms and diminish or eliminate post-acute withdrawal syndrome (PAWS) often in a single treatment. Ibogaine is also known for its visionary state. Ibogaine’s dream-like state is not fully understood but is most likely triggered by ibogaine catalyzing across multiple neurotransmitters and receptor sites including serotonin and kappa-opioid receptors, as well as sigma receptors, glutamate receptors, and the cholinergic system.

Unfortunately, ibogaine’s psychoactive mechanism of action is still poorly understood. EEGs performed have shown a similar process to rapid-eye-movement (REM) occurring, classifying ibogaine as an oneirogen and not a traditional hallucinogen. It is theorized there is a state of neuroplasticity during the “waking dream” that allows for rapid reconsolidation of learning as well as “unlearning” of reactive behaviors. The insights one receives during this experience may help individuals get to the roots of their dependency and move forward with new habits.

However, individuals with significantly large opiate habits may not see their dependency eliminated with a single ibogaine “flood dose”, a large dose of ibogaine that “floods” the receptors and puts the participant in a waking dream state (flood dosage is individualized to the participant’s physiology, weight, ECG, size of opioid habit, and sensitivity to ibogaine). They may also need a short series of booster doses administered in the days following their flood dose if PAWS is an issue.

Long-acting opioids like buprenorphine (Suboxone) and methadone have created some diversion from well-practiced ibogaine treatment protocols. According to many ibogaine providers in the field, long-acting and synthetic opioids may require a long period of time on a short-acting opiate (SAO) before treatment to avoid breakthrough and post-acute withdrawals (PAWS). Before we dive into the new challenges of ibogaine treatment, we will review some basics about opiate dependence and treatment today.

Opiate dependency

Opium has been used in traditional medicinal remedies for millennia. Short-acting opiates (SAOs) such as heroin are derived from opium. Opiates are drugs that work by binding to opioid receptors, which inhibit pain signals from being sent to the brain. This makes opiates powerful medicines for alleviating pain and easing suffering.

In addition to their analgesic effects, they produce pleasurable effects such as euphoria or feelings of relaxation. However, because they bind so tightly with these receptors, it can lead to dependence and addiction when abused for an extended period of time. The most common types of street opioids are heroin and the synthetic opioid fentanyl, while buprenorphine (Suboxone) and methadone remain popular maintenance opioids.

Maintenance opioids such as Suboxone and methadone are semi-synthetic and synthetic long-acting opioids. These are usually prescribed to help people stop using opiates like heroin. Suboxone binds to the receptors in the brain that would normally be occupied by heroin, reducing withdrawal symptoms and blocking the effects of other opiates.

Opiate withdrawal

Symptoms of opiate withdrawal mimic a severe-flu like illness with the addition of depression. If untreated, persistent vomiting or diarrhea can lead to electrolyte imbalances and stress the heart. The onset of withdrawal for short-acting opioids such as heroin is usually between 8-24 hours since last use and lasts for 4-10 days.

Withdrawal with synthetics such as fentanyl, Suboxone, and methadone is longer. The onset of withdrawal can begin 12-72 hours after last use and last for weeks and even months. There are many anecdotal reports of people who are prescribed Suboxone being in withdrawal for up to 90 days, as well as people who use fentanyl and methadone being in withdrawal for weeks or longer, despite current literature that suggests withdrawals from these synthetics should be much shorter. This creates challenges for ibogaine providers who need protocols that will guarantee a person can leave an ibogaine treatment without withdrawals.

Mesolimbic reward system and withdrawal

One of the brain circuits activated by opioids is the mesolimbic (midbrain) reward system. This system generates signals in a part of the brain called the ventral tegmental area (VTA) that result in increased release of dopamine, causing euphoria and pleasure associated with opioid use.

“Conditioned associations” are links between an individual’s environment and how they feel when that environment triggers thoughts of drug use. These are memories imprinted in the brain, and encountering these places, and people can lead to cravings for drugs, feelings of withdrawal, or feelings of pleasure.

The mesolimbic system is involved with tolerance, cravings, and dependence; as a result of repeated opioid use, the reward center becomes less responsive to naturally rewarding stimuli such as food and sex.

Kratom as an opiate substitute

Some people who experience opiate dependencies turn to kratom, an extract from a tree in the coffee family that grows in sub-tropical regions such as Thailand and Malaysia. Kratom has different effects at different doses, and in higher doses, it can be used as an opioid substitute and in managing opiate withdrawal symptoms.

Kratom is currently legal in the U.S. aside from five states and can be bought without a prescription at health food stores, gas stations, tobacco shops, and other stores. Some states have introduced restrictions such as age (Oregon), but kratom remains largely unregulated in the U.S.

Kratom contains a compound called mitragynine that is cardiotoxic, prolonging the QT interval and potentiating Torsades de Pointes. Kratom is contraindicated with ibogaine as a result of its cardiotoxicity and complex pharmacology, specifically at serotonin transmitters.

Tramadol, a synthetic opioid with a low affinity at opioid receptors that also acts as an SNRI, can also possess withdrawal symptoms similar to antidepressants. Tramadol and kratom may have similar withdrawal symptoms. Some ibogaine providers advocate for longer times away from these substances before ibogaine to bypass the antidepressant withdrawal effects and cardiotoxicity in the case of kratom.

Finding an ibogaine clinic

Prospective clients will need to seek out an ibogaine clinic that is proficient with opiate detoxes and has the capability to stabilize them on an SAO for multiple days before treatment. This will allow a provider to get to know the client’s rate of opiate metabolism, physiology, and sensitivity to ibogaine before the ibogaine treatment begins. Ibogaine clinics are located around the world, mostly concentrated in Mexico and Central America. Vet options thoroughly as opiate detoxes can be complex and carry higher risk, and as we discuss in this article, fentanyl and the new era of opioid use has created the need for new ibogaine protocols that not all providers adhere to.

Ibogaine treatment for opiate withdrawals

Once ingested, ibogaine is metabolized by the liver and converted into a compound called noribogaine. This molecule interacts across many brain systems, including opioid receptors, and may be responsible for many of ibogaine’s long-lasting benefits.

Ibogaine is typically administered in a “flood” dose by ibogaine providers in a clinic about 9-12 hours after a client’s last opiate dose. In several studies on ibogaine, opiate withdrawals, tolerance, and cravings were completely eliminated within the first 48 hours of treatment, with initial withdrawals subsiding within the first three hours.

In one study, post-acute withdrawal syndrome (PAWS), drug cravings, and depressive symptoms measured by the Beck’s Depression Inventory were significantly alleviated and documented in observational studies in the days after ibogaine treatment. Patients also experienced psychological introspection and insight.

Finally, there seems some variability in ibogaine’s ability to interrupt withdrawal symptoms with synthetic opioids like fentanyl. Most providers will suggest a “switch-over” time to an SAO to avoid PAWS and medical complications during treatment.

Ibogaine safety with opiates

A prolonged QT interval is a QTc at or above 440ms in men and 460ms in women. Borderline QTc ranges used in ibogaine treatment to screen for potential ibogaine candidates may vary but are often around 420-440ms. Ibogaine prolongs the QT/QTc, which increases adverse reactions such as fatal arrhythmias.

In a 2020 study, 14 opioid-dependent individuals (all screened for exclusion criteria) were stabilized with morphine for eight days and then given 10mg/kg of ibogaine HCL to assess average QTc prolongation. Half of the participants had a QTc above 500ms. After 24 hours, half of the participants were still prolonged over 450ms. The study highlights the dramatic impact of ibogaine on QT/QTc even in a relatively small flood dose. The study also suggested that repeated low dosing protocols should be further explored, especially for higher-risk clients.

A repeated and low dosing protocol is a newer protocol some providers advocate for individuals who don’t meet all of the inclusion criteria for a flood dose or those on long-acting opioids that cannot complete a switch-over to an SAO. However, it requires vigilant safety and a provider proficient in the methodology. It cannot be stated enough to vet providers thoroughly.

Ibogaine is often dose-dependent for opiate habits. The larger an opiate habit, the more ibogaine someone might need. QTc may prolong with dose as well. People who use opioids are advised to exercise caution when choosing a center and be evaluated thoroughly by an ibogaine provider.

New challenges in ibogaine therapy

Ibogaine works as a rapid and effective addiction “interrupter” for short-acting opiates (SAO) such as heroin, oxycodone, hydromorphone, hydrocodone, codeine, and morphine. However, many providers report that persons using maintenance opioids, semi-synthetic, and synthetic opioids sometimes experience breakthrough withdrawals during a flood dose and may experience post-acute withdrawal syndrome (PAWS) for many weeks or months if they don’t switch to an SAO for an extended period of time beforehand. PAWS is characterized by impairments that can last for weeks or months and relate to mood disorders, insomnia, and anxiety following withdrawal from some drugs.

In recent years, ibogaine treatment for opiates has become less straightforward with the many different opioid options we have today. Nearly all street opiates may be cut with fentanyl, reports of a quinine cut source of heroin called “scramble” has been found on the east coast (thus automatically prolonging the QT), kratom — while not a traditional opioid — appears to cause opioid-like withdrawals, and a rise of people interested in quitting buprenorphine (Suboxone and Subutex) and methadone have all created unique challenges with ibogaine treatment protocols. The number one challenge is that without a switch-over to an SAO for a sufficient amount of time, withdrawals are a part of treatment, defeating one of the main reasons people seek out ibogaine.

New synthetic opioid treatment protocols. What is the answer?

Ibogaine providers and former people prescribed Suboxone repeatedly talk about post-acute withdrawal syndrome (PAWS) after ibogaine on internet forums and within the ibogaine community and the need for longer switch-over times industry-wide; it was even a topic at the 2014 Global Ibogaine Therapy Alliance annual conference. Some providers agree that switching to an SAO for 90 days is the only way to guarantee an absence of PAWS. There is currently no research regarding the protracted withdrawals for months that ibogaine seekers and those who opt for tapering off Suboxone sometimes experience.

Withdrawals from synthetics and long-acting opioids, including compounds like kratom are anecdotally very individualized. Some people need less time than others, but there is no diagnostic tool to predict who will need less time. The question has to be asked, is it worth rushing into treatment to possibly have withdrawals for weeks or months? Currently, some ibogaine providers ask for a 90-day switchover in someone prescribed Suboxone, citing they haven’t seen any withdrawals or PAWS if an individual waits this long. Some providers also ask for at least a month on an SAO for methadone, two weeks for fentanyl, one to three weeks for kratom (often depending on diagnostic tests and habit size), and tramadol can vary from 2-6 weeks (also depending on habit size and length).

One thing that all of these opioids have in common is they are semi-synthetic or synthetic opioids. Natural occurring short-acting opiates do very well with ibogaine. The other thing they all have in common is that they present very unique challenges for ibogaine providers and those seeking out ibogaine treatment. Protocols tend to be individualized to fit each client’s needs, but making an incorrect guess for a switch-over time may lead to debilitating withdrawal symptoms. In the case of synthetic opioids, longer time off may be better.

Where is ibogaine treatment for opiates headed?

Unfortunately, fentanyl and heroin use is at an all-time high, which will invariably lead to more prescriptions of Suboxone and methadone. The desire to quit opioids without withdrawals is not a sentiment that is going away. The ibogaine community needs to brainstorm programs and protocols to assist persons who have found themselves in the challenging category of needing multiple weeks or months on an SAO to serve their client base better. Internet forums often contain posts of people leaving centers in withdrawal.

Until research dives into the neurobiology of why people experience withdrawals for so long, the ibogaine community is left with questions, baseless theories, and many people who are desperate for help. This desperation in an unregulated industry has left a space for some centers to promise they can detox people straight off Suboxone or methadone. Educating people who are interested in ibogaine treatment is the best way to protect people.

The good news is that ibogaine remains to seamlessly eliminate short-acting opiate withdrawals such as heroin, morphine, and oxycodone. It is still possible to get treated for opiate dependency, but some people might have a longer path to treatment.

We do not have clinical evidence for why fentanyl, Suboxone, methadone, kratom, tramadol, and other synthetics produce such variable withdrawal times in individual people. This article offers anecdotal evidence and observational claims from ibogaine providers who have a combined 25 years of experience with ibogaine, as well as many stories from former clients. Also, a thank you to Agnes Bos for her continued insight and knowledge.

*From the article here :

The New Era of Ibogaine Treatment and Opiates: What You Need to Know

Ibogaine for Opioid Addiction Ibogaine and Substance Abuse Disorder Ibogaine is well known for its role in opiate addiction treatment. Ibogaine has been

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Ibogaine’s unique impact on Neuroplasticity

by Katie Stone | Psychable | 3 Apr 2022

The idea that the human brain can change its physical structure and function in response to changes in environmental input has been around since the late 19th century, but it was only recently that technology allowed us to measure these changes objectively.

It was even more recently when we learned that certain psychedelics support neurogenesis (the growth of new brain cells) and neuroplasticity (the ability for your brain to create new neural pathways and connections). Ibogaine, a psychedelic medicine derived from the iboga shrub native to Gabon, is one of those psychedelics that may be quite beneficial in this regard.

Ibogaine is most well-known for its ability to address opiate withdrawal. While the exact mechanism by which it accomplishes that is unknown, research is finding that ibogaine interacts with the nervous system by activating numerous neurotransmitters that create a wide range of effects in the brain, including neuroplasticity.

Before we get into the specifics about ibogaine’s impacts on neuroplasticity, we’ll dive a little deeper into the science behind it.

What is Neuroplasticity

For much of the history of psychology, researchers were under the impression that the adult personality is established around age thirty and has very little room for change. There was even a belief that one had a limited number of brain cells and that these cells could not be replaced – a hypothesis that has been disproven.

The discovery of neuroplasticity has changed this view. We now know that the brain can evolve throughout life in response to internal factors and external events or stressors. It is understood that the brain can change throughout life in response to experience, both positive and negative.

There are three significant proteins we will talk about that mediate neuroplasticity in the brain. The first is BDNF (brain-derived neurotrophic factor), the second protein is called GDNF (glial cell-line derived neurotrophic factor), and the third is NGF (nerve growth factor). Ibogaine acts on receptors that modulate the release of all three of these proteins — which makes ibogaine different from other psychedelic compounds.

These proteins are known as neurotrophic factors, and they work together to promote survival, growth, and maintenance of the central nervous system (CNS). It has long been known that these proteins are essential during childhood development, but they have recently been recognized as critical to the adult brain as well.

BDNF and GDNF have also been shown to play a role in modulating addiction behaviors in animal trials.

Ibogaine and BDNF

BDNF is a protein that is released in response to neuronal activity. It stimulates the growth, survival, and differentiation of neurons as well as their connections with each other. These connection points are called synapses. Classical psychedelics like psilocybin increase BDNF by acting on the same receptor as serotonin, the neurotransmitter that regulates mood. Low levels of BDNF have been linked to diseases like Alzheimer’s, Parkinson’s, and Huntington’s disease.

Ibogaine and GDNF

GDNF is a protein that is responsible for maintaining the health and survival of dopaminergic and motor neurons in the brain. GDNF may also stimulate the release of dopamine and other neurotransmitters in synapses, affecting synaptic plasticity. GDNF also plays a role in neurodegeneration, which is thought to be connected to Parkinson’s disease, specifically at the dopamine receptor. As far as we know, ibogaine is the only compound that can stimulate the release of GDNF naturally.

Ibogaine and NGF

NGF works to maintain the health of nerve cells called neurons. NGF is essential for learning and memory, playing a vital role in the preservation of brain cells. It has also been shown to stimulate new neuron growth, which can be beneficial during recovery after a stroke or traumatic brain injury to replace damaged tissue.

Ibogaine supports Neuroplasticity

Neuroplasticity refers to “the ability of neural networks in the brain to change through growth and reorganization.” One way that brain cells grow is through a process called dendritic branching. Dendrites are the branching roots of the nerve cell that connect to other nerve cells, creating spaces of connection called synapses where neurotransmitters interact and can be taken up into the cell for transport to the appropriate channels of activation.

Once ibogaine is metabolized in the liver into noribogaine, noribogaine then binds to specific receptors and begins to active neurotransmitters that stimulate the release of neurotrophic factors. So while ibogaine is the starter compound, once it has been ingested and metabolized, noribogaine is leading to the resulting neurogenesis.

In one study involving rats, ibogaine was found to catalyze neuroplasticity in a dose-dependent manner. The researchers demonstrated that ibogaine alters the cellular transcription levels of both GDNF and BDNF. This means that ibogaine regulates the rate at which the neurons produce and release these compounds.

The researchers administered ibogaine to rats in a time and dose-dependent manner, analyzing the various neurotrophic factors present in the brain post-mortem. After checking the rats’ brains for variations across dose, time, brain region, and concentration of neurotrophic factors, researchers suggest there could be potential for ibogaine to support neurodegenerative diseases such as Parkinson’s.

It is already well established in the literature that an increase in serotonin transmission results in an increase in BDNF expression. It is further well established that ibogaine and its metabolite noribogaine increase serotonin transmission because both compounds are serotonin-reuptake inhibitors, meaning that they help keep serotonin available for interaction in the synapses.

Ibogaine also interacts with NGF, which may be involved in specific areas of the brain connected to substance-seeking behavior. However,t this protein is less studied than BDNF and GDNF. There is evidence that NGF levels are decreased in the brains of alcohol-treated mice, specifically in the hippocampus and hypothalamus. These conditions were also apparent in the serum of chronic heroin and cocaine users, which might suggest a common relationship between NGF and addictive behavior.

Ultimately, this study revealed that ibogaine administration impacts the expression of three neurotrophic factors: BDNF, GDNF, and NGF, resulting in the production of neuroplasticity. This verifies another study that classified ibogaine as a “psychoplastogen” for its ability to rapidly promote neurogenesis. While these are all promising results, until we have clinical trials to further investigate these effects in humans, we will not know the full impacts of ibogaine on neuroplasticity.

Ibogaine's Unique Impact on Neuroplasticity

Medical Editor: Dr. Lynn Marie Morski, MD, Esq Ibogaine and Neuroplasticity: An Overview The idea that the human brain can change its physical structure

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