What is Ibogaine?
Ibogaine is a psychoactive alkaloid derived from the root bark of some plants found in the West African rainforest (Tabernanthe iboga, Voacanga africana, and Tabernaemontana undulata). It has been traditionally used by tribes in Central Africa in ceremonies and religious rituals for its energizing and aphrodisiac properties .
Because of safety concerns, ibogaine is currently banned in the United States, Australia, and many European countries, including Belgium, Denmark, and Switzerland. It is legal in several other countries, including Canada and Mexico, where it’s mainly used for addiction treatment [2, 3].
Ibogaine, when consumed, is broken down in the liver and gut wall into noribogaine (12-hydroxyibogamine) .
Ibogaine and noribogaine have similar properties, but noribogaine remains in the body longer .
Mechanism of Action
The mechanism of action of ibogaine remains unclear. Some of its effects include:
- Inhibition of serotonin transporters: Ibogaine inhibits the reabsorption of serotonin from serotonin transporters, an action similar to many antidepressants, such as fluoxetine .
- Inhibition of dopamine transporters: Ibogaine has the same effects on dopamine transporters, resulting in higher dopamine levels. Dopamine levels in addicted individuals are altered due to the excessive use of abused drugs, such as cocaine. Ibogaine can reset the dopamine levels to pre-addiction levels, without leading to a new addiction .
- Inhibition of nicotinic acetylcholine receptors: These receptors are part of the neuronal pathway that modulates the brain’s reward system. Because of this, they are involved in the mechanism of addiction. Ibogaine blocks nicotinic acetylcholine receptors, thereby maintaining healthy levels of acetylcholine for longer periods of time [9, 10].
- Inhibition of NMDA receptors: Ibogaine blocks NMDA receptors, which accounts for its hallucinogenic effects .
- Opioid receptors: Although ibogaine and noribogaine bind to opioid receptors, they do not block them. This may explain why ibogaine does not reduce pain sensations but enhances the pain-relieving effects of morphine. Also, when used in high doses for opioid detoxification, it does not produce signs of overdose in people who are not addicted to opioids and cannot tolerate them [12, 13].
Uses of Ibogaine
1) May Be Used To Improve Addiction
Ibogaine was first introduced as an anti-addictive treatment in 1962 .
It reduces opioid use and withdrawal symptoms and stops drug cravings. In contrast to other drug therapies, such as methadone maintenance treatment, even a single dose of ibogaine can lead to opioid detoxification lasting up to 12 months post-treatment .
In a recent observational study, a single ibogaine treatment was administered to 14 opioid addicts. In the 12 months following the treatment, opioid use and craving were significantly reduced and in some cases even eliminated .
One study of 27 opioid addicts withdrawing from methadone opioid substitution therapy found that noribogaine was well tolerated, but only moderately improved opioid withdrawal symptoms .
Opioid detoxification as a result of ibogaine consumption was achieved in rats, mice, and primates .
Ibogaine also reduced symptoms of heroin withdrawal in 7 heroin-dependent patients .
2) May Act As An Antioxidant
3) May Boost Mood
Purified ibogaine hydrochloride was marketed under the name Lambarene in France (1939-1970) as an antidepressant and stimulator of mental state .
However, recent studies failed to confirm any specific beneficial effects on mood .
4) May Suppress Appetite
Synthetic iboga alkaloids have been proposed as a treatment for obesity in rats. Chronic administration of this substance in rats prevented increases in body weight, decreased fat deposition, and reduced sugar consumption .
5) Has Antimicrobial Properties
Studies in mice showed that iboga alkaloids reduced the number of deaths caused by Candida albicans infections. Ibogaine inhibits the activity of enzymes called lipases, which are used by Candida albicans to infect human cells. Therefore, when combined with a commonly used antibiotic, it suppressed fungus development .
Additionally, ibogaine has antimycobacterial activity, as shown by the reduction of bacterial cultures of several pathogenic microorganisms .
Finally, experiments conducted on human blood cells showed that ibogaine interrupts the replication of retroviruses (such as HIV–1), and blocks the infection process .
6) Has Anticancer Properties
In the lab, ibogaine reversed multidrug resistance in human cancer cells .
Ibogaine has been used as a natural treatment for infertility by the African community of Bwiti .
However, there are no available studies supporting this claim.
1) Ataxia and Vomiting
Two of the most commonly reported side-effects of ibogaine is involuntary and uncontrollable movement (ataxia) and vomiting .
2) Cardiac Arrest/Arrhythmia
Ibogaine can cause direct damage to the heart muscle or disrupt the electrical activity of the heart. In both humans and animals, high doses of ibogaine decreased the heart rate.
It does so by blocking the activity of an ion channel (ERG potassium channel), which transports electrical signals in the heart cells and regulates the beating of the human heart. This, in turn, results in arrhythmia (abnormal heart rhythm) and a high probability of sudden death .
3) Sudden Death
Several deaths have been reported to be attributed to the use of ibogaine. However, some of these fatalities may be due to preexisting medical conditions, such as heart disease or drug use during treatment [32, 31, 33].
There have been 3 reported cases where the use of ibogaine, either for self-treatment of addictions or psycho-spiritual experimentation, resulted in mania .
There has been 1 case in which ibogaine worsened symptoms of schizophrenia and induced psychotic episodes .
Although ibogaine has been widely suggested to reduce epileptic seizures, there have been reports of whole body tremors and epileptic seizures .
This difference could be due to the dose-dependent mechanism of action of ibogaine. In higher doses (35 mg/kg), ibogaine could trigger epileptic seizures, while in lower doses it generally has an anticonvulsant (anti-seizure) effect .
Administration of ibogaine has resulted in neuronal degeneration of Purkinje cells in the rat brain. The Purkinje cells are some of the largest neurons forming the human brain and are located in the cerebellum. This brain toxicity was observed at doses higher than the ones used for invoking its anti-addictive properties (50 to 100 mg/kg) .
On the other hand, noribogaine is considered less toxic to the nervous system than ibogaine .
However, the neurotoxic effects of ibogaine have only been verified on rats and no research has been done in humans yet.
This enzyme is responsible for the metabolism of many other substances in the human body. This similar route of metabolism may lead to dangerous drug interactions, which may increase the heart cell toxicity effects of ibogaine and enhance its side effects.
Some substances that could dangerously interact with ibogaine are :
The doses commonly used for opioid detoxification is in the range of 1 to 2 g, More specifically, it has been administered as a single oral dose in the range of 10 to 25 mg/kg of body weight [12, 39, 40].
Ibogaine was well tolerated with no adverse effects when administered in very low doses of 20 mg in one Phase I study (21 healthy participants) .
Similarly, a Phase I study (ascending single-dose, placebo-controlled, randomized, double-blind, parallel group) was conducted to test the safety and toxicity of noribogaine. Single doses of 3 to 60 mg of noribogaine were administered to 36 healthy drug-free volunteers and no adverse effects were observed .
CYP2D6 is responsible for the metabolism of amphetamine-like drugs, opioids, antidepressants, and numerous other pharmaceutical products .
People are divided into different classes of metabolizers, based on the allelic variants in their genome: Ultra-rapid, extensive, intermediate, and poor .
When administered with ibogaine, CYP2D6’s extensive metabolizers have lower ibogaine and higher noribogaine blood levels, compared to CYP2D6’s poor metabolizers that have a reverse pattern. Moreover, poor metabolizers were more prone to reach maximum blood concentrations of the drug. This condition makes poor metabolizers more vulnerable to heart problems caused by ibogaine .
Ibogaine is naturally present in three African plants:
- Tabernanthe iboga 
- Voacanga africana 
- Ervatamia officinalis (synonym to Tabernaemontana undulata) 
In Tabernanthe iboga, ibogaine is more concentrated in the root bark of the plant .
Ibogaine vs. 18-methoxycoronaridine (18-MC)
Derived from ibogaine, 18-MC is a synthetic iboga alkaloid. Although there are no studies yet testing its safety on humans, data from animal studies are very promising. 18-MC has all the anti-addictive properties of ibogaine .
Similar to ibogaine, 18-MC reduces the self-administration of several drugs of abuse in rats (morphine, cocaine, alcohol, and nicotine). It also improves opioid withdrawal symptoms .
Interestingly, 18-MC does not produce the unwanted neuronal and heart cell toxicity related to ibogaine. Given that 18-MC does not raise extracellular levels of serotonin or bind to the serotonin transporter, it is predicted that it will not have any hallucinogenic properties [47, 48].
Limitations and Caveats
Ibogaine’s prohibition in many countries worldwide has led to a limited amount of clinical and pharmaceutical research. Apart from its beneficial characteristics, the use of ibogaine has severe risks that are not fully researched or understood.
Further investigation of the short- and long-term effects of ibogaine, noribogaine, and 18-MC is needed. Although 18-MC seems like a safe and effective treatment for multiple forms of drug abuse, clinical trials need to be performed to verify its safety and effectiveness.