The historical use of Ibogaine dates back to the 18th century when it had crucial importance in Bwiti practice. By nature, this compound is an indole alkaloid and is a natural constituent of the plant Tabernanthe iboga. Tabernanthe iboga is a shrub native to Western Africa, and it was often used for religious or healing purposes by the tribes of Gabon. The bark or root of the plant is known for containing a high percentage of the substance ibogaine.
During the 19th century, this substance became the center of interest in the research of medicine after identifying its psychoactive properties. Several studies show that ibogaine possesses some anti-addictive properties that make it an effective choice to treat addiction, particularly opiate addiction.
Even though many experts believe ibogaine can be an alternative way to treat addiction, it has not yet been approved for legal use by Food and Drug Administration (FDA). Even in the US, Drug Enforcement Agency (DEA) has classified it as a Schedule 1 drug which means that no one is allowed the legal use of ibogaine to achieve any kind of physiological or pharmacological effects.
How does Ibogaine Acts Inside The Body?
Mechanism of Action
Being a tryptamine, ibogaines hows interacts with different neurotransmitter systems when it enters the body. The receptors for which ibogaine has been observed showing a greater affinity are:
Kappa-opioid and mu-opioid receptors
Sigma-2 receptor and
Besides possessing significant affinities towards these receptors, ibogaine has also been reported for interacting with the dopamine, acetylcholine, and serotonin systems. It also tends to alter the expression of some important proteins, which include substance P and brain-derived neurotrophic factor (BDNF).
It is said that the psychoactive effects of ibogaine result from its action at the kappa-opioid receptor. Furthermore, ibogaine also shows an agonistic effect on the serotonin 5HT2A receptor, which is not strong but plays a role in imparting ibogaine the hallucinogenic effects. Ibogaine also contributes to reducing dopamine levels in your body alongside the increase in the breakdown of dopamine. It works against opioid addiction by the reversal of opioid effects on gene expression. This causes the neuroreceptors to return to a pre-addiction state. Similarly, addictive pathways and loops are also reversed.
Metabolism of Ibogaine
Ibogaine is metabolized by the enzyme cytochrome P4502D6 and converted into its major metabolite Noribogaine (12hydroxyibigamine). This metabolism takes place through O-demethylation by cytochrome P4502D6. The process is rapid and occurs inside the gut wall and liver.
For nor ibogaine, it is reported that it possesses a slightly longer half-life than the parent compound and hence shows a higher plasma concentration than ibogaine. Noribogaine is also known as a more potent serotonin reuptake inhibitor and an agonist of kappa-opioid and weak mu-opioid receptors.
Due to the agonist action of nor ibogaine, it is considered a vital factor for the psychoactive effects observed after ibogaine intake.
The Pharmacological Effects Produced By Ibogaine
The pharmacological effects produced by ibogaine are of two types; hallucinogenic and anti-addictive. The hallucinogenic effect is produced when ibogaine binds with the receptors acting as an agonist, and when it acts as an antagonist, we achieve anti-addictive effects. Since ibogaine can bind with several receptors, it has complex pharmacological properties, and therefore, its clinical importance is gaining attention.
Among the multiple receptors, we listed above, when ibogaine binds with NMDA, it acts as an antagonist. Hence, it blocks the NMDA receptor activity. NMDA is the messenger of glutamate, aspartate, glycine, calcium, and amino acid. Glutamate is a vital neurotransmitter that acts as a booster for the central nervous system. Though glutamate is essentially required for normal brain functioning, its levels need to be strictly regulated because prolonged activation of glutamate receptors results in neurotoxicity that leads to loss of neuronal function and eventually cell death. To reduce this glutamate-induced cell death, ibogaine can be used, which will act as a noncompetitive inhibitor or antagonist of the NMDA receptor. This way, one will be protected against NMDA-induced convulsions. This activity of ibogaine can also be described as a mitigation of excitotoxic damage to the brain. Here the exact mechanism of action of ibogaine is not known yet.
Side Effects of Toxicities
O'Hearn and Molliverused a 100 mg/kg dose of ibogaine to administer to the rats and observe if the substance has any neurodegenerative effects. The results showed the signs of neurotoxicity in rats which were probably mediated by inferior olive stimulation. This degeneration occurred in the cerebellar Purkinje cells due to excitotoxic effects. However, this experiment has been recently carried out again by administrating 25 mg/kg drug intraperitoneally to the rats. Here, rats injected with lower doses did not show any neurotoxic effects. This reveals that the effects of ibogaine are quite dose-dependent, and there is a major difference between the anti-addictive and psychoactive effects of the drug.
The recommended therapeutic concentration of ibogaine can pose the risk of life-threatening cardiotoxicity. This cardiotoxic effect has been first reported in the case of a woman. Ibogaine was shown to interact with her hERG potassium channels located in the heart. These channels play a significant role during the repolarization phase. Ibogaine acts as a blockade of this repolarization resulting in delaying the phase. This causes the prolongation of QT waves that reduces the heart rate and ultimately develop arrhythmias and sudden cardiac arrest.
Among those who ingested ibogaine and had any pre-existing cardiovascular condition, 27 deaths have been reported. However, 8 cases of ventricular tachyarrhythmias have also been reported in people without pre-existing cardiovascular disease.
Toxicity from Drug-Drug Interaction
There are several drug-drug interactions encountered between ibogaine and other pharmaceuticals. Some of them are severe, while others are of moderate intensity. However, care should be taken in all conditions to avoid irreversible damages.
Following are a few of those interactions for your knowledge:
Paroxetine: Using ibogaine along with this drug can slow down the metabolism of ibogaine. It will result in severe side effects due to the high plasma concentration of ibogaine for a longer time.
Anticholinergic drugs: Anticholinergic drugs are used to treat conditions such as chronic obstructive pulmonary disorder and overactive bladder. These drugs block the activity of the neurotransmitter acetylcholine. However, ibogaine has opposite effects as it can cause a rise in the levels of acetylcholine. Therefore, taking both medications at the same time will block the effects of anticholinergics.
Cholinergic drugs: Both cholinergic drugs and ibogaine can increase the level of acetylcholine in the body. It will result in a significantly higher concentration, leading to many side effects.
Medications causing irregular heartbeat: Some medications may cause irregular heartbeat as a minimal side effect. However, using ibogaine with these drugs will increase the risk of heart problems as it can also produce similar effects.
Since sufficient information is not available, it is safe to avoid using ibogaine during pregnancy and breastfeeding.
What Is The Goal To Use Ibogaine?
Ibogaine and Opiate Addiction
Opiates or opioids are a class of drugs that have been primarily prescribed over a long period for their analgesic (pain relief) and anesthetic effects. However, these substances for tending to develop physical dependence were then prohibited to prescribe. But, the use of opioids had become common, and several people started using them to get high. To avoid encountering these psychedelic effects, the concentration of opioids ingested must be tightly regulated. Since the drug was readily accessible, it became quite challenging to control the drug abuse. This addiction that develops from prescription medicine abuse urged the need to formulate a medicine for the addiction treatment.
Ibogaine, a natural alkaloid, was found to have dual characteristics of anti-addictive and hallucinogenic. The effects produced vary from the intake of ibogaine. The studies that have been made after discovering the anti-addictive properties of ibogaine claimed that the substance can help reduce cravings as well as relieve opiates withdrawal symptoms which are very painful.
The current status of ibogaine is that it is legally banned in the United States. However, several rehab centers are allowed to use ibogaine for opioids and other addictions as well in Germany, Canada, France, and United Kingdom. Though ibogaine is in use in different parts of the world, it is suggested to use it under the experts’ supervision within the clinical practice as self-admiration may cause more harm rather than benefits.
Recommended Therapeutic Dose
Whenever ibogaine is used for its anti-addictive effects, one should strictly follow the recommended dose range to prevent the adverse effects that we have discussed earlier.
After some investigation that has been done to test the desired effects and associated risks, it is concluded that a 10-20 mg/kg dosage is regarded safe with minimal signs of neurotoxicity for the addiction treatment. Furthermore, if it is required for minor treatment, 5 mg/kg body weight will be enough but, to manage intense poly-substance addiction, a dosage up to 30 mg/kg can be administered.
Studies have also been made to determine the dose at which maximum toxicity will be observed. By conducting experiments on rats, it was reported that one-third of the sample rats developed neurodegeneration upon administration of 50 mg/kg ibogaine. While the dosage of 75 mg/kg caused all of them to develop Purkinje neuron degeneration.