By Tessa Eskin
Ibogaine recently made headlines with the commencement of Phase I/IIa trial testing treatment for opioid addiction at MAC Clinical Research. Opioid use disorder is widespread and notoriously difficult to treat, and the withdrawals can be physically and psychologically devastating. Ibogaine not only appears to reset the brain to a pre-addictive state but reduces many of the withdrawal symptoms.
Ibogaine is a natural psychoactive and opioid antagonist, or “addiction interrupter”. It is found in the root bark of Tabernanthe iboga, native to central west Africa, Cameroon, and Congo. For hundreds of years, the Punu and Mitsogo people of Gabon have ingested the root during Bwiti ignition rites. Boys coming of age embark on a dreamy trip that can last for days, emerging as fully initiated adults. The Bwiti religion also uses T.iboga bark to treat health issues, reduce fever, and as an aphrodisiac.
Dybowski and Landrin first isolated Ibogaine in 1901, and it was fully synthesized in 1966. Since then, researchers have developed several synthetic versions with the aim of treating substance use disorders. Studies in the late ’80s and ’90s focused on opioid withdrawal, with testing on rats and animals. Preclinical studies showed a reduction of cocaine and morphine abuse, and reward response to nicotine in animals. Ibogaine appears to ease withdrawal symptoms and reduces the craving for cocaine, morphine, alcohol, and psychostimulants.
What is it?
Tabernanthe iboga is a leafy green shrub with yellow or pink flowers and sweet fruits. The psychoactive alkaloids are located in the root bark, including ibogaline, ibogamine, and tabernanthine. Ibogaine, in small doses, acts as a mild stimulant. Larger doses produce an intense psychedelic trip with visual hallucinations and dissociative effects that can last up to 30 hours.
The initial effects start within 45 minutes of ingestion and last up to four hours. It’s common to experience auditory and visual hallucinations, or to feel as if you’re in a waking dream. Many then enter a phase of reliving impactful life experiences. This phase sometimes lasts up to 20 hours and may include deep insight into the psyche. In Ibogaine addiction treatment, this is the phase in which patients process the root cause of their addictive behaviors.
This dreamy psychotropic trip is caused by activation of the serotonin 2A receptor, similar to most psychedelics. The trip is also affected by a “voltage-dependent block” of NMDA receptors for glutamine. Glutamine is a prime neurotransmitter booster of the central nervous system which modulates cognition, memory, and mood. Over-activation of glutamate receptors may result in cell death, often associated with alcoholic or toxic neurodegeneration. By blocking these receptors, Ibogaine reduces the “excitotoxic damage” in the brain caused by substance dependency.
The natural indole alkaloid also targets opioid and acetylcholine. When ingested, Ibogaine converts to noribogaine, a metabolite that remains in the system for up to four months. It makes serotonin readily available, assisting with low moods, cravings, and other symptoms of withdrawal. Noribogaine targets brain regions affected by addiction, essentially rewiring the brain and reverting it to its pre-addictive state.
This allows for a 3-6 month reprieve from opioid cravings in which the brain returns to the plasticity of fetal development. Patients are able to process traumatic memories and reset habitual motor patterns that have been impacted by addiction.
Opioid withdrawal syndrome is not only an excruciating experience but can actually be life-threatening. The addiction quickly puts the body into a state of “artificial homeostasis”, becoming biologically dependant on the drug. The physiological mayhem of withdrawal includes a nasty list of responses such as craving, anxiety, fever, nausea, cramps, palpitations, and paranoia. Ibogaine not only gives the addicted brain a reset but also blocks many withdrawals symptoms. Administrators of the drug have also noted a rapid decline of post-withdrawal depression when given to recovering opioid addicts.
Ibogaine treatment still has a fair way to go in terms of mitigating certain risks, especially that of heart attacks or heart failure. This is due to its fatty structure which blocks hERG potassium ion channels that regulate the beating of heart cells. Researchers are currently exploring several structural variations to isolate any harmful effects. The most promising result is the compound tabernanthalog (TBG), shown to promote dendritic spine growth in cells. A team at the University of California found that TBG reduces alcohol and heroin addiction in mice and rats. A single injection protects heroin relapse for up to two weeks.
According to pharmacologist Bryan Roth, the TGB binds to serotonin receptors just like LSD and psilocybin without stimulating the brain’s reward centers. This means patients may soon be able to receive the psychological benefits of psychoactive drugs without hallucinations or any risk of dependency.
The upcoming rollout of clinical trials is a huge milestone, sparking new hope in the battle against opioid abuse and addiction. Additionally, Ibogaine is garnering interest as a potential treatment for depression, anxiety, and PTSD, which often overlap with addictive behaviors. With the world in a mental health crisis and exasperated by Covid-19 restrictions, these treatments couldn’t come soon enough.