DARK Classics in Chemical Neuroscience: Ibogaine

Abstract

The West African iboga plant has been used for centuries by the Bwiti and Mbiri tribes to induce hallucinations during religious ceremonies. Ibogaine, the principal alkaloid responsible for iboga's psychedelic properties, was isolated and sold as an antidepressant in France for decades before its adverse effects precipitated its removal from the market. An ibogaine resurgence in the 1960s was driven by U.S. heroin addicts who claimed that ibogaine cured their opiate addictions. Behavioral pharmacologic studies in animal models provided evidence that ibogaine could blunt self-administration of not only opiates but cocaine, amphetamines, and nicotine. Ibogaine displays moderate-to-weak affinities for a wide spectrum of receptor and transporter proteins; recent work suggests that its actions at nicotinic acetylcholine receptor subtypes may underlie its reputed antiopiate effects. At micromolar levels, ibogaine is neurotoxic and cardiotoxic and has been linked to several deaths by cardiac arrest. Structure-activity studies led to the isolation of the ibogaine analog 18-methoxycoronaridine (18-MC), an α3β4 nicotinic receptor modulator that retains ibogaine's anticraving properties with few or no adverse effects. Clinical trials of 18-MC treatment of nicotine addiction are pending. Ibogaine analogs may also hold promise for treating anxiety and depression via the "psychedelic-assisted therapy" approach that employs hallucinogens including psilocybin and methylenedioxymethamphetamine ("ecstasy").

Psychedelic Treatment for Trauma-Related Psychological and Cognitive Impairment Among US Special Operations Forces Veterans

“… 24 Ibogaine was used in France for over 30 years as an anti-depressant and a stimulant until the mid-1960s. 25 Ibogaine treatment is reported to alleviate a spectrum of mood and anxiety symptoms 25 – 28 and is associated with self-reported improvements in cognitive functioning in individuals with substance use disorders. 29 – 31 During treatment, ibogaine allows the evocation and reprocessing of traumatic memories and occasions therapeutic and meaningful visions of spiritual and autobiographical content, 26 , 29 , 30 , 32 which are of central relevance in addressing PTSD-related psychological content.…”

A Single Administration of the Atypical Psychedelic Ibogaine or Its Metabolite Noribogaine Induces an Antidepressant-Like Effect in Rats

“…Ibogaine is the main indole alkaloid isolated from the root bark of the African shrub Tabernanthe iboga (Figure 1). [1][2][3] It is considered an atypical psychedelic drug capable of inducing waking dream-like states (oneirogenic effects) and vivid memory recall and replay. 4,5 Anecdotal reports and open label case studies with volunteers seeking detoxification from heroin and cocaine indicated ibogaine's ability to interrupt the drug dependence phenotype via rapid and lasting relief of drug withdrawal symptoms and cravings.…”

A non-hallucinogenic psychedelic analogue with therapeutic potential

“… The psychedelic alkaloid ibogaine has anti-addictive properties in both humans and animals. 1 Unlike most substance use disorder (SUD) medications, anecdotal reports suggest that ibogaine possesses the potential to treat patients addicted to a variety of substances including opiates, alcohol, and psychostimulants. Like other psychedelic compounds, its therapeutic effects are long-lasting, 2 which has been attributed to its ability to modify addiction-related neural circuitry through activation of neurotrophic factor signaling.…”