Pharmaceutical Roots: “Opening Your Head” with Ibogaine Hydrochloride

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  • Source: LGC Mikromol
  • Date: October 07, 2022

Pharmaceutical Roots is a series of content from LGC Mikromol that investigates and describes the natural origins of pharmaceutical substances and provides a deeper dive into their uses, risks and mechanisms of action.

Introduction

tabernanthe iboga (iboga) is a native plant of Gabon, the Democratic Republic of Congo and the Republic of Congo. Its root bark contains the psychoactive substance ibogaine, an indole alkaloid that “packs a serious psychedelic punch” and would have acts on the brain “like a hybrid of PCP and LSD”.

Although ibogaine has been illegal in the United States since 1967, both anecdotal reports aand search

studies suggest that it is a very promising candidate as an addiction treatment. For example, a small one-year study in New Zealand reported significant successs to prevent opiate-dependent participants from using drugs.

Meanwhile, a program that treated 51 US veterans for trauma-related psychological and cognitive disorders with ibogaine and 5-methoxy-N,N-dimethyltryptamine reported “big and very big discounts in a range of symptoms, including depression and post-traumatic stress disorder (PTSD).

Some countries, including UK, Canada and Mexico, allow ibogaine to be prescribed by clinicians to treat addiction, when there is growing interest researchers in developing the compound and its analogs to treat opioid addiction and a range of large-scale mental health conditions.

Story

Extracts from the iboga shrub have traditionally been used in healing rituals and initiation ceremonies by followers of the Bwiti religion in West Africa. At the turn of the 20e century, scientists Dybowski and Landrin observed canoeists and other inhabitants of the French Congo using the plant as a stimulant, noting: “They claim that the absorption of a certain quantity of the plant restores strength and makes it possible to resist fatigue for a long time, suppressing all need for sleep”. Dybowski and Landrin became the first to isolate ibogaine in 1901, and before being banned in the 1960s, it was sold in France as an antidepressant and stimulant called Lambarene.

During the 1950s, the United States Central Intelligence Agency (CIA) reportedly carried out secret research on the effects of drugs – the use of people dependent on opiates sentenced to compulsory rehabilitation a hospital in Lexington, Kentucky. The experiments would have been part of the notorious CIA program MK-ULTRA program who tried to find “a mind control drug that could be weaponized against enemies”.

More peaceful researchers led by former heroin addict Howard Lots then launched a series of clinical trials to study ibogaine’s ability to cure opioid addiction. Many of them, who in 1962 had experimented with ibogaine and discovered that he suddenly “kicked out” his addiction, found that seven other heroin addicts also had the same experience after taking ibogaine during “lay” drug trials he organized. During the 1980s, Lots worked with a Belgian company to produce a tablet form of ibogaine for placebo-controlled clinical trials, which demonstrated attenuation of opioid withdrawal in rats. Later studies showed that ibogaine was also apparently effective in reducing cocaine and alcohol addiction in rats, while a phase I human trial also showed that 25 out of 33 heroin addicts treated with the drug”showed improvement in their opioid withdrawal symptoms.”

ibogaine for treatment

Risks and Complications of Use Ibogaine’s growing reputation as a potential treatment for serious addiction, coupled with its continued illegality, has led to the emergence of a dangerous underground therapy market.

According to an article by Voice of the village, at least 19 people died between 1991 and 2013 while undergoing such treatments – “almost always by combining the hallucinogen with other drugs”. But, even for those who survive, taking ibogaine in an unauthorized setting can be extremely unpleasant. Bwiti practitioners describe the “journey” as break the headwhile other dangerous side effects include intense nausea and cardiac arrhythmia.

Modern ibogaine researchers, however, are confident that such side effects can be safely eliminated. managed in controlled laboratory environments, with appropriate medical support.

According to Dr. Srinivas Rao, Chief Scientific Officer at drug developers atai Life Sciences, careful dosing and further testing should in particular reduce the cardiovascular dangers that have traditionally been associated with the use of ibogaine. Rao also argues that – with America in the throes of an opioid crisis – finding an effective treatment for addiction would be probably justify a certain level of cardiovascular risk.

ibogaine

Action mechanism

Ibogaine is obtained by extraction from the iboga plant, or by semi-synthesis from voacangine, another plant alkaloid. It is highly lipophilic and subject to extensive biotransformation, primarily by the enzyme cytochrome P450 (CYP450) 2D6. It disappears from the bloodstream fairly quickly, with a half-life of 7.5 hours. Ibogaine and its analogs act on several neurotransmitter systems in the brain that may contribute to the ability to suppress autonomic changes, objective signs, and subjective distress associated with opiate withdrawal. It binds to many sites in the central nervous system, including serotonin, dopamine and sigma receptors, kappa and mu-opioid receptors, and the n-methyl-d-aspartate ion channel.

Outlook

Interest in the study of ibogaine experienced a lull after 1995, when the U.S. National Institutes of Health canceled its research program in it. But new companies have recently arose in hopes of developing commercially viable ibogaine-based treatments, as well as designing new analogues that could cure addiction without the “travel” associated with the drug.

Atai’s subsidiary DemeRx is currently conduct phase I/IIa clinical trials in the UK to assess the safety, tolerability, pharmacokinetics and efficacy of ibogaine, with initial data expected this year. However, atai is also investigating the potential of noribogaine, the main psychoactive metabolite of ibogaine, as it does not produce hallucinogenic effects and may therefore be suitable as a “maintenance treatment” that can be taken in the office or at home.

Meanwhile, David Olson, a professor of chemistry and neuroscience at the University of California, is looking to develop non-psychoactive analogues of compounds like ibogaine as treatments for drug addiction, depression and dementia.

His modified ibogaine molecule, Delix-7, attracted interest from the US National Institute of Drug Abuse, as well as considerable funding from commercial investors.

Designed to stimulate neuroplasticity in the brain via the 5-HT-2A receptor, the so-called psychoplastogens are currently scheduled for clinical trials in late 2022.

After four decades of being considered dangerous or subversive, psychoactive compounds such as MDMA, LSD and psilocybin are now firmly in the mainstream of pharmaceutical research, with 17 clinical trials of psychedelic drugs listed as ongoing in 2020. Ibogaine, with its longstanding reputation as a powerful therapeutic, now also appears ready for its own “moment”, and may yet provide the basis for treatments of tomorrow for substance abuse and mental disorders. troubles.

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