Posted on 02/14/2025 6:41:02 AM PST by Red Badger
In a study appearing in Nature Chemistry, UC Davis researchers report the successful total synthesis of ibogaine, ibogaine analogs, and related compounds from pyridine — a relatively inexpensive and widely available chemical. Here we see a neuron treated with the ibogaine analog (-)-10-fluoroibogamine, which showcased exceptional effects on neuronal growth and connection. Credit: Andy Domokos/UC Davis
The discovery opens up opportunities to study the therapeutic properties of ibogaine and related compounds. Ibogaine, a psychoactive plant derivative, has garnered attention for its anti-addictive and antidepressant properties. However, it is a finite resource, extracted from African plants such as the iboga shrub (Tabernanthe iboga) and the small-fruited voacanga tree (Voacanga africana). Additionally, its use can cause irregular heartbeats, posing safety risks and highlighting the need for a deeper understanding of how its molecular structure drives its biological effects.
In a study published in Nature Chemistry, researchers at the University of California, Davis Institute for Psychedelics and Neurotherapeutics (IPN) report the successful total synthesis of ibogaine, along with ibogaine analogs and related compounds, from pyridine—a relatively inexpensive and widely available chemical.
The team’s strategy enabled the synthesis of four naturally occurring ibogaine-related alkaloids as well as several non-natural analogs. Overall yields ranged from 6% to 29% after only six or seven steps, a marked increase in efficiency from previous synthetic efforts to produce similar compounds.
“Ibogaine’s complex chemical structure makes it hard to produce in significant quantities, and this challenging chemistry has historically limited medicinal chemistry efforts to develop improved analogs,” said the study’s corresponding author David E. Olson, director of the IPN and a professor of chemistry and biochemistry and molecular medicine at UC Davis. “Performing total synthesis solves both problems. We can make it without having to harvest tons and tons of plant material and we can also make analogs, several of which are demonstrating really interesting properties.”
Neurons (Nerve Cells) Treated With a Synthetic Analog of Ibogaine
Researchers at the UC Davis Institute for Psychedelics and Neurotherapeutics have found a route to synthesize the psychoactive drug ibogaine and related compounds. This will make it easier to study the therapeutic properties of ibogaine and similar drugs. Image shows neurons (nerve cells) treated with a synthetic analog of ibogaine. Credit: Andy Domokos/UC Davis
Despite the cardiac risk of ibogaine, Olson noted that the compound is gaining popularity as a treatment for substance use disorders, traumatic brain injury, and other conditions.
“Some people want to find ways to administer ibogaine more safely and you might be able to mitigate risk with careful cardiac monitoring and magnesium supplementation,” he said. “But maybe we just need ibogaine 2.0, a better version that still produces these profound anti-addictive and anti-depressant effects but doesn’t have that cardiac risk.”
Analogues of interest
Olson highlighted two ibogaine analogs of interest from the study.
The first analog was the mirror image of ibogaine. In chemistry, this mirror image trait is referred to as chirality. Like your left and right hands, such molecular compounds can’t be superposed on each other.
“Nature only produces one version and if the therapeutic effects of ibogaine are coming from interactions with another chiral entity, like an enzyme or receptor, then you would expect only the natural version to have an effect,” Olson said. “But if it’s non-specific, then both compounds would produce an effect.”
When the researchers tested the effects of ibogaine and its mirror image compound on neurons, they discovered that only the natural one promoted neuronal growth.
“This allowed us to show for the first time that ibogaine’s effects are probably the result of it being bound to a particular receptor,” Olson said. “We don’t have all the details of what receptor that is, but the unnatural compound is a good tool for probing this biology.”
The second analog of interest was (-)-10-fluoroibogamine. During experiments, the compound exhibited exceptional effects on neuronal structure and function, promoting growth and reconnection. Additionally, it showcased powerful effects on serotonin transporters, which are proteins that regulate serotonin levels at synapses.
“The serotonin transporter is the target of many antidepressants and is hypothesized to be relevant to ibogaine’s therapeutic efficacy,” Olson said.
The findings, according to researchers, indicate that (-)-10-fluoroibogamine should be further investigated as a treatment for substance use disorders, depression, and related neuropsychiatric diseases.
Safer and more effective medicines
According to Olson, the research was 10 years in the making with the team exploring multiple synthesis routes, each with varying levels of effectiveness.
“A lot of these iboga alkaloids and ibogaine analogs are not made from cheap, readily available starting materials,” Olson said. “The difference with our strategy is that we rely on very abundant, inexpensive chemicals, and we can assemble the pieces in just a few steps. Overall, our goal was to create a more efficient process.”
The research team hopes that their total synthesis strategy will provide researchers with a roadmap for efficiently accessing ibogaine analogs, ultimately leading to safer and more effective medicines
Reference:
“Efficient and modular synthesis of ibogaine and related alkaloids”
by Rishab N. Iyer, David Favela, Andras Domokos, Guoliang Zhang, Arabo A. Avanes, Samuel J. Carter, Andrian G. Basargin, Alexis R. Davis, Dean J. Tantillo and David E. Olson, 6 February 2025, Nature Chemistry.
DOI: 10.1038/s41557-024-01714-7
Research reported in this publication was supported by the National Institute of General Medical Sciences and National Institute on Drug Abuse of the National Institutes of Health under award numbers R35GM14182 and R01DA056365. The research was also supported by the Camille Dreyfus Teacher-Scholar Award.
BETTER LIVING THROUGH CHEMISTRY!........................
xxxxxxxxxxxxxxx
far out
Oh great, just when you thought that the 60’s and 70’s with tie dyed shirts, bell bottom pants, and a lack of hygiene was over, along comes another psychedelic
Yield was 6% to 29% from pyridine. I would bet the process that the plant uses has a much better yield and uses much less energy.The plant probably synthesizes the left—handed molecule predominately, whereas our chemical procedures have both left and right sided molecules coming out of the reaction tank.....they mentioned that other analogs were produced...that means they didn’t just get their desired molecule only..they got other undesired compounds...pretty sloppy, but state of the art.
Funny how the tiny cells of the plant can make, with high specificity and low energy, a desired molecule in a microscopic confined space. Wonder how it “learned” how to do that.
Totally random accident occurrence they would have us believe............
If you are not a chemist, it is difficult to understand that 6-29% yield for a 6-7 steps synthesis is an excellent number, especially for a synthetic scheme that produced the desired product first time. Usually this process can be optimized and/or changed with time to achieved even better efficiency.
Its not new. Hunter Thompson tells about an Ibogaine crazed hippie causing havoc on George McGovern’s train car during his presidential campaign. Book - “Fear and Loathing on the Campaign Trail 1972”.
I lived during the 60s. Even went to Woodstock in 69.
Never heard of it
This is a new one...............
Far out, man!
This is a new one...............
BRAVE AI:
Tabernanthe iboga
species of plant
The iboga shrub, scientifically known as Tabernanthe iboga, is a perennial rainforest shrub native to central western Africa. It is cultivated across Central Africa for its medicinal and ritualistic uses. The plant belongs to the Apocynaceae family and is known for its psychoactive properties, particularly from the root bark which contains ibogaine, a chemical that can cause hallucinations and has been used in religious ceremonies as a ‘bridge to the ancestors’ in the Bwiti religion.
The iboga shrub reaches about 1.5 to 2 meters in height and has yellowish or pinkish flowers that turn into sweet fruits. However, the psychoactive alkaloids are found in the roots and bark, not the fruits.
It is important to note that ibogaine is illegal in the US due to its high potential for abuse and the risks it poses, including irregular heartbeat, low blood pressure, seizures, paralysis, difficulty breathing, and death.
Yeah. I looked it up too. New to me.
“Don’t eat the green acid”
and Don’t eat that yellow snow!.............
“ and Don’t eat that yellow snow!.............”
Indubitably…….especially in the winter.
There was something about noon and some drug crazed lunatic on a train too if my memory is right- and salacious accusations-
Found in the Roots and Bark of the Iboga Shrub.
.
Sounds British.
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