The psychoactive alkaloid Ibogaine which stems from Tabernanthe iboga plants in West Africa maintains it’s interest for its possible anti-addictive and anti-depressive properties. Due to its rarity in nature and heart risks associated with ibogaine remains unfit for widespread medical applications. The University of California, Davis published research about their total synthesis of ibogaine alongside its related compounds that opens pathways for scientific advances together with possible medical applications. A link to the research can be found below:
Iyer, R.N., Favela, D., Domokos, A. et al. Efficient and modular synthesis of ibogaine and related alkaloids. Nat. Chem. (2025). https://doi.org/10.1038/s41557-024-01714-7
Researchers at the UC Davis Institute for Psychedelics and Neurotherapeutics (IPN) have developed an efficient synthesis route to produce ibogaine and its analogs from pyridine, an inexpensive and widely available starting material. Their method, detailed in Nature Chemistry, enables the synthesis of four naturally occurring ibogaine-related alkaloids and several non-natural analogs with yields ranging from 6% to 29% in a much more efficient way than what was previously done.
At present scientists face difficulties with ibogaine synthesis due to the structural complexity of the molecule. An updated chemical synthesis method resolves these challenges because it produces more efficient assembly processes that build efficient analogues from nonplant materials.
“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,”
stated 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. He went onto say:
“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.”
One of the key findings of the study was the importance of chirality in ibogaine’s biological activity. The researchers synthesised both the enantiomers of the molecule and found that only the natural form promoted neuronal growth. This suggests that ibogaine’s effects are likely linked to a specific receptor interaction, providing a new tool for identifying its biological mechanism.
“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.”
Another analog, (–)-10-fluoroibogamine, demonstrated increased effects on neuronal growth and reconnection, as well as strong interactions with serotonin transporters; key targets in many antidepressant therapies.
Despite its potential, ibogaine poses a risk of cardiac complications, making its clinical application challenging. Some efforts have been made to mitigate these risks through careful monitoring and magnesium supplementation, but a more effective solutions may need to be developed involving safer analogs.
“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.”
Research investigators aim to create a new generation of ibogaine-inspired medications through their synthetic strategy. With their improved synthetic method implementing basic chemical starting materials they seek to support ibogaine-based research about mechanisms and possible medical applications.
Hassan graduated with a Master’s degree in Chemical Engineering from the University of Chester (UK). He currently works as a design engineering consultant for one of the largest engineering firms in the world along with being an associate member of the Institute of Chemical Engineers (IChemE).
