A non-hallucinogenic psychedelic analogue with therapeutic potential.
Lindsay P Cameron, Robert J Tombari, Ju Lu, Alexander J Pell, Zefan Q Hurley, Yann Ehinger, Maxemiliano V Vargas, Matthew N Mccarroll, Jack C Taylor, Douglas Myers-Turnbull, Taohui Liu, Bianca Yaghoobi, Lauren J Laskowski, Emilie I Anderson, Guoliang Zhang, Jayashri Viswanathan, Brandon M Brown, Michelle Tjia, Lee E Dunlap, Zachary T Rabow, Oliver Fiehn, Heike Wulff, John D McCorvy, Pamela J Lein, David Kokel, Dorit Ron, Jamie Peters, Yi Zuo, David E Olson
Nature January 1, 2021 DOI: 10.1038/s41586-020-3008-z via PubMed
Summary
AI-generated from the abstractIbogaine, a psychedelic alkaloid, shows anti-addictive effects in humans and animals but has safety issues including toxicity and heart arrhythmias. Researchers engineered tabernanthalog, a water-soluble, non-hallucinogenic, non-toxic analogue made in a single step. In rodents, tabernanthalog promoted structural neural plasticity, reduced alcohol- and heroin-seeking behavior, and produced antidepressant-like effects. This demonstrates that careful chemical design can create safer, non-hallucinogenic variants of psychedelic compounds with therapeutic potential.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rodents |
| Intervention | Tabernanthalog |
| Keywords | Addiction treatment Substance use disorders Alcohol seeking Heroin seeking Psychedelic research |
| Citations | 468 |
| Key finding | Tabernanthalog, a non-hallucinogenic ibogaine analogue, promoted structural neural plasticity, reduced alcohol- and heroin-seeking behavior, and produced antidepressant-like effects in rodents. |
Abstract
The psychedelic alkaloid ibogaine has anti-addictive properties in both humans and animals1. Unlike most medications for the treatment of substance use disorders, anecdotal reports suggest that ibogaine has the potential to treat addiction to various substances, including opiates, alcohol and psychostimulants. The effects of ibogaine-like those of other psychedelic compounds-are long-lasting2, which has been attributed to its ability to modify addiction-related neural circuitry through the activation of neurotrophic factor signalling3,4. However, several safety concerns have hindered the clinical development of ibogaine, including its toxicity, hallucinogenic potential and tendency to induce cardiac arrhythmias. Here we apply the principles of function-oriented synthesis to identify the key structural elements of the potential therapeutic pharmacophore of ibogaine, and we use this information to engineer tabernanthalog-a water-soluble, non-hallucinogenic, non-toxic analogue of ibogaine that can be prepared in a single step. In rodents, tabernanthalog was found to promote structural neural plasticity, reduce alcohol- and heroin-seeking behaviour, and produce antidepressant-like effects. This work demonstrates that, through careful chemical design, it is possible to modify a psychedelic compound to produce a safer, non-hallucinogenic variant that has therapeutic potential.