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Monday, May 20, 2024

Psychedelic drug analog shows potential to treat mental illnesses

Researchers synthesize compound from ibogaine without hallucinogenic effects

Psychedelic drugs often carry the stigma of only being used recreationally to experience extravagant hallucinations and achieve heightened sensory awareness. Yet the Olson Laboratory, led by David Olson, an assistant professor in the department of chemistry at UC Davis, found that one of these compounds could be rewired to create a substance to potentially help mental illnesses. After experimenting with the psychedelic drug ibogaine, Olson and his research group created a synthetic analog named tabernanthalog (TBG) that may be able to help treat depression and addiction.

“Our group has been very interested in developing neural plasticity-promoting drugs to treat mental illness by rewiring the brain,” Olson said via email. “In 2018, we discovered the psychedelic compounds were particularly good at promoting plasticity in the brain.”

Lindsay Cameron, a neuroscience PhD candidate, explained that ibogaine has been used for centuries in West African rituals. In one anecdotal account from the 1960s, 19-year-old Howard Lotsof claimed to feel cured of his addiction to heroin after taking ibogaine. Cameron elaborated that this report spurred many scientists to study ibogaine. From their studies, many found it held the potential to treat addiction. Olson hypothesized that this may be due to its ability to rewire neural circuitry. 

Despite the benefits ibogaine offers, there are still dangers associated with the drug such as hallucinations and heart attacks. According to a press release by UC Davis, ibogaine is a Schedule 1 controlled substance under U.S. law. The U.S. Drug Enforcement Administration states that a Schedule 1 drug has a high potential for abuse and to create severe psychological or physical dependence. The UC Davis article further elaborated that Olson’s lab is one of the very few in the U.S. licensed to work with such substances.  

In order to synthesize a compound without these effects, Cameron explained that the Olson lab essentially broke ibogaine down into various components and identified what each was responsible for. Once they were able to identify the areas that led to cardiotoxicity and hallucinations, they cut these parts off, leaving only the beneficial aspects in the new TBG molecule. 

“For decades, many people have assumed that hallucinations are necessary for achieving the therapeutic effects of psychedelics,” Cameron said via email. “This research demonstrates that hallucinations are not necessary to achieve therapeutic effects!”

Though they are still not entirely sure how TBG works, Robert Tomabari, a PhD candidate in the department of chemistry, says the lab hypothesizes the compound is able to promote the growth of cortical neurons, which often atrophy in several psychiatric disorders. Olson added that the next steps in their research will be to understand the compound’s mechanism of action. 

Olson elaborated that in addition to the lack of cardiotoxic and hallucinogenic effects of TBG, this compound is significantly easier to synthesize than ibogaine, meaning it can be produced on a large scale to increase its chances of going through human clinical trials. TBG is also water soluble, which allows it to be easily distributed throughout the body through the bloodstream. 

“Our work is a significant step toward developing a drug inspired by the structure of a psychedelic compound that is safe enough for you to store it in your medicine cabinet, just like you would aspirin,” Olson said.

Cameron explained that she joined the Olson lab after being fascinated by the fact that psychedelic drugs are so powerful and yet so little is known about them. Tombari added that when he first came across the Olson lab, he found the research to be at the frontier of combining the fields of chemistry and biology. He was drawn to their work in synthesizing novel compounds and testing them in biological assays to explore questions about neuroscience. 

“This study demonstrates the kind of science that a well-rounded team can achieve when working together,” Tombari said via email. “Hopefully in the future, we can take what we learned from this study and use it to combat a number of neurological disorders.”
Written by: Michelle Wong —science@theaggie.org


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